Drug Registration Guidance Document (DRGD)  
DRUG REGISTRATION  
GUIDANCE DOCUMENT 
(DRGD)  
 NATIONAL PHARMACEUTICAL REGULATORY DIVISION  
                         MINISTRY OF HEALTH , MALAYSIA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Second Edition  – September 2016, revised July 2018 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Please visit the N PRA  website for  the latest updates  
 
 
 
 Address:  
 
Lot 36, Jalan Un iversiti, 46200 Petaling Jaya, Selangor Darul Ehsan, Malaysia  
    + 603-7883 5400     
   + 603 -7956 2924, 7956 7075    
 
    http://npra.moh.gov.my/  
 
Certified to ISO 9001:2015  
Cert. No. : QMS 00894  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
2 
  
GUIDELINE HISTORY  
 
 
 
No. Guideline  Description of 
Amendment  Effective date  
1. a) Guidelines for Application for 
Registration of 
Pharmaceutical Products , 
Third Edition  
 
b) Permohonan Pendaftaran 
Keluaran Ubat Tradisional , 
Second E dition  Initial Publication  a) October 
1993  
 
b) December 
1998  
2. Drug Registration Guidance 
Document (DRGD)  Merging of  
1(a) and 1(b)  * 2004  
3. Drug Registration Guidance 
Document (DRGD) ,  
First Edition - January  2013  Revision of DRGD 
Nove mber 2012  1st January  2013  
4. Drug Registration Guidance 
Document (DRGD) ,  
Second Edition – September 
2016  Revision of DRGD , First 
Edition - January 2013  1st September  
2016  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
3 
  
 
 
 
This guidance document is issued by the Director of 
Pharmaceutical Services  under Regulation 29,  
Control of Drug s and Cosmetics Regulation s 1984.  
 
NPRA  reserves the right to amend an y part of  
the guidance document whichever it deems fit.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Rights Reserved.  
No part of this guidance document may be reproduced, stored in a retrieval system, or 
transmitted, in any form or by any means, electronic, mechanical, microfi lming, 
recording or otherwise, without written permission from the Senior Director  of 
Pharmaceutical Services, Ministry of Health, Malaysia.  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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PREAMBLE  
 
 
❖ This “ DRUG REGISTRATION  GUIDANCE DOCUMENT  (DRGD) ” will serve as the 
reference guide for the registrati on process including quality control, inspection & 
licensing and post -registration activities of medicinal products.  
 
❖ This DRGD shall  be read in conjunction with the current laws and regulations 
together with other relevant legislations, where applicable,  governing pharmaceutical 
and natural products for human use in Malaysia, which include but not limited to the 
following:  
 
a) Sale of Drugs Act 1952;  
b) Control of Drugs and Cosmetics Regulations 1984;  
c) Dangerous Drugs Act 1952;  
d) Poisons Act 1952;  
e) Medicine s (Adver tisement & Sale) Act 1956;  
f) Patent s Act 1983 ;  
g) Wildlife Conservation Act 2010 (Laws of Malaysia Act 716 ); and  
h) International Trade in Endangered Species Act 2008 (Act 686) . 
 
The written laws shall take precedence over this guidance document in any event of 
discrepancy . 
 
❖ The scope  of this DRGD includes information relating to administrative requirements 
and procedures for:  
a) Submission of an application for the  registration of medicinal  products, which 
is based on the ASEAN Common Technical Dossier/ Requirements  (ACTD/ 
ACTR) , where applicable ; 
b) Submission of an application for the licensing of manufacturers, importers and 
wholesalers;  
c) Submission for amendments to a registered medicinal product; and  
d) Post-registration activities.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
5 
 • Applicants shall familiarize with  the contents of this guidance document and the 
governing legislations before they submit applications for medicinal product 
registration.  
 
• The Authority  may request for information or specify conditions not described in this 
document that is deemed necess ary to ensure the quality, safety and efficacy of the  
product.   
 
• An on -going review of regulatory policies  will continue  taking into account the global 
regulatory environment, to allow for timely and pertinent changes.  
For more information, please refer to  Circulars  and Publications . 
 
• Applicants are advised to refer to  NPRA ’s websi te for the latest updates of the 
DRGD and other related guidelines . Separate guidelines  are available for 
Cosmetic s and Veterinary products . 
 
• The Authority  reserves the right to amend any part of the DRGD whenever it deems 
fit. 
 
• Any enquiry on registration of products may be submitted to:  
 
Secretary,  
Drug Control Authority,  
National Pharmaceutical Regulatory Division , 
Minis try of Health Malaysia,  
Lot 36, Jalan Universiti , 
46200 Petaling Jaya, Selangor.  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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 ABBREVIATIONS AND ACRONYMS  
 
 
ACCSQ -  ASEAN Consultative Committee on Standards and Quality/  
PPWG  Pharmaceutical Product Working Group  
 
ACTD           ASEAN Common Technical D ossier  
 
ACTR   ASEAN Common Technical Requirement  
 
AMV   Analytical Method Validation  
 
ANOVA  Analysis of Variance  
 
API Active Pharmaceutical Ingredient (Interchangeable with drug su bstance or 
active substance).  
 
ASEAN  Association of Southeast Asian Nations  
 
ATC  Anatomical Therapeutic Chemical  
 
BA  Bioavailability  
 
BE  Bioequivalence  
 
BET   Bacterial Endotoxins Test  
 
BMF   Batch Manufacturing Formula  
 
BP  British Pharmacopoeia  
 
BSE  Bovine Spongiform Encephalopathy  
 
CCL   Centre for Compliance and Licensing  
 
CDCR   Control of Drugs & Cosmetics Regulations 1984  
 
CEO   Chief Executive Officer  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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 CEP  Certificate of Suitability  
CEP is referring to Certificate of Suitability of European Pharmacopoei a 
monographs issued by the EDQM  
 
CFC   Chlorofluorocarbons  
 
CFS  Certificate of Free Sales  
 
CI  Confidence Interval  
 
CMC   Chemistry, Manufacturing And Controls  
 
CoA  Certificate of Analysis  
 
COH  Change of Product Registration Holder (Previously known as Change of 
Marketing Authorization Holder)  
 
COMBO  Combination Pack  
 
COS   Change of Manufacturing Site  
 
CPP  Certificate of Pharmaceutical Product  
 
CTX  Clinical Trial Exemption  
 
CTIL   Clinical Trial Import Licence  
 
DCA   Drug Control Authority  
 
DE  Data Exclusivity  
 
DMF   Drug Master File (interchangeable with Active Substance Master File)  
 
DNA   Deoxyribonucleic acid  
 
DRGD   Drug Registration Guidance Document  
 
EDQM  European Directorate for the Quality of Medicine and Healthcare  
 
ELC   Endotoxin Limit Concentration  
 
EMA   European Medicines Agency  
 
EP  European Pharmacopoeia  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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 FDA  Food and Drug Administration  
 
FDI   Food -Drug Interphase  
 
FEO  For Export Only  
 
FPQC  Finished Product Specification  
 
FSQD  Food Safety and Quality Division  
 
FTIR   Fourier Transform Infrared  
 
g  gram   
 
GABA   Gamma -Amino Butyric Acid  
 
GC   Gas Chromatograp hy 
 
GCP   Good Clinical Practice  
 
GDP   Good Distribution Practice  
 
GMP   Good Manufacturing Practice  
 
HACCP  Hazard analysis and critical control points  
 
HBsAg  Surface Antigen of the Hepatitis B Virus  
 
HBV   Hepatitis B Virus  
 
HCV   Hepatitis C Virus  
 
HDPE   High-density polyethylene  
 
HIV  Human immunodeficiency virus  
 
HPLC   High Performance Liquid Chromatography  
 
HS  Health Supplement  
 
ICH International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use  
 
INN   Intern ational Non -proprietary Names  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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IPQC   In-Process Quality Control  
 
ISO  International Organization for Standardization  
 
JAKIM   Malaysia Department of Islamic Development  
(Jabatan Kemajuan Islam Malaysia ) 
 
JP  Japanese Pharmacopoeia   
 
L  Litre 
  
LAL   Limulus Amebocyte Lysate  
 
LOA  Letter of Authorization  
 
LOC  Letter of Commitment  
 
LOI   Letter of Intent  
 
mAb   monoclonal antibody  
 
MaV  Major Variation   
 
max  maximum  
 
MCB   Master Cell bank  
 
MDDCI  Medical Device -Drug -Cosmetic Inter phase  
  
MiV-PA  Minor Variation Prior Approval  
 
MiV-N  Minor Variation Notification  
 
mL  milliLitre 
 
MPN   Most -Probable Number  
 
MSM   Methylsulphonylmethane  
 
MVD   Maximum Valid Dilution  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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 NAT   Nucleic Acid Testing  
 
NCE   New Chemical Entity  
 
NDP   New Drug Product  
 
NMT   Not More Than  
 
NPRA   National Pharmaceutical Regulatory Division  
 
NRV   Nutrient Reference Value  
 
OTC   Over -the-Counter  
 
Ph. Eur.  European Pharmacopoeia   
 
PI  Package Insert  
 
PIC/S  Pharmaceutical Inspection Co -operation Scheme  
 
PMF   Plasma Master File  
 
POA   Protocol of Analysis  
 
ppm parts per million  
 
PRH  Product Registration Holder  
(Previously known as Marketing Authorization Holder, MAH)  
 
PSUR  Periodic Safety Update Report  
 
PV  Process Validation  
 
RiMUP  Consumer Medication Information Leaflet (RiMUP ) 
(Previously known as Patient Information Leaflet  or PIL)  
 
RNA   Ribonucleic acid  
 
RSD   Relative Standard Deviation  
 
SIRIM   Standards and Industrial Research Institute of Malaysia  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
11 
  
SPC  Summary of Product Characteristics  
 
spp.  Species  
 
Syn.  Synonym  
 
TAM C  Total Aerobic Microbial Count  
 
TGA  Therapeutic Goods Administration  
 
TLC  Thin Layer Chromatography  
 
TSE  Transmissible Spongiform Encephlopathies  
 
TYMC  Total Yeasts and Moulds Count  
 
USP   United State Pharmacopeia  
 
USPI   US Package Insert  
 
UV  Ultra-Violet  
 
VVM   Vaccine  Vial Monitor  
 
WCB   Working Cell Bank  
 
WHO   World Health Organisation  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
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 GLOSSARY  
 
 
Bulk Product: A product that has completed all processing stages up to, but not 
including, final packaging.  
 
Contract Manufacturer:  Any person who ma nufactures any product on the order of 
another person to whom a manufacturer’s licence has been  issued under these 
Regulations (as defined in Regulation 2, CDCR 1984 ) 
 
Finished Product: A product that has undergone all stages of production and quality  
control, including packaging in its final container and labelling.  
 
Indigenous Medicine:  As defined under Regulation 2, the CDCR 1984, indigenous 
medicine  means a system of treatment and prevention of disease established through 
traditional use of naturally oc curring substances . 
 
Licensed I mporter:  A person to whom an import license has been issued under 
Regulation 12, CDCR 1984 ( as defined in Regulation 2, CDCR 1984 )   
 
Licensed Manufacturer: A person to whom a manufacturer’s licence has been issued 
under thes e Regulations, and i ncludes a contract manufacturer (as defined in 
Regulation 2, CDCR 1984 ) 
 
Licensed W holesaler: A person to whom a wholesaler's licence has been issued 
Regulation 12, CDCR 1984 ( as defined in Regulation 2, CDCR 1984 ) 
 
Manufacturer : A pers on carrying out one or more of the steps specified in the definition 
of manufacture.  
 
Manufacture , in relation to any product includes – 
a) The making or assembling of the product;  
b) The enclosing or packing of the product in any container in a form suitable fo r 
administration or application, and  the labelling of the container  and; 
c) The carrying out of any process in the course of any of the foregoing activities.  
(as defined in Regulation 2, CDCR 1984 ) 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
13 
 Medicinal Product:  The term refers to ‘product’ as st ated in  Regulation 2, CDCR 1984 
which is applicable to pharmaceutical and natural products  
 
OTC:  Refers to Generic product (Non -Scheduled Poison)  
 
Product O wner:  A person, company or entity who is the legal/ registered owner of the 
product formulation and/or proc ess with whom the marketing authorization holder has a 
contract  (glossary used in ACTD and ACTR).  
 
Product Registration Holder:  The company or corporate or legal entity in the field of 
pharmaceuticals whose name the marketing authorization has been granted . This party 
is responsible to all aspects of the product, including quality and compliance with the 
conditions of marketing authorization. The authorized holder must be subjected to 
legislation in the country that issued the marketing authorization, which  normally means 
being physically located in that country  (glossary used in ACTD and ACTR) . 
 
Repacker:  *Please refer “Explanatory Notes for Repackers”  as below  
 
The Authority:  Refers to Drug Control Authority (DCA)  
 
The System:  Refers to QUEST system  in web site of NPRA  
 
 
*EXPLANATORY NOTES FOR REPACKERS  
 
1. Introduction  
 
This chapter is intended to provide guidance to those engaged in repackaging of 
finished products with the aim to provide information to any person/  establishments who 
removes finished prod ucts from their original container -closure system and repackages 
them into a different container -closure system for sale and/or for distribution.  
 
2. Objectives  
 
a) To provide uniform guidance and a means of assessing the operations of 
repackers/ relabelers  as they relate to the provisions of the GMP and GDP  
requirements.  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
14 
 b) To identify the type of repacking activity and whether there is a need to comply 
with GMP and GDP requirements.  
 
  
3. Definitions  
 
Terms  Definitions  
Manufacture  Manufacture, in relation  to any product includes – 
a) The making or assembling of the product;  
b) The enclosing or packing of the product in any container in a form 
suitable for administration or application, and the labelling of the 
container and;  
c) The carrying out of any process in th e course of any of the 
foregoing activities.  
Packaging  All operations, including filling & labelling, that a bulk product has to 
undergo in order to become a finished product. Filling of a sterile product 
under aseptic conditions or a product intended to  be terminally sterilized, 
would not normally be regarded as part of packaging.  
Packaging 
Material  Any material employed in the packaging of a material or product or 
cosmetic, including any other packaging used for transportation or 
shipment. Packaging m aterials are referred to as primary or secondary 
according to whether or not they are intended to be in direct contact with 
the product.  
Printed 
packaging 
material  Packaging material which is imprinted with text or numbers or a 
combination of both . 
Labelling  The term ‘labeling ’ designates all labels and other written, printed, or 
graphic matter upon, or in, any package or wrapper in which it is 
enclosed, except any outer shipping container. A shipping container, 
unless such container or the outside of the consumer package, is 
exempted from labelling requirements.  
Labeller/  
relabeller  A company that affixes the original label to a finished product (i.e labeller) 
or changes in any way the labelling on a product without affecting the 
product or its cont ainer (i.e . relabeller).  
Packaging 
system  Composed of a container system with its closure. This system may 
include several layers of protection for the Pharmacopeia preparation 
along with any sealing devices, delivery devices, labelling and package 
inserts. Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
15 
 Terms  Definitions  
Repacker  A company who removes a finished product from its final packaging  and 
places the finished products into a different container which  is labelled or 
to be labelled before the product is for sale and/or distribution for human  
use. Repacker may consist of primary and secondary repacker . 
Primary 
repacker  A company who  performs repacking activity that places the finished 
products into a primary/  immediate container which labelled or to be 
labelled before the product is for sale and/or distributi on for human  use. 
Secondary 
repacker  A company who does the repacking activity relating to  
a) labelling of the product container; and/or  
b) packing the finished product which is already enclosed in its labelled 
primary container into a carton which is label led or to be labelled.  
 
before the product is for sale and/or distribution for human  use.  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
16 
 4. Examples of types of repacking activity  
 
No. Description of Repacking Activity  Require 
GMP/GDP 
Control  Product to be 
included in 
Manufacturing 
License Lis t Responsibility  Remarks (If any)  
1. Packing/  blistering of imported product 
(tablet/capsule/liquid/etc .) into a different 
container  √ √ Primary 
repacker   
2. De-blistering of blister strips of tablets/capsules 
to repack into a new blister pack/container  √ √ Primary 
repacker  e.g. Blister packs de -
blistered and repack 
into new blis ter pack 
due to market 
purposes, etc.  
3. To form a sec ondary packaging material (unit 
box) to pack blister strips, bottles, etc . into this 
packaging material  √ √ Secondary 
repacker  e.g. 5 strips in a unit 
box to be repack to 1 
strip in a unit box  
4. To affix an immediate label to a container of 
product tha t contains information such as 
Product Name, Dosage Form, Name of Active 
Substance(s), Strength of Active Substance(s), 
Batch Number, Manufacturing Date, Expiry 
Date, Route of Administration, Storage 
Condition, etc . √ √ Primary 
repacker/ 
Secondary 
repacker  Refer  Appendix 9:  
Labelling Requirement  
for Immediate Labels  
5. To affix label of outer carton that contains 
information such as Product Name, Dosage 
Form, Name of Active Substance(s), Strength of 
Active Substance(s), Bat ch Number,  
Manufacturing Date, Expiry Date, Route of 
Administration, Storage Condition, etc . √ √ Secondary 
repacker  Refer Appendix 9: 
Labelling Requirement  
for Unit Outer  Carton  Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
17 
 No. Description of Repacking Activity  Require 
GMP/GDP 
Control  Product to be 
included in 
Manufacturing 
License Lis t Responsibility  Remarks (If any)  
6.  To affix country specific label requirements for 
Malaysia  
a) Name & content of preservative(s) where 
present  
b) The words “Keep medicine o ut of reach of 
children” or words bearing similar meaning 
in both Bahasa Malaysia & English  
c) The words “Controlled Medicine/  Ubat 
Terkawal” (For scheduled poisons only)  
d) Security label (Hologram)   
 
 
√* 
 
 
√*  
 
 
√*  
 
 
√*  
 
 
X 
 
  
X  
 
 
X  
 
 
X Importer/ 
Primar y 
Repacker/ 
Secondary 
Repacker  The importer/  repacker 
shall maint ain the 
relevant documents 
(e.g. hologram records, 
stock card)  
7. To insert new Package Insert / to change original 
Package Insert into the inside of the secondary 
packaging product (unit bo x)  √ √ Secondary 
repacker  e.g. Remove Germany 
package insert from  the 
product and replace 
with Malaysia specific 
Package Insert  
8. To attach/  tape Package Insert on the outside of 
the secondary packaging product (unit box)  √ √ Secondary 
repacker   
9. To in kjet the Product Registration Number on 
the primary/secondary packaging material (unit 
box)  √ √ Primary/  
Secondary 
repacker   
10. To inkjet of the Manufacturing Date, Expiry Date 
and Batch Number on the primary/secondary 
packaging material (unit box)  √ √ Primary/  
Secondary 
repacker   Drug Registration Guidance Document (DRGD)  
National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
18 
 No. Description of Repacking Activity  Require 
GMP/GDP 
Control  Product to be 
included in 
Manufacturing 
License Lis t Responsibility  Remarks (If any)  
11. To affix specific labelling requirement of a 
product  √ √ Primary/  
Secondary 
repacker  Refer Appendix 9:  
Labelling 
Requirements  
12. To inkjet/  affix label ‘ Sample Not For Sale ’/ 
‘Physician ’s sample not for sale ’/ ‘Professional 
sample not for sale ’/ etc. onto the secondary 
packaging material  √* X Secondary 
repacker/  
Importer   
13. To affix label  ‘Diimport/diedarkan oleh ’ onto the 
primary/  secondary packaging material  √* X Primary/  
Secondary  
repacker/  
importer   
14. To affix ‘ Halal’ label onto the primary/  secondary 
packaging material  √* X Primary/  
Secondary 
repacker/  
importer   
15. To shrink wrap several boxes or bottles together  √* X Secondary 
repacker/  
Importer   
16. To repack finished p roducts into tertiary 
packaging materials without any changes to the 
product  √* X Secondary 
repacker/  
Importer   
17. To repack several registered finished product s 
as a convenient  pack for promotional sale only 
without changing the product immediate and u nit 
outer carton label  √* X Secondary 
repacker/  
Importer  Refer 16.5 Application 
for a Convenient Pack  
18. To affix security seal onto the secondary/  tertiary 
packaging material  √* X Secondary 
repacker/  
Importer   Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
19 
 5. Additional note s  
5.1 √* denotes that the repacking activity has to be done in a Good Distribution Practise 
(GDP) controlled or licensed facility.  
5.2 The repacking activities as listed in Para 4 is non -exhaustive. Product and license 
holders shall be  responsible to ensure that the registered products are repacked in 
an appropriate manner and all relevant documents is maintained (batch packaging 
records/logbooks/inventory records/  procedures).  
5.3 The conditions of the product must meet the storage re quirements as stated in the 
Good Distribution Practice Guideline by National Pharmaceutical Regulatory 
Division  (NPRA ).  
5.4 In deciding whether a particular bulk product is suitable for repacking, the repacker 
should take into consideration any available information from the manufacturer, 
published literature and any reference pharmacopoeia .  
 
6. Reference s  
 
6.1 Drug Registration Guidance Docume nt; First Edition; January 2013  
6.2 Good Distribution Practice Guideline, 1st Edition; 2011  
6.3 Control of Cosm etic Products  
6.4 USP 31; Volume 1, 2008  
6.5 Guidance for Industry Container Closure Systems for Packaging Human Drugs and 
Biologics; May 1999  
6.6 Irish Medicine Boards Guide to Parallel Imports; AUT -G0006 -4.9  
6.7 WHO GMP: Main Principles for Pharmaceut ical Products.  
 
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
20 
 Glossary for Homeopathic Products:  
 
Active substance: Active substances are considered to be source materials processed 
by one or a sequence of homeopathic manufacturing procedures listed in 
pharmacopoeias in official use and other offi cially recognized documents (e.g. mother 
tinctures, dilutions or triturations).  
 
Diluent: Substance used for the preparation of a stock/  starting material or the 
potentisation process and which may also represent the substance of the dosage form. 
Liquid di luents usually consist of purified water, aqueous solution, glycerol or ethanol of 
a suitable concentration or for which there is an appropriate monograph. The 
commonest solid diluent is usually lactose  monohydrate.  
 
Dilution: Dilution has two meanings in  homeopathy:  
• For a product, a dilution is a liquid homeopathic preparation which is potentised as 
described below (see the definition of potentisation). Individual dilutions are also 
called potencies;  
• As a procedure, dilution means the de -concentration pro cess of a liquid or a solid 
preparation. One part of each stage in the preparation of a homeopathic medicine 
from its stock or previous dilution (potency) by adding one part of a previous solid or 
liquid phase to a predetermined weight or volume of the dil uent (see Potentisation 
below). Dilution occurs at all stages of production of the homeopathic medicines 
whether by addition of solid excipient in trituration or the addition of diluent in the 
liquid phase and succussion.  
 
Dosage form: a dosage form in hom eopathy complies with any relevant specifications 
for that dosage form for which an appropriate characterization exists in a 
pharmacopoeia in official use, or in other officially recognized documents. The most 
commonly encountered homeopathic dosage form, the globule (pillule or pellet) , is a 
solid spherule which consists of lactose, sucrose or any other suitable vehicle. Usually, 
preformed globules are impregnated with a dilution or directly by a mother tincture. The 
homeopathic dosage form tablet is a sol id preparation which complies with any relevant 
characterization in the pharmacopoeia in official use (or in other officially recognized 
documents) for tablets. Homeopathic medicines in tablet form are either prepared by 
impregnation of preformed tablets o r by compression of triturations with the vehicle. The 
most commonly used liquid homeopathic medicines are either alcoholic solutions or oral 
liquids.  
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
21 
 Excipient:  Substance needed for manufacturing a dosage form (used after 
potentisation) such as wheat sta rch and magnesium stearate for tablets. It may also 
represent the substance of the dosage form.  
 
Homeopath: A qualified provider (practitioner) of homeopathic treatment.  
 
Homeopathic medicines: Any medicine prepared in accordance with a homeopathic 
manufac turing procedure described by a pharmacopoeia in official use or other officially 
recognized documents. A homeopathic medicine may contain a number of homeopathic 
preparations.  
 
Homeopathy: Classical homeopathy is a system of medicine using preparations of  
substances whose effects, when administered to healthy subjects, correspond to the 
manifestations of the disorder in the individual pat ients.     
 
Mother tincture (also called tincture): The initial homeopathic preparation made from 
source material that ca n be further potentised (also called “liquid stock”), sometimes 
used as homeopathic medicines, is regarded as the most concentrated form of a 
finished homeopathic medicine. Mother tinctures are obtained classically by maceration 
or percolation (sometimes a lso by digestion, infusion, decoction or fermentation) 
techniques from source materials according to a procedure prescribed by a recognized 
homeopathic pharmacopoeia. Sometimes a mother tincture corresponds to the first 
decimal dilution, “1D” or “1X” (10 -1), mostly when dry plant material is used as starting 
material.  
 
Nosodes: Homeopathic medicines prepared from disease products from humans or 
animals; from pathogenic organisms or their metabolic products; or from decomposition 
products of animal organs.  
 
Potency: The denominated degree of serial trituration or dilution and succession that is 
reached for each homeopathic medicine. The degrees of dilution or potencies are 
normally indicated by the letters D, DH or X for successive 1 to 10 (decimal) dilution s, 
the letters C, CH or K or CK for successive 1 to 100 (centesimal) dilutions while Q or LM 
denote successive 1 to 50 000 (Hahnemannian quinquagintamillesimal) dilutions. 
Dilution by 1 to 10 denotes 1 part processed with 9 parts of diluent (Hahnemannian 
decimal), dilution by 1 to 100, 1 part processed with 99 parts (Hahnemannian or 
Korsakovian centesimal), and so on. The number preceding the letters (e.g. D, C or LM) 
normally indicates the number of dilution steps employed (Table 1).  
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
22 
 As a consequence of d ifferent views in various approaches in homeotherapy and 
because the notion of these terms may depend on the nature of the starting materials, 
the terms “high potency” and “low potency” cannot be defined unambiguously.  
 
Potentisation (also called dinamizat ion): The combined process of serial dilution and 
succussion or trituration at each step in the manufacture of homeopathic medicines 
from stocks. (According to the tenet of homeopathy, potentisation represents the 
process by which the activity of a homeopa thic medicine is developed.)  
 
Table 1:  Potency table  
 
Dilution ratio  Common 
designation(s)  Examples  
1:10a X 1X, 2X, 3X, etc.  
1:10a D D1, D2, D3, etc.  
1:10a DH DH1, DH2, DH3, etc.  
1:100b C 1C, 2C, 3C, etc.  
C1, C2, C3, etc.  
1:100b CH 1CH, 2CH, 3CH, etc.  
CH1, CH2, CH3, etc.  
1:100b CK 1CK, 2CK, 3CK, etc.  
CK1, CK2, CK3, etc.  
1:100b K 1K, 2K, 3K, etc.  
K1, K2, K3, etc.  
1:50 000a LM 1LM, 2LM, 3LM, etc.  
1:50 000a Q Q1, Q2, Q3, etc.  
aFor 1:10 and 1:50 000 dilution ratios only the Hahnemannian method of manu facture 
(multi -flask method) is used.  
bFor 1:100 dilution ratios a C potency is assumed to use the Hahnemannian method of 
manufacture (multi -flask method) and can also be denoted as CH. When the 
Korsakovian method of manufacture (single -flask method) is us ed, the potency is 
designated as CK or K.  
 
Sarcodes: Homeopathic medicines made from healthy animal tissues or secretions. In 
Greek, sarcode means fleshly.  Drug Registration Guidance Document (DRGD)  
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Source material (raw material, starting material, mother substance): Source 
material is the origina l raw material used for the production of homeopathic medicines. 
This material is obtained from natural sources, e.g. of botanical, zoological, 
microbiological, mineral, chemical, animal and human  origin, or synthetic procedures. 
Source materials may under go preliminary treatment in order to be further processed.  
 
Stock: Substances or preparations made from the source materials (e.g. by 
maceration, succussion or trituration) used as starting points for the produc tion of 
homeopathic medicines.  
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
24 
 TABLE OF CONTENTS  
 
GUIDELINE HISTORY  ................................ ................................ ................................ . 2 
PREAMBLE  ................................ ................................ ................................ ...............  4 
ABBREVIATIONS AND ACRONYMS  ................................ ................................ ...........  6 
GLOSSARY  ................................ ................................ ................................ ..............  12 
TABLE OF CONTENTS  ................................ ................................ ..............................  24 
 
 
SECTION A: GENERAL OVERVIEW  
 
1. INTRODUCTION  ................................ ................................ ............................  33 
1.1 REGISTRATION OF PRODUCTS  ................................ ................................ .......  35 
1.1.1  REGISTRABLE PRODUCTS  ................................ ................................ .................  36 
1.1.2  NON -REGISTRABLE PRODUCTS  ................................ ................................ ........  36 
1.1.3  EXEMPTIONS FOR PRODUCTS USED IN CLINICAL TRIALS AND 
MANUFACTURING SAMPLES FOR REGISTRATION  ................................ ........................  39 
1.2 CATEGORIES OF PRODUCT  ................................ ................................ .............  41 
1.2.1  NEW DRUG PRODUCTS  ................................ ................................ ....................  41 
1.2.2  BIOLOGICS ................................ ................................ ................................ ........  43 
1.2.3  GENERICS  ................................ ................................ ................................ .........  45 
1.2.4  HEALTH SUPPLEMENTS  ................................ ................................ ...................  45 
1.2.5  NATURAL PRODUCTS  ................................ ................................ .......................  46 
1.3 FOOD - DRUG INTERPHASE PRODUCTS  ................................ ..........................  48 
1.3.1  INTRODUCTION  ................................ ................................ ...............................  48 
1.3.2  DEFINITION OF FDI PR ODUCTS  ................................ ................................ ........  49 Drug Registration Guidance Document (DRGD)  
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 1.3.3  CLASSIFICATION FOR FDI PRODUCTS  ................................ ..............................  50 
1.3.3.1   NEGATIVE LIST FOR FDI  ................................ ................................ ...................  52 
1.3.3.2  GENERAL CLASSIFICATION FLOWCHART OF FOOD -DRUG INTERPHASE (FDI) 
UNDER FOOD OR DRUG  ................................ ................................ ................................  56 
1.3.4  ADDITIONAL NOTES  ................................ ................................ .........................  57 
1.3.5      PICTORIAL GUIDE TO CLASSIFICATION OF FOOD OR DRUG PRODUCTS  .........  58 
1.4 MEDICAL DEVICE - DRUG - COSMETIC INTERPHASE PRODUCTS  ......................  59 
1.4.1  INTRODUCTION  ................................ ................................ ...............................  59 
1.4.2  CLASSIFICATION CRITERIA  ................................ ................................ ...............  60 
2. DATA EXCLUSIVITY  ................................ ................................ .......................  77 
2.1  HOW TO APPLY  ................................ ................................ .............................  77 
2.2 APPLICABILITY AND DATE OF COMING INTO FORCE  ................................ .......  78 
2.3 GRANT OF DATA EXCLU SIVITY  ................................ ................................ .......  79 
2.4 CONSIDERATION OF OTHER APPLICATIONS UPON THE GRANT OF DATA 
EXCLUSIVITY  ................................ ................................ ................................ .. 80 
2.5 NON -APPLICATION OF DATA EXCLUSIVITY  ................................ .....................  81 
2.6 APPEAL  ................................ ................................ ................................ .........  81 
3. APPLICATION FORMALITIES  ................................ ................................ ..........  82 
3.1 WHO CAN APPLY  FOR PRODUCT REGISTRATION  ................................ ............  82 
3.2 RESPONSIBILITY OF APPLICANT  ................................ ................................ ..... 82 
3.3 HOW TO APPLY  ................................ ................................ .............................  83 
4.   FEES  ................................ ................................ ................................ .............  84 
4.1 FEES IMPOSED  ................................ ................................ ...............................  84 
4.2 MODE OF PAYMENT  ................................ ................................ ......................  84 
5. TYPES OF APPLICATION  ................................ ................................ ................  85 
5.1 REGISTRATION OF PRODUCTS  ................................ ................................ .......  85 Drug Registration Guidance Document (DRGD)  
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 5.1.1  APPLICATION FOR PRODUCT REGISTRATION FOR THE FOLLOW ING 
CATEGORIES:  ................................ ................................ ................................ .................  85 
5.1.2  REGISTRATION OF COMBINATION PACK (COMBO PACK)  ...............................  85 
5.1.3  REGISTRATION OF STARTER PACK/ PATIENT INITIATION  PACK  ......................  87 
5.1.4  REGISTRATION OF PRODUCT FOR EXPORT ONLY (FEO)  ................................ .. 88 
5.1.5  REGISTRATION OF ORPHAN PRODUCT  ................................ ............................  89 
5.2 AMENDMENTS TO PARTICULARS OF A REGISTERED PRODUCT  .......................  94 
5.2.1  VARIATION  ................................ ................................ ................................ .......  94 
5.2.2  CHANGE  IN MANUFACTURING SITE  ................................ ................................  94 
5.2.3  CHANGE IN PRODUCT REGISTRATION HOLDER  ................................ ..............  95 
5.2.4  NEW/ ADDITIONAL INDICATION  ................................ ................................ ...... 95 
5.2.5  APPLICATION FOR A CONVENIENT PACK  ................................ .........................  96 
5.3 RENEWAL OF PRODUCT REGISTRATION  ................................ .........................  96 
5.4 CERTIFICATES  ................................ ................................ ................................  97 
5.4.1  CERTIFICATE OF PHARMACEUTICAL PRODUCT (CPP)  ................................ ..... 97 
5.4.2  GOOD MANUFACTURING PRACTICE (GMP) CERTIFICATE  ...............................  97 
5.5 LICENSES  ................................ ................................ ................................ .......  98 
5.6 CLINICAL TRIAL IMPORT LICENCE (CTIL)/ CLINICAL TRIAL EXEMPTION (CTX)  ... 98 
6. GENERAL CONDITIONS FOR REGISTRATION OF DRUG PRODUCTS UNDER 
THE CONTROL OF DRUGS AND COSMETICS REGULATIONS 1984  ............................  99 
6.1 REGISTRATION CODE/ NUMBER  ................................ ................................ .... 99 
6.2 PRODUCT PARTICULAR  ................................ ................................ ................  100 
6.3 LABELLING AND PACKAGING  ................................ ................................ .......  100 
6.4 PRODUCT AUTHEN TICATION  ................................ ................................ .......  101 
6.5 INDICATIONS, SPECIAL CONDITIONS  ................................ ............................  102 
6.6 ADVERSE REACTIONS, COMPLAINTS  ................................ ............................  102 
6.7 HOLDER OF REGISTERED PRODUCT  ................................ ..............................  102 
6.8 WITHDRAWAL FROM REGISTRATION  ................................ ...........................  102 Drug Registration Guidance Document (DRGD)  
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 6.9 CANCELLATION, SUSPENSIO N, AMENDMENT BY THE AUTHORITY  ................  102 
6.10  DIRECTIVES  ................................ ................................ ................................ . 103 
6.11 CONDITIONS PERTAINING TO PATENT  ................................ .............................  103 
7. USE OF HALAL  LOGO  ................................ ................................ ..................  104 
 
 
SECTION B: PRODUCT REGISTRATION PROCESS  
 
8. FLOW OF REGISTRATION PROCESS  ................................ .............................  105  
8.1 PRE-SUBMISSION OF APPLICATION  ................................ ..............................  106 
8.1.1  CATEGORY OF PRODUCT  ................................ ................................ ...............  106 
8.1.2  METHOD OF EVALUATION  ................................ ................................ .............  106 
8.1.3  REQUIREMENTS FOR PRODUCT REGISTRATION  ................................ ...........  110 
8.1.4  CONDITIONS APPLIED ON PRODUCT REGISTRATION  ................................ .... 111 
8.1.5  MULTIPLE APPLICATIONS  ................................ ................................ ..............  112 
8.1.6  SECOND OR THIRD SOURCE  ................................ ................................ ...........  113 
8.1.7  VARIANTS  ................................ ................................ ................................ .......  117 
8.1.8  LANGUAGE  ................................ ................................ ................................ ..... 117 
8.2 SUBMISSION OF APPLICATION  ................................ ................................ ..... 118 
8.3 SCREENING OF APPLICATION  ................................ ................................ .......  119 
8.3.1  SATISFACTORY  ................................ ................................ ...............................  119 
8.3.2  NON -SATISFACTORY  ................................ ................................ ......................  120 
8.4 EVALUATION OF APP LICATION  ................................ ................................ .... 121 
8.4.1  INITIATION OF REVIEW  ................................ ................................ ..................  121 
8.4.2  PRIORITY REVIEW  ................................ ................................ ..........................  121 
8.4.3  CORRESPONDENCE  ................................ ................................ ........................  122 
8.4.4  TIMELINE FOR PRODUCT REGISTRATION  ................................ ......................  123 
8.5 REGULATORY OUTCOME  ................................ ................................ .............  124 Drug Registration Guidance Document (DRGD)  
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 8.5.1  DECISIONS OF THE AUTHORITY  ................................ ................................ ..... 124 
8.5.2  PRODUCT REGISTRATION NUMBER  ................................ ..............................  124 
8.5.3  CERTIFICA TE OF REGISTRATION  ................................ ................................ .... 124 
8.6 POST -REGISTRATION PROCESS  ................................ ................................ .... 125 
8.7 REJECTED APPLICATION  ................................ ................................ ...............  125 
8.7.1  PROCESS OF APPEAL  ................................ ................................ ......................  126 
8.7.2  TEMPLATE FOR AN APPEAL LETTER  ................................ ...............................  127 
 
 
SECTION C: QUALITY CONTROL  
 
9. GUIDE LINE FOR THE SUBMISSION OF PROTOCOL OF ANALYSIS (POA)  ........  130  
9.1 GENERAL REQUIREMENTS  ................................ ................................ ...........  130 
9.2 SPECIFIC REQUIREMENTS  ................................ ................................ ............  131 
10. GUIDELINE FOR THE SUBMISSION OF ANALYTICAL   METHOD VALIDATION 
(AMV) DOCUMENTS  ................................ ................................ ..............................  137  
10.1  TYPES OF ANALYTICAL PROCEDURES TO BE VALIDATED  ...............................  137 
10.2  TYPICAL VALIDATION PARAMETERS FOR CHEMICAL TESTS  ...........................  137 
10.2.1  FULL VALIDATION FOR IN -HOUSE METHODS  ................................ ................  137 
10.2.2  PARTIAL VALIDATION FOR COMPENDIAL/PHARMACOPOEIAL METHODS  ... 139 
10.3  TYPICAL VALIDATION CHARACTERISTICS FOR MICROBIOLOGICAL TESTS:  ..... 140 
11. GUIDELINE FOR THE SUBMISSION OF PRODUCT SAMPLES FOR 
LABORATORY TESTING  ................................ ................................ .........................  141  
11.1  GENERAL REQUIREMENTS  ................................ ................................ ...........  141 
11.2  SPECIFIC REQUIREMENTS  ................................ ................................ ............  142 
11.2.1  NATURAL PRODUCTS  ................................ ................................ ....................  142 
11.2.2   PHARMACEUTICAL PRODUC TS ................................ ................................ .... 142 Drug Registration Guidance Document (DRGD)  
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 SECTION D: INSPECTION AND LICENSING  
 
12. INSPECTION  ................................ ................................ ...............................  144  
12.1  FOREIGN GMP INSPECTION  ................................ ................................ .........  145 
12.2     MANAGING CHANGES OF MANUFACTURERS FACILITY  ................................ . 146 
13. LICENSING  ................................ ................................ ................................ .. 152  
13.1  TYPES OF LICENSES  ................................ ................................ ......................  152 
13.2  LICENSE APPLICATION FORM  ................................ ................................ .......  152 
13.3  ADDITIONAL  PRODUCT LIST OF LICENSE FOR REGISTERED PRODUCTS  ..........  153 
13.4  GMP CERTIFICATE  ................................ ................................ .......................  153 
 
 
SECTION E: POST -REGISTRATION PROCESS  
 
14. MAINTENANCE OF REGISTRATION  ................................ .............................  155 
14.1  REQUIREMENT  ................................ ................................ ...............................  156 
14.2  APPLICATION FOR PEODUCT RE-REGISTRATION  ................................ ..............  159 
15. WITHDRAWAL OF PRODUCT REGISTRATION  ................................ ..............  160  
16. AMENDMENTS TO PARTICULARS OF A REGISTERED PRODUCT  ...................  160  
16.1  VARIATION  ................................ ................................ ................................ .. 161 
16.1.1 VARIATION APPLICATION FOR PHARMACEUTICAL PRODUCTS  .......................  161 
16.1.2 VARIATION APPLICATION FOR HEALTH SUPPLEMENT AND NATURAL PRODUCTS
 ................................ ................................ ................................ ................................ ..... 162 
16.1.3 VARIATION APPLICATION FOR BIOLOGICAL PRODUCTS  ................................ .. 163 
16.2  CHANGE OF MANUFACTURING SITE  ................................ ............................  163 
16.2.1 CO NDITIONS ON APPLICATION FOR COS:  ................................ ........................  164 
16.2.2 CONDITIONS ON GOOD MANUFACTURING PRACTICE (GMP):  ........................  164 Drug Registration Guidance Document (DRGD)  
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 16.2.3 TYPES OF MANUFACTURING S ITE CHANGES (COS) ................................ ..........  165 
16.2.4 MODE OF SUBMISSION  ................................ ................................ ....................  166 
16.2.5 OTHER INFORMATION  ................................ ................................ ......................  167 
16.3  CHANGE OF PRODUCT REGISTRATION HOLDER  ................................ ............  168 
16.3.1  INTRODUCTION  ................................ ................................ .............................  168 
16.3.2  CONDITIONS  ................................ ................................ ................................ .. 168 
16.3.3  APPLICATION  ................................ ................................ ................................ . 169 
16.3.4  PROCESSING FEE  ................................ ................................ ............................  169 
16.3.5  SUPPORTING DOCUMENTS  ................................ ................................ ...........  170 
16.3.6  SUPPORTING DOCUMENT FORMAT EXAMPLE  ................................ .............  171 
16.3.7 FLOWCHART FOR THE CHANGE OF PRODUCT REGISTRATION HOLDER  ..........  173 
16.4  NEW/ ADDITIONAL INDICATION  ................................ ................................ .. 174 
16.4.1  FULL EVALUATION PROCESS  ................................ ................................ ..........  174 
16.4.2  VERIFICATION PROCESS  ................................ ................................ .................  174 
16.5  APPLICATION FOR A CONVENIENT PACK  ................................ ......................  175 
17. POST -MARKETING ACTIVITIES  ................................ ................................ .... 178  
17.1  PHARMACOVIGILANCE  ................................ ................................ ................  178 
17.1.1  ADVERSE DRUG REACTION REPORTING AND SAFETY UPDATES  ...................  178 
17.2 POST -MARKET SURVEILLANCE  ................................ ................................ ..... 178 
17.2.1  PRODUCT COMPLAINTS  ................................ ................................ .................  179 
17.2.2  PRODUCT RECALLS  ................................ ................................ ........................  179 
17.3  PUNITIVE ACTION FROM THE AUTHORITY  ................................ ...................  180 
17.3.1  ADULTERATION ................................ ................................ ..............................  180 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
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Second Edition, September 2016, Revised July 2018  
 
31 
 APPENDICES  
APPENDICES  ................................ ................................ ................................ .........  181  
APPENDIX 1:  FEES  ................................ ................................ .............................  182  
APPENDIX 2:  REQUIREMENTS FOR PRODUCT REGISTRATION  ............................  187  
APPENDIX 3:  GUIDELINES ON REGISTRATION OF BIOLOGICS  .............................  206  
APPENDIX 4: GUIDELINE ON REGISTRATION OF HEALTH SUPPLEMENTS  ..............  230  
SECTION A:  PRODUCT PARTICULARS  ................................ ................................ .... 249 
SECTION B:  PRODUCT FORMULA  ................................ ................................ ..........  252 
SECTION C:  PARTICULARS OF PACKING  ................................ ................................ . 263 
SECTION D:  LABELLING REQUIREMENTS  ................................ ...............................  264 
SECTION E:  PARTICULAR OF PRODUCT OWNER, MANUFACTURER, IMPORTER AND  
OTHER MANUFA CTURER  ................................ ................................ ... 271 
SECTION F:  SUPPLEMENTARY DOCUMENTS  ................................ ..........................  271 
APPENDIX 5:  GUIDELINE ON REGISTRATION OF NATURAL PRODUCTS ...............  291  
APPENDIX 6 :  GUIDELINE ON REGULATORY CONTROL OF ACTIVE 
PHARMACEUTICAL INGREDIENTS (APIs)  ................................ ...............................  370  
APPENDIX 7:  SPECIAL CONDITIONS FOR REGISTRATION FOR A PARTICULAR 
PRODUCT OR GROUP OF P RODUCTS  ................................ ................................ .... 393  
APPENDIX 8:  LIST OF PERMITTED, PROHIBITED AND RESTRICTED SUBSTANCES  396  
APPENDIX 9:  LABELLING REQUIREMENTS  ................................ ..........................  411  
9.1 GENERAL LABELLING REQUIREMENTS  ................................ ..........................  412 
9.1.1  LABEL (MOCK -UP) FOR IMMEDIATE CONTAINER AND OUTER CARTON  .......  415 
9.1.2  PROPOSED PACKAGE INSERT  ................................ ................................ .........  417 
9.1.3  CONSUMER MEDICATION INFORMATION LEAFLET (RiMUP)  ........................  418 Drug Registration Guidance Document (DRGD)  
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 9.1.4   PRODUCT NAME  ................................ ................................ ...........................  419 
9.1.5  PROHIBITED VISUAL/ GRAPHICS/ STATEMENTS ON LABEL  ...........................  422 
9.2 SPECIFIC LABELLING REQUIREMENTS  ................................ ...........................  426 
APPENDIX 10 :  GUIDELINE ON PATIENT DISPENSING PACK FOR 
PHARMACEUTICAL PRODUCTS IN MALAYSIA  ................................ .......................  604  
APPENDIX 11 :  GUIDELINE ON FILLING T HE ONLINE APPLICATION FORM FOR 
PRODUCT REGISTRATION VIA QUEST SYSTEM  ................................ ......................  615  
11.1  PRODUCT CLASSIFICATION  ................................ ................................ ..........  617 
11.2  SUBMISSION OF APPL ICATION  ................................ ................................ ..... 618 
SECTION A: PRODUCT PARTICULARS  ................................ ................................ ..........  624 
SECTION B: PRODUCT FORMULA  ................................ ................................ ................  630 
SECTION C: PARTICULARS OF PACKING  ................................ ................................ .......  632 
SECTION D: LABEL (MOCKUP) FOR IMMEDIATE CONTAINER, OUTER CARTON AND 
PROPOSED PACKAGE INSERT  ................................ ................................ ......................  633 
SECTION E/ SECTION F: SUPPLEMENTARY DOCUMENTATION (AND PARTICULARS OF 
PRODUCT OWNER, MANUFACTURER, IMPORTER AND OTHER MANUFACTURER)  ... 633 
APPENDIX 12 :  CONDITIONS AND SUPPORT ING DOCUMENTS REQUIRED FOR 
AN APPLICATION OF VARIATION  ................................ ................................ ..........  638  
APPENDIX 13 :  SUPPORTING DOCUMENTS REQUIRED FOR CHANGE OF 
MANUFACTURING SITE (COS) APPLICATION  ................................ .........................  662  
APPENDIX 14 :  GUIDELINES ON SAFETY DATA REQUIREMENTS FOR 
COMPLEMENTARY MEDICINE PRODUCTS  ................................ ............................  667  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
33 
 SECTION A: GENERAL OVERVIEW  
 
1. INTRODUCTION  
 
The Control of Drugs and Cosmetics Regulations (CDCR) 1984  were promulgated 
under the Sale of Drug s Act 1952 . The Authority (known as Drug Control Authority, 
DCA) established under these Regulations , is tasked with ensuring the quality, safety 
and efficacy of medicinal products through the registration,  including quality control, 
inspection & licensing  and post -registration  activities. The National Pharmaceutical 
Regulatory Division  (NPRA ) acts as the secretariat to the Authority .  
 
Under the CDCR 1984 , Regulation 7(1) : Except as otherwise provided in these 
Regulations, no  person  shall manufacture, sell, supply, impor t, possess or administer 
any product unless : 
(a) the product is a registered product; and  
(b) the person holds the appropriate licence required and issued under these 
Regulations . 
 
The phases of implementation for product registra tion are as shown in Figure 1  below:  
 
 
 
* 1st July 2012:  
All manufacturers shall be certified for GMP as dire cted by  the Senior Director Pharmaceutical 
Services under Regulation 29, Control of Drugs and Cosmetics Regulation 1984;  
Directive No .  1 Year  2012. Direktif Mengenai Syarat Pendaftaran Produk Farmaseutikal Dari Luar 
Negara Berkaitan Keperluan Amalan Perkilangan Baik (APB).  
Reference: Circulars  Bil (25) dlm BPFK/PPP/01/03 Jld 1   and Bil (96)dlm.BPFK/PPP/01/03 Jld. 2  Drug Registration Guidance Document (DRGD)  
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 Registration process includ es quality control, ins pection & licensing as well as  post-
registration process  of medicinal products  is illustrated in Figure 2  below:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Good Manufacturing Practice (GMP) Certification  
**    For natural products only   
***  Application for Manufacturer, Import and/or Wholesale Licens e  Data Evaluation  ** Sample testing  * GMP Inspection  
and Certification  
*** Licensing  Submission of Registration 
Application and Screening Process  
Meeting of the Drug Evaluation Committee  
Meeting  of the Authority  Pre-Submission of Registration  
Application  
Approval  Rejection  Appeal  Regulatory Outcome  
Post -Registration Process  
 Drug Registration Guidance Document (DRGD)  
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Second Edition, September 2016, Revised July 2018  
 
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 1.1 REGISTRATION OF PRODUCTS  
 
Under the CDCR 1984, Regulation 2: “Product ” means:  
(a) a drug1 in a dosage unit or otherwise, for use wholly or mainly by being 
administered to one or more human beings or animals for a medicinal purpose2; or  
(b) a drug1 to be used as an ingredient of a preparation for a medicinal purpose2. 
 
 
Under Sales of Drug Act 1952, Section 2 :  
1 “drug ” includes any substance, product or article intended to be used or capable, or 
purported or cla imed to be capable, of being used on humans or any animal, whether 
internally or externally, for a medicinal purpose.  
 
2 “medicinal purpose ” means any of the following purposes:  
(a) alleviating, treating , curing or preventing a disease or a pathological cond ition or 
symptoms of a disease;  
(b) diagnosing a disease or ascertaining the existence, degree or extent of a 
physiological or pathological condition;  
(c) contraception;  
(d) inducing anaesthesia;  
(e) maintaining, modifying, preventing, restoring, or interfering with, the normal 
operation of a physiological function;  
(f) controlling body weight;  
(g) general maintenance or promotion of health or wellbeing.  
 
 
 
 
 Note:  
In this DRGD, the term “medicinal product” refers  to the term “product” as s tipulated  
in the Regulation 2,  CDCR 1984 . Drug Registration Guidance Document (DRGD)  
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 1.1.1  REGISTRABLE PRODUCTS  
 
Any product as defined in 1.1 shall be registered with the Authority.  
 
The products incl ude, but not limited to the following:  
 
a) Pharmaceutical products containing scheduled poisons  
 
b) Pharmaceutical products containing non -scheduled poisons  
(For examples:  Medicated plaster with medicine, antiseptic/ disinfectants for use 
on the human body, dia gnostic agents for human use (in -vivo) and health 
supplement such as probiotics and chitosan)  
 
c) Natural products  
Includes herbal and traditional products  
 
                                                                                                              
1.1.2  NON -REGISTRABLE PRODUCTS  
 
i) Diagnostic agents and test kits for laboratory/ in -vitro use  
 
Diagnostic agents/  test kits for laboratory use must be labeled ‘FOR 
LABORATORY USE ONLY’ .   
  
 
 
 
 
 Note:  
Products which are not labelled as su ch shall be deemed to be for human or 
animal use and need to be registered with the Authority.  Drug Registration Guidance Document (DRGD)  
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 ii) Medical Devices  
 
“Medical device ” means any instrume nt, apparatus, implement,  machine, 
appliance, implant, in vitro  reagent or calibrator, software, material or other 
similar or related article  intended by the manufacturer to be used, alone or in 
combination, for human beings for the purpose of : 
  
(i) diagnos is, prevention, monitoring, treatment or alleviation of disease;  
(ii) diagnosis, monitoring, treatment, alleviation of or compensation for an injury;  
(iii) investigation, replacement or modification, or support of the anatomy or of a 
physiological process;  
(iv) support or  sustaining life;  
(v) control of conception;  
(vi) disinfection of medical device; or  
(vii) providing information for medical or diagnostic purpose by means of in vitro  
examination of specimens derived from the human body,  
 
These products  do not achieve its primary intend ed action in or on the human 
body by pharmacological, immunological or metabolic means, but that may be 
assisted in its intended function by such means.  
 
This includes but is not limited to the following:  
 
- Non-medicated bandages, plaster  
- Surgical dres sings, w ound care/  dressing materials containing hydrogel, 
collagen, calcium alginate  
- Visco -elastic products for mechanical or physical protection of tissues during 
or after surgical procedures  
- Instruments, apparatus, syring es, needles, sutures, catheters  
- Disinfect ants for equipments/ devices  Drug Registration Guidance Document (DRGD)  
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 - Lubricants for gl oves, condoms and endoscope s  
- Contact lens care products  
- Copper IUDs  
- Bone cement, tissue adhesives  
- Dental fillings  
- Blood bag s containing anti -coagulants  
- Non-medicated medical and contraceptive devices  
 
For more information, please refer Medical Device Authority . 
 
 
iii) Food  
 
As defined under the Food Act 1983 and Food Regulations 1985, includes every 
article manufactured, sold or represented for use as food or drink for human 
consumption or which enters into or is used in the composition, preparation, and 
preservation, of any food or drink and includes confectionery, chewing 
substances and any ingredient of such food, drink, confectionery or chewing 
substances. This inclu des food for special dietary use for persons with a specific 
disease, disorder or medical condition, and food which contain quantities of 
added nutrients allowable under the Food Act 1983 and  Regulations . 
 
For more information, please refer  Food Safety & Quality Division, Ministry of 
Health Malaysia . 
 
 
iv) Sports Nutrition , such as  body -building products containing protein/ whey/ soya 
bean  
 
 
v) Raw herbs used in extemporaneous preparations , including those that are dried 
& cut  into pieces , without dosage instructions and indications  
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vi) Insect repellants, insecticides, pesticides and parasiticides  
 
Products containing pesticides as listed under First Schedule of Pesticide Act 
1974 for external use only  shall be controlled by the  Pesticide Board.  
 
For more info rmation, please refer  http://www.doa.gov.my  
 
 
vii) Detergents/ disinfectants for domestic use  
 
 
1.1.3  EXEMPTIONS FOR PRODUCTS USED IN CLINICAL TRIALS AND 
MANUFACTURING SAMPLES FOR REGISTRATI ON 
 
a) Clinical Trial Import License  (CTIL)  
Products which are not registered with the Authority and are intended to be 
imported for the purpose of clinical trial shall have a Clinical Trial Import License .  
 
This is in accordance to the Regulation 12(1)(c), CDCR 1984: “The Director of 
Pharmaceutical Services may, subject to the provisions of these Regulations, 
issue the following license  subject to such conditions as he may impose, a 
clinical trial import license  in Form 4 in the Schedule, authorizing the lic ensee to 
import any product for purposes of clinical trials, notwithstanding that the product 
is not a registered product ”. 
 
b) Clinical Trial Exemption (CTX) & Exemption for Manufacturing Sample for 
Registration  
i) Products which are not registered with the Aut hority and are intended to be 
manufactured locally for the purpose of clinical trial  shall require Clinical 
Trial Exemption (CTX) from the Director of Pharmaceutical Services; and  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
40 
 ii) Any person who wishes to manufacture any product solely for the purpose 
of producing a sample for registration  should apply for an exemption for 
manufacture of sample. (Applies to locally manufactured products only ). 
 
This is in accordance to the Regulation 15(5), CDCR 1984: “Any person who 
wishes to manufacture any product solely  for the purpose of producing samples 
for clinical trials, for registration or issuance of notification note under these 
Regulation may on application be exempted by the Director of Pharmaceutical 
Services from the provisions of regulation 7 (1) or regulat ion 18A”.  
 
 
For more information,  please refer  Regulation 15, CDCR 1984: Exemptions & 
Saving; and  Guidelines on Clinical Trial .  
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
41 
 1.2 CATEGORIES OF PRODUCT  
 
 
 
 
 
 
 
Medicinal products for  registration are classified under the following categories:  
 
 
1.2.1  NEW DRUG PRODUCTS  
 
New Drug Product s (NDP) is defined as any pharmaceutical product s that have 
not been previously registered in accordance with the provisions of the CDCR 
1984.  
 
An NDP may be classified according to the following categories:  
 
a) New Chemical Entity  (NCE) / Radiopharmaceutical Substance  
 
A new pharmaceutical product containing any of the following:  
 
i. New Chemical Entity  (NCE)  
Defined as an active moiety that has not been regis tered in any 
pharmaceutical product.  
 
ii. Radiopharmaceutical substance  
Defined as a radionucleotide, ligand or the coupling mechanism to 
link the molecule and the radionucleotide that has not been 
registered in any pharmaceutical product.  
 
b) New Combination Pro duct 
 
A new pharmaceutical product containing two or more drugs that are 
physically, chemically or otherwise combined or mixed and produced 
as a single pharmaceutical product, in a combination that has not been Note:  
Before submission of application for a product registration, applicants may 
submit for product classification  if unsure of the product category.   Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
42 
 registered in any other pharmaceutical produc t. This includes any of 
the following:  
 
i. Combination of New Chemical Entities;  
 
ii. Combination of registered chemical entity(s) AND  New Chemical 
Entity(s);  
 
iii. Combination of registered chemical entities;  
 
iv. Combination of registered chemical entities in a new chem ical 
forms;  
 
v. Combination of registered chemical entity(s) in new chemical 
form(s) AND  New Chemical Entity(s);  
 
vi. Combination of registered chemical entity(s) in new chemical 
form(s) AND  registered chemical entity(s).  
 
c) Supplemental Product  
 
A new pharmaceuti cal product containing a drug that has been 
previously registered as a pharmaceutical product but differing in 
properties with regards to safety and/or efficacy from the product that 
has been previously registered.  
 
This includes any of the following:  
 
i. Registered chemical entity in a new chemical form;  
 
ii. Registered chemical entity in a new dosage form;  
 
iii. Registered chemical entity in a new dosage strength with a change 
in dosing/ posology;  
 
iv. Registered chemical entity for use by a new route of administration;  
 
v. Registered chemical entity for new indication(s), dosage 
recommendation(s) and/or patient population(s).  
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
43 
 1.2.2  BIOLOGICS  
 
1. Definition:  
 
The term ‘biopharmaceutical’ was coined in the 80’s to define proteins that were 
made by recombinant DNA technology [ which includes hybridoma technology for 
monoclonal antibody (mAb) production] . 
 
1.1 Biologic/ Biological product refers to a product whose active substance is 
made by or derived from a living organism (plant, human, animal or 
microorganism) and may be produced  by biotechnology methods and 
other cutting -edge technologies.   This product imitates natural biological 
substances in our bodies such as hormones, enzymes or antibodies.  
 
1.2 Biological substance is defined as a substance that is produced by or 
extracted fro m a biological source and that needs, for its characterization 
and the determination of its quality , a combination of physicochemical -
biological testing together with the production process and its controls.  
 
1.3 Biopharmaceuticals/ Biologics/ Biological produ cts can also be defined as:  
 
“a protein (including antibodies) or nucleic acid -based pharmaceuticals 
used for therapeutic, which is produced by means other than direct 
extraction from a native (non -engineered) biological source”.   This 
corresponds to the n ew biotechnology view (that is, by elimination, it is 
largely restricted to recombinant/ genetically engineered and mAb -based 
products) .  
 
1.4 The term ‘Biotechnology product’ and ‘Biological product’ are used to 
broadly refer to all biopharmaceuticals (by the  broad biotechnology view).  
 
Note:   
Today, biologics have become inextricably intertwined with biopharmaceuticals, 
to the point where they are synonymous.   The general consensus is that the term  
‘Biologic’ and ‘Biopharmaceutical’ are in terchangeable .  
 
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
44 
 Biologics include a wide range of products such as:  vaccines , blood products , 
monoclonal antibodies (therapeutics) , recombinant proteins  (including but not 
limited to insulins, hormones, erythropoetins and other hematopoietic factors), 
cytokines (including  but not limited to interferons, interleukins, colony -stimulating 
factors, tumour necrosis factors), cell and gene therapy products (CGTPs).  
 
But does not include:  
 
• Metabolites from microorganisms; e.g . antibiotics and some 
hormones;  
• Macromolecules produce d by chemical synthesis; e.g . peptides/ oligo -
nucleotides  produced by chemical synthesis;  
• Whole blood or cellular blood components.  
 
2. For detail on registration of Biologics products, please refer Appendix 3:  
Guideline on Registration of Biologics.  
 
Note:   This document  is not intended to apply  on the control of genetically 
modified live organisms designed to be used directly in humans, e.g. live 
vaccines  
 
3. Unlike small -molecule generic drugs, exact copies of biolo gics are 
impossible to produce because these are large and highly complex molecules 
produced in living cells.  A ‘biosimilar’medicinal product (a short designation for 
‘similar biological medicinal product’) is considered as a new biological medicinal 
product developed to be similar in terms of quality, safety and efficacy to an 
already registered, well established, medicinal product.  For details, please refer 
to Guideline on Registration for  Biosimilars in Malaysia.  
 
4. Cell and gene therapy products (CGTPs) is regulated as Biologic 
products.  Unlike biotechnology products which are mostly purified proteins of  
cells, CGTPs contain living and functional cells.  Therefore, CGTP is regulated 
under a separate framework.  For details, please refer to: Guidance Document 
and Guidelines For Registratio n of Cell and Gene Therapy (CGTPs).  
This document provides information for manufacturers, applicants, healthcare 
professionals and the general public on legal arrangements in Malaysia for the 
registration of CGTPs.  The implementation of the guideline wil l be compulsory 
on 1 January 2021 as stated in the Directive No. 6 Year 2017.  Ref: 
BPFK/PPP/07/25(11)Jld.1:  Direktif Untuk Menguatkuasakan Penggu naan 
Guidance Document And Guideline For Registration Of Cell And Gene Therapy Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
45 
 Products (CGTPs), December 2015  Dan Good Tissue Practice Guideline, 2ND 
Edition, December 2015).  
  
1.2.3  GENERICS  
 
A generic product is a product that is essentially similar to a currently                                 
registered product in Malaysia. However, the  term generic is not applicable to 
Biologics.  
 
Generics  may be further classified into two groups:  
 
1. Scheduled Poison  
(Known as Controlled Medicine/ Controlled Poison)  
 
Products containing poisons as listed  in the First Schedule  under Poisons Act 
1952 . 
 
2. Non-scheduled Poison  
(Known as Non -Poison or “Over -the-Counter”, OTC)  
 
Product s conta ining active ingredients which are  not listed  in the First Schedule 
under Poisons Act 1952 ; and is excluding active ingredient which is categori zed 
under health supplement s or natural product s or cosmetic s. 
 
1.2.4  HEALTH SUPPLEMENTS  
 
A Health Supplement (HS) means any product that is used to supplement a diet 
and to maintain, enhance and improve the health function of human body. It is 
presented i n small unit dosage forms (to be administered) such as capsules, 
tablets, powder, liquids and shall not include any sterile preparations (i.e. 
injectable s, eyedrops). It may contain one or more, or the following combination:  
 
i) Vitamins, minerals, amino acid s, fatty acids, enzymes, probiotics, and 
other bioactive substances ; 
ii) Substances derived from *natural sources, including animal, mineral and 
botanical materials in the forms of extracts, isolates, concentrates, 
metabolite ; Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
46 
 iii) Synthetic sources of ingredients mentioned in (i) and (ii) may only be used 
where the safety of these has been proven . 
 
For details, please refer to  Appendix 4:  Guidelines for Registration of Health 
Supplements  
 
1.2.5  NATURAL PRODUCTS  
 
a) Traditiona l medicine  (as defined under the Control of Drugs and Cosmetics 
Regulations 1984) : 
Any product used in the practice of indigenous medicine, in which the drug  
consist solely of one or more naturally occurring substances of a plant, animal 
or mineral, of par ts thereof, in the unextracted or crude extract form, and a 
homeopathic medicine.  It shall not include any sterile preparation, vaccines, 
any substance derived human parts, any isolated and characterized chemical 
substances.  
 
b) Finished Herbal Product  
Finis hed herbal products consist of herbal preparations made from one or 
more herbs. If more than one herb is used, the term “mixture herbal product” 
can also be used. Finished herbal products and mixture herbal products may 
contain excipients in addition to th e active ingredients. However, finished 
products or mixture herbal products to which chemically defined active 
substance have been added, including synthetic compounds and/ isolated 
constituents from herbal materials, are not considered to be herbal.  
 
c) Herb al Remedy  
Any drug consisting of a substance or a mixture of substances produced by 
drying, crushing or comminuting, but without subjecting to any other process, 
a natural substance or substances of plant, animal or mineral origin, or any 
part of such subs tance or substances.  
 
d) Homeopathic Medicine  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
47 
 Any pharmaceutical dosage form used in the homeopathic therapeutic system 
in which diseases are treated by the use of minute amounts as of such 
substances which are capable of producing in healthy persons symptoms  
similar to those of the disease being treated.  
 
For details, please refer t o Appendix 5:  Guidelines for Registration of Natural 
Products  
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
48 
 1.3 FOOD - DRUG INTERPHASE PRODUCTS   
 
This guide serves to assist in deter mining if a product is to be regulated by the National 
Pharmaceutical Regulatory Division  (NPRA ) or by the Food Safety and Quality Division 
(FSQD) of the Ministry of Health Malaysia.  
 
1.3.1 INTRODUCTION  
 
Malaysians are now more health conscious and there  is generally greater awareness of 
the importance of nutrition to overall well -being. In recent years, many consumers also 
rely on a variety of “dietary supplements” to improve their health. These diverse 
products are freely available through a myriad of o utlets. A variety of products are 
available in the market, supposedly for the maintenance, prevention and even treatment 
of chronic diseases. These products may range from foods modified to have special 
properties or pure forms of vitamins and minerals to extract of various botanical or 
animal products.  
 
It is important to monitor and regulate the marketing and sale of these products 
so as to protect the interest and health of the consumer. Some of these products are not 
clearly defined as “food” or “drugs ” but are freely marketed. Such products include a 
variety of so -called health products and have been termed as “food -drug interphase 
(FDI) products”.  
 
In order to better define and regulate the FDI products, both the NPRA and the 
FSQD, Ministry of Health Malaysia formed the Committee for the Classification of Food -
Drug Interphase Products in 2000. The main Terms of Reference of the Committee is to 
assist both Divisions in classifying, in a consistent manner, an application from the 
industry which is not cl early defined either as a food or drug product. The Committee 
also serves as a platform in strengthening and updating the relevant regulations as well 
as to provide scientific input on these products.  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
49 
 1.3.2  DEFINITION OF FDI PRODUCTS  
 
Generally FDI produc ts are products with  combination of food ingredients and active 
ingredients for oral consumption.   Examples of food ingredients are fruit, vegetables, 
meat, poultry, milk, cocoa and cereal. Examples of active ingredients  are vitamins, 
minerals, herbs, enzy mes, probiotics, prebiotics, amino acids, peptides, coral calcium, 
fatty acids, collagen, chia seed, astaxanthin, lutein and other ingredients that are not 
traditionally consumed as food . FDI products may be presented in the form of powder, 
liquid, semisol id forms such as gel/jelly, chewable tablet, drops, granule etc.  
 
Such products as below are not categorized as FDI products due to its presentation and 
function:  
 
A. FOOD PRODUCTS THAT ARE NOT CATEGORIZED AS FDI 
PRODUCTS AND REGULATED BY FSQD INCLUDE :  
 
1. 100% food ingredients.  
 
2. Food products with or without  active ingredients (eg; herbs, vitamins, minerals, 
etc) as below:  
i) Instant drink products containing sugar and creamer (e.g. premix coffee, 
tea, chocolate, soy, cereal).   
ii) Meat essence products (liquid)  (e.g. chicken essence, ostrich essence, 
duck essence, fish essence etc.)  
iii) Ready to drink products (beverages) without dosing instruction in cheered 
pack/ canned / packet drinks.  
iv) Cordial products with recommended dilution ratio (e.g. dates cordial, grape 
cordial)  
v) Vinegar products (liquid) (e.g. apple vinegar, dates vinegar etc.)  
vi) Honey products (liquid).  
   
3. Isotonic drink products, sport nutrition products and special purpose food 
products.  
 
4. Products in conventional food form e.g. biscuit, cake, confectioner y, 
candy/sweet, gummy, noodle.  
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
50 
 5. Products used for cooking and food preparation (e.g. cooking oil (olive oil, 
coconut oil, sunflower oil), herbs and spices).  
 
6. Herbs and spices in crude form without medicinal/health claim.   
 
 
B. PRODUCTS THAT ARE NOT CATEG ORIZED AS FDI PRODUCTS AND 
REGULATED BY NPRA INCLUDE :   
 
1. Products containing active ingredient(s) with or without excipient ; or  
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
2. Products containing specific active ingredients which possess high 
pharmacological or therapeutic potencies. Examples of t he ingredients are 
paracetamol, glucosamine, tranexamic acid, aspirin, substances listed in Poisons 
Act 1952 ; or  
 
3. Products containing specific active ingredients which possess dose -related 
therapeutic potencies such as:  
• Plant sterols/ stanols and esters t hat are consumed ≥ 3.5g/day  
• Psyllium husk that are consumed ≥ 3.5g/day  
• Products containing senna ≥ 0.5g ; or  
 
4. Products in pharmaceutical dosage form such as soft gel, capsule or tablet (that 
is to be directly swallowed), sublingual, buccal, spray into the mouth, etc.  
 
1.3.3  CLASSIFICATION FOR FDI PRODUCTS  
 
It is important to determine the category of a product that falls within the food -drug 
interphase (FDI) whether the products are regulated as drug (under the NPRA’s 
purview) or, as food (under the FSQ’s p urview) because different regulatory 
requirements apply.  
 
The classification of FDI products are based on criteria, as outlined below:  
 
a) Main criteria  
  
i) Negative List For FDI as listed in Table 1: Negative List For FDI : 
 
- FDI products containing ingredient( s) from Negative List for FDI shall be 
regulated by NPRA ; or  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
51 
  
ii) Medicinal/ health claim refer to the term “medicinal purpose” as 
stipulated in the Sales of Drug Act 1952, Section 2:  
 
- FDI products not containing ingredient(s) from Negative List For FDI and 
with medicinal/ health claim shall be regulated by NPRA ; or  
 
- FDI products not containing ingredient(s) from Negative List For FDI and 
without medicinal/ health claim shall be regulated by FSQD.  
 
 iii)  Products intended to be used or capable, or purported  or claimed to be  
       capable for a medicinal purpose (e.g. products used for the health  
       benefit of eyes, body weight control, gastrointestine, brain, etc.)  shall be 
       regulated by NPRA.  
 
 
b) Other criteria  
 
- When there is greater uncertainty regarding the safety of a FDI product, 
such shall be regulated by NPRA. This is to enable closer monitoring of 
such products, so as to safeguard the health of the  consumer.  
 
Reference : Pekeliling Kriteria Baru Pengkelasan Produk (07 August 
2014)    
 Circular No. (19)dlm.BPFK/PPP/01/03 Jld.3 )   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
52 
 1.3.3.1  NEGATIVE LIST FOR FDI  
 
Table 1: Negative List For F DI  
 
No. Ingredient  Common/Other name  
1 Actaea racemosa  Black Cohosh, Cimicifuga racemosa  
2 Antiaris toxicaria (Pers.) Lesch.  Bark cloth tree, antiaris, false iroko, 
false mvule, upas tree  
3 Artemisia Spp. (all species)  Wormwood, Mugwort  
4 Aspidosperm a Quebracho -Blanco 
Schltdl  Kebrako, White Quebracho  
5 Atropa Spp. (all species)  Antropa belladonna (deadly 
nightshade)  
6 Azadirachta indica  Nimba, Neem  
7 Bile  
8 Brucea javanica, Brucea amarissima  Sumatrana amarissimus, Java brucea  
9 Bufo gargarizans Cantor, Bufo 
melanostictus Schneider, Bufo 
vulgaris Lour  Toad, Samsu, kodok, kerok  
10 Calotropis Spp. (all species)  Apple of Sodom, Crown flower  
11 Cannabis Spp. (all species)  Marijuana, Hemp  
12 Catharanthus Spp. (all species)  Periwinkle  
13 Chelidonium  majus  Celandine, Great Celandine, 
Nipplewort  
14 Chondodendron Spp. (all species)   
15 Claviceps Spp. (all species)  Ergot  
16 Colchicum Spp. (all species)  Autumn crocus, Meadow saffron, 
Naked lady  Drug Registration Guidance Document (DRGD)  
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Second Edition, September 2016, Revised July 2018  
 
53 
 17 Conium maculatum  Hemlock  
18 Coptis chinensis, Coptis teeta  Chinese Goldthread  
19 Croton tiglium L.  Croton  
20 Datura spp. (all species)  Jimson weed, Devil’s apple, Green 
Dragon, Zombie’s Cucumber, Moon 
Weed, Trumpet Lily, Stinkweed  
21 Digitalis spp.(all species)   
22 Dioscorea Hispida   
23 Dryobalanops lan ceolata Burck  Borneo camphor, Kapur, Malay 
Camphor, Sumatra camphor  
24 Dryopteris Spp. (all species)  Mountain woodfern, Spinulose 
woodfern, Spreading woodfern, Fancy 
fern 
25 Euphorbia Spp. (all species)  Spurge  
26 Fritillaria spp.  Fritillary Bulb  
27 Gam ma-amino Butyric Acid (GABA)   
28 Garcinia Morella Desr.  Gamboge  
29 Gelsemium semperi virens  Palaung Thay  
30 Glucosamine   
31 Glutathione   
32 Gypsum Fibrosum   
33 Hyaluronic acid   
34 Hyoscyamus Spp. (all species)   
35 Hypericum perforatum  St. John’s Wo rt 
36 Juniperus sabina  Savin, Savine  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
54 
  
37 Mahonia aquifolium, Mahonia repens, 
Mahonia nervosa  Mahonia Aquifolium: Oregon Grape, 
Mountain Grape, Barberry. Mahonia 
Repens: Creeping Barberry, Creeping 
Mahonia, Creeping Oregon -Grape  
38 Melanorrhoea usitata  Wall.  Vanish tree  
39 Monascus purpureus  Red yeast rice  
40 Mucuna pruriens  Cowhage, Cowage  
41 Mylabris phalerata, Mylabris cichorii  Blister beatle, Mylabris  
42 Natto extract  Fermented soy bean extract  
43 Nerium indicum  Indian oleander, Exile Tree . 
44 Nerium oleander  Indian oleander, Exile Tree.  
45 Pearl   
46 Phellodendron amurense, 
Phellodendron chinense  Amur Cork tree  
47 Placenta   
48 Plumbago indica  Rose -coloured leadwort  
49 Plumbago zeylanica  White leadwort  
50 Psilocybe cubensis  Boome rs, Gold caps  
51 Rauvolfia Spp. (all species)   
52 Resveratrol   
53 Sanguinaria canadensis  Bloodroot, Indian Paint  
54 Scilla sinensis   
55 Simmondsia Chinesis  Jojoba  
56 Sophora tomentosa  Sea coast Laburnum, Silver Bush  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
55 
 57 Spigelia marilandica  Worm g rass, Pinkroot  
58 Stichopus spp.  Gamat  
59 Strophanthus spp.(all species)  Kombe  
60 Strychnos ignatii, Strychnos lucida, 
Strychnos roberans  Nux-vomica  
61 Symphytum peregrinum  Comfrey  
 
Notes:  
 
This list :  
• is a compilation by the FDI committee.  
• is not  meant to be exhaustive and will be reviewed from time to time.  
• shall be read in conjunction with the current laws and regulations together with 
other relevant legislations, where applicable, governing pharmaceutical and 
natural products for human use in M alaysia  
 
Notes:  
Applicant may verify on FDI product classification with NPRA in order to determine 
whether the product shall be registered by the Authority or otherwise by seeking 
classification service from NPRA ( http://npra.moh.gov.my/index.php/application -forms ). 
 
Reference Circular: Bil.(97)dlm.BPFK/PPP/01/03 Jld. 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
56 
 1.3.3.2  GENERAL CLASSIFICATION FLOWCHART OF FOOD -DRUG 
INTERPHASE (FDI) UNDER FOOD OR DRUG  
 
• It is important to determine the category of a product that falls within the food -drug 
interphase (FDI) whether the products are regulated as drug (he alth supplement or 
natural product under the NPRA’s purview) or, as food (under the FSQ’s purview) 
because different regulatory requirements apply. Therefore, the following flowchart 
serves only as guide to help you determine the category of the product th at falls within 
the FDI.  
• Should you have any doubt or uncertainty pertaining to the category of your product, you 
may contact the relevant regulatory agencies for clarification, or seek classification 
service from the NPRA by submitting a classification a pplication.  
• Please take note that you are encouraged to familiarize yourself with the governing 
legislations and other regulatory requirements and guidelines that apply to your product 
before using this guide.   
 
Note:   ** NPRA reserves the right to use it s discretion to make decision if issue of subjectivity arises.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 1. Product Formulation  
 
Does the product contain any substance  / 
ingredient from the Negative List f or FDI ? 
 
Important Note:  Substances listed in the List of 
Prohibited/ Banned Substances of DRGD are 
NOT PERMITTED for use in any product that 
falls within the FDI.  
 
3.  ** Product Presentation  
 
Does the product label artwork imply any 
medicinal purpose  and/or packaged in any 
form of packaging which resembles the 
packing of drug pro duct (e.g. blister pack) ? 
 2.  ** Medicinal/Health Claim  
 
Is the product indicat ed for medicinal purpose, 
or does the product label/packaging contain 
any statement that indicates or implies any 
medicinal purpose (e.g. body weight control; 
for the health benefit of eyes specific human 
organs/ systems, such as gastro -intestine 
and/or br ain)?  
NO NO YES Product that falls 
within the FDI  
Drug  1. Product 
Formulation  
 
3. Product 
Presentation  
 YES NO 
YES 
Food  Drug  
 
Drug  
 2. Medicinal/ 
Health Claim  
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Second Edition, September 2016, Revised July 2018  
 
57 
 1.3.4  ADDITIONAL NOTES  
 
1. Substances listed in the prohibited/ banned ingredient list of the Drug 
Registration Guidance Document (DRGD) and Schedu le Poison shall not be 
permitted for use in any FDI products.  
2. Products categorized as a natural product are not allowed to contain creamer.  
3. Food products are not allowed to be packed in blister pack/ any other form of 
packaging which resembles the packing of drug product.  
4. Any foods or combination of foods that are regulated by FSQD shall not be in 
pharmaceutical dosage form, such products are advised to reformulate into a 
non-pharmaceutical dosage form.  
5. Products containing only ingredient(s) such as rosell e, jasmine, rose, chamomile, 
chrysanthemum flower, ginger (rhizome), vanilla(stem), mint leaf, lemon peel and 
cinnamon bark (with/without C amelia sinensis ) will be regulated by FSQD.  
6. Fruit ingredients that are not commonly consumed as food in Malaysia wil l be 
considered as active ingredient.  
 
  Drug Registration Guidance Document (DRGD)  
National  Pharmaceutical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, September 2016, Revised July 2018  
 
58 
 Legend :  1.3.5 PICTORIAL GUIDE TO CLASSIFICATION OF FOOD OR DRUG PRODUCTS  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Regulated by FSQD  
 Regulated by NPRA  
 Classification of FDI 
under food or drug  
DRUG  FOOD  
1.   100% food ingredients  
2.    Food products with or witho ut active ingredients  
       as bel ow; 
 i)    Instant drink p roducts containing sugar and/or  
  creamer (e.g. premix coffee, tea, chocolate, soy,   
             cereal)  
 ii)    Meat essence products (liquid) (e.g. chicken  
  essence, ostrich essence, duck essence, fish   
  essence and etc. ) 
 iii)  Ready to drink pr oducts (beverages) without dose 
  instruction in cheered pack/ can ned /packet drinks  
 iv)  Cordial products with recommended dilution ratio 
  (e.g. dates cordial, grape cordial)  
 v)   Vinegar products (liquid) (e.g. apple vinegar,  
  dates vinegar and etc.)  
 vi)  Honey products (liquid)    
3.    Isotonic drink products, sport nutrition products  
       and special purpose food products  
4.    Products in conventional food form e.g. biscuit,  
       cake, confectionery, candy/sweet, gummy, noodle  
5.    Products used for cooking and food preparation  
       (e.g. cooking oil  (olive oil, coconut oil, sunflower  
       oil), herbs and spices ) 
6.    Herbs and spices in crude form without 
 medicinal/health claim   
Products not 
containing 
ingredient(s) from 
Negative List for FDI 
and withou t 
medicinal/ health 
claim.  
 1. Products containing 
ingre dient(s) from 
Negative List For  FDI 
 
2. Products not 
containing 
ingredien t(s) from 
Negative List For 
FDI and with 
medicinal  / health 
claim  
 
3. Products intended to 
be used or capable, or 
purported or claimed to 
be capable for a 
medic inal purpose.  
(e.g. products used for 
the health benefit of 
eyes, body weight 
control,  gastroi ntestine, 
brain, etc.)  1. Products as defined in the 
Regulation 2, CDCR 1984.  
 
2. Products containing 100% 
active ingredient(s) with or 
without exc ipient . 
 
3. Products containing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
specific active ingredients 
which possess high 
pharmacol ogical or 
therapeutic potencies.  (e.g. 
paracetamol, glucosamine, 
tranexamic acid, aspirin, 
substances listed in Poison s 
Act 1952 ). 
 
4. Products containing 
specific active ingredients 
which possess dose – 
related therapeutic 
potencies such as:      - 
Plant sterols/ stanols and 
esters that are consumed          
≥ 3.5g/day  
- Psyllium husk that are 
consumed ≥ 3.5g/day  
- Products containing senna      
≥ 0.5g  
 
5. Products in 
pharmaceutical dosage 
form  such as soft gel, 
capsule or tablet (that is to 
be directly sw allowed), 
sublingual, buccal, spray into 
the mouth, etc.  
 
 PRODUCT  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 59  1.4 MEDICAL DEVI CE - DRUG  - COSMETIC  INTERPHAS E 
PRODUCTS  
 
1.4.1  INTRODUCTION  
 
Medical Device -Drug -Cosmetic Interphase (MDDCI) Products are those products that are 
not clearly defined as a medical device or drug/cosmetic in accordance to the Medical 
Device Act 737 , Control  of Drugs and Cosmetics Regulations 1984 and Sale of Drugs Act 
1952.  
 
Registration of drug products / notification of cosmetics  that has been classified must follow  
the requirements  that have been set forth as follows:  
 
a) Drugs & Cosmetics  – The registration / notification regulated by the NPRA  is in 
accordance with  the requirements  set forth in the  Poisons Act  1952  and its 
Regulations,  Sales of  Drugs  Act 1952  and the Control of Drugs  and Cosmetics 
Regulations 1984 ; 
b) Medical Device  – The registration regulated by Medical Device Authority  is in 
accordance with  the requirements  set forth in  the Medical Devices Act  2012 (Act 
737). 
Combination products i ncludes:  
i) A product comprised of two or more regulated components, i.e., drug/device, 
biological/device, or drug /device/biological, that are physically, chemically, or otherwise 
combined or mixed and produced as a single entity;  
ii) Two or more separate products packaged together in a single package or as a unit and 
comprised of drug and device products, device and biological products.  
 
For Interphase  Product and Combination Product (Device -Drug or Drug -Device),  it will be 
regulated according to the classification that has been made and by the relevant agencies.  
 
Please refer  ; 
(i) Directive No. 4 Year 2017 , Ref. (9) dlm.BPFK/PPP/07/25 Jld. 1 : DIREKTIF 
KUATKUASA PEMAKAIAN GUIDELINE FOR REGISTRATION OF DRUG -MEDICAL 
DEVICE AND MEDICAL DEVICE -DRUG COMBINATI ON PRODUCTS  
(ii) Guideline For Regis tration Of Drug -Medical Device a nd Medical Device -Drug 
Combination Products  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 60  1.4.2  CLASSIFICATION CRITERIA  
 
The following may be used as criteria to assist in the classification of products:  
a) The primary intended purpose of the product;  
b) The primary mode of action/ the principal mechanism of action by which the claimed 
effect or purpose of the product is achieved;  
• Drug is based on pha rmacological, immunological or metabolic action in/on 
the body; but  
• Medical device does not achieve its primary mode of action in or on the 
human body by pharmacological, immunological or metabolic means, but may be 
assisted in its intended function by suc h means. ;  
c) Active ingredient, indication and pharmaceutical dosage form (these are the main 
criteria for classification of the drugs);  
d) Classification of the products in reference countries.  
 
For classification of MDDCI products and combination products as decided by the 
committee, please refer to Table III . It shall be used as guidance for classification  only.  
 
Applicant shall verify on MDDCI product classification with NPRA  in order to determine 
whether the product shall be registered by the Authority or o therwise.  
 
Table III: SUMMARY OF MED ICAL DEVICE -DRUG -COSMETIC INTERPHASE  (MDDCI) 
PRODUCT CLASSIFICATION DECISION  
 
NO PRODUCT  INTENDED PURPOSE/ 
INDICATION AND MODE 
OF ACTION (MOA)  CATEGORY  CUSTODI
AN 
DIVISION  
1.  Aqueous Cream 
Product  As an emollient cream wi th 
moisturizing properties to 
promote healing and relief to 
the symptoms of skin 
dryness,  impaired barrier 
function, skin problems/ 
diseases.  OTC DRUG  NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 61  2. Blood bag 
containing 
anticoagulant/ 
preservation agent  To collect and preserve blood 
and its co mponents (for use 
with cytapheresis device 
only)  
 
NOTE :  
It is not for direct intravenous 
infusion.  MEDICAL 
DEVICE   
MDA  
3. Catheter Lock/ Flush 
Solutions  
(eg. heparinised 
saline, sodium citrate 
solution)  As an anticoagulant for use 
as a catheter lock / f lush 
solution for flushing off 
catheters and cannulas to 
maintain catheter/ cannula 
patency and to prevent 
coagulation of blood or 
infection in the cathether.  
 
NOTE :  
- It is not indicated for 
therapeutic use.  
- Contraindicated for direct 
systemic administ ration.  MEDICAL 
DEVICE  
  
MDA  
4. Collagen Hemostatic 
Agents (fibrillar or 
soft, pliable 
pad/sponge or loose 
fibres)  A sterile, bioabsorbable 
device derived from animal 
collagen (e.g., bovine or 
porcine collagen) designed to 
produce a rapid haemostasis 
through platelet 
activation/aggregation (which 
initiates the haemostatic 
cascade leading to a fibrin 
clot) during a surgical 
procedure. It is applied 
directly to the wound where it 
remains to be absorbed by 
the body; it is not dedicated 
to a specific 
anatomy/a pplication and 
does not contain an 
antimicrobial agent  
 MEDICAL 
DEVICE   
MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 62  5. Dental Products  
 i. Fluoride dental 
preparations  
    (eg. toothpaste, 
tooth powder, 
mouthwash , dental 
varnish ) a. To maintain oral 
hygiene.  COSMETIC  
(If 
concentration 
of fluoride 
≤1500ppm)  NPRA  
b. To maintain oral 
hygiene and prevent 
oral diseases.  DRUG  
(If 
concentration 
of fluoride is 
>1500ppm)  NPRA  
c. A liquid substance 
used for the protection 
of pulpal tissue and to 
provide a marginal 
seal to newly placed 
amalgam restorations. 
A thin coating of this 
solution is applied over 
the tooth’s surfaces 
before placement of 
restorations. It is used 
as a protective agent 
for the tooth against 
constituents of 
restorative materials. 
After application, this 
device  cannot be 
reused.  MEDICAL 
DEVICE   
MDA  
 
 
 
d. As a desensitizing 
agent for the treatment 
of hypersensitive teeth, 
for sealing the dentinal 
tubules for cavity 
preparations or on 
sensitive root surfaces 
or to line cavity 
preparations under 
amalgam restoration s. MEDICAL 
DEVICE  MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 63   ii. Root canal filling 
incorporating 
antibiotic  
 To seal the canal and 
disinfect the dentinal walls 
by diffusing through 
dentine. The antibiotic 
provides ancillary actions 
as bactericidal antibiotic 
and anti -inflammatory 
agent to assist  in reducing 
pain and in maintaining a 
bacteria -free environment 
within the root canal.  Device -Drug 
combination 
product 
regulated as 
MEDICAL 
DEVICE  MDA  
6. Dialysis Products  
i. Peritoneal 
dialysis 
dialysate  It is used for the exchange 
of solutes across the 
peritoneum of the patient 
(in this case, used as a 
semi -permeable 
membrane)  DRUG  
 NPRA  
ii. Haemofiltration 
solution  It is used for the exchange 
of solutes with blood 
through a system of 
extracorporeal filters.  DRUG  NPRA  
iii. Haemodialysis 
dialysate   
 It is used  for the exchange 
of solutes with blood 
through a semi -permeable 
membrane in the dialyser 
of a haemodialysis system.  MEDICAL 
DEVICE  MDA  
iv. Haemodiafiltrati
on solution  It is used as a replacement 
solution in 
haemodiafiltration.  
NOTE  :  
Haemodiafiltration is  the 
combination of 
haemodialysis and 
haemofiltration performed 
either simultaneously or 
sequentially.  DRUG  NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 64  7. Drug -Eluting Beads  
(Produced from 
biocompatible polyvinyl 
alcohol hydrogel  
modified with sulphonate 
groups  in phosphate 
buffered saline.)  
 It is an embolic agent 
which is intended to be 
loaded with a 
chemotherapy agent, eg. 
doxorubicin for the purpose 
of treatment of malignant 
hypervascularised 
tumour(s) by embolisation 
of vessels and occlusion of 
blood flow supplying 
malignant 
hypervasculari sed 
tumour(s) and as a 
secondary action, 
delivers/elutes a local, 
controlled, sustained dose 
of the chemotherapy agent 
directly to the tumour(s).  If the beads 
are sold 
separately 
from the drug, 
it will be 
classified as 
MEDICAL 
DEVICE  
 
If the beads 
and drug  are 
packaged and 
sold together, 
it will be 
classified as 
Drug -device 
combination 
product 
regulated as 
DRUG   
MDA/NPRA  
8. Drug -Eluting Stents 
(DES)  For use in angioplasty or 
coronary stenting 
procedures.  Device -Drug 
combination 
product 
regulated as 
MEDICAL  
DEVICE  MDA  
9. Drug - Delivery 
Products Regulated as 
Drug Products  
(eg. insulin prefilled pen/ 
syringes, asthma 
inhalers, intrauterine 
contraceptives whose 
primary purpose is to 
release progestogens)  
 To administer  
pharmacologically active 
substance  Drug -device 
combination 
product 
regulated as 
DRUG  
 
NOTE:  
The device 
component will 
be regulated 
on a case to 
case basis.  
 NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 65  10. Enteral Feeding Kit 
(containing Iodine Pack 
drug)  A collection of sterile 
devices that includes 
tubing and other materials 
inten ded to administer 
nutrient liquids directly into 
the stomach, duodenum, 
or jejunum of a patient by 
means of gravity or an 
enteral pump.  Device -Drug 
combination 
product 
regulated as 
MEDICAL 
DEVICE  MDA  
11. Eye Products  
i. Eye/ ocular 
lubricants, 
including 
artificial tears  
 
 
 A sterile substance used to 
provide supplemental 
lubrication/hydration/ 
moisturization to the eyes 
to treat/ alleviate 
symptoms of soreness, 
burning, irritation and 
discomfort caused by dry, 
tired, and/or strained eyes 
resulting from dry  eye 
syndrome, ageing/ 
hormone changes 
(menopause), or 
environmental factors (e.g., 
pollution, dust, heat, 
smoke and air 
conditioning).  MEDICAL 
DEVICE  
(If it contains 
an active 
substance with 
pharmacologic
al, 
immunological 
or metabolic 
primary mode 
of acti on, it will 
be classified 
as DRUG ) MDA  
ii. Aqueous/vitreou
s humour 
replacement 
medium  It is used to assist in 
performing ophthalmic 
surgery, e.g., to maintain 
the shape of the eyeball 
during the intervention, 
preserve tissue integrity, 
protect from surgical 
trauma, or to function as a 
tamponade during retinal 
reattachment.  MEDICAL 
DEVICE  MDA  
iii. Cold Sensation 
Eye Pillow  To reduce fatigue from 
work stress or lack of 
sleep.  MEDICAL 
DEVICE  MDA  
12. General Purpose To isolate a site of surgical  MEDICAL MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 66  Surgical or Barrier 
Drapes  
(A sterile protective  
covering made of natural 
or synthetic materials, or 
both.)  incision or a surgical  field 
from contamination (e.g., 
microbial, substance) in 
various clinical settings 
(e.g., in an operating room 
or catheterization 
laboratory). The device 
may also be used to 
protect a patient from 
heat/flame during a 
surgical  procedure. This is 
a reusable or single use 
device.  DEVICE  
(If it 
incorporates 
an ancillary 
pharmacologic
ally active 
substance, it 
will be 
classified as 
Device -Drug 
combination 
product 
regulated as 
MEDICAL 
DEVICE)  
13. General -body orifice  
lubricant  
 Lubricant intended to 
facilitate entry of a 
diagnostic or therapeutic 
device into a body orifice 
by reducing friction 
between the device and 
the body;  
Lubricant duri ng 
catherisation, 
probing,endoscopy, 
changing fistula 
catheters,intubation,and 
prevention of iatrogenic 
injuries to the rectum and 
colon.  
E.g ancillary local 
anaesthetic: lidocaine   
MEDICAL 
DEVICE  
 
(If it 
incorporates 
an ancillary 
pharmacologic
ally active 
substance, it 
will be 
classified as 
Device -Drug 
combination 
product 
regulated as 
MEDICAL 
DEVICE   
MDA  
 
 
 
14. Heat Pad/ Cooling Pad  To relief aches and pains.  MEDICAL 
DEVICE  MDA  
15. In vivo  diagnostic 
agents  a. For diagnostic 
purposes, eg. :  
- X-ray / MRI contr ast 
media  
- NMR enhancing 
agents  
- Opthalmic 
diagnostic agents, DRUG  
 NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 67  eg. staining agent 
such as fluorescent 
ophthalmic strips for 
diagnostic purposes  
- Carrier solutions to 
stabilize 
microbubbles for 
ultrasound imaging  
- Radiopharmaceutic
als for diagnostic 
use eg 14C- Urea 
Capsule for H pylori 
test 
b. As Diagnostic Test Kit 
consist of drug and 
analyser  
 DRUG -
DEVICE 
combination 
product 
regulated as 
DRUG  
NOTE:  
The device 
component will 
be regulated 
on a case to 
case basis.  NPRA  
 
 
c. As diagnostic analyser 
only (without drug)  MEDICAL 
DEVICE  MDA  
16. Irrigation solutions   
 
 
 For mechanical cleansing 
and rinsing including those 
used in the eye such as for 
cleansing of the eye, body 
tissues, body cavities, 
wounds or irrigation of a 
special tube called a 
catheter w hich is used to 
drain the bladder.  
 MEDICAL 
DEVICE  
 
(If it contains a 
pharmacologic
ally active 
substance, it 
will be 
classified as 
DRUG ) MDA  
17. 
 Medical gases   
 a. To be used in 
anaesthesia and 
inhalation therapy, 
including their 
primary containers.  DRUG  
 NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 68  b. For in -vivo 
diagnostic purposes 
including lung 
function tests.  DRUG  
 NPRA  
18. Medicinal Patch  
 To relieve fatigue, body 
aches, joint pains;  
To regulate hormone 
imbalance  DRUG  
 NPRA  
19. Nail Anti -fungal 
Products  
(eg. pen applicator 
containing acet ic acid/ 
lactic acid)  
 Treatment of 
onychomycosis (fungal nail 
infection) by lowering the 
pH of the nail bed, thus 
creating a micro -
environment that is hostile 
to fungal growth.  
 
 MEDICAL 
DEVICE  MDA  
20. Nasal inhaler  
 A hand -held device 
designed to admini ster 
substances directly into the 
nares of a patient, to serve 
as a barrier against 
external influences by 
formation of a moisturizing 
film on the nasal mucosa .  MEDICAL 
DEVICE  MDA  
21. Oral care products  
 Artificial Saliva / Saliva 
Substitute/ 
Replacemen t 
 Solutions used to mimic 
and replace/substitute 
normal saliva in the 
symptomatic treatment of 
dry mouth (xerostomia). 
Generally contain 
viscosity -increasing 
agents, such as mucins or 
cellulose derivatives such 
as carmellose as well as 
electrolytes, inclu ding 
fluoride. They seldom 
relieve  
symptoms for more than 1 
or 2 hours and does not 
stimulate saliva production.  MEDICAL 
DEVICE  
  
MDA  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 69  22. Other topical antiseptics/ disinfectants  
 i. Swabs/ Wipes 
containing 
antiseptics/ 
disinfectants/ 
antimicrobial 
substa nces      
(eg. alcohol, 
chlorhexidine, 
iodine, cetrimide ) For use on human skin and 
intended to be used for a 
medical purpose, eg 
pre/post injection, wound 
cleaning etc.  DRUG  NPRA  
 ii. Preparations 
(including 
swabs/ wipes) 
containing 
antiseptics/ 
disinfectant s/ 
antimicrobial 
substances      
(eg. alcohol, 
chlorhexidine, 
iodine, cetrimide ) Intended for the 
disinfection of medical 
devices.  MEDICAL 
DEVICE  MDA  
23. Peeling/Exfoliator 
Products  
(eg. Products containing 
glycolic acid and 
salicylic acid)  
 
 To improve skin texture 
due to unaesthetic skin 
appearance caused by 
pigmentation, post acne 
scars, photo damage, etc.  
 
NOTE :  
The ingredient and 
intended use should 
comply with the Guidelines 
for Control of Cosmetic 
Products in Malaysia.  COSMETIC  
 NPRA  
24. Personal  Care Products  
 i. Personal 
Intimate Hygiene  
 a. For female/  male 
intimate hygiene   
NOTE  :  
The product should be 
rinsed off.  COSMETIC  
 NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 70  b. For symptomatic 
relief of vaginal 
irritation/ infections 
by changing the 
vaginal pH.  DRUG  
 NPRA  
 ii. Vaginal Douche  Vaginal douching is the 
process of intravaginal 
cleansing with a liquid 
solution for :  
- personal hygiene or 
aesthetic reasons  
- preventing or 
treating/managing vaginal 
infections  
- symptomatic relief of 
minor vaginal soreness, 
irritation, itching  
- cleansin g and 
deodorizing after 
menstruation  
- washing out vaginal 
medication, if so instructed 
by the physician  
- deodorizing and washing 
out the accumulations of 
normal secretions  
- removing contraceptive 
creams and jellies  
- cleansing the vaginal 
vault after s exual relations  
 
NOTE :  
- Douching is not 
recommended during 
pregnancy  
- A douch is to be used as 
a cleanser and it should 
not be used as a 
contraceptive  MEDICAL 
DEVICE  
(If it contains a 
pharmacologic
ally active 
substance, it 
may be 
classified as 
DRUG ) 
 MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 71   
 iii. Hand sanitizer  
(eg. gel, foam, 
liquid)  For general hand hygiene 
without therapeutic claims.  COSMETIC  
 NPRA  
 iv. Personal 
Intimate 
Lubricant  
 To use as a vaginal 
lubricant during the 
climaterium (pre -
menopause, menopause, 
post-menopause) and to 
treat i rritations in vaginal 
epithelium in cases of 
physiological decrease of 
lubrication and consequent 
increase in vaginal 
dryness.  MEDICAL 
DEVICE  
(If it contains a 
pharmacologic
ally active 
substance, it 
may be 
classified as 
DRUG ) 
 MDA  
25. Skin Barrier Product  
(eg. lotion, emulsion, 
ointment, cream)  
 a. To form a physical 
barrier between the 
skin and the 
environment to seal 
out moisture in 
order to promote 
healing and relief to 
the symptoms of 
skin dryness,  
impaired barrier 
function, skin 
problems/ diseases.  MEDIC AL 
DEVICE  
(If it contains a 
pharmacologic
ally active 
substance, it 
may be 
classified as 
DRUG ) 
  
MDA  
b. Soothe and prevent 
diaper rash 
discomfort.  DRUG  
 NPRA  
c. To maintain/ 
improve normal skin 
condition without 
any therapeutic 
claims.  COSMETIC  NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 72   
26. Soft tissue filler/ 
Dermal filler  To correct cutaneous 
contour deformities of the 
skin (e.g., moderate to 
severe facial wrinkles and 
folds such as nasolabial 
folds, scars), particularly in 
cases of aging or 
degenerative lesions.  
 MEDICAL 
DEVICE  
(If it 
incorporates 
an ancillary 
local 
anaesthetic eg. 
lidocaine, it will 
be classified 
as a Device -
Drug 
combination 
product 
regulated as  
MEDICAL 
DEVICE)   
MDA  
 
 
27. Synthetic fluid tissue 
reconstructive material  As a submucosal implant 
in the urinary tract for 
urinary incontinence or 
vesicoureteral reflux.  
 
It may also be injected into 
the vocal cords to treat the 
effects of paralysis, 
atrophy, or scarring. After 
application, this device 
cannot be reused.  
 MEDICAL 
DEVICE  
(If it 
incorporates 
an ancillary 
pharmacolog ic
ally active 
substance eg. 
local 
anaesthetic 
such as 
lidocaine, it will 
be classified 
as a Device -
Drug 
combination 
product 
regulated as  
MEDICAL 
DEVICE)  
28. Synovial joint 
replacement fluid    
(Joint lubricant)  To help cushion the joint, 
especially in ca ses of 
reduced endogenous 
synovial fluid viscosity from 
degenerative disease.  MEDICAL 
DEVICE   
MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 73  29. Wart Products  
(eg. pen applicator 
containing a caustic 
agent, cyryogenic kit 
with refrigerant)  a. Containing a caustic 
agent eg. 
trichloroacetic acid 
(TCA) that destroys 
warts by chemical 
coagulation of 
proteins.  
 
 DRUG  
 
NOTE :  
If a device 
component is 
present, it will 
be regulated 
on a case to 
case basis  NPRA  
  b. Cryotherapy which 
destroys warts by 
freezing them using a 
very cold substance 
eg. liquid nitrog en or 
refrigerant made from 
dimethyl ether and 
propane.  
 MEDICAL 
DEVICE  MDA  
30. Wound care/ treatment products  
 i. Comprising a 
matrix (eg. 
dressing, gauze, 
swabstick, 
plaster, sponge)  a. To administer a 
medicinal substance to 
the wound eg. 
antimicrobial/ 
antiseptic agent for the 
purpose of controlling 
infection .  
DRUG  
  
NPRA  
b. To provide a protective 
layer/barrier to the 
wound and prevent 
microbial penetration 
and create healing 
environment. It may 
incorporate an 
ancillary medicinal 
substance eg. 
antimicrobi al/ 
antiseptic agent.  MEDICAL 
DEVICE  MDA  
 
ii. Comprising a 
matrix, typically 
of living cells To facilitate the infiltration 
of native skin elements 
(e.g. fibroblasts, MEDICAL 
DEVICE  MDA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 74  (fibroblasts) 
and/or structural 
proteins  leukocytes, blood vessels) 
for skin regeneration.  
iii. Topical 
preparation  for 
application to a 
skin wound  
(e.g., abrasion, 
laceration, cut, 
ulcer)   To facilitate local 
haemostasis. It is available 
in various forms (e.g., gel, 
spray, powder, ointment, 
plaster/gauze pad) that can 
be applie d directly to the 
wound where it forms a 
seal of transparent layer.  MEDICAL 
DEVICE  MDA  
 
iv. Deep cavity 
wounds 
dressing for 
application to a 
surgical wound  To use as the wound 
covering material for deep 
body cavity to reduce the 
adhesion of surrounding 
tissues by applying to the 
surgical area  
  
 
MEDICAL 
DEVICE   
MDA  
v. Silver -
containing 
topical 
preparations for 
application to a 
skin wound  
(eg. silver 
nitrate/ silver 
sulfadiazine/ 
colloidal silver 
gel, cream)  
 To administer/ apply an 
antiseptic to wounds with 
mild to moderate exudates 
such as:  
- First and second degree 
burns  
- Traumatic wounds  
- Surgical wounds  
- Partial full thickness 
wounds  
- Grafted wounds and 
donor sites  
- Lacerations and 
abrasions  
  
 
 
DRUG   
 
NPRA  
 vi. Intravascular 
catheter 
securement 
device 
containing 
antimicrobial/ant
iseptic agent 
(e.g. 
chlorohexidine 
gluconate, CHG)  An intravascular catheter 
securement device is a 
device with an adhesive 
backing that is placed over 
a needle or catheter and is 
used to keep the hub of the 
needle or the catheter flat 
and s ecurely anchored to 
the skin. The antimicrobial 
agent provides ancillary 
antimicrobial activity to 
reduce skin colonization 
and catheter colonization, DEVICE -
DRUG  
combination  
product 
regulated  
as MEDICAL  
DEVICE  MDA  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 75  supress regrowth of 
microorganism’s, and 
reduce catheter -related 
bloodstream infections 
(CRBSI) in patien ts with 
central venous or arterial 
catheters.  
 
 
 
 
Note:  
- The above table is to be used as guidance for classification  only.  
- The registration/notification  of products  that have been classifie d must follow  the 
requirements  that have been set forth as follows:  
i- Drug & Cosmetic  – The registration/notification  is in accordance with  the 
requirements  set forth in the  Poisons Act  1952  and its Regulations,  Sale of  
Drugs  Act 1952  and the Control of Drug s and Cosmetics Regulations 1984 . 
ii- Medical Device  – The registration  is in accordance with  the requirements  set 
forth in  the Medical Devices Act  2012 (Act 737) . 
- Medical  Device  will be regulated  by MEDICAL DEVICE Authority.  
- Drug  & Cosmetic  will be regulated by the  NATIONAL PHARMACEUTICAL 
REGULATORY DIVISION , Ministry of Health Malaysia.  
- Drug  – Device Combination  Product  will be regulated according to  the classification  
that has been made and by the relevant agencies.  
Reference : Pekeliling Mengenai Pengkelasan Semula Produk -produk Daripada Kategori  
Ubat (Drug) Kepada Kategori Peranti P erubatan (Medical Device) (09 December 2014).  
Circular : Bil (21) dlm.BPFK/PPP/01/03 Jld. 3)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 76  GUIDANCE FOR THE CLASSIFICATION OF MEDICAL DEVICE -DRUG -COSMETIC INTERPHASE 
(MDDCI) PRODUCTS  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Legend:  
 
 Submission to MDA  
 Submission to NPRA  
 INTERPHASE  
(Refer Table III)  MEDICAL DEVICE  
As defined in Section 
2 of Medical Device 
Act 737  
 
No
 PRODUCT  
Product ca tegorised 
in Table III?  
 
Refer to NPRA  Refer to MDA with 
notification letter from 
NPRA  DRUG/  
COSMETIC  
As defined in 
Regulation 2, 
CDCR 1984  
 Categorised as 
medical device  Categorised as 
drug/cosmetic  
No
 
Yes Is it a drug/cosmetic based 
on notification letter?  NPRA  issues notification letter  Apply For Classification to NPRA  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 77  2. DATA EXC LUSIVITY  
Data exclusivity refers to protection of undisclosed, unpublished and non -public domain 
pharmaceutical test data, the origination of which involves a considerable effort, submitted 
as required to the Director of Pharmaceutical Services for the pur pose of scientific 
assessment in consideration of the:  
a) Quality, safety and efficacy of any new drug product containing a New Chemical Entity  
  
b) Safety and efficacy for a second indication of a registered drug product as a condition 
for registration of any n ew drug product containing a New Chemical Entity; or approval 
for a Second Indication of a registered drug product.  
For information pertaining to  Register of Data Exclusivity Granted in Malaysia, please refer : 
Register of Data Exclusivity Granted in Malaysia (New Drug) and Register of Data 
Exclusivity Granted in Malaysia (Second Indication)  
 
2.1  HOW TO APPLY  
 
An application for Data Exclusivity (DE) can be made via a Letter of Intent (LOI)  in 
conjunction with the :  
 
a) Application for registration of a new drug product containing a New Chemical Entity ; or  
b) Application for a Second Indication of a registered drug product.  
 
The LOI sh all be addressed and submitted manually to  the Director of NPRA . 
 
The application must comply with all terms and conditions stated in the d irective  Arahan 
Bagi Melaksanakan Data Eksklusiviti Di Malaysia, Bilangan 2 Year  2011.    
 
The following details are extracted from the Directive on Data Ex clusivity (DE) issued by 
the Director of Pharmaceutical Services under Regulation 29 , Control of Drugs and 
Cosmetics Regulations 1984, Bil (11) dlm  BPFK/PPP/01/03 Jld 1 , 28 February 2011.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 78  2.2 APPLICABILITY AND DATE OF COMING INTO FORCE  
 
The directive is applicable to:  
i) New drug product containing a new chemical entity; and  
ii) Second indication of a registered drug product.  
 
New drug product containing  any new chemical entity  means a product that contains 
an 1active moiety  that has not been registered in accordance with the provisions of 
the CDCR 1984.  
 
1An active moiety  is defined as the molecule or ion, excluding those appended 
portions of the molecul e that cause the drug to be an ester, salt (including a salt with 
hydrogen or coordination bonds) or other non -covalent derivative (such as a 
complex, chelate or clathrate) of the molecule, responsible for the physiological or 
pharmacological action of the  drug substance.  
 
Second indication for a registered drug product  means a single or cluster of 
therapeutic indications applied subsequent to the first indication(s) approved at the 
point of registration of the product. The application for approval of the s econd 
indication contains reports of new clinical investigations other than bioavailability 
studies.  
 
The directive shall come into force on 1st March 2011.  
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 79   
2.3 GRANT OF DATA EXCLUSIVITY  
 
Any person may apply for Data Exclusivity. Such application s hall be made upon  
submission of documents to the Director of Pharmaceutical Services for the:  
a) Registration of a new drug product containing a new chemical entity; or  
b) Approval for second indication of a registered drug product.  
 
An application for Data Excl usivity shall only be considered if the application in 
Malaysia for:  
a) New drug product containing a new chemical entity is made within eighteen (18) 
months from the date the product is first registered or granted marketing 
authorization; AND  
 
Granted Data E xclusivity/ Test Data Protection in the country of origin or in any 
country, recognized and deem appropriate by the Director of Pharmaceutical 
Services.  
 
b) Second indication of a registered drug product is made within twelve (12) months 
from the date the sec ond indication is approved; AND  
Granted Data Exclusivity/ Test Data Protection in the country of origin or in any 
country, recognized and deemed appropriate by the Director of Pharmaceutical 
Services.  
 
 Before the Data Exclusivity is granted:  
a) The applicant  of a new drug product containing a new chemical entity shall 
provide to the Director of Pharmaceutical Services the undisclosed, unpublished 
and non -public domain pharmaceutical test data, the origination, of which 
involves a considerable effort; OR  
 
b) The applicant for a second indication of a registered drug product shall provide to 
the Director of Pharmaceutical Services, the reports of new clinical investigations 
other than bioavailability studies, conducted in relation to the second indication 
and the o rigination of which has involved considerable effort.  
 
The Director of Pharmaceutical Services shall decide on whether the application will 
be granted the Data Exclusivity. The period of the Data Exclusivity granted shall be 
made on a case to case basis.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 80  The period of the Data Exclusivity shall not  be more than:  
a) Five (5) years for a new drug product containing a new chemical entity; and  
b) Three (3) years for a second indication of a registered drug product. The period 
of Data Exclusivity is for the data con cerning the second indication only.  
 
Calculation of the period of Data Exclusivity:  
a) For a new drug product containing a new chemical entity, the period of Data 
Exclusivity shall be calculated from the date the product is first registered or 
granted marketi ng authorization AND granted Data Exclusivity/ Test Data 
Protection in the country of origin or in any country recognized and deemed 
appropriate by the Director of Pharmaceutical Services.  
 
b) For a second indication of a registered drug product, the period o f Data 
Exclusivity shall be calculated from the date the second indication is first 
approved AND granted Data Exclusivity/ Test Data Protection in the country of 
origin or in any country recognized and deemed appropriate by the Director of 
Pharmaceutical S ervices.  
 
 
2.4 CONSIDERATION OF OTHER APPLICATIONS UPON THE 
GRANT OF DATA EXCLUSIVITY  
 
For a registered new drug product containing a new chemical entity, registration of 
any other drug product where the active moiety is in all respect the same as the 
active moiety in the registered drug product which has been granted Data Exclusivity 
in Malaysia can be considered if:  
a) The applicant provides undisclosed, unpublished and non -public domain 
pharmaceutical test data, the origination of which involves a considera ble effort 
to demonstrate the quality, safety and efficacy if the drug product submitted for 
registration; OR  
 
b) The applicant has obtained consent in writing for right of reference or use of the 
test data from a person authorised by the owner of the registe red new drug 
product containing a new chemical entity.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 81   
2.5 NON -APPLICATION OF DATA EXCLUSIVITY  
 
Nothing in the Data Exclusivity shall:  
a) Apply to situations where compulsory licences have been issued or the 
implementation of any other measures consistent with the need to protect public 
health and ensure access to medicines for all; or  
b) Prevent the Government from taking any necessary action to protect public 
health, national security, non -commercial public use, national emergency, public 
health crisis or ot her extremely urgent circumstances declared by the 
Government.  
 
2.6 APPEAL  
 
Any person aggrieved by the decisions of the Director of Pharmaceutical Services 
may make a written appeal to the Minister within fourteen (14) days  from the date 
the decision is m ade known to him and any decision of the Minister made on an 
appeal shall be final.  
 
A person making an appeal may submit any supporting data or documents to the 
Director of Pharmaceutical Services not later than:  
 
a) 120 days for application of new drug prod ucts containing any new chemical 
entity; or  
b) 90 days for the application for second indication of a registered drug product.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 82  3. APPLICATION FORMALITIES  
 
3.1 WHO CAN APPLY FOR PRODUCT REGISTRATION  
 
The applicant for product registration shall be known as t he Product Registration 
Holder (PRH) and must be  a locally incorporated company, corporate or legal entity , 
with permanent address and registered with Companies Commission of Malaysia 
(with the scope of business related to the health/ pharmaceutical produc t). 
 
The name of the PRH, including product manufacturer shall not  reflect the following:  
a) Name of a government agency;  
b) Name of a research/ institute of higher education;  
c) A name that reflects the quality of pharmaceutical product  
e.g. “ Amalan Perkilangan Ba ik (APB) ”, Good Manufacturing Practice (GMP);  
d) Name of a disease;  
e) Name of an organ . 
e.g. Heart, Brain, Kidney etc.  
 
The PRH (if the company is not the product owner) should be authorized in writing 
by the product owner to be holder of the product registrati on and be responsible for 
all matters pertaining to quality, safety and efficacy of the product.  This shall include 
updating any information relevant to the product/ application.  
  
 
3.2 RESPONSIBILITY OF APPLICANT   
 
a) To ensure that all transactions with NPR A shall be done by their appointed 
person (s);  
 
b) Responsible for all information pertaining to quality, safety and efficacy in support 
of the product registration application; and shall inform the Authority in a timely 
manner any change in product informati on during course of evaluation;  
 
Under the CDCR 1984, Regulation 8(9) : Any person who knowingly supplies any 
false or misleading information to the Authority with his application for the 
registration of a product commits an offence.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 83  c) Responsible for all ma tters pertaining to quality, safety and efficacy of the 
registered product, including:  
 
i. Data updates on  product quality, safety and efficacy or current Good 
Manufacturing Practice (cGMP) compliance of the manufacturers (and 
repackers, where  applicable) . 
 
Under the CDCR 1984,  Regulation 8(5) : Any change in any document, 
item, sample, particulars or information which shall be notified in writing by 
the applicant to the Authority within fourteen (14) days from the date of 
such change . 
 
ii. Any decision to withdraw  the registration of the product with reasons.  
 
d) To notify the Authority of any change in correspondence details, including the 
name, address, contact person, telephone number, fax number and email;  
 
e) To notify the Authority immediately upon cessation of th e applicant as the 
product registration holder;  
 
 
3.3 HOW TO APPLY  
 
For registration of products, only web -based online submissions via QUEST at 
http://npra.moh.gov.my/  shall be accepted.  
 
To conduct transactions via QUEST system,  the a pplicant must first register a 
membership for QUEST system with NPRA  and purchase a USB Token  that 
contains a User Digital Certificate , from MSC Trustgate.com Sdn. Bhd. , which shall 
be installed to the applicant ’s computer.   
 
For details , please refer to  Frequently Asked Questions on QUEST System . 
 
For charges regarding QUEST USB token , please refer to Appendix 1:  Fees. 
 
The applicant shall be r esponsible for a ny act of fraudulence or misuse per taining to 
its authorized QUEST USB token (s). 
 
The NPRA  reserves the rights to approve or reject any application for the  QUEST 
membership.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 84   
 
4.   FEES  
 
Under the CDCR 1984, Regulation 8(3): The Authority may charge any ap plicant 
such costs as it may incur for the purpose of carrying out any evaluation or 
investigation prior to the registration of any product.   
 
Any payment made shall NOT  be REFUNDABLE  once the application has been 
submitted and payment confirmed.  
 
Applica tions without the correct fees will not be processed.  
 
 
4.1 FEES IMPOSED  
 
Please refer to Appendix 1:  Fees  for fees imposed, which include:  
 
a) Charges for USB Token of QUEST Membership;  
b) Processing and Analysis Fee for Pro duct Registration;  
c) Charges for Application of Licence;  
d) Charges for Amendments to Particulars of a Registered Product;  
e) Fee for C ertificate s; and  
f) Charges for Product Classificaton.  
 
 
4.2 MODE OF PAYMENT  
 
The processing fee and any other charges shall be pai d in the form of bank draft/  
banker’s cheque/ money order/ postal order made payable to “Biro Pengawalan 
Farmaseutikal Kebangsaan” . 
 
A separate bank draft/ banker’s cheque/ money order/ postal order are required for 
each application.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 85  5. TYPES OF APPLICATI ON 
 
5.1 REGISTRATION OF PRODUCTS  
 
5.1.1  APPLICATION FOR PRODUCT REGISTRATION FOR THE 
FOLLOWING CATEGORIES:  
 
a) New Drug Products;  
b) Biologics;  
c) Generic;  
d) Health supplements; and  
e) Natural Products.  
 
For details, please refer to Section A, 1.2 Categories of Product  and Section 
B: Product Registration Process . 
 
 
5.1.2  REGISTRATION OF COMBINATION PACK (COMBO PACK)  
 
a) Refers to products which are packed together in combination for a 
therapeutic regim en such as for the treatment of Helicobacter Pylori , 
Hepatitis C, etc.).   
Note:  Products which are packed together in combination NOT FOR 
THERAPEUTIC REGIMEN but for convenience of the consumers (e.g. 
capsules of five health supplement products in a bliste r pack) will not be 
considered for registration as a combo pack.  
b) Shall be registered as a single product.  
c) Must consist of registered products only : 
i. Where a combination pack consists of registered and unregistered 
products, the unregistered product needs to  be registered first, prior 
to submission of the application;  
 
ii. Where a combination pack consists of registered products from 
different product owners/ PRH, letters  of authorization which Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 86  include product name and product registration number from each 
produc t owner shall be submitted.  
 
d) A product which is packed together with diluent(s)/ adjuvant(s) is NOT 
considered as a combination p ack. 
 
e) Labelling requirement specifically for combination p ack is shown in                                   
Table IV : 
 
No. Oute r Label  Immediate Label  
1. Name of combination pack  Individual name for each products 
OR name of combination pack  
2. Registration number for the 
combination pack  Individual registration number for 
each products OR registration 
number for combination pack  
3. Name and address of 
manufacturer and product 
registration holder  Name and address of 
manufacturer and product 
registration holder  
4. Batch number of the 
combination pack product  Individual batch number for each 
products  
5. Expiry date  
(according to  the shortest 
expiry date from the individual 
products)  Individual expiry date for each 
products  
Note:  
These labeling requirements for a combo pack shall as well be subjected 
to other labelling requirements as stated in Appendix 9.1 : Label (mock -up) 
for Immediate Container, Outer Carton and Proposed Package Insert)  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 87  5.1.3  REGISTRATION OF STARTER PACK/  PATIENT INITIATION 
PACK  
 
a) Starter pack /patient initiation pack may consist of:  
i) Combination of products with differe nt strengths which are packed 
together in one packaging such as blister or calendar pack.  
ii) Combination of more than one pre -filled pen containing different strengths 
of preparation in one packaging.  
iii) Must be registered under the same product owner and PRH.  
 
b) Justified and proven specific dosing regimen demonstrated through clinical 
studies.  
 
c) Each product must be differentiated in terms of its physical description, e.g. 
colour, shape/size etc. to avoid confusion during drug administration.  
 
d) For products in cal endar pack packaging type, additional beneficial criteria 
such as different strength of tablets arranged in order of the day available per 
week can be implemented to assist the patients.  
 
e) Labelling requirement specifically for starter pack /patient initiat ion is shown in  
Table V : 
No. Outer Label  Immediate Label  
1. Statement of starter pack/patient 
initiation pack  
Individual name for each products  Individual name for each products  
2. Individual registration number for 
each products  Individual registrati on number for 
each products  
3. Name and address of 
manufacturer and product 
registration holder  Name and address of 
manufacturer and product 
registration holder  
4. Individual batch number for each 
products  Individual batch number for each 
products  
5. Manufacturing date  Manufacturing date  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 88  (according to the earliest 
manufacturing date from the 
individual products)  (according to the earliest 
manufacturing date from the 
individual products)  
6. Expiry date  
(according to the shortest expiry 
date from the ind ividual products)  Expiry date  
(according to the shortest expiry 
date from the individual products)  
Note:  
These labeling requirements for a starter pack/patient initiation pack shall 
as well be subjected to other labelling requirements as stated in Appendix 
9.1: Label (mock -up) for Immediate Container, Outer Carton and Proposed 
Package Insert)  
 
 
5.1.4  REGISTRATION OF PRODUCT FOR EXPORT ONLY  (FEO)  
 
a) Refers to locally manufactured products  for exporting purpose only and 
not marketed locally.  This does not apply to imported products meant to 
be packed/repacked locally and to be re -export (the application falls under 
Regulation 7(2)(b), Control of Drugs and Cosmetic Regulations 1984.  A 
separate application form  may be obtained from the NPRA website).  
b) Applications for registration of FEO products are only accepted in the 
following condition(s) and to be supported with evidenc e issued by the 
competent Authority of the importing countries (self -declaration is not 
accepted):  
(i) Countries which do not impose specific regulatory requirements as 
Malaysia (e.g. formulation with banned/ prohibited ingredients, 
zone IVB stability study, b ioavailability/ bioequivalence study, API 
evaluation etc.); OR  
(ii) Countries which have different requirements such as different 
formulation (e.g. colour or strength of ingredients), shape or 
manufacturing process, etc. as compared to a registered product; 
OR 
(iii) Difference in classification category of the products (e.g. as food in 
the importing country) for health supplements and traditional 
products.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 89  c) Applicant may apply for  a Certificate of Pharmaceutical Product (CPP)  for 
the registered  FEO products . 
d) For a regi stered product intended for exportation as well as to be sold in 
Malaysia:  
• New application for  registration for export only will  NOT  be required  if 
there is no change in the formulation and appearance of the registered 
product.   
• Applicant may apply a  CPP for the registered product  and together 
with an explanation/ declaration letter of any difference(s) to the 
importing country (e.g. a product exported with a different product 
name ). 
e) For a registered product, now intended to be for export only and no 
longe r for sale in Malaysia:  
• Application for registration as a FEO product is required.  
• The existing registration number (i.e. MAL number) will remain the 
same but with the addition of the administrative code  E (For Export 
Only)  
f) Applications for registration of FEO products are processed based on 
abridged evaluation.   However, the additional following requirements 
must be filled for pharmaceutical products (not applicable to health 
supplements and traditional products):  
(i) Certificate of Analysis (COA) of finishe d product for at least 1 pilot 
batch; AND  
(ii) Minimum 6 months stability data (real time and accelerated stability 
study) for at least 1 pilot batch.  
g) Application  is via online submission in QUEST system.  
 
Reference:  Bil (11)dlm.BPFK/07/25 Jld.2  Direktif Kaji Semula Pendaftaran Produk Untuk Tujuan 
Eksport Sahaja (FEO)  
 
 
5.1.5  REGISTRATION OF ORPHAN PRODUCT  
 
1. As defined in the Malaysian National Medicines Policy 2012 (DUNas) , an 
orphan product is:  
 
i. a medicine,vaccine or in vivo  diagnostic agent that is intended to treat, 
prevent or diagnose a rare disease  
or Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 90  ii. not commercially viable to supply to treat, prevent or diagnos e another 
disease or condition.  
 
2. For all categories of products namely new chemical entities/new drugs , 
biologics and generics (including Non -Scheduled Poison product) : 
 
i. Application for registration that being submitted to National 
Pharmaceutical Regulator y Division  (NPRA ) will only be accepted/ 
considered after the products have bee n designated as orphan products.  
ii. Application for registration must be submitted  via online system  and with 
appropriate processing fee . 
iii. Upon receipt of complete application, the application will be processed 
within ninety ( 90) working days.  
iv. Once an orphan  product is registered by the Drug Control Authority (DCA) , 
registration number  with the addition of  special alphabet , MAL ----------  AY / 
MAL  ----------  XY will be given to ease  identification  for the purpose of 
surveillance  or monitoring.  
v. If the product  has been registered  with some flexibilities  in terms of   
registration requirements , surveillance activities and monitoring  of quality, 
safety , and efficacy  will be implemented wit hin six months  after the 
product  is registered.  Surveillance  procedures and requirements  are as 
follows:  
a) The product  registration holder  must  report any  adverse reactions  
involving  orphan  product to NPRA  (please refer  to the guideline  for 
adverse drug reac tions  reporting on  NPRA  website ) 
b) Periodic  Safety  Updates  Report  (PSUR)/Periodic Benefit Risk 
Evaluation Report (PBRER) must be submitted to  NPRA  for orphan  
products  in the category of  new chemical  entities/new products and 
biologics every  6 months  for the first 2 years  and once a year  for the 
following 3  years.  
c) Products  will be  sampled  and tested  to ensure that it complies to the 
established standards and specifications . Actions  will be taken  
against products  that do not comply to the established  standards.  
 
3. For orphan  products in the category of  new chemical entities  or new drugs , 
other than  the requirements as stated in  para 2, the followings  are also 
required : 
i. For new active ingredients , data on pre-clinical  and clinical studies  must 
be submitted  to suppo rt the  safety  and efficacy  of the product.  In addition, 
the product  must be  registered  in at least one  reference  country . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 91  ii. If the product  / active ingredient  has been  established , published  
literature  to support the  safety  and efficacy  of the product is  sufficient and 
pre-clinical  or new clinical studies  are not required . In addition, the  
product  must  be registered  in at least  one country.  
iii. The p roduct can be  manufactured  in countries  where  the health  
authorities  is not the participating authority in the  Pharmaceutical  
Inspection  Cooperation  / Scheme ( PIC/S) . However, the product 
registration is valid only for 2  years  and the  inspection of Good 
Manufacturing  Practice  (GMP) will be conducted by NPRA  within  that 
period of time.  
iv. Stability data  and storage condi tion of the product is not limited  to the  
requirements of  Zone  IVB provided  that post-approval commitment  will be 
given  and requirements  to Zone  IVB will be complied  during  the renewal 
of product registration.  
v. If applicants are unable  to submit the process  validation  report  and 
analytical validation  report , the product samples should be tested  by 
NPRA  within 6 months  from the date the product  is registered . However, 
applicant s are  still required to submit  the protocol of  analysis   to be 
evaluated  together w ith the registration application.  
 
4. For orphan  products  in the category of generics  in which the innovator with 
the same active ingredients  and same dosage forms  previously registered with 
DCA but  its registration  status  has changed to  expired/  terminated/  withdrawn , 
bioequivalence study  reports  is not required.  This product  can also be 
registered  with the requirements  pertaining to GMP , stability  data,  process 
validation and analytical  validation report as allowed  for the products of new 
chemical entities  or new drugs  as stated in  para 3 . 
 
5. For orphan  products  in the category of biologics , requirements and conditions 
for registration as per para 2 can be considered. However, flexibilities or other 
conditions as per para 3 will only be considered on a case by  case basis.  
 
6. Requirements and other conditions that are not mentioned  here such as 
labelling requirements etc. are in accordance with the existing policies as 
required in the Drug Registration Guidance Document (DRGD), related 
directives and circulars.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 92  Summary of Procedures, Requirements and Conditions For Registration of Orphan 
Products  by Product Categories  
 
No. Procedures/Requirements/Conditions 
For Registration  New 
Chemical 
Entity/New 
Drug 
Products  Biologic  
Products  Generic 
Products  
(Including 
Non-
Scheduled 
Poison)  
1. Upon receipt of complete application, the 
application will be processed within ninety 
(90) working days (submitted  via online 
system  and with appropriate processing 
fee).  
  
√  
√  
√ 
2. Pre-clinical  and clinical studies  must be 
submitt ed to support the  safety  and 
efficacy  of the product.  The product  must 
be registered  in at least one  reference  
country . 
 √ Case -by-
case basis  Not 
applicable  
3. If the product  / active ingredient  has been  
established , published  literature  is 
sufficient to support the  safety  and efficacy  
of the product and  pre-clinical  or new 
clinical studies  are not required . The 
product  must  be registered  in at least  one 
country.   
 √ Case -by-
case basis  Not 
applicable  
4. The p roduct can be  manufactured  in 
countries  where  the health  authorities  is 
not the participating authority in the  
Pharmaceutical  Inspection  Cooperation  / 
Scheme ( PIC/S). However, the product 
registration is valid only for 2 years  and the  
inspection of Good Manufacturing  Practice  
(GMP) will be conducted by NPRA   within  
that period of time.  
 √ Case -by-
case basis  √ 
5. Stability data  and storage condition  of the 
product are not limited  to the  requirements 
of Zone  IVB provided  that post-approval 
commitment  will be given  and requirements  √ Case -by-
case basis  √ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 93  to Zone  IVB will be complied  during  the 
renewal of product registration  
 
6. If applicants are unable  to submit the  
process  validation report  and analytical 
validation  report , the product samples 
should be tested  by NPRA  within 6 months  
from the date the product  is registered . 
However, appl icant s are  still required to 
submit  the protocol of analysis  to be 
evaluated  together with the registration 
application.  
 √ Case -by-
case basis  √ 
7. Bioequivalence study reports are not 
required if the innovator product is no 
longer registered in Malaysia.  
 Not 
applicable  Not 
applicable  √ 
8. Registration number with the addition of  
special alphabet  , MAL ----------  AY / MAL --
--------  XY 
  
√  
√  
√ 
9. Surveillance activities and monitoring  of 
quality, safety , and efficacy  will be 
implemented within  six months after the 
product  is registered.  
  
√  
√  
√ 
  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 94  5.2 AMENDMENTS TO PARTICULARS OF A REGISTERED 
PRODUCT  
 
5.2.1  VARIATION  
 
Variation refers to change of particulars of a registered product.  
 
a) For pharmaceutical products, there are three (3) types of varia tion, which are 
Major Variation (MaV), Minor Variation Prior Approval (MiV -PA) and Minor 
Variation Notification (MiV -N). For details, please refer Malaysian Variation 
Guideline (MVG) . 
b) For health supplement and natural product, there are three (3) types of 
variation, which are Major Variation (MaV), Minor Variation Prior App roval 
(MiV-PA) and Minor Variation Notification (MiV -N).  For details, please refer 
Malaysian Variation Guideline (MVG) For Natural (Traditio nal Medicine & 
Homeopathy) And Health Supplement Products (Abridged Evaluation).  
 
c) For biologic products, please refer to the Malaysia Variation Guidelines for 
Biologics (MVGB)  and Section E: 16.1.3 Variation Application for Biologic 
Products.  
 
No change of any particulars of a registered product (except for Minor Variation 
Notification) shall be made without prior a pproval from NPRA . The registration of a 
product shall be reviewed for suspension or cancellation  if changes are made 
without prior approval of the Authority.  
 
 
5.2.2  CHANGE IN MANUFACTURING SITE  
 
Change of Manufacturing Site (COS) refers to change of manu facturing site 
for certain part or all of the manufacturing process of a product, but it does not 
cover changes related to a new site, where only:  
a) batch release takes place OR  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 95  b) to a new packager (secondary packaging or labelling) , as these changes 
are cov ered under applications for amendments to the particulars of a 
registered product (variation) .  
However, a change of manufacturing site for biologics  shall require a new 
product application only if the change is extensive that will have an impact on 
the qu ality, safety and efficacy profile of the final product.  
 
For details, p lease refer to Section E: 16.2 Change of Manufacturing Site .  
 
5.2.3  CHANGE IN PRODUCT REGISTRATION HOLDER  
 
It refers to a transfer of  marketing au thorization  from the existing product 
registration  holder ( PRH ) to another proposed new holder . This application  
allows the same registration number  of the registered product to be 
maintain ed. 
 
For details, p lease refer to Section E: 16.3 Change of Product Registration 
Holder .  
 
 
5.2.4  NEW/ ADDITIONAL INDICATION  
 
It is defined as an indication which was not initially approved for a registered 
pharmaceutical product. This shall include new therapeutic indication or 
indicati on for a new age group, such as usage in children and shall not 
include changing/ rephrasing of sentences.  
 
There are two (2) types of evaluation process available for a new/ additional 
indication application, i.e . full evaluation process and verification process.  
 
For details, p lease refer to Section E: 16.4 New/ Additional Indication .  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 96   
5.2.5  APPLICATION FOR A CONVENIENT PACK  
 
a) Refers to products which are packed together in a single packaging unit 
for convenience  of the consumers , such as a Confinement Set  or Set 
Jamu Bersalin .  
b) Shall  consist of registered products only.  
c) The convenient pack is a pplicable for registered products in the 
categories of;  
i) Health supplements .  
ii) Natural products . 
Or registered products fro m both categories (i) and (ii)  
iii) Non-Scheduled Poison (OTC)  
(Only between OTC products with Abridge Evaluation category ) 
d) Application for a convenient pack  shall be made via the variation process.  
 
For details, please refer to Section E: 16.1 Variation  and Section E: 16.5 
Application for a Convenient Pack .  
 
 
5.3 RENEWAL OF PRODUCT REGISTRATION  
 
The registration shall be valid for five (5) years or such a period as specified in t he Authority 
database  (unless sooner suspended or cancelled by the Authority);  
 
The renewal of product registration  should be submitted  within six (6) months prior to the 
expiry of the validity period of a product registration , together with the appropriat e fee.  
 
Please refer also at Section E: 14 Maintenance of Registration . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 97   
5.4 CERTIFICATES   
 
5.4.1  CERTIFICATE OF PHARMACEUTICAL PRODUCT (CPP)  
 
A CPP  which follows the format recommended by WHO shall be  issued to l ocally 
manufactured  products that are to be exported.  For application of CPP, applicant 
shall fill in form BPFK 412.2 : Permohonan Perakuan Keluar an Farmaseutikal.  
 
A fee, as stated in Appendix 1:  Fees , is payable on the issue of such certification . 
 
Upon receipt of complete application, the certificate shall be issued within fifteen (15) 
working days.  
 
5.4.2  GOOD MANUFACT URING PRACTICE (GMP) CERTIFICATE  
 
According to the CDCR 1984, compliance to Good Manufacturing Practice (GMP) is 
prerequisite to application of a manufacturing license, as well as product registration/ 
cosmetic notification.  
 
GMP is a standard which shall be followed by the manufacturers to ensure that the 
products manufactured are safe, efficacious and of quality.  
 
Upon complete application, a GMP certificate will be issued and a  fee, as stated in 
Appendix 1 : Fees , is payable on the issue of such certification . 
 
If a manufacturer who wish es to bu ild a new manufacturing premise , the 
manufacturer may submit a propos ed premise layout plan to the Centre for 
Compliance and L icensing, NPRA  for evaluation . 
 
For more information, please r efer Section D: 13.4 GMP Certificate .  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 98  5.5 LICENSES  
 
 
 
 
 
 
 
 
 
According to the CDCR  1984, any company who wishes  to manufacture, import and/or 
wholesale any registered products need s to have Manufacturer’s Licen ce, Import Licence 
and/or Wholesaler’s Lic ense.  
 
For more information pertaining application of appropriate licences, please refer Section D:  
13. Licensing  or contact Licensing U nit, Centre for Compliance and Licensing (CCL) , NPRA  
or NPRA  website . 
 
As for processing fee for these applications, please refer to Appendix 1:  Fees  
 
 
5.6 CLINICAL TRIAL IMPORT LICENCE (CTIL)/ CLINICAL 
TRIAL EXEMPTION (CTX)  
 
For more information  pertaining to any matters of clinical trial , please refer to NPRA  
website . Note:  
In addition to the relevant laws and regulations as stated in this DRGD, 
manufacturers are required to comply with the principles of Good Manufacturing 
Practice (GMP) and Good Distribution Practice (GDP). Meanwhile, Importers an d 
Wholesalers are required to comply with the principles of Good Distribution Practice 
(GDP).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 99  6. GENERAL CONDITIONS FOR REGISTRATION OF DRUG 
PRODUCTS UNDER THE CONTROL OF DRUGS AND 
COSMETICS REGULATIONS 1984  
 
6.1 REG ISTRATION CODE/ NUMBER  
 
The product registered with the Registration Number as stated in the Authority 
database  shall have the name, composition, characteristics, specifications and origin 
as specified in the registration documents  and Authority database . 
 
   Registration number appears as MALYYMM$$$$@##, e.g. MAL11070001ACERS Y:  
- MAL refers to “Malaysia ” 
- YYMM refers respectively to year and month of registration by the Aut hority (e.g. 
1107: July 2011);  
- $$$$ refers to a serial number for a product being reg istered (e.g. 0001);  
- @ refers to category of product being registered i.e. A/ X/ N/ T/ H; and  
- ## refers to administrative code used by NPRA  i.e. C/ E/ R/ S / Y. 
- The symbols @ and ##  refer to :  
a) A= Scheduled Poison  
b) X= Non -scheduled Poisons  
c) N= Health Supplemen ts 
d) T= Natural Products/ Traditional Medicines  
e) H= Veterinary Products  
f) C= Contract Manufactured ( the product  is manufactured by a GMP certified  
      contract manufacturer)  
g) E= For Export Only (FEO) ( the product  is to be sold for export only and  not for  
      sale in the local market)  
h) R= Packed and/or r epacked ( the product  is packed and/or repacked by an  
       approved GMP certified packer and/or repacker)  
i) S= Second source ( the product  is from a second source/ approved second   
       manufacturer)  
j) Y= Orp han products  
k) Z= Products gazetted as zero -rated under the Goods and Services Tax Act  
       2014, Goods and Services Tax (Zero -Rated Supplies ) Order 2014.   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 100   
6.2 PRODUCT PARTICULAR  
 
The holder of the registered product  shall supply such documents, items,  samples, 
particulars or information as the Authority may require in relation to the registered 
product.  
No change in name, composition, characteristics, origin, specifications, 
manufacturer, packing, indications, labeling, package insert, product literatu re or any 
relevant particulars of the registered product shall be made without prior approval of 
the Authority.  
 
 
6.3 LABELLING  AND PACKAGING  
 
6.3.1 SHRINK WRAPPING  
 
Shrink wrapping of multiple boxes of approved pack sizes are allowable provided the 
follow ing conditions are met:  
a) This refers to multiple boxes of approved pack sizes of a single or multiple 
registered  products which are shrink wrapped and marketed together fo r 
convenience of the consumers.  
b) This only applies to registered products from the Health Supplements, Natural 
Products/ Traditional Medicines and Non -scheduled Poisons category (category 
T, N and X).  
c) The shrink wrap does not come into contact with the dosage form.  
d) There are no qualitative or quantitative changes to the approved registered 
primary packaging and the outer packaging.  
e) There are no changes to the label contents of the product, and the label 
contents are not obscured.  
f) The s hrink wrap used must be completely transparent and does not contain any 
stickers/ wordings/ graphics.  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 101   
6.4 PRODUCT AUTHENTICATION  
 
The registered product shall be affixed with the security device approved by the 
Authority . The said security device  (hologram) , which is serialized, shall be used to 
authenticate and verify that the product is registered with the  Authority , and will be 
affixed to each unit pack of the product, whether locally manufactured or imported.   
 
The security device shall be affixed onto the outer packaging of the product, (or, 
where there is no outer packaging, on the immediate packaging),  on the front panel 
of the product label. None of the product particulars on the label shall be covered 
over by the security device.  
 
Please refer to : 
a) Appendix 9:  Labelling Requirements  where the security devic e/ label  may be 
affixed on the product label ;  
b) FAQ no. 20 on hologram; and  
c) Circulars and directives pertaining to security label (hologram):  
i) Bil (32) dlm BPFK/02/5/1.3  
Keputusan Mengenai Tarikh Perlaksanaan Penggunaan Label Hologram 
Meditag  (6 August 2004)  
 
ii) Bil (36) dlm BPFK/02/5/1.3  
Keputusan Pihak Berkuasa Kawalan Dadah Berhubung Penggunaan Label 
Hologram (Product Authentication) (5 November 2004)  
 
iii) Bil (62) dlm BPFK/02/5/1.3   
Menaiktaraf Ciri -ciri Keselamatan Label Meditag (15 August 2006)  
 
iv) (1)dlm.BPFK/PPP/ 07/25 Jld. 1  
Peraturan -peraturan Kawalan Dadah dan Kosmetik 1984. Arahan Pengarah 
Kanan Perkhidmatan Farmasi Bil 2 Tahun 2013 : Direktif Pelaksanaan dan 
Pengendalian Label Keselamatan (4 April 2013)  
 
v) Bil (26) dlm. BPFK/PPP/07/25 Jld. 1  
Direktif Berhubung Penggunaan Label Keselamatan Hologram Meditag™ 4  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 102  6.5 INDICATIONS, SPECIAL CONDITIONS  
 
The registered product shall only be indicated for  use as approved by the Authority.                                                   
The importation, manufacture, sale and supply of the registered product shall comply 
with all other specific conditions imposed by the Authority.  
 
6.6 ADVERSE REACTIONS, C OMPLAINTS  
 
The product registration holder or any person who possesses any registered product 
shall inform the Senior Director of Pharmaceutical Services immediately of any 
adverse reactions arising from the use of the registered product.  
 
6.7 HOLDER OF REGISTERED PRODUCT  
 
The holder of the registered  product shall inform the Authority of any change in his 
name or address.  
 
6.8 WITHDRAWAL FROM REGISTRATION  
 
The holder of the registered  product shall notify the Authority  with regards to  any 
decision to withd raw registration of a product and shall state reasons for the 
decision.  
 
The holder shall also notify the Authority when he is no longer authorized to be the 
holder of the registered  product  
 
6.9 CANCELLATION, SUSPENSION, AMENDMENT BY THE 
AUTHORITY  
 
The Au thority may, at any time and without assigning any reason suspend or cancel 
the registration of any product, and may amend the conditions of registration.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 103  6.10 DIRECTIVES  
 
The Senior Director of Pharmaceutical Services may issue written directives or 
guideli nes to any person or a group of persons as he think necessary for the better 
carrying out of the provisions of these Regulations and which in particular relate to:  
a) Product quality, safety and efficacy;  
b) Labeling;  
c) Change of particulars of a product;  
d) Transfer of licens es;  
e) Manufacturing;  
f) Storage includes requirements as to containers;  
g) Retailing;  
h) Promotion of sale including product information;  
i) Product recall;  
j) Product disposal;  
k) The cost of product recall or product disposal;  
l) Clinical trials; or  
m) Reco rds and statistics pertaining to manufacture, sale, supply, import or export of 
any products.  
 
 
6.11 CONDITIONS PERTAINING TO  PATENT  
 
For the purpose of registration of generic products, PRH shall provide patent declarations 
as below : 
i) PRH shall comply wit h all legal provisions in Malaysia;  
ii) The government/ authority is not liable for any offence committed by the PRH as 
a result of any breach of any law; and  
iii) PRH shall indemnify the government if any claim is made against the 
government as a result of any bre ach of any law by the applicant whether 
intentionally or otherwise.  
 
PRH shall conform to Patent Act 1983 (A ct 291) and shall not market, sell, offer for sale, or 
store any registered product containing any patented active ingredient(s) of which the 
patent  duration is yet to expire.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 104  7. USE OF HALAL  LOGO  
 
Halal logo may be used  voluntarily  on registered product label for  the following 
categories, for both local and export market, provided that such products have been 
certified and approved halal  by the  Malaysia Department of Islamic Development  
(Jabatan Kemajuan Islam Malaysia , JAKIM ): 
 
a) Non-scheduled poison, excluding veterinary products;  
Reference:  
Circular  (95)dlm.BPFK/PPP/01/03 Jld. 2  
Penggunaan Logo Halal Bagi Produk Farmaseutikal Berdaftar Kategori Produk 
Bukan Racun (Over The Counter, OTC) (26 December 2012).  
Directive  (6)dlm.BPFK/PPP/07/25  
Peraturan -peraturan Kawalan Dadah dan Kosmetik 1984. Arahan Pengarah Kanan 
Perkhidmatan Farmasi Bilangan 7 Tahun 2013 : Direktif Perluasan Skop 
Penggunaan Logo Halal Bagi Produk Farmaseutikal Berdaftar Kategori Produk 
Bukan Racun Berjadual Dalam Bentuk Parenteral. (8 November 2013).  
b) Health  supplements ;  
c) Natural products ; and  
d) Cosmetics . 
 
However, the  logo is NOT  allowed  to be used on label of registered products other than 
the categories as listed above.  
 
Only halal  logo issued by JAKIM or any Islamic Body  which is recognized by JAKIM 
shall be accepted.  
 
Consideration by the Authority for use of halal  logo on  product label of such products 
shall be  based on application as it is not a mandatory requirement.  
 
Applicant shall submit an application for product registration variation to NPRA  for 
approval to affix halal  logo on product label of a registered product , of which a halal  
certification has been granted. A copy of the halal  certificate must  be submitted as 
supporting document.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 105  SECTION B: PRODUCT REGISTRATION PROCESS  
 
 
The process of product registration  ensures that pharmaceutical products are eval uated for 
its safety, efficacy and quality, whereas natural products are evaluated for its safety and 
quality, prior to being registered by the Authority and finally released into the market.  
 
 
8. FLOW OF REGISTRATION PROCESS  
 
Figure 4 :  
 
Process of Prod uct Registration  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Rejected  
Approved  Non-Satisfactory  
Satisfactory  Submission  of 
Application  
Screening of  
Application  
Evaluation of  
Application  
Regulatory  
Outcome  
Post-Registration 
Process  Application 
Rejected  
Appeal  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 106  8.1 PRE-SUBMISSION OF APPLICATION  
 
Prior to submission of an application for product registration, applicant shall determine/ 
understand:  
a) The category of the product (different product category requires different data);  
b) Method of evaluation;  
c) General and specific requirements;  
d) Conditions applied;  
e) Multiple applications;  
f) Variants; and  
g) Language.  
 
A product shall only be registered if it fulfills regulatory requirements imposed by the 
Authority, especially with respe ct to quality, efficacy and safety of the product and 
taking into consideration on the following criteria:  
a) Necessity of the product;  
b) Potential for abuse; and  
c) Therapeutic advantages.  
 
 
8.1.1 CATEGORY OF PRODUCT  
 
Applicant shall determine on the category of  a product, as described under Section A - 
General Overview . 
 
If the product category is uncertain, applicant may submit a Classification Form  to Section 
of Regulatory Coordination, Centre for Product Registration, NPRA  for verification.  
 
 
8.1.2 METHOD OF EVALUATION  
 
Method  of evaluation for registration of a product is divided into two (2) typ es, which are:  
a) Full Evaluation; and  
b) Abridged Evaluation.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 107  Table V I: Method of Evaluation According to Product Categories  
 
No. Product Category  Method of Evaluation  
Full 
Evaluation  Abridged Evaluation  
1. New Drug Products  √ Not Applicable  
2. Biologics  √ Not Applicable  
3. Generics  
(Scheduled Poison)  √ Not Applicable  
4. Generics  
(Non -Scheduled 
Poison)  
[or known as OTC]  * All products 
from this 
category, 
unless stated 
in Abridged 
Evaluation  Includes, but not limited to t he following:  
• Antiseptics/ skin disinfectants;  
• Locally -acting lozenges/ pastilles;  
• Topical analgesic/ counter -irritants;  
• Topical nasal decongestants;  
• Emollient/ demulcent/ skin protectants;  
• Keratolytics;  
• Anti-dandruff;  
• Oral care;  
• Anti-acne;  
• Medicated plast ers/ patch/ pad; and  
• Topical antibacterial.  
5. Health Supplements  
a) General or 
Nutritional Claims  
b) Functional 
Claims (Medium)  
c) Disease Risk 
Reduction Claims 
(High)   
 
 
Not Applicable  
 
 
Not Applicable  
 
 
√ √ 
 
 
√ 
 
 
 
Not Applicable  
6. Natural Products  Not Applicable  √ 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 108  * Table VI I:  
Products containing Glucosamine, Chondroitin and Methylsulphonylmethane (MSM)  
 
No. Product  Product 
Category  Route of 
Evaluatio
n Condition 
on Product 
Indication  Remark  
1. Prod ucts 
containing 
Glucosamine  As single 
active 
ingredient  OTC  Full 
evaluation  As adjuvant 
therapy for 
osteoarthritis  Products 
containing 
glucosamine in 
combination with 
other health 
supplement 
ingredients are 
only allowed to be 
registered for 
therapeutic 
purposes and 
NOT allowed to 
be registered as 
Health 
Supplement 
Product.  As 
combination 
with 
Chondroitin 
and/ or MSM  OTC  Full 
evaluation  As adjuvant 
therapy for 
osteoarthritis  
2. Products 
containing 
Chondroitin  As single 
ingredient  
 
OR 
 
In 
combination 
with other 
supplement 
ingredients  Health 
supplement  Abridged 
Evaluation  No 
therapeutic 
claims are 
allowed  - 
3. Products 
containing 
MSM  As single 
ingredient  
 
OR 
 
In 
combination 
with other 
supplement 
ingredients  Health 
supplement  Abridged 
Evaluation  No 
therape utic 
claims are 
allowed  - Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 109  As 
combination 
with 
Chondroitin  Health 
supplement  Abridged 
Evaluation  No 
therapeutic 
claims are 
allowed  - 
 
Reference: Circular  
1) Bil (66) dlm BPFK/02/5/1.3  
Produk yang Mengandungi Glucosamine dan Chondroitin  (14 November 2006).  
2) Bil. (20) dlm.BPFK/PPP/0 1/03 
Produk yang mengandungi Glucosamine, Chondroitin dan Methylsulfonylmethane 
(MSM) (31 Disember 2008) . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 110  8.1.3 REQUIREMENTS FOR PRODUCT REGISTRATION  
 
Applicant shall submit the following requirements to support an application for product 
registration, a pplicable according to different category of product:  
 
a) General r equirements  (either for full or abridged evaluation);  
 
i) Full Evaluation ; 
(In accordance to ASEAN ACTD/ ACTR or ICH guidelines)  
 
▪ Part I   - Administrative data and product information;  
▪ Part II  - Data to support product quality  (Quality Document) ;  
▪ Part III  - Data to support product safety (Nonclinical Document ); and  
▪ Part IV - Data to support product safety and efficacy (Clinical Document).  
 
OR 
 
ii) Abridged Evaluation . 
 
For details, please refer Appendix 2:  Requirements for Product Registration . 
 
b) Specific requirements according to category of product  (biologics, health supplements 
and natural products).  
 
- Biologics  : Refer Appendix 3:  Guideline on Registration of Biologics  
- Health 
supplements  : Refer Appendix 4:  Guideline on Registration of Health 
Supplements  
- Natural 
products  : Refer Appendix 5:  Guideline on Registration of Natural 
Products  
 
For regulatory control of active pharmaceutical ingredient (API), it is applicable to all 
pharmaceutical products  either local ly manufactured or imported,  excluding  biologics, 
health supplements and natural products.  
 
The implementation  began  with voluntary submission fo r New Drug Product s in April  2011 
and was followed by;  
 
• Phase 1  - New Drug Products (NDP)   : January 2012    
• Phase 2  - Generics ( Scheduled Poison )  : July  2014 (by phases)  
• Phase 3  - Generics  (Non-scheduled Poison ): (to be determined )  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 111  No separate application for registration of the API is required. However, the required 
technical documentation pertaining to each API at Part 2.S ACTD  (Part II Quality: Drug 
Substance) shall be submitted as part of the application for product registration.   
 
For details pertaining to regulatory control of API, please refer Appendix 6:  Guideline on 
Regulatory Control of Active Pharm aceutical Ingredients (API) . 
 
 
 
8.1.4  CONDITIONS APPLIED ON PRODUCT REGISTRATION  
 
Applicant shall comply with the following conditions applied on product registration. Failure 
to do so shall results in rejection of the application by the Authority.  
 
a) Applicant shall comply with all requirements as specified in the following appendices 
and directions from the Authority : 
i) Appendix 7:   
Special Conditions for Registration for a Particular Product or Group of Products ; 
ii) Appendix 8:   
List of Permitted, Prohibited and Restricted Substances ; 
iii) Appendix 9:   
Labelling Requirements ; 
iv) Appendix 10:  
Guide line on Patient Dispensing Pack for Pharmaceutical Products i n Malaysia  
(Applicable to pharmaceutical products only).  
 
b) Applicant shall provide supplementary data/ information, documentation or samples , if 
requested by the Authority;  
 
c) Applicant shall respon d and provide feedback for the requested supplementary data/ 
information, documentation or samples  by the Authority within the specified timeframe. 
If the applicant is unable to submit the requirements within the specified timeframe, a 
written request for an extension sh all be submitted  to NPRA ;   
 
d) Application shall be rejected if the applicant fails to submit required supple mentary data/ 
information or documentation within six (6) months  from the first correspondence date;  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 112  e) Applicant shall submit sample  of natural product for laboratory testing to the Centre for 
Quality Control, NPRA  within fourteen (14) working days  from date of confirmed 
payment. Failure to do so within thirty (30) days from the date of the payment shall 
result in rejection of the appl ication. 
 
 
8.1.5 MULTIPLE APPLICATIONS  
 
Separ ate application for product registration  shall be  required for each  product  for the 
following conditions:  
a) Products containing the same ingredients but ma de to different specifications, in terms 
of strength/  content of ingredient(s),  dosage form, description, etc.;  or  
b) Different manufacturer.  
 
However, d ifferent packings (materials) or pack sizes (quantity/  volume) of a product made 
by the same manufacturer to the same specifications, formulation and dosage form 
(including parenteral preparations, peritoneal dialysis fluids and haemofiltration solutions 
which are introduced into human  bodies) shall require only one application for product 
registration. The product registration shall be for the packings and pack siz es stated in the 
registration documents only.  
 
 
 
 
 
 Note:  
Registration of same product in all aspects but with different product name by the same 
PRH is not allowed by the Authority . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 113   
8.1.6 SECOND OR THIRD SOURCE  
 
It is defined as  product which is the same as the product from first source  in all aspects , 
except for the site of manufacture.  
 
An application for a second source may be considered by the Authority but only with 
justification.  
 
A second source produc t, excluding biologic products, may differ  for the following aspects:  
a) equipments/ machines ; 
b) minor manufacturing process (e .g. blending time, number of su b-parts);  
c) batch size;   
d) packaging materials, thickness of same p ackaging materials, pack sizes;  
(Note:  Use of different packaging material shall be supported with stability study report.)  
e) manufacturer of API ; and  
f) source of excipients ; 
 
EXCEPT  differences in shape, embossment and  thickness of tablet, in order to avoid 
change in product identity and subsequently causing confusion.  
 
The manufacturer shall declare with support of manufacturing validation process data that 
there is no change in formulation, specification of active in gredient(s) and excipient(s), and 
finished product for the second source product compared to the first source.  
 
For pharmaceutical product, no third source is allowed for same product unless in 
emergency situation such as outbreak of infectious disease.  
 
A second source product is defined as a product which is the same as product from the first 
source in all aspect, except for the site of manufacture. Similarly to Biologics,an application 
for a new product from a second source may be considered by the Autho rity but with 
justification.  A third source may be also be considered if justified.  
 
The manufacturer shall declare with support of manufacturing validation process data that 
there is no change in formulation, specification of active ingredient(s) and exc ipient(s), and 
finished product for the second source product compared to the first source. There is no 
difference in product identity and presentation, to avoid confusion.  
 
Biologics are highly sensitive to manufacturing condition. Therefore if any of the  conditions 
outlined are not fulfilled, the application is automatically considered as new application.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 114  a) The following application procedures apply:  
 
Second or third source for biologic products  
  
Conditions  All the following conditions are 
fulfilled:  
1. The proposed facility is 
approved for manufacturing 
activities for the same 
company/sponsor  
2. No change in the composition, 
manufacturing process and  
drug substance  & drug product 
specifications  
3. No change in the 
container/closure system  
4. The same validated 
manu facturing process is used  
5. The newly introduced product 
is in the same family of 
product(s) or therapeutic 
classification as the one of 
those already approved at the 
site and uses the same filling 
process/equipment  
6. Only one Final Release Site  
 Conditions 1.  to 6. are not 
fulfilled  
 
 
Supporting 
data 
 1. GMP certification  
2. Updated relevant sections in 
ACTD Part II (P)  
3. Confirmation that information 
on the drug product has not 
changed as a result of the 
submission (e.g. other than 
change in facility) or revised 
information of the drug product, 
if any of the attributes have 
changed  
4. Name, address and 
responsibility of the proposed 
production facility involved in 
manufacturing and testing  
5. Process validation and/or 
evaluation studies (e.g. 
equipment qualification, media  
fills, as appropriate), to 1. A complete product dossier 
specific to the new drug 
product manufacturing site 
can be made available 
(ACTD Parts I, II; ACTD 
Parts III, IV can refer to the 
first source product 
registered with DCA)  
2. Manufacturer’s declaration 
of no change in 
formulation, specification of 
active ingredient(s) and 
excipient(s), and finished 
product for the second 
source compared to the 
first source  
3. Quality comparability data 
(manufacturing process 
validation data, batch Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 115  demonstrate comparability 
between both current and 
proposed manufacturing sites  
6. Process validation study 
reports. The data should 
include transport between sites, 
if relevant.  
7. Description of the batches and 
summary of results as  
quantitative data, in a 
comparative tabular format, for 
at least 3 consecutive 
commercial scale batches of 
the approved and proposed 
drug product, to demonstrate 
comparability between both 
current and proposed 
manufacturing sites  
8. Summary of stability test ing and 
results (e.g. studies conducted, 
protocols used, results 
obtained), to demonstrate 
comparability between both 
current and proposed 
manufacturing sites  
9. Stability test results from: 
accelerated testing (usually a 
minimum of 3 months) or, 
preferably, forced degradation 
studies under appropriate time 
and temperature conditions for 
the product; and 3 months of 
real time testing at time of 
submission (6 months real time 
testing data at time of 
registration approval) on three 
commercial scale batches of 
the drug product manufactured 
using the proposed 
manufacturing facility, or longer 
if less than 3 time points are 
available (including the zero 
time point), as well as 
commitment to notify NPRA  of 
any failures in the ongoing long 
term stability studies.  analyses, stability)  
4. Real-time stabilit y data to 
support proposed shelf -life 
(no extrapolation allowed 
by ICH Q5C: Stability 
Testing of 
Biotechnological/Biological 
Products)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 116  10. Certificates of analysis for drug 
products manufactured at the 
new manufacturing site  
11. Rationale for considering the 
proposed formulation/filling 
suite as equivalent  
12. Information on the proposed 
production facility involved in 
the manufacture of the drug 
produc t, including the complete 
set of floor plans and flow 
charts (drawings, room 
classification, water systems, 
HVAC systems), as well as the 
cleaning and shipping 
validation, as appropriate [if 
applicable]  
13. Information describing the 
change -over procedures for  
shared product -contact 
equipment or the segregation 
procedures, as applicable. If no 
revisions, a signed attestation 
that no changes were made to 
the change -over procedures [if 
applicable]  
14. Results of the environmental 
monitoring studies in classified 
areas [if applicable]  
Fees  
 RM1000 (processing fee)  
 
+ RM3000  
(analysis fee – single active ingredient)  
OR 
+ RM4000 (analysis fee – two or  more active ingredients)  
 
Processing 
timeline  
 120 working days  245 working days  
NOTE: There can be only one Final Release Site for each MAL no.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 117  8.1.7 VARIANTS  
 
Variants refer to products  with differences in terms of fragrance/ flavour or consequen tly 
colour .  
 
When variants are registered:  
a) The variants  should only differ in terms of fragrance/ flavour and colour.  
b) Product name  of the variants  shall remain the same, with the addition of an identifying 
variant name.  
c) Each variant shall be registered  as one (1) product with a different registration number.  
 
Variants  to the registered product may be considered for the following dosage forms:  
 
a) Products Containing Scheduled Poison  
 
 ONLY  for pediatric oral liquid preparations   
 
b) Products Containing Non -Scheduled Poison  
 
i) Lozenges;  
ii) Chewable tablets;  
iii) Effervescent powders/ tablets;  
iv) Powder;  
v) Granule;  
vi) Oral liquid;  
vii) Dental preparations (rinses, dent ifrices);  
viii)Medicated soaps (bar, liquid) ; and  
ix) Vaginal creams and douches.  
 
 
8.1.8 LANGUAGE  
 
All data and i nformation including supporting  documents for product registration  such as 
certificates, letters and product labels shall be in English or Bahasa Malaysia .  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 118  8.2 SUBMISSION OF APPLICATION  
 
 
Application of product registration shall be submitted via the online QUEST system  at 
http://npra.moh.gov.my/ .  
 
Applicant shall ensure  all data requirements needed to support the application is fulfilled 
before submission.  
 
Upon submission, the application shall be given a call numb er for reference, which is 
specific to a particular product. Applicant shall refer to this call number during all 
correspondence pertaining to the registration of the product.  
 
Applicants are advised to read the explanatory notes as stated in Appendix 11:  Guideline 
on Filling the Online Application Form for Product Registration via Quest System , and also  
relevant ASEAN or ICH guidelines and checklists, for full information on requirement for 
product registration . 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 119  8.3 SCREENING OF APPLICATION  
 
After an online submission of the product registration application has been done, the 
application shall be undergone an initial evaluation (or known as screening process) which 
shall ensure the required data/ information of the submitted application are complete.  
Further evaluation shall be done after payment for the application has been made . 
 
 
8.3.1 SATISFACTORY  
 
Only a complete application shall be acc epted and approved for payment. Upon screening 
approval, the applican t is requested to proceed for payment and submission of hard copy 
documents (if applicable).   
 
Submission of hard copy documents:  
 
No. Category of 
Product  Online 
Submission  Hard copy submission  
1. NDPs  All documents as 
required under 
Part I – IV - A copy of  CD and a copy of documents 
as required under Part I – IV; 
- Nine (9) copies of indexed fold ers 
containing proposed package  insert and 
published clinical papers and/or in -
house synopses ; 
- A copy of CD and a copy of documents 
as required under Appendix 6, Tabl e 1 
(for drug substance/ API ); 
- Further documentations may be 
requested from case -to-case as deemed 
necessary.  
2. Biologics  All documents as 
required under 
Part I – IV Part I – IV including published clinical 
papers (6 sets – indexed, listing with 
summary/  abstracts of each paper)  
3. Generics 
(Scheduled 
Poison)  All documents  As requested  
e.g. big file size, unable to be submitted 
online   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 120  No. Category of 
Product  Online 
Submission  Hard copy submission  
4. Generics (Non -
Scheduled Poison)  All documents  As requested  
e.g. big file size, unable to be submitted 
online  
5. Health 
Supplements  All documents  As requested  
e.g. big file size, unable to be submitted 
online  
6. Natural Products  All documents  All Sections (Section A -F) 
 
 
For payment, applicant shall submit two (2) copies of printed payment voucher together 
with appropriate fees to the Finance Department, NPRA  for payment confirmation. The 
applicant is advised to keep a copy of the payment voucher as reference. A product 
reference number shall be given to the application upon payment confirmation.  
 
Payment has to be made within thirty (30) days from the date of approval for screening. 
The application  form wil l be deleted from the system if payment has not been made within 
this stipulated time . 
 
 
8.3.2 NON -SATISFACTORY  
 
If the application is found incomplete during the screening process, the application shall be 
rejected and the applicant shall be notified via the system.  
 
 
 
 
 
 
 
 
 
 Note:  
 
If there is any decision made by the applicant / required by the Authority in certain cases  
to withdraw a submitted application for registration of a product, at any stage of 
evaluation prior to its approval, the applicant shall notify the Authority and shall state the 
reasons for the decision.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 121  8.4 EVALUATION OF APPLICATION  
 
 
8.4.1 INITIATION OF REVIEW  
 
Upon confirmation of payment, the application with the submitted data shall be evaluated. 
Review of applications shall follow a queue system .  There shall be separate queues for the 
different categories of products and/or according to level of claims (e.g. general, medium or 
high claim  for health supplements) . 
 
 
8.4.2 PRIORITY REV IEW 
 
1. Priority review may be granted for new product application (in the category of New 
Drug Products, Biologics and Generics) which fulfils either one of the following 
conditions;  
 
a) Product which is intended for:  
(i) Unmet medical needs (e.g. medicines for rar e diseases, new vaccines, 
etc.),  
(ii) Life-saving such as for treatment/ prevention of serious medical 
conditions (e.g. anticancer, antiretroviral, etc.),  
(iii) Treatment/ prevention in pandemic/ endemic situations, for the interest 
of public health,  
(iv) Emergency supply / crucial for treatment purpose according to the 
current needs in the country,  
(v) Supply to the Ministry of Health Malaysia under circumstances where 
alternative product with the same active ingredient is unavailable,  
b) Product which involves a change in the fo rmulation due to the decision/ 
instruction by the Drug Control Authority (DCA), for the purpose of formulation 
improvement with appropriate scientific justification(s),  
c) Product which is the first generic product, or the first locally manufactured 
generic p roduct.  
 
2. An application for Priority Review should be submitted via a formal letter addressed 
to the Director of NPRA once the screening has been approved.   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 122  3. The approval of Priority Review is subjected to the decision of the Drug Evaluation 
Committee Mee ting upon submission of complete product registration 
documentation and does not exempt applicant from any product registration 
requirements.  
 
4. The timeline for evaluation for product granted Priority Review is as below;  
 
No. Product Category  Duration  
(Star ting from the date of 
approval of Priority Review)  (A) Full Evaluation  
1. New Drug Products  120 working days  
2. Biologics  120 working days  
3. Generics (Scheduled Poison)  100 working days  
4. Generics (Non -Scheduled Poison)  100 working days  
 
 
 
8.4.3 CORRESPONDENCE  
 
Correspondence via the system shall be sent to the applicant if there is any clarification and 
further supplementary data/ information or  documentation pertaining to the application, if 
deemed necessary by the Authority.  
 
Application shall be rejected if the applicant fails to respond to the correspondence from 
NPRA  to submit the required supplementary data/ information or  documentation within six 
(6) months  from the first correspondence date.  
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 123  8.4.4 TIMELINE FOR PRODUCT REGISTRATION  
 
Table VII I: 
 
No. Product Category  * Duration  
(Inclusive screening process)  (A) Full Evaluation  
1. New Drug Products  245 working days  
2. Biologics  245 working days  
3. Generics (Scheduled Poison)  210 working days  
4. Generics (Non -Scheduled Poison)  210 working days  
(B) Abridged Evaluation  *Duration  
(Inclusive screening process)  
5. Generics (Non -Scheduled Poison)  
(Product categories as stated in Table V above)  
a) Single active ingredient  
b) Two (2) or more active ingredients  a) 116 working days  
b) 136 working days  
6. Natural Products  
a) Single active ingredient  
b) Two (2) or more active ingredients   
a) 116 working days  
b) 136 working days  
7. Health Supplements  
a) ** Single active ingredient  
b) ** Two (2) or more active ingredients  
 
**   Applicable for:  
i) General or Nutritional Clai ms; and  
ii) Functional Claims (Medium Claims)  
 
c) Disease Risk Reduction Claims  
(High Claims)   
a) 116 working days  
b) 136 working days  
 
 
 
 
c) 245 working days  
  
* Upon receipt of complete application.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 124  8.5 REGULATORY OUTCOME  
 
8.5.1  DECISIONS OF THE AUTHORITY  
 
A regula tory decision shall be made based on the outcome of the evaluation of the 
submitted documentation, and samples (if applicable). An application may be 
approved or rejected by the Authority, and the Authority decision will be sent via 
email/ official letter to the product registration holder.  
 
As stipulated  under the CDCR 1984, Regulation 11(1) , the Authority may, at any 
time reject , as well as cancel or suspend the registration of any product if there are 
deficiencies in safety, quality or efficacy of the p roduct or failure to comply with 
conditions of registration.  
 
8.5.2  PRODUCT REGISTRATION NUMBER  
 
As stipulated in Regulation 8(8), CDCR 1984, upon registration of a product by the 
Authority, the product registration holder shall be notified by the Authorit y and a 
product  registration number (i.e. MAL number ) shall be assigned to the registered 
product via the system.  
The registration number is specific for the product registered with the name, identity, 
composition, characteristics, origin (manufacturer) an d product registration holder, 
as specified in the registration documents. It shall NOT be used for any other 
product.  
 
8.5.3  CERTIFICATE OF REGISTRATION  
 
Form 1 (C ertificate of R egistration ) for a product with the provisions, conditions, 
limitations and etc. of the registration , as stipulated in Regulation 8(8) of CDCR 
1984,  has been deleted from the regulation in year 2006 via amendment of PU(A) 
336/06. Therefore, the certificate will no longer  be issu ed by the Authority .  
 
Applicant shall refer to the p roduct registration approval notification sent by the 
Authority  or the Approved Product Registration List  in NPRA  website . 
Reference: Circular (100)dlm.BPFK/PPP/01/03 Jld. 2 . Pemansuhan Pengeluaran 
Sijil Perakuan Pendaftaran (SPP) (21 January 2013).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 125  8.6 POST -REGISTRATION PROCESS  
 
Regis tration status  of a product shall be valid for five ( 5) years or such period as specified 
in the Authority database (unless the registration is suspended or cancelled by the 
Authority).  
 
Upon approval for product registration by the Authority, applicants s hall fulfill all 
commitments and conditions imposed during approval of the product registration and shall 
be responsible for the maintenance of the product in terms of quality, safety and efficacy 
throughout the validity period of registration. Failure to do so may result in rejection of 
application for renewal of product registration.  
 
The Authority shall be notified of any changes to the product’s efficacy, quality and safety,  
as described in detail at Section E: Po st-Registration Process . 
 
8.7 REJECTED APPLICATION  
 
As stipulated in Regulation 18, CDCR 1984:  
a) Any person aggrieved by the decision of the Authority or the Director of Pharmaceutical 
Services, a written appeal may be made to the Minister of Health Malays ia; 
b) All notice of appeals  shall be made within  fourteen (14) days  from the date of 
notification from the Authority;  
 
- A period of 60 days from the date of appeal confirmation is given for submission of 
any additional information/ supplementary data/ documen ts for all categories of 
product.  
 
- The appeal shall not be considered  if all the required information is not submitted 
within the specified timeframe given. Any request for extension of this period 
shall not be considered too.  
 
c) Any decision of the Minister  made on an appeal shall be final.  
 
Re-submission for product registration of a rejected application due to reason of safety and 
efficacy shall not be accepted within two (2)  years after the rejection. However, if the 
product is registered in the reference  countries, submission of application can be made 
earlier.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 126  8.7.1  PROCESS OF APPEAL  
 
Figure 5: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Approved  **Note:  
a) 60 days  is a timef rame given to applicant 
applicable for rejected application for all 
product categories and cancelled registration . 
b) Additional information/ supplementary data/ 
documents shall be submitted  via online/  
manually  to Section of Regulatory 
Coordination, Centre f or Product 
Registration, NPRA.  
 
 *Applic ants may confirm to 
appeal for rejected application of 
any product  within 14 days 
from the date of notification 
from the Authority  
Applicant shall submit appeal 
letter to NPRA as per address 
stated in the template appeal 
letter  
**Applicant shall submit  
required additional information/ 
supplementary data/ documents 
within 60 days from the date 
of appeal confirmation  
Rejected  ***Evaluation by the Authority  
Memorandum of appeal 
prepared by the Authority and 
sent to the Minister of Health  
Regulatory outcome  
Post-Registration Process  Appeal rejected  * Note:  
For suspended/ cancelled  registration of a 
product, applicant may confirm to appeal 
manually  by sending an appeal letter to 
NPRA within fourteen (14) days from the 
date of notification from the Authority, and it 
shall be subjected to the same process of 
appeal.  
 
***Note:  
a) 120 days  for evaluation of NCE, Biologic, 
prescription and non -prescription (full 
evaluation) products.  
b) 90 days  for evaluation of non -prescriptio n 
(abridged evaluation), health supplement 
and natural products . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 127  8.7.2  TEMPLATE FOR AN APPEAL LETTER  
 
 
  
LETTERHEAD  SYARIKAT PEMEGANG PENDAFTARAN PRODUK  
Nama dan alamat pemegang  
 
Tarikh:   
 
Y. B. Menteri Kesihatan Malaysia  
d/a Bahagian  Regulatori Farmasi Negara  
Kementerian Ke sihatan Malaysia  
Lot 36, Jalan Universiti,  
46200 Petaling Jaya  
(u.p. Setiausaha PBKD)  
 
Y. B.,  
 
PERATURAN 18 – RAYUAN TERHADAP PENOLAKAN PERMOHONAN 
PENDAFTARAN  
 
NAMA PRODUK  :  Sila nyatakan nama produk (Please state the product name ) 
NO. RUJUKAN  :  Sila ny atakan nombor pendaftaran produk  
                                         (Please state reference number of the product ) 
 
Dengan segala hormatnya, pihak kami ingin membuat rayuan terhadap penolakan 
permohonan produk seperti di atas.  
 
2. Alasan – alasan ra yuan serta data tambahan/ maklumat akan dihantar kepada pihak 
Y.B. dalam tempoh 60 hari  dari tarikh pengesahan penerimaan rayuan oleh pihak Y.B.  
 
Sekian, terima kasih.  
 
Yang benar,  
 
Tandatangan Wakil Pemegang  
 
(NAMA WAKIL PEMEGANG)  
Jawatan Wakil Pemegang  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 128  SECTION C: QUALITY CONTROL  
 
 
The requirement for the submissi on of the protocol of analysis (POA), analytical 
method validation (AMV) and product samples for laboratory testing are presented in 
this section.  
 
The submission of POA and AMV to the Centre for Quality Control  shall be done via 
the online system (Quest system). Documents to be submitted are listed below:  
 
 
Documents to be submitted via online Quest system  for finished product:  
1. E12 : Complete protocol of analysis for finished product including 
preservatives and diluents (if any).  
2. E13 : 1. Complete tes ting methods and results for the AMV with all 
relevant validation parameters, including acceptance criteria and 
supporting raw data (e.g. chromatograms, spectrums etc.)  
2. Summary of AMV which includes all the relevant validation 
characteristics, its accep tance criteria and results.  
* For Biologics, all documents above mentioned except raw data.   
 
Documents to be submitted as hardcopy  for finished product [applicable for 
Biologics]:  
1. Certificate of analysis for active drug substance (2 batches) and recent b atches of 
finished product (local manufacturer 1 batch, overseas manufacturer 2 batches)  
2. Complete protocol of analysis for finished product (including preservatives and 
diluents, if any)  
3. Complete testing method for the AMV.  
4. Complete results for the AMV w ith all relevant validation parameters, including 
acceptance criteria and supporting raw data (e.g. chromatograms, spectrums etc.)  
 
Note:  
1.   A cover letter consisting of the following information should be enclosed with  
every hard copy document submissi on: 
i) Name of product;  
ii) Reference Number/ Protocol Number;  
iii) Contact person (name/ email address/ telephone no.);  
iv) Name and address of company.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 129  2. Documents submitted should be well organized and indexed.  
 
Documents to be submitted via online Quest system for for  Active 
Pharmaceutical Ingredient, API:  
1. S 4.2  : Complete protocol of analysis for drug substance(s)  
2. S 4.3  : Complete testing methods and results for the AMV for drug 
substance(s) with all relevant validation parameters, including 
acceptance criteria  and supporting raw data (e.g. 
chromatograms, spectrums etc.)  
 
Documents to be submitted as CD [applicable for Active Pharmaceutical 
Ingredient, API]:  
1. Certificate of analysis for active drug substance(s) (2 batches).  
2. Complete protocol of analysis for dru g substance(s).  
3. Complete testing method for the AMV for drug substance(s).  
4. Complete results for the AMV for drug substance(s) with all relevant validation 
parameters, including acceptance criteria and supporting raw data (e.g. 
chromatograms, spectrums etc. )  
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 130  9. GUIDELINE FOR THE SUBMISSION OF PROTOCOL OF 
ANALYSIS  (POA)   
 
This guideline consists of general and specific requirements for the POA submission. 
The general requirements are referred to POA content whilst details of the test 
methods are  illustrated in the specific requirements  
 
9.1 GENERAL REQUIREMENTS  
 
a) The POA shall be written in Bahasa Malaysia  or English only.  
 
b) The POA shall contain the following information:  
 
i) Name of product;  
ii) Name and address of manufacturer;  
iii) Name, signature and desi gnation of authorized person;  
iv) Effective date and Review date.  
 
c) The POA shall comply with the following requirements :  
 
i) To provide updated testing methods, shelf -life specifications and certificate of 
analysis for the intended product to be registered.  
ii) Refe rences used must be clearly stated.  
iii) The latest version of British Pharmacopoeia (BP) and United State 
Pharmacopeia (USP) shall be used as the main references.  
iv) All tests and its specification listed in BP and/or USP in General Monographs 
and Specific Monogr aphs shall be the minimum requirement.  However, a 
specific testing method for quantitative analysis shall be accepted.   
v) All test specifications set by the manufacturer shall be in line or more stringent 
than official pharmacopoeias (BP and USP).  
 
d) Details of test methods shall  include the following items:  
i) List of equipment and apparatus;  
ii) List of chemical, reagents and media;  
iii) Preparation of solutions such as sample, standard, mobile phase, medium etc.;  
iv) Setting up of analytical instrumentation;  
v) System suitabi lity tests (resolution, percentage of Relative Standard Deviation 
(%RSD), tailing factor and theoretical plate for High Performance Liquid 
Chromatography (HPLC) and Gas Chromatography (GC) methods);  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 131  vi) Complete formula for calculation and interpretation of r esults;  
vii) Specification or acceptance criteria.  
 
e)  Photocopies or methods directly copied from pharmacopoeias shall not be 
accepted. In cases where test methods are adopted from official pharmacopeia, 
details of specifics requirements should be submitted.  
 
f)  All relevant data collected during chemical and microbiological testing such as 
chromatograms HPLC/ GC, test reports and formulae used  for calculating should 
also be submitted.  
 
g)  All documents should be arranged and labeled accordingly.  
 
 
9.2 SPECIFIC REQUI REMENTS  
 
The specific requirements for test methods are based on type of tests and dosage 
forms of product as stated in Table IX  below:   
 
 
Categories  Type of Tests  Specific Requirements  
 
 
Physical & 
Performance 
Tests  Physical test (friability, 
uniformity of weight, 
pH, etc)   
Specific method for the intended analysis  
Disintegration test  Specific method for related dosage forms  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 132  Categories  Type of Tests  Specific Requirements  
Dissolution test  
  
a. Dissolution parameters should include:  
i) type of apparatus  
ii) type and volume of dissolution 
medium  
iii) rotation rate  
iv) temperature of solution  
v) sampling time  
b. Complete formula for calculation 
especially for extended and delayed 
release products.  
c. Method of analysis for example HPLC, 
UV, etc.  
 
Quality Test  Identification test   
such as color test, 
Fourier Transform 
Infrared (FTIR), Thin 
Layer Chromatography 
(TLC) etc.   
Specific method for the intended analysis  
 
Impurities/ 
degradation/ purity test  a. Analysis method should include: - 
i) Placebo solution (if any)  
ii) Relative retention times of impurities 
or degradation product  
b. Complet e formula for calculation  
c. Method of analysis for example HPLC, 
TLC, etc.  
Assay and uniformity 
of content  Specific method for the intended analysis  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 133  Categories  Type of Tests  Specific Requirements  
 
Biological Assay of 
Antibiotics  
  
a. Procedure for preparation of following 
solutions/ substances: - 
i) Cultur e medium  
ii) Buffer solutions  
iii) Diluents  
iv) Microorganisms used in assay  
b. Detailed test method (diffusion or 
turbidimetric method), which  includes:  
i) Preparation of standard solutions 
(including steps to counteract the 
antimicrobial properties of any 
preservatives, e tc present in the 
sample)  
ii) Preparation of test solutions 
(including any steps to neutralize the 
antimicrobial properties of any 
preservatives, etc present in the 
sample)  
iii) Test for Media Sterility and Growth 
Promotion Test  
iv) Dilution schemes for test and 
standa rd solutions.  
• Application of test & standard 
solutions (volume, use of latin 
squares, etc.)  
• Incubation temperature & time  
• Interpretation of result  
• Detailed calculation for the test 
including ANOVA table and other 
data showing validity of test 
results.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 134  Categories  Type of Tests  Specific Requirements  
 
 
 
 
 
 
 
 
Safety tests  Pyrogen Test  a. List of depyrogenated or pyrogen -free 
apparatus, glassware and reagents  
b. Temperature recording system  
c. Retaining conditions of the animals  
d. Selection of animals for test  
e. Preliminary test/ Sham test procedure  
f. Detailed test proced ure 
g. Volume and dose of injection  
h. Interpretation of test results  
Bacterial Endotoxins 
Test (BET) or Limulus 
Amebocyte Lysate 
(LAL) Test  
 a. Certificate of analysis for endotoxin and 
LAL (limulus amebocyte lysate) reagent  
b. List of depyrogenated or pyrogen -free 
apparatus, glassware and reagent  
c. Preparation of standard solutions, LAL 
reagent/ substrate, sample  
d. Detailed calculation for determination of 
maximum valid dilution (MVD)  
e. The product's endotoxin limit 
concentration (ELC) and source of 
information  
f. Detailed  calculation for determination of 
endotoxin limit concentration if the ELC 
is not in BP, USP, JP or EP  
g. Detailed test procedure  
h. Calculation and interpretation of test 
result  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 135  Categories  Type of Tests  Specific Requirements  
Sterility Test  
  
a. List of media and reagent  
i) Culture media  
ii) List of rinsing solution , buffer 
solution and diluent  
iii) Neutralizing agent (if any)  
b. Preparation of media & Composition of 
Rinsing Buffer  
c. Test for Media Sterility and Growth 
Promotion Test  
d. Preparation of test sample (including 
steps to eliminate antimicrobial activity 
due to antibi otic samples or samples 
which contain preservatives).  
e. Detailed test procedure for sterility test  
i) Quantity of sample / Volume of 
sample  
ii) Membrane filtration / Direct 
inoculation  
iii) Open System or Closed System (if 
uses Membrane filtration method)  
iv) Volume of rin sing fluid  
Microbial 
Contamination Test  
 Required for ALL non -sterile products   
a. Preparation of media  
b. Test for Growth Promoting, Inhibitory  
and Indicative Properties of Media  
c. Preparation of test sample (including 
neutralizing of preservatives for 
sample s that contain preservatives)  
d. Total Viable Aerobic Count  
•  Detailed test procedure for Total 
Aerobic Microbial Count TAMC) and 
Total Yeasts and Moulds Count 
(TYMC) by Plate Count, Membrane 
Filtration or Most -Probable Number Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 136  Categories  Type of Tests  Specific Requirements  
(MPN) method.  
e. Test for Specified  Microorganisms  
• Detailed  test procedure for each 
specific microorganism tested 
(including identification and 
confirmation test)  
• Specification and acceptance 
criteria  
For details, please refer circular ; 
 Bil (4) dlm. BPFK/PKK/12/05 .  
Maklumat Lanjutan Tentang 
Spesifikasi Baru Untuk Ujian 
Kontaminasi Mikrobial (30 Mac 
2010).  
 Quality Testing for 
Specific Ingredient  For a product con taining specific ingredient 
such as Aphanizomenonflosaquae, Red 
Yeast Rice (Monascus purpureus), 
ingredient(s) derived from seafood and 
placenta, please refer to Appendix 4 and 
Appendix 5 for the testing requirement(s).  
 
 
Note:  
1. Finished product testin g shall be conducted on every batch produced as per approved 
finished product specifications.   
2. Manufacturer shall ensure that products manufactured locally or overseas are free from 
any contamination of Burkholderia cepacia . Please refer to these circulars  for details:  
Ref. (90)dlm.BPFK/PPP/01/03/ Jld. 2   
Ujian Kontaminasi Burkholderia cepacia  (19 December 2012).  
3. Products are  not allowed to send for gamma radiation treatment for the control of microbial 
contamination. Please refer to this circular for details:  
Ref. (54)dlm .BPFK/02/5/1.3.  
Aktiviti Pendedahan Produk Berdaftar kepada Sinar Gamma (18 April 2006)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 137  10. GUIDELINE FOR THE SUBMISSION OF ANALYTICAL   
METHOD VALIDATION (AMV) DOCUMENTS  
 
10.1 TYPES OF ANALYTICAL PROCEDURES TO BE 
VALIDATED  
 
a) Identification tests  
b) Quantita tive tests for impurities' content  
c) Limit tests for control of impurities  
d) Quantitative tests of the active ingredient in the sample (assay and dissolution)  
e) Pyrogen or Bacterial endotoxin test  
f) Sterility test  
g) Microbial Contamination Test  
h) Biological Assay of A ntibiotics  
 
10.2 TYPICAL VALIDATION PARAMETERS FOR CHEMICAL 
TESTS  
 10.2.1  FULL VALIDATION FOR IN -HOUSE METHODS  
 
  Please refer to Table IX on next page.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 138  TABLE IX : 
 
Characteristics  Type of Analytical Method  
Identification  Testing for Impurities   
Assay:  
- dissolution  
(measurement only)  
- content/ potency  
 
 Quantitation  Limit  
Accuracy   √  √ 
Precision 
Repeatability  
Interm. Precision    
√ 
     √ (1)   
√ 
     √ (1) 
Specificity (2)  √ √ √ √ 
Detection Limit   (3) √  
Quantitation Limit   √   
Linearity   √  √ 
Range  √  √ 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 139  10.2.2  PAR TIAL VALIDATION FOR COMPENDIAL/ PHARMACOPOEIAL 
METHODS  
 
TABLE X : 
 
Note:  
 
√ signifies that this characteristic is normally evaluated.  
 
(1)  In cases where reproducibility has been performed , intermediat e precision is not 
needed.  
 
(2)  Lack of specificity of one analytical procedure could be compensated by other 
supporting analytical procedure(s).  
 
(3)   May be needed in some cases.  
 
 
 
 Characteristics  
 
 Type of Analytical Method  
Identification  Testing for Impurities  Assay:  
- dissolution  
(measurement only)  
- content/ potency  Quantitation  Limit  
Precis ion  
Interm ediate  Precision    
√ (1)   
√ (1) 
Specificity (2)  √ √ √ √ 
Detection Limit   (3) √  
Quantitation Limit   √   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 140  10.3 TYPICAL  VALIDATION CHARACTERISTICS FOR 
MICROBIOLOGICAL TESTS:  
 
Table X I: 
Microbiological tests  Validation characteristics  
Bacterial Endotoxin Test  a. Test for Confirmation of Labelled Lysate 
Sensitivity(Verification of criteria for standard curve)  
b. Test for Interfering Factors (Inhibition/  Enhancement tests)  
Sterility T est Validation (Bacteriostasis or Fungistasis) Test  
• Quantity of Sample / Volume of Sample  
• Membrane filtration / Direct inoculation  
• Open System or Closed System (if uses Membrane 
filtration method)  
• Volume of rinsing fluid  
Microbial Contamination 
Test a. Validat ion of total viable aerobic count (suitability of the 
counting method in the presence of product)  1 batch  
b. Validation of test for specified microorganism (suitability of 
the test method)  1 batch  
Microbiological Assay of 
Antibiotics  Linearity of the dose re sponse relationship  
 
Note:  
1. All the analytical validation done by the industry should be in accordance to ASEAN 
Guidelines for Analytical Procedures, ICH Technical Requirements for Registration of 
Pharmaceuticals for Human Use under Validation of Analytica l Procedures: Text and 
Methodology Q2 (R1 ), British Pharmacopoeia (BP),  United State s Pharmacop oeia 
(USP) , or Japanese Pharmacop oeia (JP) . 
2. The applicants should ensure all documents available in the online Quest system are of 
the latest versions. All corre spondence on the protocol of analysis and analytical 
method validation should comply with any relevant circulars regarding the registration 
process. Failure to do so may cause cancellation or rejection of product registration . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 141  11. GUIDELINE FOR THE SUBMIS SION OF PRODUCT 
SAMPLES FOR LABORATORY TESTING  
 
The submission of sample for laboratory testing is as part of the registration process. This 
guideline consists of the general and specific requirements for the submission of samples 
to the Centre for Quality  Control for laboratory testing. The general requirements define the 
condition of the samples to be submitted whereas the specific requirements illustrate the 
additional details needed according to the category of product.  
 
The applicant is given a period of 14 working days  from the date of screening approval to 
send samples for laboratory testing. If the samples are not submitted within the specified 
time frame, the application will be rejected .  
 
The applicants shall comply with these requirements and fai lure to meet any of these 
requirements may cause rejection of the samples.  
 
 
11.1 GENERAL REQUIREMENTS  
 
a) After the screening  has been approved, applicants must make appointment with the 
Laboratory Services Unit for the submission of registration samples for  laboratory 
testing.  
b) Requirements for samples:  
i) A cover letter consisting of the following information should enclosed with 
every sample submission :  
▪ Name and reference no of product;  
▪ Name and address of holder;  
▪ Name, email address and contact number of aut horized person;  
 
ii) Samples submitted must be in their original packaging & labeling.  
iii) Samples submitted must be from the same manufacturing premise as stated 
in the application for registration.  
iv) Samples submitted must have an expiry date of least one (1) year  from the 
date of submission and must be from the same batch number  
c)  For imported products, applicants are required to submit the original import permit 
together with the samples for laboratory testing.The import permit will be issued by Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 142  the Centre for Reg istration for natural product and Centre for Quality Control for 
pharmaceutical products . The applicant should ensure that the import permit is 
endorsed by the enforcement officer at the entry point.  
 
11.2 SPECIFIC REQUIREMENTS  
 
11.2.1  NATURAL PRODUCTS  
 
a) Quantity of samples submitted must be:  
i. a minimum of 6 separate containers of all dosage forms with total 
contents of not less than 200 g or 200 mL; OR  
ii. a minimum of 60 pieces of plasters or patches with total of not less than 
200g.  
 
b) Centre For Quality Contr ol will conduct testing for Heavy Metals, Microbial 
Contamination Test, Disintegration Test, Uniformity Of Weight and screening 
for adulteration for the samples submitted.  
 
c) The result of the tested sample is final and there is no provision for appeal.  
 
11.2.2   PHARMACEUTICAL PRODUCTS  
  (Upon request from NPRA ) 
 
a) An official certificate of analysis and the recent shelf -life specification from the 
manufacturer for the same batch of sample must be submitted with the sample.  
 
b) Quantity of samples submitted must  be in accordance with the quantity 
requested.  
 
c) Other materials such as HPLC columns, reagents, etc must be submitted when 
requested.  
 
d) Reference standards are required to be submitted along with the 
pharmaceutical products. Requirements for these reference  standards are as 
follows:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 143  i) The type & quantity of reference standards submitted must be in 
accordance with the type & quantity requested;  
ii) Reference standards submitted must have an expiry date of least one (1) 
year from the date of submission. In special s ituations, an expiry date of 
not less than six (6) months can be accepted;  
iii) All reference standards must be accompanied by an official certificate of 
analysis for the same batch with the stated purity (as is, dried, anhydrous 
etc.) and all other relevant in formation (water content, loss on drying 
etc.);  
iv) All reference standards must be properly labeled with name, batch 
number, purity and expiry date;  
v) All reference standards must be submitted in small sealed air -tight amber 
glass containers.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 144  SECTION D : INSPE CTION & LICENSING  
 
Inspection and licensing of manufacturing premises or facilities, importers and wholesalers 
of registered products or notified cosmetics on the basis of compliance with Good 
Manufacturing Practice (GMP) as well as Good Distribution Practice (GDP)  are vital 
element of drug control. Compliance to GMP and GDP are  prerequisite for the application 
of a manufacturing license as well as product registration or cosmetic notification whereas 
compliance to GDP is a prerequisite for the application of a wholesale license or import 
license.  
 
12. INSPECTION  
 
Inspection of GMP and GDP are conducted to ensure  manufacturers’, importers’ and 
wholesalers’ compliance towards the current GMP and GDP requirements  besides 
ensuring the registered products and notified cosmetics that are put in the market are safe, 
efficacious and of quality.  
 
The related GMP and GDP g uidelines referred are as below  in Table XII I: 
 
Guidelines  Product Type/ Category  
PIC/S Guide to Good Manufacturing 
Practice for Medicinal Products  * • Pharmaceuticals  (Poison and 
Non-Poison)  
• Veteri nary Medicinal Products  
• Investigational Medicinal Products  
• Active Pharmaceutical Ingredients  
GMP Guideline for Traditional Medicines 
and Health Supplements, 1st Edition, 2008  • Traditional Products   
• Health Supplements  
Guidelines on Good Manufacturing Practice 
(GMP) for Cosmetic (Annex 1, Part 10) • Cosmetics  
Guideline on Good Manufacturing Practice 
(GMP) for Veterinary Premixes, 1st Edition, 
January 2015  • Veterinary  Products  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 145  Guidelines on Good Distribution Practice 
(GDP); 2nd Edition 20 13 
 
Supplementary Notes For Management Of 
Cold Chain Products/ Materials Chapter 15 
Guidelines On Good Distribution Practice 
(GDP)  • For activities related to the 
storage and distribution by 
manufacturers, importers and 
wholesalers (where applicable)  
 
* Refer to Pharmaceutical Inspection Co -operation Scheme (PIC/S) website at www.picscheme.org   
 
Additional Information:  
1. For manufacturing activity via campaign basis for carbapenem and monobactam 
product in area or manufacturing facility for cephalosporin product, please refer 
circular  (1)dlm.BPFK/ 30/06/2 Bhgn 2 . 
2. Please refer (8)dlm.BPFK/PPP/07/25  Directive No. 2 Year 2014  for the requirement 
on Head of Production for pharmaceutical, radiopharmaceutical and veterinary 
manufacturer.  
 
 
12.1 FOREIGN GMP INSPECTION  
 
PRH  must provide acceptable evidence to show that the manufacturer of the product 
follows an internationally accepted standard of Good Manufacturing Practi ce (GMP) and 
recognized by the A uthority in Malaysia.  
 
The Control of Drugs and Cosmetics Regulations 1984 (CDCR) requires that the standard 
of manufacture and quality control of medicinal products manufactured outside Malaysia be 
taken into consideration before the pr oducts are registered with the A uthority. NPRA  as the 
secretariat to the DCA is responsible for ensuring  all manufa cturers of registered products 
in Malaysia are able to provide acceptable evidence that the manufacturing premises 
conform to current GMP requirements. Hence, foreign manufacturers are also subjected to 
GMP conformity assessments through acceptable GMP evi dence or GMP inspection.  
 
For further details and forms , please refer Guidance Document on Foreign GMP 
Inspection.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 146  12.2 MANAGING CHANGES OF MANUFACTURERS FACILITY  
 
This se ction only focuses on manufacturing and its storage / warehouse facilities .  Changes 
on products particulars should be addressed under the Section E of Post Registration 
Process whereby it discusses on Amendments to Parti cular of a Registered Products.  
 
Changes at manufacturers ’ facility can potentially have a quality and safety impact.  It is the 
responsibility of the site to assess information on the changes occurs through formal 
change control system and risk management, where applicable.  Manufacturers,  Importers 
and Wholesalers are recommended to have a system for categorizing types of changes.  
All changes to the facility are required to be notified to the  Centre for Compliance & 
Licensing (CCL) prior to implementation . 
 
Notification of changes will be  review to assess the significance and it may be verified 
during scheduled GMP inspection. The CCL will communicate further and arrange for an 
investigative/for -cause inspection focusing on these changes, if deemed necessary.  
 
Additional Information:  
1. This section is applicable to local manufacturer only. Read further on change 
of importer or wholesaler particulars under Section E of Post Registration 
Process.  
 
2. For further details, please refer to Table of Example Immediate and Periodical 
Notification.  
 
 
Types of notification are as follow:  
 
12.2.1   Immediate notification  
 
This notification is applicable to manufacturers who plan/undergo a 
major/significant/substantial change that could have an impact on the product quality and 
safety.   The Immediate Notifi cation shall be made to or approved by the  Centre for 
Compliance and Licensing (CCL) prior to implementation.  The Immediate Notification can 
be submitted as follows:   
 
 
a) Completing ‘Borang Permohonan Penilaian Pelan Susun Atur Premis Pengilang, 
BPFK -503 fo r changes related to manufacturing layout and process flow  
 
OR Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 147   
b) Official writing which may include at least information such as;  
• Description of changes to the facility  
• Plan of changes (For example: Gantt Chart, Validation Master Plan, etc)  
• Details of the p roducts affected, where applicable  
 
Types of changes are listed in Table A. Example of Immediate Notification  
 
 
12.2.2  Periodical Notification  
 
This notification is applicable to manufacturer  that plan/undergo a minor change that would 
not give any impact to the product quality and safety.  The Periodical Notification can be 
submitted in the form of official writing which may include at least information such as;  
• Description of changes  
• Plan of changes (For example: Gantt Chart, Validation Master Plan, etc)  
 
Example of changes that require Periodical Notification are as per Table B. Example of 
Periodical Notification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 148  Table A. Example of Immediate Notification  
Items  Example  Description  Requirement of 
BPFK -503 Type of 
Application 
under BP FK-
503 Documentation 
Required  Remarks (If 
any) 
1. Change of 
manufacturing  
site (including 
drug 
substance if 
any) 
 Require submission of new 
layout plan  YES 
 New premise 
layout  
(Processing 
Fee= 
RM1000.00)  As per BPFK -
503 
requirement   
2. Change of 
warehous e 
facility  Addition of new warehouse or 
alternative warehouse which 
affecting overall 
manufacturing / operation 
process  e.g. addition of 
sampling room, cold room , 
new warehouse block  
 YES 
 New premise 
layout  
(Processing 
Fee= 
RM1000.00)  
OR  
Revision of 
existing 
premise 
layout or 
addition new 
warehouse in 
the same 
licensed 
premise  
Processing As per BPFK -
503 
requirement  
  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 149  Fee= 
RM500.00)  
3. Change of 
equipment or  
manufacturing 
process  a. Applicable for c hange s of 
critical equipment  NO NOT 
APPLICABLE  Notification  to 
CCL, NPRA  Please refer 
further to 
Section E  
Verification of 
information by 
GMP 
inspection if 
necessary.  
c. Change of critical step in 
manufacturing (including 
packaging) process  NO NOT 
APPLICABLE  Notification to 
CCL , NPRA  
4. Major 
renovation or 
introduction 
of new line  a. Addition of n ew 
manufacturing and/ or 
packaging line  
 YES 
 Revision of 
existing 
premise 
layout 
(Processing 
Fee= 
RM500.00)  
  
As per BPFK -
503 
requirement  
 
   
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 150  b. New production block  YES 
 Revision of 
existing 
premise 
layout  or 
addition new 
production 
block in the 
same 
licensed 
premise  
layout  
(Processing 
Fee= 
RM5 00.00)   
As per BPFK -
503 
requirement   
 
 
 
 
Verification of 
information by 
GMP 
inspection if 
necessary.  
d. Change or addition of 
critical utility such as water 
system, pharma ceutical 
gases and HVAC  NO NOT 
APPLICABLE  Notification to 
CCL, NPRA   
5. Change of 
manufacturing 
rooms  Rename or relocate of 
manufacturing rooms without 
affecting process flow  
E.g. Tabletting Room to 
Compression Room  YES 
 Revision of 
existing 
premise 
layout  
(Processing 
Fee= 
RM500.00)  As per BPFK -
503 
requirement   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 151  Table B.  Example of Periodical Notification  
Items  Example  Description  Requirement 
of BPFK -503 Type of 
Application 
under BPFK -
503 Documentation 
Required  Remarks (If any)  
1. Change of or 
additi on of QC 
facility  E.g. Retention sample, 
microbiological lab oratory , 
stability chamber , etc.  NO NOT 
APPLICABLE  Notification to 
CCL, NPRA   Verification of 
information by GMP 
inspection if 
necessary.  
2. Change of key 
personnel  Applicable to  QA/QC Manager,  
Head of Production, 
Production Pharmacist  NO NOT 
APPLICABLE  Notification to 
CCL  May involve 
information for 
manufacturing 
license holder  
3. Addition of 
manufacturing 
equipments  
without 
affecting 
existing 
manufacturing 
layout plan  New capsulation or tabl etting 
machine in the available room  NO NOT 
APPLICABLE  Notification to 
CCL  Verification of 
information by GMP 
inspection if 
necessary.  
4. Change of 
company 
name or 
address  Change of building number, 
postal code, street name etc.  NO NOT 
APPLICABLE  Notific ation to 
CCL  Please refer further 
to Section E  
May involve 
information for 
manufacturing 
license  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 152  13. LICENSING  
 
According to the Controls of Drugs and Cosmetics Regulations 1984, any company that 
want to manufacture, import or wholesale any registered p roducts need to have a valid 
Manufacturer’s License, Import License or Wholesale License.   
 
 
13.1 TYPE S OF LICENSES  
 
Table XIV : 
 
Type of Licenses  Activity  
Manufacturer’s License  Licensee is authorized to manufacture the registered 
products in the premises specified in the license and to sell 
by wholesale or  supply the products  
Import License  Licensee is author ized to import and sell by wholesale or 
supply the registered products from the address of the 
premises  
Wholesaler’s License  Licensee is authorized to sell by wholesale or supply the 
registered products from the address of the business 
premises specified in the license  
 
 
13.2 LICENSE APPLICATION FORM  
 
1. The li cense a pplication for registered products (Manufacturer’s License, Import License 
and Wholesaler’s License) shall be submitted by filling Borang BPFK -413 Application for 
License for Registered Product.  
 
2. Application form must be submitted with the following supporting documents.  
 
a)   A copy of Company/ Busines s Registration Certificate  
b)   A copy of Business License (Local Authority) for business premise or store (if any)  
c)   A copy of Applicant’s/License Holder’s Identity Card  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 153  d)  A copy of Annual Retention Certificate and/or Type A License (This document is  
necessary if products manufactured/ imported/ wholesale are Scheduled Poison A 
products or any other products that require a Pharmacist)  
 e)   A copy of previous license (For renewal application)  
 
3. An application shall only be processed if it is complete a nd payment has been 
approved.  
 
4. The processing fee shall not be refundable. The processing fee of an application for a 
Manufacturer’s License is RM  1,000.00 and RM  500.00 for an Import License  or a 
Wholesaler’s License.  
 
5. Each license is valid for one (1) ye ar. 
 
 
13.3 ADDITIONAL  PRODUCT  LIST OF LICENSE FOR REGISTERED 
PRODUCTS  
 
1. Additional product list of License is issued based on the application submitted when the 
products are newly registered, change of manufacturer or importer or any registered 
products whi ch are not listed  from the products list of Manufacturer’s License and 
Import License.  
 
2. When submitting the application form for Additional  Product  List of License for 
Registered Products the documents that shall be attached together are a copy of 
Manufact urer’s License/ Import License and a copy of approval letter from the Authority 
(The Authority’s meeting result).  
 
3. The a pplication of additional list shall be submitted by filling Borang BP FK-413T  
Application for (Additional) Product List of License for Registered Product.  
 
 
13.4 GMP CERTIFICATE  
 
1. GMP Certificate is  issue d for the purpose of expor ting locally manufactured registered 
products. It endorses that the local manufacturer complies with the  current GMP 
requirements. These  certific ate are required  by the overseas  regulatory agencies for 
products registration in their countries.  Thus, when filling in the GMP C ertificate Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 154  application form, the correct address of the overseas  regulatory a gencies given by the 
company is crucial.  
 
2. The a pplication of GMP Ce rtificate shall be submitted online through QUEST3+ which is 
equivalent to the manual form Borang BPFK -420 Permohonan Siji l Amalan Perkilangan 
Baik (APB) that is no longer in used.  
 
3. A fee of RM50.00 is payable on the issue of such certification.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 155  SECTION E: POST -REGISTRATION PROCESS  
 
14. MAINTENANCE OF REGISTRATION  
 
Registration  of a product shall be valid for five ( 5) years or such period as specified 
in the Authority database (unless the registration is suspended or cancelled by the 
Authority).  
 
Application for re -registration (renewal of product registration) of a product shall be 
submitted  within six (6) months prior to the expiry of the validity period of a 
product registration. A letter of reminder for product re -registration will be issued to 
the product registration holder 3 months prior to the expiry date of a product 
registration.  
 
After the expiry date, the status of product registration shall be automatically 
changed to ‘expired’, and applicant will not be able to submit the application for 
product re -registration. Any form of appeal shall not be considered  if re-registration 
applic ation is not submitted before the expiry date of a product registration since 
reminder letter is issued 3 months prior to the expiry date. A new registration 
application shall be submitted if applicant wishes to continue to market the product.  
 
After the e xpiry of product registration date, the product is deemed unregistered.  
Products of which their re -registration is on hold due to unmet requirements but has 
passed its registration expiry date, the new registration date shall be updated 
according to the DC A Meeting date where the re -registration application is approved 
by the DCA.  
 
The application for product re -registration shall only be submitted when all of the 
registration requirements have been complied with. Failure to do so shall 
result in the re -registration application being rejected by the Authority.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 156  14.1 REQUIREMENT  
 
The requirements for product re -registration as aforementioned are as follows:  
 
a) Patient dispensing pack size for pharmaceutical product containing scheduled 
poison or non -schedule d poison with tablet/capsule dosage form, including oral 
liquid preparation and dermatological preparation.  
Note:  Please refer Appendix 10: Guideline on Patient Dispensing Pack for 
Pharmaceutical.  
 
b) Bioequivalance study report for all registered generic pro ducts containing 
scheduled poison with immediate release, oral, solid dosage form (came into 
force starting from 1st January 2013)  
Reference:  
(10) dlm.BPFK/PPP/01/03 Jld.1  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 1 Tahun 2011 : Direktif 
Penguatkuasaan Keperluan Kajian Bioekuivalens Bagi Semua Produk Generik 
“Immediate Release, Oral, Solid Dosage Form” Yang Mengandungi Bahan Aktif 
Racun Berjadual Serta Akreditasi Pusat Kajian BioEkuivalens (2 March 2011)  
 
c) Bioequivalence study report for all registered generic products containing 
scheduled poison with effervescent, dispersible, orodispersible, sublingual, 
buccal and chewable dosage form (c omes into force for product registration 
which is expiring starting from 1st January 2019)  
Reference:  
(27) dlm. BPFK/PPP/07/25  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 3 Tahun 2015 : Direktif 
Penguatkuasaan Keperluan Kajian Bioekuivalens (BE) Bagi Semua Produk 
Generik Dalam Bentuk Dos Oral Tablet/Kapsul Yang Bersifat Effervercent, 
Dispersible, Orodispersible,  Sublingual, Buccal  Dan Chewable  Yang 
Mengandungi Bahan Aktif Racun Berjadual (23 February 2015)  
 
(45) dlm.BPFK/PPP/01/03 Jld.3  
Lanjutan Tarikh Penguatkuasaan Untuk Memenuhi Keperluan Kajian 
Bioekuivalens (BE) Bagi Produk Generik Dalam Bentuk Dos Oral Tablet/Kapsul 
Yang Bersifat Effervescent, Dispersible, Orodispersib le, Sublingual, Buccal  dan 
Chewable  Yang Mengandungi Bahan Aktif Racun Berjadual (31 May  2016)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 157  d) Regulatory control of active pharmaceutical ingredient (API) for all dosage form 
of registered pharmaceutical products containing scheduled poison (comes into 
force for product registration which is expiring starting from 1st January 2020)  
• API information shall be submitted at least one year prior to the product 
registration expiry date.  
• Please refer also Appendix 6: Guideline on Regulatory Control of Active 
Phar maceutical Ingredients  
 
Reference:  
(7) dlm.BPFK/PPP/07/25  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 8 Tahun 201 3 : Direktif 
Perluasan Skop Pelaksanaan Kawalan Regulatori Ke Atas Bahan Aktif 
Farmaseutikal Bagi Produk Generik Yang Mengandungi Racun Berjadual (Fasa 
II) (16 January 2014)  
 
(11) dlm.BPFK/PPP/01/03 Jld.3  
Lanjutan Tarikh Pelaksanaan Pengawalan Bahan Aktif Farmaseutikal (API) Bagi 
Produk Farmaseutikal Berdaftar Yang Mengandungi Racun Berjadual (27 June 
2014)  
 
e) For pharmaceutical pr oducts which were submitted for registration before the 
year 2009, applicants shall ensure that stability study for the products at zone IV 
B has been conducted and granted variation approval before submission of re -
registration application.  
Reference:  
(1) dlm. BPFK/PPP/01/03 Jld.3  
Keperluan Data Kajian Stabiliti Dalam Zon IV B Bagi Produk Farmaseutikal 
Berdaftar (05 April 2013)  
 
(5) dlm. BPFK/PPP/01/03  
Lanjutan Tarikh Berkuatkuasa Untuk Memenuhi Keperluan Data Kajian Stabiliti 
Dalam  Zon IV B Bagi Produk Farmaseutikal Berdaftar (14 August 2013)  
 
For pharmaceutical products that required exemption from zone IV B 
requirements, applicants shall submit the exemption request via variation 
application MiV -PA through the current online syste m. 
 
f) Valid GMP document/certificate for imported product (came into force starting 
from 1st January 2014)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 158  To maintain the registration of an imported product, the PRH shall comply with 
GMP requirement as stated in the directive issued by the Director of 
Pharmaceutical Services under Regulation 29, CDCR 1984.  
Note:  Please refer also Guidance Document for Foreign GMP Inspection (5th 
Edition March 2018)  
 
Reference:  
Bil (25) dlm BPFK/PPP/01/03 Jld.1   
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 1 Tahun 2012 : Syarat 
Pendaftaran Produk Farmaseutikal Dari Luar Negara Berkaitan Keperluan 
Amalan Perkilangan Baik (APB) (09 February 2012)  
 
Bil (96)dlm.BPFK/PPP/01/03 Jld.2  
Surat Pekeliling Bagi Direktif Mengenai Syarat Pendaftaran Produk 
Farmaseutikal Dari Luar Negara Berkaitan Keper luan Amalan Perkilangan Baik 
(APB) (28 December 2012)  
 
(32) dlm. BPFK/PPP/07/25  
Arahan Pengarah Kanan Perkhidmata n Farmasi Bil.1 Tahun 2016: Direkfif 
Mengenai Keperluan Pemeriksaan Amalan Perkilangan Baik (APB) Luar Negara 
Bagi Tujuan Pendaftaran/Pendaftaran Semula Produk Farmaseutikal Berdaftar 
Dengan Pihak Berkuasa Kawalan Dadah (PBKD) (22 January 2016)  
 
(123) dlm. BPFK/30/05/1 Bahagian 4  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil.11 Tahun 2016: Direkfit 
Mengenai Penerimaan P engesahan Pematuhan Amalan Perkilangan Baik (APB) 
Bagi Tujuan Pendaftaran Semula Produk Farmaseutikal Berdaftar dengan Pihak 
Berkuasa Kawalan Dadah (PBKD) (30 June 2016)  
 
Bil (15) dlm. BPFK/PPP/06/06 Jld.47  
Pendaftaran Bersyarat Bagi Produk -Produk Dengan Sijil Amalan Perkilangan 
Baik (APB) dari Ministry of Economic Affairs, Taiwan (1 February  2017)  
 
Bil. (4) dlm. BPFK/PPP/07/25 Jld.2  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil. 4 Tahun 2018: Direkfit 
Mengenai Penerimaan Pengesahan Pematuhan Amalan Perkilangan Baik (APB) 
Bagi Pengilang Farmaseutikal Bagi Tujuan Pendaftaran Baru/Pendaftaran 
Semula Produk Farmaseutikal Berdaftar Dengan Pihak Berkuasa Kawalan 
Dadah (PBKD) (16 May 201 8) 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 159  g) Amendment of product name consisting only generic name for registered 
pharmaceutical product containing scheduled poison and non -scheduled poison 
(came into force starting 1 Janaury 2017)  
Reference:  
(39) dlm. BPFK/PPP/01/03 Jld.3  
Pekeliling Penggunaan Nama Generik Pada Nama Produk Bagi Produk 
Farmseutikal (21 December 2015)  
 
h) Endorsement le tter of ancillary medical device component (from Medical Device 
Authority, Malaysia) for re -registration of drug -medical device combination 
product (comes into force for product registration which is expiring starting from 1 
July 2019)  
Note:  Please refer a lso Guideline for Registration of Drug -Medical Device and 
Medical -Device -Drug Combination Products.  
 
Reference:  
(9) dlm. BPFK/PPP/07/25 Jld.1  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil.4 Tahun 2017: Direktif 
Kuatkuasa Pemakaian Guideline for Registration of Drug -Medical Device and 
Medical D evice -Drug Combination Products (10 March 2017)  
 
 
14.2 APPLICATION FOR PRODUCT RE -REGISTRATION  
 
 The application for product re -registration shall be submitted and herein paid via the 
current online system.  
 
a) The non -refundable processing fees for product re-registration are as follow:  
i. Traditional Product    : RM   500.00 per product  
ii. Pharmaceutical Product (including  
Health Supplement)    : RM1,000.00 per product   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 160   
15. WITHDRAWAL OF PRODUCT REGISTRATION  
 
The Product Registration Holder  shall inform the Authority pertaining to decision to 
withdraw the registration of a product before the end of the  validity of such 
registration and shall state the reasons for the decision. The o nus is on the holder to 
inform the manufacturer/ contract manufacturer.  
 
The regis tration of a produ ct, once withdrawn, shall not be reinstated and  certificate 
of registration  of the withdrawn product , if any, shall be invalid.  
 
A new applicati on shall be submitted if the product registration is required again at a 
later date . 
 
 
16. AME NDMENTS TO PARTICULARS OF A REGISTERED 
PRODUCT  
 
Throughout the life cycle of a  registered product, changes to improve the product’s 
efficacy, quality and safety are likely to occur.  Therefore, applicant shall inform the 
Authority  pertaining to any changes or amendment made to particulars of a 
registered product via variation applications.  
 
An applicant who wishes to apply for any application for imported products of which 
GMP requirement is a consideration , such as change of manufacturing site and 
variatio n, shall comply with the requirement , as stated in directive issued by the 
Director of  Pharmaceutical Services under Regulatio n 29, CDCR  1984 . The 
Authority shall not consider any application in which the requirement is failed to 
comply with.   
Reference : 
a) Bil (25) dlm BPFK/PPP/01/03 Jld 1   
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 1 Tahun 2012 : Syarat 
Pendaftaran Produk Farmase utikal Dari Luar Negara Berkaitan Keperlua n 
Amalan Perkilangan Baik (APB) (09 February 2012)  
b) Bil (96)dlm.BPFK/PPP/01/03 Jld. 2  
Surat Pekeliling Ba gi Direktif Mengenai Syarat Pendaftaran Produk 
Farmaseutikal Dari Luar Negara Berkaitan Keperluan Amalan Perkilangan Baik 
(APB) (28 December 2012)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 161  16.1 VARIATION  
 
16.1.1  VARIATION APPLICATION FOR PHARMACEUTICAL  
PRODUCTS  
 
Variation application for pharmace utical  products shall follow Malaysian Variation 
Guideline (MVG)  as stated in the directive issued by the Director of Pharmaceutical 
Services under Regulation 29, CDCR 1984 .  
Reference: (2) dlm BPFK/P PP/07/25 .) 
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 3 Tahun 2013:  Direktif untuk 
melaksanakan Malaysian Variation Guideline (MVG)  (29 April 2013)  
 
If deemed necessary, NPRA  reserves the right to request for additional supporting 
documents and variat ion approval letters from other regulatory bodies for all 
categories of product.  
 
The registration of a product shall be reviewed for suspension or cancellation  if 
changes that fall under Major Variation (MaV) and Minor Variation Prior Approval 
(MiV-PA) ar e implemented without prior approval of the Authority.  
 
For drug substance that are yet to be regulated by NPRA , application for variations 
and supporting documents related to drug substance at  Appendix 12  are still 
applic able until further notice.  
 
 
MODE OF SUBMISSION  
 
Applicant shall submit the variation application through the current online system.   
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 162  16.1.2 VARIATION APPLICATION FOR HEALTH SUPPLEMENT AND 
NATURAL PRODUCTS  
 
Variation application for Health Suppleme nt Products and Natural Products shall 
follow Malaysian Variation Guideline (MVG) For Natural (Traditional Medicine & 
Homeopathy) And Health S upplement Products (Abridged Evaluation)  as stated in 
the directive issued by Director of Pharmaceutical Services under Regulation 29, 
CDCR 1984; Directive No. 14 Year 2016.  Ref: BPFK/PPP/07/25(45):  Direktif Untuk 
Melaksanakan  Malaysian Variation Guideline (MVG) For Natural (Traditional 
Medicine & Homeopathy) And Health Supplement Products (Abridged Evaluation )  
 
Variation refers to change of particulars of a registered product. No change of any 
particulars of a registered product shall be made without prior approval from NPRA. 
The registration of a product shall be reviewed for suspension or cancellation if 
changes are implemented wi thout prior approval of the Authority.  
 
All supporting documents in accordance to the specified conditions laid down for 
each type of variation should be submitted. For further information pertaining to 
conditions and supporting documents required for an application of variation, please 
refer toMalaysian Variation Guideline (MVG) For Natural (Traditional Medicine & 
Homeopathy) And Health Supplement Products (Abridged Evaluation).  
 
If deemed necessary, NPRA reserves the right to request for additional suppo rting 
documents and variation approval letters from other regulatory bodies for all 
categories of products.  
 
 
MODE OF SUBMISSION  
 
Applicant shall submit the variation application through the current online system.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 163  16.1.3 VARIATION APPLICATION FOR BIOLO GICAL PRODUCTS  
 
Variation application for biologics shall follow the Malaysian Variation Guidelines for 
Biologics ( MVGB)  as stated in the directive issued by Director of Pharmaceutical 
Services under Regulation 29, CDCR 1984; Directive No. 2 Year 2017. Ref: 
BPFK/PPP/07/25(7)Jld.1:  Direktif Untuk Melaksanakan Malaysian Variation 
Guideline For Biologics (MVGB)  
 
The MVGB will serve as a main document for all variation applications.  The MVG 
will serve as a secondary document for all administrative changes.   If there are 
variations that are not covered in both MVGB and MVG, the PRH should determine 
the classification of change based on a change -specific risk assessment using the 
principles and examples that have been set out in the MVGB.  Please refer to 
section 3.0 (General Considerations) of the MVGB for further details.  
 
All applications submitted either via the QUEST3+ system or manually shall be 
accompanied by a cover letter, of which the content of the cover letter shall be in 
accordance to 4.1.2 and 4. 1.3 of the MVGB.  
 
 
16.2 CHANGE OF MANUFACTURING SITE  
 
Change of Manufacturing Site (COS) refers to change of manufacturing site for 
certain part or all of the manufacturing process of a product, but it does not cover 
changes related to a new site, where on ly:  
a) batch release takes place OR  
b) to a new packager (secondary packaging or labelling) , as these changes are 
covered under applications for amendments to the particulars of a registered 
product (variation) . Please refer to paragraph Section E: 16.1 Variation . 
However, a change of manufacturing site for biologics  shall require a new product 
registration  if the change is extensive and will have an impact on the quality, safety 
and efficacy profile of the final product.  
Upon receipt of complete application, the application shall be processed within sixty 
(60) working days.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 164  16.2.1 CONDITIONS ON APPLICATION FOR COS:  
 
Change in Manufacturing Site is only applicable  for the following situations:  
a) a change in manufacturing site for the same company, including rationalization in 
the event of mergers ; or 
b) a company which previously contracts out the manufacture of its product(s) , 
transfers the manufacture of the product to its  own manufacturing premises; or  
c) a company appoints a cont ract manufacturer in Malaysia for pharmaceutical 
products i.e. scheduled poison, non -scheduled poison & health supplement 
products except natural products. This change includes a change from a 
contract manufacturer to a local contract manufacturer or a cha nge from own 
manufacturing premise to a local contract manufacturer.  
Note: The change in manufacturing site for this condition will not be considered if 
the change is made without acceptable justification or submitted too frequently.  
 
A change of manufactu ring site under a crisis situation may be considered for the 
following:  
a) A change between contract manufacturers for natural products;  
b) A change to a contract manufacturer outside of Malaysia for pharmaceutical 
products.  
 
Validity of registration for a produ ct which has been approved for change of 
manufacturing site remains unchanged . 
 
16.2.2 CONDITIONS ON GOOD MANUFACTURING PRACTICE (GMP):  
 
a) The new manufacturing site shall comply with current Good Manufacturing 
Practice (cGMP);  
b) Local manufacturing sites are subjected to pre -licensing inspections by the 
NPRA  inspectors;  
c) For manufacturing sites outside Malaysia, certification on GMP by the competent 
authority is acceptable.  
d) The Authority reserves the  right to conduct an inspection on any manufacturing 
site. 
e) For further information pertaining to the requirements on GMP, please refer to 
these circulars and directive.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 165  i) Bil (35) dlm. BPFK/PPP/01 /03 
Pemeriksaan Amalan Pengilangan Baik Bagi Pengilang Di Luar Negara (03 
June 2009)  
ii) Bil (40) dlm. BPFK/PPP/01/03   
Pekeliling Peme riksaan Amalan Pengilangan Baik Bagi Pengilang Di Luar 
Negara ( 08 September  2009)  
iii) Bil (25) dlm BPFK/PPP/01/03 Jld 1   
Arahan Penga rah Kanan Perkhidmatan Farmasi Bil 1 Tahun 2012 : Syarat 
Pendaftaran Produk Farmaseutikal Dari Luar Negara Berkaitan Keperluan 
Amalan Perkilangan Baik (APB) (09 February 2012)  
iv) Bil (96)dlm.BPFK/PPP/01/03 Jld. 2  
Surat Pekeliling Bagi Direktif Mengenai Syarat Pendaftaran Produk 
Farmaseutikal Dari Luar Negara Berkaitan Keperluan Amalan Perkilangan 
Baik (APB) (28 December 2012)  
 
 
16.2.3 TYPES OF MANUFACT URING SITE CHANGES (COS)  
 
Table XVI II: 
No. Types of COS  Description  
1. Type I  Change of 
manufacturing 
site within 
Malaysia  Change in the location of the site of manufacture 
within Malaysia only. This change may be due to 
upgrading of facilities, and/or ex pansion of 
manufacturing activities or moving to a newly 
constructed plant, or appointment of a contract 
manufacturer for pharmaceutical products.  
2. Type II  Change of 
manufacturing 
site from 
foreign country 
to Malaysia  Change in location of the site of m anufacture from 
outside of Malaysia to a location in Malaysia. This 
change may be due to the ability of the local 
counterpart to manufacture the product, or 
appointment of a contract manufacturer for 
pharmaceutical products.  
3. Type III  Change of 
manufac turing 
site located 
outside 
Malaysia  Change of location of the site of manufacture to 
manufacturing facilities located outside Malaysia. This 
may be due to a merger or rationalization of 
manufacturing sites in line with multinationals’ 
manufacturing strate gies.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 166  No. Types of COS  Description  
4. Type IV  Change of 
manufacturing 
site for sterile 
products  i) Transfer of manufacturing of an aseptically 
processed sterile product to a:  
a) newly constructed or refurbished aseptic 
processing facility or area;  
b) an existing processing facility or area t hat does 
not manufacture similar approved products.  
    (For example, transferring the manufacture of a 
lyophilized product to an existing aseptic 
process area where there is no approved 
lyophilized product is manufactured).  
ii) Transfer of a finished product  sterilized by terminal 
processes to a newly constructed facility at a 
different manufacturing site.  
5. Type V  Change of 
manufacturing 
site in crisis 
situation  i) Change of location of the site of manufacture that is 
deemed necessary due to certain circum stances such 
as natural disasters, closure or suspension of premise 
(revocation of manufacturing license), bankruptcy and 
matters related to breach of product qua lity, safety and 
efficacy ONLY.  
 
ii) Prior to submission of Type V COS,  approval letter 
issue d by the secretariat of the Authority shall be 
obtained.  
 
iii) Applicat ion for Type V COS must be made within 
three (3) months  from the date of the crisis.  
 
iv) Type V COS ap plications for natural products and 
health supplements are only applicable for loc al 
manufacturers.  
 
 
16.2.4 MODE OF SUBMISSION  
 
 Applicant shall submit the application through the current online system.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 167  16.2.5 OTHER INFORMATION  
 
a) Application for COS will be rejected if applicant failed to submit required data 
within six (6) months  from the first correspondence date;  
 
b) All supporting documents in accordance to the specified conditions laid down for 
each type of COS should be submitted. For details , please refer to Appendix 13: 
Supporting Documents Requi red for Change of Manufacturing Site Application.  
 
c) If deemed necessary, NPRA  reserves the right to request for additional 
supporting documents.  
 
d) For further information pertaining to COS , please refer these circulars.  
 
i) Bil (59) BPFK/17/VF/9.2   
Prosedur Permohonan Pertukaran Tapak Pengilang Produk Berdaftar: Polisi 
Menolak Permohonan Pertukaran Tapak Pengilang Sekiranya 'Tiada 
Maklumbalas / Maklumbalas Tidak Lengkap' Dikemukakan Oleh Pemohon 
Dalam Tempoh Enam (6) Bulan Dari Tarikh Permintaan'  (20 May 2009)  
ii) Bil (22) dlm. BPFK/PPP/01/03   
Keperluan  Kajian BioEkuivalens Bagi Produk “Generic Immediate Release 
Oral Solid Dosage Form ” yang Bertukar Tapak Pengilangan  (01 February 
2009)  
iii) Bil (31) d lm. BPFK/PPP/01/03  
Makluman  Susulan Berkaitan Kajian Bioekuivalens bagi Produk 'Generic 
Immediate Release Oral  Solid Dosage Form' yang Bertukar Tapak 
Pengilangan  (13 May 2009)  
iv) Bil (39) dlm. BPFK/PPP/01/03  
Permohonan Pertukaran Tapak Pengilang Jenis V Iaitu Pada Situasi Krisis 
(16 July 2009)  
v) (10) dlm.BPFK/PPP/01/03 Jilid 1  
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 1 Tahun 2011 : Direktif 
Penguatkuasaan Keperluan Kajian Bioekuivalens Bagi Semua Produk 
Generik “Immediate Release, Oral, Solid Dosage Form” Yang Mengandungi 
Bahan Akt if Racun Berjadual Serta Akreditasi Pusat Kajian BioEkuivalens (2 
March 2011)  
vi) Bil (7)dlm.BPFK/PPP/01/03 Jld. 3  
Kebenaran Pertukaran Tapak Pengilang Ke Pengilang Kontrak Tempatan (18 
February 2014)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 168  16.3  CHANGE OF PRODUCT REGISTRATION HOLDER  
[Reference: Directive (3)dlm.BPFK/PPP/07/25 ] 
Arahan Pengarah Kanan Perkhidmatan Farmasi Bil 4 Tahun 2013 : Direktif Untuk 
Meminda Prosedur Permohonan Pertukaran Pemegang Pendaftaran Produk (03 
June 2013)  
 
16.3.1 INTRODUCTION  
 
A transfer procedure for the purpose of changing the existing product registration 
holder (PRH) that is authorized to market a registered product in Malaysia to another 
holder.  This procedure allows the registered product to maintain the same 
registration number.  
Upon receipt of complete online application via QUEST system and hardcopy of 
original documents, the change of PRH application shall be processed within forty -
five (45) working days.  
 
16.3.2 CONDITIONS  
 
The application is subjected to  the following conditions:  
1) An application to transfer the marketing authorization of a registered product 
shall be submitted by the existing PRH . 
2) The new PRH shall be a registered company/ business with Companies 
Commissioner of Malaysia and a registered Q UEST user with National 
Pharmaceutical Regulatory Division (NPRA).  
3) The registered product intended to be transferred to a new PRH shall have a 
remaining registration validity period of at least six (6) months . If the 
registration validity is less than six (6) months, the existing PRH shall first apply 
for the renewal of this registered product.  
4) No change /s can be made  to the technical data or approved pharmaceutical / 
pharmacological information, including the texts of the product label and leaflet, 
except  the name and address of the approved PRH.  
5) In the interim, the existing PRH shall still bear the marketing authorization 
responsibility of the said registered product.  
6) The transfer shall come into effect on the day the DCA makes a decision on the 
outcome of the Change of PRH application. Upon the transfer of product Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 169  registration to the new PRH, the authorization issued to the previous PRH will be 
cancelled as the product cannot be marketed simultaneously by two different 
PRHs. The new PRH shall then bear r esponsibility for the said product.  
7) However, the existing PRH is allowed to deplete the stocks and will still be held 
liable should any pharmacovigilance issues or quality defects associated with the 
product arise during the interim of the transfer.  
8) The ex isting PRH or newly approved PRH shall submit a written request to 
deplete the existing stocks after DCA approval has been obtained for the 
transfer. The PRH that submits the request shall be held responsible for the 
batches and quantity requested in the e vent any pharmacovigilance issues or 
quality defects associated with those product batches arise.  
9) Application shall be rejected if the applicant fails to provide satisfactory required 
documents within 30 working days starting from the first date of corresp ondence 
by the evaluator.  
 
16.3.3 APPLICATION  
 
 The existing PRH shall submit the following documents and payment to NPRA : 
1. Fill and submit application online via the current QUEST system  
2. Processing Fee (refer 16.3.4)  
3. Original Supporting Documents (refer 16 .3.5) 
 
16.3.4 PROCESSING FEE  
 
1. NON -REFUNDABLE processing fee : 
- For a Traditional Product    : RM    500.00  
- For a Pharmaceutical Product  (including  : RM 1,000.00  
Health Supplement)  
 
2. The processing fee shall be paid online via QUEST immediately after the 
chang e of PRH application has been submitted.  
 
3. Foreign currenc y is not accepted.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 170   
16.3. 5 SUPPORTING DOCUMENTS  
 
 
1. List of required supporting documents : 
 
i) Letter of Authori zation (LOA) issued by the P roduct Owner . If the Product 
Owner is an entity registered outs ide of Malaysia then the LOA must be  
certified by the Notary Public from the country of origin of said Product 
Owner. However, if the Product Owner is a Malaysian registered entity 
then the LOA must be certified by a local Commissioner for Oaths The 
LOA sh all consist  of the following information:  
a. The registered name and registration number of the product(s) concerned.  
b. Company name, business registration number and address of the 
proposed new PRH as registered in QUEST.  
c. Company name, business registration nu mber and address of the existing 
PRH as registered in QUEST.  
d. Effective date of the appointment and termination given by the product 
owner. If the effective date is not mentioned, the date of the LOA issued 
will be considered as the effective date.  
e. Signatu re of the Managing Director/ Director/ President/ Chief Executive 
Officer/ General Manager who has overall responsibility for the company 
or organization.  
f. Full and complete name, address, email address (if available), telephone 
and fax number (if available ) of the Product Owner as registered in 
QUEST.  
g. The Product Owner name and address in the letterhead of the LOA must 
be identical to the information of the Product Owner registered in QUEST 
for the product(s) concerned.  
 
*Note : LOA format example (Please re fer 16.3.6 Supporting Document Format Example)  
 
ii) Resolution by the Company Board of Directors of local Product Owner 
verifying that ALL the Board of Directors/ Partners have given their consent to 
the Change of PRH.  This resolution must be signed by ALL the  Board of 
Directors/ Partners. If the Product Owner is not a local entity, please omit.  
iii) Latest document indicating details of director/s and shareholder/s of local 
Product Owner  (e.g. Corporate Information, Summary of Share Capital, 
Directors/Officers, Sha reholders/Members from the MyData SSM website).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 171  These documents must be certified by the Commissioner for Oaths (i.e. 
Statutory Declaration).  If the Product Owner is not a local entity, please omit.  
iv) Resolution by the Company Board of Directors of existin g PRH verifying that 
ALL the Board of Directors/ Partners have given their consent to the Change 
of PRH.   This resolution must be signed by ALL the Board of Directors/ 
Partners.  
v) Latest document indicating details of director/s and shareholder/s of existing  
PRH  (e.g. Corporate Information, Summary of Share Capital, 
Directors/Officers, Shareholders/Members from the MyData SSM website).  
These documents must be certified by the Commissioner for Oaths (i.e. 
Statutory Declaration).  
vi) The Company/ Business Registra tion Certificate of the proposed new PRH 
certified true copy by a MAICSA accredited company secretary or by the 
Companies Commission of Malaysia (e.g. Form 9 and/ or Form 13).  
vii) Statement of Acceptance as Product Registration Holder, NPRA -430.5(3)  to 
be filled by the proposed new PRH.  
2. The ORIGINAL documents listed above shall be submitted to the Centre of 
Product Registration, NPRA once payment for the appli cation has been made.  
Photocopies of documents will not be accepted.  
3. Date of the documents including date of stamps/signatures of certifying bodies 
must be recent, i.e. not exceeding six (6) months from the date of application.  
4. Each page of attachment (if  any) i.e. product list must be endorsed by the 
signatory.  
5. The Secretariat, if necessary, has the right to request further supplementary 
information or documentation.  Failure to provide these additional information or 
documentation(s) will result in the r ejection of the transfer application.  
 
 
16.3.6  SUPPORTING DOCUMENT FORMAT EXAMPLE  
 
Suggested format example for the Letter of Authorization.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 172  PRODUCT OWNER Letter Head (full and complete address, email address, telephone and fax number)  
 
(Please state) Da te of LOA  (the existing PRH shall submit an application within 6 months from this date)  
 
Drug Control Authority,  
Lot 36, Jalan Universiti,   
46200 Petaling Jaya,  
Selangor, Malaysia.  
 
Dear Sir/ Madam,  
 
LETTER OF AUTHORIZATION FOR TRANSFER OF PRODUCT REGISTR ATION HOLDER  
 
The above subject matter is referred.  
 
Due to ( please state) reason of the transfer ,  
 
2. We, Name of registered Product Owner , the undersigned as the product owner for the said product(s) 
listed below:  
     Name of Product(s)    Registration Num ber 
  (If number of product > 10, endorsed attachment is allowed.)  
 
hereby authorize  
Company name with business registration number and full address of the proposed new PRH   
to be the Product Registration Holder and to act on our behalf/ responsible for a ll matters pertaining to the 
registration of the listed product(s) including obtaining approval for any subsequent product variation and 
maintenance of the product(s) registration.  
 
3. Therefore, we hereby terminate marketing authorization of the existing Pro duct Registration Holder  
Company name with business registration number and full address of the existing PRH  
for the listed product(s) effectively on  date of authorization / termination.  
 
4. We shall confirm that the entire dossier of the listed product(s) in cludes all the data in support of the 
original application, together with all correspondence with the Drug Control Authority (DCA)/ National 
Pharmaceutical Regulatory Division  concerning the listed product(s), to be transferred from Company name 
of the exi sting PRH  to Company name of the proposed new PRH upon the approval from DCA.  
 
Thank you.  
 
Sincerely,  
 
*Company officer’s signature(s)  
*Full name & Title/ Positition  
Company stamp  
 
cc:  Company of proposed new PRH  
 Company of existing PRH  
 Product Manu facturer  
 
 
 
 
 IMPORTANT NOTICE:  
1. *LOA shall be signed by Managing Director/ Director/ President/ Chief Executive Officer/ 
General Manager who has overall responsibility for the company or organization.  
2. **LOA shall be certified by Notary Public of the country of origin for overseas company or 
Malaysia Commissioner for Oath for local company.  (A copy of LOA shall be sent to 
these companies by the 
Product Owner)  **Certified by 
Notary Public/ 
Commissioner 
for Oath  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 173  16.3. 7 FLOWCHART FOR THE CHANGE OF PRODUCT REGISTRATION 
HOLDER  
 
 
 Company (Existing PRH)  
Submit complet e application to NPRA  as below;  
1. Fill and submit application online via QUEST system.  
2. Processing Fee (refer 16.3.4) . 
3. Submit original su pporting documents (refer 16.3.5) to Centre 
for Product Registration.  
 
 
 
 
 Secretariat  
Receive and evaluate application and original documents.   
       
 
  
 Secretariat  
 Processing of evaluated application ; 
1. Satisfactory:  
a) Table to DCA meeting for appro val 
2. Non-satisfactory:  
b) Table to DCA meeting for rejection (processing fee is 
NON -REFUNDABLE in the event the application is 
rejected)  
 
 
 
 DCA Meeting  
 
 
 
  
 
 
 Non-satisfactory  
Secretariat  
Processing of  DCA meeting outcome ;  
1. Notification of transfer approval to new proposed PRH and 
termination notification to existing PRH for approved 
application; OR  
2. Notification of transfer rejection to existing PRH for rejected 
application  Satisfactory  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 174   
16.4 NEW/ ADDITIONAL INDICATION  
 
New/  additional indication is defined as an indication whi ch is not initially approved 
for a registered pharmaceutical product. This shall include  new therapeutic indication 
or indication for new age group, such as usage in children, and shall not include 
changing/ rephrasing of sentences.  
 
There are two (2) type s of evaluation process available for a new/ additional 
indication application : 
 
 
16.4.1  FULL EVALUATION PROCESS  
 
For new indication which has been registered in any one of the Authority’s eight (8) 
reference countries (United Kingdom, Sweden, France, Unit ed States of America, 
Australia, Canada, Japan and Switzerland).  
 
This application will require specialists’ comments.  
 
 
16.4.2  VERIFICATION PROCESS  
 
For new indication which has been registered by any two  reference country’s 
authorities (United Kingdom, Sweden, France, United States of America, Australia, 
Canada, Japan, Switzerland and EMA).  
 
Note :  
The approved new indication in these countries should be the same as that of the 
proposed new indication.  
 
Other supporting documents that are deemed necessar y shall be submitted upon 
request to support the efficacy and safety of the proposed additional indication.  
 
The supporting documents may include b ut not limited to the following : 
 
a) Approval of Additional Indication(s) in country of origin ; 
b) Approval  status in reference countries, its co rresponding approval letter and 
approved Package Insert ; Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 175  c) Approval Indication status in ASEAN Member States and its approved 
corresponding package insert ;  
d) Revised Package Insert ; 
e) World Wide Approval status ; 
f) Consumer Medication  Information Leaflet  (RiMUP ); 
g) Clinical Expert Reports ; 
h) Synopsis of Individual Studies ; 
i) Clinical Studies Report/ In -House Clinical Trials ; 
j) Published Clinical Papers ; 
k) Current Periodic Safety Update Report (PSUR) . 
 
 
16.5 APPLICATION FOR A CONVENIENT PACK  
 
a) This type of application is referring to registered products which are packed 
together in a single packaging unit for convenience of the consumers , such as 
a Confinement Set or Set Jamu Bersalin . 
 
b) Individual registered products are allowed to be packed togeth er and 
marketed as a convenient pack, provided that the application is justified 
satisfactorily.  
 
c) The convenient pack is applicable for registered products in the categories of;  
i) Health supplements .  
ii) Natural products.  
Or registered products from both categ ories (i) and (ii)  
iii) Non-Scheduled Poison (OTC)  
(Only between OTC products with Abridge Evaluation category)  
 
d) Application for a convenient pack  shall be made via the process of variation  
Type II . 
 
The holder has to submit the convenient pack label and also the individual 
label via application for variation under Part D2 (outer label). The convenient 
pack label shall contain the  same information as in the primary label.  
 
For details  of variation , please refer to Section E: 16.1 Variation . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 176  e) Individual registered products involved in the convenient pack can be sold 
individually or as a pack.  
 
f) Conditions for application:  
i) Individual registered products proposed to be packed together as a 
convenient pack shall be sourced from th e same product owner/ PRH;  
 
ii) Submission of the application shall be made by the same PRH.  
 
iii) The manufacturing site for the convenient pack shall be a GMP certified 
facility.  
 
g) Approved indication of each individual registered product in the convenient 
pack re mains unchanged. There is no common specific indication for the 
convenient pack.  
 
h) Labelling requirement specifically for convenient pack:  
 
  Table XIX : 
 
Outer Label  Immediate Label  
Contents in the labelling of each 
individual registered product have to 
be included in the outer label of the 
convenient pack.  As per labelling requirements for 
registered products.  
 
Note:  
For the purpose of application submission, if the individual registered product 
is also marketed independently, outer label of the packaging  sold 
independently and outer label of the convenient pack sh all be submitted 
together.  
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 177  i) Additional information on differentiation from Combination Pack                                               
(Combo Pack)  and Starter Pack/Patient Initiation P ack: 
 
Table X X: 
 
No. Particulars  Convenient 
Pack  Combination 
Pack  
(Combo Pack)  Starter Pack/ 
Patient 
Initiation Pack  
1. New registration 
number (MAL No.) 
to be assigned 
upon approval  No Yes No 
2. Mode of application  Variation 
Type II  Application for 
registration as 
a new product  Application for 
registration as 
a new product 
and variation  
3. Purpose of product  For 
convenience 
of the 
consumer  For therapeutic 
regimen  For dosing 
regimen  
4. New indication  No Yes No 
5. Sale of product  Can be sold 
individual ly or 
as a pack  Only to be sold 
as a pack  Only to be sold 
as a pack  
6. Example  Confinement 
Set or Set 
Jamu 
Bersalin  Klacid HP7  
(for treatment 
of peptic ulcer 
diseases 
associated 
with H. pylori 
infection)  Products that 
require dose 
tapering either 
to reduc e 
systemic side 
effect or for 
dose 
adjustment to 
achieve the 
desired 
maintenance 
dose  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 178  17. POST -MARKETING ACTIVITIES  
 
17.1 PHARMACOVIGILANCE  
 
17.1.1  ADVERSE DRUG REACTION REPORTING AND SAFETY 
UPDATES  
 
In accordance with Regulation 28 : Reporting advers e reaction under Control of 
Drugs and Cosmetics Regulations 1984, Sale of Drugs Act 1952 (amendment 2006), 
the product registration holders or any person who possesses any registered 
product shall inform immediately the Director of Pharmaceutical Services of any 
adverse reaction arising from the use of the registered product.  
 
All product registration holders must ensure that a pharmacovigilance system is in 
place by the company and appropriate action is taken, when necessary.  
 
Product registration holders  are required to monitor and report any product safety 
issues that arises locally or internationally to the NPRA  and comply with all safety -
related directives issued by the Authority.  
 
The product registration may be cancelled if the product  registration  holder fails to 
inform the Authority  of any serious adverse reacti ons upon receipt of such reports.  
 
The WHO encourages reporting of ALL adverse drug reactions.  
 
For further information, please refer Malaysian Guidelines for the Reporting & 
Monitoring . 
 
 
17.2 POST -MARKET SURVEILLANCE  
 
a) It is the prime responsibility of the holder to ensu re products marketed are in 
accordance to the standards and requirements of the Authority ; 
 
b) Registered products may be sampled and tested for compliance with official or 
pharmacopoeia standards or specifications agreed by the manufacturer. Labels and Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 179  packa ge inserts of the samples will also be checked to ensure compliance to the 
requirements as approved.  
 
c) The Authority will take necessary action on products which do not conform to the 
standards/ specifications and requirements in the form of warnings or rec alls. The 
product registration holder has up to thirty (30) days to identify the cause of defect 
and actions to be taken  for improve ment . 
 
 
17.2.1  PRODUCT COMPLAINTS  
 
a) The product registration holder should notify the NPRA  of any product quality related 
problems (with registered products) that the holder is aware of;  
b) It is also the responsibility of the prescribers, pharmacists, as well as all other health 
professionals who come into contact with the drug to report to NPRA  by using the 
NPRA  complaint form i. e. BPFK 419  / BPFK 418.4  together with complaint sample (if 
any).  
c) All complaints received will be investigated by the NPRA  as well as product 
registration holder/ manufacturer. It is the responsibility of the company to determine 
the appropriate corrective and preventi ve action.  
Guidelines on Good Distribution Practice, Chapter 9.  
 
 
17.2.2  PRODUCT RECALLS  
 
a) The decision for re call of a product shall be made when there is or may cause 
potential risk to the user of the products. Recalls may be done voluntarily by the 
product registration holder or as directed by the Director of Pharmaceutical Services 
Division, Ministry of Health  Malaysia;  
b) The product registration holder is responsible for conducting recalls of defective or 
unsafe products. No recall should take place without first consulting/ informing the 
Authority.  
Guidelines on Good Distribution Practice, Chapter 10.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 180  17.3 PUNITIVE ACTION FROM THE AUTHORITY  
 
17.3.1  ADULTERATION  
 
As stated in circular Bil (30) BPFK/PPP/01/03 , Tindakan Punitif Ke Atas Syarikat Yang 
Terlibat Dengan Kes Produk Campur Palsu ( 13 May 2009 ), punitive action shall be taken 
against companies who are involv ed in adulteration.  
 
Any registered product s found to have been adulterated , the following action shall be taken 
by the Director of Pharmaceutical Services:  
 
a) The registration of the related product shall be cancelled and recall of all batches of 
the prod uct shall be done immediately;  
 
b) The manufacturer’s license of the related manufacturer shall be revoked for six (6) 
months for the first offence and one (1) year for the subsequent offence, from the date 
of revocation letter;  
 
c) All transactions (including a pplication for product registration, application for change of 
product registration holder, application for change of manufacturing site) for the 
adulterated product registration holder shall be frozen for six (6) months for the first 
offence and one (1) y ear for the subsequent offence, from the date of cancellation 
letter from the Authority.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 181  APPENDICES  
 
 
Appendix 1  Fees  
Appendix 2  Requirements for Product Registration  
Appendix 3  Guidelines on Registration of Biologics  
Appendix 4  Guideline on Registr ation of Health Supplements  
Appendix 5  Guideline on Registration of Natural Products  
Appendix 6  Guideline on Regulatory Control of Active Pharmaceutical Ingredients 
(API)  
Appendix 7  Special Conditions for Registration for a Particular Product or Group o f 
Products  
Appendix 8  List of Permitted, Prohibited and Restricted Substances  
Appendix 9  Labelling Requirements  
Appendix 10  Guideline on Patient Dispensing Pack for Pharmaceutical Products in 
Malaysia  
Appendix 11  Guideline on Filling the Online Applic ation Form for Product 
Registration via Quest System  
Appendix 12  Conditions and Supporting Documents Required for Application of 
Variation Type I & Type II  
Appendix 13  Supporting Documents Required for Change of Manufacturing Site 
(COS) Application  
Appe ndix 14  
 Guidelines On Safety Data Requirements For Complementary 
Medicine Products  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 182  APPENDIX 1:  FEES  
 
Outline:  
 
1.1 Charges for USB Token of QUEST Membership;  
1.2 Processing and Analysis Fee for Product Registration;  
1.3 Charges for Application of Licence;  
1.4 Charges  for Amendments to Particulars of a Registered Product;  
1.5 Fee for Certificate s; and 
1.6 Charges for Product Classification.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 183  1.1 CHARGES FOR USB TOKEN OF QUEST MEMBERSHIP  
 
No. Type  Validity Period  
1 year  
(RM)  2 years  
(RM)  
1. Main User – New, Replacement, 
Chang e of Authorized Person  
 
(Certificate  + USB Token ) 260 290 
2. Supplementary User – New, 
Replacement, Change of 
Authorized Person  
 
(Certificate  + USB Token ) 245 275 
3. Change Authorized Person  
 
(Certificate Only) 48 95 
4. Renewal  
 
(Digital Certificate onl y – using 
existing MSC USB Token)  48 95 
5. Postage (Semenanjung Malaysia)  10 
6.  Postage (Sabah/ Sarawak)  20 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 184  1.2 PROCESSING AND ANALYSIS FEE FOR PRODUCT REGISTRATION  
 
 
Every application for registration shall be accompanied with a processing and 
analysis fee, as specified below (effective 1st January 2007):  
No. Category of 
Product  * Processing 
Fees  Analysis Fees  Total Fees  
1. Pharmaceutical  
a) New Drug 
Products  
 
b) Biologics  RM 1,000.00  Single active ingredient :  
RM 3,000.00  RM 4,000.00  
Two or more active ingredients : 
RM 4,000.00  RM 5,000.00  
2. Pharmaceutical  
  
a) Generic 
(Scheduled 
Poison)  
 
b) Generic 
(Non -
Scheduled 
Poison)  
 
c) Health 
supplement  RM 1,000.00  Single active ingredient :  
RM 1,200.00  RM 2,200.00  
Two or more active ingredients: 
RM 2,000.00    RM 3,0 00.00  
 3.   
Natural Product  
  RM   500.00  RM 700.00  RM 1,200.00  
* As stipulated in the CDCR 1984, Regulation 8.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 185  1.3 CHARGES FOR APPLICATION OF LICENS ES 
After a product is registered, the applicant shall apply for a manufacturer/ import/ wholesale 
license. The processing fees are as specified below:  
 
License  Processing fee  Timeline  Validity  
1. Manufacturer  RM 1,000.00  4 working days upon 
receipt of complete 
application  1 year  
2. Import  RM 500.00  4 working days upon 
receipt of complete 
application  1 year  
3. Wholesale  RM 500.00  4 working days upon 
receipt of complete 
application  1 year  
 
 
1.4 CHARGES FOR  AMENDMENTS TO PARTICULARS OF A 
REGISTERED PRODUCT  
 
Types of Amendment  Processing fee  
Pharmaceutical  Natural Product  
1. Change of Manufacturing Site  
           (Type I)  RM 1,000.00  RM 100.00  
2. Change of Manufacturing Site  
(Type II, III, IV, V)  RM 1,000.00  RM 500.00  
3. Change of Product Registration 
Holder  RM 1,000.00  RM 500.00  
4. Minor Variation Prior Approval  
(MiV-PA) RM 150.00  RM 50.00  
5. Major Variation (MaV)  RM 300.00  RM 100.00  
6. Additional Indication  RM 1000.00  Not applicable  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 186  1.5 FEE FOR CERTIFICATE S 
 
Under the CDCR 1984, Regulation 16: “The Director of Pharmaceutical Services may issue 
such certification on any matter relating to any product where such certificat ion is required 
by any country importing such a product.”  
Certificates  Fee Validity  
Issuance of one (1) Certificate of 
Pharmaceutical Product  RM 50.00  2 years  
Issuance of one (1) Certificate of Good 
Manufacturing Practice (GMP)  RM 50.00  2 years  
Issuance  of one (1) Certificate of Declaration 
(Sijil Deklarasi)  RM 50.00  - 
Issuance of one (1) Certificate of Indication  
(Sijil Indikasi)  RM 50.00  - 
 
1.6 CHARGES FOR  PRODUCT CLASSIFICATION  
Processing fee  Timeline  
RM 300  
per product  
for each application  7-14 workin g days  
upon receipt of complete and  
satisfactory application  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 187  APPENDIX 2:  REQUIREMENTS FOR PRODUCT REGISTRATION  
 
 
 
 
 
 
 
 
 
 
 
 
This appendix comprises of two (2) parts which are:  
 
2.1 General requirements for:  
 
2.1.1  Full Evaluation;  
(In accordance to ASEAN ACTD/ ACTR or ICH guidelines)  
 
▪ Part I  - Admi nistrative data and product information  
▪ Part II  - Data to support product quality (Quality Document)  
▪ Part III  - Data to support product safety (Nonclinical Document)  
▪ Part IV  - Data to supp ort product safety and effi cacy (Clini cal 
Document)  
 
2.1.2  Abridged Evaluation.  
 
2.1.3  Additional Information on  Requirement of : 
 
▪ Bioavailability (BA) Study  
 
▪ Bioequivalent (BE) Study  
 
2.2 Product Specific Requirements   
IMPORTANT NOTES:   
1. This appe ndix is for reference purpose only, where applicable, and it may not 
follow the sequence as in the online product registration application forms (in 
QUEST system).  
2. Online application forms are available for different product categories.  
3. Applicant shall fo llow and comply with all requirements in the online application 
forms as well as any supplementary documentation requested by the Authority, 
whichever it may deems fit.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 188  2.1 GENERAL REQUIREMENTS  
 
Data to be submitted as general requirement to suppo rt an application for product 
registration is  based on the product category as shown below : 
 
(A) FULL EVALUATION (based on ACTD/ ACTR)  
No. Product Category  Part I  Part II  Part III  Part IV  
1. New Drug Products  √ √ √ √ 
2. Biologics  √ √ √ √ 
3. Generics  
(Scheduled Poison)  √ √ Not 
Applicable  Not 
Applicable  
4. Generics  
(Non -Scheduled Poison)  √ √ Not 
Applicable  Not 
Applicable  
5. Health Supplements:  
 
Disease Risk Reduction 
Claims (High)  √ √ √ √ 
(B) ABRIDGED EVALUATI ON 
No. Product Category  
1. * Generics  
(Non -Scheduled Poison)  
2. Health Supplements:  
 
a) General or Nutritional Claims  
b) Functional Claims (Medium)  
3. Natural Products  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 189  * Generics (non -scheduled poison) which are evaluated under abridged evaluation include, 
but not limited , to the following:  
 
a) Antiseptics/ skin disinfectants;  
b) Locally -acting lozenges/ pastilles;  
c) Topical analgesic/ counter -irritants;  
d) Topical nasal decongestants;  
e) Emollient/ demulcent/ skin protectants;  
f) Keratolytics;  
g) Anti-dandruff;  
h) Oral care ; 
i) Anti-acne;  
j) Medicated plasters/ patch/ pad; and  
k) Topical antibacterial.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 190  2.1.1 GENERAL REQUIREMENTS  FOR FULL EVALUATION   
 
No. Step I: Product Validation  
1. Is your product has a brand name? (Yes/ No)  
(If yes, please provide brand name and product name)  
2. Dosage Form  
3. Active Ingredient(s)  
a) Active Ingredient Name  
b) Strength of Active Ingredient (Quantity unit/ dose)  
c) Source of Active Ingredient (Animal – e.g. Bovine, Porcine, Ovine or 
Others/ Plant/ Others)  
d) Form of Active Ingredient  
e) Remarks (if any)  
4. Excipient(s)  
a) Excipient name  
b) Strength of Excipient (Quantity unit/ dose)  
c) Function of excipient (e.g. absorbent, diluents, bulking agent, coating 
agent, anti -caking agent etc.)  
d) Source of excipient  
e) Remarks (if any)  
5. Is there any source of ingredients deri ved from animal origin, including active 
ingredient? (Yes/ No)  
6. Manufacturer (Name and Address)  
7. Is the selected manufacturer a contract manufacturer? (Yes/ No)  
8. Is the product from second source? (Yes/ No)  
If yes, please provide:  
a) Letter of declar ation stating that this product is a second source product  
b) Registration number and product name of the first source  
9. Is this product containing any premix? (Yes/ No)  
a) State your premix form  
b) Manufacturer name  
c) Manufacturer address  
d) Certificate of Good Manu facturing Practice (GMP)  
e) Formulation  
f) Manufacturing Process  
g) Specification of Analysis  
h) Certificate of Analysis (CoA)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 191  No. Step I: Product Validation  
10. Is this a replacement product? (Yes/ No)  
If yes, please provide:  
a) Letter of Declaration stating that this product is a replacement produ ct 
b) Registration number and product name of the replaced product  
11. Is there any other manufacturer (repacker)? (Yes/ No)  
a) Manufacturer (repacker) name  
b) Manufacturer (repacker) address  
c) Certificate of Good Manufacturing Practice (GMP)  
d) Packaging Process  
12. Is this an imported product? (Yes/ No)  
 
 
Step II:  
Part I: Administrative Data And Product Information  
No. Section A: Product Particulars  
1. Product Name  
2. Name & Strength of Active Substance and Excipient  
3. Dosage Form  
4. Product Description  
5. Pharmacodynamics  
6. Pharmacokinetics  
7. Indication  
8. Recommended Dose  
9. Route of Administration  
10. Contraindication  
11. Warning and Precautions  
12. Interaction of Other Medicaments  
13. Pregnancy and Lactation  
14. Side Effects  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 192  Step II:  
15. Symptoms and Treatment of Overdose  
16. Storage Condition  
17. Shelf Life  
18. Therapeutic Code/ ATC Code  
No. Section B:  Product Formula  
1. Batch Manufacturing Formula  
2. Attachment of Batch Manufacturing Formula Documentation  
No. Section C: Particulars of Packing  
- Please refer Appendix 10:  Guide for Implementation of Patient Dispensing 
Pack for Pharmaceutical Products in Malaysia  
1. Pack Size  
(Fill details by weight/ volume/ quantity)  
2. Immediate Container Type  
(Container Type and Description)  
e.g. Aluminium/ Glass/ Metal/ Paper/ Plastic/ Others  
3. Barcode/ Serial No. (Optional)  
4. Recommended Distributor’s Price (RM) (Optional)  
5. Recommended Retail ’s Price (RM) (Optional)  
No. Section D: Label (Mock -up) For Immediate Contai ner, Outer Carton, 
Proposed Package Insert  
- Please refer Appendix 9:  Labelling Requirements  
1. Proposed Label Mock -up for Immediate Container  
2. Proposed Label Mock -up for Outer Carton  
3. Proposed Package Insert  
No. Section E: Supplementary Documentation  
1. Product Owner  
2. Letter of Authorization from Product Owner  
3. Letter of Appointment of Con tract Manufacturer from Product Owner  (if 
applicable)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 193  Step II:  
4. Letter of Acceptance f rom Contract Manufacturer   
(if app licable)  
5. Is the active ingredient(s) patented in Malaysia?  
(Yes/ No)  
(If yes, please attach the related document)  
6. Certificate of Pharmaceutical Product (CPP)  
7. CPP Issuing Body  
8. Is this product licensed to be placed on the market for use in t he exporting 
country? (Yes/ No)  
(If no, please state the reason)  
9. Is the product on the market in the exporting country? (Yes/ No)  
(If no, please state the reason)  
10. Date of Issue of CPP  
11. Date of Expiry of CPP  
12. Certificate of Free Sale (CFS)  
13. CFS Issuing Body  
14. Date of Issue of CFS  
15. Date of Expiry of CFS  
16. Certificate of Good Manufacturing Practice (GMP)  
17. Certificate of GMP Issuing Body  
18. Date of Issue of Certificate of GMP  
19. Date of Expiry of Certificate of GMP  
20. Summary of Product Characteristics  
(Product Data Sheet)  
21. Consumer Medication Information Leaflet (RiMUP)  
[Previuosly known as Patient Information Leaflet (PIL) ] 
22. *Attachment of Protocol Analysis  
23. *Attachment of Analytical Validation  
24. *Certi ficate of Analysis  (CoA)  
25. Other Supporting Document (if any)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 194  Step II:  
26. Manufacturer (Name and address)  
27. Importer (if any)  
28. Other manufacturer(s) involved, e.g. repacker (if any)  
(Please attach Certificate of GMP, if yes)  
29. Store Address  
PART II:  QUALITY  OF PRODUCT  
No. Section P: Drug Product (Finished Product)  
1. Description and Composition  
2. Pharmaceutical Development  
 a) Information on Development Studies  
 b) Components of the Drug Product  
 c) Finished Products  
 d) Manufacturing Process Development  
 e) Container Closure System  
 f) Microbiological Attributes  
 g) Compatibility  
3. Manufacturer  
 a) Batch Manufacturing Formula  
 b) Manufacturing Process and Process Controls  
 c) Manufacturing Process Flowchart  
 d) Control of Critical Steps & Intermediates  
 e) Process Val idation and/or Evaluation  
4. Control of Excipients  
 a) Specifications  
 b) Analytical Procedures  
 c) Validation of Analytical Procedures  
 d) Justification of Specifications  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 195  Step II:  
 e) Excipient of Human or Animal Origin  
 f) Novel Excipients  
5. Control of Finished Products  
 a) Specifications  
 b) Analytical Procedures  
 c) Validation of Analytical Procedures  
 d) Batch Analyses  
 e) Characterization of impurities  
 f) Justification of Specifications  
6. Reference Standard s or Material s 
7. Container Closure System  
8. Stability  
9. Product I nterchangeability/ Equivalent Evidence (Bioavailability/ 
Bioequivalence, BA/BE)  
- Please refer 2.1.3 Additional information on requirements of BA and 
BE. 
No. Section S: Drug Substance  
1. General Information  
 a) Nomenclature  
 b) Structure and Attachment for St ructure of Drug Substance  
 c) General Properties  
2. Manufacturer  
 a) Manufacturer Name and Address  
 b) Description of Manufacturing Process and Process Controls  
 c) Controls of Materials  
 d) Controls of Critical Steps and Intermediates  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 196  Step II:  
 e) Process Validation and/or E valuation  
 f) Manufacturing Process Development  
3. Characterisation  
 a) Elucidation of Structure and Characteristics  
 b) Impurities  
4. Control of Drug Substances  
 a) Specifications  
 b) Analytical Procedures  
 c) Validation of Analytical Procedures  
 d) Batch Analysis  
 e) Justification of Specifications  
5. Reference Standards or Materials  
6. Container Closure System  
7. Stability  
PART III: NONCLINICAL DOCUMENT  
 Section A: Table of Contents  
No. Section B: Nonclinical Overview  
1. Overview of the Nonclinical Testing Stra tegy 
2. Pharmacology  
3. Pharmacokinetics  
4. Toxicology  
5. Integrated Overview & Conclusions  
6. List of Literature Citations  
 Section C: Nonclinical Written and Tabulated Summaries  
 Section D: Nonclinical Study Reports  
 Section E: List of Key Litera ture References  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 197   
PART IV: CLINICAL DOCUMENT  
 Section A: Table of Contents  
No. Section B: Clinical Overview  
1. Product Development Rationale  
2. Overview of Biopharmaceutics  
3. Overview of Clinical Pharmacology  
4. Overview of Efficacy  
5. Overview of  Safety  
6. Benefits & Risks Conclusions  
No. Section C: Clinical Summary  
1. Summary of Biopharmaceutics Studies and Associated Analytical Methods  
2. Summary of Clinical Pharmacology Studies  
3. Summary of Clinical Efficacy  
4. Summary of Clinical Safety  
5. Synopses of Individual Studies  
 Section D: Tabular Listing of all Clinical Studies  
 Section E: Clinical Study Reports  
 Section F: List of Key Literature References, Published Clinical Papers 
and Latest Periodic Safety Update Report (PSUR)  
 
Notes : 
 
*  Evaluated by Centre for Quality Control.  For details, please refer to  Section C: 
Quality Control in the main DRGD.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 198  2.1.2  GENERAL REQUIREMENTS FOR ABRIDGED EVALUATION  
 
No. Step I: Product Validation  
1. Product Name  
2. Dosage Form  
3. Active Ingre dient(s)  
a) Active Ingredient name  
b) Strength of Active Ingredient (Quantity unit per dose)  
c) Source of Active Ingredient (Animal – e.g. Bovine, Porcine, Ovine or 
Others/ Plant/ Others)  
d) Form of Active Ingredient  
e) Remarks (if any)  
4. Excipient(s)  
a) Excipient name  
b) Strength of Excipient (Quantity unit per dose)  
c) Function of excipient (e.g. absorbent, diluents, bulking agent, coating 
agent, anti -caking agent etc.)  
d) Source of excipient  
e) Remarks (if any)  
5. Is there any source of ingredients derived from animal origin, inc luding 
active ingredient? (Yes/ No)  
6. Manufacturer (Name and Address)  
7. Is the selected manufacturer a contract manufacturer? (Yes/ No)  
8. Is the product from second source? (Yes/ No)  
If yes, please provide:  
a) Letter of declaration stating that this pr oduct is a second source 
product  
b) Registration number and product name of the first source  
9. Is this product containing any premix? (Yes/ No)  
a) State your premix form  
b) Manufacturer name  
c) Manufacturer address  
d) Certificate of Good Manufacturing Practice (GMP)  
e) Formulation  
f) Manufacturing Process  
g) Specification of Analysis  
h) Certificate of Analysis (CoA)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 199  No. Step I: Product Validation  
10. Is this a replacement product? (Yes/ No)  
If yes, please provide:  
a) Letter of Declaration stating that this product is a replacement product  
b) Registration number and  product name of the replaced product  
11. Is there any other manufacturer (repacker)? (Yes/ No)  
a) Manufacturer (repacker) name  
b) Manufacturer (repacker) address  
c) Certificate of Good Manufacturing Practice (GMP)  
d) Packaging Process  
12. Is this an imported produ ct? (Yes/ No)  
 
 
Step II:  
No. Section A: Product Particulars  
1. Product Name  
2. Product Description  
3. Dosage Form  
 a) Source of Capsule Shell  
 b) Certificate to verify the source of the capsule shell  
 c) Coloring agent used in capsule shell  
 (Please attac h COA of the capsule shell)  
4. Product Indication/ Usage  
5. Dose/ Use Instruction  
6. Contraindication  
7. Warning and Precautions  
8. Drug Interaction  
9. Side Effects/ Adverse reaction  
10. Signs and Symptoms of Overdose and Treatment  
11. Storage Co ndition  
12. Shelf Life  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 200  Step II:  
13. Therapeutic Code/ ATC Code  
No. Section B:  Product Formula  
1. Batch Manufacturing Formula  
a) Batch Size  
b) Unit 
2. Active Ingredients  
a) Active Ingredients Name  
b) Quantity  
c) Source  
d) Form of Substance  
e) Overage (%)  
f) Remarks   
3. Excipients  
a) Active Ingredients Name  
b) Quantity  
c) Function  
d) Source  
e) Overage (%)  
f) Remarks  
4. Attachment of Batch Manufacturing Formula Documentation  
5. Manufacturing Process  
6. Attachment of Manufacturing Process Documentation  
7. In-Process Quality Control  
8. Attachment of Finished Product Specification Documentation  
9. Attachment of Stability Data Documentation  
(For two batches) - Compulsory for imported product  
No. Section C: Particulars of Packing  
- Please refer Appendix 10 : Guide for Imp lementation of Patient Dispensing 
Pack for Pharmaceutical Products in Malaysia  
1. Pack Size  
(Fill details by weight/ volume/ quantity)  
Measurement Type  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 201  Step II:  
2. Immediate Container Type  
(Container Type and Description)  
e.g. Aluminium/ Glass/ Metal/ Paper/ Pl astic/ Others  
3. Barcode/ Serial No. (Optional)  
4. Recommended Distributor’s Price (RM) (Optional)  
5. Recommended Retail ’s Price (RM) (Optional)  
6. Other Related Attachment (if any)  
No. Section D:  Label (Mock -up) For Immediate Container, Outer Carton,  
Proposed Package Insert  
- Please refer Appendix 9:  Labelling Requirements  
1. Proposed Label Mock -up for Immediate Container  
2. Proposed Label Mock -up for Outer Carton  
3. Proposed Package Insert  
No. Section E: Particulars of Product Owner, Manufacturer, Importer and 
Other Manufacturer(s)  Involved and Store address  
1. Product Owner  
2. Manufacturer  
3. Other Manufacturer(s) involved (if any)  
a) Manufacturer Name and Address  
b) Processing Steps Involved  
c) Certificate of Good Manufac turing Practice (GMP)  
4. Store Name and Address  
5. Importer  
No. Section F:  Supplementary Documentation  
1. Letter of Authorization from Product Owner  
2. Letter of Appointment of Contract Manufacturer from Product Owner (if 
applicable)  
3. Letter of Acc eptance from Contract Manufacturer  
(if applicable)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 202  Step II:  
4. Is the active ingredient(s) patented in Malaysia?  
(If yes, please attach the related document)  
5. Certificate of Pharmaceutical Product (CPP)  
6. CPP Issuing Body  
7. Is this product licensed to be p laced on the market for use in the exporting 
country?  
(If no, please state the reason)  
8. Is the product on the market in the exporting country?  
(If no, please state the reason)  
9. Date of Issue of CPP  
10. Date of Expiry of CPP  
11. Certificate of Fre e Sale (CFS) (if any)  
12. CFS Issuing Body  
13. Date of issue of CFS  
14. Date of expiry of CFS  
15. Certificate of Good Manufacturing Practice (GMP)  
16. Certificate of GMP Issuing Body  
17. Date of issue of Certificate of GMP  
18. Date of expiry of  Cer tificate of GMP  
19. Summary of Product Characteristics  
(Product Data Sheet)  
20. Consumer Medication Information Leaflet (RiMUP)  
[Previously known as Patient Information Leaflet (PIL) ] 
21. Attachment of Protocol Analysis  
22. Attachment of Certificate o f Analysis (CoA)  
(For two batches)  
* Compulsory for imported products  
23. Attachment of Specifications and Certificate of Analysis of Active Ingredient  
24. Other Supporting Documents (if any)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 203  2.1.3  ADDITIONAL INFORMATION ON:  
 
A)  BIOAVAILABILITY (BA ) STUDY  
 
For modified -release products , dosage recommendations and regime must be supported 
by bioavailability studies.  
 
Studies comparing availability or establishing equivalence of similar products would be 
useful.  
 
 
 
B) BIOEQUIVALENCE (BE) STUDY  
 
Note:  This requirement is applicable to generics (scheduled poison) only.  
 
With the increasing availability of generic products, a mechanism is required to ensure that 
such products are therapeutically equivalent to the innovators’ products and are clinically 
interchangeable.  
In practice, demonstration of bioequivalence (BE) is generally the most appropriate method 
of substantiating therapeutic equivalence between medicinal products. A list of drug 
substances, which, when formulated in oral solid dosage forms, require BE data as a 
prerequisite for registration, has been established by the  authority (please refer to NPRA  
website at http://npra.moh.gov.my/ ). This list is updated based on the requirements.  
 
Bioequivalence (BE ) Study Requirements for Generic Product in Immediate Release, 
Oral Solid Dosage Form Submitted as a Second Source Application  
 
In general, for a second source application of a generic product (immediate release, oral 
solid dosage form), BE study report fr om the actual manufacturing site must be submitted 
during the submission of application for registration. The base of this requirement is due to 
the difference in manufacturing site from the first source that may change the characteristic 
and specification s of a second source product.  
 
However, biowaiver can be considered, provided that Comparative Dissolution Profile 
(CPD) report against the registered first source product is submitted as a surrogate to 
bioequivalence study conducted for the second source  product and all the following 
conditions sh all be fulfilled:  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 204  a) Bioequivalence study conducted using the registered first source product has been 
evaluated by the NPRA  and found satisfactory.  
 
b) The second source product is the same as registered first source  product used in the 
bioequivalence study in terms of:  
 
i) Product formulation;  
ii) Equipment used in the manufacturing process;  
iii) Source and supplier of raw material;  
iv) Quality control and specifications of raw material;  
v) Manufacturing process of product and standard  operating procedures;  
vi) Environmental conditions during the manufacturing process of product;  
vii) Quality control and specifications of finished product.  
 
c) Comparative Dissolution Profile must be conducted in accordance to ASEAN 
Guidelines for the Conduct of Bio availability and Bioequivalence Studies  including the 
calculation of similarity factor (f2) to prove the similarity  of these two products.  
 
d) Process validation has been conducted on 3 pilot or commercial batches of the 
second source product and found satisf actory by the NPRA . 
 
This exemption is not applicable for any new submission of application for registration of a 
first source product.  BE study  must be conducted for this produ ct which is 
manufactured at the actual manufacturing site submitted for regis tration .  
(Reference: Circular  Bil.(10)dlm.BPFK/PPP/07/18Jld.1  , 2 Jun 2011)  
 
Starting on 1st of January 2012, bioequivalence (BE) study is re quired for all application of 
registrations for generic products containing scheduled poison in the form of immediate 
release, oral, solid dosage form  whereas renewal of registered products, the effective date 
is on 1st January 2013.  
(Directive Arahan di B awah Peraturan 29, Peraturan -peraturan Kawalan Dadah dan  
Kosmetik 1984  Bil. 1 Year  2011 , 2 March 2011  Bil (10) dlm BPFK/PPP/01/03 Jld 1 ) 
 
Sponsors or BE study centers are compulsory to notify the Authority pertaining to all BE 
studies which do not require Clinical Trial Import Licence (CTIL) or Clinical Trial 
Exemptions (CTX) and are going to be done at either local or overseas BE study center s 
for registered products or products to be registered in Malaysia (Directive Arahan di Bawah 
Peraturan 29, Peraturan -peraturan Kawalan Dadah dan Kosmetik 1984  Bil. 13 Year  2011 , 
14 October 2011 , Bil (23) dlm BPFK/PPP/01/03 Jld 1 ). 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 205   
Note:  The two above directives shall be read in conjunction with the supplementary circular 
that further explains the procedure for evaluation of BE centre in spection reports in line with 
the requirement of accreditation of BE Centres. (Reference: Circular dated 12 September 
2013; Bil(6)d lm.BPFK/PPP/01/03 Jld 3. ) 
 
Effective 1st March 2013, biowaiver may be granted to generic immediate release oral solid 
dosage form products containing BCS Class I active ingredients listed in the Guidance On 
Biopharmaceuticals Classification System (BCS) – Based Biowaiver document. BCS Based 
biowaivers takes the three major factors that govern the rate and extent of drug absorption 
from immediate -release solid dosage forms into accounts i.e. solubility and permeability of 
the drug substance/ API, and dissol ution characteristics of the dosage form. This BCS 
approach provides an opportunity to waive in vivo  pharmacokinetic bioequivalence testing 
for certain categories of immediate -release drug products.  
(Directive Arahan di Bawah Peraturan 29, Peraturan -peratu ran Kawalan Dadah dan 
Kosmetik 1984  Bil. 1 Year  2013, 14 October 2011 , 28 February 2013, Bil 
(101)dlm.BPFK /PPP/01/03 Jld 2 ). 
 
For more information on BE, please refer  Bioequivalence (BE) .  
 
 
 
2.2 SPECIFIC REQUIREMENTS  
 
 
For biologics, health supplements and natural products, please refer  guidelines for the 
respective product category at : 
 
a) Appendix 3 : Guidelines on Registration of Biologics  
b) Appendix 4:  Guideline on Registration of Health Supplements  
c) Appendix 5:  Guideline on Registration of Natural Products  
 
Please refer as well on Appendix 11 : Guideline on Filling the Online Application Form for 
Product Registration via Quest System  before submission of an application for product 
registration.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 206  APPENDIX 3:  GUIDELINES ON REGISTRATION OF BIOLOGICS  
  
 
 
 
 
1. This document shall be read in conjunction with the relevant sections of the main 
guidance document: Drug Registration Guidance Docum ent (DRGD), which is in 
accordance to the legal requirements of the Sale of Drugs Act 1952 and the 
Control of Drugs and Cosmetics Regulations 1984.  
2. The National Pharmaceutical Regulatory Division ’s (NPRA ) requirements for registration 
of biologics/ biophar maceuticals products are aligned with the scientific guidelines and 
recommendations for quality, clinical efficacy and safety and non -clinical of the World 
Health Organization (WHO), European Medicines Agency (EMA) and International 
Conference of Harmoniza tion (ICH).  
3. Where appropriate, the relevant WHO, EMA and ICH guidelines on biologics/ 
biopharmaceuticals  shall be consulted.  
• WHO  (http://www.who.int/boodproducts/en/index.html ) 
• EMA   (http://www.ema.europa.eu ) 
• ICH   (http://www.ich.org ) 
 
4. Every biologic is regulated as a new product and also considered ‘high risk’, both 
substance and drug product production must comply to Good Manufacturing 
Practice strictly.  Adoption of GMP as an essential tool of Quality Assurance System.  
 
5. The requirements for registration of biologics/ biopharmaceuticals shall be in 
accordance to the ASEAN Common Technical Dossier (ACTD)  format and in 
adhere nce to the general regulatory requirement as described in sections of the main 
DRGD.  It covers:  
• Administrative information  
• Product quality data  
• Product safety data  
• Clinical data, demonstrating clinical efficacy and capacity to meet therapeutic 
claims, thr ough clinical studies.  
 
6. Animal derived materials/ products are commonly used in the manufacture of biologics/ 
biopharmaceuticals. Please provide detail information regarding the rationale for use of  
IMPORTANT NOTES:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 207  such material, the source etc., as per Checklist A  and Checklist B ; and also provide a 
confirmation on the presence/ absence of the animal materials in the final product.  
 
7. Since biosimilars are follow -on products of the original biopharmaceutical products 
(well-characterised recombinant proteins), this document also is applicable to 
biosimilars.  Additionally, a separate Guideline for Registration of Biosimilars  is 
available.  
 
8. Although a CGTP is regulated separately under different framework, the Guidance 
Document dan Guidelines For Registration of Cell and Gene Therapy Products 
(CGTPs), December 2015  should be read in conjunction with this document because a 
high risk CGTP which is categorized as class II, is regulated as a biologic product.  A 
class II cell therapy is “highly processed”, used for other than normal function, is 
combined with non -tissue components, or is used for metabolic purposes”. For further 
details, please refer to  Directive No. 6 Year 2017.  Ref: BPFK/PPP/07/25 (11) Jld.1:  
Direktif Untuk Menguatkuasakan Penggunaan Guidance Document And Guideline For 
Registration Of Cell And Gene Therapy Products (CGTPS),  December 2015  Dan Good 
Tissue Practice Guideline, 2ND Edition, December 2015).  
 
9. This document is intended to provide guida nce for the registration of biologics.  
However, the document will serve as a living document that will be updated/ revised 
further in the line with the progress in scientific knowledge and experience.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 208  Outline:  
 
   
3.1 General Information   
 3.1.1  Defin itions   
 3.1.2  Introduction   
3.2 Specific Requirements for Registration of Biologics   
 3.2.1   Requirements for Registration of Biologics  
 (Vaccines and Biotechnology Products)   
 a) Vaccines   
 i) Definition of Vaccine   
 ii) Requirements for Registration of Va ccines  
(Chemistry, Manufacturing And Controls, CMC)   
 b) Biotechnology Products   
 i) Definition of Biotechnology Product   
 ii) Additional Requirements for Registration of Biotechnology 
Products   
 c) References   
 3.2.2  Requirements for Registration of Blood Produc ts  
 a) Definition of Blood Product   
 b) Requirements for Registration of Blood Products   
 c) Checklist of Plasma Master File for Blood Products   
 d) References   
3.3 Checklists of Registration for Products Containing Materials of 
Animal Origin:   
 3.3.1  Checklist A:  Products Containing Animal -Derived Materials with 
a valid TSE risk evaluation Certificate of Suitability 
(CEP)   
 3.3.2  Checklist B:  Products Containing Animal -Derived Materials 
without  a valid TSE risk evaluation Certificate of 
Suitability (CEP)   
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 209  3.1 GENERAL I NFORMATION  
 
3.1.1  DEFINITIONS:  
 
i) Biopharmaceutical/ Biotechnology Product  
ii) Biologic/ Biological Product  
 
• The term ‘biopharmaceutical’ was coined in the 80’s to define proteins that were 
made by recombinant DNA technology [which includes hybridoma technology for 
monoclonal antibody (mAb) production].  
 
• Biologic/ Biological product refers to a product whose active substance is made 
by or derived from a living organism (plant, human, animal or microorganism) 
and may be produced by biotechnology methods and other cutting -edge 
technologies.  This product imitates natural biological substances in our bodies 
such as hormones, enzymes or antibodies.  
 
• Biopharmaceuticals/ Biologics/ Biological products can also be defined as:  
“a protein (including antibodies) or nucleic  acid-based pharmaceuticals used for 
therapeutic, which is produced by means other than direct extraction from a 
native (non - engineered) biological source”.  This corresponds to the new 
biotechnology view (that is, by elimination, it is largely restricted  to recombinant/ 
genetically engineered and mAb -based products).  
 
• The term ‘Biotechnology product’ and ‘Biological product’ are used to broadly 
refer to all biopharmaceuticals (by the broad biotechnology view).  
 
Note:   Today, biologics have become inextri cably intertwined with 
biopharmaceuticals, to the point where they are synonymous.  The general 
consensus is that a ‘Biologic’ and ‘Biopharmaceutical’ are interchangeable 
terminology, but a biologic might incorporate some other products (e.g. allergenics, 
somatic cells etc.).  
 
Biologics include a wide range of products such as:  
1. Vaccines;  
2. Blood products;  
3. Monoclonal antibodies (therapeutics);  
4. Recombinant proteins:  
- Insulins  
- Hormones  
- Erythropoetins and other hematopoietic factors  
- Cytokines: i nterferons, inter leukins, colony -stimulating factors, tumour 
necrosis factors.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 210  5. Cell and Gene Therapy Products (CGTPs)  
But does not include:  
• Metabolites from microorganisms; e.g antibiotics and some hormones.  
• Macromolecules produced by chemical synthesis; e.g peptides/oligo -nucleotides 
produced by chemical synthesis.  
• Whole blood or cellular blood components.  
Note:  This document is not intended to apply to the control of genetically -modified 
live organisms designed to be used directly in humans, e.g. live vaccines.  
 
 
 
3.1.2  INTRODUCTION  
 
It is acknowledged that biological substances used in the practice of medicines 
make a vital contribution to health care.  Nevertheless, because of their nature, 
biologicals demand special attention with regard to their regulations to assure 
quality, efficacy and safety.  
Biologicals  are inherently variable due to their biological nature, produced from 
biological materials, and often tested in biological test systems, themselves variable, 
a feature that has important consequences for the safety and efficacy of the resulting 
product. Each product must be evaluated on its own merits.  A prerequisite for the 
use of biological is therefore to assure the consistency of quality and safety from lot -
to-lot.  
Today, the biological field is one of enormous  expansion and increasing diversity, 
most especially in the area of new biotechnologies.  The revolution of DNA -based 
and other cell technologies has opened up a new and exciting vista, and in many 
instances, traditional products are being replaced by equi valents derived by 
recombinant DNA technologies or other cutting -edge technologies.  
It is important to note that the demonstration that a product consistently possesses a 
desired characteristics of safety and efficacy will depend on a multifaceted approach  
on the part of manufacturer and the regulatory authority - drawing on thorough 
characterization of starting materials, demonstration of consistency of production, 
and appropriate selection of lot release tests - all under the stringent and 
documented cont rols imposed by good manufacturing practices - as well as rigorous 
post marketing surveillance activities.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 211  3.2 SPECIFIC REQUIREMENTS FOR REGISTRATION OF BIOLOGICS  
 
Specific requirements for registration of biologic/ biopharmaceutical are described as 
follows: 
1. Requirements for Registration of Biologics (Vaccines and Biotechnology 
products);  
2. Requirements for Registration of Blood Products.  
 
 
3.2.1  REQUIREMENTS FOR REGISTRATION OF BIOLOGICS (VACCINES AND 
BIOTECHNOLOGY PRODUCTS)  
 
a) VACCINES:   
 
i) DEFINITION OF VACCINE  
 
A vaccine contains an active component (the antigen). A vaccine is an immunogen, 
the administration of which is intended to stimulate the immune system to result in 
the prevention, amelioration or therapy of any disease or infection.  
 
Vaccines fo r human use  include one or more of the following:  
a) microorganisms inactivated by chemical/ physical means that retain appropriate 
immunogenic properties;  
b) living microrganisms that have been selected for their attenuation whilst retaining 
immunogenic prop erties;  
c) antigen extracted from microorganisms, secreted by them or produced by 
recombinant DNA technology;  or  
d) antigen produced by chemical synthesis in vitro .  
 
The antigens may be in their native state, truncated or modified following 
introduction of m utations, detoxified by chemical or physical means and/or 
aggregated, polymerized or conjugated to a carrier to increase immunogenicity. 
Antigens may be presented plain or in conjunction with an adjuvant, or in 
combination with other antigens, additives an d other excipients.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 212  ii) REQUIREMENTS FOR REGISTRATION OF VACCINES  
(CHEMISTRY, MANUFACTURING AND CONTROLS, CMC)  
 
A. DESCRIPTION  
 ▪ Description - Information on the source materials: source materials include any 
component/ unformulated active substance used i n the manufacture of the 
product (e.g microorganisms, cells/ cell subtrate, immunogen) including their 
specifications and the tests used to demonstrate compliance with the 
specifications. For combination vaccines, each active substance, which will be 
poole d, combined with other antigens and formulated, shall be described.  
▪ Any chemical modification or conjugation of the drug substance shall be 
described in detail.  
▪ List of inactive substances, which may be present in the drug substance.  
B. METHOD OF MANUFACT URE/ PRODUCTION  
1. Manufacturing Formula:  
 
▪ List of all materials (culture media, buffers, resins for peptide synthesis, 
chemicals, columns etc.) and their tests and specifications, or reference to 
pharmacopoeia.  
▪ Complete formula inclusive of any adjuvants , diluents, preservatives, additives, 
stabilisers etc.  
▪ Production of each antigen in the vaccine (i.e. fermenter or culture volumes for 
each bulk batch size as applicable and typi cal bulk volumes per production run).  
▪ Batch formula for each batch size and f inal formulated bulk product.  
▪ Lot numbering system for intermediates and final product.  
 
 
2.  
Manufacturing Process:  
Flow Charts/ Diagrams be Accompanied by a Descriptive Narrative:  
 
▪ Detailed description of manufacturing process and characterization of t he  
product.  Include complete history and characterization/  characteristics of each 
species, strain, cell banking systems - Master Cell bank (MCB) and Working Cell 
Bank (WCB), cell/ seed lot system, cell substrate system, animal sources 
(including fertili zed avian eggs), virus source or cellular sources.  
 
Ref:  WHO TRS 878 (1998) Annex 1: Requirements for the use of animal cells 
as in vitro substrates for the production of biologicals.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 213   
▪ The flow chart should show the steps in production and a complete l ist of the in -
process controls and tests performed on the product at each step.  
▪ In-process holding steps, with time and temperature limits indicated.  
▪ Description of the manufacturing processes (flow diagram) in detail to support 
the consistency of manufact ure of drug substance - cell growth and harvesting.  
▪ Identification of any processes or tests performed by contract manufacturers or 
testers.  
▪ Animal cells: Cells of animal origin may harbour adventitious agents and 
consequently pose a potentially greater ri sk to humans. Description of measures 
taken to remove, inactivate, or prevent contamination of the product from any 
adventitous agent present.  
▪ Information on measures to prevent any catastrophic events that could render 
the cell banks unusable and to ensur e continuous production of vaccines is 
crucial.  
For recombinant vaccines: description of the construction and characterization of 
the recombinant vector as well as source of master cell bank/ constructs.  
 
3. Process Validation Program:  
▪ Describe general po licy for process validation and provide process validation 
activities performed.  
 
4. Handling, Storage and Packaging:  
▪ All arrangements for the handling of starting materials, packaging materials, bulk 
and finished products, including sampling, quarantine,  release and storage.  
 
C. QUALITY CONTROL  
1. Starting Materials:  
▪ List of all control tests performed on raw materials, with appropriate 
characterisation on starting materials.  
▪ List of raw materials meeting compendia specifications.  
▪ List of raw materials meeting in -house specifications including the tests 
performed and specifications  
▪ Biological starting materials (human or animal origin) with information on the 
requirements to avoid risk of transmissible spongiform encephlopathies (TSEs) 
and human disease s (HIV, hepatitis,etc) in the final product including Certificate 
of Suitability (CEP).  Please refer Checklist A & B  
 
Ref: WHO Guidelines on Transmissible Spongiform Encephalopathies in relation to 
Biological and Pharmaceutical products (2010).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 214  2. Interm ediate Products (as appropriate):  
▪ List the routine tests performed and   specifications for intermediates.  
3. Finished Products (including diluents):  
▪ List routine tests performed and   specifications for final product.   
▪ Description of the method and retest  criteria.  
4. Analytical Validation Activities Performed:  
▪ Include complete description of the protocol used for each bioassay, the control 
standards, the validation of inherent variability of test and the establishment of 
acceptance limits for each assay.  
D. STABILITY  
(http://www.who.int/biologicals/publications/trs/areas/vaccines/stability/en/  ) 
 ▪ Information on stability of intermediates and final product, qualit y control methods   
and rationale for the choice of tests for determining stability.  
▪ Information on the dates of manufacture of the lots, the lot numbers, the vial and 
dose size, and the scale of production.  
▪ Describe the policy for assigning the date of ma nufacture of each component as 
well as the final product (e.g combination vaccine) and diluents, as appropriate.  
▪ In addition to final product stability data at the recommended storage 
temperature, the accelerated stability data at elevated temperatures sho uld be 
sufficient to justify the choice of Vaccine Vial Monitor (VVM) for use with the 
product [Vaccine Vial Monitor WHO/PQS/E06/IN05.1]  
E. LOT SUMMARY PROTOCOL AND LOT RELEASE FOR VACCINE  
 ▪ Lot Summary Protocol - a document which describes the key steps  and critical 
test results at each step of the production process must be submitted.  
▪ Lot release is a basic principle in the control of vaccine.  The aim of lot release is 
the confirmation of consistency of production as each lot of vaccine is unique.  
▪ Subm it Lot/ Batch Release Certificate issued by the competent authority.  
 
Reference : Guidelines for Independent Lot Release of Vaccines by Regulatory 
Authorities World Health Organization 2010  
Circular Ref : (23) dlm.BPFK/PPP/07/25  Directive No.  16 Year  2014.  
Direktif Pelaksanaan Vaccine Lot Release ke atas Semua Produk  Vaksin Berdaftar di 
Malaysia  
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 215  F. NONCLINICAL STUDIES FOR VACCINE  
 ▪ Vacci nes are a diverse class of biological products and their nonclinical testing 
programs will depend on product -specific features and clinical indications.  
▪ Preclinical testing is a prerequisite to moving a candidate vaccine  from the 
laboratory to the clinic and includes all aspects of testing, product 
charaterization, proof of concept/ immunogenicity studies and safety testing in 
animals conducted prior to clinical testing in humans.  
▪ Some live attenuated vaccines must be tested for safety in animals before th ey 
are used in humans.  
 
Ref: WHO TRS 927 (2005) Annex 1: WHO guidelines on nonclinical evaluation of 
vaccines  
G. CLINICAL STUDIES FOR VACCINE  
 ▪ Clinical studies designed and conducted to meet WHO and international GCP 
principles.  
▪ Tabulated summary of the clinical development program of the vaccine, in which 
critical parameters that may have changed during the clinical development.  
▪ Copies of publications about these trials should accompany the submission.  
▪ Clinical summary: Provide detailed summary and intep retation of the safety and 
efficacy data obtained from clinical studies that supports the current prescribing 
information.  
▪ Clinical Expert Report:  Provide an independent clinical expert report on the 
clinical studies (evidence of expertise and independenc e should be provided)  
Ref:  
3. WHO TRS 924 (2004)  Annex 1: WHO guidelines on clinical evaluation of 
vaccines:Regulatory expectations.  
4. WHO TRS 850 (1995)  Annex 3: Guidelines for good clinical practice (GCP) for trials 
on pharmaceutical products.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 216   
H. POST MAR KETING SURVEILLANCE FOR VACCINES  
 ▪ Provide an outline of the post marketing pharmacovigilance plan for the vaccine.  
▪ Periodic safety update report (PSUR) in accordance to ICH Guideline E2C(R1) 
Clinical Safety Data Management: Periodic Safety Update Reports for Marketed 
Drugs.  
▪ In the case of vaccines that have recently been registered/ licensed, provide 
information on any ongoing phase IV studies or on any active monitoring of the 
safety profile that is taking place including adverse events following 
immuniz ation(AEFI).  
▪ Risk management plan.  
 
Please also refer to:  NPRA ’s Guidelines for Pharmacovigilance on Safety of 
Vaccines in Malaysia (January 2010) ISBN 978 -967-5570 -05-6 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 217  b) BIOTECHNOLOGY PRODUCTS  
 
i) DEFINITION  
 
Biotechnological products includes the use of the new genetic tools of recombinant 
DNA to make new genetically modified organisms or genetic engineering products.  
 
Products of recombinant technology  are produced by genetic modification in which 
DNA coding for the required product is introduced, usua lly by means of a plasmid or 
viral vector into a suitable microorganism or cell line, in which DNA is expressed and 
translated into protein. The desired product is then recovered by extraction and 
purification.  
 
ii) ADDITIONAL REQUIREMENTS FOR REGISTRATION OF BIOTECHNOLOGY 
PRODUCTS:   
 
I. PRODUCTION PROCESSES  
 ▪ The production system shall be well defined and documented.  
▪ The effectiveness of the overall purification process for active substance shall be 
demonstrated.  
▪ Validation of procedures for removing contami nating cellular DNA, viruses and 
impurities.  
J. HOST CELL AND GENE CONSTRUCT  
 ▪ Source of host cells, characterisation, stability, purity and selection.  
▪ Information on gene construct, amino acid sequence, vector information and 
genetic markers for characte risation of production cells.  
▪ Cloning process to form the final gene construct and mapping of sited used in 
constructions of final recombinant gene construct.  
▪ Method of gene construct amplication and selection of recombinant cell.  
K. SPECIFICATIONS  
 
 ▪ Drug substances should include assays for identity, purity, potency, 
physiochemical and stability.  
▪ Identity and quantity of impurities along with analytical data which supports 
impurities profile  
▪ Acceptable limits of impurities and should be included in the s pecifications if 
present in finished products.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 218   
L. CHARACTERISATION  
 ▪ Analytical testing performed to characteris e the drug substance with respect to 
identity, purity, potency, and stability.  
▪ Characterisation of drug substance include physiochemical char acterisation, 
immunological properties and biological activity.  
▪ Sufficient sequence information to characterise the product should be obtained.  
▪ Post translational modifications should be identified and adequetly characterised, 
especially when such modifica tions are likely to differ from those found in natural 
counterpart and may influence biological, pharmacological and immunological 
properties of the product.  
M. NONCLINICAL STUDIES  
 
▪ Preclinical testing is a prerequisite to moving a candidate biotechnolog y products  
from the laboratory to the clinic and includes all aspects of testing, product 
charaterization, proof of concept/ immunogenicity studies and safety testing in 
animals conducted prior to clinical testing in humans.  
▪ The primary goals of nonclinic al studies/preclinical safety evaluation are  to 
identify an initial safe dose and subsequent dose escalation schemes in humans, 
potential target organs for toxicity (whether such toxicity is reversible) and safety 
parameters for clinical monitoring  
 
Ref: ICH Topic S6 Preclinical Safety Evaluation of Biotechnology -Derived 
Pharmaceuticals.  
N. CLINICAL STUDIES  
 ▪ Clinical studies designed and conducted to meet WHO and international GCP 
principles.  
▪ Overall approach to the clinical developement of a medicinal pr oduct.  
▪ Overview of the clinical findings and provide an evaluation of benefits and risks 
based upon the conclusions of the relevant clinical studies.  
▪ Interpretation of how the effic acy and safety findings support the proposed dose 
and target indication.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 219   
O. POST MARKETING SURVEILLANCE FOR BIOTECHNOLOGY PRODUCT  
 ▪ Provide an outline of the post marketing pharmacovigilance plan.  
▪ Periodic safety update report (PSUR) in accordance to ICH Guideline E2C(R1) 
Clinical Safety Data Management: Periodic Safety Updat e Reports for Marketed 
Drugs.  
▪ All relevant clinical and nonclinical safety data should cover the period of the 
report with exception of updates of regulatory authority or product registration 
holder (PR H) actions taken for safety reasons, as well as data o n serious, 
unlisted adverse drug reactions (ADRs), which should be cumulative.  
▪ Risk management plan  
 
 
c)  REFERENCES FOR VACCINES AND BIOTECHNOLOGY PRODUCTS:  
 
i) Vaccines:  
 
WHO (http://www.who.int/biologicals/vaccines)  
i) WHO Technical Report Series: Vaccines   
 
 
ii) Biotechnology Products:  
WHO  
i) WHO Technical Report Series 1991 No. 814, Annex 3. Guidelines for assuring the 
quality of pharmaceutical and biological products prepared by recombinant DNA 
technology. (under revision)  
ii) WHO Technical Report Series 1991 No 822,  Annex 3. Guidelines for assuring the 
quality of monoclonal antibodies for use in humans.  
iii) WHO Technical Report Series No 878, Annex 1 and Addendum. Requirements for 
the use of animal cells as in vitro substrates for the production of biologicals.  
iv) WHO Techn ical Report Series No.786, Annex 3.Requirements for human interferons 
prepared from lymphoblastoid cells (Requirements for biological substances N0.42)  
v) WHO Technical Report Series No.771, Annex 7 Requirements for human interferons 
made by recombinant DNA t echniques (Requirement for biological substance No. 
41) Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 220   
EMA  
i) CHMP/BWP/157653/07. Production and Quality Control of Monoclonal Antibodies 
and Related Substances.  
ii) CPMP/BWP/328/99. Development Pharmaceutics for Biotechnological and 
Biological Products - Anne x to Note for Guidance on Development Pharmaceutics.  
iii) CHMP/BWP/157653/2007. Guideline on Development, Production, Characterisation 
and Specifications for Monoclonal Antibodies and Related Products.  
iv) EMEA/410/01 Rev. 3 Minimising the Risk of Transmitting Anim al Spongiform 
Encephalopathy Agents via Human and Veterinary Medicinal Products.  
 
ICH 
i) ICH Topic Q5A Viral Safety Evaluation Of Biotechnology Products Derived From 
Cell Lines Of Human Or Animal Origin.  
ii) ICH Topic Q5B Quality of Biotechnological Products: Ana lysis of the Expression 
Construct in Cell Lines used for Production of r -DNA derived Protein Products.  
iii) ICH Topic Q5D Quality of Biotechnological Products: Derivation and 
Characterisation of Cell Substrates used for Production of Biotechnological/ 
Biologica l Products.  
iv) ICH Topic Q5C Quality of Biotechnological products: Stability Testing of 
Biotechnological/ Biological Products.  
v) ICH Topic Q5D Derivation and Characterisation of Cell Substrates Used for 
Production of Biotechnological/ Biological Products.  
vi) ICH T opic Q5E Comparability of Biotechnological/ Biological Products Subject To 
Changes in Their Manufacturing Process.  
vii) ICH Topic Q6B Specifications: Test Procedures and Acceptance Criteria for 
Biotechnological/ Biological Products.  
viii)ICH Topic Q2 Validation of A nalytical Procedures: Text and Methodology.  
ix) ICH Topic Q8 Pharmaceutical Development.  
x) ICH Topic Q11 Development and Manufacture of Drug Substances (Chemical 
Entities and Biotechnological/ Biological Entities).  
xi) ICH Topic S6 Preclinical Safety Evaluation of B iotechnology -Derived 
Pharmaceuticals.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 221   
3.2.2  REQUIREMENTS FOR REGISTRATION OF BLOOD PRODUCTS  
 
Note:  This document is applicable to all plasma -derived products containing an active and 
inactive ingredient that is derived from human blood.  
 
 
a) DEFINITION  OF BLOOD PRODUCT  
 
Any therapeutic product derived from human blood or plasma and produced by a 
manufacturing process that pools multiple units.   
 
Plasma -derived therapies and their recombinant analogs are unique among 
pharmaceuticals and biologics.  Thei r production begins with a biological starting material, 
human plasma. Each therapy has a unique biochemical profile as a result of differences in 
production and processing methods that can lead to differing clinical responses and 
efficacy among patients.   
 
Hence, from the starting material, through manufacturing and final distribution to patients, 
the complexities of producing blood products places it in a unique class of biologics.  
 
Blood products are regulated as medicinal product. Blood products are in herently variable 
due to their biological nature, and the biological methods to test them. They are subjected 
to comprehensive assessment of the quality, efficacy and safety.   
 
Four (4) principal complementary approaches are adopted:  
 
▪ Starting material:   Assurance of the quality and safety of the plasma for 
fractionation.  
▪ Manufacturing technique:   Control of the fractionation and subsequent 
manufacturing procedures for isolation, purification, viral inactivation and/or removal 
steps.  
▪ Good manufacturing pr actice (GMP):   Strict adherence to GMP.  Adoption of GMP 
as an essential tool of Quality Assurance System.  
▪ Product Compliance:   Standardization of biological methods needed in 
characterisation of in -process and finished products.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 222  Plasma for fractionation  and blood products that are regulated by National Pharmaceutical 
Regulatory Division  (NPRA ) includes:  
 
▪ Plasma products derived from plasma collected and fractionated in Malaysia for use 
in Malaysia;  
▪ Plasma products derived from plasma collected and fracti onated overseas for use in 
Malaysia; and  
▪ Plasma products derived from overseas -sourced plasma fractionated in Malaysia for 
use overseas.  
 
 
b) REQUIREMENTS FOR REGISTRATION OF BLOOD PRODUCTS  
 
1. QUALITY OF PLASMA SOURCE MATERIAL  
 Plasma Master File (PMF).   It can also be a stand -alone document. Document 
pertaining to the collection and controls of source materials.  Key elements of PMF 
are:  
▪ Requirements for a formal contract governing purchase and supply of plasma.  
▪ Source plasma.  
▪ GMP status of the blood esta blishments/ collection centers.  
▪ Description of the quality assurance system applying to plasma supply and 
use. 
▪ Arrangements for donor selection, selection/exclusion criteria.  
▪ Data on population epidemiology and blood -borne infections.  
▪ Requirements for test ing of samples of donations and pools. Mandatory 
serology on all plasma donations.  Each unit of source material tested for 
HBsAg, anti -HIV and anti -HCV  
▪ Plasma bags, plasma quality and plasma specifications.  
▪ Arrangement for communication and review of post -donation information.  
▪ Plasma inventory hold.  
▪ Traceability from donor to end product and vice versa.  
 
Ref: CHMP/BWP/3794/03 Rev. 1 Scientific data Requirements for Plasma Master 
File (PMF) and also the checklist.  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 223  2. MANUFACTURING PROCESS AND CONTROL  
 Documents that verify each batch of source material intended for manufacture has 
been serological tested for hepatitis B (HBV), hepatitis C (HCV) and HIV.  Each 
batch of source material must also be tested for HCV RNA by Nucleic Acid Testing 
(NAT) and (in creasingly for other viruses including HIV, HBV, B19, and HAV) and 
exclusion of reactive donations.  
 
Characterization: Physicochemical and biological characterization: Specific tests 
that will provide information regarding identity, purity, potency, stabil ity and 
consistency of manufacture for the drug substance.  
 
Manufacture and Controls:  
i) Formula:  
▪ Include a list of all starting materials, reagents, monoclonal antibodies, 
intermediate products and auxiliary materials (buffers, sera, antibiotics etc.) 
with s pecifications or statement of quality for each.  
▪ Excipients:  List of excipients.   
▪ For non -compendial excipients: Describe tests and specifications.  
▪ For novel excipients: Include description for preparation, characterisation and 
controls.  
▪ When used as exc ipient in the product, the expiry date of the plasma -derived 
product should not be earlier than that of the finished product.  
 
ii) Manufacturing:  
▪ Detailed description of manufacturing process and controls to demonstrate 
proper quality control or prevention of  possible contamination with adventitious 
agents.  
▪ In-process and final controls.  
• Viral inactivation and/ or removal processes  
• Viral validation studies and report  
• Pathogen safety document inclusive of Transmissible Spongiform 
Encephalopathies (TSEs) risk as sessment  
• Information or certification supporting the freedom of reagents, inactive 
ingredients of human or animal origin from adventitious agents.  
• Process consistency  
• Analytical validation studies  
• Process validation studies (purification, sterility etc.)  
• Batch record and batch release specifications  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 224  3. THE FINAL PRODUCT  
 ▪ Finished product testing and quality control  
▪ Stability study program and expiration date  
▪ Product history  
▪ Container closure system, storage and handling  
▪ Package insert and labels  
▪ Lot/ batc h release protocols  
▪ Certificate of batch review and release from a competent authority  
4. CLINICAL STUDIES  
 ▪ Demonstrating product’s efficacy  
5. POST MARKETING SURVEILLANCE – mandatory follow -up 
 ▪ Periodic Safety Update Report (PSUR)  
▪ Risk Management Plan s 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 225  c) Checklist of Plasma Master File for Blood Products  
 
Section  Documents  Yes/No  
1. General Information   
1.1 Plasma Derived Products’ List   
1.2 Overall Safety Strategy  
• Collection of plasma  
• Testing  
• Storage   
1.3 General Logistics  
• Flowchart of supply chain of plasma   
2. Technical Information on Starting Materials/Plasma   
2.1 Plasma Origin  
• Information on Collection Centers  
• Information on Testing Centers  
• Selection/ Exclusion Criteria for Donors  
• Traceability   
2.2 Plasma Quality and Safety  
• Compliance wi th Ph. Eur. Monographs or relevant 
monographs  
• Screening Tests for Markers of Infection  
• Technical Characteristics of Bags and Bottles for Blood 
and Plasma Collection, Including Information on 
Anticoagulant Solutions Used  
• Storage and Transport  
• Procedures for  any Inventory Hold Period  
• Characterisation of the Fractionation Pool   
2.3 Contract Between Manufacturer and Blood Collection 
Establishment(s)  
• System in place between the manufacturer and/or 
plasma fractionators/ processor on one hand, and blood 
collectio n establishments on the other hand which 
defines the conditions of their interaction and their 
agreed specifications   
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 226  d) REFERENCES FOR BLOOD PRODUCTS:   
 
The National Pharmaceutical Regulatory Division ’s requirements for registration of blood 
products are  aligned with the scientific guidelines and recommendations for quality, clinical 
efficacy and safety and non -clinical of the World Health Organization (WHO), European 
Medicines Agency and International Conference of Harmonization (ICH).   
 
Where appropriat e, the relevant WHO, EMA and ICH guidelines on blood products 
shall be consulted in particular the followings:  
 
WHO (http://www.who.int/boodproducts/en/index.html ) 
i) WHO Technical report Series 941,  Annex 4, Recommendations for production, 
control and regulation of human plasma for fractionation.  
ii) WHO Technical report Series 924, Annex 4, Guidelines on viral inactivation and 
removal procedures intended to assure the viral safety of human plasma produc ts. 
iii) WHO Guidelines on tissue infectivity distribution in Transmissible Spongiform 
Encephalopathies.  
 
EMA  (http://www.ema.europa.eu)  
i) EMA/CHMP/BWP/706271/2010 Committee for medicinal products for human use 
(CHMP) Guideline on plasma -derived medicinal product s 
ii) CHMP/BWP/3794/03 Rev. 1 Scientific data Requirements for Plasma Master File 
(PMF)  
iii) CPMP/BWP/268/953AB8A Virus Validation Studies: The Design, Contribution and 
Interpretation of Studies validating the Inactivation and Removal of Viruses  
iv) EMEA/410/01 Rev. 3 Minimising the Risk of Transmitting Animal Spongiform 
Encephalopathy Agents via Human and Veterinary Medicinal Products  
v) Guideline on the clinical investigation of recombinant and human plasma -derived 
factor VIII products, European Medicines Agency, EMA/CHM P/BPWP/144533/2009.  
vi) Note for Guidance on the Clinical Investigation of Human Plasma Derived Factor VIII 
and IX products, European Medicines Agency, CPMP/BPWG/198/95REV.1.  
vii) Guideline on the Clinical Investigation of Human Normal Immunoglobulin for 
Intravenou s Administration (IVIg), European Medicines Agency, 
EMA/VHMP/BPWP/94033/2007 REV.2.  
 
ICH (http://www.ich.org ) 
i) ICH Topic 5QC Quality of Biotechnological products: Stability Testing of 
Biotechnological/  Biological Products.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 227  3.3 CHECKLISTS  
 
3.3.1  Checklist A:  
 
Products Containing Animal -Derived Materials WITH  a valid TSE risk evaluation 
Certificate of Suitability (CEP)  
 
No. Documents  Yes/ No  
1. TSE Risk Evaluation Certificate of Suitability (CEP)   
2. Basic information providing a bri ef description of the following:   
3. Rationale for using animal -derived materials   
4. Source of Animals  
• Declaration of materials of porcine origin  
• Declaration of materials of other animal origin   
5. Declaration of the nature of the animal tissue/ parts of animal 
used.   
6. Description of the tissue/ organ -collection procedures and 
measures in place to avoid cross -contamination.   
7. Nature and quantity of each animal -derived material used:  
• As a drug substance.  
• As an excipient or adjuvant.  
• As a starting m aterial used in the manufacture of a drug 
substance.  
• As a starting material used in the manufacture of 
excipient.  
• As a reagent or culture media component used in 
manufacture.  
• As a reagent or culture media component used in 
establishing master cell banks.  
• As a reagent or culture media component used in 
establishing working cell banks.  
• Others, please provide details   
8. Declaration that the final product does not contain any animal -
containing materials with the relevant evidence (if applicable)   
9. Other su pporting documents e.g. Halal  Certification of the animal 
derived ingredient from a competent Halal Certification Authority.   
10. Labelling of the animal derived materials.   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 228  3.3.2  Checklist B:  
 
Products Containing Animal -Derived Materials WITHOUT  a valid TSE r isk evaluation 
Certificate of Suitability (CEP)  
 
Section  Documents  Yes/ No  
1. Detailed Assessment Report for the risk of TSE.  
The scope of this assessment report should include the 
following:   
2. Rationale for using animal -derived materials   
3. Source o f Animals  
• Declaration of materials of porcine origin  
• Declaration of materials of other animal origin   
4. Declaration of the nature of the animal tissue/ parts used.   
5. Description of the tissue/ organ -collection procedures and 
measure in place to avoid cross -contamination.   
6. Detail of the risk factors associated with the route of 
administration and maximum therapeutic dosage of the product.   
7. Nature and quantity of each animal -derived material used:  
• As a drug substance  
• As an excipient or adjuvant  
• As a starting material used in the manufacture of a drug 
substance.  
• As a starting material used in the manufacture of 
excipient.  
• As a reagent or culture media component used in 
manufacture.  
• As a reagent or culture media component used in 
establishing master  cell banks.  
• As a reagent or culture media component used in 
establishing working cell banks.  
• Others, please provide details.   
8. Relevant information to support the claim that the manufacturing 
process is capable of inactivating TSE agents.   
9. Certifi cates of analysis for each animal -derived materials used.   
10. Declaration that the final product does not contain any animal -
containing materials with the relevant evidence (if applicable)   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 229  Section  Documents  Yes/ No  
11. Other supporting documents eg. Halal Certification of the a nimal 
derived ingredient from a competent Halal Certification Authority.   
12. Labelling of the animal derived materials.   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 230  APPENDIX 4: GUIDELINE ON REGISTRATION OF HEALTH 
SUPPLEMENTS  
 
 
 
 
  
 
 
 
Outline:  
 
4.1 Definition  
4.1.1  Health Supplement (H S)  
4.1.2  Indication  
4.1.3  Route o f Administration  
4.1.4  Exclusion as Health Supplement  
4.1.5  Exemption  
4.2 Active Ingredients  
4.3 Maximum Daily Levels of Vitamins and Minerals for Adults Allowed in  
Health Supplements  
4.4 Health Supplement Claim   
4.4.1  Conditions  
4.4.2 Types and Evidence of Claims  
4.4.3  Claims Substantiation  
4.4.4 Illustrative Substantiation Evidence  
4.5 Specific Dossier Requirement for Registration of Health  Supplements  
 
Attachment 1:  Checklist of Dossier Requirement  for Health Supplement s 
Attachment 2:  Table 20: Allowable Claims for Specific Active Ingredients in 
Health Supplements  
Acknowledgements   
IMPORTANT NOTES:   
This guideline will serve as an additional reference guide for the registration of 
health supplement products which consist of pharmaceutical active ingredients for 
human use as well as ingredients derived from natural sources.  
 
Applicants are advised to refer to Drug Registration Guidance Document for the 
common requirements for the preparation of a well -structured dossier application 
to be submitted for product registration.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 231  4.1  DEFINITION  
 
4.1.1 HEALTH SUPPLEMENT (HS)  
 
A Health Supplement (HS) means any product that is used to supplement a diet and to 
maintain, enha nce and improve the health function of human body. It is presented in small 
unit dosage forms (to be administered) such as capsules, tablets, powder, liquids and shall 
not include any sterile preparations (i.e. injectable, eyedrops). It may contain one or more, 
or the following combination:  
i) Vitamins, minerals, amino acids, fatty acids, enzymes, probiotics, and other 
bioactive substances ; 
ii) Substances derived from *natural sources, including animal, mineral and botanical 
materials in the forms of extracts, iso lates, concentrates, metabolite ; 
iii) Synthetic sources of ingredients mentioned in (i) and (ii) may only be used where the 
safety of these has been proven . 
 
 
4.1.2 INDICATION  
 
i) Used as a Health Supplement ; 
ii) Vitamin  and mineral supplements for pregnant and lactat ing women.  
 
 
4.1.3 ROUTE OF ADMINISTRATION  
Oral 
  
 
4.1.4 EXCLUSION AS HEALTH SUPPLEMENT S: 
 
Health Supplements shall NOT  include:  
i) Any product as a sole item of a meal ; 
ii) Any injectable and sterile preparation ; 
iii) Any cells, tissues, organs or any substance deriv ed from the human body ; 
iv) Any substance listed in the Schedule of the Poison Act ; 
v) Any other route of administration other than the oral route . 
 
 
4.1.5 EXEMPTION  
 
Extemporaneous preparations that have been prepared and given directly to the patient by 
a healt hcare practitioner during the course of treatment . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 232  4.2 ACTIVE INGREDIENTS  
 
Listed active ingredients can be checked trough http://npra.moh.gov.my/  of product search.  
 
 
 
4.3 MAXIMUM DAILY LEVELS OF VITAMINS AND MINERA LS FOR 
ADULTS ALLOWED IN HEALTH SUPPLEMENTS  
 
NO. VITAMINS & MINERALS  UPPER DAILY LIMIT  
1.  Vitamin A  5000 IU  
2.  Vitamin D  1000 IU  
3.  Vitamin E  800 IU  
4.  Vitamin K (K1 and K2) 1 0.12mg  
5.  Vitamin B1 (Thiamine)  100 mg  
6.  Vitamin B2 (Riboflavine)  40 mg  
7.  Vitami n B5 (Panthothenic Acid)  200 mg  
8.  Vitamin B6 (Pyridoxine)  100 mg  
9.  Vitamin B12 (Cyanocobalamin)  0.6 mg  
10.  Vitamin C (Ascorbic Acid)  1000 mg  
11.  Folic Acid  0.9 mg  
12.  Nicotinic Acid  15 mg  
13.  Niacinamide (Nicotinamide)  450 mg  
14.  Biotin  0.9 mg  
15.  Boron  6.4 m g 
16.  Calcium  1200 mg  
17.  Chromium  0.5 mg  
18.  Copper  2 mg  
19.  Iodine  0.3 mg  
20.  Iron 2 20 mg  
21.  Magnesium  350 mg  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 233  NO. VITAMINS & MINERALS  UPPER DAILY LIMIT  
22.  Manganese  3.5 mg  
23.  Molybdenum  0.36 mg  
24.  Phosphorus  800 mg  
25.  Selenium  0.2 mg  
26.  Zinc 15 mg  
 
Note:  
1. Vitamin K (K1 and K2) is restricted only for combi nation with other vitamins and 
minerals in oral preparations. Vitamin K (K1 and K2) as a single ingredient in an  
oral preparation is not allowed.  
2. For pre and antenatal use, as part of a multivitamin and mineral preparation, 
levels higher than the 20mg limi t established for adults may be permitt ed at the 
discretion of the Authority.  
3. Any form of fluoride as an ingredient is not permitted in formulation of health 
supplement  products.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 234  4.4 HEALTH SUPPLEMENT CLAIM  
 
 
4.4.1  CONDITIONS  
 
All claims made for HS sha ll: 
 
i) be consistent with the definition of HS ; 
ii) enable consumers to make an informed choice regarding products ; 
iii) not be misleading or false ; 
iv) support the safe, beneficial and appropriate use of the product ; 
v) maintain the level of scientific evidence which is pr oportional to the type of 
claims ; 
vi) be for health maintenance and promotion purpose only ; 
vii) not be medicinal or therapeutic in nature, such as implied  for treatment, cure or 
prevention of disease . 
 
 
4.4.2  TYPES AND EVIDENCE OF CLAIMS  
 
i) A health supplement cla im refers to the beneficial effects of consuming HS to 
promote good health and well -being (physical and mental) by providing nutrition, 
enhancing body structure/ function, relieving physiological discomfort and/or 
reducing the risk of health related condit ions or diseases.  
 
ii) Types of HS claims are : 
o General or Nutritional Claims ; 
o Functional Claims  (medium) ; 
o Disease Risk Reduction Claims (high) .  
 
iii) For a HS product making a General or  Functional Claim on vitamin(s) and/or 
mineral(s), it must contain minimum of  15% of the Codex Nutrient Reference Value 
(NRV) per daily dose of the vitamin(s) and/or mineral(s). Other ingredients must be 
substantiated by the evidences to which it has been supported.  
For example , if vitamin is less than 15% NRV, then the specifi c claim for this vitamin 
is not allowed unless there is evidence to support effect below this value.  
 
iv) For a HS product making Disease Risk Reduction Claim, it must be substantiated by 
the evidences to which it has been supported.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 235  (i) Table 1: General or Nutr itional Claims  
 
Level of 
claim  Definition  Examples/ 
Wording of 
claim  Criteria  Evidence to 
substantiate HS 
claims  
General 
or 
Nutritional 
Claims  
 ▪ General Health 
Maintenance  
 
▪ Benefits derived 
from 
supplementation 
beyond normal 
dietary  intake  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 ▪ Supports 
healthy 
growth and 
development  
 
▪ Nourishes 
the body  
 
▪ Relieves 
general 
tiredness, 
weakness  
 
▪ Helps to 
maintain 
good health  
 
▪ For energy 
and vitality  
 
▪ For 
strengthening 
the body  
 
 
 
 ▪ Is in line with 
established nutrition 
knowledge in 
reference texts  
 
▪ Is related to general 
well-being in line 
with scientific 
knowledge  
 
▪ Claim does not refer 
to the structure 
and/or function of 
the human body  
 
▪ In accordance to HS 
principles and 
practice in Malaysia  
 
 
  
 
 
 
 1 or more of the 
following 
evidences:  
 
i) Standard  reference 
e.g. reference 
textbooks, 
pharmacopoeia, 
monographs  
 
ii) Recommendations 
on usage from 
reference 
regulatory 
authorities or 
reference 
organisations  
 
 
 
 
 
Please refer to Illustrative  Substantiation Evidence List for the list of acceptable references , 
organisations and authorities.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 236  (ii) Table 2: Functional Claims (medium)  
 
Claims must be adequately substantiated through ing redient -based evidence and when 
necessary through product -based evidence.  
Types of 
HS claim  Definition  Examples/ 
Wording of 
claim s Criteria  Evidence to substantiate 
HS Claims  
Functional 
Claims  
(medium)  
 ▪ Maintains or 
enhances the 
structure or 
function of 
the human 
body, 
excluding 
disease -
related claims  
 
 Acceptable 
claims based 
on the single 
ingredient  
e.g. 
▪ Vitamin A 
helps to 
maint ain 
growth, vision 
and tissue 
development  
 
▪ Vitamin D 
helps in 
normal 
development 
and 
maintenance 
of bones and 
teeth.  
 
▪ Chondroitin 
helps to 
promote 
healthy joints  
 
 For claims on 
established 
nutrients and 
ingredients  such 
as vitamins & 
minerals with 
daily 
recommended 
values  
 
▪ Meet the 
conditions for 
nutrient function 
claims  as set 
by the Authority  
 
▪ Claims have 
consistent 
scientific 
support 
according to 
scientific review 
and evaluation  
 
▪ In accordance 
to HS principles 
and practice in 
Malaysia  
 1 or more of th e following 
evidence:  
i) Standard reference e.g. 
reference textbooks, 
pharmacopoeia, 
monographs  
ii) Recommendations on 
usage from reference 
regulatory authorities or 
reference organisations  
iii) Good quality scientific 
evidence from human 
observational studies 
(refer to ASEAN 
Guidelines on efficacy 
data requirement) (only in 
the event that human 
experimental study is 
not ethical, animal 
studies will be accepted 
together with 
epidemiological studies 
or other scientific 
literature and 
documented traditional 
use) 
iv)  Peer -reviewed scientific 
data or meta -analysis  
Please refer to Illustrative  Substantiation Evidence List for the list of acceptable references, 
organisations and authorities . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 237  (iii) Table 3 : Disease risk reduction (high)  
Types of 
HS claim  Definition  Examples/ 
Wording of 
claims  Criteria  Evidence to 
substantiate HS Claims  
Disease 
risk 
reduction  
 ▪ Significantly 
altering or 
reducing a 
risk factor of 
a disease or 
health related 
condition.  ▪ Helps to 
reduce risk of 
osteoporosis 
by 
strengthening 
bone  
 
▪ Helps to 
reduce the  risk 
of 
dyslipidaemia  
  
 ▪ The relationship 
between the HS 
ingredient or product 
and disease risk 
reduction is 
supported by 
consistent scientific 
evidence  
 
▪ Documented in 
authoritative 
reference texts  
 
▪ Recognised by the 
Authority reference 
or international 
organisations or 
regulatory 
authorities  
 
▪ Adheres to the key 
principles of HS 
claims  
 
 Compulsory evidence:  
i) Scientific evidence 
from human 
intervention study on 
ingredient and/or 
product  
ii) Toxicological study 
(chronic)  
iii) Pharmacological 
study  
At least 1 additi onal 
evidence:  
i) Standard reference 
e.g. reference 
textbooks, 
pharmacopoeia, 
monographs etc.  
ii) Recommendations 
on usage from 
reference regulatory 
authorities or 
reference 
organisations  
iii) Evidence from 
published scientific 
reviews or meta -
analysis  
iv) Report  prepare d by 
expert committees/ 
expert opinion 
(subject to the 
Authority approval)  
Please refer to Illustrative  Substantiation Evidence List for the list of acceptable references, 
organisations and authorities .Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 238  4.4.3  CLAIMS SUBSTANTIATION  
 
Claims must be in line  with the respective HS principles and supported by adequate 
evidence.  To reflect the total available usage evidence (including relevant scientifi c 
evidence), the evidence shall  be summarized as part of the substantiation do cument for the 
claim as in the Table 4  below.  
 
Indicati
on/ 
claim  Produc
t/ 
Ingredi
ent 
studied  Dosage 
and 
administra
tion route  Durati
on of 
treatm
ent Type 
of 
eviden
ce 
(scienti
fic 
eviden
ce) Stud
y 
desi
gn Study 
populat
ion Summ
ary of 
finding
s Limitati
ons of 
the 
study  Source of 
evidence  
i) Author  
ii) Title 
iii) Public
ation 
details  
iv) Year 
v) Type 
(text,
…) 
 
 
 
 
 
 
 
          
 
Note:  Evidence not summarised as in the above format will not be further evaluated.Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 239  4.4.4  ILLUSTRATIVE SUSBSTANTIATION EVIDENCE  
 
i) Reference texts  
 
a. Martindale, latest edition. The Complete Drug. Phar maceutical Press, 2009.  
b. The ABC Clinical Guide to Herbs. American Botanical Council  
c. WHO Monographs on Selected Medicinal Plants  
d. British Pharmacopoeia  
e. United States Pharmacopoeia  
f. Indian Pharmacopoeia  
g. Chinese Pharmacopoeia  
h. Natural Standards ( www.naturalstandard.com ) 
i. Office of Dietary Supplements, National Institutes of He alth - Dietary Supplement 
Fact Sheets 
(http://ods.od.nih.gov/Health_Information/Information_About_Individual_Dietary_Sup
plements.aspx ) 
 
ii) Organisations  
 
a. American Botanical Council ( www.herbalgram.org ). 
b. American Nutraceutical Association ( www.ana -jana.org ) 
c. CODEX Alimentarius  
d. Global Information Hub for Integrated Medicine ( http://www.globinmed.com ) 
e. National Centre for Complementary and Alternative Medicine (http://nccam.nih.gov/ ) 
f. Office of Dietary Supplements, Nati onal Institutes of Health (USA) 
(http://ods.od.nih.gov ) 
 
iii) Reference regulatory authorities  
 
a. Australia TGA  
b. Chinese Health Authority on Chinese medicinal herbs  
c. European Commission  
d. Health  Canada  
e. United States FDA  
 
Notes:  
1. This list is not meant to be exhaustive and will be reviewed from time to time.  
2. The Authority will nonetheless conduct a detailed evaluation of the evidence included in the 
report to ensure that the health claim is substan tiated.  
3. The Authority will be willing to consider review other than the listed above, if the standards of 
evidence are consistent with those of the Authority.  
4. All references must be current . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 240  4.5 SPECIFIC DOSSIER REQUIREMENT FOR REGISTRATION OF 
HEALTH SUPP LEMENTS  
 
PRODUCT  VALIDATION  
 
1. PRODUCT NAME  
• May include product name, dosage form and strength (e.g. XYZ Capsule 500mg)  
• Dosage form and strength of product would need to be entered as part of product 
name to allow for multiple dosage forms (e.g. tablet,  capsule) and strengths (e.g. 
200mg and 400mg) for any particular named (proprietary or generic) product.  
• In any event if found that registered product name is similar to another registered 
product, NPRA  reserve the rights to request for the change in the product name.  
• Product with more than 1 active ingredient could not include strength of active 
ingredients in the product name.  
• Product name may be included together with the brand name or trademark name, if 
applicable.  
• Any product name which is the same o r similar either in writing/ pronunciation, with 
the product name of an adulterated product is prohibited . 
 
Table 5:  List of Non -Permissible Product Name for Health Supplement Products  
 
No. Issue  Example  
1. Prohibited use of disease names as stated 
in th e Medicines (Advertisement and Sale) 
Act 1956 (revised 1983)  Diabetes, Asthma, Cancer  
2. Prohibited use of a single active ingredient 
as a product name in products containing 
more than one active ingredient unless 
product name contains words such as 
‘Plus , Compound, Complex, Herbanika  If the product contain Vitamin C, 
Vitamin E and Fish Oil  
 
Product name: “Vitamin C” is not 
allowed but product name: 
“Vitamin C Plus” is allowed.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 241  No. Issue  Example  
3. Prohibited use of superlative  
Names which indicates superiority inefficacy  Power, Superior, Pure, Mustajab, 
Safe, Healthy, Penawar, VIP, 
Good, World Number 1  
4. Prohibited use of spelling of words which 
may cause confusion  
i)Words which involve names of/part  
thereof:  
20 disease names prohibited in the Medicines  
(Advertisement an d Sale) Act 1956 (Revised  
1983)  
ii) Other diseases without scienti fic proof  
iii) Prohibited indication  Go Out = GOUT (label)  
Utix 
5. Prohibited use of names which may cause 
ambiguity  
Ambiguous product name  B For Energy?  
6. Prohibited use of names which m ay be  
offensive or indecent  SENXBIG=SEnXBIG(label)  
Sexy, Enjoy, Paradise, Heavenly, 
Blue boy, Casanova, Desire  
7. Product name which is not congruent with 
the active ingredient.  The active ingredient is Evening 
Primrose oil (EPO) and the 
product name: “Ma rine tablet” is 
not allowed.  
8. Prohibited use of product names which has 
elements of ludicrous belief  
Statements referring to ancient 
believe/negative spirits/supernatural power  Words such as miracle, magic, 
magical, miraculous, saintly, 
heavenly  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 242  No. Issue  Example  
9. Prohibited use of product names similar to 
the existing approved product names  
Product name similar to the spelling and 
pronunciation of words of an existing product 
names  Elegen vs L -gen vs L -jen Forte 
vs Fort  
10. Prohibited use of product names which 
may c ause ambiguity in the nature of 
product (drug/ food/ beverage)  
Product name similar to a food/ beverage 
name  Juice, Health drink, Beverage, 
Kooky  
11. Prohibited use of product names which 
represents professional advice or opinion  Dr Sunny, Professor  
12. Product name that symbolize a claim  Vigour, Youthful, High, Hi  
13. Product name that uses strength but 
formulation contains more than one active 
ingredient.  If the product contains 
multivitamins and minerals.  
 
Product name:  
“XXX multivitamins and minerals  
500mg” is not allowed.  
14. Other prohibited product names  
 Minda, IQ, Smart, Unique, Ultra 
Mega, Detox , Defence, Immunity  
15. Names of organs and brain  Heart, kidney, skin, liver  
 
Note:  
1. This list is not meant to be exhaustive and will be reviewed from  time to time.  
2. The Authority reserves the right to disallow any other words, phrases or graphics for product 
label which in its opinion is misleading, improper or not factual.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 243  2. DOSAGE FORM  
 
• Dosage form s allowed:  
 
a) Tablets  
- Caplet, Lozenge, Chewable tablet , Dispersible tablet, 
Effervescence tablet, uncoated tablet, enteric coated tablet, Sugar 
coated tablet, Film coated tablet, extended release tablet ; 
b) Capsules  
- Soft capsule, Hard capsule, Enteric coated capsule, Chewable soft 
capsule, Extended released caps ule; 
c) Powder/  Granules ; 
d) Liquid  
- Emulsion, syrup, spray, suspension.  
• Products in th e shape of animal dosage forms are not allowed.  
• Supporting data from established reference (e .g. Standard Pharmacopeia) shall be 
required for new dosage form.  
• The form that c orrectly describes it in terms of its product quality control 
speci fications and performance shall  be selected.  
• A separate application  for registration is required for each dosage form.  
• The following documents will have to be provided during submission of product 
dossier  for Sustained -release/  Extended -release/  Timed -release dosage form  
i) Protocol of analysis;   
ii) In-Process Quality Control (IPQC);  
iii) Finish ed Product Specification (FPQC);  
iv) Certificate of Analysis (COA).  
 
 
3. ACTIVE INGREDIENT  
 
Name of Active Ingred ient:  
• Please select active ingredient from the search database. If substance is not listed, 
please select the ‘Not Listed Ingredient’ button. Automatic e -mail will be send to 
NPRA  for notification.  
• Approved names, pharmacopoeia names of ingredients shall be used whenever 
possible.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 244  Strength of active ingredient :  
• To enter the content of active ingredients (numerical) and then select the weights 
and measures from the given list.  
• Content of ingredient s shall  be expressed as approp riate in the following manne r: 
a. quantity per dose unit (e.g. for unit dose formulations  - tablet, capsule, lozenge, 
etc.) 
b. percentage composition - %w/w, %w/v, %v/v, etc.  
c. weight per ml. (e.g. for solutions,suspension etc.)  
d. quantity (percentage or amount) per measured dose (e.g. oral li quids,  drops, 
etc.) 
• Metric weights and measures shall be used.  
 
Source of Active ingredient : 
• To specify the source such as animal, plant, synthetic or others  (to specify)  
 
USE OF PROTECTED/ ENDANGERED INGREDIENTS  
 
a) PROTECTED/ ENDANGERED WILDLIFE SPECIES   
 
It is the responsibility of the applicant to ensure that the ingredient(s) derived 
from wildlife species its parts and derivtives used in the formulation COMPLIES 
with the Wildlife Conservation Act 2010 (Act 716) and International Trade in 
Endangered Spec ies Act 2008 (Act 686). Both guidelines can be downloaded 
through this link http://www.wildlife.gov.my . 
The applicant shall contact the following department to obtain the necessary 
permit/ license.  A copy of the  permit/ license shall be attached together with the 
application form for product registration.  
Department of Wildlife and National Parks, Peninsular Malaysia  
Km. 10, Jalan Cheras,  
56100 Kuala Lumpur,  
Tel: +603 -90866800, Fax: +603 -90753873  
 
b) ENDANGERED BOTANICAL SPECIES   
 
It is the responsibility of the applicant to declare the source of the botanical 
ingredient if it is listed under the International Trade in Endangered Species Act Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 245  2008 (Act 686). If the ingredient is from a local source, a special permit / license 
shall be obtained from the:  
Division of Protection and Quarantine of Plants,  
Department of Agriculture,  
Tingkat 1 -3, Wisma Tani,  
Jalan Sultan Salahuddin,  
50632 Kuala Lumpur.  
Tel: +603  - 20301400, Fax: +603 - 26913550.  
 
 
Remarks on active ingredi ent (if any ):  
• To specify the equivalent/providing amount of active component from the raw 
material (e.g: Sodium ascorbate 520 mg providing.... Vitamin C)  
• Declaration of species name from natural source (plant, animal or others)  
 
 
Table 6:   Additional data  to support a new health supplement active ingredients : 
 
No. Types of documents  Checklist  
1. Standard/ established 
references  • Martindale, Pharmacopeias, Monograph 
etc. 
2. Information from the 
competent authorities of 
reference countries  • Information shall  be provided from the 
competent authorities of reference 
countries (Refer to 9.6.5)  
• Example of supporting documents:  
➢ Registration status and maximum 
registered dosage as health 
supplement  
➢ established monograph  
➢ GRAS status  
3. Clinical studies or scientif ic 
evidences  • Full published articles  
• Unpublished  data may be considered     
• Mandatory for high claim  
 4. Non-clinical studies to support 
long term -use Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 246  No. Types of documents  Checklist  
5. Toxicology studies with the 
determination of NOAEL (No 
observed adverse effect level)  
6. Pharm acological study  
7. Justification for the use of new 
active ingredient  as health 
supplement   
8. Registration status worldwide  • Registered and Marketed Date  
 
Note:   The documentation must support the safety use and dose of new active ingredients 
as a hea lth supplement.  
 
 
4. ANY ANIMAL ORIGIN  
Any source from animal origin must be declared and to specify the type of animal.  
 
 
 
5. MANUFACTURER  
 
The requirements for Good Manufacturing Practice  (GMP)  of the premises are  in Table 7 
as followed:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 247   
Level of clai ms Requirements for GMP  
 
General/ Functional   
a) Malaysia Guidelines on Good Manufacturing Practice for 
Traditional Medicine and Health Supplement latest edition . 
 
Or 
 
b) The accepted standards for GMP will be determined by 
the category the  product is classifi ed in the  country of 
origin.  
For example,  if the product is classified  as food in the 
country of origin, GMP certificate of food standard issued 
by relevant country authority will be  accepted on condition 
that the standards are similar to those practices in 
Malaysia.  
 
Or 
 
c) If the product is not regulated in the  country of origin and 
does not require GMP certification, the manufacturer will 
have to produce a GMP certificate issued by  an 
independent body recognised by the Authority. Information 
including the standard/ regulations/ legislation to which the 
inspection was based upon must be mentioned.  
 
Disease Risk 
Reduction   
a) Malaysia Guidelines on Good Manufacturing Practice for 
Traditional Medicine and Health Supplement latest edition  
 
Or 
 
b) The Pharmaceutical  Inspection Convention and 
Pharmaceutical Inspection Co -operation Scheme (PIC/S) 
Standards.  
                                           Or 
 
c) GMP certificates issued by relevant country authority will 
be accepted on condition that the standards are similar to  
PIC/S Standards  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 248  6. CONTRACT MANUFACTURER  
Contract manufacturer is ap plicable when product owner is not the product manufacturer  
 
 
7. SECOND SOURCE INFORMATION  
An application for a second source may be considered where deemed necessary. This 
second source  product shall be the same as the first product in all respects except for the 
site of manufacture.  
 
 
8. PRODUCT CONTAINING PREMIX  
Premixed active ingredient(s) is a combination of two or more active ingredients that are 
previously manufactured by a diffe rent manufacturer.  
Certificate of GMP for manufacturer/  supplier is required for the premixed ingredient(s) in 
formulation . The requirements for GMP are same as in Field 5 as above.  
 
 
9. REPLACEMENT PRODUCT  
A product registration holder is not allowed to register/ hold two or more products with 
similar formulation (same active ingredient of raw material, strength and dosage form) at 
any one time unless product variant.  
Letter of justification for replacement by product holder is required.  
 
 
10. OTHER MANU FACTURER  
Any manufacturer involved in Assembly, Fill & Finish, Active Ingredients, Packing, Labeling  
etc. 
 
 
11. IMPORTED PRODUCTS  
Imported product needs to be declared.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 249  SECTION A:  PRODUCT PARTICULARS  
 
Product Description:  
State, briefly, visual and phy sical characteristics of the product, including as in the 
following Table 8  (where applicable) : 
 
No. Dosage Form  Description  
1. Tablet  Shape, size, colour, odour, taste, marking, emboss, type of 
tablet (e.g. coated, uncoated, film, sugar etc.)  
2. Capsule  Shape, size, colour, odour, taste, marking, emboss, coating, 
content of capsule, type of capsule (e.g.: soft, hard, chewable 
etc.)   
3. Liquid  Clarity, type (e.g. solution/ suspension/ emulsion etc.), taste, 
odour, colour.  
4. Powder  Colour, odour, taste  etc. 
5. Pill Colour, odour, taste, size etc.  
6. Granules  Colour, odour, taste, size etc.  
 
• Indication/  Usage  
State briefly recommended  use(s) of product.  The following indications are allowed:  
➢ Used as a Health Supplement ; or 
➢ Vitamins and mineral supple ments for pregnant and lactating women.  
 
• Recommended Dose (Dose/  Use Instruction) & Route of 
administration  
State the dose (normal dose, dose range) and dosage schedule (frequency, duration if 
applicable).  Dosage for adults and  children (where appropriate ) shall be stated.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 250  • Contraindication  
State conditions for which o r under which the product shall  not be used.  
Note  1 :  Indica te clearly which conditions are :  
- absolutely contraindicated,  
- contraindicated but may be used under special circumstances and w hat 
precautions to be taken in such cases.  
- If there is no information available for this section, please state as 'Unknown'.  
 
• Warnings and Precautions  
State briefly precautions and warnings necessary to ensure safe use of the product e.g. 
caution against g iving to children and elderly; use in pregnancy and lactation; in infants; 
etc. 
Note : If there is no information available for this section, please state as 'Unknown'.  
 
• Drug Interactions  
State only interactions which are observed and/or for which there is  potential clinical 
significance. Interactions may occur with  
- other medicinal products used ; 
- other herbs/ substance ; 
  - meals, or specific types of food.  
Note : If there is no information available for this section, please state as 'Unknown'.  
 
• Side Effect s/ Adverse Reactions  
State in order of severity and frequency, the side effects, adverse reactions, toxic 
effects, etc. (i.e. reactions, toxic effects, other than those desired therapeutically) 
including reactions such as allergy, hypersensitivity, depende nce, addiction, 
carcinogenicity, tolerance, liver/  kidney toxicity etc.  
Indicate also symptoms and sites of effects/reactions.  
Note 1  : Reactions, whether minor or serious,  shall be stated.  
Note 2  : Severity, reversible , frequency of occurrence shall be in dicated  wherever 
possible.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 251  Note 3  :Clinical tests for detection of ‘s ensitive’ patients, measure for m anagement of 
adverse reactio ns developed shall be described wherever possible.  
Note : If there is no information available for this section, please state  as 'Unknown'.  
 
• Pregnancy and Lactation  
Please state any effect on pregnancy and lactation if applicable.  
 
• Signs and Symptoms of Overdose and Treatment  
State briefly symptoms of overdose/  poisoning, and where possible, recommended 
treatment and antidotes for overdose/  poisoning.  
Note : If there is no information available for this section, please state as 'Unknown'.  
 
• Storage Conditions  
State the recommended storage conditions ( specific temperature  eg: 30oC, humidity, 
light etc.).  
Information shall also inc lude storage condition before first opening, after reconstitution 
and/or after opening and for all the listed pack types where applicable. Stability data to 
supp ort such storage condition shall  be available.  
 
• Shelf Life  
The shelf life for all the listed pa ck types shall  be supported by stability data.  
Information shall also include shelf life before first opening, after reconstitution and/or 
after opening where applicable. Stability data to support such shelf life shall be 
available.  
Evidence is required to  demonstrate that the product is stable (meets the finished 
product shelf life specifications thro ughout its proposed shelf -life). 
 
• Therapeutic Code (If any)  
Please select “Health Supplement”  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 252   
SECTION B:  PRODUCT FORMULA  
 
Change of formulation whether for  active ingredient or excipient is 
not allowed during product evaluation.  
 
• Batch Manufacturing Formula  
State the batch size and actual batch manufacturing master formula. Data from 
validation step will be captured in terms of substance name, type (active ingredient or 
excipient), function and quantity per unit dose. Other information will need to be 
entered.  
An attachment of the Batch Manufacturing Formula documentation must be provided.  
The documents must be verified by authorized personel.  
 
Example of BM F documentation:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 ABC Sdn. BHD.  
Batch Manufacturing Formula  
Product Name:  
Batch Quantity: 1,000,000 capsules  
 
Name  Function  Quantity 
per capsule  Batch 
quantity  Overage  
Pyridoxine HCl  Active  _ mg  _ kg _ % 
Cholecalciferol  Active  _ mg  _ kg _ % 
Glycerin  Excipient  _ mg  _ kg None  
Gelatin  Excipient  _ mg  _ kg None  
Purified water  Excipient  0 mg *  _ kg None  
  Total: _ mg  Total: _ kg   
 
* evaporated, do es not exist in final formulation  
 
(Signature)  
Post of authorized person  
Name of authorized person  
Date : 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 253   
• Manufacturing process  
State a brief description of the manufacturing process. Essential points of each stage of 
manufacturing process and a description of the assembling of the product into final 
containers shall be covered. If the product is repacked/assembled by another 
manufacturer, details of repacking/assembly and quality control must be supplied.  
An attachment of the manufacturing process, in the form of a flow chart can be  made.  
 
• In Process Quality Contr ol (IPQC)  
To provide a summary of the tests performed, stages at which they are done, and the 
frequency of sampling and number of samples taken each time. Specifications for 
quality assurance of the product shall be supplied.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 254  Example of In Process Quality  Control:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Finished Product Quality Specification  
• Provide details of quality control specifications including a list of 
tests for both release and shelf life specifications (if they are different) 
and state the limits of acceptance.  
 Company Name/ Address:  
 
Applicant/ Client Name/  Address:  
 
Date:  
 
In-Process Quality Control: Test performed during manufacturing process  
 
No. Test Do ne 
 
(example)  Stage Done  
 
(example)  Frequency 
of testing  
(example)  Quantity 
sample 
taken  
(example)  Specifications  
 
(example)  Method  
 
(example)  
1. Appearance  Before 
weight, after 
encapsulation  2 10 gram  Blue like 
orange  Organoleptic 
test 
2. Disintegration  After 
compression  2 10 tablet  NMT 30 
minutes  Equipment 
etc 
3. Uniformity of 
weight  After 
tableting,  
Packaging  4 20 Tablets  1 gram/tab   
 
 
* Declaration (if any)  
Signature (authorized personnel)  
Name : 
Designation : 
 
* The above parameters are only as an ex ample; other test may be  required for specific 
product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 255  Example of Finished Product Qualit y Specification  
 
Finished Product Quality Control (FPQC) - Finished product Specification/ 
Specification Sheet  
 
Company name/Address:  
Product Name:  
Batch no.  
Dosage form:  
Packaging:  
Date of manufacture:  
Date of expi ry: 
 
No. Test Method  Specification  Reference  
1. Appearance/ 
Organoleptic:  
Odour  
Colour  Ex: 
Macroscopic/ 
Microscopic  To describe 
the 
characteristic  In-house/ 
pharmacopoeia 
(e.g. BP/USP etc)  
2. Assay:  
(All active ingredients/ 
compounds claim on 
label)  HPLC / GC/ 
MS/ UV  To specify  To specify  
3. Disintegration/Dissolution  To specify  DRGD  DRGD  
4. Uniformity of weight  To specify    
5. Water content  To specify    
6. Microbial contamination  
TAMC, TYMC, specified 
microorganism  To specify  DRGD  DRGD  
7. Heavy Metal 
Contamination:  
Lead, Arsenic, Cadmium, 
Mercury  To specify  DRGD  DRGD  
8. Etc:    
 
Signature : 
Name : 
Designation : (At least by Quality Assurance Manager or equivalent)  
Date of signature : 
 
* The above parameters are only as an example; other test may b e required for 
specific product.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 256  • Certificate of Analysis of Finished Product  
Starting from 1st January 2018, 2 batches of Certificate of Analysis (COA) for 
Finished Product must be submitted upon submission of new prod uct 
registration for Natural Product / Health Supplement with the general claim.  
 
 
(Reference: Directive No.3 Year 2017, BPFK/PPP/07/25(8)Jld 1 : Direktif Untuk 
Menguatkuasakan Keperluan Sijil Analisa Produk Siap (Certificate of   Analysis (COA) 
For Finis hed Product) Semasa Permohonan Pendaftaran Baru Produk Semulajadi dan 
Produk Suplemen Kesihatan Dengan General Claim)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 257   
Example of Certificate of Analysis for Finished Product (Health Supplement ) 
 
 
 Certificate of Analysis  
Company name/ Address  :  
Product Name    :  
Batch no.    :  
Dosage form    :  
Packaging    :  
Date of manufacture   :  
Date of expiry    :  
Test Parameter  Specifications  Results  Method  
Appearan ce/ Organoleptic:  
Odour  
Colour   
To describe the 
characteristic  
   
Disintegration   
DRGD  
   
Uniformity of weight     
Assay :  
(All active ingredients/ 
compound s claim on label)   
To specify  
   
Microbial Contamination Test  
TAMC, TYMC, specified 
microor ganism  
  
DRGD  
   
Heavy Metal Contamination     
Lead (Pb)  NMT  10 ppm    
Cadmium (Cd)  NMT  0.3 ppm    
Mercury (Hg)  NMT  0.5 ppm    
Arsenic (As)  NMT  5 ppm    
NMT = Not More Than  
 
Signature   :  
Name    :  
Designation   : (At least by Quality Control  Manager or equivalent)  
Date of signature  :  
 
Note: The above parameter are only as an example, other tests may be required for specific product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 258  • Stability Data  
 
Table 9:  
 
No. Stability Study  Shelf Life  
 
1.  
i)  2 batches of complete real -time stability 
study at 30 ± 2 ºC / RH 75± 5% for the 
claimed shelf -life. 
OR 
 
ii) 2 batches of on -going real time             
stability study  ( at least 6 months) at 30 ± 2 ºC 
/ RH 75 ± 5%  + Letter of commitment 
(LOC)  to submit complete real time stability 
data when study is complete/ when 
requested.  
                         AND  
 
2 batches of 6 months accelerated stability 
study at 40ºC.    
- Shelf life will be based 
on data stabili ty at 30oC 
of not more than 5 years.  
 
 
 
- 3 years  
 
2.  
i) 2 batches of complete real time  stability 
study at a temperature and relative humidity 
(RH) different from the Zone IVB for at least 2 
years + LOC to conduct real time stability 
study at Zone IVB an d submit when the study 
is complete/ when requested  
OR 
 
ii) 2 batches of on -going real time and 
accelerated stability study (at least 6 months) 
at a temperature/ relative humidity (RH) 
different from Zone IVB  + LOC to conduct real 
time stability study at Z one IVB and submit 
when the study is complete/ when requested.   
- Shelf life will be based 
on data stability at 
specified temperature.  
 
 
 
 
 
- 2 years at specified 
temperature in the 
stability study.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 259   
3.  
2 batches of complete real -time stability study 
at temp erature and RH other than zone IVB for 
very unstable active ingredient(s)/ product 
(must be substantiated).    
- Shelf life will be based 
on data stability at 
specified temperature.  
 
 
 
Storage Conditions with T ype of Container Closure System / Stability Study  
 
Table 10:  
 
No. Type of Container Closure System/ Study  Storage Condition  
1. Products in primary containers permeable  
to water vapour  30°C + 2°C/75% RH + 5%RH  
2. Products in primary containers impermeable  
to water vapour  30°C + 2°C 
3. Accelerated studi es 40°C + 2°C/75% RH + 5%RH  
 
 
Reports of stability studies shall  provide details of:  
• the batches placed under study (a minimum of 2 batches are required).  
• containers/  packaging type . 
• conditions of storage during study (temperature, humidity, etc).  
• duratio n of study and frequency (interval) of the tests/  observations . 
• the tests performed and acceptance limits . 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 260  Example of Stability Data  
STABLITY DATA  
PRODUCT NAME :  TABLET ABC 500MG   BATCH NO.:   
MANUFACTURING DATE :  dd/mm/yy     TEMPERATURE:  30 °C ± 2 °C  
EXPIRY DATE :   dd/mm/yy     RELATIVE HUMIDITY : 75 % ± 5%  
Tests  Specification  Frequency of Testing  
0 3 6 9 12 18 24 36 
Product description  Film-coated tablet, brownish in 
colour          
Disintegration test  NMT 30 minutes          
Assays  eg: 90% -120% (ref….)          
Microbial Contamination 
test: 
 
Total Aerobic Microbial 
Count  
 
Total Yeasts & Moulds 
Count  
 
Test for Specified 
Microorganisms   
 
 
NMT 2 x 104 
 
 
NMT 2 x 102 
 
 
➢ NMT 2 x 102 CFU of bile -
tolerant gram - negative 
bacteria in 1g or 1ml  
 
➢ Absence of S almonella in 
10g or 10ml  
 
➢ Absence of Escherichia 
coli in 1g or 1ml  
 
➢ Absence of 
Staphylococcus   
 
 
        
Heavy metal test:  
 
Lead  
Arsenic  
Mercury  
Cadmium   
 
≤10.0 mg/kg  (≤ 10ppm)  
≤5.0 mg/kg (≤ 5ppm)  
≤0.5 mg/kg (≤ 0.5ppm)  
≤0.3 mg/kg (≤ 0.3ppm)    
 
 
 
                                 NA  
 
 
 
Conclusion  ------------------------------------------------------------  
Analyst name :       ( signature)      Verified by :   (signature ) 
Name:        Name : 
Designation       Designation  
Date:        Date:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 261   
Stability study data checklists are as in Table 11  below:  
 
Data Required  Remarks  
Company name  - From pr oduct holder/ manufacturer/ third party lab  
Product name  - To be same w ith other documentation  
Dosage form  - To be same with A3  
Packaging 
particulars  - Material and pack size must  be stated  
- To be same with C1  
Storage 
condition  
 - Temperature and humidity must be stated  
- Shall comply with ASEAN Zone IV  requirement 
(30±2°C/ 75±5%RH)  
- If different storage condition (e.g. 25°C, 2 -8°C), must provide 
justification/ supporting data.  
Frequency of 
testing  
 For example:  
- 0, 3, 6, 9, 12, 18, 24 months and annually for the proposed 
shelf life  
List of relevant 
tests  - All tests required f or each dosage form shall be conducted, 
for example:  
o Physical appearance changes  
o Disintegration test (if applicable)  
o Chemical Assays for active ingredients (if applicable)  
o Microbial tests  
Specifications  - Acceptance limit for each test must be stated  
- To be supported by established references (e.g. USP, BP) if 
available  
Results for each 
test - Must meet the specifications  
Approval by 
authorized 
person  - Must have the name, post and signature of authorized person  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 262   
 
Testing Parameters of Stability Study f or each type of dosage forms  are shown in Table 12  
below:  
 
Testing Parameters  
 
 
Dosage  
Form  
Appearance / 
organoleptic 
(odor, color, taste)  
Assay * 
Hardness/ 
friability  
Disintegration  or 
dissolution rate  
Moisture  
content  
Viscosity  
pH 
Microbial content  
Granules/ Particle 
Size variation  
Re-suspendability  
Oral powder  √ √   √   √   
Hard capsule  √ √  √ √   √   
Soft capsule  √ √  √    √   
Coated and U ncoated 
Tablet  √ √ √ 
(uncoated)  √ √   √   
Coated and Uncoated 
Pill/ Pellet  √ √  √ √   √   
Suspension  √ √    √ √ √ √ √ 
Solution  √ √    √ √ √   
Emulsion  √ √    √ √ √   
Granules  √ √   √   √ √  
 
*Notes:  
 
1. The list of tests for each product is not intended to be exhaustive, nor is it expected that every 
listed test to be included in the design of the stability  study protocol for a particular finished product.  
 
* Assay to determine the stability of a single active ingredient or a single marker/surrogate indicator 
that is susceptible to change during storage and is likely to influence quality shall be sufficient  to 
infer the overall stability of the TM/HS product irrespective of whether the finished product contains 
single or multiple active ingredients.  
 
2. Justification must be given if one of the tests is not conducted for relevant dosage form.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 263  SECTION C:  PARTICULARS OF PACKING  
 
• Packaging  
 
➢ Maximum pack size allowed for tablets, pills, capsules is based on daily dosing for a 
quantity not exceeding six (6) months usage.   
 
➢ Maximum pack size allowed  with disease risk reduction claim for 1 month supply of  
product s unless justified.  
 
➢ Product with dosage form of softgel with tail (twist and squeeze) shall come with  
children proof cap.  
 
• Packing particulars to the listing of packing as follows ;  
- C1: pack size and fill details by weight, or volume or quantity;  
- C2 : cont ainer type  
- C3 : B arcode/ serial No (optional ); 
- C4 : recommended dis tributor’s price (optional ); 
- C5 : recommen ded retail price (optional ); 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 264  SECTION D:  LABELLING REQUIREMENTS  
 
• The information shall present on the label of a product at outer carton, immedia te 
container or blister/ strips:  
 
Please refer Appendix 9: Labelling Requirements  for: 
 
a) General Labelling Requirements - Label (mock -up) for 
immediate container and outer carton;  
b) Consumer Medication Information Leaflet (RiMU P); 
(For health supplement with high claims/ disease risk reduction)  
c) Specific Labelling Requirement  
(For specific substances, e.g. alfalfa, arginine, bee pollen, chitosan , Boswellia 
serrata etc.)  
 
• Additional Requirements for Labelling  
➢ Information on the Product Name; and Name and Strength of active ingredient(s) 
must be printed repeatedly (for blister/ strip).  
➢ Product with dosage form of soft gel with tail (twist and squeeze) shall include the 
statement ‘ Under parent supervision’  in the label.  
➢ For product s containing animal origin(s) , please add this statement: This product 
contains substance(s) from animal origin.  
➢ For products containing porcine , please add this statement: This product 
contains animal part(s) (porcine/pig).  
 
• Health supplement products wit h disease risk reduction claims (high) are 
encouraged to be dispensed under the supervision of pharmacists or medical 
practitioners. At such, the label and package insert of health supplement products 
with disease risk reduction claims (high) shall have th e following statement : 
“Please consult a doctor/ pharmacist  before taking this product”.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 265  • Standard Labelling for Health Supplements  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  
- Product label shall follow the standard labelling for Health Supplement.  
- Information state d in the left and right panel is interchangeable.  
- All information on the label must be truthful and not misleading to the consumers.  
- Batch number, manufacturing date, expiration date: can be stated on label, on top of 
cap or bottom of bottle.  
- The front pan el must contain the information as above. However, the information on 
the side panels is interchangeable. Additional cautionary labelling relating to the safety 
of the product may be imposed.  
 
 
 
 • Name and Strength of  
active substances  
• RDA (optional)  
• Preservative(s) (where  
present)  
• Alcohol (where present)  
 
• Indication  
• Dose /  Usage  Instruction  
 
 
• Functional Claim  (if applicable)  
• Warnings (If applicable)  
 
 
 
• Storage Condition  
• Keep out of reach              
of children / Jauh kan daripada   
capaian kanak -kanak  
 
 
  • Name & address of 
Product Registration 
Holder  
• Nam e & address of 
Manufacturer  
 
 
• Sources (animal 
origin)  
• Source of capsule 
shell (if applicable)  
 
• Batch Number  
• Manufacturing Date  
• Expiry Date  
 
MAL ……………………...  • Pack Size  
• Dosage Form   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 266  • Package inserts (Optional ) 
 
The following information is req uired to be included in a package insert:  
 
(i) Brand or Product Name  
(ii) Name and Strength of Active Substance(s)  
(iii) Product Description  
(iv) Indication  
(v) Dose/ Use Instruction  
(vi) Contraindications  
(vii) Warnings and Precautions  
(viii) Interactions with Other Medications  
(ix) Statement on usage during pregnancy and lactation  
(x) Adverse Effects/ Undesirable Effects  
(xi) Overdose and Treatment  
(xii) Storage Conditions (may be omitted if the information is stated on the label 
or outer carton labels)  
(xiii) Dosage Forms and packaging available  
(xiv) Name and Address of m anufacturer/ product registration holder  
(xv) Date of Revision of Package Insert  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 267  • Prohi bited Visual/ Graphics on Label, as shown in  Table 1 3 below:  
 
No. Issue  Example  Note  
1.  Marketing strategy  
 Example:  
“Money back guarantee”  
“Buy 1 free 1”  
“Backed by RM5 mi llion 
product Liability Insurance”  Such statements 
are prohibited on 
labels, as per 
Medicines 
(Advertisement 
and Sale) Act 
1956 guideline 
requirements  
2.  Usage guide which 
promotes use of  
other product(s)  Example:  
“After consumption of this 
product (Produc t A), for 
better results, it is 
recommended to take 
Product B”  Prohibited on 
product label  
3.  Consumer testimonial   Prohibited on 
product label  
4.  Clinical Trial results or 
any information on 
clinical trial done on 
product  
 Example :  
“Clinically Tested”  
“Ran domized Double Blind 
Placebo Control Clinical 
Study”  Such statements 
are prohibited on 
labels (as per 
Medicines 
(Advertisement 
and Sale) Act 
1956  guideline  
Requirement  
5.  Reference to Hadith/ Al -
Quran/ Bible/ Religious 
books   Prohibited on 
product label  
6.  Opinion of prominent 
ﬁgure(s) on  
product or its active 
ingredient/  
content  Example:  
Opinion of 
product/formulation inventor  Prohibited on 
product label  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 268  No. Issue  Example  Note  
7.  Label design (graphic 
and color) similar to 
labels from another  
company   Prohibited on 
product label  
8.  Statement on active 
ingredient origin  Example:  
Source from the Mountains 
of Alps  Allowed if proven 
true 
9.  Introduction of founder/  
Manufacturer   Prohibited on 
product label  
10.  Logo with certiﬁcation  Example:  
SIRIM/ ISO / GMP/ HACCP  Prohibited on 
product la bel 
because 
certiﬁcation 
renewal is on a 
yearly basis  
11.  Name/ Statement/ 
Logo/ registered  
trademark which does 
not satisfy the 
speciﬁcations  Example:  
“Dr.ABC’s Formula”  
“Nothing like it”  
 Prohibited on 
product label  
12.  Patency claim/ Patency 
number/ Specia l 
technique used/ 
superiority in 
ingredients (Example:  
capsule coat)  Example:  
Patented technique  Allowed if proven 
true 
13.  Nutritional claims with 
analysis certiﬁcate 
attached  Example:  
Calorie, Fat, Protein and  
others  Prohibited on 
product label  
14.  Graphi cs or picture of 
internal organs  Example:  
Kidney, Heart, Nerves.  Prohibited on 
product label  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 269  No. Issue  Example  Note  
15.  Gender  symbol  
(male or female)  (♀ and/or ♂) Prohibited on 
product label  
16.  Indecent photographs/ 
pornography / graphics/ 
images   Prohibited on 
product label  
17.  Graphics which are 
incoherent with  
the indication  Example:  
- Noted indication is for 
constipation, but graphics 
on label shows a slim -
looking lady which 
denotes indication for 
weight loss  
- Indication for urination but 
label graphics contains 
picture of a water  hose.  Prohibited on 
product label  
18.  Highlighting 
unnecessary body parts  Example:   
Indication is for general 
health but graphics on label 
highlights male and female 
sexual organ parts  Prohibited on 
product label  
19.  Graphics of plants or 
animal which  
may ca use confusion  Example:  
Radix Ginseng which is  
improvised as a male  
sexual part  Prohibited on 
product label  
20.  Photograph of 
celebrities  Example  
- Artiste, sports person(s), 
politician  Prohibited on 
product label  
21.  Statement on sugars  Example  
- This pr oduct contains no 
added sugar  Allowed on 
product label 
provided the 
product contains 
no fructose, 
glucose, sucrose, 
or other kind of 
sugars with a Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 270  No. Issue  Example  Note  
potential to affect 
diabetics are not 
included in the 
formulation  
22.  Negative statement  Example  
-  No glut en, yeast etc  Prohibited on 
product label  
23.  Other statements  Example:  
- This product is blended 
with premium quality  
- Certiﬁed chemical residue 
free Prohibited on 
product label  
Notes:  
1. The list is not meant to be exhaustive and wi ll be reviewed from time to  time. 
2. The Authority reserves the right to disallow any other words, phrases or graphics for product 
label which in its opinion is misleading, improper or not factual . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 271  SECTION E:  PARTICULAR OF PRODUCT OWNER, 
MANUFACTURER, IMPORTER AND OTHER MANUFA CTURER  
 
• Please select  whether the product owner is the product holder, manufacturer or both 
product holder and the manufacturer.  
• If the product owner is neither product holder nor the manufacturer, please select name 
and address of the product owner (applicable  for imported product only).  
•  Other details such as product owner, manufacturer, repacker, other manufacturer 
involved in the manufacturing process, store address and importer (If any) have to 
filled. It is mandatory for the repacker to acquire GMP certif icate.  
 
 
SECTION F:  SUPPLEMENTARY DOCUMENTS  
 
• Letter  of authorization of product owner  
This is applicable for imported product in which the product owner appoints the product 
holder (in Malaysia) as their product holder in Malaysia  
 
• Letter of appointment of  contract manufacturer and/ or repacker  
Applicable if the product is contract manufactured by a manufacturer who is not the product 
holder.  
 
• Letter of acceptance as contract manufacturer and/ or repacker  
Applicable if the product is contract manufactured b y a manufacturer who is not the product 
holder.  
 
• Certificate Of Pharmaceutical Product (CPP), Free Sale Certificate (CFS) and Good 
Manufacturing Practice (GMP)  
CPP can be attached as a replacement of CFS and GMP certificate if the product is 
classified as pharmaceutical pr oduct in the country of origin:  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 272  GMP/  CFS Template  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Attachment of Protocol Analysis  
Protocol analysis is attached here.   
 
• Finished Product  Quality Control (FPQC)  
➢ The certificate must be complete with the product specificatio n and result. The list of 
tests and specifications must be same with finished product specification document.  
➢ Quality Control Test For Health Supplement Product  are as follows:  
 
1. Limit Test for Heavy Metals  
a) Lead   : NMT 10.0 mg/kg or 10.0 mg/litre (10.0 ppm)  
b) Arsenic   : NMT 5.0 mg/kg or 5.0 mg/litre (5.0ppm)  
c) Mercury   : NMT 0.5 mg/kg or 0.5 mg/litre (0.5ppm)  
d) Cadmium  : NMT 0.3 mg/kg or 0.3 mg/litre (0.3ppm)  
 
* Required for products with ingredients from natural sources.  
The test shall be conducted on the finished product.   
Authority name, address, country  
 
Type of certificate  
 
Company name (product owner/ manufacturer)  
Product name  
Product formulation if available  
Dosage form  
 
Statement of freely sold (similar meaning) if for CFS certificate  
Standard of GMP and compliance status if for GMP certificate  
Duration of certification  
 
Name, signa ture and designation of authorized personnel  
Date of signature  
 
Note:  The certificate must be in English or translated into English  
(certified true by issuance or embassy or notary public)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 273   2. Disintegration Test (for tablets, capsules and pills)  
        Disintegration time:  
a) Uncoated tablets   : NMT  30 minutes  
b) Film-coated tablets   : NMT 30 minutes  
c) Sugar -coated tablets  : NMT 60 minutes  
d) Enteric -coated tablets  : Does not di sintegrate for 120 minutes in  
          acid solution but to disintegrate within 60  
          minutes in  buffer solution  
e) Capsules    : NMT 30 minutes  
f) Pills     : NMT 120 minutes  
 
3. Test for Uniformity of Weight (tablets and capsules only)  
i) Tablet  
- For tablet with average weight of 130mg or less: Not more than 2 tablets differ 
from the average weight by more than 10% AND no tablets differ from the 
average weight by more than 20%  
- For tablet with average weight between 130 -324mg: Not more than 2 tablets 
differ from the average weight by more than 7.5% AND no tablet differs from 
the average weights by more than 15%  
- For tablets with average weight more than 324mg: Not more than 2 tablets 
differ from the average weight by more than 5% AND no tablet differs fro m 
the average weight by more than 10%  
 
ii) Capsule  
Individual weight of the capsule to be wit hin the limit of 90 -110% of the average 
weight.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 274  4. Tests for Microbial Contamination , as shown in  Table 1 4 below:  
 
Route of Administration  TAMC  
(CFU/g or 
CFU/ml)  TYMC  
(CFU/g or 
CFU/ml)  Specified micro -organisms  
Non-aqueous preparations 
for oral use  NMT 2 x 103 NMT 2 x 102 Absence of Escherichia coli  (1 g or 1 ml)  
Aqueous preparations for 
oral use  NMT 2 x 102 NMT 2 x 101 Absence of Escherichia coli  (1 g or 1 ml)  
Special Ph. Eur. provision 
for oral dosage forms 
containing raw materials of 
natural (animal, vegetal or 
mineral) origin for which 
antimicrobial pretreatment is 
not feasible and for which 
the competent authority 
accepts TAMC of the raw 
material exceeding 1 03 
CFU/g or CFU/mL.  NMT 2 x 104 NMT 2 x 102 Not more than 102 CFU of bile -tolerant 
gram -negative bacteria (1 g or 1 ml)  
Absence of Salmonella  (10 g or 10 ml)  
Absence of Escherichia coli  (1 g or 1 ml)  
Absence of Staphylococcus aureus (1 g 
or 1 ml)  
 
Notes:   
TAMC  : Total Aerobic Microbial Count  
TYMC  : Total Yeasts & Moulds Count  
NMT  : Not more than  
[Reference: British Pharmacopoeia 2012]  
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 275  • Specifications and Certificate of Analysis of Active Ingredient  
 
Certificate of analysis for each active ingredi ent (raw material) is required pre -registration. 
The certificate must consist of  specification s and result s of analyses.  
 
 
• Other Supporting documents  
 
➢ For the submission of other supporting documents.  
 
➢ Additional requirement for safety and quality of activ e ingredient/ product  (e.g.; dose 
for children, pregnant etc .) 
 
➢ Quality testing for specific ingredient : 
- For product containing Aphanizomenon flos -aquae, applicants would have to 
provide certificates of analysis showing that the microcystin -LR or total 
microcystins content of the raw material does not exceed 1μg/g and the finished 
product has been tested for microcystin -LR using an acceptable method  
 
➢ Quality testing for specific product : 
- Certificate of Analysis for the level of dioxin (PCDDs and PCDFs) and dioxin -like 
polychlorinated biphenyls (PCBs) is required for product containing ingredient(s) 
derived from seafood. (The acceptable limit for these tests shall follow standard 
references such as United States Pharmacopoeia (USP) and European 
Regulation.)  
- Certificate of Analysis for proof of hormone -free is required for product containing 
placenta  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 276  ATTACHMENT 1  
 
CHECKLIST OF DOSSIER REQUIREMENT  FOR HEALTH SUPPLEMENT S 
 
• Depending on the level of c laims, submission may follows the route as outlined:  
i) General / Nutritional and Medium Claims  - Abridge evaluation  
ii) Disease Risk Reduction Claims - Full evaluation  
 
Table 1 5: Checklist for General/  Nutritional and Medium Claim  
 
No. Field  General or 
Nutritional Claims  Functional 
Claims  
A1 Product Name  
√ √ 
Brand na me and product name  
A2 Product Description  
√ √ - Describe visual and physical characteristics of 
the product including shape, size, superficial 
markings, colour, odour, taste, type of 
coating, type of capsule etc where applicable  
- Animal shape is on ly allowed for ‘For Export 
Only’ (FEO) Products  
A3 Dosage Form  
√ √ - COA capsule shell is required  
- Colouring agent used in capsule  
- Letter to verify the source of gelatin used  
A4 Product indication/ Usage  √ √ 
A5 Dose/ Use Instruction  
√ √ - Quantity and frequency  
- Dosing schedule must be stated  
(e.g. take before/ after/ with meal)  
A6 Contraindication, if applicable  √ √ 
A7 Warning/ Precautions, if applicable  √ √ 
A8 Drug Interaction, if applicable  √ √ 
A9 Side Effects/ Adverse Rea ctions, if applicable  √ √ 
A10 Signs and Symptoms of overdose and 
treatment, if applicable  √ √ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 277  No. Field  General or 
Nutritional Claims  Functional 
Claims  
A11 Storage Condition  
√ √ 
- According to stability data  
A12 Shelf life  
√ √ - Must be supported by stability study  
- Please refer to B5  
A13 Therapeutic Co de 
√ √ 
- As a health supplement  
B1.1 Batch Manufacturing Formula  √ √ 
B1.2 List of Active ingredient(s)  √ √ 
B1.3 List of excipient(s)  √ √ 
B1.4 Attachment of Batch Manufacturing Formula  
√ √ - Shall be on the product owner’s/ 
manufacturer’s original  letterhead,  product 
details, date and signature & designation of 
authorized personnel  
B2.1 Manufacturing Process   √ √ 
B2.2 Attachment of Manufacturing Process 
Document or Manufacturing Flow Diagram  √ √ 
B3 In-Process Quality Control (IPQC)  √ 
*LOC to  submit data 
during post 
registration  √ 
 
B4 Finished Product Specification (FPQC)  √ 
* LOC to submit data 
during post 
registration  √ 
 
B5 Stability Data (Please refer page 24)  √ √ 
D1 Label for immediate container  √ √ 
D2 Label for outer carton (if applica ble) √ √ 
D3 Proposed package insert / Product information 
leaflet (if applicable)  √ √ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 278  No. Field  General or 
Nutritional Claims  Functional 
Claims  
E1 Company name and address of product owner  √ √ 
E2 Company name and address of 
manufacturer(s)  √ √ 
E3 Company name and address of repacker  
(if applicable)  √ √ 
E4 Company name and address of other 
manufacturer (if applicable)  √ √ 
E5 Store address(s)  √ √ 
E6 Importer(s)  √ √ 
F1 Letter of authorization from product owner to 
product registration  holder (if applicable)  √ √ 
F2 Letter of Appointment of Contract 
Manufactu rer/ Repacker from Product Owner  
(if applicable)  √ √ 
F3 Letter of Acceptance from Contract 
Manufacturer/ Repacker (if applicable)  √ √ 
F4 Certificate of Pharmaceutical Product (CPP)  
- Applicable to imported products, must be 
issued by the competent autho rity in the 
country of origin. CPP issued by reference 
country may be considered.  √ √ 
F5 Certificate of Free Sale (CFS)  
- Applicable if CPP is not available, must be 
issued by the competent authority in the 
country of origin/ products owner country.  √ √ 
F6 Certificate of Good Manufacturing Practice 
(GMP)  
- Applicable if CPP is not available, must be 
issued by the competent authority in the 
manufacturing country.  √ √ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 279  No. Field  General or 
Nutritional Claims  Functional 
Claims  
F9 Attachment of protocol analysis  
 √ 
- dosage form 
extended release  
 
* LOC to submit 
during p ost for other 
types of dosage form  √ 
- dosage form 
extended 
release  
- validation of 
analytical 
method for 
new actives 
or new 
combination 
dosage  
F10 Attachment of Certificate of finished product 
(COA of finished product)  √ √ 
F11 
 Attachment of Specifications and Certificate of 
Analysis (COA) of Active Ingredient  √ √ 
F12 Examples of supporting documents    
Dioxin level test results (for product containing 
ingredients derived from seafood)  
√ √ Certificate of Good Manufacturing Practice 
(GMP) for premixed ac tive ingredients  
Hormone free test results  
(for placenta products)  
Declaration letter from product manufacturer on 
the hormone - free status for product containing 
placenta  
Manufacturing process validation report if 
applicable  
Letter of co mmitment if applicable  
Etc. Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 280  No. Field  General or 
Nutritional Claims  Functional 
Claims  
* Complete stability study conducted at 30 ± 2 ºC / RH 75 ± 5%, IPQC, FPQC, protocol analysis 
and COA of finished product are required to be submitted 2 years after product registration with 
SAMPLE of the products. Failur e on submission will cause the product be suspended until the 
complete documents are submitted, the registration of the product will be terminated if the 
complete documents still cannot be produced upon renewal of product registration.  
 
• Dossier Requiremen t for Disease risk reduction as in Table 1 5 above  and                             
Table 1 6 below : 
 
Table 1 6: Additional Quality Data Check list for Disease Risk Reduction Claim    
 
No. Field  Disease Risk Reduction Claim  
 
PART 
P  
P. HEALTH SUPPLEMENT PRODUCT  
P1. Description and Composition  
P2.  Pharmaceutical Development  
P2.1 Information on Development 
Studies  
P2.2 Components of the Health 
Supplement Product  
P2.3 Finished Product  
P2.4 Manufacturing Process 
Development  
P2.5 Container Closure System  
P2.6 Microb iological Attributes  
P2.7 Compatibility  
P3. Manufacturer  
P3.1  Batch Manufacturing Formula  
P3.2 Manufacturing Process & 
Process Control  
P3.2.1  Manufacturing Process 
Flowchart  
P3.3 Control of Critical Steps & 
Intermediates  
P3.4 Process Validation and 
Evalua tion 
P4. Control of Excipients  
 P4.1 Specifications   
 
 
 
 
 
 
 
 
√ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 281  No. Field  Disease Risk Reduction Claim  
 P4.2 Analytical Procedure  
P4.3 Validation of Analytical 
Procedures  
P4.4 Justification of Specification  
P4.5 Excipient of Human or Animal 
Origin  
P4.6 Novel Excipients  
P5. Control of Finished Product  
P5.1 Specification  
P5.2 AnalyticalProcedures  
P5.3 Validation of Analytical 
Procedures  
P5.4 Batch Analyses  
P5.5 Characterization of impurities  
P5.6 Justification of Specification  
P6. Reference Standards or Materials  
P7. Container Closure System  
P8. Stability  
P9. Product Interchangeability/Equivalent 
 evidence  
 
PART 
S  
S. HEALTH SUPPLEMENT 
 SUBSTANCE  
S1. General Information  
S1.1 Nomenclature  
S1.2 Structure  
S1.3 General Properties  
S2. Manufacture  
S3. Characterisation  
S4. Control of Health Supplement  
 Substance  
S4.1 Specification  
S4.2 Analytical Procedures  
S4.3 Validation of Analytical 
Procedure  
S4.4 Batch Analysis  
S4.5 Justification of Specification  
S5. Reference Standards or Materials  
S6. Container Closure System  
S7. Stability  
  
 
 
 
 
 
 
√ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 282   
PART III: NON -CLINICAL DATA  
 
- Applicable to disease risk reduction claims  
(For new active ingredient, new combination of active ingredients and new dose)  
 
Table 1 7: 
 
No. Field  Disease Risk Reduction Claims  
1. Overview of non -clinical testing strategy  
√ - nomenclature  
- structure  
- general properties  
2. Pharmacology  
√ - related information (including academic 
literature) of pharmacology studies on the 
declared efficacy  
3. Pharmacokinetics  
√ - related information (including academic 
literature) of pharmacokinetics studies on the 
declared efficacy  
4. Toxicology  
√ - related information (including academic 
literature) of toxicology studies  
5. Integrated overview and conclusions  √ 
6. Other toxicity studies if available  √ 
7. References  √ - List of references used  
 
- All information must be provided in the following format/  table:  
 
Study 
Title Type 
of 
Study  Product  
(formulation)  Study Summary  
- Study  Design (e.g. case 
control, randomised 
placebo controlled, in 
vitro data, cohort study)  
- Dosage  
- Subject  
- Study Duratio n 
- Outcome parameters  Summary findings  
(Includes scientific details such as 
strength of evidence [e.g. p -
values], conclusions, any 
shortcomings, etc.  
 
For traditional evidence include 
enough information to 
demonstrate relevance)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 283  PART IV: CLINICAL DOCUMENT S   
 
- Applicable to disease risk reduction claims (for new active ingredient, new combination 
of active ingredients and new dose).  
 
Table 1 8: 
 
No. Field  Disease Risk Reduction Claims  
1. Clinical overview  √ 
2. Production Development Rational  √ 
3. Overview  of Bio -pharmaceutics  
√ 
- To include associated analytical methods  
4. Overview of Clinical Pharmacology  
√ 
- Summary of clinical pharmacology studies  
5. Overview of Efficiency  
√ 
- Summary of clinical efficacy  
6. Overview of Safety  
√ 
- Summary of  clinical safety  
7. References  
√ - List of all clinical studies  
- List of key literature references  
- Published clinical papers  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 284  - All information must be provided in the following format/table:  
 
Forms of 
study  Sample size  Duration  Randomisati on 
of groups  Endpoint  
 Statistical analysis of 
data 
Randomised, 
controlled, 
and 
preferably 
blinded 
intervention 
studies  Must be 
justified and 
must involve 
sufficiently 
large number of 
subjects to 
estimate 
incidence and 
nature of 
potential 
adverse 
reaction s Must be 
justified and 
must be of 
sufficient 
duration to 
ensure no 
safety 
concerns 
with respect 
to long term 
use All groups shall 
have 
comparable 
baseline 
values, 
particularly for 
those factors 
that are known 
to be, or may 
be, 
confounders or 
risk factors  As a 
decrease 
incidence of 
the disease 
or a 
reduction of 
a factor, or a 
surrogate 
thereof, of 
the many 
that 
contribute to 
the 
development 
of a disease  Methods to calculate 
the sample size, 
setting the power 
and the significance 
level at conventional 
80% an d p<0.05 
respectively shall be 
utilised  
 
Meta -analysis shall 
combine only studies 
with similar design, 
populations, 
interventions and 
outcome measure  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 285  ATTACHMENT 2  
 
Table 19: Allowable claims for specific active ingredients in HS products  
 
Ingredients  
 Claims  
General  Functional  Reduced Risk 
Reduction Claim  
Vitamin A  • Maintenance 
of good health  
 • Helps to maintain 
growth, vision and 
tissue 
development  
• Aids in 
maintaining the 
health of the skin 
and mucous 
membrane   
Vitamin C   • For healthy 
bones, 
(cart ilage),  teeth, 
gums as well as 
general make -up 
of the body   
Vitamin D  • Maintenance 
of good health  
 
 • Helps in normal 
development and 
maintenance of 
bones and teeth  
• Helps the body 
utilize calcium 
and phosphorus  
• Claim for specific 
population 
subgroups: 
Elderly people 
who are confined 
indoors   
Vitamin E  • Maintenance 
of good health    Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 286  Ingredients  
 Claims  
General  Functional  Reduced Risk 
Reduction Claim  
Beta Carotene  • Maintenance 
of good health  • Helps in 
maintenance of 
growth, vision and 
tissue 
differentiation   
Vitamin B1 (Thiamine)  • Helps to 
maintain good 
health  
 • Helps in 
maintenance of 
growth, vision and 
tissue 
differentiation   
Riboflavin (Vitamin B2)  • A factor in 
maintenance 
of good health  
 • Helps the body to 
utilize energy 
from food/ 
metabolize 
protein, fats and 
carbohydrates  
• Claim for specific 
population 
subgroups:  
-Additional 
amounts of 
Riboflavin are 
required during 
pregnancy and 
breast feeding 
when diet does 
not provide a 
sufficient daily 
intake   
Niacin (Vitamin B3)  • A factor in 
maintenance 
of good health  
 • Helps normal 
growth and 
development  
• Helps the body in 
utiliza tion of 
energy from food   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 287  Ingredients  
 Claims  
General  Functional  Reduced Risk 
Reduction Claim  
Pyridoxine (Vitamin B6)  • A factor in 
maintenance 
of good health  
 • Helps the body to 
metabolize 
proteins, fats and 
carbohydrates   
Cyanocobalamine 
(Vitamin B12)  • Helps in 
maintenance 
of good health  • Helps in the 
formation of red 
blood cell   
Folic Acid   • Helps in formation 
of red blood cell  
 • Helps prevent 
neural tube 
defects for 
women who are 
planning a 
pregnancy before 
conception and 
during 12 weeks 
of pregnancy at a 
dose of 400 mcg 
daily 
Biotin  • Helps in 
maintenance 
of good heal th  • Helps to 
metabolize fats 
and 
carbohydrates   
Panthothenic Acid  • Helps in 
maintenance 
of good health  
 • Helps to 
metabolize fats 
and 
carbohydrates   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 288  Ingredients  
 Claims  
General  Functional  Reduced Risk 
Reduction Claim  
Calcium  • Helps in 
maintenance 
of good health  
 • Helps in the 
formation and 
maintenance of 
bones and teeth  
• Claim for specific 
subgroup:  
- Additional 
calcium is 
required for 
pregnant and 
lactating 
women, when 
diet does not 
provide a 
sufficient daily 
intake to help 
in proper bone 
formation in 
developing 
baby  
Phosphorus  • Helps in 
maintenance 
of good health  
 • Helps  in the 
formation and 
maintenance of 
bones and teeth   
Magnesium  • Helps in 
maintenance 
of good health  • Helps the body to 
metabolize 
carbohydrate   
Iron • Helps in 
maintenance 
of good health  • Helps in the 
formation of red 
blood cell  
 • Helps to prevent 
iron a nemia  
• Helps to prevent 
anemia due to 
iron deficiency   
Iodine  • Helps in 
maintenance 
of good health  • Helps in the 
function of the 
thyroid glands   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 289  Ingredients  
 Claims  
General  Functional  Reduced Risk 
Reduction Claim  
Zinc • A factor in 
maintenance 
of good health  • Helps to 
metabolize 
carbohydrates, 
fats and protein   
Copper  • A factor in 
maintenance 
of good health  • Helps in the 
formation of red 
blood cell   
Manganese  • A factor in 
maintenance 
of good health  • Helps to 
metabolize 
carbohydrates 
and proteins   
Probiotics   • Helps to improve 
a beneficial 
intestinal 
microflora   
 
Notes : 
 
1. This list is not meant to be exhaustive and will be reviewed from time to time.  
2. The Authority will nonetheless conduct a detailed evaluation of the evidence included in the 
report to ensure that the health claim is substantiated.  
3. The Authority will be w illing to consider review other than the listed above, if the standards of 
evidence are consistent with those of the Authority.  
4. All references must be current . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 290   
ACKNOWLEDGEMENTS  
 
The National Pharmaceutical Regulatory Division  acknowledges its indebtedne ss to the 
members from the industries, government agencies and universities as stated below, who 
provided comments and advices during the preparation of these guidelines.  
 
Government agencies:  
i) Bahagian Keselamatan dan Kualiti Makanan (BKKM), KKM  
ii) Bahagian P erubatan Tradisional & Komplementari, KKM  
iii) Institut Penyelidikan dan Perubatan (IMR), KKM  
iv) Kementerian Pertanian & Industri Asas Tani Malaysia  
v) Unit Perancang Ekonomi, Jabatan Perdana Menteri  
 
 
Universities:  
i) Jabatan Pemakanan dan Dietetik, Fakulti Perubatan & Sains Kesihatan, Universiti 
Putra Malaysia  
ii) Jabatan Pemakanan dan Dietetik, Fakulti Sains Kesihatan Bersekutu, Universiti 
Kebangsaan Malaysia  
iii) Pejabat Dietetik, Pusat Perubatan Universiti Malaya  
iv) Program Sains Makanan, Fakulti Sains dan Teknologi, Universit i Kebangsaan 
Malaysia  
 
Industries/  Associations:  
i) Biotropic Malaysia Berhad  
ii) Direct Selling Association of Malaysia (DSAM)  
iii) Federation of Chinese Physician and Medicine -Dealers Association of Malaysia 
(FCPMDAM)  
iv) Malaysian Biotechnology Corporation (BiotechCorp ) 
v) Malaysian Dietary Supplement Association (MADSA)  
vi) Malaysian Direct Distribution Association (MDDA)  
vii) Persatuan Industri Farmaseutikal Malaysia (MOPI)  
viii)Persatuan Pengeluar -pengeluar Ubat Tradisional Melayu Malaysia (PURBATAMA)  
ix) Perubatan Traditional India Mala ysia (PEPTIM)  
x) Pharmaceutical Association of Malaysia (PhAMA)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 291  APPENDIX 5:  GUIDELINE ON REGISTRATION OF NATURAL 
PRODUCTS  
 
 
 
 
 
 
 
 
 
 
 
Outline:  
1. General Information  
1.1 Definitions  
1.1.1  Traditional Medicines  
1.1.2  Finished Herbal Product  
1.1.3  Herbal Rem edy 
1.1.4  Homeopathic Medicine  
1.2 Exemption from Product Registration  
1.3 Preparations which are not allowed to b e registered  
1.4 Classification for Specific Active Ingredients  
1.4.1  Products Containing Cassia/ Senna  
1.4.2  Products Containing Psyllium Husk/ Pla ntago Ovata  
2. General Requirements for R egistration of Natural Products  
2.1 Ingredients  
 2.1.1  Active Ingredients   
IMPORTANT NOTES:   
1. This document shall be read in conjunction w ith the  relevant sections of the 
main DRGD.  
2. Natural products will be evaluated based on the criteria for safety and quality 
of the product and where appropriate efficacy/ claimed benefits . 
3. This document is intended to provide guidance for the registration of natural 
products .  However, the document will serve as a living document that will be 
updated/ revised further in the line with the progress in scientific knowledge 
and experience.  
4. The following lists are by no means exhaustive. It may be reviewed as an d 
when it is deemed necessary.  
• ................................ ................................ ................................ ..........   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 292  2.1.2  Premix  
 2.1.3  Prohibited/ Banned Ingredients  
 2.1.4  Use of Protected/ Endangered Ingredients  
2.2 Excipients  
2.3 Indications  
 2.3.1  Indications Acceptable f or Natural Products  
 2.3.2  Non-Permissible Indications  
2.4 Product Name  
2.5 Quality Control  
2.5.1  Sample f or Testing  
2.5.2  Quality Testing f or Specific Ingredient  
2.5.3  Limit Test f or Heavy Metals  
2.5.4  Disintegration Test  
2.5.5  Test for Uniformity of Weight (For Tablets a nd Capsules Only)  
2.5.6  Tests for Microbial Contamination  
2.5.7  Certificate of Analysis (Active Ingredient)  
2.5.8  Certificate of Analysis (Finished Product)  
2.6 Stability Data  
2.7 Labelling Requirement  
2.7.1  Statements to be stated o n Product Label     
2.7.2  Specific L abelling Statements/ Warning & Precautions   
2.7.3  Cautionary Statement f or Products Specially Used  in Women  
2.7.4  Prohibit ed Visual/ Graphics/ Statement o n Label of Natural Product s in 
Women  
2.8 Particulars of Packing  
3. Product Specific Requirements:  
3.1 Foot P atch 
3.2 Herbal Tea  
3.3 Homeopathic Products  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 293  1. GENERAL INFORMATIONS  
 
1.1 DEFINITIONS  
 
1.1.1  Traditional medicine  
As defined under the CDCR  1984 , traditional medicine refers to a ny product used in 
the practice of indigenous medicine, in which the drug  cons ist solely of one or more 
naturally occurring substances of a plant, animal or mineral, of parts thereof, in the 
unextracted or crude extract form, and a homeopathic medicine.  It shall not include 
any sterile preparation, vaccines, any substance derived hu man parts, any isolated 
and characterized chemical substances.  
 
1.1.2  Finished Herbal Product  
Finished herbal products consist of herbal preparations made from one or more 
herbs. If more than one herb is used, the term “mixture herbal product” can also be 
used.  Finished herbal products and mixture herbal products may contain excipients 
in addition to the active ingredients. However, finished products or mixture herbal 
products to which chemically defined active substance have been added, including 
synthetic comp ounds and/ isolated constituents from herbal materials, are not 
considered to be herbal.  
 
1.1.3  Herbal Remedy  
Any drug consisting of a substance or a mixture of substances produced by drying, 
crushing or comminuting, but without subjecting to any other process, a natural 
substance or substances of plant, animal or mineral origin, or any part of such 
substance or substances.  
 
1.1.4  Homeopathic Medicine  
Any pharmaceutical dosage form used in the homeopathic therapeutic system in 
which diseases are treated by the use of m inute amounts as of such substances 
which are capable of producing in healthy persons symptoms similar to those of the 
disease being treated.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 294  1.2 EXEMPTION  FROM PRODUCT REGISTRATION  
 
The following preparations do not require registration with the Authorit y: 
a) Extemporaneous preparation that has been prepared and given directly to the 
patient by any traditional practitioner during the course of treatment;  
b) Traditional preparation containing plants, animal parts or mineral substance or a 
mixture of these substa nces of natural origin that is produced only through drying, 
without any treatmen t/process involved. For example,  raw herbs ; 
c) Traditional preparation containing plants, animal parts, mineral substance / extracts 
or a mixture of these substances of natural or igin traditionally used as food, spices 
or flavouring of food which do not have any medicinal claim;  
d) Traditional preparation that is used for cosmetic purposes such as to whiten or 
improve the appearance of skin, hair, teeth, etc . has to be notified  as cos metic 
product.  
 
 
1.3  PREPARATIONS WHICH ARE NOT ALLOWED TO  BE REGISTERED  
 
a) Traditional preparation with the indication as listed in  “List of Non Permissible 
Indications for Natural Product”  
(Reference: Medicine Advertisement and Sale Act 1956)  
b) Traditional  preparation containing herbal ingredients as listed under Poison Act 1952 
except for those exempted for homeopathic preparation .                                      
Please refer to Section 4  - General guidelines for the regis tration of homeopathic 
produc ts. 
c) Traditional pre paration containing ingredient known or reported to cau se any 
adverse effect on humans. Please refer to List of Botanicals (& botanical ingredients) 
which are banne d due to reported adverse event . 
d) Traditional preparation containing combi nation of plants, animal parts or mineral 
substance of natural origin with chemical/ synthetic substance with therapeutic 
effect.  
e) Traditional preparation containing combination of plants, animal parts or mineral 
substance of natural origin with vitamins an d amino acids.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 295  f) Traditional products are prohibited from containing ingredients derived from  human 
origin. For e xamples:  
i) CRINIS CARBONISATUS = Carbonised human hair  
(Reference: Pharmacopoeia Of The People’s Republic Of China: English Edition 
1992)  
ii) HUMAN P LACENTA  
 
 
1.4 CLASSIFICATION FOR SPECIFIC ACTIVE INGREDIENTS  
 
1.4.1  PRODUCTS CONTAINING CASSIA/ SENNA:  
Finished  products containing cassia/senna as an active ingredient with a daily dose 
of less than 0.5g of the crude drug or 20 mg sennoside (standardized  preparation) 
shall be classified as traditional products and restricted to traditional claims. Active 
ingredient consumed more than this  daily limit  will  be classified as pharmaceutical 
product, depending on the product formulation.  
 
1.4.2  PRODUCTS CONTAININ G PSYLLIUM HUSK/ PLANTAGO OVATA  
Finished products containing psyllium husk as an active ingredient and with a total 
daily consumption of l ess than 3.5g per day shall be classified as a non -drug. 
However, daily doses above this amount and up to 6.9 g will r equire this product to 
be registered under the traditional product category.    
 (Reference: Circular on 14 May 2010 - Bil (24) dlm.BPFK/PPP/07/11Jld 5 ) 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 296   
2. GENERAL REQUIREMENTS FOR REGISTRATION OF NATURAL PRODUCTS  
 
2.1 INGREDIENTS  
 
 2.1.1  ACTIVE INGREDIENTS  
 
a) Active ingredients are those substances that have a therapeutic role in the 
formulation. Substances that are included in the formulation as active  ingredients 
must make a contribution to the proposed indications for the product. Where a claim 
links the presence of an ingredient to the product indication, that ingredient must 
contribute to that indication. The evidence may be scientific and or tradit ional.  
 
b) Overages of active ingredient  
Overages may be used during manufacture. An overage is where the amount of an 
ingredient added during manufacturing that is greater than the nominated on the 
product label. Details of the overage used must be available  
 
c) Listed active ingredients can be checked through http://npra.moh.gov.my/  of product 
search. Ingredients not  listed will require safety and /or efficacy data evaluation prior 
to addition to this list.  
 
d) For new active ingredients or new combination products , the following information 
shall be required:  
➢ Product containing new single ingredient:  
i) Extract form  
- Information on the taxonomy of the ingredien t; 
- Techniques and methods in preparing/  processing the extract and 
subs equently  the product ; 
- Information on the use and safety of the ingredient and the product Quality 
standard.  
 
ii) Powder/ Granules  
- Information on the taxonomy of the ingredient ; 
- Techniques and methods in preparing/  processing the extract and 
subsequently  the pr oduct ; Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 297  - Information on the use and safety of the ingredient and the product . 
 
➢ Product containing multiple ingredients (contains ingredients which are known to 
be used traditionally):  
- The source of the product formulation ; 
e.g. Chinese Pharmacopoeia  
- Proof or  evidence of the use, traditionally . 
 
➢ Product containing multiple ingredients (contains ingredients which are not 
known to be used traditionally):  
- Information on the use and safety of every new ingredient ; 
- Safety data on the new formulation ; 
- Regu latory sta tus in other countries.  
 
 
2.1.2  PREMIX  
 
Effective from 1 December 2007, premixed ingredient(s) shall not be used in a 
traditional product formulation , as directed in circular Bil (71) dlm BPFK/02/5/1.3 , 1 
Jun 2007  
 
 
2.1.3  PROHIBITED/ BANNED INGREDIENTS  
 
The following lists are prohibited/ banned ingredients which are not allowed in the 
formulation of natural products registered by the Authority:  
a) Botani cals (and botanical ingredients) containing scheduled poisons as listed 
under the Poisons Act 1952 ; 
b) Botanicals (& botanical ingredients) which are banned due to reported adverse 
event ; 
c) Ingredients (botanicals and substance derived from animals) which are b anned 
due to safety reasons.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 298   
Table 1: Botanicals (and botanical ingredients) containing scheduled 
poisons as listed under the Poisons Act 1952  
Genus  Species  Common/ 
Local Name  Part of plant 
prohibited  
(whole plant 
unless 
otherwise 
specified)  Constituent(s ) of 
concern  
Aconitum  All species    Aconite  
Asidosperma  quebracho  White 
quebracho   Asidospermine, 
yohimbine  
Atropa  belladonna  Deadly 
nightshade   Atropine, 
hyoscine 
(scopolamine), 
hyoscyamine  
Cabola  albarrane  Squill   Glycoside  
Cannabis  
(controlled und er 
Dangeroud Drug 
Act 1952)  All species  Marijuana   Cannabinoids  
Catharanthus  roseus  Periwinkle 
Madagascar, 
Old Maid, 
Vinca rosea, 
Myrtle  
Syn: Vinca 
balcanica , 
Vinca 
difformis , 
Vinca 
heracea , 
Vinca major , 
Vinca minor , 
Vincae  Vinca, Vincristi ne, 
Vinblastine  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 299  Genus  Species  Common/ 
Local Name  Part of plant 
prohibited  
(whole plant 
unless 
otherwise 
specified)  Constituent(s ) of 
concern  
minoris herba  
Chondodendron  tomentosum  Curare, Velvet 
leaf, Ice Vine,   Tubocurarine  
Claviceps  purpurea  Ergot   Ergometrine  
Colchicum  autumnale  Autumn 
Crocus/ 
Meadow 
Saffron/ Naked 
Lady)   Colchicine  
Datura  metel  Devil’s 
Trumpet, 
Metel, J 
California 
Jimson Weed  
Syn.: Datura 
wrightii   Atropine, 
Scopolamine  
Datura  stramonium  Jimson Weed/ 
Gypsum 
Weed,Loco 
Weed   Atropine, 
Hyoscyamine, 
Scopolamine  
Delphinium  staphysagria  Lice bane, 
Stavesacre   Delphinine  
Digitalis  purpurea  Common 
Foxglove, 
Purple 
Foxglove,  
Kecubung  Leaf Glycoside  
Drimia  maritima  Squill   Glycoside  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 300  Genus  Species  Common/ 
Local Name  Part of plant 
prohibited  
(whole plant 
unless 
otherwise 
specified)  Constituent(s ) of 
concern  
Syn.: Urginea 
maritima, Scilla 
maritima  
Related 
substance: 
Urginea indica, 
Urginea 
pancreatium, 
Urginea scilla  
Ephedra  All species  Ma Huang   Ephedrine, 
Pseudoephedrine  
Gelsemium  sempervirens  Yellow 
Jessamine,Eve
ning 
Trumpet,Caroli
na Jessamine   Gelsemine  
Hyoscyamus  muticus  Egyptian 
henbane   Hyoscyamine  
Hyoscyamus  niger  Black henbane   Hyoscyamine -
atropine  
Lobelia  inflata  Lobelia, 
pokeweed, 
Indian tobacco, 
gagroot, 
asthma weed, 
vomitwort, 
bladderp od,rap
untium 
inflatum.   Lobeline  
Lobelia  nicotianifolia  Wild Tobacco   Lobeline  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 301  Genus  Species  Common/ 
Local Name  Part of plant 
prohibited  
(whole plant 
unless 
otherwise 
specified)  Constituent(s ) of 
concern  
Mitragyna  speciosa  Daun Ketum   Mitra gynine  
Nicotiana  tabacum  Common 
tobacco   Nicotine  
Papaver  somniferum  Opium poppy   Morphine, 
codeine, 
hydrocodone, 
meperidine, 
methadone, 
papaverine  
Pausinystalia  yohimbe  Yohimbe, 
Johimbe  
Syn.  
Corynanthe 
johimbi,Coryna
nthe yohimbi   Yohimbine  
Physostigma  venenosum  Calabar bean   Physostigmine  
Pilocarpus  microphyllus  Pilocarpus 
jaborandi, 
jaborandi   Pilocarpine  
Punica  granatum  Pomegranate  Bark Iso-Pellatrierine  
Rauwolfia  serpentina  Indian 
snakeroot, 
Serpentine 
root  Reserpine  
Rauwolfia  vomitoria  African 
serpentwood   Reserpine  
Schoenocaulon  officinale  Veratrum  Sabadilla, Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 302  Genus  Species  Common/ 
Local Name  Part of plant 
prohibited  
(whole plant 
unless 
otherwise 
specified)  Constituent(s ) of 
concern  
officinale  Veratrine  
Scillae  bulbus  Sea onion, 
Squill    
Solanum  nigrum  Black 
nightshade   Solanine  
Strychnos  nux-vomica  Poison nut, 
Quaker button, 
strychnine 
tree, ma qian 
zi/maqianzi   Strychnine  
Valerian  All species   All parts 
except for 
root part  Valepotriates  
Veratrum  All species     
Vinca  All species  Including 
Catharanthus 
roseus   Vinca, Vincristine, 
Vinblastine, 
Vinpocetin  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 303  a) Table 2 : Botanicals (& botanical ingredients) which are banned due to reported 
adverse event  
 
Genus  Species  Common/ Local 
Name  Part of 
plant 
prohibited  Reason for 
prohibition  
Aristolochia  
 All species    Contain Aristolochic 
Acid  reported to 
cause kidney toxicity 
(**Please refer to 
footnote below)  
Berberis  All species    Berberine  
*Other herbs 
containing naturally -
occuring berberine 
are allowed to be 
registered with 
specific 
requirements. Plea se 
refer to Appendix 9  
Notes: Only 
prohibited for oral 
preparation.  
Dioscorea  hispida  Ubi gadong, 
Gadong, Gadog, 
Gadong Lilin, 
Gadong Mabok, 
Ubi Arak, Ubi 
Akas, Taring 
Pelanduk, Susur 
Gadong, 
Gadongan, 
Kedut dan Ubi 
Bekoi  All parts  Contain dioscorine 
and dioscorinine 
reported to cause 
burning sensation in 
the throat, giddiness, 
followed by 
haematemesis, 
sensation of 
suffocation, 
drowsiness and 
exhaustion  
Not allowed for oral 
preparation  
Drybalanops  aromatica  Borneo Whole herb  Contain camphor - not Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 304  Genus  Species  Common/ Local 
Name  Part of 
plant 
prohibited  Reason for 
prohibition  
/Malay/Sumatra 
Camphor, Pokok 
Kapur  allowed for oral 
preparation  
Borneolum  syntheticum  Bingpian,borneol   Contain borneol - not 
allowed for oral 
preparation  
 
Larrea  tridenata   
Chapparal   Reported to cause 
liver toxicity  mexicana  
Hydrastis  canadensis  Golde nseal,Eye 
Balm, Indian 
Dye  Reported to cause 
disturbance of the 
nervous system  
Magnolia  officinalis  Houpu, 
Magnolia   Reported to cause 
kidney toxicity  
Stephania  tetrandra    
Piper 
methysticum   Kava -kava    
 
 
 
Reported to cause 
liver toxicity  
 
 
 
 
 
Report ed to cause 
liver toxicity   
Symphytum  officinale  
 
Comfrey   
asperum   
x. uplandicum   
 
 
 
Senecio  aureus  Life root   
jacobaea  Tansy ragwort, 
Tansy 
Butterweed   
bicolor  Silver ragwort   
nemorensis  Alpane ragwort, 
Wood ragwort   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 305  Genus  Species  Common/ Local 
Name  Part of 
plant 
prohibited  Reason for 
prohibition  
vulgaris  Comm on 
groundsel, 
Groundsel, Old -
man-in the -
spring    
longilobus  
-syn .with 
douglasii, 
filifolius  Threadleaf 
groundsel, 
Threadleaf 
ragwort   
Scandens 
Buch. -Ham  German/African/
Cape Ivy, 
Climbing 
Groundsel   
**  To identify the Botanicals which may contain A ristolochic Acid besides the 
Aristolochia genus, please refer the following lists on the next page : 
a. List A - Botanicals Known or Suspected to contain Aristolochic Acid  
b. List B - Botanicals which may be Adulterated with Aristolochic Acid  
 
Note s:   
Products c ontaining any of the listed herbs (EXCEPT for Aristolochia spp. which is 
totally banned) will have to be sent to any governmental doping centre for testing and 
the result shall be attached with the registration form.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 306  (Source for Lists A and B)  
U. S. Food and Drug Administration  
Center for Food Safety and Applied Nutrition  
Office of Nutritional Products, Labeling, and  
Health  Supplements  
[Revised April 9, 2001]  
 
List A: Botanicals Known or Suspected to Contain Aristolochic Acid  
Table 3:  
Botanical Name*  Commo n or Other Names  
Asarum canadense Linn.  
Syn. Asarum acuminatum (Ashe) E.P. Bicknell  
Syn. Asarum ambiguum (E.P. Bicknell) Daniels  
Syn. Asarum canadense var. ambiguum (E.P. 
Bicknell) Farw.  
Syn. Asarum canadense var. reflexum (E.P. Bicknell) 
B.L.  
Rob.  
Syn. Asarum furcatum Raf.  
Syn. Asarum medium Raf.  
Syn. Asarum parvifolium Raf.  
Syn. Asarum reflexum E.P. Bicknell  
Syn. Asarum rubrocinctum Peattie  Wild ginger  
Indian ginger  
Canada  
snakeroot  
False coltsfoot  
Colic root  
Heart snakeroot  
Vermont  
snakeroot  
Southern  
snakeroot  
Asarum himalaicum Hook. f. & Thomson ex Klotzsch 
or  
Asarum himalaycum Hook. f. & Thomson ex 
Klotzsch  Tanyou -saishin  
(Japanese)  
Asarum splendens (F. Maek.) C.Y. Cheng & C.S. 
Yang  Do-saishin  
(Japanese)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 307  Botanical Name*  Commo n or Other Names  
Bragantia wallich ii R.Br.  
Specimen exists at New York Botanical Gardens. 
Tropicos  
does not list this species as a synonym for any 
Thottea  
species. Kew Gardens Herbarium does not 
recognize the  
genera Bragantia. Until additional information is 
obtained we  
will use the n ame as cited in J. Nat. Products 
45:657 -666  
(1982)   
 
 
List B: Botanicals which may be Adulterated with Aristolochic Acid  
Table 4 : 
Botanical Name*  Common or Other Names  
Akebia spp.  
 Akebia  
Mu tong  
Ku mu tong  
Zi mutong  
Bai mu tong  
Mokutsu (Japanese ) 
Mokt'ong (Korean  
Akebia quinata (Houtt.) Decne.  
Syn. Rajania quinata Houtt.  
 Chocolate vine  
Fiveleaf akebia  
Mu tong  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 308  Botanical Name*  Common or Other Names  
Yu zhi zi  
Mokutsu (Japanese)  
Akebia trifoliata (Thunb.) Koidz.  Mu tong  
Three leaf akebia  
Yu zhi zi  
Asarum forbesii Maxim.  
 Batei-saishin  
(Japanese)  
Asarum heterotropoides F. Schmidt  
Syn. Asarum heterotropoides F. Schmidt  
Syn. Asiasarum heterotropoides (F. Schmidt) F. 
Maek.  
 Keirin -saishin  
(Japanese)  
Chinese wild ginger  
Manchurian wild  
ginger  
Bei xi xin  
Xin xin  
Asarum sieboldii Miq.  
Syn. Asarum sieboldii fo. seoulense (Nakai) C.Y. 
Cheng &  
C.S. Yang  
Syn. Asarum sieboldii var. seoulensis Nakai  
Syn. Asiasarum heterotropoides var. seoulense 
(Nakai) F.  
Maek.  
Syn. Asiasarum sieboldii (Miq.) F. Maek.  Usuba -saishin  
(Japanese)  
Chinese wild ginger  
Xi Xin  
Hua Xi Xin  
Manchurian wild  
ginger  
Siebold's wild ginger  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 309  Botanical Name*  Common or Other Names  
Clematis spp.  
 Clematis  
Mufangji  
Clematidis  
Ireisen (Japanese)  
Wojoksum (Korean)  
Clematis armandii Franch.  
Syn. Clematis armandii fo. farquhariana ( W.T. 
Wang)  
Rehder & E.H. Wilson  
Syn. Clematis armandii var. biondiana (Pavol.) 
Rehder  
Syn. Clematis biondiana Pavol.  
Syn. Clematis ornithopus Ulbr.  Armand's clematis  
Chuan mu tong  
(stem)  
Xiao mu tong  
Armand's virgin  
bower  
Clematis chinensis Osb eck.  
 Chinese clematis  
Wei ling xian (root)  
Clematis hexapetala Pall.   
Clematis montana Buch. -Ham. ex DC.  
Syn. Clematis insulari -alpina Hayata   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 310  Botanical Name*  Common or Other Names  
Clematis uncinata Champ. ex Benth.  
Syn. Clematis alsomitrifolia Hayata  
Syn. Clematis chinensis var. u ncinata (Champ. ex 
Benth.)  Kuntze  
Syn. Clematis drakeana H. Lév. & Vaniot  
Syn. Clematis floribunda (Hayata) Yamam.  
Syn. Clematis gagnepainiana H. Lév. & Vaniot  
Syn. Clematis leiocarpa Oliv.  
Syn. Clematis ovatifolia T. Ito ex Maxim.  
Syn. Clematis unc inata var. biternata W.T. Wang  
Syn. Clematis uncinata var. coriacea Pamp.  
Syn. Clematis uncinata var. floribunda Hayata  
Syn. Clematis uncinata var. ovatifolia (T. Ito ex 
Maxim.)  
Ohwi ex Tamura  
Syn. Clematis uncinata var. taitongensis Y.C. Liu & 
C.H. O u   
Cocculus spp.  Cocculus  
Cocculus carolinus (L.) DC.  
Syn. Cebatha carolina Britton  
 
Syn. Epibaterium carolinum (L.) Britton  
Syn. Menispermum carolinum L.   
Cocculus diversifolius DC.  
Syn. Cocculus madagascariensis Diels   
Cocculus hirsutus (L.)  Diels  
Syn. Cocculus villosus DC.  
Syn. Menispermum hirsutum L.   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 311  Botanical Name*  Common or Other Names  
Cocculus indicus Royle  
Syn. Anamirta paniculata Colebr.  Indian cockle  
 
Cocculus laurifolius DC.  
Syn. Cinnamomum esquirolii H. Lév.   
Cocculus leaebe DC.   
Cocculus madagascariensis D iels  
Syn. Cocculus diversifolius DC.   
Cocculus orbiculatus DC.  
Syn. Cissampelos pareira Linn.  
Cocculus orbiculatus (L.) DC.  
Syn. Cocculus cuneatus Benth.  
Syn. Cocculus sarmentosus (Lour.) Diels  
Syn. Cocculus sarmentosus var. linearis Yamam.  
Syn. C occulus sarmentosus var. pauciflorus Y.C. Wu  
Syn. Cocculus sarmentosus var. stenophyllus Merr.  
Syn. Cocculus thunbergii DC.  
Syn. Cocculus trilobus (Thunb.) DC.  
Syn. Menispermum orbiculatus L.  
Syn. Menispermum trilobum Thunb.  
Syn. Nephroia sarmentosa Lour.  Moku -boui  
(Japanese)  
 
 
 
 
 
 
 
  
Cocculus palmatus (Lam.) DC.  Columba  
Columbo  
Cocculus pendulus Diels  
Syn. Cebatha pendula (J.R. & C. Forst.) Kuntze  
Syn. Epibaterium pendulus Forst. f.  
Syn. Cocculus Epibaterium DC.   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 312  Botanical Name*  Common or Other Names  
Cocculus pendulus (Forst . & Forst.) Diels   
Cocculus palmatus Hook.  
Syn. Jateorhiza Miersii Oliver  Colombo  
 
Cocculus thunbergii DC.   
Diploclisia affinis (Oliv.) Diels  
Syn. Diploclisia chinensis Merr.  
Syn. Cocculus affinis Oliv.   
Diploclisia chinensis Merrill  Xiangfang chi  
Menispernum dauricum   
Saussurea lappa (Decne.) Sch. Bip. / Aucklandia 
Lappa  Mokkou (Japanese)  
Sinomenium acutum (Thunb.) Rehder & E.H. Wilson  
Syn. Cocculus diversifolius var. cinereus Diels  
Syn. Cocculus heterophyllus Hemsl. & E.H. Wilson  
Syn. Menispermum acutum Thunb.  
Syn. Sinomenium acutum (Thunb.) Rehder & E.H. 
Wilson  
var. cinereum (Diels) Rehder & E.H. Wilson  
Syn. Sinomenium diversifolium (Diels) Diels  
 
 Orientvine  
Xunfengteng  
Dafengteng  
Daqingmuxinag  
Zhuigusan  
Da ye qingshener  
Mufangji  
Hanfangji  
Tuteng  
Zhuigufeng  
Maofangji  
Stephania spp. (except for Stephania Tetrandra 
which is banned)  Stephania  
Vladimiria souliei (Franch.) Ling Sen-mokkou  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 313   
b) Ingredients (Botanicals and Substance Derived from Animals) which are 
banned due t o safety reasons:  
Table 5 : 
Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
Abrus  precatorius  Seed  Abrin, Agrus, 
Agglutinin  - Potent inhibi tor of protein  
and DNA synthesi s 
- Severe diarrhea  
- Severe stomach cramp  
- Severe gastroenteritis  
Adonis  vernalis   Adonitoxin  Uncontrolled dose can 
damage heart and cause 
death  
Animal parts containing hormones (All species)  
Antiaris  toxicaria  Latex, sap  Cardiac glycoside 
(antiarin), 
Cardenolides & 
alkaloids with 
cardiac arresting 
potential  - Latex is highly poisonous  
- Paralyze heart muscle and 
cause death  
Aristolochia  All species   Aristolochic acid  Reported to cause kidney 
toxicity, interstitial 
nephropathy  
Calotropis  gigantean  
Latex  Cardiac glycosides, 
calotropin   
Severe mucous membrane 
irritation characterized by 
vomiting, diarrhea, 
bradycardia, convulsion and 
death  
 procera  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 314  Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
Catharanthus  roseus   Vinca alkaloids  Bone marrow depression, 
central and perip heral 
(including autonomic) 
neurotoxicity  
Cerbera  manghas  Seed  Digitoxynglycoside, 
Cerberine, 
Cerberoside, 
thevetin  - Drastic purgative and emeti c 
- Burning in the stomach 
sensation, vertigo, nausea, 
violent purgation and colic  
- Heart failure  
odollam  Seed  Cerberine, 
Cerberoside, 
odollin, odolotoxin, 
thevetin and 
cerapain  - Gastro intestinal symptoms  
- cardiac toxicity  
- Nausea, severe retching, 
vomiting, abdominal pain, 
blurring of vision  
- Arterial block and nodal 
rhtym, hyperkalaemia  
- Irregular respiration, collapse  
and death from heart failure  
Cinchona  All species   Quinine and 
derivatives  - Resistance of malarial vector  
- Use of bark is 
contraindicated in pregnancy 
and ulcers, intestinal or 
gastric, and if taken 
concommitant ly with 
anticoagulants can increased 
their ef fects 
- Can elicit thrombocytopenia 
with purpura  
- Cinchona alkaloids are toxic.  
Can cause symptoms such Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 315  Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
as blindness, deafness, 
convulsions and paralysis  
Citrullus  Colocynthis  Seed, fructus  Curcubitacin  - Carcinogenic effects, induce 
infertility in both sexes  
- Enterohepatonephro -toxicity  
Dryopteris  filix-mas Rhizome  Filicin, aspidinol  Hepatotoxic and blindness  
Euphorbia  antiquorum  
Latex  Apha euphorbol, 
Beta amyrin 
cycloartenol Euphol  Inflammation of the 
gastrointestinal mucous 
membrane, irritate skin, 
difficul t respiration, eyes 
pupil dilated  trigona  
Excoecaria  agallocha  Latex  Excoecaria  
phorbol  
 - Highly irritant to skin  
- Cause blindness if it enters 
the eye  
- Biocidal  
Garcinia  acuminate  
Gum resin  Cambogic acid, β -
guttiferin, α -1 
guttiferin  Vomiting, hyperca rthasis, 
sympathetic irritation of 
sympathetic nervous system, 
caused death by gastro -
enteritis  hanburyi  
morella  
Gelsemium  elegans  Root, leaf , 
rhizome  Gelsemine & 
gelseminine 
(Gelsemium indole 
alkaloid)   
Paralysis, shortness of 
breath, muscle 
stiffeningcoma, hypocyclosis  
Hyoscyamus  muticus   Hyoscyamine, 
atropine, hyoscine  Difficulty in swallowing and 
talking, transient bradycardia 
followed by tachycardia with 
palpitation and arrhythmias, 
CNS depression, coma  
Jatropha  multifida  Fruit, seed  Phyto toxin  Nausea, vomiting, serious Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 316  Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
(toxalbumin  - 
Curcin  purgative action  
Lantana  camara   Lantadene, 
Lancamaron  Cause toxicity in buffalo, 
cattle, sheep and goat. 
Symptoms include 
photosensitive dermatitis, 
jaundice and yellowing of 
mucous membrane and loss 
of appetite with a decrease in 
ruminal motility  
Lobelia  chinensis  
 Lobeline  - Stimulant and has peripheral 
and central effects  
- Excessive use can cause 
nausea, vomiting and 
dizziness  
tupa - Stimulant and has peripheral 
and central effects  
- Caused arrhythmias  
Lytta vesicatoria  Whole body, 
tincture  Cantharidin  - Excessive salivation, 
abdominal pain, swelling of 
kidney and urogenital 
system, headache, vomiting 
and diarrhea accompanied 
by bleeding  
- Burning of the mouth, 
dysphagia, nausea, 
hematemesis, gross 
hematur ia and dysuria  
- Renal dysfunction and 
related to acute tubular 
necrosis and glomerular 
destruction  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 317  Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
Melaleuca  alternifolia   Tea tree oil  Skin irritation, respiratory 
distress, vomiting, diarrhea 
and cytotoxic for oral 
administration.  
* Banned in  oral prepar ation  
Papaver  All species   Morphine and 
derivatives, 
codeine  - Potential abuse  
- Dependence, palpitation, 
hallucination, euphoric 
activities, CNS depression  
- Nervous system toxicity  
- Possible death from 
circulatory and respiratory 
failure  
Pilocarpus  pinnatifol ius Bark 
Pilocarpine  Bronchospasm, ocular 
problem, miosis, blurred 
vision  jaborandi   
Podophyllum  emodii  
Root, leaf  Podophyllin resin  - Serious systemic toxicity with 
excessive amounts  
(persistent nausea and 
vomiting, tachypnea, fever, 
stupor, coma, tac hycardia, 
neuropathy and death)  
- Renal failure and 
hepatotoxicity  peltatum  
Solanum  dulcamara  Leaf, 
flowering 
tops Solanaceous 
alkaloids  Typical antimuscarinic  effect 
e.g. dry mouth, mydriasis  
Strophantus  All species   Strophantus 
alkaloids  Cardiac ef fect similar to 
digoxin  
Symphytum  pregrinum   Pyrrolizidine Reported to cause liver Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 318  Genus  Species  Part of 
Plant/ 
Animal 
Prohibited  
(whole plant / 
animal 
unless 
otherwise 
specified)  Constituent of 
Concern Reasons 
for P rohibition  Reasons for Prohibition  
alkaloid  toxicity  
 
 
2.1.4  USE OF PROTECTED/ ENDANGERED INGREDIENTS  
 
a) PROTECTED/  ENDANGERED WILDLIFE SPECIES   
 
It is the responsibility of the applicant to ensure that the ingredient(s) derived 
from wildlife species its parts and derivatives used in the formulation 
COMPLIES with the Wildlife Conservation Act 2010 (Act 716) and 
International Trade in Endangered Species Act 2008 (Act 686). Both 
guidelines can be downloaded thr ough this link http://www.wildlife.gov.my . 
 
The applicant shall contact the following department to obtain the necessary 
permit/  licens e.  A copy of the permit/  license shall be attached together with 
the applica tion form for product registration.  
  
Department of Wildlife and National Parks, Peninsular Malaysia  
Km. 10, Jalan Cheras,  
56100 Kuala Lumpur,  
Tel: +603 -90866800, Fax: +603 -90753873  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 319   
b) ENDANGERED BOTANICAL SPECIES   
 
It is the responsibility of the applica nt to declare the source of the botanical 
ingredient if it is listed under the International Trade in Endangered Species 
Act 2008 (Act 686). If the ingredient is from a local source, a special permit/  
license shall be obtained from the:  
 
Division of Protec tion and Quarantine of Plants,  
Department of Agriculture , 
Tingkat 1 -3, Wisma Tani,  
Jalan Sultan Salahuddin,  
50632 Kuala Lumpur.  
Tel: +603  - 20301400, Fax: +603  - 26913550.  
 
2.2 EXCIPIENTS  
 
a) Excipients are substances used to assist in the manufacture of act ive substance into 
dosage forms suitable for administration to consumers. Each excipient ingredient 
included in a formulation must have a justifiable excipient role and shall be controlled 
by specifications. The intended use of an excipient shall be approp riate.  
 
b) New excipient will require safety and/or other additional data to support the function 
in the product prior to addition into the Quest 3 database.  
 
c) LIST OF RESTRICTED EXCIPIENTS:  
 
 
 
 
 Specific Excipient  Limits (Not allowed)  
1. Menthol  - Oral (0.4mg/kg body  weight/day ) 
- External (>10%)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 320   
2.3 INDICATIONS  
General note: The indications listed below will serve as a guide for the applicant. 
For traditional medicines, only low level claim (s) will be accepted. Other 
indication with the same level of claims may  be considered if supported with 
traditional use.  
 
 2.3.1  INDICATIONS ACCEPTABLE FOR NATURAL  PRODUCTS  
 
a) General Health Maintenance / Kesihatan Am  
 
“Traditionally used…./ “Digunakan secara tradisional….  
“Digunakan secara homeop ati untuk.../ “Homeopathically u sed....  
 
1. For general health/ for health / untuk kesihatan . 
2. General health maintenance / for general well being.  
3. For he alth and strengthening the body / untuk kesihatan dan menguatkan 
badan .  
4. For relief of body heatiness / untuk melegakan panas badan . 
5. For gener al debility, weakn ess after illness or childbirth/ untuk letih lesu / 
kelesuan badan selepas sakit atau selepas bersalin.   
6. For loss of appetite / untuk kurang selera makan.  
7. For difficulty in sleep / bagi melegakan kesukaran untuk tidur.  
8. For relief of fatigue / untuk melegakan kepenatan.  
9. As an aid to overcome f atigue during physical exertion / membantu melegakan 
kepenatan fizikal.   
10. To expel wind and i nvigorate vital energy / untuk membuang angin dan 
menambah tenaga.  
11. To improve appetite / untuk menambah selera ma kan. 
12. For relievi ng waist ache and body weakness / untuk melegakan sakit 
pinggang dan lemah anggota badan.  
13. For relieving dizziness, sw eating, and difficulty in sleep / untuk melegakan 
pening, berpeluh berlebihan dan sukar untuk tidur.  
14. For reducing body odou r/ untuk mengurangkan bau badan.  
15. For reducing toothache / untuk mengurangkan sakit gigi.   
16. To relieve tired eyes/ untuk  melegakan kepenatan mata.  
17. For healthy eyes/ untuk kesihatan mata . 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 321  b) Blood & Body Fluid / Darah & Cecair Badan  
 
“Traditionally used…./ “Digunakan secara tradisional….  
 
1. For improving blood circulation / untuk melancarkan perjalanan darah.   
2. To improve urination / untuk melawaskan kencing / buang air kecil.  
3. For improving bowel movement / untuk melawaskan buang air besar.   
4. For relieving mild vomiti ng/ untuk melegakan muntah ringan.  
5. For reducing minor swelling / untuk melegakan bengkak -bengkak ringan.   
 
 
c) Bone, Muscle &  Joint/ Tulang, Otot & Sendi  
 
“Traditionally used…./ “Digunakan secara tradisional….  
 
1. For st rengthening muscle and bone / untuk menguat kan otot dan tulang.  
2. For relieving muscular ache / untuk melegakan sakit otot.  
3. For re lieving waist ache and backache / untuk melegakan sakit pinggang dan 
sakit belakang.  
4. For rel ief of joints and muscular pain / untuk melegakan sakit sendi dan otot.   
5. For re lieving muscles sprain / untuk melegakan terseliuh / terkehel.  
 
 
d) Pain & Fever / Sakit Am & Demam  
 
“Traditionally used…./ “Digunakan secara tradisional….  
 
1. To relieve/ alleviate pain / untuk melegakan kesakitan.   
2. For relieving fever / untuk melegakan demam .  
3. For relieving headache / untuk melegakan sakit kepala.   
4. For relieving pain  and itchiness related to piles / untuk melegakan kesakitan 
dan rasa gatal akibat buasir.  
5. For sympt omatic relief of body heatiness / body heat / untuk melegakan panas 
badan.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 322   
e) Cough & Cold / Batuk & Selsema  
 
“Traditionally used……/ “Digunakan secara tradisional…..   
 
1. For relief of fever, cough and cold / untuk melegakan demam, batuk dan 
selsema.  
2. For relief of sore throat / untuk melegakan sakit tekak.  
3. For reducing phlegm and relief of coug h, sore thro at and body heatiness / 
untuk mengurangkan kahak dan melegakan batuk, sakit tekak dan panas 
badan.   
4. For relief of throat irritations and cough / untuk melegakan sakit tekak dan 
batuk.  
5. For relief of nasal congestion / untuk melegakan hidung tersum bat.  
6. For relief of sore throat and cough/ untuk melegakan sakit tekak dan batuk.  
7. For relief o f mouth ulcers due to heatiness / untuk melegakan sakit mulut 
akibat panas badan.  
8. To relieve sinusitis/ untuk melegakan resdung . 
 
 
f) Digestive System / Sistem Pence rnaan  
 
“Traditionally used…./ “Digunakan secara tradisional….  
 
1. For relief of stomach ache, mild diarrhoea / untuk melegakan sakit perut, cirit-
birit ringan.  
2. For relief of flatulence, stomach ache, mild diarrhoea , and loss of appetite / 
untuk melegakan kembu ng perut, sakit perut, cirit -birit ringan dan kurang 
selera makan.  
3. For relief of mild diarrhoea , vomiting and improve appetite / untuk melegakan 
cirit-birit, muntah ringan dan menambah selera makan.  
4. For relief of mild constipation / untuk melegakan sembeli t ringan.  
5. To improve appetite and digestion / untuk menambah selera makan dan 
pencernaan.  
6. For relievin g abdominal pain and flatulence / untuk melegakan sakit perut dan 
kembung perut.  
7. For relief of stomach ache, constipation , mild vomiting and indigestion / untuk 
melegakan sakit perut, sembelit, muntah ringan dan makanan tidak hadam .  
8. Aid in digestion / untuk membantu penghadaman.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 323   
g) Women’s Health / Kesihatan Wanita   
 
“Traditionally used…../ “Digunakan secara tradisional….  
 
1. To relieve menstrual pain, headac he and to regulate menstruation / untuk 
melegakan senggugut, sakit kepala dan melancarkan perjalanan haid.  
2. To reduce body weigh t/ untuk mengurangkan berat badan.  
3. For relief of vaginal discharge / untuk melegakan keputihan.   
4. For women after childbirth / untuk wanita lepas bersalin.  
5. For general wellbeing and stren gthen the body after childbirth / untuk 
kesihatan dan menguatkan badan wanita selepas bersalin.  
6. For women after c hildbirth to reduce body weight / untuk ibu -ibu selepas 
bersalin untuk mengurangkan ber at badan.  
7. For symptomatic relief of vaginal discharge and mild itch / untuk melegakan 
keputihan dan gatal -gatal ringan.  
8. To improve menstrual flow, for relief of menstrual pain, v aginal discharge and 
flatulence / untuk melancarkan haid, melegakan senggugut,  keputihan dan 
kenbung perut.   
9. For strengthening body muscle and reducing body weight / untuk 
mengencangkan otot -otot tubuh dan mengurangkan berat badan.  
10. For general h ealth of women after childbirth / untuk menyihatkan rahim 
selepas melahirkan anak.  
11. To rel ieve symptoms of menopause / untuk melegakan simptom menopause. 
[Note:  For specific active ingredient only, examples: red clover (trifolium 
pratense) and black cohosh ( cimicifuga racemosa )] 
 
 
h) Men’s Health / Kesihatan Lelaki  
 
“Traditonally used…./ “Digunakan secara tradisional….  
 
1. For men’s health and energy / for vitality / untuk memulihkan tenaga dan 
kesihatan lelaki.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 324   
i) Skin And External Usage/ Kulit Dan Kegunaan Luar   
 
“Traditionally used…../ “Digunakan secara tradisional…  
 
1. For symptomatic relief of pain an d itch ass ociated with insect bites / untuk 
melegakan sakit dan gatal -gatal digigit serangga.  
2. For relief of minor burns / untuk melegakan melecur ringan.   
3. For relief minor cuts / untuk melegakan luka -luka ringan.  
4. For relief of minor bruises / untuk melegakan  lebam yang ringan.   
5. For reducing pimples / untuk mengurangkan jerawat.   
6. To help maintain ing healthy skin, nail and hair / untuk kesihatan kulit, kuku 
dan rambut.  
7. For reducing pimples and mild itch / untuk melegakan jerawat dan gatal -gatal 
ringan.  
 
 
2.3.2  NON -PERMISSIBLE INDICATIONS  
 
Table 6: 
NO. NON -PERMISSIBLE INDICATIONS   
1.  Penyakit atau kecacatan ginjal  / Disease or defects of the kidney  
2.  Penyakit atau kecacatan jantung  / Disease or defects of the heart  
3.  Kencing manis  / Diabetes  
4.  Epilepsi atau sawan  / Epile psy or fits  
5.  Kelumpuhan  / Paralysis  
6.  Tibi / Tuberculosis  
7.  Asma  / Asthma  
8.  Kusta  / Leprosy  
9.  Kanser  / Cancer  
10.  Kepekakan  / Deaf ness  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 325  NO. NON -PERMISSIBLE INDICATIONS   
11.  Ketagihan dadah  / Drug addiction  
12.  Hernia atau pecah  / Hernia or rupture  
13.  Penyakit mata  / Disease of the eye  
14.  Hiperten si (Darah Tinggi)  / Hypertension  
15.  Sakit otak  / Mental disorder  
16.  Kemandulan  / Infertility  
17.  Kaku  / Frigidity  
18.  Lemah fungsi seks atau impoten  / Impairment of sexual function or 
impotency  
19.  Penyakit venerus  / Venereal disease  
20.  Lemah urat saraf atau aduan atau kelemahan lain timbul daripada 
atau berhubung  kait dengan perhubungan seks  / Nervous debility 
or pother complaint of infirmity arising from or relating to sexual 
intercourse.  
 
 
2.4 PRODUCT NAME  
 
a) If the product owner wishes to use a formulary name, any am endments made to the 
product formulation such as the addition of active ingredients, removal of active 
ingredients or change in strength of active ingredients will not  be permitted.  
b) A brand name in front of the formulary name shall be required to be added,  in order to 
differentiate and identify that their product from products with the same formulary name.  
c) Any product name which is the same or similar either in writing/ pronunciation, with the 
product name of an adulterated product is prohibited . 
d) For produc ts in which the product name is the name of active ingredient or the product 
name is a common name, e.g. Kapsul Kacip Fatimah; Misal Kucing Tea ; Ortosiphon 
Capsule; Herbal Rub; Natural Herb Capsule, a brand name shall be added to the 
product name, in order  to differentiate and identify this specific product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 326  e) For single -ingredient products, in the case where the product name bears the name of 
the active ingredient, strength should be added to the product name. Example: Sunsky 
Tongkat Ali 500 mg Capsule  
f) The d osage form is required to be added to the product name in the system (i.e  in 
section A1)   
g) Justification will be required to prove the “claim” made in the product name. Example: 
“Double Strength/ Acticoat/WaterSol”  
h) Product name supported by a registered t rade mark certificate will not be accepted if 
deemed inappropriate by the Authority/ not following the regulations stated in this 
Appendix.  
i) Replacement product may used the same product name as a previously registered 
provided that the formulation (strengt h of active ingredient), product registration holder 
and dosage form of the product remains the same.  
j) The name of the active ingredient is not allowed to be used as brand name.  
k) The name of active ingredient combined with product indication is not allowed t o be 
used as product name.  
l) Product names which are not permitted to be registered are as specified in                      
Table 7  below:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 327  Table 7 :  
 
No. Non-Permissible Product Names  Example  
1.  Prohibited use of disease names as 
stated in the Medicines ( Advertisement 
and Sale) Act 1956 (Revised 1983)  Example :  
Diabetes, Asthma, Cancer  
2.  Prohibited use of a single active 
ingredient as a product name in 
products containing more than one 
active ingredient unless product name 
contains words such as ‘Plus, 
Com pound, Complex, Herbanika  Example :  
Tongkat Ali Capsule ---- 
But product contains tongkat ali, 
ginseng, ect.  
3.  Prohibited use of superlative - Names 
which indicates superiority in  efﬁcacy  Example :  
Power/ Kuasa, Superior, Pure, 
Mustajab, Safe, Healthy/ Sihat, 
Penawar/ Shifa, VIP, Good, Heal/ 
Sembuh, Premium, Mustajab, 
Men/ Women/ Children Complete, 
Men/ Women/ Children Enriched, 
Paradise/ Syurga, Menawan , 
Booster  
4.  Prohibited use of  spelling of words 
which may cause confusion  
 
Words which involve names of/part 
thereof:  
i) 20 disease names prohibited in the 
Medicines (Advertisement and Sale) 
Act 1956 (Revised 1983)  
ii) Diseases without scientiﬁc evidence of 
efficacy/ prescription medication to 
treat diseases/ parameters that 
indicate certain diseases (e.g. insulin, 
glucose)  
iii) Prohibited indication (e.g. to detoxify 
body)  Example :  
a) Go Out = GOUT  
b) UTix = Urinary Tract Infection  
c) Diabecine = Diabetes  
d) Metformon = Metformin  
e) Insuprem = Insulin  
f) Glucosey = Glucose  
g) DetoxB = Detox body  
5.  Prohibited use of names which may 
cause ambiguity  
Ambiguous product name  Example:  
B For Energy?  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 328  No. Non-Permissible Product Names  Example  
6.  Prohibited use of names which may be 
offensive or indecent  Example:  
SENXBIG=SEnXBIG(label)  
Sexy, Enjoy,  Paradise,  
Heavenly, Blue boy, Casanova, 
Desire (Dezire),Sensual 
(Xenxual),Asmara,Syok  
7.  Prohibited use of product names which 
are incoherent with the approved 
indication  
Name containing a product claim whereas 
product is indicated for more than the 
approve d indication  Example:  
Cough Syrup X= Approved 
indication for cough, dizziness, ﬂu 
and itch  
8.  Prohibited use of product names which 
has elements of ludicrous belief  
Statements referring to ancient believe/ 
negative spirits/ supernatural power  Example:  
Words such as miracle, magi c, 
magical, miraculous, saintly, 
heavenly  
9.  Prohibited use of product names similar 
to the existing approved product names  
Product names similar to the spelling and 
pronunciation of words of the existing 
product names  Example:  
Tenormin vs Tenormine vs 
Teno rmy 
Re-Liv vs Re -Lif 
10.  Prohibited use of product names which 
may cause ambiguity in the nature of 
product (drug/ food/ beverage)  
Product names similar to a food/ beverage 
product  Example:  
Juice, Health drink, Beverage, 
Kooky  
11.  Prohibited use of product nam es which 
represents professional advice or 
opinion  or referring to the profession  Example:  
Dr Sunny, Dr Noortier Rooibose 
Tea, Professo r, Herbalist, Doctor  
12.  Prohibited use of product names which 
represent weight loss/ slimming 
properties/ names that can b e  
associated with weight loss/ slim  Example:  
Slim, Langsing, Trim, Trimnfit,  
Sleen, Kurus, Susut perut,Xlim, 
Weight watcher  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 329  No. Non-Permissible Product Names  Example  
13.  Prohibited use of product names 
referring to any religious content  Example:  
Maksum, Mahmudah, Arifbillah  
14.  Name of internal orga n Example:  
Liver, Brain, Kidney, etc.  
15.  Use of abbreviation as a product name 
unless it carries no meaning  Example:  
TB, UTI, HB, etc.  
16.  Other prohibited product names  Example:  
Minda, IQ, Smart, Genius, Ultra 
Mega, Detox , Immune, Phase 2, 
Defense, Prime  
Note:  
1. This list is not meant to be exhaustive and will be reviewed from time to time  
2. The Authority reserves the right to disallow any other words or phrases for product names which 
in its opinion is misleading, improper or not factual.  
 
2.5 QUALITY C ONTROL  
 
2.5.1  SAMPLE FOR TESTING  
 
Sample for testing shall be submitted to the Center of Quality Control , NPRA  within 
14 working days from the screening approval date.  Import permit will be issued after 
screening approval for imported products.  
Applicant need to proceed for payment within 30 days once the sample is submitted.  
Delay in submission / payment will result in rejection of the new product registration 
application.  
For further information , please refer Section C:  Guideline f or Submission of 
Produc t Samples f or Laboratory Testing  in the main DRGD .  
 
2.5.2  QUALITY TESTING FOR SPECIFIC INGREDIENT  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 330  i) For  product containing Aphanizomenon flosaquae, applicants would have to  
provide certificates of analysis showing that the microcystin -LR or total 
microcystins  content of the raw material does not exceed 1μg/g and the finished 
product has  been tested for microcystin -LR using an acceptable method ; 
ii) For products  containing Red Yeast Rice ( Monascus purpureus ), applicants shall 
provide certificates of analysis (for both raw material and finished prod uct) 
showing the Monacolin -K content. The percentage of Monacolin -K shall not 
exceed 1% and the Monakolin -K consumed  shall not exceed 10 mg per day.  
 
 
2.5.3  LIMIT TEST FOR HEAVY METALS  
 
Limit for heavy metals:  
i) Lead  : NMT 10.0 mg/kg or 10.0 mg/litre (10.0ppm)  
ii) Arsenic  : NMT 5.0 mg/kg or 5.0 mg/litre (5.0ppm)  
iii) Mercury  : NMT 0.5 mg/kg or 0.5 mg/litre (0.5ppm)  
iv) Cadmium  : NMT 0.3 mg/kg or 0.3 mg/litre (0.3ppm)  
 
 
2.5.4  DISINTEGRATION TEST  
 
Disintegration time  for tablets, capsules and pills  
i) Uncoated table ts : NMT30 minutes  
ii) Film-coated tablets  : NMT 30 minutes  
iii) Sugar -coated tablets  : NMT 60 minutes  
iv) Enteric -coated 
tablets  : Does not disintegrate for 120 minutes in acid 
solution but to disintegrate within 60 minutes in 
buffer solution  
v) Capsu les : NMT 30 minutes  
vi) Pills : NMT 120 minutes  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 331  2.5.5 TEST FOR UNIFORMITY OF WEIGHT (FOR TABLETS AND CAPSULES 
ONLY)  
 i)  Tablet  
- For tablet with average weight of 130mg or less: Not more than 2 tablets differ 
from the average weight by more  than 10% AN D no tablets differ  from the 
average weight by more than 20%  
- For tablet with average weight between 130 -324mg: Not more than 2 tablets 
differ from the average weight by more than 7.5% AND no tablet differs from 
the average weights by more than 15%  
- For tabl ets with average weight more than 324mg: Not more than 2 tablets 
differ from the average weight by more than 5% AND no tablet differs from 
the average weight by more than 10%  
 
ii)   Capsule  
Individual weight of the capsule to be within the limit of 90  - 110% of the 
average weight.  
 
 
2.5.6 TESTS FOR MICROBIAL CONTAMINATION  
 
TABLE 8: 
 
A. Herbal medicinal products containing herbal drugs, with or without excipients, 
intended for the preparation of infusions and decoctions using boiling water (for 
example herbal t eas, with or without added flavourings)  
Microbiological Quality  Acceptance Criteria  
TAMC  NMT 5 x 107 CFU/g  
TYMC  NMT 5 x 105 CFU/g  
Escherichia coli  NMT 1 x 103 CFU/g  
Salmonella  Absence (25 g)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 332   
B. Herbal medicinal products containing, for example, extr acts and/or herbal drugs, 
with or without excipients, where the method of processing (for example, 
extraction) or, where appropriate, in the case of herbal drugs, of pre -treatment 
reduces the levels of organism to below those stated for this category  
Micro biological Quality  Acceptance Criteria  
TAMC  NMT 5 x 104 CFU/g or CFU/mL  
TYMC  NMT 5 x 102 CFU/g or CFU/mL  
Bile-tolerant gram -negative 
bacteria  NMT 1 x 102 CFU/g or CFU/mL  
Escherichia coli  Absence (1 g or 1 mL)  
Salmonella  Absence (25 g or 25 mL)  
 
 
C. Herb al medicinal products containing, for example, extracts and/or herbal drugs, 
with or without excipients, where it can be demonstrated that the method of 
processing (for example, extraction with low strength ethanol or water that is not 
boiling or low tempe rature concentration) or, in the case of herbal drugs, of pre -
treatment, would not reduce the level of organisms sufficiently to reach the 
criteria required under B  
Microbiological Quality  Acceptance Criteria  
TAMC  NMT 5 x 105 CFU/g or CFU/mL  
TYMC  NMT 5 x  104 CFU/g or CFU/mL  
Bile-tolerant gram -negative 
bacteria  NMT 1 x 104 CFU/g or CFU/mL  
Escherichia coli  Absence (1 g or 1 mL)  
Salmonella  Absence (25 g or 25 mL)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 333   
D. Special Ph. Eur. provision for oral dosage forms containing raw materials of 
natural (ani mal, vegetal or mineral) origin for which antimicrobial pretreatment is 
not feasible and for which the competent authority accepts TAMC of the raw 
material exceeding 103 CFU/g or CFU/mL.  
Microbiological Quality  Acceptance Criteria  
TAMC  NMT 2 x 104 CFU/g o r CFU/mL  
TYMC  NMT 2 x 102 CFU/g or CFU/mL  
Bile-tolerant gram -negative 
bacteria  NMT 1 x 102 CFU/g or CFU/mL  
Salmonella  Absence (10 g or 10 mL)  
Escherichia coli  Absence (1 g or 1 mL)  
Staphylococcus aureus  Absence (1 g or 1 mL)  
 
E. Herbal Medicine for Exte rnal use  
Route of 
Administration  TAMC  
(CFU/g or 
CFU/ml)  TYMC  
(CFU/g or 
CFU/ml)  Specified micro -organisms  
Oromucosal use  
Gingival use  
Cutaneous use  
Nasal use  
Auricular use  NMT 2 x 102 NMT 2 x 101 Absence of Staphylococcus aureus  
(1 g or 1 ml)  
 
Absence of Pseudomonas aeruginosa  
(1 g or 1 ml)  
Transdermal 
patches (limits for 
one patch 
including 
adhesive layer 
and backing layer)  NMT 2 x 102 NMT 2 x 101 Absence of Staphylococcus aureus  
(1 patch)  
 
Absence of Pseudomonas aeruginosa  
(1 patch)  
 
Notes:  
TAMC  : Total Aerobic Microbial Count  
TYMC  : Total Yeasts & Moulds Count  
NMT  : Not more than  
  [Reference: British Pharmacopoeia 2012]  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 334  2.5.7 CERTIFICATE OF ANALYSIS  (Active Ingredient)  
Applicants will have to submit a certificate of analysis for each  active ingredi ent 
used , which may  be purchased from the supplier. This requirement is not applicable 
for raw materi als that are processed in -house . 
 
2.5.8 CERTIFICATE OF ANALYSIS  (Finished Product)  
Starting from 1st January 2018, 2 batches of Certificate of Analysis (CO A) for 
Finished Product must be submitted upon submission of new product registration 
for Natural Product / Health Supplement with the general claim.  
 
           (Reference: Directive No.3 Year 2017, BPFK/PPP/07/25(8)Jld 1 :  
Direktif Untuk Menguatkuasaka n Keperluan Sijil Analisa Produk Siap (Certificate of Analysis 
(COA) For Finished Product) Semasa Permohonan Pendaftaran Baru Produk Semulajadi 
dan Produk Suplemen Kesihatan Dengan General Claim)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 335   
Example of Certificate of Anal ysis for Finished Product  (Natural Product)  
 
 Certificate of Analysis  
Company name/ Address  :  
Product Name   :  
Batch no.    :  
Dosage form    :  
Packaging    :  
Date of manufacture  :  
Date of expiry   :  
Test Parameter  Specifications  Results  Method  
Appearance/ O rganoleptic:  
Odour  
Colour   
To describe the 
characteristic  
   
Disintegration  DRGD  
   
Uniformity of weight     
Assay : 
(All standardize compound s 
claim ed on label)   
To specify  
   
Microbial Contamination 
Test  
TAMC, TYMC, specified 
microorganism  
  
DRG D 
   
Heavy Metal Contamination     
Lead (Pb)  NMT  10 ppm    
Cadmium (Cd)  NMT  0.3 ppm    
Mercury (Hg)  NMT  0.5 ppm    
Arsenic (As)  NMT  5 ppm    
NMT = Not More Than  
 
Signature   :  
Name    :  
Designation   : (At least by Quality Control Manager or equiv alent)  
Date of signature  :  
 
Note: The above parameter are only as an example, other tests may be required for specific product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 336   
 
2.6 STABILITY DATA  
 
General:  
-  The s tabilityof the product is important to ensure the quality of the traditional 
medicines and health supplement  
(TMHS) product. This is to ensure that the product specificat ions are maintained 
throughout the shelf life of product.  
 
-  Effective from 27 Nov 2014, a shelf life of 2 years will be approved for both local and 
imported products. Proposed shelf life exceeding this period will have to be 
supported by stability study  data conducted in Malaysia under zone IVb conditions 
(30±2 °C, 75±5%). For further information, please refer to the circular  Bil (27).dlm 
BPFK/ PPP/06/04Jld.7  Tempoh Hayat Simpanan (Shelf -Life) Bagi Produk Tradisional 
dan Suplemen Kesihatan (27 November 2014).  
 
- Should the applicant wish  to declare the percentage or content of the isolated 
compound of a standardized extract, the stability study should state the results of the 
assay of the isolated compound which is conducted along the proposed shelf -life. If 
results of the assay are not provided, the shelf life period approved will be not more 
than 2 years.  
 
-    The testing frequency of the stab ility data is as described below:  
 
Storage condition  Testing frequency  
Real time  Time 0, 3, 6, 9, 12, 18, 24 months a nd annually there 
after through  
Accelerated  0, 3 and 6 months  
 
Please refer to the ASEAN Guidelines on Stabiliy Study and Shelf Life o f Traditional 
Medicines and Health Supplements for further details  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 337  Stability data as shown in the following example shall be submitted for evaluation.  
 
RECOMMENDED PRESENTATION OF THE SUMMARY TABLE OF STABILITY RESULTS  
 
Product Name  : Storage Temperature , 
Relative Humidity  :  
 
Dosage Form  : Batch No.  : 
Strength  : Manufacturing Date  : 
Container/Packaging  : Date Of Report  : 
Pack Size  : Period Of The Study  : 
Testing Parameters  
(as applicable)  Specifications  Testing Frequency (Months)  
0 3 6 9 12 18 24 36 
Appearance/ 
Organoleptic 
characteristics:  
Odour  
Colour  To describe the characteristics          
Disintegration  DRGD          
Uniformity of weight  DRGD          
Assay:  
(All standard ized 
compounds claimed on 
label, if applicable)  To specify          
Microbial 
Contamination Test  
-Total Aerobic Microbial 
Count  
 
-Total Yeasts & Moulds 
Count  
 
-Test for Specified 
Microorganisms   
 
-NMT 2 x 104 CFU/g or CFU/mL  
 
 
-NMT 2 x 102 CFU/g or CFU/mL  
 
 
-NMT 1 x 102 CFU of bile -tolerant 
gram -negative bacteria in 1g or 1m L 
 
-Absence of Salmonella in 25g or 25mL  
 
-Absence of Escherichia coli in 1g or 
1mL 
 
-Absence of Staphylococcus aureus in 
1g or 1mL          
Heavy Metal 
Contamination  
-Lead (Pb)  
-Cadmium (Cd)  
-Mercury (Hg)  
-Arsenic (As)   
 
-NMT 10 ppm  
-NMT 0.3 ppm  
-NMT 0.5 ppm 
-NMT 5 ppm          
NMT = Not More Than  
Conclusion:  
 
Prepared by: (signature)    Checked by: (signature)    Approved by: (signature)  
Name:      Name:      Name:  
Designation:     Designation:     Designation:  
Date:      Date:      Date:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 338  The tabulated list of p arameters for each dosage form is presented as a guide for the 
following types of tests to be included in a stability study.  
 
Tabulated list of stability indicating parameters for traditional medicine  
 
Testing Parameters  
 
 
 
 
 
Dosage Form  
 
Organoleptic 
characteristics  
Assay  
Hardness/ 
friability  
Dissolution/ 
Disinteration  
Water content  
Viscosity  
pH 
Microbial content  
Granules/ 
Particle Seize 
variation  
Resuspendability  
Adhesiveness  
Oral powder  √ √   √   √    
Hard capsule  √ √  √ √   √    
Soft capsule  √ √  √    √    
Coated and Uncoated 
Tablet  √ √ √ √ √   √    
Coated and Uncoated 
Pill/ Pellet  √ √  √ √   √    
Suspension  √ √    √ √ √ √ √  
Solution  √ √    √ √ √    
Emulsion  √ √    √ √ √    
Semi Solid 
Preparations 
(Ointment/ Cream/ 
Gel/ Lotion/ Paste)  √ √    √ √ √    
Plaster  √ √      √   √ 
Granules  √ √   √   √ √   
Herbal Infusion Bag/ 
Herbal Tea Bag  √ √   √   √    
Pastilles  √ √   √   √    
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 339  2.7 LABELLING  REQUIREMENT  
 
a) The following information as shown in Table 9  shall be included  in the product label . 
Please refer example of label for natural products approved by the Authority, as 
shown below.  
 
No. Items  Immediate 
Label  Outer Label  Package 
Insert  Blister 
Pack  
1. Product name      
2. Dosage Form  √ √ √ √ 
3. Name of active ingredients, 
including part of  plant used      
4. Strength of active ingredient 
in weight      
5. Indication      
6. Batch number      
7. Manufacturing date      
8. Expiry date      
9. Dosage/ Use instruction      
10. Storage condition(s)  
- state temperature used in  
the stability study  
- state “Protect from light 
and moisture” (If product 
is not packed in moisture 
resistant container)      
11. Registration number (MAL)      Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 340  No. Items  Immediate 
Label  Outer Label  Package 
Insert  Blister 
Pack  
12. Name and address of 
product registration holder  
(Example: Product 
Registration Holder:  XXXXX)      
13. Name and address of 
manufacturer  
(Example: Manufacturer: 
XXXXX)   
At least name 
of town/ city 
and country 
of 
manufacturer   
At least name 
of town/ city 
and country 
of 
manufacturer    
14. Warning label (if applicable)  
e.g. Ginseng, Bee Pollen etc. 
as required under 2.7.2 
Specific Labelling 
Statements/ Warning & 
Precautions  
Note: Please refer Appendix 
9: Labelling Requirements      
15. Pack size (unit/ volume)      
16. Name and strength of 
preservativ e     
17. Name and content of 
alcohol,  where present      
18. To declare source of 
ingredients derived from 
animal origin (active 
and excipient) including 
starting materials and 
gelatine (capsule shell).      
19. Additional statement  
(if applica ble)     Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 341  No. Items  Immediate 
Label  Outer Label  Package 
Insert  Blister 
Pack  
20. Contraindication/ Precaution  
(if any)      
21. Security Label (Hologram)    #   
22. Product Description      
23. Date of Revision      
 
b) All labels and package inserts must be in Bahasa Malaysia  or English. In additional 
to this, tra nslation to another language will be allowed.  
 
c) # In case of a product without an outer carton, the security label shall be applied 
onto the immediate label. The security label shall however not be  applied onto the 
outer shrink wrap of the  product.  
 
d)  Font s ize of the product name on the label, including alphabets and numbers, 
should be equal in size.  
 
e) For a product containing 2 or more active ingredients, font size of each active 
ingredient that is highlighted on the inner/ outer carton must be of equal size  and 
equal prominence  (Note: this is not referring to the product name, but the statement 
made on the label).Justification for highlighting certain ingredients only on the 
product name / label must be provided and subject to approval by the Evaluation 
Com mittee.  
 
f) Please ensure all requirements as specified below  are stated on  the labels and 
package inserts:  
• State the weight per dosage form  
• State the quantity / content of active ingredients per dosage form  
• For products in liquid form (syrup), content of act ive ingredients shall be stated 
as follows:  
“Each ____ml (per dosage) product contains extract of the following ingredients”  
Herb X = ___mg  
Herb Y = ___mg  
• Check and correct all spelling/  grammar and translations . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 342   
g) For products meant for traditional prac titioner/ physician use, please state its primary 
use by the related traditional physician/ practitioner on the label.  
 
For example: ‘For Chinese Physician Use Only’ OR  
                      ‘For Ayurvedic Practitioner Use Only’.   
 
 
Example of label appr oved by the Authority:  
 
 
 
 
 
 
 
 
 
2.7.1 STATEMENTS TO BE STATED ON PRODUCT LABEL  
 
The following statements shall also  be sta ted on the product label, where applicable:  
• For product with an indication “F or gen eral health/ well being” or “Untuk 
kesihatan  umum ”, please state:  
- “Please consult your pharmacist /  doctor before taking this product or Sila 
merujuk kepada ahli farmasi/  doktor sebelum mengambil produk ini .” 
 
• For product with an indication “T o relieve  symptoms for…. (any illness)”  or 
“untuk mengur angkan tanda -tanda/ si mptom ….”, please state:   
 
KAPSUL PQR 
500MG  
 
 
MALXXXXXXXX T 
 
50 CAPSULE  
Hologram  This is a traditional medicine  
 
 
Please consult your pharmacist/ 
doctor before taking this product  
 
Jauhkan dari pada  capaian  
kanak -kanak  
Keep out of reach of children  
 
Indication : Traditionally used for 
women’s health  
 
Warning : Pregnancy and 
breastfeeding: Insufficient reliable 
data 
 
Keep below 30 ° celcius  
Protect from light and moisture  
 
Manufacturing date : 
Expiry date : 
Batch No. : 
 
 
 
 
 
 
 
 
Manufacturing date  : 
Expiry date : 
Batch No.  : 
 
 
 Each Capsule (Vegetable capsule) 
contains :  
 
Folium XX            200 mg 
Fructus QY          300mg  
 
Dosage  :  2 capsule taken twice a 
day after food  
 
 
 
 
Marketing authorization holder:  
Syarika t XYZ Sdn Bhd  
18, Jalan Utama  
47000 Sungai Buloh  
Selangor  
 
Manufactured by:  
Syarikat ABC Sdn Bhd  
3, Jalan Universiti  
46730 Petaling Jaya  
Selangor  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 343  - “Please consult your pharmacist / doctor if symptoms persist/  worsen  or Sila 
merujuk kepada ahli farmasi/ doktor jika simptom berlarutan/  bertambah 
teruk .” 
 
• For product with indication “To regulate menstruation/  To improve menstrual 
flow” , please state:  
“Contraindicated in pregnant women.”  
 
• For product with indication ‘ To reduce body weight’, please  state these 
statements, (unless proven otherwise):  
- “Balanced diet and regular exercise are essential.”  
- “Safety on long term use has not been established.”  
 
• “This is a traditional medicine/ Ini adalah ubat tradisional .” OR “This is a 
homeopathy medicine /Ini adalah ubat homeopati.”  
 
• Unless otherwise supported, all herbal/ traditional products label shall state 
the follo wing general cautionary statement , EXCEPT  for product with 
indication for men’s health or product for children use only:  
 “Pregnancy and breastfeeding: Insufficient reliable data”  
 
• For product with an indication to be taken/ used specially for women,  please 
refer to para 2.7.3 Cautionary Statement for Products Specially Used in 
Women.  
 
• “Keep out of reach of children & Jauh kan daripada  capaian kanak -kanak ” (in 
both Bahasa Malaysia  and English).  
 
• “Protect from light and moisture .” 
 
• Please s tate the storage c ondition according to the temperature stated in 
stability data . 
 
• For products containing  ingredients  as specified below, please add the 
required statements:  
i) Animal part(s ):  
“This product contains animal part(s). ” 
ii) Animal origin(s ):  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 344  Example: for active ing redients such as pearl, shell of oyster (Concha), 
pearl, etc  
“This product contains substance(s) from animal origin.”  
iii) Porcine :  
“This product contains animal part(s) (porcine/ pig).”  
iv) Alcoho l:  
- “This product contains alcohol .”  
- Please declare the percentage  of alcohol contained in the 
product.  
 
• For the following dosage forms , please add this statement:  
i) Topical preparations:  “For external use only.”  
ii) Liquids and suspensions:  “Shake well before use”  
 
• Labels that have the picture/graphic of the herb/ animal, sho uld not have the 
picture/graphic of only 1 particular active ingredient if the product formulation 
contains more than 1 ingredient. For multiple ingredients exceeding 2, the 
label should have picture/graphics of at least 2 ingredients on the label.  
 
• Any pa tent/ special/specific name of active ingredient/extract stated on the 
label should be positioned away from name of the active ingredient in the 
product formulation  
 
• For products to be sold in Kedai Rakyat 1 Malaysia (KR1M), logo of the 
KR1M is allowed to  be printed on the label.   However, the application has to 
be supported with the approval letter from Ministry of Economic Trade and 
Consumer Affairs Malaysia.  
 
• Any picture of the founder placed on the label must be decent and should not 
exceed 1/10th of the panel.  
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 345  2.7.2  SPECIFIC LABELLING STATEMENTS/ WARNING & PRECAUTIONS  
 
• Please refer Appendix 9: Labelling Requirements  for common substance 
(e.g. alfalfa, bee pollen, black cohosh etc.)  
• For products containing the f ollowing substance s, specific cautionary 
statement  as specified shall be included:  
No.  Substance  Specific Cautionary Statement  
1.  For product containing 
‘Anti -diarrhoea’ , 
please state:  “Contraindicated in children below 1 
year old” ( to be stated for produ cts with 
children dosing only)  
2.  For product containing 
Benzyl Alcohol/ 
Phenylmethanol (as 
preservative) , please 
state:   
3.  For products 
containing Camphor : i) The following warning  shall be stated on 
the label : 
WARNING:  
 
 
 
 
 
 
 
PRECAUTION:   
It is dangerous t o place any camphor – 
containing product into the nostril of 
children. A small amount applied this 
way may cause immediate collapse.  
- Avoid contact with the eyes.  
- Do not apply to wounds or 
damaged skin.  
ii) The following warning and precaution  
shall be stated o n product leaflet : As this preparation contains 
benzyl alcohol, its use  shall be 
avoided in children under 2 years 
of age. Not to be used in neonates.  
CAN CAUSE CONVULSION  
CONTRAINDICATED IN  CHILDREN  BELOW 
2 YEARS OF AGE.  
CAUTION MUST BE EXERCISED WHEN 
OLDER CHILDREN ARE TREATED.  
AVOID DIRECT APPLICATION INTO 
NOSTRILS  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 346  No.  Substance  Specific Cautionary Statement  
WARNING: “This product is 
contraindicated in children under 2 
years of age. Caution must be 
exercised when older children are 
treated.”  
PRECAUTION: “It is dangerous to 
place any camphor containing 
product into the nostrils of children. 
A small amount applied this way may 
cause immediate collapse.”  
4.  For pack size meant as 
samples, please state:   
 
 
2.7.3  CAUTIONARY STATEMENT FOR PRODUCTS SPECIALLY USED IN 
WOMEN   
 
Special precaution shall be given to ingredients taken during pregnancy. The 
Authority urges pregnant women to consult their medical/  traditional health care 
provider prior to taking any herbal or traditional products.   
 
Unless otherwise supported, all herbal/  traditional products label shall state  the 
following general  cautionary sta tement:  
“Pregnancy and breastfeeding: Insufficient reliable data ” 
 
However, for products containing any ingredients as listed in the following lists, i.e. 
List of Prohibited Ingredients in Pregnancy and List of Restricted Ingredients in 
Pregnancy, the foll owing cautionary statement shall be stated in the product label:  
 
i) Prohibited Ingredients in Pregnancy:  
“Contraindicated in pregnant women . Insufficient reliable data in 
breastfeeding women ” 
ii) Restricted Ingredients in Pregnancy:   Samp le not for sale  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 347  “To be used with caution in  pregnancy.  Insufficient reliable data in 
breastfeeding women ” 
 
The list of her bs contraindicated in pregnancy is rarely in agreement as most herbal 
products are used in combination. The following list has been compiled based on 
well documented information  as an ai d to the industry to comply with the labelling 
requirement for products used during pregnancy.  
 
 
Table 10 : List of Prohibited  Ingredients in Pregnancy  
 
 Latin Compendium Name  Common/ Chinese 
Name  Remarks  
A Acorus Calamus  Calamus   
 Achillea Mill efolium  Yarrow   
 Aloe barbadensis  Aloe vera   
 Angelica Archangelica  Angelica   
 Angelica sinensis  Dong Quai  When taken orally  
 Artemisia Vulgaris  Mugwort   
 Arctostaphylos Uva Ursi  Uva Ursi   
 Artemisia Absinthium  Wormwood   
 Astragalus gummifer  Tragaca nth  
B Bryonia Alba  White Bryony   
 Bupleurum chinense , 
Bupleurum falcatum  Bupleurum   
C Calendula Officinalis  Calendula   
 Calomelas  Qing fen   
 Capsella Bursa -Pastoris  Shepherd’s Purse   
 Cassia Marilandica  Senna   
 Caulophyllum Thalictroides  Blue Cohos h When taken orally  
 Chamaemelum nobile 
(Anthemis nobilis)  Roman Chamomile  When taken orally  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 348   Latin Compendium Name  Common/ Chinese 
Name  Remarks  
 Chenopodium 
Ambrosioides  Epazote   
 Cichorium intybus  Chicory   
 Cimicifuga Racemosa  Black Cohosh  When taken orally  
 Cnicus Benedictus  Blessed Thistle   
 Coniu m maculatum  Hemlock   
 Convalaria Majalis  Lily of the Valley   
 Cortex Cinnamomi  Rou Gui   
 Cortex Moutan  Mu Dan Pi   
 Crocus Sativus  Saffron   
 Croton tiglium  Ba dou   
E Epimedium grandiflorum  Horny goat weed   
 Equisetum arvense L.  Horsetail   
F Flos Car thami  Hong Hua   
 Flos Genkwa  Yuan Hua   
 Folium Sennae  Fan Xie Ye   
 Fructus Aurantii  Zhi Ke   
 Fructus Aurantii Immaturus  Zhi Shi   
G Gentiana lutea  Gentian   
 Ginkgo Biloba  Ginkgo   
 Glycyrrhiza glabra/ 
Glycyrrhiza uralensis  Licorice   
H Helleborus spp.  Hellebore   
 Hyssopus officinalis  Hissopo   
I Iris Versicolor  Blue Flag   
 Ipecac Ipecachuana  Ipecac   
J Juglans Canadensis  Butternut   
 Juglans nigra  Black Walnut   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 349   Latin Compendium Name  Common/ Chinese 
Name  Remarks  
 Juniper ( Juniperus 
communis)  Juniper Berries   
L Leonurus Cardiaca  Motherwort   
M Marrub ium Vulgare  Horehound   
 Mentha Pulegium  Pennyroyal  When used orally 
or topically  
 Monarda didyma  Bee Balm   
 Moschus berezovskii 
Flerov, Moschus sifanicus 
Przewalski, Moschus 
moschferus Linnaeus 
(Moschus)  She xiang / musk   
 Mylabris / Radix Sacchari 
Arundinacei  Ban Mao   
N Natrii Sulfas  Mang Xiao   
 Nepeta cataria  Catnip   
 Nigella sativa  Black seed/ black 
cumin   
O Oenothera biennis  L. Evening Primrose   
P Panax Ginseng, Panax 
Quinquefolius  Ginseng   
 Passiflora incarnata L. Passion Flower  When taken or ally 
 Petroselinum Crispum  Parsley   
 Podophyllum Peltatum  American Mandrake   
 Polygala Senega  Senega Snakeroot   
R Radix Euphorbiae 
Pekinensis  Jing Da Ji   
 Radix et Rhizoma Rhei  Da Huang   
 Radix Kansui/ Radix 
Euphorbiae  Kansui  Gan Sui   
 Radix Phytol accae  Shang Lu   
 Rhizoma Sparganii  San Leng   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 350   Latin Compendium Name  Common/ Chinese 
Name  Remarks  
 Resina Toxicodendri/ 
Resina Rhois Praeparata  Gan Qi   
 Rhizome et Radix Veratri  Li Lu   
 Radix Achyranthis 
Bidentatae  Niu Xi   
 Rhizome Chuanxiong  Chuan Xiong   
 Rhizome Curcumae 
Longae  Jiang Huang   
 Rhamnus  Purshiana  Cascara Sagrada   
 Rhamnus Frangula  Buckthorn   
 Rheum Palmatum  Rhubarb Root   
 Ruta Graveolens  Rue  
 Rheum Australe  Turkey Rhubarb   
S Sanguinaria Canadensis  Bloodroot   
 Semen Pharbitidis  Qian Niu Zi   
 Semen Strychni  Ma Qian Zi   
 Semen Pers icae Tao Ren   
 Serenoa repens  Saw Palmetto  When taken orally  
T Tabebuia impetiginosa  Pay D’ Arco  When taken orally  
 Tanacetum parthenium  Feverfew   
 Tanacetum Vulgare  Tansy   
 Thuja Occidentalis  Arbor Vitae   
 Turnera Diffusa  Damiana   
 Trigonella foenu m-
graecum  Fenugreek   
 Trillium Erectum  Bethroot   
 Tussilago Farfara  Coltsfoot   
V Venenum Bufonis  Chan Su   
 Viscum Album  European Mistletoe   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 351   Latin Compendium Name  Common/ Chinese 
Name  Remarks  
W Whitmania pigra Whitman, 
Hirudo nipponica Whitman, 
Whitmania acranulata 
Whitman (Hirudo)  Shui Zhi   
X Xanthox ylum Americanum  Prickley Ash   
 
Note: The list is not to be exhaustive and will be reviewed from time to time’.  
 
Table 11 : Restricted  in Pregnancy  
No. Latin Compendium Name  Common/  
Chinese Name  Remarks  
1. Zingiber Officinalis  Ginger  > 1g dry 
weight/day  
 
Note: The list is not to be exhaustive and will be reviewed from time to time’.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 352  2.7.4  PROHIBITED VISUAL/ GRAPHICS/ STATEMENT ON PACKAGING MATERIAL (LABEL, BOX, 
PACKAGE INSERT OR CONSUMER MEDICATION INFORMATION LEAFLET ) 
General requirement:   
The graphics printed  on outer and inner label has to be standardized to avoid confusion to the customers . 
 
Table 12: 
No. Subject Matter  Example(s)  Notes  
1.  Marketing strategy  
 Example:  
“Money back guarantee”  
“Buy 1 free 1”  
“ Backed by RM5 million  
product Liability Insurance”  Such statements are prohibited 
on labels, as per Medicines 
(Advertisement and Sale) Act 
1956 guideline requirements  
2.  Usage guide which promotes use of  
other product(s)  Example:  
“After consumption of this product 
(Product A), for better results, it is 
recommended to take Product B”  Not allowed  
3.  Consumer testimonial   Prohibited on product label  
4.  Clinical Trial results or any 
information on clinical trial done on Example:  Such statements are prohibited 
on labels, as per Medicines Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 353  No. Subject Matter  Example(s)  Notes  
product  
 “Clinically Tested”  
“Randomized Double Blind Placebo 
Control Clinical Study”  (Advertisement and Sale) Act 
1956 requirement  
5.  Opinion/ Name of prominent 
ﬁgure(s)/  professionals on  
product or its active ingredient/  
content  Example:  
Opinion of product/  
formulation inventor  Prohibited on product label  
6.  Label design (graphic and color)  
similar to labels from another  
company   Prohibited on product label  
7.  Statement on herbal origin  Example:  
Source from the  
Mountains of Alps  Allowed if proven true  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 354  No. Subject Matter  Example(s)  Notes  
8.  Introduction / description of  founder/ 
manufacturer / professionals  i.e.  
elaboration on the  identity of the 
founder or manufacturer  Example:  
“Manufacturer ABC is a GMP 
certified manufacturer and has 
manufactured many products.”  
“Founder Dr. ABC is a world 
renowned surgeon.”  Prohibited  on product label  
 
9.  Logo with certiﬁcation  Example : 
SIRIM/ ISO / GMP /HACCP  Prohibited on product label 
because certiﬁcation renewal is 
on a yearly basis  
10.  Name/ Statement / Logo/ registered  
trademark which does not satisfy the 
speciﬁcations of the Tradit ional Unit  Example:  
“Dr.ABC’s Formula”  
“Nothing like it”  Prohibited on product label  
11.  Patency claim/ Patency number/  
Special technique used/ superiority in 
ingredients  
(Example:  capsule coat)  Example:  
Patented technique  Allowed if proven true  
12.  Nutrit ional claims with analysis  
certiﬁcate attached  Example:  
Calorie, Fat, Protein and  others  Prohibited on product label  
This is not a food supplement.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 355  No. Subject Matter  Example(s)  Notes  
13.  Graphics or picture of internal organs  Example:  
Kidney, Heart, Nerves.  Prohibited on product label  
14.  Photograph of celebrities  Exam ple: 
Artiste, Sports person(s),  
Politician  Prohibited on product label  
15.  Gender  symbol (male or female)  (♀ and / or ♂) Prohibited on product label  
16.  Indecent photographs/ pornography / 
graphics/ images   Prohibited on product label  
17.  Graphics which are incoh erent with  
the indication  Example:  
- Noted indication is for 
constipation, but graphics on label 
shows a slim -looking lady which 
denotes indication for weight loss  
- Indication for urination but label 
graphics contains picture of a 
water hose.  Prohibited on p roduct label  
18.  Highlighting unnecessary body parts  Example:   
Indication is for general health but 
graphics on label highlights male and 
female sexual organ parts  Prohibited on product label  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 356  No. Subject Matter  Example(s)  Notes  
19.  Graphics of plants or animal which  
may cause confusion  Example:   
Radix Ginseng which is improvised 
as a male sexual organ  Prohibited on product label  
20.  Statement on sugars in traditional 
products  Example:  
- This product contains no added 
sugar  Allowable  on product label 
provided the product contains no 
fructose, gluc ose, sucrose or 
other kind of sugars with a 
potential to affect diabetics are 
not included in the formulation  
21.  Negative statements  Example:  
- No active ingredient  
- No gluten, yeast, etc  Prohibited on product label  
22.  Other statements  Example:  
- This prod uct is blended with 
premium quality  
- Certiﬁed chemical residue free  Prohibited on product label  
Notes:  
1. This list is not meant to be exhaustive and will be reviewed from time to time  
2. The Authority reserves the right to disallow any other words, phrases or  graphics for product label which in its 
opinion is misleading, improper or not factual.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 357  2.8 PARTICULARS OF PACKING  
 
• The maximum pack size allowed for all dosage forms is based on the daily dosing 
for a quantity not exceeding six (6) months usage.  
 
• Packi ng particulars to the listing of packing as follow:  
C1: Pack size and fill details by weight, or volume or quantity.  
C2: Container type  
C3: Barcode/ serial number (optional)  
C4: Recommended distributor’s price (optional)  
C5: Recommended retail price ( optional)  
 
• Measuring spoon/ device must be provided for all products in bulk powder form  
unless it is for physician use only.  
 
• Sample pack size should not exceed 20 capsules/tablets  
 
 
3. PRODUCT SPECIFIC REQUIREMENTS  
 
3.1 FOOT PATCHES  
 
A foot p atch which  contains herbs with a health claim needs to be registered with the 
Authority . 
 
Summary of registration for foot patches  is described below : 
 
a) Product Indication  
 
- Traditionally used for  
a) General health ; 
b) Promoting blood circulation ; 
c) Relieve fatigue . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 358  - If there  are other indications other than those mentioned above, applicant is required 
to submit clinical study data to support the proposed indication.  
 
b) Active ingredient/ Excipient  
 
- May only contain active ingredient which are classified under the category of Na tural 
Products (Traditional) . 
- Pharmaceutical ingredients which have dual -function as an active ingredient and 
excipient, e.g. Vitamin C can be used as excipient.  
- However the maximum allowable amount for the excipient in the traditional product 
has to foll ow the pharmacopoeia limits established. If for example in this case the 
amount of Vitamin C is more than 0.1%, the product shall be classified as an OTC 
product. The product will then have to fulfill the requirement for the registration of an 
OTC product.   
 
c) Certificate of Analysis for Finished Product  
- It is required with at least one batch data for registration.  
 
d) Certificate For Free Sale  
- CFS from the regulatory authority of the country of origin of the product depending 
on the product classification of t hat product in that country . 
 
e) Good Manufacturing Practice  
- GMP from the governmental issuing body declaring manufacturer adherence to 
GMP/ ISO or other standards depending on the classification of the product in the 
country of origin . 
 
 
3.2 HERBAL TEA  
 
Please refer to Circular Ref: (19)dlm.BPFK/PPP/01/03 Jld.3 . Pekeliling Kriteria Baru 
Pengkelasan Produk Food -Drug Int erphase (FDI).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 359   
 
3.3 HOMEOPATHIC PRODUCTS  
 
The following guidance notes are published as First Edition in October 2010  and the latest 
revision is on October 2012.  
 
This guidance notes serve  as an additional reference on the requirements for the 
registrati on of homeopathic products. Other aspects of registration requirements are 
covered in the Drug Registration Guidance Document. Applicants for product registration 
are also requested to refer to the latest edition on the Guidelines of Good Manufacturing 
Practices (GMP) for Traditional Medicines.  
 
2nd Revision  
Acknowledgements  
 
The National Pharmaceutical Regulatory Division  acknowledges its indebtedness to the 
Malaysia Homeopathic Medical Council and the Traditional & Complementary Medicine 
Division, Ministr y of Health who provided comments and advice during the preparation of 
these guidelines.  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 360  Outline:  
 
 
1. Introduction    
2. Exemptions   
3. Preparations not considered by the Authority  for registration    
4. Ingredients    
5. Quality    
6. Good Manufacturing Practice    
7. Label ling     
8. Indications for use  
Attachments:           
▪ Attachment 1: List of exempted Single Homeopathic Potentised Dilutions  
▪ Attachment 2: Negative List    
▪ Attachment 3: List of acceptable references    
▪ Attachment 4: List of endangered animal species/  protected wildlife   
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 361  1. INTRODUCTION  
 
Regulation 7(1)(a) of the Control of Drugs and Cosmetics  Regulations  (CDCR)  1984  
requires all produc ts to be registered with the Authority  prior to being manufactured, sold, 
supplied, imported or possesse d for sale, unless the product is exempted under the specific 
provisions of the regulations . 
 
Under Regulation 2, CDCR 1984, “Homeopathic medicine ” means any pharmaceutical 
dosage form used in the homeopathic therapeutic in which diseases are treated by th e use 
of minute amounts of such substances which are capable of producing in healthy persons 
symptoms similar to those of the disease being treated. This would include preparations 
that are to be chewed, sucked, swallowed whole and applied topically.  
 
Applicants are reminded that it is their responsibility to ensure that their products comply 
with these regulations and also other related legislations namely:  
(i)  Sale of Drugs Act 1952  
(ii)  Dangerous Drugs Act 1952  
(iii)  Poisons Act 1952  
(iv)   Medicines (Advertisement & Sa le) Act 1956  
(v)  Wildlife Protection Act 1972  
 
 
2. EXEMPTION  
 
All homeopathic products are registrable under the Control of Drugs and Cosmetics 
Regulations 1984 . Exemption to this are:  
i) single homeopathic potentised dilution ;  
ii) extemporaneous preparation for  an individual patient by a registered/ licensed 
homeopathic practitioner ; 
iii) All Mother Tinctures;  
iv) Unmedicated sugar globules and tablets.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 362   
3. PREPARATION NOT CONSIDERED BY THE AUTHORITY  FOR REGISTRATION  
 
The Authority  will only register homeopathic produc ts used for oral administration, nasal or 
mouth sprays and external application only. The following dosage forms will not be 
considered for registration.  
- Sterile preparations such as e ye-drops and injectables;  
- Suppositories and vaginal tablets;  
- Transderma l patch;   
- Sublingual preparations;  
- Preparation in combination with non -home opathic active ingredient, such as vitamins, 
minerals and herbs.  
- Preparations containing substance listed in the Poison List ( except Attachment 1 ). 
 
 
 
4. INGREDIENTS  
 
Homeopathic pr oducts are prepared from natural or synthetic sources that are referenced 
in pharmacopoeia monographs or other recognized documents. Not considering 
imponderable, the source materials for homeopathic medicines may consist of the 
following:  
- Plant material s uch as: roots, stems, leaves, flowers, bark, pollen, lichen, moss, ferns 
and algae;  
- Microorganisms such as: fungi, and plant parasites;  
- Animal materials such as: whole animals, animal organs, tissues, secretions;  
- Minerals and chemicals.  
 
For each medicina l ingredient, a copy of the monograph from the pharmacopoeia to which 
the applicant attests must be provided. Also for homeopathic medicines with a specific 
claim, it must be supported by the same level of evidence as for traditional products.  
 
Products c ontaining a combination of homeopathic and non -homeopathic medicinal 
ingredient will not be evaluated as a homeopathic product.  
   
 4.1 POSITIVE LIST  
 
Homeopathic medicinal ingredients are allowed as multi ingredient in homeopathic 
products and the active  ingredient must be documented in a monograph as a Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 363  homeopathic medicinal ingredient as stated in the current edition of Homeopathic 
Pharmacopoeias recognized by the Authority  listed in Attachment  3.  
 
Homeopathic products are allowed to be registered when the homeopathic medicinal 
ingredients used in their products are more than 2C or 4X.  
 
 
4.2 NEGATIVE LIST  
 
Homeopathic products containing single or multiple ingredients in Attachment 2  and 
Attachment 4  will not be registered by the Authority.  
 
 
4.3 LIMIT O F HOMEOPATHIC INGREDIENTS IN MULTI INGREDIENT 
HOMEOPATHIC   PRODUCTS  
  
Homeopathic Products are allowed to contain a maximum of 12 potentised single 
homeopathic dilutions.  
  
 
5. QUALITY  
 
A certificate of analysis (CoA) for raw material potentised dilution a nd finished product must 
be provided as proof on the dilution used.  
 
 
6. GOOD MANUFACTURING PRACTICE  
 
The requirements for Good Manufacturing Practice of the premises as outlined in the 
Guidelines on Good Manufacturing Practice (GMP) for Traditional Medici nes apply to all 
homeopathic products.  
 
 
7. LABELLING  
 
The labelling of homeopathic products is the same as for traditional products in DRGD with 
the following additional requirements:  
 
On the label of this homeopathic product:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 364  a) The word ‘homeopathic produc t’, ‘homeopathic medicine’, ‘homeopathic preparation’, 
‘homeopathic remedy’  (either one) - must appear on the innermost label of the 
container.  
b) The scientific name or common name of the active ingredient.  
c) Potency and type of scale use.  
d) Declare the percenta ge of alcohol contained in the product.  
 
 
8. INDICATIONS FOR USE  
 
Indications allowed for homeopathic product is the same as those allowed for traditional 
products in the DRGD.  
 
Recommended use or indications for specific claims must be supported by evide nce for the 
multi ingredient homeopathic products.  
 
No indication will be allowed for single homeopathic potentised dilution in the form of raw 
material and finished homeopathic product. No indications are also allowed for mother 
tinctures.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 365  ATTACHMENTS  
 
Attachment 1:  
 
List of “Single Homeopathic Potentised Dilution  (2C or 4X or 1:10000)”  exempted 
from the Poisons List.  
 
No. Ingredient  
1. Aconite  
2. Amyl nitrite  
3. Antimony  
4. Apomorphine  
5. Arsenic  
6. Barium  
7. Belladonna  
8. Bismuth  
9. Boric Acid  
10. Caffeine  
11. Cantharidin  
12. Colchinine  
13. Coniine  
14. Creosote  
15. Curare  
16. Digitalis  
17. Ephedra  
18. Ergot  
19. Gelsemium  
20. Hydrogen Cyanide  
21. Hyoscine  
22. Iodine  
23. Jaborandi  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 366  No. Ingredient  
24. Lead Acetate  
25. Lobelia Inflata  
26. Mercury  
27. Morphine  
28. Nicotine  
29. Nux Vomica  
30. Phosphorus  
31. Physostigmine  
32. Picric Acid  
33. Piper Methysticum (Kava -kava)  
34. Quebracho  
35. Quinine  
36. Radium  
37. Rauwolfia  
38. Sabadilla  
39. Santonin  
40. Sparteine  
41. Stavesacre  
42. Strophanthus  
43. Thallium  
44. Veratrum  
45. Vinca  
46. Yohimba  
  
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 367  Attachment 2:  
 
Negative List  
 
NO. SUBSTANCES  
1. Mother tincture of Narcotics   
 Homeopathic Products  
 Cannabis  
 Cocainum  
 Cocainum muriaticum  
 Coca leaves  
 Narceinum  
 Opium  
2. Mother tincture of Radiopharmaceuticals  
 Uranium  
 X-ray 
3. Mother tincture of Animal materials: Nosodes, toxins and blood 
products  
4. Mother tincture of human or human organ  
5. Mother tincture of Bacteria  
6. Mother tincture of Vir uses  
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 368   
Attachment 3:  
 
Homeopathic Pharmacopoeia from t he Follow ing Countries Will Be Accepted a s 
References  
 
NO. COUNTRIES  
1. Germany (GHP)  
2. Britain  
3. France (Phf)  
4. USA (HPUS)  
5. Pakistan  
6. India (HPI)  
7. European Pharmacopoeia  
 
 
 
 
 
 
 
Attachment 4:  
 
List of Endangered Anim al Species/ Protected Wildlife  
 
As listed in the Wildlife Protection Act.  
 
Notes:  
These lists are not exhaustive and will be amended from time to time as and when the 
need arises  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 369  REFERENCES  
 
 
a) List of Ingredie nts Prohibited and Restricted in Pregnancy  
 
1. Benchmarks for training in traditional Chinese medicine (WHO)  
2. American Pregnancy Association  
3. Natural Standards  
4. Health Canada  
5. TCM Discovery (Contraindication of Chinese Medicinal Herbs)  
6. Motherlove Herbal Company ( Herbs  to avoid while Pregnant)  
7. Green Earth Herbs (Herbs Contraindicated  in Pregnancy)  
8. Home. Caregroup.Org (Herbs during Pregnancy and Lactation)  
 
 
b) Homeopathic Products:  
 
1. Safety Issues in the Preparation of Homeopathic Medicines, World Health 
Organization , 2009.  
 
     Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 370  APPENDIX 6  : GUIDELINE ON REGULATORY CONTROL OF 
ACTIVE PHARMACEUTICAL INGREDIENTS 
(APIs) 
(Version 2 .3) 
 
 
 
Outline:  
 
 
1. Introduction  
2. Definition  
2.1 Definition o f Activ e Pharmaceutical Ingredient (API ) 
2.2 Classification o f Activ e Pharmaceutical Ingredi ent (API ) 
3. Scope  
4. Procedure f or Submission  and Related Information  
4.1 How t o Submit  
4.2 Required Information  
4.3 Other Considerations  
4.4 Processing Fee  
5. Option 1: Drug Master File (DMF)  
6. Option 2 : Certificates of Suitability (CEP)  
7. Option 3 : Full details of “Part II -S ACT D” in the Product Dossier  
8. Stability Data of API  
9. Manufacturing Site  Inspection  
10. Maintenance of Approval Status  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 371  1. INTRODUCTION  
 
1.1. A significant part of the quality of a finished product is dependent on the quality of 
the Active Pharmaceutical ingredients (APIs)  used for its formulation. Thus, a 
proper system of qualification of suppliers is necessary to ensure a constant 
sourcing of APIs of appropriate quality and to safeguard the public health interests. 
This will be done through standardized quality assessment  and inspection 
procedures.  
 
1.2. The National Pharmaceutical Regulatory Division  (NPRA ) under the purview of the 
Ministry of Health Malaysia has introduce d mandatory control of APIs as part of the 
requirements in the product registration application.  
 
1.3. The implementation began with  voluntary submission fo r New Drug Products in 
April 2011 and followed by;  
 
• Phase 1  - New Drug Products (January 2012)  
 
• Phase 2  - Scheduled Poison  
 
a) New Application (Generic Product): - 
i. Parenteral Dosage Form  : 1July 2014  
ii. Oral Dosage Form   : 1July 2016  
iii. Others     : 1 July 2018  
 
b) Registered Product (Pharmaceutical products containing Scheduled 
Poison): - 
All Dosage Form : Expire on 1 January 2020  onwards  
   
* API Information must be submitted at least one year before the expiry 
date.  
 
Refe rence:  
i) Bil (12) dlm BPFK/PPP/01/03 Jld 1 17 March 2011    
ii) BPFK/PPP/07/25 (7)  16 January 2014  
iii) Bil (11) dlm BPFK/PPP/01/03 Jld 3 27 June 2014  
 
• Phase 3  - Generic Product NOT  containing Scheduled Poison (to be 
determined)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 372   
1.4 The procedure for contr ol of APIs established by the NPRA  is based on the 
following  principles:  
 
• A general understanding of the production and qu ality control activities of the 
manufacturer;  
• Assessment of API s data and information, including changes and variations, 
submitted by  the product registration holder (PRH) /API Manufacturer . These 
data should include  the manufacturing process, material specifications and test 
data and results;  
• Assessment of the manufacturing site(s) for consistency in production and 
quality control of ra w materials, with specific emphasis on key raw materials 
and APIs  during and after purification through compliance with  Good 
Manufacturing Practice( GMP ); 
• Random sampling and testing of APIs (post -marketing surveillance) ; 
• Handling of complaints and recalls;  and 
• Monitoring of complaints from other agencies and countries.  
 
1.5. This guideline is intended to provide guidance regarding the requirement s to be  
included for API s in the quality part of the product dossier  (Part II -S). 
  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 373  2. DEFINITION  
 
2.1   DEFINITION OF ACTIV E PHARMACEUTICAL INGREDIENT (API)  
 
• Any substance  or mixture of substances intended to be used in the 
manufacture  of a pharmaceutical dosage form and that, when used  so, 
becomes an active ingredient of that pharmaceutical dosage form. Such 
substances are in tended  to furnish pharmacological activity or other direct 
effect in the diagnosis, cure,  mitigation, treatment or prevention of disease or to 
affect the structure and fun ction of the body (WHO Technical Report Series 
No.970,2012).  
 
2.2  CLASSIFICATION OF ACTIVE PHARMACEUTICAL INGREDIENT (API)  
 
API classification  can be divided into:  
• Inorganic substance s; 
• Organic substances (isolated from material s of animal or human or igin); 
and 
• Organic substances (synthetic or semi -synthetic or isolated from herbal 
sources or micro -organisms).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 374  3. SCOPE  
 
3.1. This Guideline encompasses the final  APIs of new products for registratio n and 
current/ exist in registered products.  This is applicable to all pharmaceutical  
products (excluding traditional products , veterinary products, and health 
supplement  products ) both locally manufactured and  imported.  
 
3.2. Biological active substances and immunological active substances are excluded 
from the scope of this Guideline . Please refer to relevant guidelines available for 
Biologics.  
 
3.3. APIs used in products for export only (FEO) are exempted from the requirement for 
submission of the Drug Master File (DMF) and Certification of Suitability (CEP)  in 
the product application.  
 
3.4. Premixing of API is part of the product manufacturing process; therefore 
information on premixed API sh ould be submitted under Part II -P. Submission for 
Part II -S solely includes information on API only.  
 
3.5. Separate registration  of the API  is not  requirement for the purpose of product 
registration. However, the required technical documentation pertaining to each API 
should be submitted with the new product registration application.  
 
3.6. Assessment of an API will be performed once sub mission of a new product 
registration application has been done.  
 
3.7. Assessment of an API will also be performed for a registered product prior to a 
product renewal application (as stated in item 1.3).  
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 375   
4. PROCEDURE FOR SUBMISSION AND RELATED INFORM ATION  
 
4.1 HOW TO SUBMIT  
 
The API (s) information can be submitted to NPRA through  one of the following three 
options:  
• Option 1: Drug Master File (DMF) procedure;  or 
• Option 2: Certificate of suitability of the European Pharmacopoeia (CEP);  or 
• Option 3: F ull details of “Part II -S ACTD” in the Product Dossier  
 
Note:  
- The PRH should attach:  
i) a cover letter (clearly indicating the product name, API name, option 
for API submission) and  
ii) API submission checklist  
http://npra.moh.gov.my/index.php/guidelines -central  
 
- The PRH shall submit Part II-S ACTD as part of product applicatio n. In cases 
where required information as per ACTD is not available,  the DMF is 
accepted.  
 
- The DMF m ust be submitted via  electronic copy (CD) directly to the NP RA to 
maintain confidentiality of the contents.  
 
- The NPRA may accept a CEP issued by European Directorate for the Quality 
of Medicine (EDQM) in lieu of the DMF of an API.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 376  4.2 REQUIRED INFORMATION  
 
4.2.1  Documents required for each option of API Information submission are 
summarized as in table 1:  
 
Table 1:  
Summary of documents required for API Information Submission:  
 
Option  Documents required  
Option 1  
(DMF)  • Part II -S ACTD via the online system  (Open Pa rt only)  
• DMF ( See Section 5  for details ) 
• Current GMP certificate or any other evidence of GMP 
compliance from a regulatory authority; and  
• Current Certificates of Analysis of API from API 
Manufacturer and finished product manufacturer (2 
batches each).  
Option 2  
(CEP)  • Part II-S ACTD via the online system  (as deemed 
appropriate)  
• CEP ( See Section 6  for details ); and,  
• Current Certificates of Analysis of API from API 
Manufacturer and finished product manufacturer (2 
batches each).  
Option 3  
(Full 
ACTD)  • Full d etails of  Part II -S ACTD  via the online 
system. (See Section 7 for details)  
• Current GMP certificate or any other evidence of GMP 
compliance from a regulatory authority; and,  
• Current Certificates of Analysis of API from API 
Manufacturer and finished product  manufacturer (2 
batches each).  
*GMP certificates for ALL manufacturers involved in manufacturing 
process of API.  
 
 
4.2.1    Separate API information must be provided for each  API for:  
i. Finished product contains more than one API  
ii. API from different manufacturing site 
iii. API from different synthesis route  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 377  4.2.2  In order to gain approval for an API;  
• The data should be sufficient to justify the specifications and testing of 
the API (including validated analytical  methods);  
• The information should confirm the identity a nd stability of the API by 
providing appropriate structure elucidation and stability studies ; and  
• The control of the API manufacturing process as well as the ability to 
produce a n API with reproducible physical p roperties and impurity 
profiles should be de monstrated.  
 
4.2.3  The NPRA reserves the right to request for any additional information about 
the API when deemed appropriate.  
 
 
4.3 OTHER CONSIDERATIONS  
 
In the spirit of harmonis ation of r egulatory activities and optimis ation of efficient 
assessment, The NPRA may  take into consideration the evaluation of relevant 
APIs by the regulatory authorities of the reference countries (Australia, Japan, 
France,  Switzerland, United Kingdom, Canada, Sweden, and the United State of 
America ) and, other PIC/S countries  and World Health Organization (WHO).  
 
 
4.4 PROCESSING FEE  
 
Not required as the API applica tion is already incorporated in the application for 
product  registration . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 378  5. OPTION 1 : DRUG MASTER FILE (DMF)  
 
5.1. The Drug Master File (DMF) is a document that  may used to  provide  confidential 
detailed information about facilities, processes, or articles used in the 
manufacturing, processing, packaging, and storing of one or more human drugs.  
 
5.2. The DMF submitted to the NPRA should contain the information as required  
under se ctions listed in Part II -S ACTD.  
 
5.3. DMF is generally created to allow an  authorized party other than the holder of the 
DMF to refer the DMF  without disclosing the contents of the file to any other  
party.  
 
5.4. The ICH M4Q Technical Guideline  and ASEAN Common Tech nical 
Requirements (ACTR) / ACTD  provide details on the information to be included 
in the API sections of an application dossier.  
 
5.5. Where the API and the finished product are manufactured by the same 
manufacturer, information on the production, quality cont rol and stability of the 
API may be submitted as part of the dossier for the finished product (ACTD) 
rather than in a separate DMF. However, the company is not precluded from 
submitting a DMF for the API.  
 
5.6. The DMF is divided into two parts , namely  the Open  (or PRH’s) part and the 
Closed (or restricted) part.  
 
5.7 The documents required  for an application making a reference to a DMF are as 
follows:  
 
• From the PRH :  
o Open part  of the DMF, as part of the submitted  product dossier (t he open 
part contains most of the  information in  Part II-S (ACTD) - i.e. sections S1, 
S2.1 and S3 to S7 ); 
▪ S1 General Information  
  1.1 Nomenclature  
  1.2 Structure  
  1.3 General Properties  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 379  ▪ S2 Manufacture  
  2.1 Manufacture (s)/Site of Manufacture  
- ALL manufacturers involved in manufactu ring process of API.   
 
▪ S3 Characterisation  
  3.1 Elucidation of Structure and other Characteristics  
  3.2 Impurities  
 
▪ S4 Control of API/Drug Substance  
From API manufacturer:  
 4.1 Specification  of API  
 4.2 Analytical Procedures  
 4.3 Validation of Analytica l Procedures  
 4.4 Batch Analysis -minimum  three  batches  
Certificate of Analysis (COA) -minimum two batches.  
4.5 Justification of Specification  
 
 From Finished p roduct manufacturer:  
     4.1 Specification of API  
Certificate of Analysis (COA) -minimum two batches.  
 
▪ S5 Reference Standards or Materials  
( from API manufacturer AND  finished product manufacturer).  
 
▪ S6 Container Closure System  
 
▪ S7 Stability  
 
• From the API Manufacturer:  
o The Complete DMF (open part AND closed part); S1-S7. 
The closed part contains the confi dential information in section Part II -S 
ACTD  - i.e. section S2); 
▪ S2 Manufacture  
2.1 Manufacture (s)/ Site of Manufacture  
2.2 Description of Manufacturing Process and Process 
Controls  
2.3 Control of Materials  
2.4 Controls of Critical Steps and  Intermediates  
2.5 Process Validation and/or Evaluation  
2.6 Manufacturing Process Development  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 380   
 
o An original Letter of Access.  
The Letter of Access from API Manufacturer/ holder of the DMF authorizes 
the NPRA to refer to the DMF, in support of the application for a finished 
product . Thus, the Letter of Access must state the following:  
 
• The name of the finished product (product name, dosage form and 
product strength) to be registered;  
• The PRH responsible for finished product registration; and, 
• A declaration that both the  PRH and the NPRA shall be notified of any 
change in the API specification or in the manufacturing  process that 
will likely affect the product’s quality or safety.  
 
The PRH is responsible  to ensure that the complete DMF (i.e. both the Open part 
and the closed part ) submitted to NPRA directly by the API Manufacturer . 
 
5.8. The API Manufacturer may submit the DMF via electronic copy ( CD) directly to 
the NPRA to maintain confidentiality of the contents. The information contained 
in the closed part of  the DMF will be regarded as confidential and will only be 
evaluated in support of the applications mentioned in the Letter of Access. The 
confidential information will not be disclosed to any third party without a written 
authorization from the API Manufacturer.  
 
5.9. Sepa rate DMF must be provided for each  API for:  
i. Finished product contains more than one API  
ii. API from different manufacturing site  
iii. API from different synthesis route  
 
5.10.  Upon receipt of the DMF, a BPFK/NPRA  DMF  number will be assigned to the 
application for produc t registration. For future correspondences, the PRH and 
the API Manufacturer should make a reference to the BPFK/NPRA  DMF 
number.  The NPRA will directly contact API Manufacturer for any 
correspondence pertaining to API information in closed part. The PRH i s 
required to include a copy of the API Manufacturer’s Letter of Access in the 
application.  
 
5.11.  API Manufacturer  is responsible to maintain and update the DMF. The PRH  
should  file a variation once they are notified with the  changes to the DMF.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 381  5.12.   API Manufact urer Obligations:  
• Any change or addition, including a change in authorization related to specific 
PRH , shall be submitted to the NPRA in duplicate and adequately cross -
referenced to previous submission(s). The reference should include the 
date(s), volume(s ), section(s), and/or page number(s) affected.  
• Should any change to a DMF is necessary, the API Manufacturer shall notify 
each affected PRH who has referenced the DMF of the pertinent change. 
Such notice should be provided well before making the change in order to 
permit the PRH to supplement or amend any affected application(s) as 
needed.  
 
5.13.  The DMF is not required for common inorganic salts (for example, sodium 
chloride, and other common electrolytes) used and regarded as API in products 
such as injections and dialysis solutions, and simple organic compounds 
available commercially in high purity (for example, natural occurring organic 
acids and their salts, including ascorbic acid and sodium citrate, and simple 
mono - and disaccharides such as glucose and suc rose). Although a DMF is not 
required for these  API, evidence needs to be submitted by the  PRH that the API 
is obtained from a reliable source and consistently comply with the applicable 
pharmacopoeial specifications. Any non -pharmacopoeial specifications need to 
be assessed by the NPRA to determine their appropriateness and adequacy to 
ensure the quality of the API.  
 
5.14.  Where a DMF is submitted for an API controlled according to a pharmacopoeia 
monograph, the DMF should include a discussion of the potential i mpurities 
most likely to arise during synthesis using the  actual manufacturing process 
described in the DMF together with evidence that these impurities are 
adequately controlled by the test procedures described in the pharmacopoeia 
monograph. Where partic ular impurities found in the substance are not listed in 
the monograph, a justification (including toxicological data, if appropriate) should 
be provided. Details on the principles for the control of impurities (e.g. reporting, 
identification and qualifica tion) are outlined in the ICH Q3Aand Q3C guidelines.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 382  6. OPTION 2  : CERTIFICATES OF SUITABILITY (CEP)  
 
6.1. CEP stands for certification of suitability of European Pharmacopoeia 
monographs/Certificate of Pharmacopoeia.  
 
6.2. The CEP is a document that used to demon strate the purity of a given API 
produced by a given manufacturer is suitably controlled by the relevant 
monograph(s) of the European Pharmacopoeia. By demonstrating grant a CEP  for 
given API , the suppliers of  the API can prove such suitability to their 
pharmaceutical  industry clients and  the NPRA.  
 
6.3. The PRH should submit a copy of the most current  CEP including all annexes , 
together with the following:  
 
• A written assurance that  no significant changes in the manufacturing method s 
or processing have taken pl ace following the granting of the certificate or its 
last revision  and  
• A declaration from the API Manufacturer that the PRH and the NPRA shall be 
notified of any future change in the API specifications or in the manufacturing 
process that  will likely aff ect the product’s quality or safety.  
 
Note:    All such written statements must state the  name of the finished product  
(product name, dosage form and product strength) to be registered and the 
PRH  shall responsible for finished product registration.  
 
6.4. Along with the CEP, the PRH should submit the following information in the 
product dossier.  
 
▪ S1 General Information  
▪ S.1.1 Nomenclature  
▪ S.1.2 Structure  
 
▪ S.1.3 General properties  - discussions on any additional applicable 
physic ochemical and other relevant API properties that are not controlled by 
the CEP and Ph.Eur. monograph, e.g. solubilities and polymorphs as per 
guidance in this section.  
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 383  ▪ S2 Manufacture  
  2.1 Manufacture(s) / Site of Manufacture  
- ALL manufacturers invol ved in manufacturing process of API.   
 
2.5 Process Validation and/or Evaluation  
In the case of sterile APIs, data on the sterilization process of 
the API, includ ing validation data, should be included in the 
product dossier(S 2.5).  
 
▪ S.3.1Elucidation of st ructure and other characteristics - studies to identify 
polymorphs (exception: where the CEP specifies a polymorphic form) and 
particle size distribution, where applicable, as per guidance in this section.  
 
▪ S.4.1 Specification  
i. The specification from the AP I manufacturer  
ii. The specification of the finished product manufacturer  
 
Note: Specification should include  all tests and limits of the CEP and 
Ph.Eur. monograph and any additional tests and acceptance criteria 
that were  not controlled in the CEP and Ph.Eur.  monograph, such as 
polymorphs, impurities and/or particle size distribution.  
 
▪    S.4.2/ S.4.3 Analytical procedures and validation – for any methods used 
by the API manufacturer and  in addition to those in the CEP and Ph.Eur. 
monograph.  
 
▪ S.4.4 Batch analy sis 
i. Results from minimum three  batches of at least pilot scale, 
demonstrating compliance with Ph. Eur. monograph and including 
any additional tests/limits listed on the CEP (e.g. residual solvents, 
additional impurity tests) . 
ii. Certificate of Ana lysis (COA) -minimum two batches each from both  
API manufacturer and finished product manufacturer.  
 
▪ S.5 Reference standards or materials  – information on reference standards 
from both  API manufacturer and finished product manufacturer.  
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 384  ▪ S.6 Container closure syste m- specifications including descriptions and 
identification of primary packaging components. Exception:  where the CEP 
specifies a container closure system and the PRH  declares to use the same 
container closure system.  
 
▪ S.7 Stability  
i. Proposed retest period , or shelf life  
ii. Proposed storage condition (temperature and packaging)  
iii. Stability data  
Exception : where the CEP specifies a re -test period that is the same as 
or of longer duration, and storage conditions which are the same or 
higher temperature and humid ity as proposed by the PRH.  
 
6.5 The NPRA reserves the right to request for any additional information about the  
API when  deemed appropriate.  
 
6.6   The PRH is responsible to submit the latest CEP updates , with annexes, as soon 
as it is available from the API Manu facturer.  
 
6.7   Separate CEP must be provided for each  API for:  
i. Finished product contains more than one API  
ii. API from different manufacturing site  
iii. API from different synthesis route  
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 385   
7. OPTION 3 : FULL DETAILS OF “PART II -S : ACTD” IN THE PRODUCT 
DOSSIER  
 
7.1. Information on the API sections  (ACTD Part II -S: S1-S7),including full details of 
chemistry, manufacturing process, quality controls during manufacturing and 
process validation for the API, should be submitted in the product dossier.  
 
7.2. The ICH M4Q Technical Guideline and ASEAN Common Technical  Requirements 
(ACTR) / ACTD  provide details on the information to be included in  the API 
sections of an application dossier.  
▪ S1 General Information  
  1.1 Nomenclature  
  1.2 Structure  
  1.3 General Properties  
 
▪ S2 Manufacture  
2.1 Manufacture(s)/ Site of Manufacture  
- ALL manufacturers involved in manufacturing process of API.   
2.2 Description of Manufacturing Process and Process Controls  
2.3 Control of Materials  
2.4 Controls of Critical Steps and Intermediates  
2.5 Process Validation and/or Evaluation  
2.6 Manufacturing Process Development  
 
▪ S3 Characterisation  
  3.1 Elucidation of Structure and other Characteristics  
  3.2 Impurities  
 
▪ S4 Control of API/Drug Substance  
 (submission should include information from API m anufacturer AND  
finished product manufacturer).  
 4.1 Specification of API  
 4.2 Analytical Procedures  
 4.3 Validation of Analytical Procedures  
 4.4 Batch Analysis -minimum  three batches,  
Certificate of Analysis (COA) -minimum two batches.  
     4.5 Justificat ion of Specification  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 386   
▪ S5 Reference Standards or Materials  
(from API manufacturer AND  finished product manufacturer).  
 
▪ S6 Container Closure System  
 
▪ S7 Stability  
 
7.3. Separate dossier (Part II-S : ACTD) must be provided for each  API for:  
i. Finished product contai ns more than one API  
ii. API from different manufacturing site  
iii. API from different synthesis route  
 
7.4. Where the API and the finished product are manufactured by the same company, 
information on the production, quality control and stability of the API may be 
submi tted as part of the dossier for the finished product (ACTD) rather than in a 
separate DMF. However, the company is not precluded from submitting a DMF for 
the API.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 387  8. STABILITY DATA OF API  
 
8.1. Current stability test data for an API should b e provided , for at least  3 primary  
batches . These data should  include:  
 
• The type of stability study and stability protocol  
• API name, API manufacturer, packaging particular  
• Batch details ( e.g., batch number, date of manufacture , batch size  
• The general test  methodology ( e.g., duration of study, storage conditions of 
temperature and humidity , list of relevant testing, testing frequency, etc.);  
• Proposed retest period or shelf -life; 
• Proposed storage condition;  
A storage temperature must be specified, e.g:  
- Do no t store above 25 °C  
- Do not store above 30 °C  
- Store in a refrigerator (2 °C to 8 °C)  
- Store in freezer  
                  Other special storage condition , e.g:  
       -     Protect from light  
       -     Protect from moisture  
 
   
• The analytical test methods (e.g., assay method of quantitation, determination 
of degr adation products, moisture etc) with reference;  
• Validation of test methods;  
• Specification ; 
• Results of tests;  and, 
• Conclusions.  
 
8.2. In circumstances where  an API retest period has not been established  and 
complete  long term  stability data is not available  at the time  of submission, the 
minimum  stability data required are as follows:  
 
• At least 12 months of long term data and 6 months of accelerated data on at 
least  3primary batches of the API ;  
• The b atches should be at least pilot scale -sized and manufactured by a method 
that simulates the final commercial process.  
 * In view of this, the re -test date may be extended beyond the end of long term 
studies which can be extrapolated not more than 12 months covered by the  long 
term data.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 388  A letter of commitment (to provide complete long term stability data when study 
is completed/when requested)  should be submitted.  
 
8.3. Where the API is sourced from multiple sites or from different route of synthesis, 
stability data from each  source should be provided.  
 
8.4. The NPRA may request for additional stability data if deemed necessary for the 
evaluation of the application.  
 
8.5. Stability data is not required  where the CEP specifies a re -test period that is the 
same as or of long er duration than the re -test period proposed by the PRH.  
 
 
9. MANUFACTURING SITE INSPECTION  
 
9.1. Depending on the outcome of the evaluation of the API dossier, a risk -based 
approach will be used in the planning of manufacturing site inspections ; the 
approach wil l take  into account the typ e of APIs as well as the  outcome, results 
and reports of  inspections conducted by other regulatory  authorities or competent 
organiz ations.  
 
9.2. The NPRA shall plan and coordinate the performance of inspections at the 
manufacturing s ite of the API  and that of the key intermediate (if relevant)  to 
assess compliance with the relevant sections of the relevant GMP Guidelines, and 
to compare the technical information on the manufacturing process given in the 
API dossier with the manufactur ing process actually carried out on the  
manufacturing  site.  
 
9.3. All such inspections shall be performed by inspectors deemed to possess sufficient 
qualifications and experience.  In order to perform such inspections, the inspectors 
have to  be competent in are as such as production and quality control of 
pharmaceuticals, and have appropriate experience  in the area of  GMP. Such 
inspectors shall perform the inspections and report on its findings in accordance  
with established S tandard Operating Procedure s (SOPs)  so as to ensure a 
standard harmoniz ed approach.  
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 389  10. MAINTENANCE OF APPROVAL STATUS  
 
10.1.  Manufacturer  of finished product should  establish a mechanism by which 
manufacturers/suppliers of an API shall provide information on any changes                 
(i.e., var iations) in manufacture and control that may have impact on the  safety, 
purity and quality of the API. The PRH is responsible to  provide  the NPRA with the 
appropriate documentation (referring to relevant parts of  the dossier) to prove that 
any intended or implemented variation will not have  an impact on the safety, purity  
and quality of the API that has been previously  approved. For those APIs approved 
by the NPRA, an evaluation of such  variations shall be performed with accordance 
to the Malaysian  Variatio n Guidelines  (MVG) . 
 
10.2.  Random samples of APIs supplied to manufacturers of finished products may be 
taken for independent testing if needed. Certificates of Analysis released by the 
API Manufacturer as well as specifications for test methods shall be provide d by 
the API Manufacturer or the PRH to the NPRA for review upon request. In the 
event of failure to meet the established criteria for testing, the NPRA shall proceed 
to investigate  and communicate this problem to the manufacturer concerned.  
 
10.3.  The NPRA may conduct a re -evaluation of the APIs at a 5 years interval. If, as a 
result of this re -evaluation, found that an API and/or specified manufacturing site(s) 
no longer complies with the recommended standards, such APIs and 
manufacturing sites will be removed  from the approved list. Prior notice to the PRH 
and API Manufacturer shall be issued from the NPRA regarding such decision.  
 
10.4.  Re-evaluation may also be done in any situation deemed necessary, including the 
following :   
• If any omissions by the manufacturer in the initial assessment procedure or 
during the follow -up activities is evident in relation to the requirements. This 
includes  compliance with GMP.  
 
• If any batch(s) of supplied API is considered not to be in compliance with the 
agreed specification of th e API;  
 
• If the CEP, or an API for which a CEP dossier was submitted, is cancelled or 
refused based on the assessment of the dossier for any other reason;  and, 
 
• If in the opinion of the NPRA, changes made in the sourcing of key 
intermediates, route of synth esis, facility or other production, require that 
reassessment be made.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 390  REFERENCES AND GUIDE LINES  
 
a) Guidelines on the Technical Requirements Related to the Quality of Active 
Pharmaceutical Ingredients  
 
The technical requirements related to the quality of act ive pharmaceutical ingredients 
have already been addressed elsewhere, (such as in the ASEAN,  WHO,  ICH, EDQM 
and EMA guidelines), and PRH  are advised to refer to these guidelines available at the 
relevant website such as:  
 
• Guideline on Submission of Documen tation for a Multisource (Generic) Finished 
Pharmaceutical Product (FPP): Quality Part  
http://apps.who.int/prequal/info_general/documents/TRS970/TRS_970 -Annex4.pdf  
 
• Guideli ne on Active Pharmaceutical Ingredient Master File (APIMF) Procedure . 
(http://apps.who.int/prequal/info_applicants/Guidelines/APIMF_Guide.pdf ) 
 
• The ASEAN  Common Technica l Dossier (ACTD) For The Registration Of 
Pharmaceuticals For Human Use Organization Of The Dossier  
http://npra.moh.gov.my/index.php/guidelines -central  
 
• The Common Technical Document For Th e Registration Of Pharmaceuticals For 
Human Use: Quality – M4Q(R1)  
(http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/CTD/M4_R1_Quality/
M4Q__R1_.pdf )  
 
• Impurities in New Drug Substances  
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3A
_R2/Step4/Q3A_R2__Guideline.pdf  
 
• Impurities: Guideline For Residual Solvents  
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C
/Step4/Q3C_R6_Step4.pdf  
 
• Specifications: Test Procedures and Acceptance Criteria for New  Drug Substances 
and New Drug Products: Chemical Substances Q6A  
http://www.ich.org/products/guidelines/quality/article/quality -guidelines.html  
 
• Good Manufacturin g Practice Guide for Active Pharmaceutical Ingredients Q7  
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/
Step4/Q7_Guideline.pdf  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 391  • Development and Manufacture of Drug Substances (Chemical Entities and 
Biotechnological/Biological Entities) Q11  
http:// www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/
Q11_Step_4.pdf  
 
• Guideline on Summary of Requirements for Active Substances . In The   Quality 
Part of the Dossier .  
(http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/
09/WC500002813.pdf ) 
 
• Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 
04 1 4R)  
http://www.edqm.eu/medias/fichiers/Content_of_the_Dossier_for_Chemical_Purity_
Microbiological_Quality.pdf  
 
• Content of the Dossier for a Substance for TSE Risk Assessment (PA/PH/CEP (06) 
2) 
http://www.edqm.eu/medias/fichiers/Content_of_the_Dossier_for_a_Substance_for_
TSE_Risk_Assessment.pdf  
 
• Certificates of Suitability for Sterile Active Substances (PA/PH/Exp. CEP/T (06) 13, 
1R) 
http://www.edqm.eu/en/New -Applications -29.html  
 
• Certification database for information on Certificates of Suitability (CEPs) granted by 
the EDQM.  
https://extranet.edqm.eu/publications/recherches_CEP.shtml  
 
• WHO  List of Prequalified Active Pharmaceutical Ingredients  
http://apps.who.int/prequal/info_applicants/API_PQ -List.htm  
 
b) Guidelines on Stability Testing  
 
 The following Guidelines may  be consulted in the context of stability testing:  
 
• WHO Technical Report Seri es, No. 953, 2009 Annex 2:  Stability testing of Active 
Pharmaceutical Ingredients and Finished Pharmaceutical P roducts   
(http://www.who.int/medicines/publications/pharm prep/PDF_TRS953_WEB.pdf ) 
 
• International Conference on Harmonisation. ICH Q1A (R2): Stability testingof new 
drug substances and products  
(http://www.ich.org/LOB/media/MEDIA419.pdf ) 
 
• International Co nference on Harmonisation. ICH Q1B: Photostability testing  of new 
drug substances and products  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 392  (http://www.ich.org/LOB/media/MEDIA412.pdf ) 
• International Conference on Harmonisation . ICH Q1C: Stabili ty testing of new dosage 
forms  
(http://www.ich.org/LOB/media/MEDIA413.pdf ). 
 
• International Conference on Harmonisation. ICH Q1D: Bracketing and  matrixing 
designs for stability testing of new drug sub stances and products  
(http://www.ich.org/LOB/media/MEDIA414.pdf ). 
 
• International Conference on Harmonisation. ICH Q1E: Evaluation for stability data 
(http://www.ich.org/LOB/media/MEDIA415.pdf ). 
 
• Note for Guidance o n Stability Testing : Stability Testing Of New Drug Substances 
And Products (CPMP/ICH/2736/99)  
(http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/
09/WC500002651.pdf ) 
 
• Note for Guidance  on Stability  Testing of Existing Active Substances and   
Related  Finished Products  
(www.ema.europa.eu/pdfs/vet/qwp/084699en.pdf ) 
 
• ASEAN Stability Guideline  
http://npra.moh.gov.my/index.php/guidelines -central  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 393  APPENDIX 7:  SPECIAL  CONDITIONS FOR REGISTRATION FOR 
A PARTICULAR PRODUCT OR GROUP OF PRODUCTS   
 
 
1. BLOOD PRODUCTS  
a) Each batch of the products must comply with WHO requirements for the 
product.  
b) Each batch of the product imported into Malaysia must be accompanied with a 
Batch Rel ease Certificate from the relevant authority in the country of 
manufacture.  
c) Each batch of the product must be accompanied with a certificate confirming 
that the blood or plasma used in the production of the lot is tested and found to 
be negative for HIV an tibody, HbsAg, HCV and high -risk donors are excluded.  
d) Each batch of the product must be accompanied with a certificate of analysis.  
 
 
2. ETRETINATE/ ACITRETIN  
a) The product shall only be sold or supplied to:  
i) Dermatologist (Skin Specialist) who are gazetted with  the Ministry of 
Health, Malaysia, or registered with the Academy of Medicine, Malaysia, 
Specialist Registry  and Approved by the Drug Control Authority .  
ii) A hospital or Institution maintained by the government, having the 
services of a skin specialist or re gistered medical practitioner with 
experience in dermatology.  
b) The container of the product shall be labeled in a conspicuous and distinct 
manner, with the following statements:  
i) “Etretinate/ Acitretin is highly teratogenic . 
ii) Pregnancy must be avoided during treatment and for at least three years 
after completing treatment.”  
c) A proper record of product supplied stating the product name, product 
registration number, name, address and contact number of purchaser 
(prescriber) shall be kept and submitted to the Aut hority upon request.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 394  d) The following records shall be maintained for the product and well kept for 
auditing by the Authority.  
 
 
 
3. HUMAN GROWTH HORMONE (Somatotropin, Somatropin)  
A proper record of product supplied stating the product name, product registrati on 
number, name, address and contact number of purchaser (prescriber) shall be kept 
and submitted to the Authority  upon request.  
 
 
4. ISOTRETENOIN/ TRETINOIN  
a) The product shall only be sold or supplied to:  
i) Dermatologist (Skin Specialist)  who are gazetted with  the Ministry of 
Health, Malaysia, or registered with the Academy of Medicine, Malaysia, 
Specialist Registry  and Approved by the Drug Control Authority . 
ii) A hospital or institution maintained by the government, having the 
services of a skin specialist or reg istered medical practitioner with 
experience in dermatology.  
b) The container of the product shall be labelled in a conspicuous and distinct 
manner, with the following statements:  
i) “Isotretinoin/ tretinoin is highly teratogenic . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 395  ii) Pregnancy must be avoided durin g treatment and for at least 1 month 
after completing treatment.”  
c) A proper record of product supplied stating the product name, product 
registration number, name, address and contact number of purchaser 
(prescriber) shall be kept and submitted to the Autho rity upon request.  
 
 
5. KETOCONAZOLE  
 
Products containing oral ketoconazole are restricted for  hospital  use only.  
 
 
6. MIDAZOLAM  
 
Products containing midazolam are restricted f or use in government and private 
hospitals  and specialist clinics  only.  
 
 
7. PARACETAMOL IN COMBINATION WITH CAFFEINE  
a) For products containing a combination of paracetamol and caffeine, dose unit 
of caffeine for adults is 65mg and maximum dose of caffeine is 520mg per 
day, meanwhile, dose unit for paracetamol is 500mg with the maximum dose 
of 4,000mg per day or 8 tablets daily.  
b) Products containing caffeine for pediatrics are not allowed.  
c) Allowable packing size should not exceed 20 tablets/ capsules.  
 
8. PARACETAMOL INTRAVENOUS INJECTION  
a) Products containing paracetamol in the form of intravenous injection are 
restricted for hospital use only.  
 
9. VACCINES  
a) Each batch of the product must comply with WHO requirements for the 
product.  
b) Each batch of the product imported into Malaysia must be accompanied with a 
batch release certificate.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 396  APPENDIX 8:  LIST OF PERMITTED, PROHIBITED AND 
RESTRICTED SUBSTANCES  
 
 
 
 
 
 
 
Outline:  
 
8.1  List of Prohibited and Restricted Active Ingredients and Combination  
 8.1.1  List of Prohibited Active Ingredients and Combinations  
  a) Specific Active Ingredients  
  b) Combinations  
 
 8.1.2  List of Restricted Active Ingredients and Combinations  
  a) Specific Active Ingredients  
  b) Combinations  
 
8.2 List of Prohibited and Restricted Excipients  
 8.2.1  List of Prohibited Excipients  
 8.2.2  List of Restricted Excipients  
 
8.3 List of Permi tted and Restricted Colouring Agents  
 8.3.1  List of Permitted Colouring Agents  
 8.3.2  List of Restricted Colouring Agents  
 
  
IMPORTANT NOTES:   
The following lists are by no means exhaustive.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 397  8.1 LIST OF PROHIBITED AND RESTRICTED ACTIVE INGREDIENTS AND 
COMBINATION  
 
 8.1.1  LIST OF PR OHIBITED ACTIVE INGREDIENTS AND COMBINAT IONS  
 
a) Prohibited Active Ingredients  
 
NO. PROHIBITED ACTIVE INGREDIENTS  
1.  1,3-dimethylamylamine (DMAA)  
2.  Aristolochic Acid  
3.  Aminopyrine/ Amidopyrine  
4.  Astemizole  
5.  Bacillus Coagulans  
6.  Berberine  
7.  Butobarbitone  
8.  Chlormezanone  
9.  Cisapride  
10.  Conjugated Lino leic Acid  
11.  Crinis Carbonisatus  
12.  Danthron  
13.  Dipyrone  
14.  Enterococcus Faecalis  
15.  Enterococcus Faecium  
16.  Ethenzamide  
17.  Euflavine  
18.  Furazolidone  
19.  Fenfluramine/ Dexfenfluramine  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 398  20.  Gadodiamide  
21.  Gentian Violet  
22.  Gamma -Butyrolactone (GBL)  
23.  Gamma -Aminobutyric Ac id (GABA)  
24.  Gamma -Hydroxybutyric Acid (G HB) 
25.  Haloquinol  
26.  Hexachlorophene  
27.  Mercurochrome  
28.  Nimesulide  
29.  Novobiocin  
30.  Oxyphenisatin Acetate/ Acetophenolisatin  
31.  Oxyphenbutazone  
32.  Pergolide  
33.  Phenacetin  
34.  Phenazone/ Antipyrine  
- Propylphenazone  
- Isopropylphen azone  
35.  Phenylbutazone  
36.  Phenylpropa nolamine  
37.  Piperazine  
38.  Prenylamine  
39.  Quinalbarbitone  
40.  Salicylamide  
41.  Sibutramine  
42.  Stanozolol  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 399  43.  Sulphaguanide  
44.  Thioridazine  
45.  Tegaserod  
46.  Terfenadine  
 
 
b) Prohibited Combinations  
 
NO. PROHIBITED COMBINATIONS   
1.  Ampicill in + Cloxacillin  
2.  Antibiotics + Papain/ Prolase  
3.  Antacid + Charcoal  
4.  Combinations With Any Barbiturates  
5.  Combinations of Two or More Analgesic with the Same Mode of 
Action  
6.  Combinations Of Vitamin (S) With Other Drugs:  
a. Vitamin (S) + Appetite Suppressa nt 
b. Vitamin (S) + Corticosteroid  
c. Vitamin (S) + Analgesic  
d. Vitamin (S) + Laxative  
e. Vitamin (S) + Slimming Agents  
7.  Cough, Cold and Allergy Products Containing:  
a. Four or More Pharmacological Groups in One Product.  
b. Two or More Drugs from the Same Pharmacological Group  
c. Antypyretic - Analgesic + Expectorant  
d. Anticholinergic + Bronchodilator  
e. Codeine + Ephedrine/ Pseudoephedrine  
f. Methapyrilene  
g. Paracetamol + Mucolytic/ Expectorant  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 400  NO. PROHIBITED COMBINATIONS   
8.  Combinations Containing Antacid and Surface Local Anaesthetic 
Agent  
9.  Combinations Conta ining Dextropropoxyphene  
10.  Combinations Containing Spironolactone  
11.  Corticosteroids + Antihistamines  
12.  Eye Drops Containing Vitamin  
13.  Gripe Water Containing Alcohol  
14.  Propanolol + Hydralazine  
15.  Propanolol + Spironolactone  
16.  Topical Preparation  Containing C ombination of Antibiotic, Antifungal 
and Steroid  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 401  8.1.2  LIST OF RE STRICTED ACTIVE INGREDIENTS AND COMBINATIONS  
 
Specific Active Ingredients  Not Allowed in the Specified 
Preparation(s) or Condition  
1. Acetic Acid  Expectorant  
2. Allantoin  Eye Drop  
3. Allergen E xtracts  Vaccines, Diagnostics  
4. Amphetamine  Cough Mixtures, Appetite Suppressants  
5. Animal Organ  All Preparations Except Natural Products  
6. Antihistamine  Topical Use 
7. Bismuth Salts Except 
Bismuth Subcitrate  Oral Preparations  
8. Boric Acid/ Borax and 
Related Sal ts Oral, Topical (Skin), Vaginal, Nasal Dosage 
Form  
9. Buprenorphine  Single Active Ingredient Sublingual Tablet 
Formulation  
10. Caffeine  All Preparations Except for an Oral 
Preparation in Combination with 
Paracetamol/ Acetaminophen or 
Combination with Ergotamin e 
11. Camphor  - Oral 
- External (>11%)  
12. Chloroform  Expectorant  
13. Codeine  Cough Syrup  
14. Cocillana Liq. Extract  Expectorant  
15. Cyproheptadine  Appetite Stimulant  
16. Dextromethorphan  Single Active Ingredient in Tablet Form , 
including lozenges  
17. Dihydrostreptomycin  Oral Anti diarrhoeals  
18. Diphenoxylate  Liquid Oral Dosage For Anti -Diarrhoeal  
19. Quinestrol, Oestrogen  Lactation Suppressant  
20. Ethynodiol Diacetate  Oral Contraceptives  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 402  21. Euphorbia Liquid Extract  Expectorant  
22. Gadopentetic acid  All except Intra -articular Formulation  
23. Gatifl oxacin  All Preparations  Except for Eye Drop  
24. Germanium  Non-Naturally Occurring  
25. Hydroquinone  Oral 
26. Lactobacillus Acidophillus  Antidiarrhoeal  
27. Loperamide  Liquid Oral Dosage For Anti -Diarrhoeal  
28. Lovastatin  In Red Yeast Rice: > 1 % w/w a nd > 
10mg/Day  
29. Lynooes trenol  Oral Contraceptives  
30. L-Tryptophan  All Preparations Except Parenteral Nutrition 
Products And Enteral Feeding Products  
31. Magnesium Ascorbryl 
Phosphate  Antipigmentation  
32. Menthol  External Preparations >16%  
33. Mestranol  Oral Contraceptives  
34. Methylene Blue  Oral Preparations  
35. Midazolam  All oral preparations, except 7.5mg coated 
tablet  
36. Morphine  Cough Mixtures  
37. Neomycin  Oral Antidiarrhoeal, Vaginal Tablets, Topical 
Powders, Aerosols, Nasal Preparations  
38. Noradrenaline  Dental Preparations  
39. Norgestrel  Oral Contrac eptives  
40. Paracetamol  Liquid Oral 500mg/5ml  
41. Penicillin  Topical Use  
42. Phenazopyridine  Urinary Analgesics  
43. Phenolphthalein  Stimulant Purgative  
44. Pizotifen  Appetite Suppressant  
45. Podophyllum Resin  Oral Preparations  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 403  46. Pseudoephedrine  All Single Active Ingredient F ormulations  
47. Sulphonamides  Topical Use  
48. Sulphur  All preparations Except External Preparation  
49. Squill  Expectorant  
50. Terpene Hydrate  Expectorant  
 
 
Combinations  Not Allowed in the Specified 
Preparation(s)  
1. Cough, Cold And Allergy 
Products Containing:  
i) Antimony  Potassium 
Tartrate  
ii) Allylisothiocyanate/ 
Mustard Oil  
iii) Turpentine Oil   
 
Expectorant  
 
Nasal Decongestant  
 
Expectorant/ Antitussive  
2. Vitamin(s)  Eye Drops  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 404  8.2 LIST OF PROHIBITED AND RESTRICTED EXCIPIENTS  
 
 
8.2.2  LIST OF RESTRICTED EXCIPIENTS  
Excipients  Restrictions  
1. Colouring Agents  
(Including in Capsule Shells)  
a) Tartrazine (CI= 1914 0, FD & C 
Yellow No.5, E102)  Not allowed in the following preparations:  
− Oral;  
− Rectal;  
− Vaginal or  
− Nasal Preparations  
b) Red 2G  
Not allowed in the following preparations:  
− Oral Preparations;  and 
− Preparations Used for  Mucosa Membrane  
2. Sweeteners/ Flavouring Agen t 
a) Menthol  0.4mg/kg body weight/day  
(dosage and use in children should be clearly 
stated).  
 
b) Saccharin and Salts  Limited to not more than 5mg/kg/day  8.2.1  LIST OF PROHIBITED EXCIPIENTS  
1. Colouring Agent s  
(Including in Capsule Shells)  
a) Amaranth (CI= 16185, FD & C Red No. 2, E123)  
2. Others  
a) Chlorofluorocarbons (CFC)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 405  c) Cyclamates  Limited to not more than 1.5mg/kg body 
weight/day  
3. Preservatives  
a) Chloroform  Limited to not mo re than 0.5% in 
Pharmaceuticals for Internal Use  
b) Thiomersal *  Not allowed in  ophthalmic Preparations  
4. Others  
a) Phthalates  Variant  Maximum Limit of  Daily 
Exposures (mg/kg 
body weight/day)  
Dibutyl Phthalate (DBP)  0.01mg/ kg/ day  
Diethyl Phthalate (DEP)  4mg/ kg/ day  
Polyvinyl Acetate 
Phthalate (PVAP)  2mg/ kg/ day  
 
* For other preparations, warning as specified in Appendix 9 : Labelling Requirement s, 
shall be included in the package insert and product literature of products  containing 
thiomersal.  
 
Additional Information  
 
1. Methylene Chloride/ Dichloromethane  are not allowed  as solvent in film-coating for 
locally manufactured pro ducts.  
For detail on implementation, please refer circular  (2)dlm.BPFK/30/06/2 Bhgn 2 . 
 
2. Alcohol  is not allowed  unless it is essential to the formulation and no suitable 
alternatives to alco hol are available. Content of alcohol shall be at the minimum level 
as possible.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 406  8.3 LIST OF PERMITTED AND RESTRICTED COLOURING AGENTS  
 
8.3.1  List o f Permitted Colouring Agents  
 
NO. COLOURING AGENTS  COLOUR 
INDEX 
NUMBER (CI)  
1.  Allura Red AC/ FD & C Red No.40  16035  
2.  Anthocyanins  
a. Those glycosides of 2 -phenylbenzopyrylium salts which 
are anthocyanins  
b. The following anthocyanidin aglycones :  
i. Pelargonidin  
ii. Cyanidin  
iii. Peonidin  
iv. Delphinidin  
v. Petunidin  
vi. Malvidin   
3.  Black PN (Brilliant Black BN)  28440  
4.  Brilliant Blue FCF 42090  
5.  Calcium Carbonate   
6.  Carbo Medicinals/ Vegetalis; (Charcoal)   
7.  Caramel   
8.  Carmoisine (or Azorubine)  14720  
9.  Carotenoids  
 
a. Alpha, Beta, Gamma -Carotene  
b. Bixin, Noribixin, Roucou  
c. Annatto  
d. Capsanthin, Capsorubin, (paprika extract)  
e. Lycopene  
f. Beta-Apo-8’ carotenal (C 30)  
g. Ethyl ester of Beta -Apo-8 Carotenoic Acid (C30)  
i. Chlorophyll  
ii. Copper complexes of Chlorophyll and 
Chlorophyllins   
 
 
 
 
 
75120  
 
40820  
 
75810  
10.  Chocolate Brown HT  20285  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 407  NO. COLOURING AGENTS  COLOUR 
INDEX 
NUMBER (CI)  
11.  Cochineal or Carminic Acid, Carmine from Cochineal  75470  
12.  Curcumin  75300 
13.  Fast Green FCF (FD & C Green No.3)  42053  
14.  Green S (Acid Brilliant Green BS, Lissamine Green)   
15.  Indigo Carmine (Indigotine)  73015  
16.  Lactoflavin, Riboflavin   
17.  Patent Blue V  42051  
18.  Ponceau 4R (Cochineal Red A)  16255  
19.  Quinoline Yellow  47005  
20.  Xanthop hylls 
 
a. Flavoxanthin  
b. Lutein  
c. Cryptoxanthin  (Kryptoxanthin)  
d. Violoxanthin  
e. Rhodoxanthin  
f. Canthaxanthin   
 
40850  
21.  The Following Colouring Matters Natural to Edible Fruits or 
Vegetables:  
 
a. Alkannin  
b. Annatto (including eye)  
c. Carotene (including eye)  
d. Chlorophyll  
e. Flavi ne 
f. Indigo  
g. Osage  
h. Orange  
i. Persian Berry  
j. Safflower  
k. Saffron  
l. Sandalwood  
m. Turmeric  
n. or their pure coloring principles whether isolated from 
such natural colors or produced synthetically  
 75530  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 408  NO. COLOURING AGENTS  COLOUR 
INDEX 
NUMBER (CI)  
22.  Bole or Iron Oxide,  
Carbon Black (or Vegetable Origin),  
Titanium Diox ide 77891  
23.  The Aluminium Salts (Lakes) of Any of the Scheduled 
Synthetic Dyes  Approved for Use,  
(a) Alumina (Dried Aluminium Hydroxide)   
 
24.  Talc  
25.  Indigo Carmine/ FD & C Blue No. 2  73015  
26.  Brilliant Blue FCF Ammonium Salt/ D & C Blue No. 4  42090  
27.  Aliza rin Cyanine Green F/ D & C Green  No. 5  61570  
28.  Toney Red/ D & C Red No. 17  26100  
29.  Eosin YS  Acid Form/ D & C Red No. 21  45380:2  
30.  Eosinys Sodium Salt/ D & C Red No. 22  45380  
31.  Phloxine B Acid Form/ D & C Red No. 27  45410:1  
32.  Phloxine B Sodium Sal t/ D & C Red No. 28  45410  
33.  Helindone Pink CN/ D & C Red No. 30  73360  
34.  Erythrosine/FD & C Red No. 3  45430  
35.  Yellow 2G (Food Yellow)   
37. Orange Yellow S  Sunset Yellow FCF  
(FD & C Yellow No. 6, E110)  15985  
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 409  8.3.2   List o f Restricted Colo uring Agents  
 
The following colo uring agents are  ALLOWED  in preparations as stated in the 
parentheses:  
 
NO. COLOURING AGENTS  COLOUR 
INDEX 
NUMBER (CI)  
1.  Dihydroxyacetone  
(external use with specific drugs only)   
2.  Bismuth Oxychloride  
(external use only, including eye)  77163 
3.  Ferric Ammonium Ferrocyanide  
(external use only, including eye)   
4.  Ferric Ferrocyanide  
(external eye only)   
5.  Chromium Hydroxide Green  
(external use only)  77289  
6.  Chromium Oxide Green  
(external use only, including eye)   
7.  Guanine  
(external us e only)  75170  
8.  Prophyllite  
(external use only)   
9.  Mica  
(external use only, including eye)  77019  
10.  Bronze  
(external use only, including eye)   
11.  Copper  
(external use only, including eye)   
12.  Zinc Oxide  
(external use only, including eye)  77947  
13.  Quini zarine Green SS/ D & C Green No. 6  
(external use only)  61565  
14.  Pyranine Concentrated/ D & C Green No. 8  
(external use only)  59040  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 410  NO. COLOURING AGENTS  COLOUR 
INDEX 
NUMBER (CI)  
15.  Orange II/ D & C Orange No. 4  
(external use only)  15510  
16.  Dibromofluorescein/ D & C Orange No. 5  
(mouth wash, dentifr ices, external use only)  45370  
17.  Diiodofluorescein/ D & C Orange No. 10  
(external use only)  45425  
18.  D & C Orange No. 11  
(external use only)   
19.  Ponceau SX / FD & C Red No. 4  
(external use only)  14700  
20.  Lithol Rubin B/ D & C Red No. 6  
(may be use in c ombination; total not more than 5mg/day)  15850  
21.  Lithol Rubin B CA/ D & C Red No. 7  
(may be used in combination; total not more than 5mg/day)  15850:1  
22.  D & C Red No. 31  
(external use only)   
23.  Deep Maroon / D & C Red No. 34  
(external use only)  15880:1  
24.  D & C Red No. 39  
(external use only, not more than 0.1%)   
25.  Uranine Acid Form / D & C Yellow No. 7                                           
(external use only)  45350:1  
26.  EXT. D & C Yellow No. 7  
(external use only)   
27.  Uranine Sodium Salt / D & C Yellow  No. 8                                       
(external use only)  45350  
28.  Tartrazine/ FD & C Yellow No. 5/MA Yellow A -2/ Aluminic Lake 
(external use only)  19140  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 411  APPENDIX 9:  LABELLING REQUIREMENTS  
 
 
This appendix comprises of two (2) parts:  
 
a) General Labe lling Requirement s for:  
 
i) Section D   : Label (Mock -Up) for Immediate Container and Outer Carton  
 
ii) Section D   : Proposed Package Insert (PI)  
 
iii) Section E8/ F8  : Consumer Medication Information Leaflet  (RiMUP ) 
 
 
b) Specific Labelling Requirements  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 412  9.1 GENERAL LA BELLING REQUIREMENTS  
 
The following information in Table 1  shall present on the label  of a produc t at o uter carton , 
immediate container or b lister/ strips:  
 
No. Parameters  Outer Carton  
(Unit Carton)  Immediate 
Labels  Blister/ 
Strips  
1. Product Name  ✓ ✓ ✓ 
2. Dosage Form  ✓ ✓* NA 
3. Name of Active Substance(s)  ✓ ✓ ✓** 
4. Strength of Active Substance(s)  ✓ ✓ ✓** 
5. Batch Number  ✓ ✓ ✓ 
6. Manufacturing Date  ✓ ✓* NA 
7. Expiry Date  ✓ ✓ ✓ 
8. Route of Administration  ✓ ✓ NA 
9. Storage Condition  ✓ ✓* NA 
10. Country’s Registration Number  ✓ ✓* NA 
11. Name & Address of Product 
Registration Holder (PRH)  ✓ ✓* Name/ Logo 
of 
Manufacturer/  
Product 
Owner  
12. Name & Address of 
Manufacturer  ✓ 
At least name 
of town/ city 
and country of 
manufacturer  ✓* 
At least name 
of town/ city 
and country 
of 
manufacturer  NA 
13. Warnings and/or Specific 
Labelling  
(if applicable)  ✓ ✓* NA 
14. Pack Sizes (unit/ volume)  ✓ ✓ NA Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 413  No. Parameters  Outer Carton  
(Unit Carton)  Immediate 
Labels  Blister/ 
Strips  
15. Name & content of 
preservative(s) where present  ✓ ✓ NA 
16. Name & content of alcohol, 
where present  ✓ ✓ NA 
17. To declare source of 
ingredients derived from animal 
origin (active and  excipient) 
including starting materials and 
gelatine . ✓ ✓ NA 
18. To declare the source of 
capsule shell (if applicable)  ✓ ✓ NA 
19. Recommended daily allowance 
(RDA) for vitamins / 
multivitamins/ mineral 
preparations used as dietary 
supplements (optional)  ✓ ✓ NA 
20. The words “Keep medicine out 
of reach of children” or words 
bearing similar meaning in both 
Bahasa Malaysia  & English  ✓ ✓* NA 
21. Other country specific labelling 
requirements  
(if applicable)  ✓ ✓* NA 
22. The words “Controlled 
Medicine/ Ubat Terkawal ”  
(For scheduled poison only)  ✓ ✓* NA 
23. Security Label (Hologram)  ✓ # - NA 
 
NA : Not Applicable  
 
* Exempted for small labels (i.e. 5ml and less ) used for ampoules/ ca rtridge, vials,  eye 
drops, ear drops, and nose drops.    
** For multi -vitamins and minerals preparations it is suggested to label as multi -
vitamins and minerals . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 414  # i. In case of a product without an  outer carton, the security label shall be applied 
onto the  immediate label.  The security label shall  however  not be applied onto the 
outer shrink wrap of the product.  
ii. Exempt ion will be  for small labels (i.e.  volume of  5ml and less ) such as for  
ampoules/ cartridge /vials. 
 
 
No. 15, 20, 22  & 23 of the above are c ountry specific  requirements  for Malaysia .   
 
• Declaration of nutrition information per serving (for example energy, carbohydrate, 
protein and fat) is not permitted in  a health supplement product label.  
 
ADDITIONAL INFORMATION:  
 
a) All labels and package inserts  must be in Bahasa Malaysia  or English. In additional to 
this, translation to another language will be allowed.  
b) If the product is without an outer carton, the inner label shall bear all the information 
that is required.  
c) Official website of the company or w ebsite for any purpose of product promotion from 
the PRH/ product owner/ manufacturer is not allowed to be printed on the product 
label (applicable to all categories of products inclusive of imported products). 
However, the email address of the company is permissible on the label.  
 
d) The colours of labels shall be differentiated between strengths of products as well as 
between products containing different active ingredients which belong to the same 
holder.  
 
e) Only a single label artwork is permitted for all pa ck sizes of a registered product.  
 
f) No stick -on label is permitted. Any usage of stick -on label shall have prior approval by 
the Authority. The Authority will only consider the following situations:  
 
i) Stick -on label of such information and printing of regist ration number for label 
redressing of a registered product is permitted:   
 
Words wit h “Controlled Medicine / Ubat Terkawal ”, “Keep  out of reach of children/ 
Jauh kan daripada capaian kanak -kanak ”, information of Product Registration 
Holder, and Malaysia Spe cific Label ling Requirements (if any) shall be printed in a 
single label.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 415  ii) The label shall  be made from good quality material and not easy to be torn out.  
 
iii) Registration number shall  be printed permanently on the product (ink -jet) and it is 
not allowed t o be printed on the stick -on label.  
g) Use of QR code is permitted only for the purpose of monitoring inventory of the 
product, such as batch number, expiry date and manufacturing date, BUT NOT for 
linkage to any website. The addition of QR code on registered  product labels without 
variation approval from NPRA  can be considered only if that is the only p roposed 
change to the currently approved labels.  
h) The label of a registered product containing any Scheduled Poison shall not have 
colourful atrwork or graphics  that can be misleading  or will adversely influence 
caregivers’/patients'/children's perceptions of the appropriateness of the medication.  
i) Font size of the product name on the label, including alphabets and numbers, should 
be equal in size.  
j) For a product c ontaining 2 or more active ingredients, font size of each active 
ingredient that is highlighted on the inner/ outer carton must be of equal size and 
equal prominence  (Note: this is not referring to the product name, but the statement 
made on the label).Ju stification for highlighting certain ingredients only on the product 
name / label must be provided and subject to approval by the Evaluation Committee.  
 
9.1.1 LABEL (MOCK -UP) FOR IMMEDIATE CONTAINER AND OUTER 
CARTON  
 
Please refer to Figure 1  as an example of a product label which in accordance to the 
labelling requirements.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 416  Figure 1:  
 
 
 
 
 
 
 
 
  PRH  
Note:  
Numerical notations shown in the above figure are in line with the numbering 
for the parameters, shown in Table 1 above, to be included in the product label 
(as identified and adopted by the ACCSQ -PPWG).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 417  9.1.2  PROPOSED PACKAGE INSERT  
 
Package insert (PI)  is required for products containing scheduled poison  and for injectable 
OTC products . PI may also be submitte d for other OTC products. The draft copy of the PI 
shall be submitted for evaluation.  
 
Sharing of PI is only allowed  for products having the same active ingredient(s) but with 
different strength s. 
 
 
The following information is required to be included in t he PI: 
 
a) Brand or Product Name  
b) Name and Strength of Active Substance(s)  
c) Product Description  
d) Pharmacodynamics/ Pharmacokinetics  
e) Indication  
f) Recommended Dosage  
g) Route of Administration  
h) Contraindications  
i) Warnings and Precautions  
j) Interactions with Other Medicame nts 
k) Statement on usage during pregnancy and lactation  
l) Adverse Effects/ Undesirable Effects  
m) Overdose and Treatment  
n) Incompatibilities (F or injections only)  
o) Storage C onditions (may be omitted if the information is stated on the label or 
outer carton labels)  
p) Dosage f orms and packaging available  
q) Name and a ddress of manufacturer/  product registration  holder  
r) Date of r evision of PI  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 418  9.1.3  CONSUMER MEDICATION INFORMATION LEAFLET (RiMUP)   
 
 
Consumer Medication  Information Leaflet or in Bahasa Malaysia  known as Risalah 
Maklumat Ubat untuk Pengguna  (RiMUP),  is compulsory for products which are self-
administered  by patients, including:  
a) Scheduled poisons (Category A);  
b) Over -the-Counter, OTC products (Category X);  
c) Herbal products;  and h ealth supplements with high claims (disease risk reduction).  
 
For details, please refer to:  
i) Direktif Penguatkuasaan Keperluan Mengemukakan Risalah Maklumat Ubat untuk 
Pengguna (RiMUP) Bil. 5 Year  2011  Bil (15) dlm BPFK/PPP/01/03 Jld 1  
ii) Garispanduan Pelaksanaan Risalah Maklumat Ubat untuk Pengguna (RiMUP)  
 
The draft copy of the RiMUP  in both English and Bahasa Malaysia  shall be submitted for 
evaluation.   
 
Note:  
RiMUP  is not compulsory to be distributed  with the product . All approved RiMUP will be 
uploaded onto NPRA  website as reference for consumers. Healthcare professionals can 
access the RiMUP and disseminate to patients if necessary.  
For OTC Products, if the product is intended to be sold without a PI or RiMUP , the 
information required to be included in the PI or RiMUP  shall be printed on the unit outer -
carton of the product.  However, submission of the RiMUP softcopy is compulsory as 
mentioned above.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 419  9.1.4   PRODUCT NAME  
 
Product  name is defined as a name  given  to a product which may  either be a proprietary 
name (an invented  name); or a generic name (common name) or scientific name, together 
with a trade mark or the name of the manufacturer . 
• Product name  shall consist of dosage form and strength  (for single acti ve ingredient 
product) . (e.g. X Brand Paracetamol Tablet 500mg)  
• The generic name cannot be used alone as product name but in combination with 
another name , other than the generic name.  
- The generic name means the international non -proprietary name recommen ded 
by WHO (rINN), or if one does not exist, the usual approved name.  
• The invented name shall not be liable to confusion with the common name.  
• Font size of the product name on the label, including alphabets and numbers, should 
be equal in size.  
• If a produc t name is found similar in terms of spelling and pronunciation to another 
registered product  or any other name which deemed inappropriate by the Authority , 
NPRA  reserves the rights to request for the change of the product name.  
 
Product names which are not  permitted to be registered are as specified in                      
Table 2 below:  
 
No. Non-Permissible Product Names  Example  
1.  20 disease names as stated in the 
Medicines (Advertisement and Sale) Act 
1956 (Revised 1983)  Example :  
Diabetes, Asthma, Cancer  
2.  Prohibited use of a single active 
ingredient as a product name in 
products containing more than one 
active ingredient unless product name 
contains words such as ‘Plus, 
Compound, Complex, Herbanika  Example :  
Tongkat Ali Capsule ---- 
But product contains tongkat ali, 
ginseng, ect.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 420  No. Non-Permissible Product Names  Example  
3.  Use of S uperlative s - Names which 
indicates superiority in efﬁcacy  Example :  
Power/ Kuasa, Superior, Pure, 
Mustajab, Safe, Healthy/ Sihat, 
Penawar/ Shifa, VIP, Good, Heal/ 
Sembuh, Premium, Mustajab, 
Men/ Women/ Children Complete, 
Men/ Women/ Children Enriched, 
Paradise/ Syurga, Menawan, 
Booster  
4.  Use of spelling of words which may 
cause confusion  
 
Words which involve names of/part 
thereof:  
iv) 20 disease names prohibited in the 
Medicines (Advertisement and Sale) 
Act 1956 (Revised 1983)  
v) Diseases without scientiﬁc evidence of 
efficacy/ prescription medicat ion to 
treat diseases/ parameters that 
indicate certain diseases (e.g. insulin, 
glucose)  
vi) Prohibited indication (e.g. to detoxify 
body)  
 Example :  
a) Go Out = GOUT  
b) UTix = Urinary Tract Infection  
c) Diabecine = Diabetes  
d) Metformon = Metformin  
e) Insupr em = Insulin  
f) Glucosey = Glucose  
g) DetoxB = Detox body  
5.  Use of names which may cause 
ambiguity  
Ambiguous product name  Example:  
B For Energy?  
6.  Use of names which may be offensive or 
indecent  Example:  
SENXBIG=SEnXBIG(label)  
Sexy, Enjoy, Paradise,  
Heaven ly, Blue boy, Casanova, 
Desire (Dezire),Sensual 
(Xenxual),Asmara,Syok  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 421  No. Non-Permissible Product Names  Example  
7.  Use of product names which are 
incoherent with the approved indication  
Name containing a product claim whereas 
product is indicated for more than the 
approved indication  Example:  
Cough Syrup X= Approved 
indication for cough, dizziness, ﬂu 
and itch  
8.  Use of product names which has 
elements of ludicrous belief  
Statements referring to ancient believe/ 
negative spirits/ supernatural power  Example:  
Words such as miracle, magic, 
magical, mirac ulous, saintly, 
heavenly  
9.  Use of product names similar to the 
existing approved product names  
Product names similar to the spelling and 
pronunciation of words of the existing 
product names  Example:  
Tenormin vs Tenormine vs 
Tenormy  
Re-Liv vs Re -Lif 
10.  Use of product names which may cause 
ambiguity in the nature of product (drug/ 
food/ beverage)  
Product names similar to a food/ beverage 
product  Example:  
Juice, Health drink, Beverage, 
Kooky  
11.  Use of product names which represents 
professional advice or opinion  or 
referring to the profession  Example:  
Dr Sunny, Dr Noortier Rooibose 
Tea, Professor, Herbalist, Doctor  
12.  Use of product names which represent 
weight loss/ slimming properties/ names 
that can be  associated with weight loss/ 
slim  Example:  
Slim, Langsing , Trim, Trimnfit,  
Sleen, Kurus, Susut perut,Xlim, 
Weight watcher  
13.  Use of product names referring to any 
religious content  Example:  
Maksum, Mahmudah, Arifbillah  
14.  Use of product names referring to  
internal organ s Example:  
Leever, Brain ey, Kidnee , etc.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 422  No. Non-Permissible Product Names  Example  
15.  Use of abbreviation as a product name 
unless it carries no meaning  Example:  
TB, UTI, HB, etc.  
16.  Use of product name which carries 
‘traditional’ and/ or ‘non -professional’ 
image for Pharmaceutical products  Example:  
Cap Ikan Emas, Brand Ayam Jati, 
Tablet Kuat  Badan  
17.  Other prohibited product names  Example:  
Minda, IQ, Smart, Genius, Ultra 
Mega, Detox  
Note:  
1. This list is not meant to be exhaustive and will be reviewed from time to time  
2. The Authority reserves the right to disallow any other words or phrases for product 
names which in its opinion is misleading, improper or not factual.  
 
9.1.5  PROHIBITED VISUAL/ GRAPHICS / STATEMENTS  ON 
LABEL  
 
The lists are a s shown in  Table 3 below:  
 
No. Issue  Example  Note  
1.  Marketing strategy  
 Example:  
“Money back guarantee”  
“Buy 1 free 1”  
“Backed by RM5 million  
product Liability Insurance”  - 
2.  Usage guide which 
promotes use of  
other product(s)  Example:  
“After consumption of this 
product (Product A), for 
better results, it is 
recommended to take 
Product B”  - Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 423  No. Issue  Example  Note  
3.  Consumer testimoni al - - 
4.  Clinical Trial results or 
any information on 
clinical trial done on 
product  
 Example :  
“Clinically Tested”  
“Randomized Double Blind 
Placebo Control Clinical 
Study”  - 
 
5.  Reference to Hadith/ Al -
Quran/ Bible/ Religious 
books  - - 
6.  Opinion of promine nt 
ﬁgure(s) on  
product or its active 
ingredient/  
content  Example:  
Opinion of 
product/formulation inventor  - 
7.  Label design (graphic 
and color) similar to 
labels from another  
company  - - 
8.  Statement on active 
ingredient origin  Example:  
Source from the Moun tains 
of Alps  Allowed if proven 
true 
9.  Introduction of founder/  
Manufacturer  - - Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 424  No. Issue  Example  Note  
10.  Logo with certiﬁcation  Example:  
SIRIM/ ISO / GMP/ HACCP  Prohibited on 
product label 
because 
certiﬁcation 
renewal is on a 
yearly basis  
11.  Name/ Statement/ 
Logo/ registered  
trademark which does 
not satisfy the 
speciﬁcations  Example:  
“Dr.ABC’s Formula”  
“Nothing like it”  
 - 
12.  Patency claim/ Patency 
number/ Special 
technique used/ 
superiority in 
ingredients (Example:  
capsule coat)  Example:  
Patented technique  Allowed if proven 
true 
13.  Nutritional claims with 
analysis certiﬁcate 
attached  Example:  
Calorie, Fat, Protein and  
others  - 
14.  Graphics or picture of 
internal organs  Example:  
Kidney, Heart, Nerves.  - 
15.  Gender  symbol  
(male or female)  (♀ and/or ♂) - 
16.  Indecent photographs/ 
pornography / graphics/ 
images  - - Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 425  No. Issue  Example  Note  
17.  Graphics which are 
incoherent with  
the indication  Example:  
- Noted indication is for 
constipation, but graphics 
on label shows a slim -
looking lady which 
denotes indication for 
weight loss  
- Indication for urination but 
label gr aphics contains 
picture of a water hose.  - 
18.  Highlighting 
unnecessary body parts  Example:   
Indication is for general 
health but graphics on label 
highlights male and female 
sexual organ parts  - 
19.  Graphics of plants or 
animal which  
may cause confusion  Exam ple:  
Radix Ginseng which is  
improvised as a male  
sexual part  - 
20.  Negative Statements/ 
Visual  Example:  
- This product is GMO/ 
LMO f ree 
- This product is free from 
animal origin  
- Free from Preservative  - 
21.  Other statements  
deemed relevant to be 
prohibited by the  
authority  Example:  
- This product is blended 
with premium quality  - 
Notes:  
1. This list is not meant to be exhaustive and will be reviewed from time to time  
2. The Authority reserves the right to disallow any other words, phrases or graphics for product 
label w hich in its opinion is misleading, improper or not factual  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 426  9.2 SPECIFIC LABELLING REQUIREMENTS  
 
Please refer Table 4: List of Substances Which Requires Specific La belling Requirements 
and Table 5 : Details of Specific Labelling Requirements.  
 
 
Table 4 : List of Substances Which Requires Specific Labelling Requirements:  
 
NO. SUBSTANCES  
1.  5-ALPHA REDUCTASE INHIBITOR (5 -ARI) 
2.  ACE INHIBITORS  
3.  ACETAZOLAMIDE  
4.  ACETYLCYSTEINE  
5.  ACETYLSALICYLIC ACID (ASPIRIN)  
6.  ACTIVATED CHARCOAL/ ATTAPULGITE  
7.  ALBENDAZOLE & BENZI MIDAZOLE ANTIHELMINTICS  
8.  ALFALFA ( MEDIC AGO  SATIVA ) 
9.  ALLOPURINOL  
10.  ALPHA DIHYDROERGOCRYPTINE  
11.  ALPRAZOLAM  
12.  AMIODARONE  
13.  AMOXICILLIN  
14.  ANTIDEPRESSANTS  
15.  ANTIEPILEPTICS  
16.  ANTIPSYCHOTIC AGENTS  
17.  APOMORPHINE  
18.  ARGININE  
19.  ARIPIPRAZOLE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 427  20.  ARTESUNATE  
21.  ASPARTAME  
22.  ATORVASTATIN  
23.  AZITHROMYCIN  
24.  BEE POLLEN  
25.  BENZODIAZEPINE  
26.  BENZOYL PEROXIDE  
27.  BENZYL ALCOHOL  
28.  BERBERINE ALKALOIDS – NATURAL OCCURING BERBERINE  E.G. 
HYDRASTIS CANADENSIS (GOLDENSEAL), COPTIS CHINENSIS 
(COPTIS OR GOLDENTHREAD), FIBRAUREA CHLOROLEUCA ETC . 
29.  BLACK COHOSH (CIMICIFUGA RACEMOSA ) 
30.  BOSWELLIA SPP.   
31.  BROMAZEPAM  
32.  BROMOCRIPTINE  
33.  BROMPHENIRAMINE  
34.  CABERGOLINE  
35.  CAMPHOR  
36.  CARBAMAZEPINE  
37.  CARBIMAZOLE  
38.  CARBOCISTEINE  
39.  CEFTRIAXONE  
40.  CETIRIZINE  
41.  CHELIDONIUM MAJUS  
42.  CHITOSAN  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 428  43.  CHLORHEXIDINE  
44.  CHLORP HENIRAMINE  
45.  CHORIONIC GONADOTROPHIN  
46.  CLEMASTINE  
47.  CLINDAMYCIN  
48.  CLOBAZAM  
49.  CLOPIDOGREL  
50.  CLOZAPINE  
51.  COBICISTAT  
52.  CODEINE  
53.  COLCHICINE  
54.  CORTICOSTEROID  
55.  COX -2 INHIBITORS  
56.  CYPROTERONE ACETATE  
57.  CYPROTERONE ACETATE WITH ETHINYLESTRADIOL IN 
COMBINATION  
58.  CYTOTOXIC AGENT  
59.  DEXBROMPHENIRAMINE  
60.  DEXTROMETHORPHAN  
61.  DIAZEPAM  
62.  DICLOFENAC SODIUM  
63.  DICYCLOMINE  
64.  DIPHENHYDRAMINE  
65.  DIPHENOXYLATE  
66.  DOMPERIDONE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 429  67.  DOPAMINERGIC INGREDIENT  
68.  DOXYCYCLINE  
69.  EFAVIRENZ  
70.  EPHEDRINE  
71.  ERYTHROMYCIN  
72.  ETHINYLESTRADIOL  
73.  ETORIC OXIB  
74.  FAMOTIDINE  
75.  FIBRATES  
76.  FILGRASTIM  
77.  FLUCLOXACILLIN  
78.  FLUCONAZOLE  
79.  FLUORIDE  
80.  FLUOROQUINOLONES  
81.  FLURAZEPAM HYDROCHLORIDE  
82.  GABAPENTIN  
83.  GADOBENIC ACID  
84.  GADOBUTROL  
85.  GADODIAMIDE  
86.  GADOLINIUM OXIDE  
87.  GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
88.  GADOTERIC ACID  
89.  GADOVERSETAMIDE  
90.  GADOXETIC ACID  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 430  91.  GAMAT/ STICHOPUS spp.  
92.  GENTAMICIN TOPICAL PREPARATIONS  
93.  GINKGO BILOBA/ GINKGO EXTRACT  
94.  GINSENG  
95.  GLUCOSAMINE  
96.  HIV PROTEASE INHIBITORS  
97.  HYDROQUINONE  
98.  HYOSCINE  
99.  IMMUNOSUPPRESANTS  
100.  INSULIN  
101.  INGREDIENTS DERIVED FROM SEAFOOD  
102.  INTERFERON ALPHA  
103.  INTERFERON BETA  
104.  KAOLIN, PECTIN, KAOLIN -PECTIN  
105.  KETOCONAZOLE  
106.  KETOROLAC TROMETHAMOL (KETOROLAC TROMETHAMINE)  
107.  LEVETIRACETAM  
108.  LEVODOPA  
109.  LEVONORGESTREL  
110.  LINCOMYCIN  
111.  LISURIDE  
112.  LIQUID PA RAFFIN  
113.  LOPERAMIDE  
114.  LORAZEPAM  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 431  115.  LOVASTATIN  
116.  MEFLOQUINE  
117.  MELALEUCA LEUCADENDRA  
118.  MESALAZINE  
119.  METFORMIN  
120.  METHYL SALICYLATE  
121.  METHYLPHENIDATE HCL  
122.  METOCLOPRAMIDE  
123.  METRONIDAZOLE  
124.  MICONAZOLE  
125.  MIDAZOLAM  
126.  MINOCYCLINE  
127.  MINOXIDIL  
128.  MOMORDICA CHARANTIA  
129.  MONTELUKAST  
130.  MUCOLYTIC AGENT  
131.  NEVIRAPINE  
132.  NIFEDIPINE  
133.  NITRATES  
134.  NITRAZEPAM  
135.  NORFLOXACIN  
136.  NORMAL GLOBULIN  
137.  NOSCAPINE  
138.  NONSTEROIDAL ANTI -INFLAMMATORY DRUG (NSAID)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 432  139.  OLANZAPINE  
140.  ONDANSETRON  
141.  OPIOID  
142.  PALIPERIDONE  
143.  PARACETAMOL  
144.  PARACETAMOL WITH CAFFEINE IN COMBINAT ION 
145.  PEGFILGRASTIM  
146.  PELARGONIUM SIDOIDES  
147.  PENICILLIN  
148.  PHENIRAMINE  
149.  PHENYLEPHRINE  
150.  PIRIBEDIL  
151.  PIROXICAM  
152.  PRAMIPEXOLE  
153.  PRAVASTATIN  
154.  PREDNISONE AND PREDNISOLONE  
155.  PROMETHAZINE HCL  
156.  PROPAFENONE  
157.  PROPOFOL  
158.  PROPOLIS (ORAL)  
159.  PROP OLIS (TOPICAL)  
160.  PROPYLTHIOURACIL  
161.  PSEUDOEPHEDRINE  
162.  PROTON PUMP INHIBITORS (PPI)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 433  163.  PSYCHOTROPIC PRODUCTS  
164.  PSYLLIUM/ PLANTAGO (SEED/ HUSK)  
165.  QUETIAPINE  
166.  QUINAGOLIDE  
167.  RISPERIDONE  
168.  RED YEAST RICE (MONASCUS PURPUREUS)  
169.  ROPINIROLE  
170.  ROSIGLITAZONE  
171.  ROSUV ASTATIN  
172.  ROYAL JELLY  
173.  SALBUTAMOL  
174.  SALICYLIC ACID (NATURALLY OCCURING IN PLANTS E.G. WILLOW 
SALIX SPP)  
175.  SEDATIVE – HYPNOTIC PRODUCTS  
176.  SELENIUM SULPHIDE  
177.  SENNA (CASSIA SPP.) – fruit/ pod/ semen and leaf and Rhubarb/ Radix et 
Rhizoma Rhei/ Rheum Palmatu m/ Rheum Officinalis – root part  
178.  SIMVASTATIN  
179.  SODIUM METABISULPHITE (EXCIPIENT)  
180.  SODIUM VALPROATE  
181.  ST. JOHN’S WORT   (Hypericum perforatum)  
182.  STATINS  
183.  STRONTIUM RANELATE  
184.  SULPHONAMIDES/ TRIMETHOPRIM  
185.  SYNTHETIC SALMON CALCITONIN  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 434  186.  TABEBUIA SPP. (PAU D’ARCO)  
187.  TEMOZOLAMIDE  
188.  TERBUTALINE  
189.  TESTOSTERONE  
190.  TETRACYCLINE SYRUP  
191.  THIOMERSAL  
192.  THROMBOLYTIC AGENTS  
193.  TIAPROFENIC ACID  
194.  TOPIRAMATE  
195.  TRAMADOL  
196.  TRETINOIN (TOPICAL)  
197.  TRIAZOLAM  
198.  TRIMETAZIDINE  
199.  TRIPROLIDINE  
200.  VARENICLINE  
201.  VITAMIN K  
202.  WARFARIN  
203.  ZIPRASIDONE  
204.  ZOLPIDEM TARTRATE  
205.  ZOPICLONE  
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 435  Table 5: Details of Specific Labelling Requirements   
 
NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
1.  5-ALPHA REDUCTASE INHIBITOR (5 -ARI) 
 
The following statement shall be included in the packa ge inserts  of products 
containing 5 -ARI: 
 
1.1 PRODUCT CONTAINING FINASTERIDE 5MG  
 
WARNINGS AND PRECAUTIONS  
 
Increased Risk of High -Grade Prostate Cancer  
 
Men aged 55 and over with a normal digital rectal examination and PSA 
≤3.0 ng/mL at baseline taking finast eride 5 mg/day in the 7 -year Prostate 
Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8 -
10 prostate cancer (finasteride 1.8% vs placebo 1.1%). Similar results 
were observed in a 4 -year placebo -controlled clinical trial with another 5 -
alpha reductase inhibitor (dutasteride, AVODART) (1% dutasteride vs 
0.5% placebo).  
 
5-alpha reductase inhibitors may increase the risk of development of high -
grade prostate cancer. Whether the effect of 5 -alpha reductase inhibitors 
to reduce prostate volum e, or study -related factors, impacted the results of 
these studies has not been established.  
 
Increased Risk of Breast Cancer  
 
Breast cancer has been reported in men taking finasteride 5 mg during the 
post-marketing period. Physicians should instruct their  patients to promptly 
report any changes in their breast tissue such as lumps, pain, 
gynaecomastia or nipple discharge.  
 
ADVERSE EVENTS: POST MARKETING EXPERIENCE  
 
Male breast cancer  
 
1.2 PRODUCT CONTAINING FINASTERIDE 1MG  
 
WARNINGS AND PRECAUTIONS  
 
Increased Risk of High -Grade Prostate Cancer  
 
Men aged 55 and over with a normal digital rectal examination and PSA  
≤3.0 ng/mL at baseline taking finasteride 5 mg/day (5 times the dose of Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 436  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
[Brand Name]) in the 7 -year Prostate Cancer Prevention Trial (PCPT) had 
an in creased risk of Gleason score 8 -10 prostate cancer (finasteride 1.8% 
vs placebo 1.1%). Similar results were observed in a 4 -year placebo -
controlled clinical trial with another 5 -alpha reductase inhibitor (dutasteride, 
AVODART) (1% dutasteride vs 0.5% place bo).  
 
5-alpha reductase inhibitors may increase the risk of development of high -
grade prostate cancer. Whether the effect of 5 -alpha reductase inhibitors 
to reduce prostate volume, or study -related factors, impacted the results of 
these studies has not be en established.  
 
Increased Risk of Breast Cancer  
 
Breast cancer has been reported in men taking finasteride 1 mg during the 
post-marketing period. Physicians should instruct their patients to promptly 
report any changes in their breast tissue such as lumps , pain, 
gynaecomastia or nipple discharge.  
 
ADVERSE EVENTS: POST MARKETING EXPERIENCE  
 
Male breast cancer  
 
1.3 PRODUCT CONTAINING DUTASTERIDE  
 
WARNINGS AND PRECAUTIONS  
 
Increased Risk of High -Grade Prostate Cancer  
 
In men aged 50 to 75 years with a prior negat ive biopsy for prostate cancer 
and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking AVODART 
in the 4 -year Reduction by Dutasteride of Prostate Cancer Events 
(REDUCE) trial, there was an increased incidence of Gleason score 8 -10 
prostate cancer compar ed with men taking placebo (AVODART 1.0% 
versus placebo 0.5%). In a 7 -year placebo -controlled clinical trial with 
another 5 -alpha reductase inhibitor (finasteride 5 mg, PROSCAR), similar 
results for Gleason score 8 -10 prostate cancer were observed (finaste ride 
1.8% versus placebo 1.1%).  
 
5-alpha reductase inhibitors may increase the risk of development of high -
grade prostate cancer. Whether the effect of 5 -alpha reductase inhibitors 
to reduce prostate volume, or study­related factors, impacted the results o f 
these studies has not been established.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 437  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference:  
a) Circular Bil (19) dlm BPFK/PPP/01/03 Jld 1:  Direktif untuk Memuatkan Kenyataan 
Amaran Berkaitan dengan Risiko High -Grade Prostate Cancer dalam Sisip Bungkusan 
Semua Produk 5 -Ari 
b) Circular Bil (64) dlm BPFK/PPP/01/03 Jld 1:  Direktif untuk Memuatkan Kenyataan 
Amaran Berkaitan dengan Risiko Kanser Payudara Di Kalangan Pesakit Lelaki dalam 
Sisip Bungkusan Semua Produk Yang Mengandungi Finasteride   
2.  ACE INHIBITORS  
 
The following statement shall be included in the package inserts  of products 
containing ACE inhibitors:  
 
WARNING  
 
• INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL 
MORBIDITY AND DEATH WHEN USED THROUGHOUT PREGNANCY  
 
USE IN PREGNANCY  
 
• INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL 
MORBIDIT Y AND DEATH WHEN USED THROUGHOUT PREGNANCY  
                                                                 
Reference: Circular Bil (65) dlm BPFK/02/5/1.3:  Produk yang Mengandungi  'ACE Inhibitors'  
3.  ACETAZOLAMIDE  
 
The following statements shall be included  in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
Acetazolamide;  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
Adverse reactions common to all sulfonamide derivatives may occur such 
as Stevens -Johnson syndrom e (SJS), toxic epidermal necrolysis (TEN), 
erythema multiforme (EM) and acute generalised exanthematous 
pustulosis (AGEP). If signs of serious reactions or hypersensitivity occur, 
discontinue use of this preparation.  
 
b) Adverse Effects / Undesirable Effects:  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 438  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Skin and Subcutaneous Tissue Disorders  
 
Frequency not known: Severe skin reactions [including Stevens -Johnson 
syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme 
(EM) and acute generalised exanthematous pustulosis (AGEP)]  
 
 
Consumer Med ication Information Leaflet (RiMUP)  
 
a) Side Effects:  
 
[Product name] may cause severe allergy and serious skin reactions. Stop 
using [Product name] and seek medical assistance immediately if you 
experience any of the following symptoms:  
 
• severe skin reacti on: skin reddening, blisters, rash, fever, sore throat 
 or eye irritation  
 
 
Reference: Directive No . 16 Year 201 8. Ref. BPFK/PPP/07/25 ( 16 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Acetazolamide : Pengemaskinian Sisip Bungkusan  Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Severe Cutaneous Adverse Reactions (SCAR s) 
 
4.  ACETYLCYSTEINE  
 
The f ollowing statements shall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
acetylcysteine;  
 
 
1. Injectable products with the indication as antidote for paracetamol 
overdose  
Package Insert  
 
a)  Warnings  and Precautions:  
 
Hypersensitivity Reactions  
Serious acute hypersensitivity reactions during acetylcysteine 
administration including rash, hypotension, wheezing, and/or shortness 
of breath, have been observed in patients receiving intravenous 
acetylcystei ne for paracetamol overdose and occurred soon after 
initiation of the infusion (see Adverse Effects/Undesirable Effects). If a Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 439  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
severe hypersensitivity reaction occurs, immediately stop the infusion of 
acetylcysteine and initiate appropriate treatment.  
 
Acute flushing and erythema of the skin may occur in patients receiving 
acetylcysteine intravenously. These reactions usually occur 15 to 60 
minutes after initiating the infusion and often resolve spontaneously 
despite continued infusion of acetylcysteine. If  a reaction to 
acetylcysteine involves more than simply flushing and erythema of the 
skin, it should be treated as a hypersensitivity reaction.  
 
Management of less severe hypersensitivity reactions should be based 
upon the severity of the reaction and incl ude temporary interruption of 
the infusion and/or administration of antihistaminic drugs. The 
acetylcysteine infusion may be carefully restarted after treatment of the 
hypersensitivity symptoms has been initiated; however, if the 
hypersensitivity reaction returns upon re -initiation of treatment or 
increases in severity, acetylcysteine should be discontinued and 
alternative patient management should be considered.  
 
b) Adverse Effects / Undesirable Effects:  
 
Immune System Disorders:  
Anaphylactic/anaphylactoid reaction  
 
Skin and Subcutaneous Tissue Disorders:  
Severe cutaneous adverse reactions (SCAR) e.g. erythema multiforme, 
Stevens -Johnson syndrome (SJS) and toxic epidermal necrolysis 
(TEN). In most of these cases reported at least one other drug was 
administ ered at the same time, which may have possibly enhanced the 
described mucocutaneous effects.  
 
 
2. All other products (not indicated for treatment of paracetamol 
overdose ) 
 
Package Insert  
 
a) Contraindications:  
 
[Product name] is contraindicated for concomitant u se with the 
medicinal products containing ombitasvir / paritaprevir / ritonavir and 
dasabuvir (See Section Warnings and Precautions and Section 
Interactions with Other Medicaments).  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 440  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
b) Warnings and Precautions:  
 
ALT elevations  
During clinical trials with pat ients treated for hepatitis C virus infections 
(HCV) with the medicinal products containing ombitasvir / paritaprevir / 
ritonavir and dasabuvir with/without ribavirin, transaminase (ALT) 
elevations higher than 5 times the upper limit of normal (ULN) occurr ed 
significantly more frequent in women using ethinylestradiol -containing 
medications such as combined hormonal contraceptives (CHCs). 
Patients who are taking ethinylestradiol -containing medicinal products 
must switch to an alternative method of contracept ion (e.g. progestin 
only contraception or non -hormonal methods) prior to initiating 
ombitasvir / paritaprevir / ritonavir and dasabuvir therapy (See Section 
Contraindications and Section Interactions with Other Medicaments).  
 
c) Interactions with Other Medica ments : 
 
Concomitant use with the medicinal products containing ombitasvir / 
paritaprevir / ritonavir and dasabuvir, with or without ribavirin may 
increase the risk of ALT elevations (See Section Contraindications and 
Section Warnings and Precautions). Ther efore, users must switch to an 
alternative method of contraception (e.g., progestogen -only 
contraception or non -hormonal methods) prior to starting therapy with 
this combination drug regimen. [Product name] can be restarted 2 
weeks following completion of treatment with this combination drug 
regimen.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before You Use <product name> : 
 
When you must not use it:  
Do not use <product name> if you have Hepatitis C and are taking the 
medicinal products containing om bitasvir / paritaprevir / ritonavir and 
dasabuvir.  
 
 Taking other medicines:  
Do not use <product name> if you have Hepatitis C and are taking the 
medicinal products containing ombitasvir / paritaprevir / ritonavir and 
dasabuvir. Your doctor will prescribe another type of contraceptive 
before starting the treatment with these medicinal products.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 441  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference: Directive No . 14 Year 201 8. Ref. BPFK/PPP/07/25 ( 14 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Carbocisteine Dan Acetylcysteine : Pengemaskinian Label, 
Sisip Bungkusan  Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat 
Keselamatan Berkaitan Anaphylactic/ A naphylactoid Reaction  Dan Severe Cutaneous Adverse 
Reactions (SCAR)   
 
5.  ACETYLSALICYLIC ACID (ASPIRIN)  
 
For products containing Acetylsalicylic acid, the following warning shall be 
included on the labels  in two languages ( Bahasa Malaysia  and English):  
 
AMA RAN  
TIDAK BOLEH DIBERI KEPADA KANAK -KANAK BERUMUR KURANG 
DARIPADA 16 TAHUN.  
 
WARNING  
NOT TO BE GIVEN TO CHILDREN UNDER 16 YEARS OF AGE.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 442  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
6.  ACTIVATED CHARCOAL/ ATTAPULGITE  
 
4.1 The following boxed warning  shall be included on the labels  of products 
containin g Activated charcoal/ attapulgite:  
 
 
4.2 The following statements  shall be included in the package inserts  of 
products containing Activated charcoal/ attapulgite:  
 
 
 
WARNING  
Activated charcoal/ attapulgite may interfere with the absorption of other 
drugs , including antibiotics, when administered concurrently.  
 
PRECAUTION  
Appropriate fluid and electrolyte therapy should be given to protect against 
dehydration. Oral rehydration therapy which is the use of appropriate fluids 
including oral rehydration salts remains the most effective treatment for 
dehydration due to diarrhoea. The intake of as much of these fluids as 
possible is therefore imperative.  
7.  ALBENDAZOLE & BENZIMIDAZOLE ANTIHELMINTICS  
 
The following statement  shall be included on the labels and in t he package 
inserts  of products containing Albendazole or Benzimidazole antihelmintics:  
 
SHOULD NOT BE ADMINISTERED DURING CONFIRMED OR SUSPECTED 
PREGNANCY  NOT RECOMMENDED FOR TREATMENT OF DIARRHOEA  
IN CHILDREN UNDER 6 YEARS OF AGE  
Not recommended for treatment of diarhoea  
in children under 6 years of age  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 443  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
8.  ALFALFA ( MEDICAGO SATIVA ) 
The following boxed warning  shall be included on the labels  of products 
containing Alfalfa  (Medico sativa ): 
9.  ALLOPURINOL  
 
The following statement  shall be included in the package inserts  of products 
containing Allopurinol:  
 
WARNING  
 
Allopurinol should be discontinued at the first appearance of skin rash or other 
signs which m ay indicate an allergic reaction. Hypersensitivity to allopurinol 
usually appears after some weeks of therapy, and more rarely immediately 
after beginning treatment.  
In some instances, a skin rash may be followed by more severe reactions such 
as exfoliativ e, urticarial and purpuric lesion as well as Stevens -Johnson 
syndrome, and/or generalized vasculitis, irreversible hepatotoxicity and even 
death.  
10.  ALPHA DIHYDROERGOCRYPTINE  
Please refer to DOPAMINERGIC INGREDIENT  
11.  ALPRAZOLAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  This product contains  Alfalfa  (Medico sativa ). 
Indivi dual with a predisposition to systemic lupus erythematosus  
should consult their physician before consuming this product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 444  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
12.  AMIODARONE  
 
The following boxed warning  shall be included on the package inserts  of 
products containing Amiodarone:  
 
13.  AMOXICILLIN  
 
The following statements shall be included in the package insert  and 
Consumer Medicati on Information Leaflet (RiMUP)  of products containing 
Amoxicillin (including combination products);  
 
Package Insert  
 
a) Warnings and Precautions:  
 
Serious and occasionally fatal hypersensitivity reactions (including 
anaphylactoid and severe cutaneous adverse reactions) have been 
reported in patients on penicillin therapy.  
 
b) Adverse Effects/ Undesirable Effects:  
 
Skin and subcutaneous tissue disorders:  
Frequency ‘very rare’: Drug Reaction with Eosinophilia and Systemic 
Symptoms (DRESS)  
 
Consumer Medication Infor mation Leaflet (RiMUP)  
 
a) Side Effects : 
 
Stop taking [product name] and contact your doctor immediately if you 
experience any of the following:  
• Serious allergic reactions such as Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS). DRESS appears in itially as flu -
like symptoms with a rash on the face and then with an extended 
rash, high temperature and enlarged lymph nodes.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 445  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference : Directive No. 8 Year 201 8. Ref. BPFK/PPP/07/25 ( 8 ) Jld 2.  Direktif Untuk 
Semua Produk Yang Mengandungi Amoxicillin Termasuk Kombinasi : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (Rimup) Dengan Memperkukuhkan 
Maklumat Berkaita n Severe Cutaneous Adverse Reactions  (Scars) Pada Bahagian Warnings 
& Precautions Dan  Amaran Berkaitan Drug Reaction With Eosinophilia And Systemic 
Symptoms  (Dress) Pada Bahagian  
Side Effects  
14.  ANTIDEPRESSANTS  
 
The following statement shall be included in  the package inserts  of products 
used as antidepressants:  
 
WARNING  
 
Suicidality in Children and Adolescents  
 
• Antidepressants increase the risk of suicidal thinking and behavior 
(suicidality) in   children and adolescents with major depressive disorder 
(MDD ) and other psychiatric disorders.  
 
• Anyone considering the use of an antidepressant in a child or adolescent 
for any clinical use must balance the risk of increased suicidality with the 
clinical need.  
 
• Patients who are started on therapy should be observed  closely for clinical 
worsening, suicidality, or unusual changes in behavior.  
 
• Families and caregivers should be advised to closely observe the patient 
and to communicate with the prescriber.  
• The indication(s) approved in paediatric for the particular drug  should be 
clearly stated / included.  
 
Reference: Circular Bil(41)dlm BPFK/02/5/1.3:  Keputusan Pihak Berkuasa Kawalan Dadah 
(PBKD) Berhubung Tambahan Amaran Berkaitan Dengan 'Suicidality In Children And 
Adolescents Treated With Antidepressants'  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 446  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
15.  ANTIEPIL EPTICS  
 
The following statement  shall be included in the package inserts  of products 
used as antiepileptics:  
 
WARNING AND PRECAUTION  
 
Potential for an increase in risk of suicidal thoughts or behaviors.  
 
Reference: Circular  Bil (43) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Berkaitan Dengan 
“Potential for an Increase in Risk of Suicidal Thoughts or Behaviours” yang Perlu Dimuatkan 
Pada Sisip Bungkusan Produk Antiepileptik  
16.  ANTIPSYCHOTIC AGENTS  
 
 
13.1 ALL ANTIPSYCHOTIC AGENTS  
 
The following statement shall be included in the package inserts  of 
products containing antipsychotic:  
 
PREGNANCY AND LACTATION  
 
Neonates exposed to antipsychotic drugs during the third trimester of 
pregnancy are at risk for extrapyramidal and/or withdrawal symptoms 
following delivery. The re have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, and feeding disorder 
in these neonates. These complications have varied in severity; while in 
some cases symptoms have been self -limited, in other cases neo nates 
have required intensive care unit support and prolonged hospitalisation.  
 
[BRAND NAME] should be used during pregnancy only if the potential 
benefit justifies the potential risk to the foetus.  
 
Reference: Circular  Bil (16) dlm BPFK/PPP/01/03 Jld 1:  Directive  Kenyataan Amaran 
Berkaitan Dengan Risiko Extrapyrimidal And/or Withdrawal Symptoms Bagi Neonat 
Yang Terdedah Kepada Produk Antipsikotik Semasa Trimester Ketiga Kehamilan Pada 
Sisip Bungkusan Semua Produk Antipsikotik  
 
 
13.2 ATYPICAL ANTIPSYCHOTIC  AGENTS  
 
The following statement shall be included in the package inserts  of 
products containing atypical antipsychotic agents:  
a. Clozapine  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 447  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
b. Olanzepine  
c. Risperidone  
d. Quetiapine  
e. Ziprasidone  
f. Aripiprazole  
  
      
WARNING  
 
Hyperglycemia and Diabetes Mellitus  
  
Hype rglycemia in some cases extreme and associated with ketoacidosis 
or hyperosmolar coma or death, has been reported in patients treated 
with atypical antipsychotics. Assessment of the relationship between 
atypical antipsychotics use and glucose abnormalities  is complicated by 
the possibility of an increased background risk of diabetes mellitus in 
patients with schizophrenia and the increasing incidence of diabetes 
mellitus in the general population. Given this confounders, the relationship 
between atypical an tipsychotic use and hyperglycemia -related adverse 
events is not completely understood. However, epidemiological studies 
suggest an increased risk of treatment -emergent hyperglycemia -related 
adverse events in patients treated with the atypical antipsychotic s. 
Precise risk estimates for hyperglycemia -related adverse events in 
patients treated with atypical antipsychotics are not available.  
 
Patients with an established diagnosis of diabetes mellitus who are 
started on atypical antipsychotics should be monitor ed regularly for 
worsening of glucose control. Patients with risk factors for diabetes 
mellitus (e.g. obesity, family history of diabetes) who are starting 
treatment with atypical antipsychotics should undergo fasting blood 
glucose testing at the beginning  of treatment and periodically during 
treatment. Any patient treated with atypical antipsychotics should be 
monitored for symptoms of hyperglycemia including polydipsia, polyuria, 
polyphagia, and weakness. Patients who develop symptoms of 
hyperglycemia dur ing treatment with atypical antipsychotics should 
undergo fasting blood glucose testing. In some cases, hyperglycemia has 
resolved when the atypical antipsychotic was discontinued; however, 
some patients required continuation of anti -diabetic treatment des pite 
discontinuation of the suspect drug.  
 
Reference: Circular Bil (31)dlm BPFK/02/5/1.3:  Tambahan Amaran Berkaitan Dengan 
Hyperglycemia Bagi Keluaran 'Atypical Antipsychotic Agents'  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 448  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
17.  APOMORPHINE  
 
Please refer to DOPAMINERGIC INGREDIENT  
18.  ARGININE  
 
The f ollowing statement  shall be included on the labels and in the package 
inserts  of oral preparations containing Arginine for health supplement 
products : 
 
WARNING  
 
Arginine is not recommended for patients following a heart attack.  
 
Reference: Circular Bil (64 ) dlm BPFK/02/5/1.3:  Pernyataan Amaran Produk Mengandungi 
'Arginine'  
19.   
ARIPIPRAZOLE  
(Please also refer to ANTIPSYCHOTIC AGENTS)   
 
The following statements shall be included in the package insert and RiMUP  of 
products containing Aripiprazole:  
 
Package Inse rt 
 
a) Warnings and Precautions:  
 
Pathological gambling and impulse -control problems  
Patients can experience increased urges, particularly for gambling, and the 
inability to control these urges while taking aripiprazole. Other urges, 
reported include: incr eased sexual urges, compulsive shopping, binge or 
compulsive eating, and other impulsive and compulsive behaviours.  
 
It is important for prescribers to ask patients or their caregivers specifically 
about the development of new or increased gambling urges,  or other urges, 
while being treated with aripiprazole. It should be noted that impulse -control 
symptoms can be associated with the underlying disorder; however, in 
some cases urges were reported to have stopped when the dose was 
reduced or the medication was discontinued. Patients who are at higher risk 
for impulse -control problems (e.g. personal or family history of obsessive -
compulsive disorder, impulse -control disorder, bipolar disorder, impulsive 
personality, alcoholism, drug abuse or other addictive b ehaviours) would Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 449  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
require closer monitoring for new or worsening of uncontrollable urges. 
Impulse -control problems may result in harm to the patient and others if not 
recognised. Consider dose reduction or stopping the medication if a patient 
develops such urges while taking aripiprazole.  
 
 
b) Adverse Effects/Undesirable Effects:  
 
Psychiatric disorders   
Pathological gambling, hypersexuality, impulse -control problems (See 
Section Warnings and Precautions).  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before you use <product name>  
 
Before you start to use it  
Talk to your doctor or pharmacist if you have:  
• a history of excessive gambling or other unusual urges (e.g. increased 
sexual urges, binge or compulsive eating, and compulsive shopping).  
 
b) Side ef fects:  
 
Side effects may include:  
• Excessive gambling or other unusual urges, such as increased sexual 
urges, binge or compulsive eating, and compulsive shopping. If you or your 
family members notice that you are having unusual urges or behaviours, 
talk to your doctor or pharmacist.  
 
 
Reference : Directive No. 22 Year 2017. Ref. BPFK/PPP/07/25 ( 27 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandung i Aripripazole : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Kesan Advers Pathological Gambling  Dan Impulse -Control Problems  
 
20.  ARTESUNATE  
 
Please refer to MEFLOQUINE for products co ntaining Mefloquine in 
combination with other active ingredients (mefloquine/artesunate)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 450  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
21.  ASPARTAME  
 
The following statement  shall be included on the labels and in the package 
inserts  of products containing Aspartame:  
 
WARNING  
Unsuitable for phenylketonu rics. 
22.  ATORVASTATIN  
 
The following statement  shall be included in the package inserts  of products 
containing A torvastatin : 
 
DOSAGE AND ADMINISTRATION  
 
Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or 
Certain Protease Inhibitors –  
In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus 
ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with [Product 
Name] should be avoided.  
 
In patients with HIV taking lopinavir plus ritonavir, caution sh ould be used 
when prescribing [Product Name] and the lowest dose necessary employed.  
 
In patients taking clarithromycin, itraconazole, or in patients with HIV taking a 
combination of saquinavir plus ritonavir, darunavir plus ritonavir, 
fosamprenavir, or f osamprenavir plus ritonavir, therapy with [Product Name] 
should be limited to 20 mg, and appropriate clinical assessment is 
recommended to ensure that the lowest dose necessary of atorvastatin is 
employed.  
 
In patients taking the HIV protease inhibitor ne lfinavir or the hepatitis C 
protease inhibitor boceprevir, therapy with [Product Name] should be limited to 
40 mg, and appropriate clinical assessment is recommended to ensure that the 
lowest dose necessary of atorvastatin is employed.  
 
WARNINGS AND PRECAU TIONS  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 451  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Skeletal Muscle Effects  
Physicians considering combined therapy with atorvastatin and fibrates, 
erythromycin, immunosuppressive drugs, azole antifungals, or lipid -modifying 
doses of niacin (≥1g/day) should carefully weigh the potential benefits and 
risks and should carefully moni tor patients for any signs and symptoms of 
muscle pain, tenderness, or weakness, particularly during the initial months of 
therapy and during any periods of upward dosage titration of either drug. 
Therefore, lower starting and maintenance doses of atorvast atin should also 
be considered when taken concomitantly with the aforementioned drugs. 
Temporary suspension of atorvastatin may be appropriate during fusidic acid 
therapy.  
 
All generic products containing Ator vastatin should update their package 
inserts re spectively according to the innovator’s information such as parts for 
Interactions, Pharmacokinetics and other parts deemed relevant.  
 
Reference: Circular Bil (17) dlm BPFK/PPP/07/25 . Directive  Bil 10 Year  2014.  
DIREKTIF  UNTUK SEMUA PRODUK ATORVASTATIN: MENGEHADKAN DOS 
PENGGUNAAN ATORVASTATIN UNTUK MENGURANGKAN RISIKO KECEDERAAN 
OTOT  
 
23.  AZITHROMYCIN  
 
1. The following statement  shall be included in the package  insert  of product 
that contains Azithromycin : 
 
Special Warnings and Precautions for Use  
 
Hypersensitivity  
As with erythromycin and other macrolides, rare serious allergic 
reactions, including angioedema and anaphylaxis (r arely fatal), 
dermatologic reactions including Stevens -Johnson Syndrome (SJS), 
Toxic Epidermal Necrolysis (TEN) (rarely fatal), and Drug Reaction with 
Eosinophilia and Systemic Symptoms (DRESS) have been reported. 
Some of these reactions with azithromycin have resulted in recurrent 
symptoms and required a longer period of observation and treatment.  
 
If an allergic reaction occurs, the drug should be discontinued and Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 452  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
appropriate therapy should be instituted. Physicians should be aware 
that reappearance of th e allergic symptoms may occur when 
symptomatic therapy is discontinued.  
 
Prolongation of the QT interval  
Prolonged cardiac repolarization and QT interval, imparting a risk of 
developing cardiac arrhythmia and torsades de pointes, have been seen 
in treatmen t with macrolides, including azithromycin (see section 4.8). 
Prescribers should consider the risk of QT  prolongation, which can be 
fatal, when weighing the risks and benefits of azithromycin for at -risk 
groups including:  
• Patients with congenital or documen ted QT prolongation  
• Patients currently receiving treatment with other active substances 
known to prolong QT interval, such as antiarrhythmics of Classes IA 
and III, antipsychotic agents, antidepressants, and fluoroquinolones  
• Patients with electrolyte distu rbance, particularly in cases of 
hypokalemia and hypomagnesemia  
• Patients with clinically relevant bradycardia, cardiac arrhythmia or 
cardiac insufficiency  
• Elderly patients: elderly patients may be more susceptible to drug -
associated effects on the QT inter val 
 
Adverse Drug Reactions  
   
Post -marketing experience:  
 
Cardiac Disorders : Palpitations and arrhythmias including ventricular 
tachycardia have been reported. There have been rare reports of QT 
prolongation and torsades de pointes (see Special Warnings a nd 
Precautions for Use) . 
Skin and Subcutaneous Tissue Disorders : Allergic reactions including 
pruritus, rash, photosensitivity, edema, urticaria, and angioedema. 
Rarely, serious cutaneous adverse reactions including erythema 
multiforme, SJS, TEN and DRESS have been reported.  
Reference: Circular Bil (34) dlm BPFK/PPP/07/25 . Directive Bil 3 Year 2016.  
Direktif Untuk Semua Produk Yang Mengandungi Azithromycin (Formulasi Sistemik): 
Pengemaskinian Sisip Bungkusan Dengan Maklumat Keselamatan Berkaitan Kesan Advers 
QT Prolongation  Dan Drug Reaction With Eosinophilia And Systemic Symptoms (DRESS)  
 
 
2. The following statement shall be included i n the package insert and 
RiMUP  of products containing azithromycin (except topical/ external and 
ophthalmic preparations);  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 453  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
Infantile hypertrophic pyloric stenosis (IHPS) has been reported 
following the use of az ithromycin in infants (treatment up to 42 days of 
life). Parents and caregivers should be informed to contact their 
physician if vomiting and/ or irritability with feeding occurs.  
 
b) Adverse Effects/Undesirable Effects:  
 
Postmarketing Experience:  
 
Gastrointe stinal Disorders: infantile hypertrophic pyloric stenosis.   
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
Side Effects  
 
If you notice that the child vomits and/or irritability with feeding occurs, 
contact doctor immediately as it may be due to the In fantile 
Hypertrophic Pyloric Stenosis (IHPS).  
 
Reference : Directive No. 28 Year 2017. Ref. BPFK/PPP/07/25 ( 33 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi Bahan Aktif Azithromycin Dan Erythromycin Kecuali 
Persediaan Topikal/ Eksternal Dan Ubat Untuk Kegunaan Mata : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Amaran Berkaitan 
Risiko Infantile Hypertrophic Pyloric Stenosis (IHPS)  
 
24.  BEE POLLEN  
 
The following statement  shall be included on the labels and in the package 
inserts  of product containing bee pollen:  
 
This product contains Bee Pollen and may cause severe allergic reactions, 
including fa tal anaphylactic reactions in susceptible individuals.  
 
Asthma and allergy sufferers may be at greater risks.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 454  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
25.   
BENZODIAZEPINE  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing benzodiazepine  such as alprazolam, 
bromazepam, chlordiazepoxide, clobazam, clonazepam, clorazepate 
potassium, diazepam, lorazepam, midazolam, nitrazepam and triazolam;  
 
 
Package Insert  
 
c) Warnings and Precautions:  
 
Risks from Concomitant Use with Opioids  
 
Profound sedatio n, respiratory depression, coma, and death may result 
from the concomitant use of <product name> with opioids. 
Observational studies have demonstrated that concomitant use of 
opioids and benzodiazepines increases the risk of drug -related mortality 
compared  to use of opioids alone. Because of these risks, reserve 
concomitant prescribing of these drugs for use in patients for whom 
alternative treatment options are inadequate.  
 
If the decision is made to newly prescribe a benzodiazepine and an 
opioid together,  prescribe the lowest effective dosages and minimum 
durations of concomitant use.  
 
If the decision is made to prescribe a benzodiazepine in a patient 
already receiving an opioid, prescribe a lower initial dose of the 
benzodiazepine than indicated in the a bsence of an opioid, and titrate 
based on clinical response.  
 
If the decision is made to prescribe an opioid in a patient already taking 
a benzodiazepine, prescribe a lower initial dose of the opioid, and titrate 
based on clinical response.  
 
Follow patie nts closely for signs and symptoms of respiratory 
depression and sedation. Advise both patients and caregivers about the 
risks of respiratory depression and sedation when <product name> is 
used with opioids. Advise patients not to drive or operate heavy 
machinery until the effects of concomitant use of the opioid have been 
determined. Screen patients for risk of substance use disorders, 
including opioid abuse and misuse, and warn them of the risk for 
overdose and death associated with the use of opioids (Se e Drug Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 455  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Interactions).  
 
d) Drug Interactions:  
 
Opioids  
Due to additive pharmacologic effect, the concomitant use of opioids 
with benzodiazepines increases the risk of respiratory depression, 
profound sedation, coma and death.  
 
The concomitant use of opioids an d benzodiazepines increases the risk 
of respiratory depression because of actions at different receptor sites in 
the central nervous system that control respiration. Opioids interact 
primarily at μ -receptors, and benzodiazepines interact at GABA A sites. 
When opioids and benzodiazepines are combined, the potential for 
benzodiazepines to significantly worsen opioid -related respiratory 
depression exists.  
 
Reserve concomitant prescribing of these drugs for use in patients for 
whom alternative treatment options are inadequate (see Warnings and 
Precautions).  
 
Limit dosage and duration of concomitant use of benzodiazepines and 
opioids, and follow patients closely for respiratory depression and 
sedation.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
b) Taking othe r medicines:  
 
Taking <product name> with an opioid medicine (medicine to relieve 
pain) can depress your central nervous system. Inform your doctor if 
you are currently taking any opioid medicine.  
 
Seek medical attention immediately if you or the person tak ing this 
medication experience(s) symptoms of unusual dizziness or 
lightheadedness, extreme sleepiness, slowed or difficult breathing, or 
unresponsiveness.  
 
 
Reference : Directive No. 23 Year 2017. Ref. BPFK/PPP/07/25 ( 28 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi Opioid Dan Benzodiazepin : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Makluma t 
Keselamatan Berkaitan Interaksi Ubat  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 456  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
26.  BENZOYL PEROXIDE  
 
The following statement  shall be included on the labels and in the package 
inserts  of products containing Benzoyl peroxide:  
 
WARNING  
 
Do not use this medication if you have sensitive skin or if y ou are sensitive to 
benzoyl peroxide. This product may cause irritation, characterized by redness, 
burning, itching, peeling, or possible swelling.  
27.  BENZYL ALCOHOL  
The following statement  shall be included on label and in package insert  of 
parenteral prod ucts containing Benzyl alcohol:  
 
28.  BERBERINE ALKALOIDS – NATURALLY OCCURING BERBERINE E.G. 
HYDRASTIS CANADENSIS (GOLDENSEAL), COPTIS CHINENSIS (COPTIS  
OR GOLDENTHREAD), FIBRAUREA CHLOROLEUCA ETC.  
The following statement  shall be included on the label and  in the package 
insert  of products containing the berberine alkaloid:  
WARNING  
Not to be taken by babies, children under 12 years of age, pregnant women or 
lactating mothers.  
Consult your practitioner if you have conditions such as :  
-Glucose -6-Phosphate De hydrogenase (G6PD) deficiency  
-Haemolytic anemia  
-Glaucoma  
-Diabetes  
-High Blood Pressure  
-History of cardiovascular disease  
-If you are using Paclitaxel, Cyclosporin, or other chemotherapeutic agents.  As this preparation contains benzyl alcohol, its use should be 
avoided in children under two years of age.  
Not to be used in neonates . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 457  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Reference :  Circular : Bil.(22)dlm.BPFK/PPP/06/12 Jld.26.  Kawalan produk mengandungi 
bahan aktif yang mempunyai berberine secara semulajadi.  
 
29.  BLACK COHOSH (CIMICIFUGA RACEMOSA ) 
 
The f ollowing statement  shall be included on the labels and in the package 
inserts  of products containing Black Cohosh  (Cimicifuga Racemosa ): 
 
WARNING  
Stop taking this product if signs and symptoms suggestive of liver injury 
develop such as tiredness, loss of a ppetite, yellowing of the skin and eyes or 
severe upper stomach pain with nausea and vomiting or dark urine and consult 
your doctor immediately.  
Patients using herbal medicinal products should tell their doctor about it.  
Reference: Circular Bil (61) dlm BP FK/02/5/1.3:  Pernyataan Amaran Produk Mengandungi 
'Black Cohosh'  
30.  BOSWELLIA S PP. 
 
The following  statement  shall be included on label and package inserts  for oral 
products containing Boswellia s pp: 
 
WARNING:  
 
Please consult your doctor/pharmacist before u sing this product if you are on 
other medicines.  
 
Reference: Directive No. 10 Year 2018. Ref. BPFK/PPP/07/25(10)Jld2.  Direktif 
Penambahan Ke nyataan Amaran Bagi Semua Produk Yang Mengandungi Boswellia Spp.  
 
31.  BROMAZEPAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  
32.  BROMOCRIPTINE  
Please refer to DOPAMINERGIC INGREDIENT  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 458  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
33.  BROMPHENIRAMINE  
 
The following statement  shall be included on the labels and in the package 
inserts  of liquid oral products containing Brompheniramine:  
 
WARNING  
 
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b) To be used with caution and doctor’s/ pharmacist’s ad vice in children 
2 to 6 years of age.  
Reference: Circular Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
34.  CAMPHOR  
1.     The following boxed warning  shall be included on the labels  of products 
containing Camphor:  
 
 
 
 
 
 
2.    The following warning and precaution  shall be included in the package 
insert of products containing Camphor:  
 
WARNING  
 
This product is contraindicated in children  below 2 years of age. Caution 
must be exercised when older children are treated.  
 
PRECAUTION:  
 
It is dangerous to place any camphor containing product into the nostr il 
of children. A small amount applied this way may cause immediate 
collapse.  CAN CAUSE CONVULSION  
CONTRAINDICATED  IN CHILDREN BELOW 2 YEARS OF AGE. 
CAUTION MUST BE EXERCISED WHEN OLDER CHILDREN ARE 
TREATED  
AVOID DIRECT  APPLICATION INTO THE NOSTRILS  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 459  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
35.  CARBAMAZEPINE  
 
The following statement  shall be included in the package insert  of products 
containing Carbamazepine:  
 
Severe dermatologic reactions including Stevens - Johnson syndrome and 
toxic epidermal necrolysis (Lyell’s Syndrome) have been reported with 
carbamazepine. Patients treated with carbamazepine should closely be 
monitored for signs of hypersensitivity reactions, particularly during the first 
month of therapy. Immed iate discontinuation of therapy should be made 
when cutaneous reactions occur.  
 
Potential for an increase in risk of suicidal thoughts or behaviours.  
36.  CARBIMAZOLE  
 
The following statement  shall be included in the package inserts  of products 
containing Ca rbimazole:  
 
WARNING  
 
Carbimazole may cause white cell disorders such as neutropenia and 
agranulocytosis, which may be fatal if treatment with carbimazole is not 
stopped promptly. These reactions usually occur during the first 3 months of 
therapy, and in mo st cases, are reversible on stopping treatment. Since 
agranulocytosis can develop very rapidly, periodic leucocyte counts alone may 
not be effective in the early detection of these reactions.  
37.  CABERGOLINE  
Please refer to DOPAMINERGIC INGREDIENT  
38.  CARBOCIS TEINE  
 
The following statements shall be included in the label, package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
carbocisteine;  
 
Label  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 460  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
<Product name > may cause severe allergy and serious skin reactions. Stop 
using  <Product name > and seek medical assistance immediately if you 
experience any of the following symptoms:  
• Severe allergy: breathing difficulties, light headedness, skin swellings or 
rash.  
• Severe skin reaction: skin reddening, blisters, rash, fever, sore thr oat or 
eye irritation.  
 
 
Package Insert  
 
a) Adverse Effects /  Undesirable Effects:  
 
Immune System Disorders:  
Anaphylactic / anaphylactoid reaction  
 
Skin and Subcutaneous Tissue Disorders:  
Severe cutaneous adverse reactions (SCAR) e.g. erythema multiforme, 
Stevens -Johnson syndrome (SJS) and toxic epidermal necrolysis 
(TEN). In most of these cases reported at least one other drug was 
administered at the same time, which may have possibly enhanced the 
described mucocutaneous effects.  
 
 
Consumer Medication Info rmation Leaflet (RiMUP)  
 
a) Side Effects : 
 
<Product name > may cause severe allergy and serious skin reactions. 
Stop using <Product name > and seek medical assistance immediately if 
you experience any of the following symptoms:  
• Severe allergy: breathing difficu lties, light headedness, skin 
swellings or rash.  
• Severe skin reaction: skin reddening, blisters, rash, fever, sore 
throat or eye irritation.  
 
 
Reference: Directive No . 14 Year 201 8. Ref. BPFK/PPP/07/25 ( 14 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Carbocisteine Dan Acetylcysteine : Pengemaskinian Label, 
Sisip Bungkusan  Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Den gan Maklumat 
Keselamatan Berkaitan Anaphylactic/ Anaphylactoid Reaction  Dan Severe Cutaneous Adverse 
Reactions (SCAR)   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 461  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
39.  CEFTRIAXONE  
 
The following statement  shall be included in the package inserts  of products 
containing Ceftriaxone:  
 
CONTRAINDICATION  
 
Ceftriaxone is contraindicated in neonates (≤28 days of age) if they require (or 
are expected to require) treatment with calcium -containing intravenous 
solutions, including calcium -containing infusions such as parenteral nutrition, 
because of the risk of precipi tation of ceftriaxone -calcium.  
 
WARNING  
• In patients other than neonates, Ceftriaxone and calcium -containing 
solutions may be administered sequentially to one another if the infusion 
lines are thoroughly flushed between infusions with a compatible fluid.  
• Diluents containing calcium, such as Ringer’s solution or Hartmann’s 
solution, are not to be used to reconstitute Ceftriaxone vials or to further 
dilute a reconstituted vial for intravenous administration because a 
precipitate can form.  Ceftriaxone must not  be administered simultaneously 
with calcium -containing intravenous solutions, including continuous 
calcium -containing infusions such as parenteral nutrition via a Y -site, 
because precipitation of ceftriaxone -calcium can occur.  
 
Reference:  Circular Bil (48 ) dlm. BPFK/PPP/01/03:  Pindaan Pada Kenyataan Amaran 
Berkaitan Dengan "Potential Risk Associated With Concomitant Use Of Ceftriaxone With 
Calcium - Containing Intravenous Solutions" Yang Perlu Dimuatkan Pada Sisip Bungkusan 
Produk Ceftriaxone  
 
40.  CETIRIZINE  
 
The following statement  shall be included in the package insert  of products 
containing Cetirizine:  
 
PRECAUTION  
 
Activities Requiring Mental Alertness: In clinical trials the occurrence of 
somnolence has been reported in some patients taking Cetirizine: d ue caution 
should therefore be exercised when driving a car or operating potentially 
dangerous machinery.                         Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 462  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
41.  CHELIDONIUM MAJUS  
 
The following statement  shall be included on the label  of products containing 
Chelidonium majus  in 2 lang uages ( Bahasa Melayu  and English) in bold font:  
 
WARNING  
 
This product may cause adverse reaction to the liver.  
 
AMARAN  
 
Produk ini mungkin boleh menyebabkan kesan sampingan pada hepar (hati).  
 
Reference:  Circular (bil 17) dlm bpfk02/5/1.3:  Label Amaran Te ntang Penggunaan Bahan 
Chelidonium majus  
42.  CHITOSAN  
 
The following statement  shall be included on the labels and package inserts  of 
products containing chitosan.  
 
“DERIVED FROM SEAFOOD”  
 
Reference:  Circular  Bil (52) dlm BPFK/02/5/1.3: Muatkan Kenyataan 'D erived From 
Seafood' Pada Label Produk Jika Bahan AKtif Adalah Dari pada  Sumber Laut'  
43.   
CHLORHEXIDINE  
 
The following statements shall be included in the package insert, label and 
RiMUP  of pharmaceutical products containing Chlorhexidine:  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
[Product Name] contains chlorhexidine. Chlorhexidine is known to induce 
hypersensitivity, including generalised allergic reactions and anaphylactic 
shock. The prevalence of chlorhexidine hypersensitivity is unknown, but 
availa ble literature suggests this is likely to be very rare. [Product Name] 
should not be administered to anyone with a possible history of an allergic 
reaction to chlorhexidine.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 463  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
If any signs or symptoms of a suspected hypersensitivity reaction such as 
itching , skin rash, redness, swelling, breathing difficulties, light headedness, 
and rapid heart rate develop, immediately stop using the product. 
Appropriate therapeutic countermeasures must be instituted as clinically 
indicated.  
 
b) Undesirable Effects/Side Eff ects:  
 
Immune system disorders  
 
Frequency not known: Hypersensitivity including anaphylactic shock  
 
 
Label and Consumer Medication Information Leaflet (RiMUP)  
 
[Product Name] contains chlorhexidine. Inform your healthcare provider if you 
have a known aller gy to chlorhexidine.  
 
Stop using this product and seek immediate medical assistance if you 
experience rash, itching, swelling, breathing difficulties, light -headedness or 
rapid heartbeat.  
 
 
Reference : Directive No. 8 Year 2017. Ref. BPFK/PPP/07/25 ( 13 ) Jld 1.  Direktif Untuk 
Semua Produk Farmaseutikal Yang Mengandungi Chlorhexidine : Pengemaskinian Sisip 
Bungkusan, Label Dan Risalah Maklumat Ubat U ntuk Pengguna (RiMUP) Dengan Maklumat 
Keselamatan Berkaitan Risiko Reaksi Hipersensitiviti  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 464  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
44.  CHLORPHENIRAMINE  
 
The following statement  shall be included on the labels and package inserts  of 
liquid oral products containing Chlorpheniramine:  
 
WARNING  
  
When  used for treatment of cough and cold;  
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amar an Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
45.  CHORIONIC GONADOTROPHIN  
 
The following  statement  shall be included in the package inserts  of products 
containing Chorionic gonadotrophin:  
 
The ovulation cycle should be monitored with oestriol levels and 
ultrasonography  
46.  CLEMASTINE  
 
The following statement  shall be included on the labels and package inserts  of 
liquid oral products containing Clemastine:  
 
WARNING  
 
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 y ears of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebaga i Bahan Aktif 
Tunggal atau Kombinasi)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 465  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
47.  CLINDAMYCIN  
 
The package insert must emphasize the possibility of pseudomembranous 
colitis with the use of the drug.  
 
The package insert  must include  the following boxed or emphasized 
statements/ warning:  
 
• Clindamyci n therapy has been associated with severe colitis which may 
end fatally.  
• It should be reserved for serious infections where less toxic antimicrobial 
agents are inappropriate.  
• It should not be used in patients with nonbacterial infections, such as 
most uppe r respiratory tract infections.  
• Its use in newborns is contraindicated.  
48.  CLOBAZAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 466  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
49.  CLOPIDOGREL  
 
The following statement  shall be included in the package inserts  of products 
containing Clopid ogrel:  
 
SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE  
Pharmacogenetics: Based on literature data, patients with genetically reduced 
CYP22C19 function (intermediate or poor metabolisers) have lower systemic 
exposure to the active metabolite of clopidogre l and diminished antiplatelet 
responses, and generally exhibit higher cardiovascular event rates following 
myocardial infarction than do patients with normal CYP2C19 function.  
 
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER 
FORMS OF INTERACTION  
Since  clopidogrel is metabolised to its active metabolite by CYP2C19, use of 
drugs that inhibit the activity of this enzyme would be expected to result in 
reduced drug levels of the active metabolite of clopidogrel and a reduction in 
clinical efficacy. Concomit ant use of drugs that inhibit CYP2C19 (e.g proton 
pump inhibitors) should be discouraged.  
 
PHARMACOKINETIC PROPERTIES  
The oxidative step is regulated primarily by Cytochrome P450 ISOENZYMES 
2B6, 3A4, 1A1, 1A2 and 2C19.  
 
Reference: Circular Bil (42) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Berkaitan Dengan 
“Possible Interaction Between Clopidogrel and Proton Pump Inhibitors” yang Perlu Dimuatkan 
Pada Sisip Bungkusan Produk Clopidogrel  
50.  CLOZAPINE  
Please refer to ANTIPSYCHOTIC AGENT  
51.  COBICISTAT  
 
The following  statements shall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
Cobicistat;  
 
 
Package Insert  
 
a) Interactions with Other Medicaments:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 467  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before you use <product name>:  
 
It is i mportant to tell your doctor if you are taking corticosteroids such as 
betamethasone, budesonide, fluticasone, mometasone, prednisone and 
triamcinolone. These medicines are used to treat allergies, asthma, 
inflammatory bowel diseases, inflammatory conditio ns of the eyes, joints Medicinal product 
by therapeutic 
areas  Effects on 
medicina l product 
levels.  Recommendation 
concerning co -
administration with [product 
name]  
All corticosteroids excluding cutaneous products  
Corticosteroids 
primarily 
metabolised by 
CYP3A (including 
betamethasone, 
budesonide, 
fluticasone, 
mometasone, 
prednisone, 
triamcinolone).  Interaction not 
studied with any of 
the components of 
[product name].  
 
Plasma 
concentrations of 
these medicinal 
products may be 
increased when co -
administered with 
[product name], 
resulting in reduced 
serum cortisol 
concentrations.  Concomita nt use of [product 
name] and corticosteroids that 
are metabolised by CYP3A 
(e.g. fluticasone propionate or 
other inhaled or nasal 
corticosteroids) may increase 
the risk of development of 
systemic corticosteroid 
effects, including Cushing's 
syndrome and adr enal 
suppression.  
 
Co-administration with 
CYP3A -metabolised 
corticosteroids is not 
recommended unless the 
potential benefit to the patient 
outweighs the risk, in which 
case patients should be 
monitored for systemic 
corticosteroid effects. 
Alternative corti costeroids 
which are less dependent on 
CYP3A metabolism e.g. 
beclomethasone for intranasal 
or inhalational use should be 
considered, particularly for 
long-term use.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 468  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
and muscles and other inflammatory conditions. If alternatives cannot be 
used, its use should only take place after medical evaluation and under 
close monitoring by your doctor for corticosteroid side effects.  
 
 
Reference : Directive  No. 2 Year 201 8. Ref. BPFK/PPP/07/25 ( 2 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Cobicistat Dan Kortikosteroid (Kecuali Produk  Untuk 
Kegunaan Luar) : Pengemaskinian Sisip Bungkusan Dan Risalah Maklumat Ubat Untuk 
Pengguna (RiMUP) Dengan Maklumat Berkaitan Interaksi Ubat  
 
52.  CODEINE  
(Please also refer to OPIOID)  
 
The following safety information/ statements  shall be included in the  package 
inserts  of products containing Codeine:  
 
Therapeutic Indications  
 
[Product name] is indicated for the relief of painful disorders such as 
headache, dysmenorrhea, conditions involving musculoskeletal pain, myalgias 
and neuralgias. It is also indica ted as an analgesic and antipyretic in conditions 
accompanied by discomfort and fever, such as the common cold and viral 
infections. [Product name] is an effective analgesic after dental work and tooth 
extractions.  
 Codeine is indicated in patients older t han 12 years of age for the treatment of 
acute moderate pain which is not considered to be relieved by other 
analgesics such as paracetamol or ibuprofen (alone).  
 
Pada bahagian Dosing and Administrations  
 
Paediatric population:  
• Children aged less than 12 y ears:   
Codeine should not be used in children below the age of 12 years 
because of the risk of opioid toxicity due to the variable and 
unpredictable metabolism of codeine to morphine.  
  [Product name] is contraindicated in children below the age of 12 year s 
for the symptomatic treatment of cold.  
 
• Children aged 12 years to 18 years:  
[Product name] is not recommended for use in children aged 12 years to 
18 years with compromised respiratory function.  
 
Contraindications  
• In children below the age of 12 years fo r the symptomatic treatment of Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 469  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
colds due to an increased risk of developing serious and life -threatening 
adverse reactions.  
• In all paediatric patients (0 -18 years of age) who undergo tonsillectomy 
and/or adenoidectomy for obstructive sleep apnoea syndrome due to 
increased risk of developing serious and life -threatening adverse 
reactions.  
• In women who are breastfeeding.  
• In patients for whom it is known they are CYP2D6 ultra -rapid 
metabolisers.  
 
Special Warnings and Precautions for use    
 
CYP2D6 metabolism  
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active 
metabolite. If a patient has a deficiency or is completely lacking this enzyme an 
adequate analgesic effect will not be obtained. Estimates indicate that up to 
7% of the Caucasian po pulation may have this deficiency. However, if the 
patient is an extensive or ultra -rapid metaboliser there is an increased risk of 
developing side effects of opioid toxicity even at commonly prescribed doses. 
These patients convert codeine into morphine r apidly resulting in higher than 
expected serum morphine levels.  
 
General symptoms of opioid toxicity include confusion, somnolence, shallow 
breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In 
severe cases this may include sympt oms of circulatory and respiratory 
depression, which may be life -threatening and very rarely fatal. Estimates of 
prevalence of ultra -rapid metabolisers in different populations are summarised 
below:  
Population  Prevalence %  
African/Ethiopian  29% 
African A merican  3.4 to 6.5%  
Asian  1.2 to 2.0%  
Caucasian  3.6 to 6.5%  
Greek  6.0%  
Hungarian  1.9%  
Northern European  1.0 to 2.0%  
 
Post-operative use in children  
There have been reports in the published literature that codeine given post -
operatively in children af ter tonsillectomy and/or adenoidectomy for obstructive 
sleep apnoea, led to rare, but life -threatening adverse events including death. 
All children received doses of codeine that were within the appropriate dose Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 470  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
range; however there was evidence that these  children were either ultra -rapid 
or extensive metabolisers in their ability to metabolise codeine to morphine.  
 
Children with compromised respiratory function  
Codeine is not recommended for use in children in whom respiratory function 
might be compromised  including neuromuscular disorders, severe cardiac or 
respiratory conditions, upper respiratory or lung infections, multiple trauma or 
extensive surgical procedures. These factors may worsen symptoms of 
morphine toxicity.  
 
3.Pregnancy and Lactation  
  
Pregn ancy  
Careful consideration should be given before prescribing the product for 
pregnant patients. Opioid analgesics may depress neonatal respiration and 
cause withdrawal effects in neonates of dependent mothers.  
As a precautionary measure, use of [Product n ame] should be avoided during 
the third trimester of pregnancy and during labor.  
 
Breastfeeding  
[Product name] is contraindicated in women during breastfeeding.  
At normal therapeutic doses codeine and its active metabolite may be present 
in breast milk at  very low doses and is unlikely to adversely affect the breast 
fed infant. However, if the patient is an ultra -rapid metaboliser of CYP2D6, 
higher levels of the active metabolite, morphine, may be present in breast milk 
and on very rare occasions may resul t in symptoms of opioid toxicity in the 
infant, which may be fatal.  
 
Reference : Directive No.  16 Year  2016. Rujukan BPFK/PPP/07/25 ( 2 ) Jld 1.  
DIREKTIF BAGI SEMUA PRODUK YANG MENGANDUNGI CODEINE DENGAN MAKLUMAT 
KESELAMATAN BERKAITAN RISIKO KESAN ADVERS  
RESPIRATORY DEPRESSION  
 
53.  COLCHICINE  
 
The following statement  shall be included in the package inserts  of products 
containing Colchicines:  
 
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER 
FORMS OF INTERACTION:  
•  
• Potential risk of severe drug interactions , including death, in certain 
patients treated with colchicine and concomitant P -glycoprotein or strong Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 471  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
CYP3A4 inhibitors such as clarithromycin, cyclosporin, erythromycin, calcium 
channel antagonists (e.g Verapamil and Diltiazem), telithromycin, 
ketoconaz ole, itraconazole, HIV protease inhibitors and nefazodone.  
•  
• P-Glycoprotein or strong CYP3A4 inhibitors are not to be used in patients 
with renal or hepatic impairment who are taking colchicine.  
•  
• A dose reduction or interruption of colchicine treatment sh ould be 
considered in patients with normal renal and hepatic function if treatment with 
a P-glycoprotein or a strong CYP3A4 inhibitor is required. Avoid consuming 
grapefruit and grapefruit juice while using colchicine.  
 
Reference: Circular Bil (45) dlm. B PFK/PPP/01/03:  Kenyataan Amaran Berkaitan Dengan 
“Severe Drug Interaction Between Colchicine and P -Glycoprotein or Strong CYP3A4 Inhibitors” 
Yang Perlu Dimuatkan Pada Sisip Bungkusan Produk Colchicine  
 
54.  CORTICOSTEROID  
 
1. The following statements shall be included in the package insert and 
RiMUP  of inhaled corticosteriod used for treatment of Chronic Obstructive 
Pulmonary Disease (COPD) such as budesonide  and fluticasone  
(product containing single active ingredient and in combination) and 
beclomethasone  (only for combination product):  
 
 
Package Insert  
 
a) Special Warnings and Precautions for Use:  
 
 Pneumonia in patients with COPD  
An increase in the incidence of pneumonia, including pneumonia 
requiring hospitalisation, has been observed in patients with COPD 
receiving inhaled corticosteroids. There is some evidence of an 
increased risk of pneumonia with increasing steroid dose but this has 
not been demonstrated conclusively across all studies.  
 
There is no conclusive clinical evidence for intra -class difference s in the 
magnitude of the pneumonia risk among inhaled corticosteroid products.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 472  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Physicians should remain vigilant for the possible development of 
pneumonia in patient with COPD as the clinical features of such 
infections overlap with the symptoms of COPD exacerbations.  
 
Risk factors for pneumonia in patients with COPD include current 
smoking status, older age, low body mass index (BMI) and severe 
COPD.  
 
b) Undesirable Effects:  
 
“Pneumonia (in COPD patients)” to be listed as “Common” adverse drug 
reaction i n the “Infections and Infestations” SOC.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Possible Side Effects  
 
Pneumonia (infection of the lung) in COPD patients (common  
side effect)  
• Tell your doctor if you have any of the following while  
taking <pr oduct name> they could be symptoms of a lung infection:  
­ Fever or chills;  
­ Increased mucus production or change in mucus colour;  
­ Increased cough or increased breathing difficulties.  
 
 
2. The following statements shall be included in the package insert and  
RiMUP  of products containing corticosteroid (except products for external 
use):  
 
(i) Products containing Beclomethasone:  
 
Package Insert   
 
a) Interactions with Other Medicaments:  
Beclomethasone is less dependent on CYP3A metabolism than 
some other corticosteroid s, and in general interactions are unlikely; 
however the possibility of systemic effects with concomitant use of 
strong CYP3A inhibitors (e.g. cobicistat) cannot be excluded, and 
therefore caution and appropriate monitoring is advised with the use 
of such agents.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 473  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Consumer Medication Information Leaflet (RiMUP)   
 
a) Before you use <product name>:  
 
Some medicines may increase the effects of [product name] and 
your doctor may wish to monitor you carefully if you are taking these 
medicines (including some medicin es for HIV such as cobicistat).  
 
 
(ii) Products containing corticosteroids other than Beclomethasone:  
 
Package Insert   
 
a) Interactions with Other Medicaments:  
Co-treatment with CYP3A inhibitors, including cobicistat -containing 
products, is expected to increase th e risk of systemic side -effects. 
The combination should be avoided unless the benefit outweighs 
the increased risk of  systemic corticosteroid side -effects, in which 
case patients should be monitored for systemic corticosteroid side -
effects.  
 
Consumer Medi cation Information Leaflet (RiMUP)   
 
a) Before you use <product name>:  
 
Some medicines may increase the effects of [product name] and 
your doctor may wish to monitor you carefully if you are taking these 
medicines (including some medicines for HIV such as cob icistat).  
 
Reference:  
1. Directive No. 9 Year 2017. Ref. BPFK/PPP/07/25 ( 14 ) Jld 1.  Direktif Untuk Semua 
Produk Inhalasi Kortikosteroid Yang Diguna kan Untuk Rawatan Chronic Obstructive 
Pulmonary Disease (COPD)  : Pengemaskinian Sisip Bungkusan Dan Risalah Maklumat 
Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Tambahan Berkenaan Peningkatan 
Risiko Pneumonia  
2. Directive No. 2 Year 2018. Ref. BPFK/PPP/07/25 ( 2 ) Jld 2.  Direktif Untuk Semua 
Produk Yang Mengandungi Cobicistat Dan Kortikosteroid (Kecuali Produk Untuk 
Kegunaan Luaran : Pengemaskinia n Sisip Bungkusan Dan Risalah Maklumat Ubat Untuk 
Pengguna (RiMUP) Dengan Maklumat Berkaitan Interaksi Ubat  
 
55.  COX -2 INHIBITORS  
 
The following statement  shall be included in the package insert  for COX -2 
Inhibitors products containing Celecoxib and Etoricox ib: 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 474  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
• Contraindication for patients who have increased risk of cardiovascular 
disease (ischeamic heart disease and stroke).  
• Warning to prescriber when prescribing COX -2 Inhibitors to patients with 
risk factors of heart disease, hypertension (high blood pres sure), 
hyperlipidemia, diabetes, smoking patient and patient with peripheral 
arterial disease.  
• Statement on limiting the period and dosing is written as ‘Given the 
association between cardiovascular risk and exposure to COX -2 
Inhibitors, doctors are advise d to use the lowest effective dose for the 
shortest possible duration of treatment’.  
• Contraindication for patient using Etoricoxib is written as ‘Contraindication 
for Etoricoxib in patients with hypertension (high blood pressure) whose 
blood pressure is no t under control’.  
 
Reference: Circular Bil (46) dlm BPFK/02/5/1.3:  Keputusan Mesyuarat PBKD - Tindakan -
tindakan regulatori terhadap Cox -2 Inhibitors: Celecocib dan Etoricoxib  
 
56.  CYPROTERONE ACETATE  
 
The following statement  shall be included in the package  inserts  of products 
containing Cyproterone acetate:  
 
WARNING  
Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, which 
has been fatal in some cases, has been reported in patients treated with 
100mg or more of cyproterone acetate. M ost reported cases are in men with 
prostatic cancer. Toxicity is dose -related and develops, usually, several 
months after treatment has begun. Liver function tests should be performed 
pre-treatment and whenever any symptoms or signs suggestive of 
hepatotox icity occur. If hepatotoxicity is confirmed, cyproterone acetate should 
normally be withdrawn, unless the hepatotoxicity can be explained by another 
cause, e.g. metastatic disease, in which case cyproterone acetate should be 
continued only if the perceived  benefit outweighs the risk.  
 
57.  CYPROTERONE ACETATE WITH ETHINYLESTRADIOL IN COMBINATION  
CYPROTERONE ACETATE 2MG AND ETHINYLESTRADIOL 0.035MG  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 475  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
The following statement  shall be included in the package inserts  of products  
containing Cyproterone acetate 2mg a nd Ethinylestradiol 0.035mg  
 
INDICATION:  
 
- Treatment of moderate to severe acne related to androgen -sensitivity (with or 
without seborrhoea) and/or hirsutism in women of reproductive age.  
- For the treatment of acne, [product name] should only be used after  topical 
therapy or systemic antibiotic treatments have failed.  
- Since [product name] is also a hormonal contraceptive, it should not be used in 
combination with other hormonal contraceptives.  
 
 
DOSAGE AND METHOD OF ADMINISTRATION  
(At the beginning part wit h bold format ting) 
 
Note:  [Product name] should not be prescribed for the purpose of 
contraception alone. However, when taken as recommended, [product 
name] will provide reliable contraception in patients treated for the above 
clinical conditions. If patie nt compliance is uncertain and contraception 
is necessary, then a supplementary non -hormonal contraceptive method 
should be considered.  
 
 
UNDESIRABLE EFFECTS:  
 
- Vascular Disorders  
- Rare: Thromboembolism  
 
58.  CYTOTOXIC AGENT  
The following boxed statement  shall be included on the label  of products 
containing Cytotoxic agents:  
 
 
Note:  The label caution should be printed prominently on the label.  
 CAUTION : CYTOTOXIC AGENT  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 476  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
59.  DEXBROMPHENIRAMINE  
 
The following statement  shall be included on the labels and package inserts  of 
liquid oral produ cts containing Dexbrompheniramine:  
 
WARNING  
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years of age.  
 
Reference:  Circular Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Ko mbinasi)    
     
60.  DEXTROMETHORPHAN  
The following statement  shall be included on the labels and package inserts  of 
liquid oral products containing Dextromethorphan:  
 
WARNING  
When used for treatment of cough and cold:  
(a) Not to be used in children less tha n 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
61.  DIAZEPAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 477  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
62.  DICLOFENAC SODIUM  
 
The following statemen t shall be included in the package inserts  of products 
containing Diclofenac sodium:  
 
PRECAUTION  
 
Severe cutaneous reactions, including Stevens - Johnson syndrome and toxic 
epidermal necrolysis (Lyell’s syndrome), have been reported with diclofenac 
sodium.  Patients treated with diclofenac sodium should be closely monitored 
for signs of hypersensitivity reactions. Discontinue diclofenac sodium 
immediately if rash occurs . 
Adverse effects: Dermatological: Occasional - rashes or skin eruptions Cases 
of hair los s, bullous eruptions, erythema multiforme, Stevens - Johnson 
syndrome, toxic epidermal necrolysis (Lyell’s syndrome), and photosensitivity 
reactions have been reported . 
 
 
DOSAGE AND ADMINISTRATION  
 
DOSAGE  
As a general recommendation, the dose should be indi vidually adjusted. 
Adverse effects may be minimized by using the lowest effective dose for the 
shortest duration necessary to control symptoms (see section WARNINGS 
AND PRECAUTIONS).  
 
ESTABLISHED CARDIOVASCULAR DISEASE OR SIGNIFICANT 
CARDIOVASCULAR RISK FA CTORS  
Treatment with diclofenac is generally not recommended in patients with 
established cardiovascular disease (congestive heart failure, established 
ischemic heart disease, peripheral arterial disease) or uncontrolled 
hypertension. If needed, patients w ith established cardiovascular disease, 
uncontrolled hypertension, or significant risk factors for cardiovascular disease 
(e.g. hypertension, hyperlipidaemia, diabetes melilitus and smoking) should be 
treated with diclofenac only after careful consideratio n and only at doses ≤100 
mg daily if treated for more than 4 weeks (see section WARNINGS AND 
PRECAUTIONS).  
 
CONTRAINDICATIONS  
Severe cardiac failure (see section WARNINGS AND PRECAUTIONS).  
 
 
WARNINGS AND PRECAUTIONS  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 478  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
CARDIOVASCULAR EFFECTS  
Treatment with N SAIDs including diclofenac, particularly at high dose and in 
long term, maybe associated with an increased risk of serious cardiovascular 
thrombotic events (including myocardial infarction and stroke).  
 
Treatment with diclofenac is generally not recommende d in patients with 
established cardiovascular disease (congestive heart failure, established 
ischemic heart disease, peripheral arterial disease) or uncontrolled 
hypertension. If needed, patients with established cardiovascular disease, 
uncontrolled hypert ension, or significant risk factors for cardiovascular disease 
(e.g. hypertension, hyperlipidaemia, diabetes melilitus and smoking) should be 
treated with diclofenac only after careful consideration and only at doses ≤100 
mg daily when treatment continues for more than 4 weeks.  
 
As the cardiovascular risks of diclofenac may increase with dose and duration 
of exposure, the lowest effective daily dose should be used for the shortest 
duration possible. The patient's need for symptomatic relief and response to 
therapy should be re -evaluated periodically, especially when treatment 
continues for more than 4 weeks.  
 
Patients should remain alert for the signs and symptoms of serious 
arteriothrombotic events (e.g. chest pain, shortness of breath, weakness, 
slurring o f speech), which can occur without warnings. Patients should be 
instructed to see a physician immediately in case of such an event.  
 
 
ADVERSE DRUG REACTIONS  
 
Cardiac Disorders  
Uncommon*: Myocardial infarction, cardiac failure, palpitations, chest pain.  
* The frequency reflects data from long -term treatment with a high dose (150 
mg/day).  
   
DESCRIPTION OF SELECTED ADVERSE DRUG REACTIONS  
 
Arteriothrombotic events  
Meta -analysis and pharmacoepidemiological data point towards an increased 
risk of arteriothrombot ic events (for example myocardial infarction) associated 
with the use of diclofenac, particularly at a high dose (150 mg daily) and during 
long-term treatment (see section WARNINGS AND PRECAUTIONS).  
 
 
Circular  : (30)dlm.bpfk/ppp/07/25  ; Arahan Pengarah Kanan Perkhidmatan Farmasi Bilangan Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 479  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
7 Year  2015 : Direktif Untuk Semua Produk Yang Mengandungi Diclofenac (Formulasi 
sistemik) : Pengemaskinian Sisip Bungkusan Dengan MaklumatKeselamatan Be rkaitan Kesan 
Advers Kardiovaskular  
63.  DICYCLOMINE  
The following boxed warning  shall be included on the labels and in the 
package inserts  of products containing Dicyclomine:  
 
64.  DIPHENHYDRAMINE  
The following statement  shall be included on the labels and in the package 
inserts  of products containing Diphenhydramine:  
 
WARNING  
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years  of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Ba han Aktif 
Tunggal atau Kombinasi)  
 
65.  DIPHENOXYLATE  
1. The following boxed warning  shall be included on the labels  of products 
containing Diphenoxylate : 
 
 WARNING  
 
Dicyclomine is not recommended for use in in fants  
under the age of six month  
NOT RECOMMENDED FOR CHILDREN UNDER 6 YEARS OF AGE.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 480  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
2. The following statement  shall be included in the package insert  of products 
containing Diphenoxyla te: 
WARNING  
 
 
PRECAUTION  
Appropriate fluid and electrolyte therapy should be given to protect against 
dehydration in all cases of diarrhoea. Oral rehydration therapy which is the use 
of appropriate fluids including oral rehydration salts remains the most effective 
treatment for dehydration due to diarrhoea. The intake of as much of these 
fluids as possible is therefore imperative. Drug -induced inhibition of peristalsis 
may result in fluid detention in the intestine, which may aggravate and mask 
dehydration  and depletion of electrolytes, especially in young children. If 
severe dehydration of electrolyte imbalance is present, diphenoxylate should 
be withheld until appropriate corrective therapy has been initiated.  
66.  DOMPERIDONE  
The following statement  shall b e included on the package inserts  of products 
containing D omperidone:  
 
THERAPEUTIC  INDICATIONS  
 
Domperidone is indicated for the relief of the symptoms of nausea and 
vomiting.  
 
This includes:  
• Nausea and vomiting of functional, organic, infectious or dietar y origin.  
• Nausea and vomiting induced by:  
- radiotherapy or drug therapy.  
- dopamine agonists (such as L -dopa and bromocriptine) used in the 
treatment of Parkinson’s disease.  
 
 
DOSAGE AND ADMINISTRATION   
 
It is recommended to take [product name] 15 -30 minutes  before meals. If taken 
after meals, absorption of the drug is somewhat delayed.  Not recommended for children under 6 years of age.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 481  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Adults and adolescents ≥ 12 years and weighing ≥35 kg and children 
weighing ≥ 35 kg   
 
The dose of [product name] should be the lowest effective dose for the 
individual situation (typically 30  mg/day) and can be increased if necessary to 
a maximum daily oral dose of 40  mg. 
 
Usual ly, the maximum treatment duration should not exceed one week for the 
treatment of acute nausea and vomiting. If nausea and vomiting persists for 
longer than one week, patients should consult their physician. For other 
indications, the initial duration of treatment is up to four weeks. If treatment 
exceeds four weeks, patients should be reevaluated and the need for 
continued treatment reassessed.  
 
Formulation 
(domperidone per unit)  Dosage  Maximum dose per 
day 
Film-coated tablets  
(10 mg/tablet)  1 tablet th ree to four 
times per day  40 mg 
(4×10 mg tablet)  
Oral suspension  
(1 mg/ml)  10 mL three to four 
times per day  40 mg  
(40 mL of 1  mg/mL 
oral suspension)  
 
Neonates, Infants and children  < 12 years of age and weighing < 35 kg, 
and adults and adolescents we ighing < 35 kg  
 
The dose of [product name] should be the lowest effective dose.  The total 
daily dose is dependent on weight (see table below). Since  metabolic functions 
and the blood -brain barrier are not fully developed in the first months of life, the 
risk of neurological side effects is higher in young children. Overdosing may 
cause nervous system disorders in children. The dose should be determined 
accurately based on body weight and not exceed the recommended maximum 
individual and daily dose in neona tes, infants, toddlers and children.  
 
Usually, the maximum treatment duration should not exceed one week for the 
treatment of acute nausea and vomiting. For other indications, the initial 
duration of treatment is up to four weeks. If treatment exceeds four  weeks, 
patients should be reevaluated and the need for continued treatment 
reassessed. Film -coated tablets and orodispersible tablets are unsuitable for 
use in children, adults and adolescents weighing less than 35  kg. 
Suppositories are unsuitable for use  in children.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 482  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Formulation 
(domperidone per 
unit)  Dosage  Maximum dose 
per day  
Oral suspension 
(1 mg/mL)  0.25 mg/kg three 
to four times per 
day 
 1 mg/kg but no 
more than 35  mL 
(35mg)  
 
Renal impairment  
Since the elimination half -life of domperidone is prol onged in severe renal 
impairment (serum creatinine > 6 mg/100 mL, i.e. > 0.6 mmol/L), the dosing 
frequency of [product name] should be reduced to once or twice daily, 
depending on the severity of the impairment, and the dose may need to be 
reduced. Patient s with severe renal impairment should be reviewed regularly.  
 
Hepatic impairment  
[Product name] is contraindicated for patients with moderate (Child -Pugh 7 to 
9) or severe (Child -Pugh >9) hepatic impairment. Dose adjustment is not 
required for patients wit h mild (Child -Pugh 5 to 6) hepatic impairment.  
 
 
CONTRAINDICATIONS   
 
[Product name] is contraindicated in the following situations:  
• Known hypersensitivity to domperidone or any of the excipients.  
• Prolactin -releasing pituitary tumour (prolactinoma).  
• In pati ents who have known existing prolongation of cardiac conduction 
intervals, particularly QTc, patients with significant electrolyte disturbances 
or underlying cardiac diseases such as congestive heart failure (see 
Warnings and Precautions).  
• co-administratio n with QT -prolonging drugs  
• co-administration with potent CYP3A4 inhibitors (regardless of their QT -
prolonging effects).  
• Whenever stimulation of gastric motility might be dangerous, e.g., in the 
presence of gastro -intestinal haemorrhage, mechanical obstruc tion or 
perforation.  
• In patients with moderate or severe hepatic impairment).  
 
 
WARNINGS AND PRECAUTIONS  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 483  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Cardiovascular effects  
Domperidone has been associated with prolongation of the QT interval on the 
electrocardiogram. During post -marketing surveillan ce, there have been very 
rare cases of QT -prolongation and torsades de pointes in patients taking 
domperidone. These reports included patients with confounding risk factors, 
electrolyte abnormalities and concomitant treatment which may have been 
contributi ng factors (see Adverse Reactions).  
 
Epidemiological studies showed that domperidone was associated with an 
increased risk of serious ventricular arrhythmias or sudden cardiac death (see 
Adverse Reactions). A higher risk was observed in patients older than  60 
years, patients taking daily doses greater than 30 mg, and patients 
concurrently taking QT -prolonging drugs or CYP3A4 inhibitors.  
 
Domperidone should be used at the lowest effective dose in adults and 
children.  
 
Domperidone is contraindicated in patien ts with known existing prolongation of 
cardiac conduction intervals, particularly QTc, in patients with significant 
electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), 
or bradycardia, or in patients with underlying cardiac diseases suc h as 
congestive heart failure due to increased risk of ventricular arrhythmia (see 
Contraindications).  
 
Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or 
bradycardia are known to be conditions increasing the proarrythmic risk.  
 
Treatment with domperidone should be stopped if signs or symptoms occur 
that may be associated with cardiac arrhythmia, and the patients should 
consult their physician.  
 
Patients should be advised to promptly report any cardiac symptoms.  
ADVERSE REACTIONS  
 
{information to be included}  
Postmarketing:  
Cardiac Disorders  
Frequency: Very rare   
Ventricular arrhythmias, QTc prolongation, Torsade de Pointes, Sudden 
cardiac death (see Warnings and Precautions)  
 
 
Reference Directive :  (28)dlm.bpfk/ppp/07/25  ; 
ARAHAN PENGARAH KANAN PERKHIDMATAN FARMASI BILANGAN 4 YEAR  2015 : Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 484  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
DIREKTIF UNTUK SEMUA PRODUK DOMPERIDONE UNTUK MENGEHADKAN 
PENGGUNAAN BER IKUTAN RISIKO KESAN ADVERS JANTUNG  
67.  DOPAMINERGIC INGREDIENT  
 
The following warning/ statement related to “Sudden sleep onset”  shall be 
included in the package insert and product literature  of products containing 
dopaminergic ingredients:  
a. alpha -dihydroerg ocryptine  
b. apomorphine  
c. bromocriptine  
d. cabergoline  
e. levodopa  
f. lisuride  
g. piribedil  
h. pramipexole  
i. quinagolide  
j. ropinirole  
 
 
SPECIAL WARNING & SPECIAL PRECAUTIONS FOR USE  
……. has been associated with somnolence and episodes of sudden onset, 
particularly in patients wi th Parkinson’s diseases. Sudden onset of sleep during 
daily activities, in some cases without awareness or warning signs, has been 
reported very rarely. Patients must be informed of this and advised to exercise 
caution while driving or operating machines d uring treatment with ……. 
Patients who have experienced somnolence and/or an episode of sudden 
sleep onset must refrain from driving or operating machines. Furthermore a 
reduction of dosage or termination of therapy may be considered.  
 
 
EFFECTS ON ABILITY T O DRIVE AND USE MACHINES  
Patients being treated with ……. and presenting with somnolence and/or 
sudden sleep episodes must be informed to refrain from driving or engaging in 
activities where impaired alertness may put themselves or others at risk of 
serious  injury or death (e.g. operating machines) until such recurrent episodes 
and somnolence have resolved (see also section on special warnings and 
special precautions for use).  
 
 
UNDESIRABLE EFFECTS  
……. is associated with somnolence and has been associated ve ry rarely with 
excessive daytime somnolence and sudden sleep onset  episodes.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 485  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference: Circular (bil 14) dlm bpfk02/5/1.3:  Keluaran yang mengandungi bahan aktif 
dopaminergik - tanda amaran berkaitan dengan ' sudden sleep onset'  
68.  DOXYCYCLINE  
 
The followin g statements shall be included in the package insert and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
Doxycycline;  
 
 
Package Insert  
 
a)   Warnings and Precautions:  
 
Some patients with spirochete infections may experience a Jarisc h-
Herxheimer reaction shortly after doxycycline treatment is started. 
Patients should be reassured that this is a usually self -limiting 
consequence of antibiotic treatment of spirochete infections.  
 
b)   Adverse Effects/Undesirable Effects:  
 
Immune system disorders  
 
Frequency not known: Jarisch -Herxheimer reaction (see Section 
Warnings and Precautions)  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a)   Side Effects : 
 
[Product name] may cause Jarisch -Herxheimer reaction which usually 
consists of fever, chills, headache, muscle pain, and skin rash. The 
reaction occurs shortly after starting [product name] for spirochete 
infections and is often self -limiting.  
 
 
Reference: Directive No . 19 Year 201 8. Ref. BPFK/PPP/07/25 ( 19 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Doxycycline : Pengemaskinian Sisip Bungkusan  Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamat an 
Berkaitan Jarisch -Herxheimer Reaction  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 486  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
69.  EFAVIRENZ  
 
The following statements shall be included in the package insert and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
Efavirenz;  
 
 
Package Insert  
 
a)   Warnings and Precautions : 
 
QTc prolongation has been observed with the use of efavirenz (see 
Section Pharmacodynamics  and Section Interaction with Other 
Medicaments). Consider alternatives to [Product name] when 
coadministered with a drug with a known risk of Torsade de Pointes o r 
when administered to patients at higher risk of Torsade de Pointes.  
 
b)   Pharmacodynamics:  
 
Cardiac Electrophysiology  
 
The effect of [Product name] on the QTc interval was evaluated in an 
open -label, positive and placebo controlled, fixed single sequenc e 3-
period, 3 -treatment crossover QT study in 58 healthy subjects enriched for 
CYP2B6 polymorphisms. The mean Cmax of efavirenz in subjects with 
CYP2B6 *6/*6 genotype following the administration of 600 mg daily dose 
for 14 days was 2.25 -fold the mean Cmax  observed in subjects with 
CYP2B6 *1/*1 genotype. A positive relationship between efavirenz 
concentration and QTc prolongation was observed. Based on the 
concentration -QTc relationship, the mean QTc prolongation and its upper 
bound 90% confidence interval are 8.7 ms and 11.3 ms in subjects with 
CYP2B6*6/*6 genotype following the administration of 600 mg daily dose 
for 14 days. (see Section Warnings and Precautions & Section Interaction 
with Other Medicaments).  
 
c)   Interactions with Other Medicaments:  
 
QT Prolonging Drugs  
 
There is limited information available on the potential for a 
pharmacodynamic interaction between [Product name] and drugs that 
prolong the QTc interval. QTc prolongation has been observed with the 
use of efavirenz (see Section Pharmacody namics and Section Warnings Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 487  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
and Precautions). Consider alternatives to [Product name] when 
coadministered with a drug with a known risk of Torsade de Pointes.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a)   Before You Use <product name>:  
 
Before yo u start to use it:  
 
Tell your doctor if you have any heart disorder . 
 
 
Reference: Directive No . 18 Year 201 8. Ref. BPFK/PPP/07/25 ( 18 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Efavirenz : Pengemaskinian Sisip Bungkusan  Dan Risalah  
Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan QTc 
Prolongation   
 
70.  EPHEDRINE  
 
The following statement  shall be included on the labels and in the package 
inserts  of products containing Ephedrine:  
 
WARNING  
When used for treatme nt of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan  
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 488  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
71.  ERYTHROMYCIN  
 
The following statement shall be included  in the package insert and RiMUP  of 
products containing erythromycin (except topical/ external and ophtalmic 
preparations);  
 
Package Insert  
 
a) Warnings and Precautions:  
 
There have been reports of infantile hypertrophic pyloric stenosis (IHPS) 
occurring in i nfants following erythromycin therapy. In one cohort of 157 
newborns who were given erythromycin for pertussis prophylaxis, seven 
neonates (5%) developed symptoms of non -bilious vomiting or irritability 
with feeding and were subsequently diagnosed as havin g IHPS 
requiring surgical pyloromyotomy. Since erythromycin may be used in 
the treatment of conditions in infants which are associated with 
significant mortality or morbidity (such as pertussis or chlamydia), the 
benefit of erythromycin therapy needs to be  weighed against the 
potential risk of developing IHPS. Parents and caregivers should be 
informed to contact their physician if vomiting and/ or irritability with 
feeding occurs.  
 
b) Adverse Effects/Undesirable Effects:  
 
Postmarketing Experience:  
 
Gastrointes tinal Disorders: infantile hypertrophic pyloric stenosis.   
 
Consumer Medication Information Leaflet (RiMUP)  
 
Side Effects  
 
If you notice that the child vomits and/or irritability with feeding occurs, 
contact doctor immediately as it may be due to the Infa ntile 
Hypertrophic Pyloric Stenosis (IHPS).  
 
Reference : Directive No. 28 Year 2017. Ref. BPFK/PPP/07/25 ( 33 ) Jld 1.  Direktif Untuk 
Semua Pr oduk Yang Mengandungi Bahan Aktif Azithromycin Dan Erythromycin Kecuali 
Persediaan Topikal/ Eksternal Dan Ubat Untuk Kegunaan Mata : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Amaran Berkaitan 
Risiko Infantile Hy pertrophic Pyloric Stenosis (IHPS ) Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 489  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
72.  ETHINYLESTRADIOL  
 
Please refer to CYPROTERONE ACETATE WITH ETHINYLESTRADIOL IN 
COMBINATION for products containing cyproterone acetate 2mg with 
ethinylestradiol 0.035mg in combination.  
 
The following statements shall be  included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
ethinylestradiol;  
 
Package Insert  
 
a) Contraindications:  
 
[Product name] is contraindicated for concomitant use with the 
medicinal products containing ombitasvir / paritaprevir / ritonavir and 
dasabuvir (See Section Warnings and Precautions and Section 
Interactions with Other Medicaments).  
 
b) Warnings and Precautions:  
 
ALT elevations  
During clinical trials with patients treated for hepatitis C virus infect ions 
(HCV) with the medicinal products containing ombitasvir / paritaprevir / 
ritonavir and dasabuvir with/without ribavirin, transaminase (ALT) 
elevations higher than 5 times the upper limit of normal (ULN) occurred 
significantly more frequent in women us ing ethinylestradiol -containing 
medications such as combined hormonal contraceptives (CHCs). 
Patients who are taking ethinylestradiol -containing medicinal products 
must switch to an alternative method of contraception (e.g. progestin 
only contraception or non-hormonal methods) prior to initiating 
ombitasvir / paritaprevir / ritonavir and dasabuvir therapy (See Section 
Contraindications and Section Interactions with Other Medicaments).  
 
c) Interactions with Other Medicaments:  
 
Concomitant use with the medicinal  products containing ombitasvir / 
paritaprevir / ritonavir and dasabuvir, with or without ribavirin may 
increase the risk of ALT elevations (See Section Contraindications and 
Section Warnings and Precautions). Therefore, users must switch to an 
alternative  method of contraception (e.g., progestogen -only 
contraception or non -hormonal methods) prior to starting therapy with 
this combination drug regimen. [Product name] can be restarted 2 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 490  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
weeks following completion of treatment with this combination drug 
regim en. 
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before You Use <product name>:  
 
When you must not use it:  
Do not use <product name> if you have Hepatitis C and are taking the 
medicinal products containing ombitasvir / paritaprevir / ritonavir and 
dasabuvir.  
 
 Taking other medicines:  
Do not use <product name> if you have Hepatitis C and are taking the 
medicinal products containing ombitasvir / paritaprevir / ritonavir and 
dasabuvir. Your doctor will prescribe another type of contraceptive 
before start ing the treatment with these medicinal products.  
 
 
Reference: Directive No. 13 Year 2018. Ref. BPFK/PPP/07/25 ( 13 ) Jld 2.  Direktif Untuk 
Semua Produk Yang Mengandungi Ethinylestradiol : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Risiko Peningkatan Paras Alanine 
Transaminase (ALT) Akibat Interaksi Dengan Produk Kombinasi Ombitasvir / Pa ritaprevir / 
Ritonavir Dan Dasabuvir  
 
73.  ETORICOXIB  
(Please also refer to COX -2 INHIBITORS)  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing Etoricoxib:  
 
 
Package Insert  
 
Dosage and Administra tion:  
 
 Rheumatoid arthritis  
The recommended dose is 60 mg once daily. In some patients with 
insufficient relief from symptoms, an increased dose of 90 mg once daily 
may increase efficacy. Once the patient is clinically stabilised, down -titration 
to a 60 m g once daily dose may be appropriate. In the absence of an 
increase in therapeutic benefit, other therapeutic options should be 
considered.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 491  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 Ankylosing spondylitis  
The recommended dose is 60 mg once daily. In some patients with 
insufficient relief from sy mptoms, an increased dose of 90 mg once daily 
may increase efficacy. Once the patient is clinically stabilised, down -titration 
to a 60 mg once daily dose may be appropriate. In the absence of an 
increase in therapeutic benefit, other therapeutic options sh ould be 
considered.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
Recommended Dose/How Much to Use   
 
 Rheumatoid arthritis  
The recommended dose is 60 mg once a day, and may increase to 90 mg 
once a day if needed.  
 
 Ankylosing spondylitis  
The recommend ed dose is 60 mg once a day, and may increase to 90 mg 
once a day if needed.  
 
Reference : Directive No. 13 Year 2017. Ref. BPFK/PPP/07/25 ( 18 ) Jld 1.  Direktif Untuk 
Semua Produk Farmaseutikal  Yang Mengandungi Etoricoxib : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat 
Berkaitan Perubahan Dos Permulaan Bagi Rawatan Rheumatoid Arthritis Dan Ankyl osing 
Spondylitis  
 
74.  FAMOTIDINE  
 
The following statement  shall be included in the package inserts  of products 
containing Famotidine:  
 
DOSAGE  
Dosage adjustment is required for patients with moderate to severe renal 
insufficiency. Since CNS adverse effects have been reported in patients with 
moderate to severe renal insufficiency, to avoid excess accumulation of the 
drug, the dose of famotidine may be reduced to half the recommended dose or 
the dosing interval may be prolonged to 36 - 48 hours as indicated b y the 
patient’s clinical response.  
 
PRECAUTION  
As elderly patients are more likely to have decreased clearance of famotidine, Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 492  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
care should be taken in dose selection and it may be useful to monitor renal 
function.  
75.  FIBRATES  
 
The following statement  shall b e included in the package inserts  of products 
containing Fibrates:  
a. Clofibrate,  
b. Bezafibrate  
c. Ciprofibrate, Etofibrate  
d. Fenofibrate  
e. Simfibrate  
f. etc. 
 
DRUG INTERACTION  
Concurrent use of fibrates with HMG -CoA reductase inhibitors may cause 
severe myositis and myo globinuria.  
76.  FILGRASTIM  
The following statement  shall be included in the package inserts  of ALL 
biosimilar products containing  FILGRASTIM  
 
WARNINGS AND PRECAUTIONS  
 
Capillary leak syndrome has been reported after granulocyte -colony 
stimulating factor admi nistration and is characterised by hypotension, 
hypoalbuminaemia, oedema and hemoconcentration. Patients who develop 
symptoms of capillary leak syndrome should be closely monitored and receive 
standard symptomatic treatment, which may include a need for in tensive care.  
 
UNDESIRABLE EFFECTS  
  
Clinical Trials  
In Cancer Patients  
 Capillary Leak Syndrome, which can be life -threatening if treatment is delaye d, 
has been reported uncommonly (≥1/1000 to < 1/100) in cancer patients 
undergoing chemotherapy following administration of granulocyte colony 
stimulating factors.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 493  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 In Normal Donors undergoing peripheral blood progenitor cell 
mobilization  
 Capillary Leak Syndrome, which can be life -threatening if treatment is delayed, 
has been reported in healthy donors undergoing peripheral blood progenitor 
cell mobilization following administration of granulocyte colony stimulating 
factors.  
 
Post Marketing  
Vascular disor ders  
Cases of capillary leak syndrome have been reported in the post marketing 
setting with granulocyte colony stimulating factor use. These have generally 
occurred in patients with advanced malignant diseases, sepsis, taking multiple 
chemotherapy medicati ons or undergoing apheresis.  
Reference:  Circular  Bil (20) dlm. BPFK/PPP/07/25.  Directive No.  13 Year  2014.  
Direktif Untuk Semua  Produk Yang Mengandungi Filgrastim Dan Pegfilgrastim : 
Amaran Berkaitan Risiko  Capillary Leak Syndrome (Cls)   Bagi Pesakit Kanser 
Dan Healthy Donor  (Filgrastim) Dan Bagi  Pesakit Kanser (Pegfilgrastim)  
77.  FLUCLOXACILLIN  
The following warning  shall be included in the package insert  of products 
containing Flucloxacillin:  
WARNING  
Liver Toxicity  
Flucloxacillin can cause severe hepatitis and cholestatic jaundice, 
which may be protracted. T his reaction is more frequent in older 
patients and those who take the drug for prolonged periods (see 
Precaution, Adverse Reactions)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 494  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
78.  FLUCONAZOLE  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing Fluconazole:  
 
 
Package Insert  
 
a) Pregnancy and Lactation:  
 
Use Du ring Pregnancy  
There have been reports of spontaneous abortion and congenital 
abnormalities in infants whose mothers were treated with 150mg of 
fluconazole as a single or repeated dose in the first trimester.  
 
Use in pregnancy should be avoided except in p atients with severe or 
potentially life -threatening fungal infections in whom <product name> 
may be used if the anticipated benefit outweighs the possible risk to the 
fetus. If this drug is used during pregnancy, or if the patient becomes 
pregnant while ta king the drug, the patient should be informed of the 
potential hazard to the fetus.  
 
Effective contraceptive measures should be considered in women of 
child-bearing potential and should continue throughout the treatment 
period and for approximately 1 week (5 to 6 half -lives) after the final 
dose.  
 
There have been reports of multiple congenital abnormalities in infants 
whose mothers were treated with high -dose (400mg/day to 800mg/day) 
fluconazole therapy for coccidioidomycosis (an unapproved indication). 
The relationship between fluconazole use and these events is unclear. 
Adverse fetal effects have been seen in animals only at high -dose levels 
associated with maternal toxicity. There were no fetal effects at 5 mg/kg 
or 10 mg/kg; increases in fetal anatomical  variants (supernumerary ribs, 
renal pelvis dilation) and delays in ossification were observed at 25 
mg/kg and 50 mg/kg and higher doses. At doses ranging from 80 mg/kg 
(approximately 20 -60 times the recommended human dose) to 320 
mg/kg, embryolethality in  rats were increased and fetal abnormalities 
included wavy ribs, cleft palate and abnormal craniofacial ossification.  
 
Case reports describe a distinctive and a rare pattern of birth defects 
among infants whose mothers received high dose (400 -800mg/day) 
fluconazole during most or all of the first trimester of pregnancy. The Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 495  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
features seen in these infants include brachycephaly, abnormal facies, 
abnormal calvarial development, cleft palate, femoral bowing, thin ribs 
and long bones, arthrogryposis, and congeni tal heart disease.  
  
Use During Lactation  
Fluconazole is found in human breast milk at concentrations similar to 
plasma. Breast -feeding may be maintained after a single dose of 150mg 
fluconazole. Breast -feeding is not recommended after repeated use or 
after high -dose flucona zole.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before you use <product name>  
 
Inform your doctor if you have such conditions:  
• Pregnant or planning to become pregnant  
<Product name> may cause harm to your unborn baby. You 
should not take <produc t name> while you are pregnant unless 
your doctor has told you to. Inform your doctor if you are 
pregnant or planning to become pregnant.  
If you are a woman of child -bearing potential, avoid becoming 
pregnant during treatment. Use effective contraception d uring 
treatment and for 1 week after treatment.  
 
• Breast -feeding  
<Product name> is excreted in human breast milk, hence its use 
in nursing mothers is not recommended.However, breast -feeding 
may be maintained if you took a single dose of <product name> 
150mg . Breast -feeding is not recommended after a high dose 
(more than 150 mg) or repeated use of <product name>.  
 
 
Reference : Directive No. 24 Year 2017. Ref. BPFK/PPP/07/25 ( 29 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi Fluconazole : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Baharu 
Berkaitan Risiko Spontaneous Abortion  Serta Memperkukuhkan Maklumat Keselamatan 
Berkaitan Multiple Congenital Abnormalities Dan Penggunaan Dalam Kalangan Ibu Menyusu  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 496  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
79.  FLUORIDE  
 
All toothpastes containing Fluorides should be labeled with the following 
additional information:  
 
a. DIRECTIONS ON USE  
• Do not swallow – spit and rinse after use.  
 
b. FOR CHILDREN BELOW 6 YEARS  
• Use a pea -sized amount of toothpaste (less than 5mm).  
• Supervise child’s brushing.  
 
c. DIRECTIONS ON DENTAL HEALTH  
• Brush at least twice a day.  
• Restrict the amount and frequency of sugary foo d. 
• Visit your dentist at least once a year.  
 
d. GRAPHICS AS SHOWN  
• Child’s use  
• Adult’s use  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 497  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
80.  FLUOROQUINOLONES  
 
The following statement  shall be included in the package inserts  of products 
containing fluoroquinolones:  
 
WARNING AND PRECAUTION  
 
Exacerbation  of myasthenia gravis  
Fluoroquinolones have neuromuscular blocking activity and may exacerbate 
muscle weakness in person with myasthenia gravis. Post marketing serious 
adverse events, including deaths and requirement for ventilator support have 
been associ ated with flouroquinolones use in persons with myasthenia gravis. 
Avoid flouroquinolones in patients with known history of myasthenia gravis  
 
ADVERSE REACTIONS/SIDE EFFECTS   
  
Exacerbation of myasthenia gravis  
Post Marketing Experience  
 
Reference: Circula r Bil (20) dlm BPFK/PPP/01/03 Jld 1:  Direktif untuk Memperkukuhkan 
Amaran Berkaitan dengan Exacerbation of Myasthenia Gravis dalam Sisip Bungkusan Semua 
Produk Antibiotik dalam Kumpulan Fluoroquinolones  
81.  FLURAZEPAM HYDROCHLORIDE  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  
82.  GABAPENTIN  
 
The following statements shall be included in the package insert and 
Consumer Medication Information Leaflet (RiMUP)  of products containing 
Gabapentin;  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
Respiratory depression  
 
Gabapentin has been associated with severe respiratory depression. Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 498  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Patients with compromised respiratory function, respiratory or 
neurological disease, renal impairment, concomitant use of central 
nervous system (CNS) depressants  and the elderly might be at higher 
risk of experiencing this severe adverse reaction. Dose adjustments 
might be necessary in these patients.   
 
b) Adverse Effects/ Undesirable Effects:  
 
Respiratory, thoracic and mediastinal disorders  
 
Frequency ‘rare’: Respiratory depression  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) While You Are Using It:  
 
Before you start to use it  
 
If you have kidney problems, nervous system disorders, respiratory 
disorders or you are more than 65 years old, your doctor may prescribe 
a different dosing regime n. 
 
Tell your doctor or pharmacist if you are taking or have been recently 
taking any medicines for convulsions, sleeping disorders, depression, 
anxiety, or any other neurological or psychiatric problems.  
 
 
b) Side Effects : 
 
Contact your doctor immediately or  go to the Emergency Department of 
your nearest hospital if you experience breathing problems such  as 
slow, shallow or weak breathing after taking this medicine as this can be 
a sign of respiratory depression.  
 
 
Reference : Directive No. 9 Year 201 8. Ref. BPFK/PPP/07/25 ( 9 ) Jld 2.  Direktif Untuk 
Semua Produk Yang Mengandungi Gabapentin : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Uba t Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Respiratory Depression   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 499  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
83.  GADOBENIC ACID  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
 
Indication  of products containing gadobenic acid shall be amended as f ollows:  
 
a)  [Product name] is a paramagnetic contrast agent for use in diagnostic 
magnetic resonance imaging (MRI) of the liver for the detection of focal 
liver lesions in patients with known or suspected primary liver cancer (e.g. 
hepatocellular carcinom a) or metastatic disease. [Product name]  should 
be used only when diagnostic information is essential and not available 
with unenhanced MRI and when delayed phase imaging is required.  
b)   Other indications including use in MRI of the brain and spine, as c ontrast -
enhanced MR - angiography & MRI of the breast shall be removed.  
 
84.  GADOBUTROL  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
85.  GADODIAMIDE  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGI NG 
86.  GADOLINIUM OXIDE  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
87.  GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
 
The following boxed warning and warning  shall be included in the package 
inserts  of pro ducts containing:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 500  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
a. Gadobenate Dimeglumine  
b. Gadobenic acid  
c. Gadobutrol  
d. Gadodiamide  
e. Gadolinium oxide  
f. Gadoteric acid  
g. Gadoversetamide  
h. Gadoxetic acid  
 
 
BOXED WARNING  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WARNING  
• Among the factors that may increase the risk for NSF are repe ated or 
higher than recommended doses of a GBCA.  
 - Exposure to gadolinium – based contrast agents (GBCAs) increases 
the risk for Nephrogenic Systemic Fibrosis (NSF) in pat ients with:  
• acute or chronic severe renal insufficiency (glomerular filtration 
rate  < 30mL/min/1.73m²), or  
• acute renal insufficiency of any severity due to the hepato -renal 
syndrome or in the perioperative liver transplantation period.  
 
- NSF is a debilitat ing and sometimes fatal disease affecting the skin, 
muscle, and internal organs  
 
- Avoid use of GBCAs unless the diagnotic information is essential and 
not available with non -contrast enhanced magnetic resonance imaging 
(MRI).  
 
- Screen all patients for renal dysfunction by obtaining a history and/ or 
laboratory tests.  
 
- When administering a GBCA, do not exceed the dose recommended 
in product labelling. Allow sufficient time for elimination of the GBCA 
prior to any readministration.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 501  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
• For patients receiving haemodialysis, healthcare professionals may 
consider prompt haemodialysis following GBCA administration in order 
to enhance the contrast agent’s elimination. However, it is unknown if  
haemodialysis prevents NSF.  
 
• Determine the renal function of patients by obtaining a medical history of 
conducting laboratory tests that measure renal function prior to using 
GBCA.  
 
• The risk, if any, for developing NSF among patients with mild to 
moderate  renal insufficiency or normal renal function is unknown.  
 
• Post-marketing reports have identified the development of NSF 
following single and multiple administrations of GBCAs.  
  
Reference: Circular Bil (2) dlm. BPFK/PPP/01/03 Jld. 1: PENAMBAHAN AMARAN 
BERKOTAK DAN AMARAN TERKINI KE DALAM SISIP BUNGKUSAN SEMUA AGEN 
"CONTRAST MEDIUM" YANG BERASASKAN GADOLINIUM (GADOLINIUM BASED) 
UNTUK TUJUAN 'MAGNETIC RESONANCE IMAGING' "  
 
88.  GADOTERIC ACID  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESON ANCE IMAGING  
89.  GADOVERSETAMIDE  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  
90.  GADOXETIC ACID  
Please refer to GADOLINIUM BASED CONTRAST MEDIUM FOR MAGNETIC 
RESONANCE IMAGING  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 502  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
91.  GAMAT/ STICHOPUS spp.   
For products containing  Gamat/ Stichopus spp. for  ORAL USE ONLY , please 
state:  
“Please consult your pharmacist, doctor, or other healthcare providers 
about any other supplements/ medications you are taking and other 
health care problems. There  may  be a potential for interactions  or side 
effects.” 
92.  GENTAMICIN TOPICAL PREPARATIONS  
The following boxed statement  shall be included in the package inserts  of 
topical Gentamicin preparations:  
 
 
93.  GINKGO BILOBA/ GINKGO EXTRACT  
 
The following statements  shall be included on the labels and  in the package 
inserts  of products containing Gingko biloba / Gingko extract:  
 
As the use of Ginkgo may increase the tendency of bleeding, please consult 
your physician/ pharmacist if you are on or intend to start using any other 
medicines and before you u ndergo any surgical/dental procedure.  
 
(Memandangkan Ginkgo boleh meningkatkan kemungkinan pendarahan, sila 
rujuk kepada doktor/ ahli farmasi sekiranya anda sedang atau akan 
menggunakan ubat lain dan sebelum prosedur pembedahan / dental 
dijalankan ). 
 
Refer ence: Circular Bil (47) dlm BPFK/02/5/1.3:  Pernyataan Amaran Pada Label Dan Sisip 
Bungkusan Produk Yang Mengandungi Ginkgo Biloba / Ginkgo Ekstrak  
 Use of topical gentamicin p reparations in closed hospital settings is 
actively discouraged  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 503  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
94.  GINSENG  
 
The following statements  shall be included on the labels and in the package 
inserts  of products c ontaining Ginseng (including all Panax genus):  
 
• Contraindicated in pregnant women.  
• Safe use in lactating women and children has not been established.  
• Do not exceed the stated dose.  
• Safety on long term use has not been established.  
95.  GLUCOSAMINE  
 
71.1 The follow ing statement  shall be included on the labels and package 
inserts  of products containing Glucosamine (derived from seafood);  
 
“DERIVED FROM SEAFOOD”   
 
71.2 The following statement  shall be included in the package inserts  of 
products containing Glucosamine:  
 
SIDE EFFECT  
 
• Cardiovascular  
Peripheral oedema, tachycardia were reported in a few patients 
following larger clinical trials investigating oral administration in 
osteoarthritis. Causal relationship has not been established.  
• Central nervous system  
Drowsiness, h eadache, insomnia have been observed rarely during 
therapy (less than 1%).  
• Gastrointestinal  
Nausea, vomiting, diarrhoea, dyspepsia or epigastric pain, 
constipation, heartburn and anorexia have been described rarely 
during oral therapy with glucosamine.  
• Skin 
Skin reactions such as erythema and pruritus have been reported 
with therapeutic administration of glucosamine.  
 
Reference:  
a) Circular Bil (52) dlm BPFK/02/5/1.3:  Muatkan Kenyataan 'Derived From Seafood' 
Pada Label Produk Jika Bahan AKtif Adalah Dari pada  Sumber Laut'  
b) Circular Bil (72) dlm BPFK/02/5/1.3:  Mengemaskini dan menyelaraskan maklumat Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 504  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
mengenai kesan sampingan pada label  & sisip bungkusan produk yang mengandungi 
glucosamine  
96.  HIV PROTEASE INHIBITORS  
 
The following statement  shall be included in the p ackage inserts  of products 
containing HIV Protease inhibitors:  
 
ADVERSE REACTION  
 
Although a causal relationship has not been definitively established, protease 
inhibitors may contribute to increase in blood sugar levels and even diabetes in 
HIV patients. Close monitoring of blood glucose level is recommended.  
 
97.  HYDROQUINONE  
 
The following warning  shall be included on the outer labels  of products 
containing Hydroquinone:  
 
WARNING:  
Some users of this product may experience skin irritations. Should this occu r, 
stop using and consult a medical doctor.  
 
For hydroquinone products that do not contain any sun screening agent, a 
statement should be included in the package insert to advise users to either 
use a sun screening agent or protect themselves from sunlight  or to use the 
products only at night.  
 
Reference: Circular (bil 26) dlm bpfkweb.bpkp.3.2000:  Amaran bagi Produk Mengandungi 
Hydroquinone  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 505  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
98.  HYOSCINE (FOR INJECTION ONLY)  
 
The following statements shall be included in the package insert  for products 
contai ning Hyoscine : 
 
 
Package Insert  
 
a) Contraindications:  
 
    <Product name> should not be administered to patients with tachycardia .   
 
b) Warnings and Precautions:  
 
<Product name> can cause tachycardia, hypotension and anaphylaxis, 
therefore use with cauti on in patients with cardiac conditions such as cardiac 
failure, coronary heart disease or cardiac arrhythmia and patients with 
cardiovascular disease (e.g. acute myocardial infarction, hypertension and 
conditions associated with tachycardia or hypertension , and in cardiac 
surgery). Monitoring of these patients is advised. Emergency equipment and 
personnel trained in its use must be readily available.  
 
c) Adverse Effects/Undesirable Effects:  
 
Immune system disorders  
Not known: anaphylactic shock including ca ses with fatal outcome, 
anaphylactic reactions.  
 
Cardiac disorders  
Common: tachycardia  
 
 
Reference : Directive No. 17 Year 2017. Ref. BPFK/PPP/07/25  ( 22 ) Jld 1.  Direktif Untuk  
Semua Produk Yang Mengandungi Hyoscine (Bentuk Dos Injeksi Sahaja) : Pengemaskinian 
Sisip Bungkusan  Dengan Maklumat Keselamatan Berkaitan Risiko Kesan Advers Serius Pada 
Pesakit Jantung Dan Kardiovaskular  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 506  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
99.  IMMUNOSUPPRESANTS  
 
The following information  shall be included in the package inserts  of products 
containing the following immunosuppressants:  
a) Sirolimus  
b) Cyclosporin  
c) Mycophenolate mofetil  
d) Mycophenolic acid  
e) Tacrolimus  
 
WARNINGS AND PRECAUTIONS  
 
Immunosuppressed patients are at increased risk for opportunistic infections, 
including activation of latent viral infections. These include BK virus associated 
nephropathy which has been observed in patients receiving 
immunosuppressants. These infections may lead to serious, including  fatal 
outcomes.  
 
Reference: Circular Bil (44) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Berkaitan Dengan 
“Increased Risk For Opportunistic Infections Such As Activation of Latent Viral Infections 
Including BK Virus – Associated Nephropathy” Yang Perlu Dimuat kan Pada Sisip Bungkusan 
Produk Immunosuppressant  
100.  INSULIN  
The label of the product shall state clearly the source  of insulin.  
101.  INGREDIENTS DERIVED FROM SEAFOOD  
 
The following statement  shall be included on the labels and package inserts  of 
products.  
“DERIVED FROM SEAFOOD”  
 
Reference: Circular  Bil (52) dlm BPFK/02/5/1.3:  Muatkan Kenyataan 'Derived From 
Seafood' Pada Label Produk Jika Bahan AKtif Adalah Dari pada  Sumber Laut'  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 507  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
102.  INTERFERON ALPHA  
 
The following statements shall be included in the package ins ert and RiMUP  of 
products containing Interferon Alpha : 
 
Package Insert  
 
a) Adverse Drug Reactions:  
 
Respiratory, thoracic and mediastinal disorders:  
Frequency ‘not known’: Pulmonary arterial hypertension (class label for 
interferon products). Cases of pulm onary arterial hypertension (PAH) have 
been reported with interferon al pha products, notably in patients with risk 
factors for PAH (such as portal hypertension, HIV infection, cirrhosis). Events 
were reported at various time points typically several months  after starting 
treatment with interferon al pha. 
 
  
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects  
 
Tell your doctor immediately if you experience:  
• Shortness of breath, persistent coughing, fatigue, chest pain, or swelling of 
the ankles,  limbs and abdomen. These may indicate pulmonary arterial 
hypertension (high blood pressure in the arteries that supply the lungs).  
 
Reference : Directive No. 1  Year 2017 . Ref. BPFK/PPP/07/25 ( 6  ) Jld 1.  Direktif Bagi 
Semua Produk Yang Mengandungi Interferon Alfa Dan Interferon Beta : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna Dengan Maklumat Keselamatan 
Berkaita n Risiko Kesan Advers Pulmonary Arterial Hypertension  (PAH ) 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 508  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
103.  INTERFERON BETA  
 
The following statements shall be included in the package insert and RiMUP  of 
products containing Interferon Beta : 
 
Package Insert  
 
a) Adverse Drug Reactions:  
 
Respiratory, tho racic and mediastinal disorders:  
Frequency ‘not known’: Pulmonary arterial hypertension (class label for 
interferon products). Cases of pulmonary arterial hypertension (PAH) have 
been reported with interferon beta products. Events were reported at various 
time points including up to several years after starting treatment with interferon 
beta.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects  
 
Tell your doctor immediately if you experience:  
• Shortness of breath, persistent coughing, fatigue,  chest pain, or swelling of 
the ankles, limbs and abdomen. These may indicate pulmonary arterial 
hypertension (high blood pressure in the arteries that supply the lungs).  
 
Reference : Directive No. 1  Year 2017 . Ref. BPFK/PPP/07/25 ( 6  ) Jld 1.  Direktif Bagi 
Semua Produk Yang Mengandungi Interferon Alfa Dan Interferon Beta : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Penggu na Dengan Maklumat Keselamatan 
Berkaitan Risiko Kesan Advers Pulmonary Arterial Hypertension  (PAH ) 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 509  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
104.  KAOLIN, PECTIN, KAOLIN -PECTIN  
The following boxed warning  shall be included on the labels : 
 
 
 
The following statement  shall be included in the package in serts  of products 
containing kaolin and/ or pectin:  
 
WARNING  
 
 
 
 
 
Severe constipation, which may lead to faecal impaction, may rarely occur in 
children and the elderly patients taking kaolin and pectin. Kaolin and pectin 
may interfere with the absorption of other drugs, including antibiotics, 
administered concurrently.  
 
PRECAUTION  
Appropriate fluid and electrolyte therapy should be given to protect against 
dehydration. Oral rehydration therapy with the use of appropriate fluids 
including oral rehydration s alts - remains the most effective treatment for 
dehydration due to diarrhoea. The intake of as much of these fluids as possible 
is therefore imperative.  
105.  KETOCONAZOLE  
 
a) Indication of products containing oral ketoconazole is restricted as follows, 
and the p ackage insert of the product shall be amended accordingly:  
 
[BRAND NAME] (ketoconazole) Tablets should be used only when other 
effective antifungal therapy is not available or tolerated and the potential 
benefits are considered to outweigh the potential ri sks. 
 
[BRAND NAME] (ketoconazole) Tablets are indicated for the treatment of the Not recommended for children under 6 years of age.  NOT RECOMMENDED FOR CHILDREN UNDER 6 YEARS OF AGE.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 510  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
following systemic fungal infections in patients who have failed or who are 
intolerant to other therapies: blastomycosis, coccidioidomycosis, 
histoplasmosis, chromomycosis, an d paracoccidioidomycosis.  
 
[BRAND NAME] (ketoconazole) Tablets should not be used for fungal 
meningitis because it penetrates poorly into the cerebrospinal fluid.  
 
Reference: Directive (9)dlm.BPFK/PPP/07/25:  Direktif untuk memperketatkan indikasi 
semua produk ketoconazole oral dan mengehadkan penggunaan di hospital sahaja berikutan 
risiko kesan advers hepatotoksisiti  
 
 
b) The following statement  shall be included in the package inserts  of 
products containing oral ketoconazole:  
 
CONTRAINDICATIONS  
 
In patients with acute or chronic liver disease.  
 
WARNINGS & PRECAUTIONS  
 
 
 
 
 
 
 
Hepatotoxicity  
Very rare cases of serious hepatotoxicity, incl uding cases with a fatal outcome 
or requiring liver transplantation have occurred with the use of oral 
ketoconazole. Some patients had no obvious risk factors for liver disease. 
Cases have been reported that occurred within the first month of treatment, 
including some within the first week.  
 
The cumulative dose of the treatment is a risk factor for serious hepatotoxicity. 
Factors which may increase the risk of hepatitis are prolonged treatment with 
ketoconazole tablets, females over 50 years of age, previo us treatment with 
griseofulvin, a history of liver disease, known drug intolerance and concurrent 
use of medication which compromises liver function. A period of one month 
should be allowed between cessation of griseofulvin treatment and 
commencement treat ment with ketoconazole tablets because of an apparent Because of the risk for serious hepatotoxicity, [BRAND NAME] should be 
used only when t he potential benefits are considered to outweigh the 
potential risks, taking into consideration the availability of other effective 
antifungal therapy.  
 
Assess liver function, prior to treatment to rule out acute or chronic liver 
disease, and monitor at fr equent and regular intervals during treatment, 
and at the first signs or symptoms of possible hepatotoxicity.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 511  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
association between recent griseofulvin therapy and hepatic reactions to 
ketoconazole tablets.  
 
Monitor liver function in all patients receiving treatment with ketoconazole 
tablets (see Monitoring of h epatic function).  
  
Patients should be instructed to promptly report to their physician signs and 
symptoms suggestive of hepatitis such as anorexia, nausea, vomiting, fatigue, 
jaundice, abdominal pain or dark urine. In these patients, treatment should be 
stopped immediately and liver function should be conducted.  
 
Monitoring of hepatic function  
Monitor liver function in all patients receiving treatment with ketoconazole 
tablets.  Monitor liver function prior to treatment to rule out acute or chronic 
liver disease (see CONTRAINDICATIONS), after two weeks of treatment and 
then on a monthly basis and at the first signs or symptoms of possible hepatic 
toxicity.  When the liver function tests indicate liver injury, the treatment should 
be stopped immediately.    
 
A risk and benefit evaluation should be made before oral ketoconazole is used 
in cases of non -life threatening diseases requiring long treatment periods.  
 
In patients with elevated liver enzymes, or who have experienced liver toxicity 
with other drugs,  treatment should not be started unless the expected benefit 
exceeds the risk of hepatic injury.  In such cases, close monitoring of the liver 
enzymes is necessary.  
 
UNDESIRABLE EFFECTS  
 
Post -marketing Experience  
 
Hepato -biliary Disorders  
Very rare: seriou s hepatotoxicity, including hepatitis cholestatic, biopsy -
confirmed hepatic necrosis, cirrhosis, hepatic failure including cases resulting 
in transplantation or death (see WARNINGS & PRECAUTIONS).  
 
Reference: Directive Bil (22) dlm BPFK/PPP/01/03 Jld 1:  Direktif memperkukuhkan amaran 
berkaitan dengan risiko hepatoksisiti yang teruk dalam sisip bungkusan semua produk oral 
ketoconazole  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 512  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
106.  KETOROLAC TROMETHAMOL (KETOROLAC TROMETHAMINE)  
 
The following statements  shall be included in the package inserts  of produ cts 
containing Ketorolac tromethamol:  
 
THE PRODUCT SHALL BE INDICATED FOR THE FOLLOWING  
For short -term management of moderate to severe acute post -operative pain 
following surgical procedures associated with low risk of haemorrhage.  
 
DOSAGE AND DURATION OF  TREATMENT  
Parenteral administration: The starting dose should be 10mg with subsequent 
doses of 10 -30mg four to six hourly as required. The lowest effective dose 
should be used. The total daily dose of 90mg for the non -elderly and 60mg for 
the elderly shou ld not be exceeded. Maximum duration of parenteral treatment 
is 2 days for all age groups. In patients who have received parenteral ketorolac 
and are converted to oral tablets, the total combined daily dose of all forms of 
ketorolac should not exceed 90mg for non -elderly and 60mg for the elderly. 
Maximum duration of treatment for the oral formulation is 7 days.  
 
CONTRAINDICATIONS  
• A history of peptic ulceration or gastrointestinal bleeding  
• A history of haemorrhagic diathesis  
• A history of confirmed or suspec ted cerebrovascular bleeding  
• Operations associated with a high risk of haemorrhage  
• A history of asthma  
• Moderate or severe renal impairment (serum creatinine > 160 mol/L)  
• Hypovolaemia or dehydration from any cause  
• Hypersensitivity to NSAIDs or aspirin  
• Durin g pregnancy, labour, delivery or lactation  
• Concomitant administration with other NSAIDs, anticoagulant including 
low dose heparin  
107.   
LEVETIRACETAM  
 
The following statements shall be included in the package insert  and 
Consumer Medication Information Leaflet  (RiMUP)  for products containing 
Levetiracetam;  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 513  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Package Insert  
 
a)   Warnings and Precautions:  
 
Acute kidney injury  
The use of levetiracetam has been rarely associated with acute kidney 
injury, with a time to onset ranging from a few days to several mont hs. 
  
 
b) Undesirable Effects:  
 
Renal and urinary disorders:  
Frequency rare: acute kidney injury.  
 
Musculoskeletal and connective tissue disorders:  
Frequency rare: rhabdomyolysis and blood creatine phosphokinase 
increased.*  
* Prevalence is significantly highe r in Japanese patients when compared to 
non-Japanese patients.  
 
Cases of encephalopathy have been rarely observed after levetiracetam 
administration. These undesirable effects generally occurred at the 
beginning of the treatment (few days to a few months)  and were reversible 
after treatment discontinuation.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects : 
 
Tell your doctor immediately if you notice any of the following:  
• Symptoms such as low urine volume, tiredness, nausea, vomiting, 
confusi on and swelling in the legs, ankles or feet, may be a sign of 
sudden decrease of kidney function.  
• Signs or symptoms including muscleache, feeling of weakness and 
dark urine may indicate the side effect of rhabdomyolysis (breakdown 
of muscle tissue).  
• If som eone around you notices signs of confusion, somnolence 
(sleepiness), amnesia (loss of memory), memory impairment 
(forgetfulness), abnormal behaviour or other neurological signs 
including involuntary or uncontrolled movements, these could be 
symptoms of an encephalopathy.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 514  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference: Directive No. 3 Year 201 8. Ref. BPFK/PPP/07/25 ( 3 ) Jld 2. Direktif Untuk 
Semua Produk Yang Mengandungi Levetir acetam  : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Acute Kidney Injury, Rhabdomyolysis/ Blood Creatine Phosphokinase Increased  Dan 
Encephalopathy  
 
108.  LEVODOPA  
Please refer to DOPAMI NERGIC INGREDIENT  
109.  LEVONORGESTREL  
 
The following statements shall be included in the package insert, label and 
RiMUP  of emergency contraceptives containing Levonorgesteral:  
 
 
Package Insert  
 
a) Recommended Dose:  
 
Women who have used enzyme -inducing drugs during the last 4 weeks and 
need emergency contraception are recommended to use a non -hormonal 
emergency contraceptive, i.e. Cu -IUD or take a double dose of 
levonorgestrel (i.e. <number of> tablets taken together) for those women 
unable or unwilling to use  Cu-IUD. 
 
b) Interaction of Other Medicaments:  
 
The metabolism of levonorgestrel is enhanced by concomitant use of liver 
enzyme inducers, mainly CYP3A4 enzyme inducers. Concomitant 
administration of efavirenz has been found to reduce plasma levels of 
levon orgestrel (AUC) by around 50%.  
   
Drugs suspected of having similar capacity to reduce plasma levels of 
levonorgestrel include barbiturates, phenytoin, carbamazepine, herbal 
medicines containing Hypericum perforatum (St. John’s wort), rifampicin, 
ritonavir , and griseofulvin.  
 
For women who have used enzyme -inducing drugs in the past 4 weeks and 
need emergency contraception, the use of non -hormonal emergency 
contraception (i.e. a Cu -IUD) should be considered. Taking a double dose of Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 515  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
levonorgestrel (i.e. 3 mg  within 72 hours after the unprotected intercourse) is 
an option for women who are unable or unwilling to use a Cu -IUD, although 
this specific combination (a double dose of levonorgestrel during 
concomitant use of an enzyme inducer) has not been studied.  
 
 
Label  
 
If you have used certain other medicines in the last 4 weeks , in particular 
treatment for epilepsy, tuberculosis, for HIV infection or herbal medicines 
containing St. John´s wort (see leaflet), <product name> may work less 
effectively. If you use these medicines take <number of>tablets of <product 
name>. If you are unsure or to ask for an alternative treatment speak to your 
doctor or pharmacist before using <product name>.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before you use <product n ame>  
 
-Taking other medicines  
 
If you have used any of the medicines below during the last 4 weeks, 
<product name> may work less effectively.Your doctor may prescribe 
another type of (non -hormonal) emergency contraceptive, i.e. a copper 
intrauterine device  (Cu-IUD). If this is not an option for you or if you are 
unable to see your doctor promptly, you can take a double dose (i.e. 
<number of> tablets) of <product name>:  
• medicines used to treat epilepsy (e.g. phenobarbitone, phenytoin, 
carbamazepine)  
• medicine s used to treat tuberculosis (e.g. rifampicin)  
• medicines used to treat HIV (e.g. ritonavir, efavirenz)  
• medicines used to treat fungal infections (e.g. griseofulvin)  
• herbal remedies containing St. John’s wort (Hypericum perforatum)  
 
Speak to your doctor or pharmacist if you need further advice on the 
correct dose for you.  
 
Consult your doctor as soon as possible after taking the tablets for further 
advice on a reliable form of regular contraception and to exclude a 
pregnancy.  
 
 
Reference : Directive No. 11 Y ear 2017. Ref. BPFK/PPP/07/25 ( 16 ) Jld 1.  Direktif Untuk Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 516  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Semua Produk Kontraseptif Kecemasan Yang Mengandungi Levonorgestrel Dengan 
Maklumat Ber kaitan Interaksi Antara Ubat -Ubatan Yang Dikelaskan Sebagai Hepatic Enzyme 
Inducer  Dan Keberkesanan Kontrasepsi  
110.  LINCOMYCIN  
 
For all products containing Lincomycin:  
 
The package insert must emphasize the possibility of  pseudomembranous 
colitis with the u se of the drug and must include the following boxed or 
emphasized statement/ warning:  
a. Lincomycin therapy has been associated with severe colitis which may 
end fatally.  
b. It should be reserved for serious infections where less toxic 
antimicrobial agents are i nappropriate.  
c. It should not be used in patients with nonbacterial infections, such as 
most upper respiratory tract infections.  
d. Its use in newborns is contraindicated.  
111.  LISURIDE  
Please refer to DOPAMINERGIC INGREDIENT  
112.  LIQUID PARAFFIN  
 
The following state ment  shall be included on the labels  of products containing 
Liquid paraffin as laxative:  
 
•  Not recommended for use in children below 3 years of age;  
•  Not recommended for use in pregnant women;  
•  Repeated use is not advisable;  
• Consult your doctor if laxative s are needed every day, if you have 
persistent abdominal pain or have a condition which makes swallowing 
difficult.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 517  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
113.  LOPERAMIDE  
1. The following boxed warning  shall be included on the labels  of products 
containing Loperamide:  
 
 
2. The following statement  shall be included in the package inserts  of 
products containing Loperamide:  
a) WARNING  
 
 
 
b) PRECAUTION  
Appropriate fluid and electrolyte therapy should be given to protect 
against dehydration in all cases of diarrhoea. Oral rehydration therapy 
which is the use o f appropriate fluids including oral rehydration salts 
remains the most effective treatment for dehydration due to diarrhoea. 
The intake of as much of these fluids as possible is therefore 
imperative. Drug -induced inhibition of peristalsis may result in flu id 
retention in the intestine, which may aggravate and mask dehydration 
and depletion of electrolytes. If severe dehydration or electrolyte 
imbalance is present Loperamide should be withheld until appropriate 
corrective therapy has been initiated.  
c) Warnings  and Precautions  
The use of higher than the recommended doses for control of the 
diarrhea may cause abnormal heart rhythms and serious cardiac events 
leading to death. However, in adult patients receiving the recommended 
dosage of loperamide, cases of sync ope and ventricular tachycardia 
have been reported. Some of these patients were taking other drugs or 
had other risk factors that may have increased their risk of cardiac 
adverse reactions.  
Abuse and misuse of loperamide, as an opioid substitute, have been  
described in individuals with opioid addiction (see Overdose).  NOT RECOMMENDED FOR CHILDREN UNDER 6 YEARS OF AGE  
Not recommended for children under 6 years of age. Its use has been 
associated with fatal epis odes of paralytic ileus in infants and young 
children . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 518  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
d) Adverse Reactions  
Post-marketing Experience  
Cardiac Disorders: QT/QTc interval prolongation, Torsades de Pointes, 
other ventricular arrhythmias, cardiac arrest, syncope, and death (see 
Warning  and Precautions)>  
e) Overdose  
In individuals who have intentionally ingested overdoses (reported in 
doses from 40 mg up to 792 mg per day) of loperamide HCL, 
prolongation of the QT/QTc interval, Torsades de Pointed, other 
ventricular arrhythmias and cardiac arrest, have been observed (see 
Warnings and Precautions). Fatal cases have also been reported.  
 
3. The following statement  shall be included in the RiMUP  of products 
containing Loperamide:  
a) If you use too much (overdose)  
If you have taken more than the rec ommended dose of [product name], 
immediately contact your doctor or go to the Emergency Department of 
your nearest hospital for advice.  
 
 Symptoms may include :  
  
• changes to your heartbeat such as increased heart rate and 
irregular heart rhythm (these sy mptoms can have potentially 
serious, life -threatening consequences)  
• muscle stiffness  
• uncoordinated movements  
• drowsiness  
• difficulty urinating  
• weak breathing  
 
 
Reference : Directive No. 14 Year 2017. Ref. BPFK/PPP/07/25 ( 19 ) Jld 1.  Direktif Untuk 
Semua Produk Farmaseutikal  Yang Mengandungi Loperamide : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklum at 
Berkaitan Risiko Kesan Advers Pada Jantung Yang Serius Susulan Pengambilan Loperamide 
Melebihi Dos Yang Disyorkan Dan Isu Penyalahgunaan  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 519  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
114.  LORAZEPAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  
115.  LOVASTATIN  
 
The following statement  shall be included in the package inserts  of products 
containing  Lovastatin:  
 
1. Contraindications:  
 
• Concomitant administration of strong CYP3A4 inhibitors (e.g. 
itraconazole, ketoconazole, posaconazole, voriconazole, HIV 
protease inhibitors, boceprevir, te laprevir, erythromycin, 
clarithromycin, telithromycin and nefazodone).  
• Concomitant administration of cyclosporine.  
 
2. Dosage and Administration:  
 
Concomitant Therapy  
The combined use of lovastatin with gemfibrozil should be avoided.  
 
In patients taking da nazol, verapamil, diltiazem, fibrates (except 
gemfibrozil) or lipid -lowering dose of niacin (≥1g/day) concomitantly with 
[Product Name], the dose of [Product Name] should not exceed 
20mg/day.  
 
In patients taking amiodarone concomitantly with [Product Name ], the 
dose of [Product Name] should not exceed 40mg/day.  
 
3. Warnings and Precautions:  
 
Colchicine:  Cases of myopathy, including rhabdomyolysis, have been 
reported with lovastatin coadministered with colchicine, and caution 
should be exercised when prescr ibing lovastatin with colchicine.  
 
4. Interactions:  
 
Contraindicated Drugs  
Strong inhibitors of CYP3A4: Concomitant use with strong CYP3A4 
inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 520  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
HIV protease inhibitors, boceprevir, telapre vir, erythromycin, 
clarithromycin, telithromycin and nefazodone) is contraindicated.  
 
Cyclosporine: The risk of myopathy/rhabdomyolysis is increased by 
concomitant administration of cyclosporine. Concomitant use of this drug 
with lovastatin is contraindic ated.  
 
 
Other Drugs  
• Gemfibrozil, other fibrates, niacin ≥1g/day :  
These drugs increase the risk of myopathy when given concomitantly 
with lovastatin, probably because they can produce myopathy when 
given alone. There is no evidence to suggest that these agents affect 
the pharmacokinetics of lovastatin. M yopathy, including 
rhabdomyolysis, has occurred in patients who were receiving 
coadministration of lovastatin with fibric acid derivatives or niacin.  
 
• Danazol, verapamil, diltiazem: The risk of myopathy/rhabdomyolysis is 
increased by concomitant administra tion of danazol, verapamil, or 
diltiazem particularly with higher doses of lovastatin.  
 
• Amiodarone: The risk of myopathy/rhabdomyolysis is increased when 
amiodarone is used concomitantly with higher doses of a closely 
related member of the HMG -CoA reductas e inhibitor class.  
 
• Colchicine: Cases of myopathy, including rhabdomyolysis, have been 
reported with lovastatin coadministered with colchicine, and caution 
should be exercised when prescribing lovastatin with colchicine.  
 
116.  MEFLOQUINE  
 
The following statem ent shall be included in the package inserts  of products 
containing Mefloquine as single ingredient or in combination with other active 
ingredients:  
1. SPECIAL WARNINGS AND PRECAUTIONS FOR USE  
 
a) Products containing Mefloquine as single ingredient : 
 
In chemopro phylaxis the safety profile of mefloquine is characterized by a 
predominance of  neuropsychiatric adverse reactions. If acute anxiety, 
depression, restlessness or confusion  occur during prophylactic use, Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 521  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
[Brand name] (mefloquine) should be discontinued and an alternative 
prophylactic  agent should be recommended. Because of the long half -life of 
mefloquine, adverse reactions  to [Brand name] (mefloquine) may occur or 
persist up to several weeks after discontinuation of the drug. In a  small 
number of patients i t has been reported that dizziness or vertigo and loss of 
balance  may continue for months after discontinuation of the drug.  
 
Eye disorders, including but not limited to optic neuropathy and retinal 
disorders, have been reported during treatment with meflo quine. Any 
patient presenting with a visual disorder should be referred to the treating 
physician, as certain conditions may require stopping treatment with [Brand 
name] (mefloquine) . 
 
b) Products containing Mefloquine in combination with other active 
ingredi entas (mefloquine/artesunate) : 
 
If acute anxiety, depression, restlessness or confusion  occur during 
treatment, [Brand name] (mefloquine/artesunate) should be discontinued 
and an alternative agent should be recommended. Because of the long 
half-life of mef loquine, adverse reactions  to [Brand name] 
(mefloquine/artesunate) may occur or persist up to several weeks after 
discontinuation of the drug. In a  small number of patients it has been 
reported that dizziness or vertigo and loss of balance  may continue for  
months after discontinuation of the drug.  
 
Eye disorders, including but not limited to optic neuropathy and retinal 
disorders, have been reported during treatment with mefloquine. Any 
patient presenting with a visual disorder should be referred to the tre ating 
physician, as certain conditions may require stopping treatment with [Brand 
name] (mefloquine/artesunate).  
 
2. POSTMARKETING ADVERSE EVENT  
 
Nervous system disorders  
Common  Dizziness, headache  
Not known  Balance disorder, somnolence, 
syncope, convul sions, memory 
impairment, peripheral sensory 
neuropathy and peripheral motor 
neuropathy (including paraesthesia, 
tremor and ataxia), encephalopathy  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 522  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 
 
References: Circular (13)dlm.BPFK/PPP/01/03 Jld.3: Pengemaskinian sisip bungkusan 
semua produk antimalaria yang mengandungi mefloquine (termasuk produk kombinasi) 
dengan maklumat kes elamatan berkaitan kesan advers pada sistem saraf (neurologik) yang 
berpanjangan dan gangguan penglihatan  
 Eye disorders  
Common  Visual impairment  
Not known  Vision blurred, cataract, retinal 
disorders and opt ic neuropathy which 
may occur with latency during or after 
treatment  
117.  MELALEUCA LEUCADENDRA  
The following statement  shall be included on the labels  of products containing  
Melaleuca Leucadendra (cajeput oil) in topical  dosage form:  
 
a) Malay  language :-  
 
    AMARAN  
Produk ini tidak boleh disapu pada muka, khususnya di kawasan 
hidung bayi dan kanak -kanak. Ia mungkin boleh menyebabkan 
masalah pernafasan / kesukaran bernafas.  
 
b) English language :- 
 
    WARNING  
This produc t should not be applied to the facial area, in particular 
around the nose of infants and small children. It might cause breathing 
problem / shortness of breath.  
 
References: Directive No. 13, Year  2016  Ref. (44)dlm.BPFK/PPP/07/25  
DIREKTIF BAGI SEMUA PRODUK  YANG MENGANDUNGI BAHAN AKTIF MINYAK 
CAJEPUT (MELALEUCA LEUCADENDRA ) DALAM BENTUK DOS TOPIKAL DENGAN 
MENAMBAH KENYATAAN AMARAN BERKAITAN RISIKO MASALAH PERNAFASAN/ 
KESUKARAN BERNAFAS  
 
118.  MESALAZINE  
The following statements shall be included in the package i nsert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
mesalazine;  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 523  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Package Insert  
 
a) Warnings and Precautions:  
 
Photosensitivity  
More severe reactions are reported in patients with pre -existing skin 
conditions such as atopic derma titis and atopic eczema.  
 
b) Adverse Effects/ Undesirable Effects:  
 
Skin and Subcutaneous Tissue Disorders  
 Frequency “rare”: Photosensitivity  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects:  
 
Photosensitivity: Itchy eruption and exaggerated s unburn on patches of 
sun-exposed skin  
 
 
Reference: Directive No . 12 Year 201 8. Ref. BPFK/PPP/07/25 ( 12 ) Jld 2. Direktif Untuk  
Semua  Produk Yang Mengandungi Mesalazine : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Amaran Kesan Advers 
Photosensitivity  
 
119.  METFORMIN  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing Metformin:  
 
 
Package Insert  
 
1. Recommended Dosage:  
 
a)  Products containing Metformin as a single active ingredient:  
 
Renal impairment  
 
A GFR should be assessed before initiation of treatment with 
metformin containing product s and at least annually thereafter. In Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 524  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
patients at an increased risk of further progression of renal 
impairment and in the elderly, renal function should be assessed 
more frequently, e.g. every 3 -6 months.  
 
GFR mL/min  Total maximum 
daily dose (to be 
divide d into 2 -3 
daily doses)*  Additional 
considerations  
60-89 3000 mg  Dose reduction may be 
considered in relation to 
declining renal function.  
45-59 2000 mg  Factors that may 
increase the risk of 
lactic acidosis should be 
reviewed before 
considering initiatio n of 
metformin. The starting 
dose is at most half of 
the maximum dose.  30-44 1000 mg  
<30 - Metformin is 
contraindicated.  
* The text “to be divided into 2 -3 daily doses” should be omitted for extended release products 
containing metformin as single agen t. 
 
b)  Combination products containing Metformin:  
 
Renal impairment  
 
A GFR should be assessed before initiation of treatment with 
metformin containing products and at least annually thereafter. In 
patients at an increased risk of further progression of re nal 
impairment and in the elderly, renal function should be assessed 
more frequently, e.g. every 3 -6 months.  
 
The maximum daily dose of metformin should preferably be divided 
into 2 -3 daily doses. Factors that may increase the risk of lactic 
acidosis shoul d be reviewed before considering initiation of 
metformin in patients with GFR <60 ml/min.  
 
If no adequate strength of <Product name> is available, individual 
monocomponents should be used instead of the fixed dose 
combination.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 525  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
GFR 
mL/min  Metformin  [other 
monocomponent]  
60-89 Maximum daily dose is 3000 mg. 
Dose reduction may be 
considered in relation to declining 
renal function.   
45-59 Maximum daily dose is 2000 mg.  
The starting dose is at most half 
of the maximum dose.  
30-44 Maximum daily dose is 1000 mg. 
The starting dose is at most half 
of the maximum dose.  
<30 Metformin is contraindicated.  
 
 
2. Contraindications:  
 
• Severely reduced kidney function (GFR <30 mL/min)  
• Any type of acute metabolic acidosis (such as lactic acidosis, 
diabetic ketoacidosis)  
 
 
3. Warnings and Precautions:  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 526  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Lactic acidosis  
 
Lactic acidosis, a very rare but serious metabolic complication, most 
often occurs at acute worsening of renal function or cardiorespiratory 
illness or sepsis. Metformin accumulation occurs at acute worsening  
of renal function and increases the risk of lactic acidosis.  
 
In case of dehydration (severe diarrhoea or vomiting, fever or 
reduced fluid intake), metformin should be temporarily discontinued 
and contact with a health care professional is recommended.  
 
Medicinal products that can acutely impair renal function (such as 
antihypertensives, diuretics and NSAIDs) should be initiated with 
caution in metformin -treated patients. Other risk factors for lactic 
acidosis are excessive alcohol intake, hepatic insuffici ency, 
inadequately controlled diabetes, ketosis, prolonged fasting and any 
conditions associated with hypoxia, as well as concomitant use of 
medicinal products that may cause lactic acidosis.  
 
Patients and/or care -givers should be informed of the risk of l actic 
acidosis. Lactic acidosis is characterised by acidotic dyspnoea,  
abdominal pain, muscle cramps, asthenia and hypothermia followed 
by coma. In case of suspected symptoms, the patient should stop 
taking metformin and seek immediate medical attention. Diagnostic 
laboratory findings are decreased blood pH (< 7.35), increased 
plasma lactate levels (>5 mmol/L) and an increased anion gap and 
lactate/pyruvate ratio.  
 
           Renal function  
 
GFR should be assessed before treatment initiation and regularly  there 
after [See Section Recommended Dosage]. Metformin is 
contraindicated in patients with GFR <30 mL/min and should be 
temporarily discontinued in the presence of conditions that alter renal 
function [See Section Contraindications].  
 
 
Consumer Medicati on Information Leaflet (RiMUP)  
 
a) Before you use <product name>:  
 
Do not take <product name>:  
• If you have severely reduced kidney function.  
• If you have lactic acidosis [too much lactic acid in the blood (see Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 527  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
“Risk of lactic acidosis” below)] or ketoacidosis.  Ketoacidosis is a 
condition in which substances called 'ketone bodies' accumulate 
in the blood and which can lead to diabetic pre -coma. Symptoms 
of acidosis may include stomach pain, abnormal breathing and 
drowsiness (if severe).  
 
b) Before you start to use it: 
 
Risk of lactic acidosis  
 
<Product name> may cause a very rare, but very serious side effect 
called lactic acidosis, particularly if your kidneys are not working 
properly. The risk of developing lactic acidosis is also increased with 
uncontrolled diabe tes, serious infections, prolonged fasting or 
alcohol intake, dehydration, liver problems and any medical 
conditions in which a part of the body has a reduced supply of 
oxygen (such as acute severe heart disease). If any of the above 
apply to you, talk to your doctor for further instructions.  
 
Stop taking <product name> for a short time if you have a condition 
that may be associated with dehydration (significant loss of body 
fluids) such as severe vomiting, diarrhoea, fever, exposure to heat or 
if you drink  less fluid than normal. Talk to your doctor for further 
instructions.  
 
Stop taking <product name> and contact a doctor or the nearest 
hospital immediately if you experience some of the symptoms of 
lactic acidosis, as this condition may lead to coma.   
 
Symptoms of lactic acidosis include:  
• vomiting  
• stomach ache (abdominal pain)  
• muscle cramps  
• a general feeling of not being well with severe tiredness  
• difficulty in breathing  
 
Lactic acidosis is a medical emergency and must be treated in a 
hospital.  
 
During treatment with <product name>, your doctor will check your 
kidney function at least once a year or more frequently if you are elderly 
and/or if you have worsening kidney function.  
 
Reference : Directive No. 25 Year 2017. Ref. BPFK/PPP/07/25 ( 30 ) Jld 1.  Direktif Untuk Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 528  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Semua Produk Yang Mengandungi Metformin : Pengemaskinian Sisip Bungkusan Dan Risalah 
Maklumat Ubat Untuk Pengguna (RiMUP) Dengan  Maklumat Berkaitan Penggunaan Dalam 
Kalangan Pesakit Yang Mempunyai Moderately Reduced Kidney Function  Dan Pengukuhan 
Amaran Lactic Acidosis  
120.  METHYL SALICYLATE  
 
The following statements  shall be included in the package inserts and product 
literature  of topical preparations containing methyl salicylate ≥5%:  
 
CAUTION  
This product contains methyl salicylate and when applied or rub on to the skin, 
can be absorbed through the skin into the blood. For patients taking warfarin, 
excessive application on to the sk in for muscle or joint pains may increase the 
chances of bleeding.  
121.  METHYLPHENIDATE  
The following boxed statement  shall be included on the labels and in the 
package insert  of products containing Methylphenidate HCl:  
 
 
 
The following statement  shall be included in the package insert  of product s 
containing Methylphenidate : 
 
 
WARNINGS AND PRECAUTIONS  
 
Priapism  
Prolonged and painful erections, sometimes requiring surgical intervention, 
have been reported with methylphenidate products in both pediatric and ad ult 
patients. Priapism was not reported with drug initiation but developed after 
some time on the drug, often subsequent to an increase in dose. Priapism has 
also appeared during a period of drug withdrawal (drug holidays or during 
discontinuation). Patien ts who develop abnormally sustained or frequent and 
painful erections should seek immediate medical attention.  
Reference: Circular (19) dlm.BPFK/PPP/07/25  Directive  No. 12 Year  2014  FOR SPECIALIST’S USE ONLY  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 529  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Direktif Untuk Semua Produk Yang Mengandungi Methylphenidate: Amaran 
Berkaitan Risiko Priapism (Kesan Ereksi Yang Berpanjangan) Di Kalangan 
Lelaki  
122.  METOCLOPRAMIDE  
 
The following statements  shall b e included in the package inserts  of products 
containing Metoclopramide:  
 
DOSAGE  
Total daily dose of metoclopramide, especially for children and young adults, 
should not normally exceed 0.5mg/kg body weight.  
 
WARNING  
• Avoid doses exceeding 0.5mg/kg/day.  
• Extrapyramidal effects, especially dystonic reaction of metoclopramide 
are more likely to occur in children shortly after initiation of therapy, and 
usually with doses higher than 0.5mg per kg of body weight per day.  
 
The following route of products containin g Metoclopramide  shall update its  
package inserts  according to the directive (24)dlm.BPFK/PPP/07/25 . As below : 
 
1) PARENTERAL ROU TE 
• Indication  
• Dose and Administration  
• Contraindication  
• Special Warnings and Precautions For Use  
 
2) ORAL ROUTE  (Tablet/ Syrup)  
• Indication  
• Dose and Administration  
• Contraindication  
• Special Warnings and Precautions For Use  
 
3) RECTAL ROUTE  (Suppository)  
• Indic ation  
• Dose and Administration  
• Contraindication  
• Special Warnings and Precautions For Use  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 530  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Reference Circular : (24)dlm.BPFK/PPP/07/ 25. Directive No.  17 Year  2014.  
Direktif Untuk Semua Produk Metoclopramide: Memperketatkan Indikasi Dan 
Mengehadkan Dos Penggunaan Berikutan Risiko Kesan Advers Neurologik  
 
123.  METRONIDAZOLE (ALL PRODUCTS EXCEPT FOR EXTERNAL USE)  
 
The following statements s hall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products (except for 
external use) containing Metronidazole;  
 
Package Insert  
 
a) Warnings and Precautions:  
 
Cases of severe hepatotoxicity/ acute hepatic failure , including cases with a 
fatal outcome with very rapid onset after treatment initiation in patients with 
Cockayne syndrome have been reported with products containing 
metronidazole for systemic use. In this population, metronidazole should 
therefore be use d after careful benefit -risk assessment and only if no 
alternative treatment is available. Liver function tests must be performed just 
prior to the start of therapy, throughout and after end of treatment until liver 
function is within normal ranges, or unt il the baseline values are reached. If 
the liver function tests become markedly elevated during treatment, the drug 
should be discontinued.   
 
Patients with Cockayne syndrome should be advised to immediately report 
any symptoms of potential liver injury to  their physician and stop taking 
metronidazole.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
b) Before you use <product name>:  
 
Inform your doctor if you are affected by Cockayne syndrome.  
 
Cases of severe liver toxicity/ acute liver failure in patien ts with Cockayne 
syndrome have been reported with products containing metronidazole.  
 
Stop taking <product name> and tell your doctor immediately if you develop:  
stomach pain, decreased appetite, nausea, vomiting, fever, unusual 
tiredness, yellowing of t he skin and the whites of the eyes, dark -coloured Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 531  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
urine, light or clay -coloured stools or itching.  
 
Reference : Directive No . 18 Year 2017. Ref. BPFK/PPP/07/25 ( 23 ) Jld 1.  Direktif Untuk  
Semua Produk Yang Mengandungi Metronidazole (Kecuali Produk Untuk Kegunaan Luar) : 
Pengemaskinian Sisip Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) 
Dengan Amaran Berkaitan Risiko Hepatotoxicity Dalam  Kalangan Pesakit Cockyne Syndrome  
 
124.   
MICONAZOLE  
 
 
1. Intravaginal preparations  
The following boxed warning  shall be included on the label and in the 
package insert  of intravaginal preparations containing Miconazole:  
 
 
 
 
 
 
 
Reference: Circular (bil 45) dlm bpfkweb.bpkp.2.2001:  Keputusan Mesyuarat Pihak berkuasa 
Kawalan Dadah (PBKD) ke 122 Berhubung Amaran Berkaitan Interaksi Ubat Bagi Semua 
Kelua ran ANTIFUNGAL INTRAVAGINAL Yang Mengandungi Miconazole  
 
 
2. Oral gel preparations  
 
The following statements shall be included in the package insert and 
RiMUP  of oral gel preparations containing Miconazole:  
 
Package Insert  
 
a) Contraindications  
 
Use of miconazol e oral gel in combination with the following drug that is 
subjected to metabolism by CYP2C9 (see Interactions):  
• Warfarin  
 
b) Interactions  Sila dapatkan nasihat doktor atau ahli farmasi sebelum menggunakan 
keluaran ini jika anda mengambil ubat warfarin, iaitu sejenis ubat 
antipembekuan darah, kerana lebam/ pend arahan pada gusi/ hidung 
boleh berlaku secara spontan.  
(Please consult your physician/ pharmacist before using this product 
if you are on the anticoagulant medicine warfarin, because bleeding 
from nose/ gums or bruising may accur spontaneously).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 532  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Miconazole can inhibit the metabolism of drugs metabolized by the 
CYP2C9 enzyme system. This can result in an increase a nd/or 
prolongation of their effects, including adverse effects.  
 
Miconazole oral gel is contraindicated with the co -administration of the 
following drug that is subjected to metabolism by CYP2C9 (see 
Contraindications):   
• Warfarin  
 
 
Consumer Medication Info rmation Leaflet (RiMUP)  
 
a) Before you use [product name]  
When you must not use it  
 
Do not use [product name] if you are on warfarin therapy.  
 
 
3. Preparations other than oral gel  
The following statements shall be included in the package insert and 
RiMUP  of prep arations (other than oral gel) containing Miconazole:  
 
Package Insert  
 
a) Warnings and Special Precautions  
 
In patients on warfarin, caution should be exercised and the 
anticoagulant effect should be monitored (see Interactions).  
 
b) Interactions  
 
Miconazole adm inistered systemically is known to inhibit CYP2C9 
enzyme system. Due to the limited systemic availability after topical 
application, clinically relevant interactions occur very rarely. In patients 
on warfarin which is subjected to metabolism by CYP2C9, cau tion 
should be exercised and the anticoagulant effect should be monitored 
(see Warnings and Special Precautions).  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 533  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
a) Before You Use [Product Name]  
Before you start to use it  
 
You must tell your doctor if you:  
• are on warfarin therapy  
 
Reference : Directive No. 10 Year 2017. Ref. BPFK/PPP/07/25 ( 15 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi M iconazole : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Interaksi Ubat  
125.  MIDAZOLAM  
(Please also refer to  BENZODIAZEPINE)  
 
The following statements  shall be included in the package in serts  of IV 
preparations containing Midazolam:  
 
WARNING  
 
IV Midazolam has been associated with severe respiratory depression and 
respiratory arrest, especially when used for conscious sedation. In some 
cases, where this was not recognized promptly and trea ted effectively, death 
or hypoxic encephalopathy resulted. IV Midazolam should be used only in 
hospital or ambulatory care settings that provide for continuous monitoring of 
respiratory and cardiac functions. Assure immediate availability of resuscitative 
drugs, equipments, appropriate antidote and personnel trained in their use. 
Dosage of IV Midazolam must be individualized for each patient. Lower doses 
are usually required for elderly, debilitated or higher risk surgical patients. 
When Midazolam is admini stered intravenously for conscious sedation, it 
should be injected slowly (over at least 2 minutes); it should not be 
administered by rapid or single bolus IV injection because of respiratory 
depression and/or arrest, especially in elderly or debilitated p atients. The initial 
dose may be as little as 1mg, but should not exceed 2.5mg in a normal healthy 
adult; administer over at least 2 minutes and allow additional 2 or more 
minutes to fully evaluate sedative effect. If further titration is necessary, use 
small increments to the appropriate level of sedation, allowing an additional 2 
or more minutes after each increment to fully evaluate sedative effect. See 
Dosage and Administration for complete dosing information.  
 
Please refer to SEDATIVE – HYPNOTIC produc ts for additional information.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 534  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
126.   
MINOCYCLINE  
 
The following statements shall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  of products containing 
Minocycline : 
 
 
Package Insert  
 
a) Warnings and Precautions : 
 
Drug React ion with Eosinophilia and Systemic Symptoms (DRESS)  
 
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 
including fatal cases have been reported with minocycline use. DRESS, 
which often occurs several weeks after initiation of treatment, consist s of a 
combination of three or more of the following: cutaneous reaction (such as 
rash or exfoliative dermatitis), eosinophilia, fever, lymphadenopathy, and 
one or more systemic complications such as hepatitis, nephritis, 
pneumonitis, myocarditis, and peri carditis. Discontinue minocycline if 
DRESS is suspected.  
 
b) Adverse Effects/ Undesirable Effects:  
 
Skin and subcutaneous tissue disorders:  
 
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)   
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side  Effects:  
 
Stop taking <product name> and contact your doctor immediately if you 
experience any of the following:  
 
• Serious allergic reactions such as Drug Reaction with Eosinophilia and 
Systemic Symptoms (DRESS). DRESS appears initially as flu -like 
symptom s with a rash on the face and then with an extended rash, high 
temperature and enlarged lymph nodes.  
 
 
Reference : Directive No. 6 Year 201 8. Ref. BPFK/PPP/07/25 ( 6 ) Jld 2. Direktif Untuk Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 535  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Semua Produk Yang Mengandungi Minocycline :  Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Drug Reaction With Eosinophilia And Systemic  Symptoms  (DRESS)  
 
127.  MINOXIDIL  
 
The label and the package insert shall include the following statement:  
To be supplied only on the prescription of a registered medical practitioner.  
 
Note:  The statement is exempted for external use preparation  containing  not more 
than 5% of Minoxidil; its salts; its derivatives   
(Please refer latest Poison List: Preparations for external use containing not more 
than 5% of Minoxidil; its salts; its derivatives, which is under Group C)  
128.  MOMORDICA CHARANTIA  
For product con taining Momordica Charantia, please state:  
- “Shall not be used in pregnant and breast -feeding women.”  
- “Be sure to tell your pharmacist, doctor, or other healthcare 
providers about any other supplements you are taking. There may 
be a potential for interact ions or side effects.”  
129.  MONTELUKAST  
The following statement shall be included in the package insert  of product that 
contains Montelukast : 
 
Addition of this statement at ADVERSE EFFECTS:  
 
Postmarketing Experience  
Blood and lymphatic system disorders : thro mbocytopenia   
 
Reference Directive : (31)dlm.bpfk/ppp/07/25  ; 
Arahan Pengarah Kanan Perkhidmatan Farmasi Bilangan 6 Year  2015 :  
Direkti f Untuk Semua Produk Yang Mengandungi Montelukast : Pengemaskinian Sisip 
Bungkusan Dengan Maklumat Kesan Advers Berkaitan Thrombocytopenia  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 536  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
130.  MUCOLYTIC AGENT  
 
1. The following warning  shall be included in the package inserts  of products 
containing:  
a) Acetylcys teine  
b) Carbocysteine  
c) Methylcarbocysteine (Mecysteine)  
 
CONTRAINDICATIONS  
 
Contraindicated in children below two (2) years of age.  
 
 
2. The following warning  shall be included in the package insert, label and 
Consumer Medication Information Leaflet (RiMUP)  of products 
containing:  
a) Ambroxol  
b) Bromhexine  
 
Package Insert  
 
a) Warnings and Precautions:  
 
Very rare cases of chronically associated severe skin impairments such 
as Stevens Johnson Syndrome, Toxic Epidermal Necrolysis (TEN), 
Erythema Multiforme (EM) and Acute  Generalized Exanthematous 
Pustulosis (AGEP) have been reported. In most cases, these could be 
explained by the severity of the underlying disease or concomitant 
administration of another drug. In the early stages of such severe skin 
reactions, initially o nly nonspecific flu -like symptoms appear, e.g. fever, 
arthralgia, runny nose, cough, and sore throat. If skin or mucous 
membrane damage occurs, seek medical advice immediately and 
discontinue treatment as a precaution.  
 
b) Adverse Effects/Undesirable Effec ts: 
 
Immune System Disorders  
Frequency not known: Anaphylactic reactions including anaphylactic 
shock.  
 
Skin and Subcutaneous Skin Disorders  
Frequency not known: Severe skin reactions (including Stevens Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 537  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Johnson syndrome, Toxic epidermal necrolysis (TEN), Erythema 
Multiforme (EM) and Acute Generalized Exanthematous Pustulosis 
(AGEP).  
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects  
 
[Product name] may cause severe allergy and serious skin reactions. 
Stop using [Product name] and seek medical a ssistance immediately if 
you experience any of the following symptoms:  
1) severe allergy: breathing difficulties, light headedness, skin 
swellings or rash  
2) severe skin reaction: skin reddening, blisters, rash, fever, sore 
throat or eye irritation  
 
 
Reference:  
1. Circular Bil (7) dlm BPFK/PPP/01/03 Jld 1:  Kemaskini Kenyataan Amaran 
“Contraindicated In Children Under 2 Years Of Ag e” Yang Wajib Dimuatkan Pada Sisip 
Bungkusan Semua Produk Carbocysteine, Acetylcysteine Dan Methylcarbocysteine 
(Mecysteine)  
2. Directive No. 1 Year 2018. Ref. BPFK/PPP/07/25 ( 1 ) Jld 2.  Direktif Untuk Semua 
Produk Yang Mengandungi Ambroxol Dan Bromhexine : Pengemaskinian Label, Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Amaran 
Kesan Advers Anafilaksis Dan Severe Cuta neous Adverse Reactions  (SCARs)  
 
131.  NEVIRAPINE  
 
The following statement shall be included in the package insert  of product that 
contains Nevirapine : 
 
Addition of this statement at approved Indication:   
“Avoid usage of Nevirapine in patient with CD4+cell co unt greater than  
250cells/mm3”.  
 
Reference: Circular Bil (43) dlm BPFK/02/5/1.3:  Pendaftaran Produk Yang Mengandungi 
Nevirapine  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 538  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
132.  NIFEDIPINE  
 
The f ollowing statement  shall be included in the package inserts  of “short 
acting” Nifedipine  products:  
 
WARNING/ PRECAUTION  
Several well documented studies have described profound hypotension, 
myocardial infarction and death when immediate release nifedipine c apsules 
are used sublingually for acute reduction of blood pressure.  
 
DOSAGE  
• Lower doses may be required in elderly patients as a result of reduced 
drug clearance.  
• For hypertension, the dose used should not exceed 60mg daily.  
133.  NITRATES  
 
The following statements  shall be included in the package inserts  of all 
“NITRATES FOR STABLE ANGINA PECTORIS ”: 
• An appropriate statement concerning the development of tolerance 
(under precaution section). A suggested statement would be as 
follows: ‘Development of tolerance may occur with all forms of nitrate 
therapy particularly with the long acting preparations that maintain 
continuously high plasma nitrate concentration’.  
• An appropriate recommendation on dosage regimens. The 
recommended dosage regimens should be one that i s able to provide a 
low-nitrate period or a nitrate -free period of 8 -12 hours every 24 hours 
to prevent the development of tolerance and thus maintain the 
antianginal effects.  
134.  NITRAZEPAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 539  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
135.  NORFLOXACIN  
 
The following statement  shall be included in the package inserts  of products 
containing Norfloxacin:  
 
PRECAUTION  
i. Should not be used in children or pregnant women  
ii. Phototoxicity may occur  
136.  NORMAL GLOBULIN  
 
INTRAMUSCULAR (IM)  
The following statem ent shall be included in the package inserts  of Normal 
globulin IM preparations:  
 
WARNING  
Do not administer this preparation intravenously because of potential for 
serious hypersensitivity reactions.  
137.  NOSCAPINE  
1. The following contraindication  shall be included on the labels  of 
products containing Noscapine:  
 
 
2.   The following statement  shall be included in the package inserts  of 
products containing Noscapine:  
 
WARNING  
Experimental data now suggests that noscapine may exhibit a mutagenic 
effect in vitro. Because of the possible consequent risk to the developing 
foetus, the products containing noscapine is contraindicated in women of 
child bearing potential, therefore pregnancy should be excluded before 
treatment, and effective contraception maintained thro ughout treatment 
with such products.  
 
PRECAUTION  
In view of potential mutagenicity shown in vitro, potential risks should be 
balanced against anticipated benefits when treating children and neonates . Contraind icated in Women of Child -bearing Potential  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 540  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
138.  NONSTEROIDAL ANTI -INFLAMMATORY DRUG (NSAID)  
 
The follo wing statement  shall be included in the package insert  of products 
containing NSAID including COX -2 Inhibitors:  
 
WARNING  
 
Risk of GI Ulceration, Bleeding and Perforation with NSAID  
Serious GI toxicity such as bleeding, ulceration and perforation can occur at 
any time, with or without warning symptoms, in patients treated with NSAID 
therapy. Although minor upper GI problems (e.g. dyspepsia) are common, 
usually developing early in therapy, prescribers should remain alert for 
ulceration and bleeding in patient s treated with NSAIDs even in the absence of 
previous GI tract symptoms.  
 
Studies to date have not identified any subset of patients not at risk of 
developing peptic ulceration and bleeding. Patients with prior history of serious 
GI events and other risk f actors associated with peptic ulcer disease (e.g. 
alcoholism, smoking, and corticosteroid therapy) are at increased risk. Elderly 
or debilitated patients seem to tolerate ulceration or bleeding less than other 
individuals and account for most spontaneous r eports for fatal GI events.  
139.  OLANZAPINE  
 
(Please also refer to ANTIPSYCHOTIC AGENT)  
 
The following statements shall be included in the package insert and RiMUP  of 
products containing Olanzapine:  
 
Package Insert  
 
a) Special Warnings and Precautions for Use : 
 
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)  
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been 
reported with olanzapine exposure. DRESS consists of a combination of three 
or more of the following: cutaneous reaction  (such as rash or exfoliative 
dermatitis), eosinophilia, fever, lymphadenopathy and one or more systemic 
complications such as hepatitis, nephritis, pneumonitis, myocarditis, and 
pericarditis. Discontinue olanzapine if DRESS is suspected.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 541  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
b) Adverse Drug Reactions : 
 
Skin and subcutaneous tissue disorders  
Very rare: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Side Effects : 
 
Very rare: Serious allergic reactions such as Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS). DRESS appears initially as flu -like 
symptoms with a rash on the face and then with an extended rash, high 
temperature, enlarged lymph nodes, increased levels of liver enzymes seen in 
blood tests and an increase i n a type of white blood cell (eosinophilia).  
 
Reference : Directive No.  17 Year  2016. Ref. BPFK/PPP/07/25 ( 5 ) Jld 1.  DIREKTIF BAGI 
SEMUA PRODUK YANG MENGANDUNGI OLANZAPINE DENGAN MAKLUMAT 
KESELAMATAN BERKAITAN KESAN ADVERS DRUG REACTION WITH EOSINOPHILIA 
AND SYSTEMIC SYMPTOMS (DRESS)  
 
140.  ONDANSETRON  
The following statements  shall be included in the package inserts  of injection 
produ cts containing Ondansetron:  
DOSAGE AND ADMINISTRATION:  
 
CHEMOTHERAPY AND RADIOTHERAPY INDUCED NAUSEA AND 
VOMITING (CINV AND RINV)  
 
CINV and RINV in Adults  
 
…. 
 
IV doses greater than 8 mg and up to a maximum of 16 mg must be diluted in 
50 mL to 100 mL of 0 .9% Sodium Chloride Injection or 5% Dextrose Injection 
before administration and infused over not less than 15 minutes.  
 
…. 
 
CINV and RINV in Elderly   Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 542  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Ondansetron is well tolerated by patients over 65 years of age.  
 
In patients 65 years of age or older, a ll IV doses should be diluted and infused 
over 15 minutes and, if repeated, given no less than 4 hours apart.  
 
In patients 65 to 74 years of age, the initial IV dose of ondansetron 8 mg or 16 
mg, infused over 15 minutes, may be followed by 2 doses of 8 mg infused over 
15 minutes and given no less than 4 hours apart.  
 
In patients 75 years of age or older, the initial IV dose of ondansetron should 
not exceed 8 mg infused over 15 minutes. The initial dose of 8 mg may be 
followed by 2 doses of 8 mg, infused ov er 15 minutes and given no less than 4 
hours apart.  
 
Reference: Zofran™ Injection package insert (June 2014 version)  
 
141.  OPIOID  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing opioid such as alfenanil, buprenorphine, 
codeine, dihydrocodeine, fentanyl, methadone, morphine, nalbuphine, 
oxycodone, pentazocine, pethidine, remifentanil, tapentadol and tramadol;  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
1. Risks from Concomitant Use with Benzodiazep ines 
 
Profound sedation, respiratory depression, coma, and death may result 
from the concomitant use of <product name> with benzodiazepines. 
Observational studies have demonstrated that concomitant use of 
opioids and benzodiazepines increases the risk of d rug-related mortality 
compared to use of opioids alone. Because of these risks, reserve 
concomitant prescribing of these drugs for use in patients for whom 
alternative treatment options are inadequate.  
 
If the decision is made to newly prescribe a benzodia zepine and an 
opioid together, prescribe the lowest effective dosages and minimum 
durations of concomitant use.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 543  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
If the decision is made to prescribe a benzodiazepine in a patient 
already receiving an opioid, prescribe a lower initial dose of the 
benzodia zepine than indicated in the absence of an opioid, and titrate 
based on clinical response.  
 
If the decision is made to prescribe an opioid in a patient already taking 
a benzodiazepine, prescribe a lower initial dose of the opioid, and titrate 
based on cli nical response.  
 
Follow patients closely for signs and symptoms of respiratory 
depression and sedation. Advise both patients and caregivers about the 
risks of respiratory depression and sedation when <product name> is 
used with benzodiazepines. Advise pat ients not to drive or operate 
heavy machinery until the effects of concomitant use of the 
benzodiazepine have been determined. Screen patients for risk of 
substance use disorders, including opioid abuse and misuse, and warn 
them of the risk for overdose an d death associated with the use of 
benzodiazepines (See Drug Interactions).  
 
2. Serotonin  Syndrome with Concomitant Use of Serotonergic Drugs  
Cases of serotonin syndrome, a potentially life -threatening condition, 
have been reported during concurrent use of <p roduct name> with 
serotonergic drugs (See Interactions with Other Medicaments). This 
may occur within the recommended dosage range.  
 
Serotonin syndrome symptoms may include mental -status changes 
(e.g. agitation, hallucinations, coma), autonomic instability  (e.g. 
tachycardia, labile blood pressure, hyperthermia), neuromuscular 
aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal 
symptoms (e.g. nausea, vomiting, diarrhoea) and can be fatal (See 
Interactions with Other Medicaments). The ons et of symptoms generally 
occurs within several hours to a few days of concomitant use, but may 
occur later than that. Discontinue <product name> if serotonin 
syndrome is suspected.  
 
3. Adrenal Insufficiency  
Cases of adrenal insufficiency have been reported wi th opioid use, more 
often following greater than one month of use. Presentation of adrenal 
insufficiency may include non -specific symptoms and signs including 
nausea, vomiting, decreased appetite, fatigue, weakness, dizziness, 
and low blood pressure. If ad renal insufficiency is suspected, confirm 
the diagnosis with diagnostic testing as soon as possible. If adrenal 
insufficiency is diagnosed, treat with physiologic replacement dosing of 
corticosteroids. Wean the patient off of the opioid to allow adrenal Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 544  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
function to recover and continue corticosteroid treatment until adrenal 
function recovers. Other opioids may be tried as some cases reported 
use of a different opioid without recurrence of adrenal insufficiency. The 
information available does not identify an y particular opioids as being 
more likely to be associated with adrenal insufficiency.  
 
4. Sexual Function/Reproduction  
Long term use of opioids may be associated with decreased sex 
hormone levels and symptoms such as low libido, erectile dysfunction, 
or infe rtility (See Postmarketing Experience)  
 
 
b) Adverse Effects/ Undesirable Effects:  
 
Postmarketing Experience:  
 
Serotonin syndrome (See Warnings and Precautions)  
 
Adrenal insufficiency (See Warnings and Precautions)  
 
Androgen deficiency: Cases of androgen defic iency have occurred with 
chronic use of opioids. Chronic use of opioids may influence the 
hypothalamic -pituitary -gonadal axis, leading to androgen deficiency that 
may manifest as low libido, impotence, erectile dysfunction, 
amenorrhea, or infertility. The causal role of opioids in the clinical 
syndrome of hypogonadism is unknown because the various medical, 
physical, lifestyle, and psychological stressors that may influence 
gonadal hormone levels have not been adequately controlled for in 
studies conducted to date. Patients presenting with symptoms of 
androgen deficiency should undergo laboratory evaluation.  
 
Infertility: Chronic use of opioids may cause reduced fertility in females 
and males of reproductive potential. It is not known whether these 
effects o n fertility are reversible.  
 
 
c) Drug Interactions:  
 
1. Benzodiazepines  
Due to additive pharmacologic effect, the concomitant use of opioids 
with benzodiazepines increases the risk of respiratory depression, 
profound sedation, coma and death.  
 
The concomitant us e of opioids and benzodiazepines increases the risk Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 545  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
of respiratory depression because of actions at different receptor sites in 
the central nervous system that control respiration. Opioids interact 
primarily at μ -receptors, and benzodiazepines interact at G ABA A sites. 
When opioids and benzodiazepines are combined, the potential for 
benzodiazepines to significantly worsen opioid -related respiratory 
depression exists.  
 
Reserve concomitant prescribing of these drugs for use in patients for 
whom alternative trea tment options are inadequate (see Warnings and 
Precautions).  
 
Limit dosage and duration of concomitant use of benzodiazepines and 
opioids, and follow patients closely for respiratory depression and 
sedation.  
 
2. Serotonergic Drugs  
The concomitant use of opioi ds with other drugs that affect the 
serotonergic neurotransmitter system has resulted in serotonin  
syndrome. If concomitant use is warranted, carefully observe the 
patient, particularly during treatment initiation and dose adjustment. 
Discontinue <product name> if serotonin syndrome is suspected. 
Examples of serotonergic drugs are selective serotonin reuptake 
inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors 
(SNRIs), tricyclic antidepressants (TCAs),  triptans, 5 -HT3 receptor 
antagonists,  drugs that affect the serotonin neurotransmitter system 
(e.g. mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) 
inhibitors (those intended to treat psychiatric disorders and also others, 
such as linezolid and intravenous methylene blue) (See Warn ings and 
Precautions).  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) While you are using it <product name> : 
 
Things to be careful of:  
- Serotonin syndrome: <Product name> may cause a rare but 
potentially life -threatening condition resulting from concomi tant 
administration of serotonergic drugs. If you have some or all of 
these symptoms: feeling confused, feeling restless, sweating, 
shaking, shivering, hallucinations, sudden jerks in your muscles 
or a fast heartbeat,  seek medical attention immediately.  
- Adrenal insufficiency: Long -term use of <product name> may 
cause adrenal insufficiency, a potentially life -threatening Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 546  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
condition that may present with non -specific symptoms and signs 
such as nausea, vomiting, decreased appetite, fatigue, 
weakness, dizziness , and low blood pressure. Seek medical 
attention if you experience a constellation of these symptoms.  
- Infertility: Long -term use of <product name> may cause reduced 
fertility. It is not known whether these effects on fertility are 
reversible.  
 
 
b) Taking othe r medicines:  
 
Taking <product name> with a benzodiazepine (medicine used as 
sedatives or to treat anxiety) can depress your central nervous system. 
Inform your doctor if you are currently taking any benzodiazepine.  
 
Seek medical attention immediately if yo u or the person taking this 
medication experience(s) symptoms of unusual dizziness or 
lightheadedness, extreme sleepiness, slowed or difficult breathing, or 
unresponsiveness.  
 
 
Reference :  
1. Directive No. 23 Year 2017. Ref. BPFK/PPP/07/25 ( 28 ) Jld 1.  Direktif Untuk Semua 
Produk Yang Mengandungi Opioid  Dan Benzodiazepin : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (R iMUP) Dengan Maklumat 
Keselamatan Berkaitan Interaksi Ubat  
2. Directive No. 2 7 Year 2017. Ref. BPFK/PPP/07/25 ( 32 ) Jld 1.  Direktif Untuk Semua  
Produk Yang Mengandungi Opioid : Pengemaskinian Sisip Bungkusan Dan Risalah 
Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Risiko Kesan Advers Serotonin Syndrome  Kesan Daripada Interaksi Dengan 
Serotonergic Drugs  Dan Risiko Kes an Advers Adrenal Insufficiency  Dan Androgen 
Deficiency  Akibat Penggunaan Jangka Panjang   
 
142.  PALIPERIDONE  
The following statement  shall be included in the package inserts  of products 
containing Paliperidone:  
 
Warnings and Precautions  
 
Intraoperative Floppy  Iris Syndrome  
 
Intraoperative floppy iris syndrome (IFIS) has been observed during 
cataract surgery in patients treated with medicines with alpha1a -adrenergic 
antagonist effect, including risperidone. IFIS may increase the risk of eye Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 547  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
complications during  and after the operation. Current or past use of 
medicines with alpha1a -adrenergic antagonist effect should be made 
known to the ophthalmic surgeon in advance of surgery. The potential 
benefit of stopping alpha1 blocking therapy prior to cataract surgery h as not 
been established and must be weighed against the risk of stopping the 
antipsychotic therapy.  
 
Undesirable Effects  
 
Postmarketing Data  
Eye Disorders  
Frequency: Not known – Floppy iris syndrome (intraoperative)  
 
References: Circular (17)dlm.BPFK/PPP/01/03 Jld.3 : Pekeliling untuk mengemaskini sisip 
bungkusan semula produk yang mengandungi Risperidone atau Paliperidone den gan amaran 
berkaitan risiko Intraoperative Floppy Iris Syndrome (IFIS) pada pesakit yang menjalani 
pembedahan katarak  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 548  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
143.  PARACETAMOL  
The following statement  shall be included on the labels , package inserts  and 
RiMUP  of ALL products containing Paracetamol:  
WARNING  
 
 
 
 
• Allergy alert:  Paracetamol may cause severe skin reactions. Symptoms 
may include skin reddening, blisters or rash.  
These could be signs of a serious condition. If these reactions occur, stop 
use and seek medical assistance right away.  
 
 
ADVER SE EFFECT/UNDESIRABLE EFFECT  
(For product with package insert)  
• Cutaneous hypersensitivity reactions including skin rashes, angioedema, 
Stevens Johnson Syndrome/Toxic Epidermal Necrolysis have been 
reported.  
 
Reference Directive : (29)dlm.bpfk/ppp/07/25  ; 
Arahan Pengarah Kanan Perkhidmatan Farmasi Bilangan 5 Year 2015 : Direktif Untuk 
Produk Yang Mengandungi Paracetamol, Termasuk Produk Kombinasi : 
Pengemaskinian Label, Sisip Bungkusan, Dan Risalah Maklumat Ubat Untuk 
Pengguna (RiMUP)  Dengan Amaran Berkaitan Kesan Advers Serius Pada Kulit  This preparation contains PARACETAMOL.  
Do not take any other paracetamol containing medicines at the same time.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 549  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
144.  PARACETAMOL WITH CAFFEINE IN COM BINATION  
 
The following statement  shall be included on the l abels and in the package 
inserts  and RiMUP  of products containing Paracetamol with Caffeine in 
combination:  
 
WARNING  
• Avoid other caffeine containing products. Too much caffeine may cause 
rapid heart rate, nervousness or sleeplessness.  
• Ask a doctor or pharm acist before use if you have high blood pressure, 
glaucoma, or overactive bladder syndrome.  
• DO NOT exceed 8 tablets in 24 hours . 
• DO NOT take more than the recommended dose unless advised by your 
doctor. Use the smallest effective dose. Taking more than the  maximum 
daily dose may cause severe or possibly fatal liver damage.  
• DO NOT use with other drugs containing paracetamol.  
• NOT recommended for children under 12  years  
• Allergy alert:  Paracetamol may cause severe skin reactions. Symptoms 
may include skin redd ening, blisters or rash.  
These could be signs of a serious condition. If these reactions occur, stop 
use and seek medical assistance right away.  
 
 
ADVERSE EFFECT/UNDESIRABLE EFFECT  
(For product with package insert)  
• Cutaneous hypersensitivity reactions i ncluding skin rashes, angioedema, 
Stevens Johnson Syndrome/Toxic Epidermal Necrolysis have been 
reported.  
  
 
Reference Directive : (29)dlm.bpfk/ppp/07/25  ; 
Arahan Pengarah Kanan Perkhidmatan Farmasi Bilangan 5 Year 2015 : Direktif Untuk 
Produk Yang Mengandungi Paracetamol, Termasuk Produk Kombinasi : 
Pengemaskinian Label, Sisip Bungkusan, Dan Risalah Maklumat Ubat Untuk 
Pengguna (R iMUP)  Dengan Amaran Berkaitan Kesan Advers Serius Pada Kulit  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 550  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
145.  PEGFILGRASTIM  
The following statement  shall be included in the package inserts  of ALL 
biosimilar products containing  PEGFILGRASTIM  
 
WARNINGS AND PRECAUTIONS  
 
Capillary leak syndrome has been reported after granulocyte -colony 
stimulating factor administration and is characterised by hypotension, 
hypoalbuminaemia, oedema and hemoconcentration. Patients who develop 
symptoms of capillary leak syndrome should be closely monitored and receive 
standa rd symptomatic treatment, which may include a need for intensive care.  
 
 
UNDESIRABLE EFFECTS  
  
Clinical Trials  
In Cancer Patients  
 Capillary Leak Syndrome, which can be life -threatening if treatment is delayed, 
has been reported uncommonly (≥1/1000 to < 1 /100) in cancer patients 
undergoing chemotherapy following administration of granulocyte colony 
stimulating factors.  
 
 In Normal Donors undergoing peripheral blood progenitor cell 
mobilization  
 Capillary Leak Syndrome, which can be life -threatening if trea tment is delayed, 
has been reported in healthy donors undergoing peripheral blood progenitor 
cell mobilization following administration of granulocyte colony stimulating 
factors.  
 
Post Marketing  
Vascular disorders  
Cases of capillary leak syndrome have been  reported in the post marketing 
setting with granulocyte colony stimulating factor use. These have generally 
occurred in patients with advanced malignant diseases, sepsis, taking multiple 
chemotherapy medications or undergoing apheresis.  
Reference:  Circula r Bil (20) dlm. BPFK/PPP/07/25.  Directive No.  13 Year  2014.  
Direktif Untuk Semua Produk Yang Mengandungi Filgrastim Dan Pegfilg rastim : 
Amaran Berkaitan Risiko  Capillary Leak Syndrome (Cls)   Bagi Pesakit Kanser 
Dan Healthy Donor  (Filgrastim) Dan Bagi Pesakit Kanser (Pegfilgrastim)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 551  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
146.  PELARGONIUM SIDOIDES  
 
The following warning  shall be included on the labels and in the package 
inserts of products containing Pelargonium Sidoides : 
 
WARNING  
In very rare cases, pelargonium sidoides  may cause hypersensitivity reactions.  
147.  PENICILLIN  
 
The following statement  shall be included on the labels  of products containing 
penicillin:  
 
‘Not to be u sed in patients with known hypersensitivity to Penicillin ’ 
148.  PHENIRAMINE  
 
The following statement  shall be included on the label and in the package 
inserts  of liquid oral products containing Pheniramine:  
 
WARNING  
 
When used for treatment of cough and cold : 
(a) Not to be used in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in 
children 2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03 : Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 552  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
149.  PHENYLEPHRINE  
The following statement  shall be included on the labels and in the package 
insert  of liquid oral products containing Phenylephrine:  
 
WARNING  
 
When used for treatment of cough and cold:  
(a) Not to be used  in children less than 2 years of age  
(b)  To be used with caution and doctor’s/ pharmacist’s advice in 
children 2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif dan Dekongestan (Sebagai Bahan Aktif 
Tunggal a tau Kombinasi)  
150.  PIRIBEDIL  
Please refer to DOPAMINERGIC INGREDIENT  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 553  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
151.  PIROXICAM  
 
The following additional information  shall be included in the package inserts  of 
products containing Piroxicam:  
 
WARNING AND PRECAUTION  
• Treatment should always be initiated by a physician experienced in 
the treatment of rheumatic diseases.  
• Use the lowest dose (no more than 20mg per day) and for the 
shortest duration possible. Treatment should be reviewed after 14 
days.  
• Always consider prescribing a gastro -protective agent.  
 
CONT RAINDICATION  
• Piroxicam should not be prescribed to patient who is more likely to 
develop side effects, such as those with a history of gastro -intestinal 
disorders associated with bleeding, or those who have had skin 
reactions to other medicines.  
• Piroxicam should not be prescribed in association with any other 
NSAID or an anticoagulant.  
       
Reference: Circular Bil (80) dlm BPFK/02/5/1.3 : Mengha dkan Indikasi bagi Produk untuk 
Kegunaan Systemic yang Mengandungi Piroxicam kepada 'For the symptomatic relief of pain 
and inflammation in patients with osteoarthritis, rheumatoid arthritis and ankylosing spondylitis' 
dan Tambahan Amaran dan Kontraindikas i terkini pada sisip bungkusan  
152.  PRAMIPEXOLE  
Please refer to DOPAMINERGIC INGREDIENT  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 554  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
153.  PRAVASTATIN  
The following additional information  shall be included in the package insert  of 
products containing Pravastatin.  
 
DOSAGE AND ADMINISTRATION  
 
Dosage in Patien ts Taking Cyclosporine  
In patients taking cyclosporine, with or without other immunosuppressive 
drugs, concomitantly with [Product Name], therapy should be initiated with 
10mg/day and titration to higher doses should be performed with caution. Most 
patien ts treated with this combination received a maximum pravastatin dose of 
20mg/day.  
 
WARNINGS AND PRECAUTIONS  
 
Skeletal Muscle Effects  
The use of fibrates alone may occasionally be associated with myopathy. The 
benefit of further alterations in lipid levels by the combined use of [Product 
Name] with fibrates should be carefully weighed against the potential risks of 
this combination.  
 
Cases of myopathy, including rhabdomyolysis, have been reported with 
pravastatin co -administered with colchicine, and caution  should be exercised 
when prescribing pravastatin with colchicine.  
Pravastatin must not be co -administered with systemic fusidic acid. There have 
been reports of rhabdomyolysis (including some fatalities) in patients receiving 
this combination. In patients  where the use of systemic fusidic acid is 
considered essential, statin treatment should be discontinued throughout the 
duration of fusidic acid treatment. The patient should be advised to seek 
medical advice immediately if they experience any symptoms of muscle 
weakness, pain or tenderness. Pravastatin therapy may be re -introduced 
seven days after the last dose of fusidic acid.  
 
INTERACTIONS  
 
Concomitant Therapy with Other Lipid Metabolism Regulators: Based on post -Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 555  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
marketing surveillance, gemfibrozil, feno fibrate, other fibrates and lipid 
lowering doses of niacin (nicotinic acid) may increase the risk of myopathy 
when given concomitantly with HMG -CoA reductase inhibitors, probably 
because they can produce myopathy when given alone. Therefore, combined 
drug therapy should be approached with caution.  
 
Gemfibrozil and nicotinic acid: Gemfibrozil and nicotinic acid do not statistically 
significantly affect the bioavailability of pravastatin. However, in a limited size 
clinical trial, a trend toward CK elevations  and musculoskeletal symptoms was 
seen in patients treated concurrently with pravastatin and gemfibrozil. 
Myopathy, including rhabdomyolysis, has occurred in patients who were 
receiving coadministration of HMG -CoA reductase inhibitors with fibric acid 
derivatives and niacin, particularly in subjects with pre -existing renal 
insufficiency.  
 
Cyclosporine: In a multicentre study, the AUC values of pravastatin were 
shown to be five -fold higher in the presence of cyclosporine. There was no 
accumulation of pravast atin after multiple doses  
 
Clarithromycin, colchicine: The risk of myopathy/rhabdomyolysis is increased 
with concomitant administration of clarithromycin or colchicine with pravastatin.  
 
Fusidic acid: The risk of myopathy including rhabdomyolysis may be in creased 
by the concomitant administration of pravastatin with systemic fusidic acid. Co -
administration of this combination may cause increased plasma concentrations 
of both agents. The mechanism of this interaction (whether it is 
pharmacodynamics or pharma cokinetic, or both) is yet unknown. There have 
been reports of rhabdomyolysis (including some fatalities) in patients receiving 
this combination. If treatment with fusidic acid is necessary, pravastatin 
treatment should be discontinued throughout the durat ion of the fusidic acid 
treatment.  
 
Reference:  Circular  Bil (15) dlm. BPFK/PPP/07/25.  Directive No.  8 Year  2014  
Direktif Untuk S emua Produk Pravastatin: Mengehadkan Dos Penggunaan 
Pravastatin Untuk Mengurangkan Risiko Kecederaan Otot  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 556  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
154.  PREDNISONE AN D PREDNISOLONE (EXCEPT TOPICAL 
PREPARATIONS)  
 
The following statements shall be included in the package insert and 
Consumer Medication  Information Leaflet (RiMUP)  for products containing 
Prednisone dan Prednisolone (except topical preparations);  
 
Package Insert  
 
a)   Warnings and Precautions:  
 
Scleroderma renal crisis  
Caution is required in patients with systemic sclerosis because of an 
increased incidence of (possibly fatal) scleroderma renal crisis with 
hypertension and decreased urinary output observed with a daily dose of 
15 mg or more prednisolone.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a)   Before you start to use it:  
 
Talk to your doctor before taking <product name>, if you have:  
Systemic sclerosis (an autoimmune disorder). Taking daily doses of 15 
mg or more may increase the risk of a serious complication called 
scleroderma renal crisis which may cause your blood press ure to 
increase and reduce urination.  
 
Reference: Directive No . 17 Year 201 8. Ref. BPFK/PPP/07/25 ( 17 ) Jld 2. Direktif Untuk  
Semua Produk Yang Mengandungi Prednisone Dan Prednisolone (Kecuali Persediaan 
Topikal) : Pengemaskinian Sisip Bungkusan  Dan Risalah Maklumat Ubat Untuk Pengguna 
(RiMUP) Dengan Maklumat Keselamatan Berkaitan Schleroderma Renal Crisis  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 557  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
155.  PROMETHAZINE HCL  
The following additional information  shall be included on the label and in the 
package insert  of liquid oral products containing Promethazine HCl:  
 
WARNING  
 
When used for treatment of cough and cold  
(a)   “It (brand or generic names) should not be used in pedia tric patients 
 less   than 2 years of age because of the potential for fatal respiratory 
 depression”.  
(b) To be used with caution and doctor’s/ pharmacist’s advice in children 2 
 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03 : Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihista min, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
156.  PROPAFENONE  
 
The following warning  shall be included in the package insert  of products 
containing propafenone:  
 
Propafenone is not recommended for treatment of less severe 
arrhy thmias such as nonsustained ventricular tachycardias or frequent 
premature ventricular contractions even if the patients are symptomatic, 
because of recent evidence in the US of increase mortality in patients 
with non -lifethreatening arrhythmias who were t reated with encainide 
and flecainide.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 558  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
157.  PROPOFOL  
 
The following statement  shall be included in the package inserts  of products 
containing Propofol:  
 
a) WARNING  
 
Propofol is not recommended for paediatric general anaesthesia and 
sedation because its safety and  effectiveness in these patients have not 
been established. There have been recent reports of adverse cardiac 
events and deaths associated with its use in paediatric intensive care. 
Although there is no evidence of a causal link of death with propofol in 
these cases, the drug could not be ruled out as a contributing factor. Until 
further data establishing its safety and delineating its appropriate dose 
range are available, propofol should not be used in paediatric intensive 
care.  
 
There have been very rare reports of epileptiform movement in epileptics 
and non -epileptics occurring during induction orbemergence from 
anaesthesia induced by propofol.  
 
b) Interactions:  
 
A need for lower propofol doses has been observed in patients taking 
valproate. When used concom itantly, a dose reduction of propofol may be 
considered.  
 
 
Reference: (b) Directive No. 7 Year 2018. Ref. BPFK/PPP/07/25 ( 7 ) Jld 2.  Direkti f Untuk 
Semua Produk Yang Mengandungi Propofol Dan Sodium Valproate :  Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat 
Keselamatan Berkaitan Interaksi Ubat   
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 559  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
158.  PROPOLIS (ORAL)  
 
For products containing Propoli s (for oral use), please state:  
- “This product contains propolis and may cause severe allergic 
reactions including fatal anaphylactic reaction in susceptible 
individuals.”  
- “Asthma and allergy sufferers may be at a greater risk.”  
159.  PROPOLIS (TOPICAL)  
 
The f ollowing information  shall be included on the labels and/ or package 
inserts  of products containing Propolis (for topical use):  
 
WARNINGS  
 
Propolis may cause allergic skin reaction.  
 
Reference:  
a) Circular Bil (48) dlm BPFK/02/5/1.3:  Pernyataan Amaran Pada Label Dan Sisip 
Bungkusan Produk Yang Mengandungi Propolis (Topikal) dan Royal Jelly (Semua 
Bentuk)  
b) Bil (56) dlm BPFK/02/5/1.3:  Pernyataan Amaran pada Label dan Sisip Bungkusan 
Produk yang Mengandungi Propolis (topikal) dan Royal Jelly (Semua Bentuk)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 560  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
160.  PROPYLTHIOURACIL  
 
 The following statement  shall be included in the package inserts  of products 
containing propylthiouracil:  
 
1WARNING AND PRECAUTION  
Potential risk of serious hepatoxicity or liver injury including liver failure and 
death. Patients who are initiated with propylthiourasil should be  closely 
monitored for signs and symptoms of liver injury (e.g. fatigue, weakness, 
vague abdominal pain, loss of appetite, itching, easy bruising or yellowing of 
the eyes or skin) especially during the first six months. If liver injury is 
suspected, prompt ly discontinue propylthiouracil therapy.   
 
Propylthiouracil should not be used in pediatric patients unless the patient is 
allergic to or intolerant of the alternatives available.  
 
2The following boxed warning  shall be included in the package inserts  of 
products containing propylthiouracil:  
 BOXED WARNING  
 
Severe liver injury and acute liver failure, in some cases fatal, have 
been reported  in patients treated with propylthiouracil. These reports 
of hepatic reactions include cases requiring liver transplantation in 
adult and pediatric patients.  
 
Propylthiouracil should be reserved to patients who cannot tolerate 
carbimazole/ methimazole and in whom radioactive iodine therapy or 
surgery are not appropriate treatments for management of 
hyperthyroidism.  
 
Because of the risk of fetal abnormalities associated with 
carbimazole/ methimazole, propylthiouracil may be the treatment of 
choice when an an tithyroid drug is indicated during or just prior to the 
first trimester of pregnancy (See Warnings & Precautions).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 561  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
  
Reference:  
Circular 1Bil (41) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Berkaitan Dengan “Potenti al for 
an Increase in Risk of Hepatotoxicity” yang Perlu Dimuatkan Pada Sisip Bungkusan Produk 
Propylthiouracil  
 
Circular 2Bil (55) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Berbentuk “Boxed Warning” 
Yang Wajib Dimuatkan Pada Sisip Bungkusan Produk Propylthiouracil Dengan “Severe Liver 
Injury”  
161.  PROTON PUMP INHIBITORS (PPI)  
(Products containing Pantoprazole, Omeprazole, Lan soprazole, 
Esomeprazole, Rabeprazole, Dexlansoprazole)  
 
The following statements shall be included in the package insert and RiMUP  of 
pharmaceutical products containing Proton Pump Inhitors (PPI):  
 
Package Insert  
 
1. Warnings and Precautions : 
 
Regular Surveil lance  
Patients on proton pump inhibitor treatment (particularly those treated for 
long term) should be kept under regular surveillance.  
 
Subacute Cutaneous Lupus Erythematosus (SCLE)  
Proton pump inhibitors are associated with very infrequent cases of 
suba cute cutaneous lupus erythematosus (SCLE). If lesions occur, 
especially in sun -exposed areas of the skin, and if accompanied by 
arthralgia, the patient should seek medical help promptly and the health 
care professional should consider stopping {product nam e}. SCLE after 
previous treatment with a proton pump inhibitor may increase the risk of 
SCLE with other proton pump inhibitors.  
 
Hypomagnesaemia  
Severe hypomagnesaemia has been reported in patients treated with 
PPI like {product name} for at least three mo nths, and in most cases for 
a year. Serious manifestations of hypomagnesaemia such as fatigue, 
tetany, delirium, convulsions, dizziness and ventricular arrhythmia can 
occur but they may begin insidiously and be overlooked. In most affected 
patients, hypoma gnesaemia improved after magnesium replacement 
and discontinuation of the PPI.  
 
For patients expected to be on prolonged treatment or who take PPI with 
digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 562  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
health care professionals should con sider measuring magnesium levels 
before starting PPI treatment and periodically during treatment.  
 
Fracture  
Proton pump inhibitors, especially if used in high doses and over long 
durations (>1 year), may modestly  increase  the  risk  of  hip,  wrist  and   
spine  fracture,  predominantly  in  the  elderly  or  in presence  of  other  
recognised  risk  factors.  Observational studies suggest that proton 
pump inhibitors may increase the overall risk of fracture by 10 –40%. 
Some of this increase may be due to other risk factors. Patients at risk of 
osteoporosis should receive care according to current clinical guidelines 
and they should have an adequate intake of vitamin D and calcium.  
 
Clostridium Difficile Diarrhea  
Published observational studies suggest that  PPI therapy may be 
associated with an increased risk of Clostridium difficile associated 
diarrhea, especially in  hospitalized patients. This diagnosis should be 
considered for diarrhea that does not improve. Patients should use the 
lowest dose and shortes t duration of PPI therapy appropriate to the 
condition being treated.  
 
Vitamin B12 Deficiency  
Daily treatment with any acid -suppressing medications over a long 
period of time (e.g., longer than 3 years) may lead to malabsorption of 
cyanocobalamin (vitamin B12) caused by hypo - or achlorhydria. Rare 
reports of cyanocobalamin deficiency occurring with acid -suppressing 
therapy have been reported in the literature. This diagnosis should be 
considered if clinical symptoms consistent with cyanocobalamin 
deficiency  are observed.  
 
 
2. Undesirable Effects/Side Effects:  
 
Subacute Cutaneous Lupus Erythematosus (SCLE)  
Skin and subcutaneous tissue disorders  
Frequency 'not known': Subacute cutaneous lupus erythematosus  
 
Interstitial Nephritis  
Renal and urinary disorders: Inte rstitial nephritis  
 
Hypomagnesaemia  
Metabolism and nutritional disorders  
Frequency “not known”: hypomagnesaemia.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 563  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Fracture  
Musculoskeletal disorders  
Frequency “uncommon”: Fracture of the hip, wrist or spine.  
 
Clostridium Difficile Diarrhea  
Infections & i nfestations: Clostridium difficile associated diarrhea.  
 
Fundic Gland Polyps (Benign)  
Gastrointestinal disorders  
Frequency “common”:  Fundic gland polyps (benign)  
 
Vitamin B12 Deficiency  
Metabolic/Nutritional: Vitamin B12 deficiency  
 
 
3. Warnings & Precaution s - Interference with laboratory tests  
 
Increased Chromogranin A (CgA) level may interfere with investigations 
for neuroendocrine tumours. If the patient(s) are due to have a test on 
Chromogranin A level, [product name] treatment should be stopped for 
at least 5 days before CgA measurements to avoid this interference (see 
section Pharmacodynamic). If CgA and gastrin levels have not returned 
to reference range after initial measurement, measurements should be 
repeated 14 days after cessation of proton pump i nhibitor treatment.   
 
 
4. Pharmacodynamic  
 
During treatment with antisecretory medicinal products, serum gastrin 
increases in response to the decreased acid secretion. Also CgA 
increases due to decreased gastric acidity. The increased CgA level may 
interfere  with investigations for neuroendocrine tumours.  
 
Available published evidence suggests that proton pump inhibitors 
should be discontinued between 5 days and 2 weeks prior to CgA 
measurements. This is to allow CgA levels that might be spuriously 
elevated f ollowing PPI treatment to return to reference range.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
i. Side Effects : 
 
When you are taking this medicine, your doctor will want to monitor you Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 564  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
(especially if you are taking it for long term). Hence, you shoul d report 
any new and exceptional symptoms and circumstances whenever you 
see your doctor. Please tell your doctor promptly if you get any of the 
symptoms below:  
 
• Rash (especially in areas exposed to the sun), possibly with pain 
in the joints.(Subacut e Cuta neous Lupus Erythematosus , SCLE)  
• Fever, extreme tiredness, pus/blood in urine.  
• Involuntary muscle contractions, disorientation, convulsions, 
dizziness, increased heart rate  
• Fracture in the hip, wrist or spine.  
• Watery stool, stomach pain and fever that do n ot go away  
• Anemic (pale skin, weakness, tiredness or lightheadedness), 
shortness of breath, a smooth tongue, nerver problems 
(numbness or tingling, muscle weakness and problems walking), 
vision loss and mental problems (depression, memory loss or 
behaviora l changes).  
 
a) Subacute Cutaneous Lupus Erythematosus (SCLE)  
  Frequency “not known”  
 
b) Interstitial Nephritis  
  Kidney problems (interstitial nephritis)  
 
c) Hypomagnesaemia  
                 Frequency “not known”: Low levels of magnesium can also lead   to 
a redu ction in potassium or calcium levels in the blood.  
 
d) Fracture  
Frequency “uncommon”: Tell your doctor if you have osteoporosis or 
if you are taking corticosteroids (which can ncrease the risk of 
osteoporosis).  
 
e) Clostridium Difficile Diarrhea  
Severe diarrhoe a which may be caused by an infection  
(Clostridium difficile) in your intestines.  
 
f)    Fundic Gland Polyps (Benign)  
  Frequency “Common”: Benign polyps in the stomach  
 
g) Vitamin B12 Deficiency  
Proton pump inhibitors may cause vitamin B12 deficiency.  
 
ii. Befo re you start to use it  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 565  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Tell your doctor before taking this medicine, if you are due to have a 
specific blood test (Chromogranin A).  
 
 
Reference :  
1. Directive No. 16 Year 2017. Ref. BPFK/PPP/07/25 ( 21 ) Jld 1.  Direktif Untuk Semua 
Produk Yang Mengandungi Proton Pump Inhibitors (PPI)  : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat 
Berka itan Risiko Kesan Advers Akibat Penggunaan Jangka Panjang  
(no. 1, 2, i)  
2. Directive No. 15 Year 2017. Ref. BPFK/PPP/07/25 ( 20 ) Jld 1. Direktif Untuk Semua 
Produk Yang Mengandungi Proton Pump Inhibitors (PPI)  : Pengemaskinian Sisip 
Bungkusan Dan Risalah Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat 
Berkaitan Elevated Circulating Levels of Chromogranin A (CgA)  
(no. 3, 4, ii)  
162.  PSEUDOEPHEDRINE  
 
The following statement  shall be included on the labels and in the package 
inserts  of liquid oral products containing Pseudoephedrine:  
 
WARNING  
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age 
(b) To be used with caution and doctor’s/ pharmacist’s advice in children 
2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/0 1/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Cough 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
 
163.  PSYCHOTROPIC PRO DUCTS  
 
The following statement  shall be included conspicuously on the labels  of all 
psychotropic products:  
 
CAUTION:  
This preparation may be habit forming on prolonged use.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 566  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
164.  PSYLLIUM/ PLANTAGO (SEED/ HUSK)  
For products containing Psyllium/ Plantago (Seed/  Husk), please state:  
- “If the constipation does not resolve within 3 days or if 
abdominal pain occurs or in case of any irregularity of faeces, 
the use of psyllium should be discontinued and medical advice 
must be sought.”  
“Please consume a large amount o f fluid/ water when taking this 
product.”  
 
165.  QUETIAPINE  
Please refer to ANTIPSYCHOTIC AGENT  
166.  QUINAGOLIDE  
Please refer to DOPAMINERGIC INGREDIENT  
167.  RED YEAST RICE (Monascus purpureus)  
 
 
 
 
 
 
 
 
 “This product contains naturally occurring lovastatin. Please consult 
your doctor/ pharmacist before using this product.”  
 
“Do not take this  product if you are already on statin products 
(lovastatin, atorvastatin, fluvastatin, prasvastatin, simvastatin, 
rosuvastatin, etc).  
 
“If you experience any allergic reactions or side effects such as lethargy, 
body and muscle aches, please stop using this  product”  
 
“Concurrent use of fibrates may cause severe myositis and 
myoglobinuria.”  
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 567  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
168.  RISPERIDONE  
Please refer to ANTIPSYCHOTIC AGENT  
 
The followi ng statement shall be included in the package inserts  of products 
containing Risperidone:  
 
Warnings and Precautions  
 
Intraoperative Floppy Iris Syndrome  
 
Intraoperative floppy iris syndrome (IFIS) has been observed during 
cataract surgery in patients treat ed with medicines with alpha1a -adrenergic 
antagonist effect, including risperidone. IFIS may increase the risk of eye 
complications during and after the operation. Current or past use of 
medicines with alpha1a -adrenergic antagonist effect should be made 
known to the ophthalmic surgeon in advance of surgery. The potential 
benefit of stopping alpha1 blocking therapy prior to cataract surgery has not 
been established and must be weighed against the risk of stopping the 
antipsychotic therapy.  
 
Undesirable Effec ts 
 
Postmarketing Data  
Eye Disorders  
Frequency: Not known – Floppy iris syndrome (intraoperative)  
 
References : Circular (17 )dlm.BPFK/PPP/01/03 Jld.3:  Pekeliling untuk mengemaskini sisip 
bungkusan semula produk yang mengandungi Risperidone atau Paliperidone dengan amaran 
berkaitan risiko Intraoperative Floppy Iris Syndrome (IFIS) pada pesakit yang menjalani 
pembedahan katarak  
 
169.  ROPINIROLE  
Please refer to DOPAMINERGIC INGREDIENT  
170.  ROSIGLITAZONE  
1. The following black box warning  shall be included in the first part of 
package inserts  of products containing Rosiglitazone as single 
ingredient or in combination with other active ingre dients :  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 568  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 
 
 
 
 
 
 
 
2.      The following information shall be included in the package inserts  of 
products containing Rosiglitazone as single ingredient or in combination 
with other active ingredients :  
 
CONTRAINDICATIONS  
 
Rosiglitazone is contraindicated i n patients with NYHA Class I to IV 
heart failure or history of cardiac failure, patients with known ischaemic 
heart disease a nd patients with Acute Coronary Syndrome (unstable 
angina, non -ST segment elevation myocardial infarction (NSTEMI) and 
ST segment e levation myocardial infarction.  
 
WARNING & PRECAUTIONS  
 
Rosiglitazone has been shown to be associated with an increased risk 
of myocardial ischaemia (angina, infarction) in pooled short term clinical 
studies compared to combined active/placebo control ( 2. 00% versus 
1.53%). Death from myocardial ischaemic events occurred in 0.15% on 
rosiglitazone – containing regimens and 0.12% on comparator regimen.  
    
Reference: Circular Bil (6) dlm BPFK/PPP/01/03 Jld 1:  Direktif Memperketatkan 
Penggunaan Rosiglitazone dan Memperkukuhkan Amaran Berkaitan Dengan Risiko Kesan 
Advers Kardiovaskular Pada Sisip Bungkusan Semua Produk Rosiglitazone  Termasuk Produk 
Kombinasi  
 • Rosiglitazone is contraindicated in patients with established NYHA 
Class I to IV heart failure and in patients with known ischaemic 
heart disease, particularly in th ose taking nitrates.  
• Thiazolidinediones, including rosiglitazone, cause or exacerbate 
congestive heart failure in some patients. Patients on rosiglitazone 
should be monitored carefully for signs and symptoms of heart 
failure (including excessive, rapid we ight gain, dyspnea, and/or 
edema). If these signs and symptoms develop, the heart failure 
should be managed according to current standards of care. 
Furthermore, discontinuation or dose reduction of rosiglitazone 
must be considered.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 569  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
171.  ROSUVASTATIN  
 
The following information  shall be included on the labels and/or package 
inserts  of products containing Rosuvastatin : 
 
DOSAGE AND ADMINISTRATION  
 
Dosage in patients with pre -disposing factors to myopathy  
The reco mmended start dose is 5 mg in patients with pre -disposing factors to 
myopathy  
 
Concomitant Therapy  
Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and 
BCRP). The risk of myopathy (including rhabdomyolysis) is increased when 
rosuva statin is administered concomitantly with certain medicinal products that 
may increase the plasma concentration of rosuvastatin due to interactions with 
these transporter proteins (e.g. certain protease inhibitors including 
combinations of ritonavir with a tazanavir, lopinavir, and/or tipranavir). 
Whenever possible, alternative medications should be considered, and if 
necessary, consider temporarily discontinuing [Product Name] therapy. In 
situations where co -administration of these medicinal products with 
rosuvastatin is unavoidable, the benefit and the risk of concurrent treatment 
and rosuvastatin dosing adjustments should be carefully considered.  
 
CONTRAINDICATIONS  
 
[Product Name] is contraindicated in patients receiving concomitant 
cyclosporine.  
 
WARNINGS  AND PRECAUTIONS  
 
Skeletal Muscle Effects  
Gemfibrozil increases the risk of myopathy when given concomitantly with 
some HMG -CoA reductase inhibitors. Therefore, the combination of 
rosuvastatin and gemfibrozil is not recommended. The benefit of further 
alterations in lipid levels by the combined use of rosuvastatin with fibrates or 
niacin should be carefully weighed against the potential risks of such 
combinations.  
All generic products containing Rosuvastatin should update their package 
inserts respectively according to the innovator’s information such as parts for 
Interactions, Pharmacokinetics and other parts deemed relevant.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 570  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference: Circular (16)dlm. BPFK/PPP/07/25  Directive No. 9 Year 2014.  
Direktif Untuk Semua Produk Rosuvastatin: Mengehadkan Dos Penggunaan 
Rosuvastatin Untuk Mengurangkan Risiko Kecederaan Otot  
172.  ROYAL JELLY  
 
The following information  shall be include d on the labels and/or package 
inserts  of products containing Royal jelly:  
 
WARNINGS  
 
This product contains royal jelly and may cause severe allergic reactions 
including fatal anaphylactic reactions in susceptible individuals. Asthma and 
allergy sufferers  may be at the greater risk.  
 
Reference:  
a) Circular Bil (48) dlm BPFK/02/5/1.3:  Pernyatan Amaran Pada Label Dan Sisip 
Bungkusan Produk Yang Mengandung i Propolis (Topikal) dan Royal Jelly (Semua 
Bentuk)  
b) Circular Bil (56) dlm BPFK/02/5/1.3:  Pernyataan Amaran pada Label dan Sisip 
Bungkusan Produk yan g Mengandungi Propolis (topikal) dan Royal Jelly (Semua 
Bentuk)  
c) Circular Bil (12) dlm. BPFK/PPP/01/03:  Pernyataan amaran pada label dan sisip 
bungkusan produk yang mengandungi royal jelly (produk kosmetik)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 571  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
173.  SALBUTAMOL  
 
1. The following information shall be included in the package inserts  of  
products containing Salbutamol in injection  dosage form:  
 
• As maternal pulmonary oedema and myocardial isch aemia have been 
reported during or following premature labour in patients receiving beta2 
– agonists, careful attention should be given to fluid balance and cardio -
respiratory function, including ECG monitoring. If signs of pulmonary 
oedema and myocardial ischaemia develop, discontinuation of treatment 
should be considered.  
 
• Due to the risk of pulmonary oedema and myocardial ischaemia that has 
been observed during the use of beta2 -agonists in the treatment of 
premature labour, before these products are give n to any patient with 
known heart disease, an adequate assessment of the patients’s 
cardiovascular status should be made by a physician experienced in 
cardiology.  
 
• Cautious use of salbutamol injections is required in pregnant patients 
when it is given for relief of bronchospasm so as to avoid interference with 
uterine contractibility. During IV infusion of salbutamol, the maternal pulse 
should be monitored and not normally allowed to exceed a steady rate of 
140 beats per minute.  
 
2. The following information s hall be included in the package inserts and 
product literature  of products containing Salbutamol in oral tablet/ capsule  
dosage form:  
 
• As maternal pulmonary oedema and myocardial ischaemia have been 
reported during or following premature labour in patients  receiving beta2 – 
agonists, careful attention should be given to fluid balance and cardio -
respiratory function, including ECG monitoring. If signs of pulmonary 
oedema and myocardial ischaemia develop, discontinuation of treatment 
should be considered.  
• Due to the risk of pulmonary oedema and myocardial ischaemia that has 
been observed during the use of beta2 -agonists in the treatment of 
premature labour, before these products are given to any patient with 
known heart disease, an adequate assessment of the p atients’s Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 572  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
cardiovascular status should be made by a physician experienced in 
cardiology.  
 
 
3.  The following warning statement  shall be included in the package inserts  of 
products containing Salbutamol in injection and oral  dosage form under 
section of Warning & Precautions : 
   
Tocolysis: Serious adverse reactions including death have been 
reported after administration of terbutaline/ salbutamol to women 
in labor. In the mother, these include increased heart rate, transient 
hyperglycaemia, hypokalaemia, car diac arrhythmias, pulmonary 
oedema and myocardial ischaemia. Increased fetal heart rate and 
neonatal hypoglycaemia may occur as a result of maternal 
administration.  
 
Reference:  
a) Circular Bil (6) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Mengenai Insiden 
Myocardial Ischaemia  pada Wanita Mengandung yang Menerima Rawatan Beta 
Agonist bagi Rawatan Melambatkan Kelahiran Pramatang pada Sisip Bung kusan 
Kumpulan Produk Ini  
b) Circular Bil (18) dlm BPFK/PPP/01/03 Jld 1 : Direktif untuk Memperkukuhkan 
Amaran Berkaitan dengan Risiko Kesan Advers Serius pada Jantung Termasuk 
Kematian dengan Penggunaan Produk Suntikan dan Oral Beta Agonis dalam 
Rawatan Kelahiran Pra -Matang  
 
174.  SALICYLIC ACID (NATURALLY OCCURING IN PLANTS E.G. WILLOW 
SALIX SPP)  
Please state: “Individual alle rgic to aspirin/ other NSAID should avoid this 
product.”  
 
  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 573  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
175.  SEDATIVE – HYPNOTIC PRODUCTS  
 
The following statement  shall be included in the package inserts  under section 
on ‘Warning’ and ‘Precaution’ of products containing:  
a. Alprazolam  
b. Bromazepam  
c. Clobazam  
d. Diazepam  
e. Flurazepam hydrochloride  
f. Lorazepam  
g. Midazolam  
h. Nitrazepam  
i. Triazolam  
j. Zolpidem tartrate  
k. Zopiclone  
 
WARNING/ PRECAUTION  
 
 
 
 
 
 
 
Reference: Circular Bil (75) dlm BPFK/02/5/1.3:  Pernyataan Amaran Pada Sisip Bungkusan 
Semua Produk Sedatif -Hipnotik Oral Berkaitan dengan Risiko Complex Sleep - Related 
Behaviors Which May Include Sleep Driving, Making Phone Calls, Preparing and Eating 
Food (While Asleep)  
176.  SELENIUM SULPHIDE  
 
The following statement  shall be included on the labels  of products containing 
Selenium sulphide:  
 
WARNING  
Do not use on broken skin or inflamed. Avoid contact with eyes.  
 
(AMARAN:  Selenium sulphide tidak boleh digu nakan pada kulit yang pecah 
dan radang. Elakkan daripada terkena mata. ) • Anaphylaxis (severe all ergic reaction) and angioedema (severe facial 
swelling) which can occur as early as the first time the product is taken  
• Complex sleep – related behaviors which may include sleep driving, 
making phone calls, preparing and eating food while  asleep  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 574  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
177.  SENNA (CASSIA SPP.) – fruit/ pod/ semen and leaf and Rhubarb/ Radix et 
Rhizoma Rhei/ Rheum Palmatum/ Rheum Officinalis – root part  
 
The following statement  shall be included on the l abels  of products containing 
senna ( cassia spp.) – fruit/ pod/ semen and leaf and Rhubarb/ Radix et 
Rhizoma Rhei/ Rheum Palmatum/ Rheum Officinalis – root part:  
• Do not use when abdominal pain, nausea or vomiting is present.  
• Frequent or prolonged use of thi s preparation may result in 
dependence towards the product and ‘imbalanced electrolytes’.  
• Please consult a health care practitioner for use beyond 7 days.  
178.  SIMVASTATIN  
 
The following statement  shall be included in the package inserts  of products 
containin g Simvastatin:  
 
1. Dosage and Administration  
 
The 80mg dose is only recommended in patients at high risk for 
cardiovascular complications who have not achieved treatment goals on 
lower doses and when the benefits are expected to outweigh the potential 
risks. 
 
Concomitant Therapy  
In patients taking fibrates (other than gemfibrozil and fenofibrate) 
concomitantly with [Product Name], the dose of [Product Name] should not 
exceed 10mg/day.  
 
In patients taking amiodarone, verapamil or diltiazem concomitantly wit h 
[Product Name], the dose of [Product Name] should not exceed 20mg/day.  
 
In patients taking amlodipine or lipid -lowering dose of niacin (≥1g/day) 
concomitantly with [Product Name], the dose of [Product Name] should not 
exceed 40mg/day.  
 
2. Contraindicatio ns 
 
• Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, 
ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, 
boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 575  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
nefazodone).  
• Concomitant administr ation of gemfibrozil, cyclosporine, or danazol.  
 
 
3. Interactions  
 
 Contraindicated Drugs  
 Potent inhibitors of CYP3A4: Concomitant use with medicines labeled as 
having a potent inhibitory effect on CYP3A4 at therapeutic doses (e.g.: 
itraconazole, ketocona zole, posaconazole, voriconazole, erythromycin, 
clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir or 
nefazodone) is contraindicated. If treatment with potent CYP3A4 inhibitors is 
unavoidable, therapy with simvastatin should be suspended during the course 
of treatment.  
 
 Gemfibrozil, cyclosporine or danazol: Concomitant use of these drugs with 
simvastatin is contraindicated.  
 
 Other Drugs  
 • Other fibrates: The dose of simvastatin should not exceed 10 mg daily  in 
patients receiv ing concomitant medication with fibrates other than  gemfibrozil 
or fenofibrate. When simvastatin and fenofibrate are given  concomitantly, 
there is no evidence that the risk of myopathy exceeds  the sum of the 
individual risks of each agent. Caution shoul d be used  when prescribing 
fenofibrate with simvastatin, as either agent can  cause myopathy when 
given alone. Addition of fibrates to simvastatin  typically provides little 
additional reduction in LDL -C, but further  reductions of TG and further 
increase s in HDL -C may be obtained.  Combinations of fibrates with 
simvastatin have been used without myopathy in small short -term clinical 
studies with careful monitoring.  
 
• Amiodarone: In a clinical trial, myopathy was reported in 6% of patients 
 receiving sim vastatin 80 mg and amiodarone. The dose of simvastatin 
 should not exceed 20 mg daily in patients receiving concomitant  medication 
with amiodarone.  
 
• Calcium channel blockers:  
- Verapamil or diltiazem: In a clinical trial, patients on diltiazem treated 
 concomitantly with simvastatin 80 mg had an increased risk of  myopathy. 
The dose of simvastatin should not exceed 20 mg daily in  patients receiving 
concomitant medication with verapamil or  diltiazem.  
 
- Amlodipine: In a clinical trial, patients on amlod ipine treated 
 concomitantly with simvastatin 80 mg had a slightly increased risk of Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 576  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 myopathy. The dose of simvastatin should not exceed 40 mg daily in 
 patients receiving concomitant medication with amlodipine.  
 
- Niacin (≥1g/day): The dose of simvastatin should not exceed 40mg daily in 
patients receiving concomitant medication with niacin  (nicotinic acid) ≥ 
1g/day. Cases of myopathy/rhabdomyolysis have  been observed with 
simvastatin co -administered with lipid -modifying  doses (≥ 1 g/day) of 
niacin.  
References : Circular (18)dlm.BPFK/PPP/01/03 Jld.3:  Pekeliling untuk mengemaskini s isip 
bungkusan semula produk yang mengandungi Simvastatin  dengan  memuatkan kontraindikasi 
dan had dos yang baru  
 
179.  SODIUM METABISULPHITE (EXCIPIENT)  
 
The following statement  shall be included in the package inserts  of products 
containing Sodium metabisulph ite: 
 
WARNING  
This preparation contains Sodium metabisulphite that may cause serious 
allergic type reactions in certain susceptible patients. Do not use if known to be 
hypersensitive to bisulphites.  
180.  SODIUM VALPROATE  
 
1. The following boxed warning  shall be included in the package insert  of 
products containing Sodium valproate:  
 
 
 
 
 
 
 
 
2. The following statement  shall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  of products containing 
Sodium Valproate:  
 
 
 PANCREAT ITIS:  
CASES OF LIFE -THREATENING PANCREATITIS HAVE BEEN 
REPORTED IN BOTH CHILDREN AND ADULTS RECEIVING 
VALPROATE. SOME OF THE CASES HAVE BEEN DESCRIBED AS 
HEMORRHAGIC WITH A RAPID PROGRESSION FROM INITIAL 
SYMPTOMS TO DEATH. CASES HAVE BEEN REPORTED SHORTLY 
AFTER INITIAL USE AS WELL AS AFTER SEVERAL YEARS OF USE. 
PATIENTS AND GUARDIANS SHOULD BE WARNED THAT 
ABDOMINAL PAIN, NAUSEA, VOMITING, AND/OR ANOREXIA CAN BE 
SYMPTOMS OF PANCREATITIS THAT REQUIRE PROMPT MEDICAL 
EVALUATION. IF PANCREATITIS IS DIAGNOSED, VA LPROATE 
SHOULD BE DISCONTINUED.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 577  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Package Insert  
 
a) Posology and Method of Administration:  
 
Female children, female adolescents, women of childbearing potential and 
pregnant women  
[Product Name] should be initiated and supervised by a specialist 
experienced in the management of epilepsy. Treatment should only be 
initiated if other treatments are ineffective or not tolerated and the benefit 
and risk should be carefully reconsidered at regular treatment reviews. 
Preferably [Product Name] should be prescribed as monotherapy and at 
the lowest effective dose, i f possible as a prolonged release formulation to 
avoid high peak plasma concentrations. The daily dose should be divided 
into at least two single doses.  
 
b) Special Warnings and Precautions for Use: 
 
Female children/Female adolescents/ Women of childbe aring 
potential/Pregnancy  
[Product Name] should not be used in female children, in female 
adolescents, in women of childbearing potential and pregnant women 
unless alternative treatments are ineffective or not tolerated because of its 
high teratogenic pot ential and risk of developmental disorders in infants 
exposed in utero to valproate.  
 
The benefit and risk should be carefully reconsidered at regular treatment 
reviews, at puberty and urgently when a woman of childbearing potential 
treated with [Product Name] plans a pregnancy or if she becomes 
pregnant.  
  
Women of childbearing potential must use effective contraception during 
treatment and be informed of the risks associated with the use of [Product 
Name] during pregnancy (see Fertility, Pregnancy and L actation).  
 
The prescriber must ensure that the patient is provided with 
comprehensive information on the risks alongside relevant materials, such 
as a patient information booklet, to support her understanding of the risks.  
 
In particular the prescriber m ust ensure the patient understands:  
• The nature and the magnitude   of the risks of exposure during 
pregnancy, in particular the teratogenic risks and the risks of 
developmental disorders.  
• The need to use effective contraception.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 578  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
• The need for regular rev iew of treatment.  
• The need to rapidly consult her physician if she is thinking of becoming 
pregnant or there is a possibility of pregnancy.  
 
In women planning to become pregnant all efforts should be made to 
switch to appropriate alternative treatment pr ior to conception, if possible:  
  
Valproate therapy should only be continued after a reassessment of the 
benefits and risks of the treatment with valproate for the patient by a 
physician experienced in the management of epilepsy.  
 
c) Fertility, Pregnancy and  Lactation:  
 
[Product Name] should not be used in female children, in female 
adolescents, in women of childbearing potential and in pregnant women 
unless other treatments are ineffective or not tolerated.  Women of 
childbearing potential have to use effecti ve contraception during treatment. 
In women planning to become pregnant all efforts should be made to 
switch to appropriate alternative treatment prior to conception, if possible.  
 
Pregnancy Exposure Risk related to valproate  
Both valproate monotherapy and  valproate polytherapy are associated with 
abnormal pregnancy outcomes. Available data suggest that antiepileptic 
polytherapy including valproate is associated with a greater risk of 
congenital malformations than valproate monotherapy.  
 
Congenital malforma tions  
Data derived from a meta -analysis (including registries and cohort studies) 
has shown that 10.73% of children of epileptic women exposed to 
valproate monotherapy during pregnancy suffer from congenital 
malformations (95% CI: 8.16 -13.29). This is a g reater risk of major 
malformations than for the general population, for whom the risk is about 2 -
3%. The risk is dose dependent but a threshold dose below which no risk 
exists cannot be established. Available data show an increased incidence 
of minor and m ajor malformations. The most common types of 
malformations include neural tube defects, facial dysmorphism, cleft lip and 
palate, craniostenosis, cardiac, renal and urogenital defects, limb defects 
(including bilateral aplasia of the radius), and multiple anomalies involving 
various body systems.  
 
Developmental disorders  
Data have shown that exposure to valproate in utero can have adverse 
effects on mental and physical development of the exposed children. The Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 579  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
risk seems to be dose -dependent but a threshold  dose below which no risk 
exists, cannot be established based on available data. The exact 
gestational period of risk for these effects is uncertain and the possibility of 
a risk throughout the entire pregnancy cannot be excluded.  
 
Studies in preschool ch ildren exposed in utero to valproate show that up to 
30-40% experience delays in their early development such as talking and 
walking later, lower intellectual abilities, poor language skills (speaking and 
understanding) and memory problems.  
 
Intelligence quotient (IQ) measured in school aged children (age 6) with a 
history of valproate exposure in utero was on average 7 -10 points lower 
than those children exposed to other antiepileptics. Although the role of 
confounding factors cannot be excluded, there is  evidence in children 
exposed to valproate that the risk of intellectual impairment may be 
independent from maternal IQ.  
 
There are limited data on the long term outcomes.  
 
Available data show that children exposed to valproate in utero are at 
increased r isk of autistic spectrum disorder (approximately three -fold) and 
childhood autism (approximately five -fold) compared with the general study 
population.  
 
Limited data suggests that children exposed to valproate in utero may be 
more likely to develop sympto ms of attention deficit/hyperactivity disorder 
(ADHD).  
 
Female children, female adolescents and woman of childbearing potential 
(see above and Special Warnings and Precautions for use)  
 
If a Woman wants to plan a Pregnancy  
• During pregnancy, maternal toni c clonic seizures and status epilepticus 
with hypoxia may carry a particular risk of death for the mother and the 
unborn child.  
• In women planning to become pregnant or who are pregnant, valproate 
therapy should be reassessed  
• In women planning to become pr egnant all efforts should be made to 
switch to appropriate alternative treatment prior to conception, if 
possible.  
 
Valproate therapy should not be discontinued without a reassessment of 
the benefits and risks of the treatment with valproate for the patie nt by a Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 580  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
physician experienced in the management of epilepsy. If based on a 
careful evaluation of the risks and the benefits valproate treatment is 
continued during the pregnancy, it is recommended to:  
- Use the lowest effective dose and divide the daily dos e valproate into 
several small doses to be taken throughout the day.  
- The use of a prolonged release formulation may be preferable to other 
treatment formulations  in order to avoid high peak plasma 
concentrations.  
- Folate supplementation before the pregnan cy may decrease the risk of 
neural tube defects common to all pregnancies. However the available 
evidence does not suggest it prevents the birth defects or malformations 
due to valproate exposure.  
- To institute specialized prenatal monitoring in order to de tect the 
possible occurrence of neural tube defects or other malformations.  
 
d) Interactions:  
 
Valproic acid may lead to an increased blood level of propofol. When co -
administered with valproate, a reduction of the dose of propofol should be 
considered.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Taking other medicines:  
 
Some medicines and sodium valproate may interfere with each other, 
these include propofol (a medicine used  before and during general 
anaesthesia). Tell your doctor that you are taking [product name] if you are 
going for an operation.  
 
 
Reference :  
1. Directive No. 17 Year 2016. Rujukan BPFK/PPP/07/25 ( 3 ) Jld 1.  Direktif Bagi Semua 
Produk Yang Mengandungi Sodium Valproate Bagi Memperkukuhkan Amaran Berkaitan 
Risiko Abnormal Pregnancy Outcomes  
2. Directive No. 7 Year 2018. Ref. BPFK/PPP/07/25 ( 7 ) Jld 2.  Direktif Untuk Semua Produk 
Yang Mengandungi Propofol Dan Sodium Valproate :  Pengemaskinian Sisip Bungkusan 
Dan Risalah Mak lumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan 
Berkaitan Interaksi Ubat  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 581  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
181.  ST. JOHN’S WORT   (Hypericum perforatum)  
The following boxed statement  shall be included on the labels  of products 
containing St. John’s Wort:  
 
 
 
 
 
182.  STATINS  
 
The fol lowing statement  shall be included in the package inserts  and RiMUP  of 
ALL products containing statins (single active or in combination):  
a. Atorvastatin  
b. Fluvastatin  
c. Lovastatin  
d. Pravastatin  
e. Rosuvastatin  
f. Simvastatin  
g. etc. 
 
Package Insert  
 
a) DRUG INTERACTION : 
 
Conc urrent use of fibrates may cause severe myositis and    
myoglobinuria.  
 
 
b) UNDESIRABLE EFFECTS : 
 
There have been rare post -marketing reports of cognitive impairment 
(e.g. memory loss, forgetfulness, amnesia, memory impairment, 
confusion) associated with stat in use. These cognitive issues have been 
reported for all statins. The reports are generally non -serious and 
reversible upon statin discontinuation, with variable times to symptom Please consult your physician/  pharmacist before using this product if you 
are on any prescription medicines as there is possibility that interactions 
may occur with certain drugs.  
 
(Sila dapatkan nasihat doktor/ ahli farma si sebelum menggunakan produk 
ini, kerana kemungkinan berlakunya interaksi dengan penggunaan ubat 
preskripsi).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 582  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
onset (1 day to years) and symptom resolution (median 3 weeks).  
 
Increases i n HbA1c and fasting blood glucose have been reported with 
statins. The risk of hyperglycemia, however, is outweighed by the 
reduction in vascular risk with statins.  
 
c) Warnings and Precautions:  
There have been very rare reports of an immune -mediated necrotiz ing 
myopathy (IMNM) during or after treatment with some statins. IMNM is 
clinically characterized by:  
• persistent proximal muscle weakness and elevated serum 
creatine kinase, which persist despite discontinuation of statin 
treatment;  
• muscle biopsy showing necrotizing myopathy without significant 
inflammation;  
• improvement with immunosuppressive agents.  
 
d)  Adverse Effects/Undesirable Effects:  
 
Musculoskeletal disorders:  
Frequency not known: Immune -mediated necrotizing myopathy   
 
 
Consumer Medication Informati on Leaflet (RiMUP)  
 
Side Effects  
 
If you have muscle problems that do not go away even after your doctor 
has told you to stop taking {product name}, please refer to your doctor. 
Your doctor may do further tests to diagnose the cause of your muscle 
problems . 
 
References:  
1. Circular (14) dlm.BPFK/PPP/07/25 . Directive No. 7 Year 2014.   Direktif Untuk Semua 
Produk Statin: Memperkukuhkan Ama ran Berkaitan Risiko Kesan Advers Kognitif Dan 
Peningkatan HBA1C Serta Fasting Blood Glucose (FBG)  
2. Directive No. 29 Year 2017. Ref. BPFK/PPP/07 /25 ( 34 ) Jld 1.  Direktif Untuk Semua 
Produk Yang Mengandungi Statin : Pengemaskinian Sisip Bungkusan Dan Risalah 
Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Berkaitan Immune -
Mediated Necrotizing Myopathy (IMNM)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 583  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
183.  STRONTIUM RANELATE  
1. The foll owing black boxed warning  shall be included in the first part of 
package inserts  of products containing Strontium Ranelate:  
 
 
 
 
 
 
 
 
2. The following statement  shall be included in the package inserts  of products 
containing Strontium Ranelate:  
 
    Indicat ion 
 
• Treatment of severe/established  osteoporosis in postmenopausal 
women at high risk of fracture  to reduce the risk of vertebral and hip 
fractures  
• Treatment of severe/established  osteoporosis in men at increased 
risk of fracture  
[Brand Name] should only be used for whom treatment with 
other medicinal products approved for the treatment of 
osteoporosis is not possible due to, for example, 
contraindications or intolerance.  
 
Contraindications  
 
• Established, current or past history of ischaemic heart disease, 
peripheral arterial disease and/or cerebrovascular disease  
• Uncontrolled hypertension  [Brand Name]  should only be used for whom treatment with 
other medicinal products approved for the treatment of 
osteoporosis is not possible due  to, for example, 
contraindications or intolerance.  
[Brand Name]  is contraindicated in patients with:  
 established, current or past history of ischaemic heart 
disease; peripheral arterial disease and/or cerebrovascular 
disease;  
 uncontrolled hypertension;  
 current or previous venous thromboembolic events (VTE);  
 temporary or permanent immobilisation.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 584  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
 
Special warnings and precautions for use : 
 
Cardiac ischaemic events  
In pooled randomised placebo -controlled studies of post -menopausal 
osteoporotic patients, a significa nt increase in myocardial infarction 
has been observed in strontium ranelate treated patients compared to 
placebo.  
Before starting treatment, patients should be evaluated with respect 
to cardiovascular risk.  
Patients with significant risk factors for card iovascular events (e.g. 
hypertension, hyperlipidaemia, diabetes mellitus, smoking) should 
only be treated with strontium ranelate after careful consideration.  
During [BRAND NAME] treatment, these cardiovascular risks should 
be monitored on a regular basis generally every 6 to 12 months.  
 
Treatment should be stopped if the patient develops ischaemic heart 
disease, peripheral arterial disease, cerebrovascular disease or if 
hypertension is uncontrolled.  
 
Undesirable  effects : 
 
SOC Cardiac disorders:  
- Common: My ocardial infarction  
 
Myocardial infarction  
In pooled randomised placebo -controlled studies of post -menopausal 
osteoporotic patients, a significant increase of myocardial infarction 
has been observed in strontium ranelate treated patients  as 
compared to pla cebo (1.7% versus 1.1%), with a relative risk of 1.6 
(95% CI = [1.07; 2.38]).  
References: Circular (16)dlm.BPFK/PPP/01/ 03 Jld.3:  Pekeliling tentang langkah -langkah 
pengurangan risiko bagi produk yang mengandungi Strontium Ranelate susulan risiko kesan 
advers kardiovaskular  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 585  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
184.  SULPHONAMIDES/ TRIMETHOPRIM  
1. The following statement  shall be included on the labels  of product s 
containing Sulphonamides and Trimethoprim as single ingredient or in 
combination of both ingredients:  
 
 
 
2. The following statement  shall be included in the package inserts  of products 
containing Sulphonamides and Trimethoprim as single ingredient or in  
combination of both ingredients:  
 
 
 Discontinue treatment with this drug immediately if skin rash or any sign 
of adverse reaction occurs.  
Fatalities associated with the administration of sulphonam ides and 
trimethoprim, either alone or in combination, have occurred due to severe 
reactions, including Steven -Johnson syndrome, toxic epidermal necrolysis 
and other reactions. The drug should be discontinued at the first 
appearance of skin rash or any sig n of adverse reaction.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 586  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
185.   
SYNTHETIC SALMON CALCITONIN  
 
1. Indication and duration of use for products containing synthetic salmon 
calcitonin (according to the stated dosage forms) are restricted as follows, 
and the package insert of the prod uct shall be amended accordingly:  
 
a) For dosage form: Injection  
Prevention of acute bone loss due to sudden immobilisation such as 
in patients with recent osteoporotic fractures.      
The duration of treatment should not be more than 4 weeks.  
For the treatme nt of Paget’s disease, only in patients who do not 
respond to alternative treatments or for whom such treatments are 
not suitable, for example those with severe renal impairment.   
The duration of treatment is limited to 3 months.  
Treatment of hypercalcaem ia of malignancy.  
b) For dosage form: Nasal spray  
Prevention of osteoporosis : In acute bone loss due to sudden 
immobilisation such as in patients with recent osteoporotic fractures. 
Miacalcic should be supplemented with adequate doses of calcium 
and Vit D, as  needed by the individual patient, to prevent further 
bone loss.  
The maximum duration of treatment is 3 months.  
Paget’s disease , only in patients who do not respond to alternative 
treatments or for whom such treatments are not suitable.  
The duration of tr eatment is normally 3 months.  
Algodystrophy or Sudeck’s Disease (Neurodystrophic disorders)  
due to various causes and predisposing factors such as 
posttraumatic painful osteoporosis, reflex dystrophy, shoulder arm 
syndrome, causalgia and drug -induced neuro trophic disorders.  
The duration of treatment is up to 6 weeks . 
 
2. Under “Dosage” in the package insert of products containing synthetic 
salmon calcitonin (injection and nasal spray), the following statement shall 
be stated:  
The treatment duration in all indications should be limited to the 
shortest period of time possible and using the lowest effective dose.  
 
Reference: Directive (10)dlm.BPFK/PPP/07/25 : Direktif untuk mengehadkan indikasi dan 
tempoh penggunaan produk yang mengandungi Calcitonin Salmon sintetik dalam bentuk 
injeksi dan Intranasal 'Nasal Spray' berikutan risiko kanser  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 587  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
186.  TABEBUIA SPP. (PAU D’ARCO)  
The following warning statement  shall be included on the labels  of products 
containing Tabebuia spp. (Pau d’arco):  
“As the use of Tabebuia spp. (Pau d’arco) may increase the tendency 
of bleeding, please consult your physician/ pharmacist if you are on or 
intend to start using any other medicine and before you undergo any 
surgical/ dental procedure.”  
(Memandangkan pengambilan Tabebuia spp. (Pau d’arco) boleh 
meningkatkan kemungkinan pendarahan, sila rujuk kepada doktor/ 
ahli farmasi sekiranya anda sedang atau akan menggunakan ubat 
lain dan sebelum prosedur pembedahan/ dental dijalankan)  
187.  TEMOZOLO MIDE  
 
The following statement  shall be included in the package inserts  of products 
containing Temozol omide:  
 
WARNINGS AND PRECAUTIONS  
 
Hepatic injury, including fatal hepatic failure has been reported in patients 
receiving temozolo mide. Baseline liver function tests should be performed prior 
to treatment initiation. If abnormal, physicians should assess the benefit/ ri sks 
prior to initiating temozolo mide including the p otential for fatal hepatic failure.  
For patients on a 42 day treatment cycle, liver function test should be repeated 
midway during this cycle. For all patients, liver function test should be checked 
after treatment cycle. For patient with significant liver  function abnormalities, 
physicians should assess the benefit/ risks of continuing treatment. Liver 
toxicity may occur several weeks or more after the last reatment of 
temozol omide.  
 
Reference: Circular Bil (18) dlm BPFK/PPP/07/25 . Directive No.  11 Year  2014.  
DIREKTIF UNTUK SEMUA PRODUK YANG MENGANDUNGI TEMOZOLOMIDE: 
MAKLUMAT KESELAMATAN BARU BERKAITAN DENGAN RISIKO 
KECEDERAAN HA TI Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 588  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
188.  TERBUTALINE  
1. The following statement  shall be included in the package inserts  of 
 products containing Terbutaline in injection  dosage form:  
 
• As maternal pulmonary oedema and myocardial ischaemia have 
been reported during or following premature labou r in patients 
receiving beta2 – agonists, careful attention should be given to fluid 
balance and cardio -respiratory function, including ECG monitoring. 
If signs of pulmonary oedema and myocardial ischaemia develop, 
discontinuation of treatment should be co nsidered.  
 
• Due to the risk of pulmonary oedema and myocardial ischaemia that 
has been observed during the use of beta2 -agonists in the 
treatment of premature labour, before these products are given to 
any patient with known heart disease, an adequate asses sment of 
the patients’s cardiovascular status should be made by a physician 
experienced in cardiology.  
 
• Cautious use of terbutaline injections is required in pregnant 
patients when it is given for relief of bronchospasm so as to avoid 
interference with ute rine contractibility. During IV infusion of 
terbutaline, the maternal pulse should be monitored and not 
normally allowed to exceed a steady rate of 140 beats per minute.  
 
2. The following information shall be included in the package insert and product 
literature  of products containing Terbutaline in oral tablet/ capsule  dosage 
form:  
 
• As maternal pulmonary oedema and myocardial ischaemia have 
been reported during or following premature labour in patients 
receiving beta2 – agonists, careful attention should b e given to fluid 
balance and cardio -respiratory function, including ECG monitoring. If 
signs of pulmonary oedema and myocardial ischaemia develop, 
discontinuation of treatment should be considered.  
 
• Due to the risk of pulmonary oedema and myocardial ischae mia that 
has been observed during the use of beta2 -agonists in the treatment 
of premature labour, before these products are given to any patient 
with known heart disease, an adequate assessment of the patients’s Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 589  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
cardiovascular status should be made by a ph ysician experienced in 
cardiology.  
 
 
3.  The following warning statement  shall be included in the package inserts  of 
products containing Salbutamol in injection and oral  dosage form under 
section of Warning & Precautions : 
 
•  Tocolysis: Serious adverse react ions including death have 
been reported after administration of terbutaline/ salbutamol to 
women in labor. In the mother, these include increased heart 
rate, transient hyperglycaemia, hypokalaemia, cardiac 
arrhythmias, pulmonary oedema and myocardial ischa emia. 
Increased fetal heart rate and neonatal hypoglycaemia may 
occur as a result of maternal administration.  
                      
Reference:  
a) Circular Bil (6) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Mengenai Insiden 
Myocardial Ischaemia  pada Wanita Mengandung yang Menerima Rawatan Beta 
Agonist bagi Rawatan Melambatkan Kelahiran Pramatang pada Sisip Bungkusan 
Kumpulan Produk Ini  
b) Circular Bil (18) dlm BPFK/PPP/01/03 Jld 1 : Direktif untuk Memperkukuhkan 
Amaran Berkaitan dengan Risiko Kesan Advers Serius pada Jantung Termasuk 
Kematian dengan Penggunaan Produk Suntikan dan Oral Beta Agonis dalam 
Rawatan Kelahiran Pra -Matang  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 590  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
189.   
TESTOSTERONE  
 
The following statements shall be included in the package insert  and 
Consumer Medication Information Leaflet (RiMUP)  for products containing 
Testosterone;  
 
 
Package Insert  
 
a) Warnings and Precautions:  
 
Drug Abuse and Dependence  
Testosterone has been subject to abuse, typically at doses higher than 
recommended for the approved indication and in combination with other 
anabolic androgenic steroids (AAS). Abuse of testosterone and other AAS 
are seen in adults and adolescents, including athletes and body builders. 
Testosterone and AAS abuse can lead to serious adverse outcomes 
particularly cardiovascular and psychiatric adver se events (See Section 
Adverse Effects/Undesirable Effects).  
 
If testosterone abuse is suspected, check serum testosterone 
concentrations to ensure they are within therapeutic range. However, 
testosterone levels may be in the normal or subnormal range in m en 
abusing synthetic testosterone derivatives. Counsel patients concerning the 
serious adverse reactions associated with abuse of testosterone and AAS. 
Conversely, consider the possibility of testosterone and AAS abuse in 
suspected patients who present wit h serious cardiovascular or psychiatric 
adverse events.  
 
Continued abuse of testosterone and other AAS may result in dependence 
and withdrawal symptoms. Individuals taking supratherapeutic doses of 
testosterone may experience withdrawal symptoms lasting fo r weeks or 
months which include depressed mood, major depression, fatigue, craving, 
restlessness, irritability, anorexia, insomnia, decreased libido and 
hypogonadotropic hypogonadism. Drug dependence in individuals using 
approved doses of testosterone for approved indications has not been 
documented.   
 
c)  Overdose:  
 
Chronic Overdose Caused by Abuse  
Chronic overdose caused by abuse of testosterone and other anabolic 
androgenic steroids (AAS) can lead to serious adverse outcomes Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 591  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
particularly cardiovascular and psychiatric adverse events (See Sections 
Warnings and Precautions and Adverse Effects/ Undesirable Effects).  
 
d) Adverse Effects/Undesirable Effects:  
 
Abuse -Related Adverse Reactions  
Serious adverse reactions have been reported in individuals who abuse 
testos terone and anabolic androgenic steroids (AAS) and include cardiac 
arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive 
heart failure, cerebrovascular accident, hepatotoxicity, and serious 
psychiatric manifestations, including major depres sion, mania, paranoia, 
psychosis, delusions, hallucinations, hostility and aggression.  
 
The following adverse reactions have also been reported in men: transient 
ischemic attacks, convulsions, hypomania, irritability, dyslipidaemias, 
testicular atrophy, su bfertility, and infertility.  
 
The following additional adverse reactions have been reported in women: 
hirsutism, virilisation, deepening of voice, clitoral enlargement, breast 
atrophy, male -pattern baldness, and menstrual irregularities.  
 
The following adv erse reactions have been reported in male and female 
adolescents: premature closure of bony epiphyses with termination of 
growth, and precocious puberty.  
 
Because these reactions are reported voluntarily from a population of 
uncertain size and may include abuse of other agents, it is not always 
possible to reliably estimate their frequency or establish a causal 
relationship to drug exposure.  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
b) How to  use <product name>:  
 
If you use too much (overdose):  
If you  have taken more than the recommended dose of <product name>, 
contact your doctor immediately or go to the Emergency Department of 
your nearest hospital. Do this even if there are no signs of discomfort or 
poisoning. You may need urgent medical attention.  
 
Taking more than the recommended dose of <product name> for a long 
period of time can cause serious health problems including effects on the 
heart, liver, and reproductive functions, as well as serious psychiatric Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 592  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
problems.  
 
b) While you are using it:  
 
Things you must not do:  
Do not take more than the recommended dose of <product name>. 
Individuals who have taken more than the recommended dose for a long 
period of time may experience withdrawal symptoms lasting for weeks or 
months after abrupt discontinua tion or a significant dose reduction of 
<product name>. These include: changes in mood and appetite, fatigue, 
insomnia, decreased sex drive as well as loss of function of the testes and 
ovaries.  
 
Reference : Directive No. 19 Year 2017. Ref. BPFK/PPP/07/25 ( 24 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi Testosteron : Pengemaskinian Sisip Bungkusan Dan 
Risalah Maklumat Ubat Untuk Pengguna ( RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Kesan Advers Susulan Penyalahgunaan Dan Kebergantungan Ubat  
190.  TETRACYCLINE SYRUP  
The following boxed warning  shall be included on the label and in the package 
inserts  of products containing Tetracycline (syrup)  
 
 
191.  THIOMERSAL  
 
Note:  Thiomersal is not allowed in ophthalmic preparations as preservative . 
 
The following statement  shall be included on the label and package inserts  of 
products containing thiomersal for preparations other than ophthalmic 
preparation:  
 
WARNING  
 
‘RISK OF SENSITIZATION IN RELATION TO THIOMERSAL AND OTHER 
PRESERVATIVES’  
 
Reference: Circular Bil (34)dlm BPFK/02/5/1.3:  Penggunaan Thiom ersal Dalam Persediaan 
Vaksin  NOT TO BE GIVEN TO CHILDREN UNDER 12 YEARS OF AGE  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 593  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
192.  THROMBOLYTIC AGENTS  
 
The following caution  shall be disclosed prominently in the package inserts  of 
products containing “systemic thrombolytic agent” in particular “the tissue 
plasminogen activators”:  
 
WARNING  
Severe bleedin g such as intracranial haemorrhage may occur following 
administration of the drug, particularly in the elderly patients. The risk must be 
balanced against the potential benefit of thrombolysis.  
 
The following precautions need to be observed:  
Patients shoul d be carefully observed for clinical signs during and following 
administration of the drug for early detection of bleeding. Frequent 
haematological tests such as blood coagulation tests are mandatory.  
 
To prevent bleeding at the site of centesis or other r egions, caution must be 
exercised concerning procedures and management of arterial/ venus puncture.  
The use of heparin in conjunction with the thrombolytic agent for the purpose 
of prevention of reocclusion may increase the risk of intracranial haemorrhage . 
Close monitoring of patients is strongly recommended.  
 
 
193.  TIAPROFENIC ACID  
 
The following statement  shall be included in the package inserts  of products 
containing Tiaprofenic acid:  
 
PRECAUTION  
Urinary symptoms (bladder pain, dysuria, and frequency), hae maturia or 
cystitis may occur. In certain exceptional cases, the symptoms have become 
severe on continued treatment. Should urinary symptoms occur, treatment with 
tiaprofenic acid must be stopped.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 594  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
194.  TOPIRAMATE  
 
The following statement  shall be included in the package inserts  of products 
containing T opiramate : 
 
SPECIAL WARNINGS AND PRECAUTIONS FOR USE  
 
Visual field defects   
 
Visual field defects have been reported in patients receiving topiramate 
independent of elevated intraocular pressure. In clinical tri als, most of these 
events were reversible following topiramate discontinuation, however some 
cases were not. In a large proportion of postmarketing case reports reversibility 
was unknown, but in cases where an outcome was reported, the majority were 
revers ible. If visual problems occur at any time during topiramate treatment, 
consideration should be given to discontinuing the drug.  
Reference Circular : (22) BPFK/PPP/07/25 . Directive No. 15 Year 2014  
Direktif Untuk Semua Produk Yang Mengandungi Topiramate: Amaran 
Berkaitan Risiko Gangguan Penglihatan  
 
195.  TRAMADOL  
(Please also refer to OPIOID)  
 
The following statements shall be included in the packa ge insert and RiMUP  of 
products containing Tramadol:  
 
 
Package Insert  
 
a) Recommended Dosage:  
 
Adults and adolescents (12 years and older)  
<Product name> is not approved for use in patients below 12 years old.
  
 
Paediatric population  
The safety and efficac y of <product name> has not been studied in the 
paediatric population. Therefore, use of <product name> is not 
recommended in patients under 12 years of age.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 595  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
b) Contraindications:  
 
- Children younger than 18 years to treat pain after surgery to remove the 
tonsils and/or adenoids.  
- Adolescents between 12 and 18 years who are obese or have conditions 
such as obstructive sleep apnea or severe lung disease, which may 
increase the risk of serious breathing problems.  
 
c) Warnings and Precautions:  
 
Paediatric popula tion 
The safety and efficacy of <product name> has not been studied in the 
paediatric population. Therefore, use of <product name> is not 
recommended in patients under 12 years of age.  
 
Respiratory depression  
Administer <product name> cautiously in patient s at risk for respiratory 
depression, including patients with substantially decreased respiratory 
reserve, hypoxia, hypercapnia, or pre -existing respiratory depression, as in 
these patients, even therapeutic doses of <product name> may decrease 
respiratory  drive to the point of apnea. In these patients, alternative non -
opioid analgesics should be considered. When large doses of tramadol are 
administered with anaesthetic medications or alcohol, respiratory 
depression may result. Respiratory depression should  be treated as an 
overdose. If naloxone is to be administered, use cautiously because it may 
precipitate seizures.  
 
Cytochromes P450 (CYP) 2D6 Ultra -Rapid Metabolism  
Some individuals may be CYP2D6 ultra -rapid metabolisers. These 
individuals convert tramado l more rapidly than other people into its more 
potent opioid metabolites O -desmethyltramadol (M1). This rapid conversion 
could result in higher than expected opioid -like side effects including life -
threatening respiratory depression. The prevalence of this  CYP2D6 
phenotype varies widely and has been estimated at 0.5 to 1% in Chinese, 
Japanese and Hispanics, 1 to 10% in Caucasians, 3% in African 
Americans, and 16 -28% in North Africans, Ethiopians, and Arabs. Data are 
not available for other ethnic groups.  
 
d) Pregnancy and Lactation:  
 
Pregnancy  
Tramadol has been shown to cross the placenta. There are no adequate 
and well -controlled studies in pregnant women. Safe use in pregnancy has Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 596  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
not been established. <Product name> is not recommended for pregnant 
women.  
 
Lactation  
Approximately 0.1% of the maternal dose of tramadol is excreted in breast 
milk. In the immediate post -partum period, for maternal oral daily dosage up 
to 400 mg, this corresponds to a mean amount of tramadol ingested by 
breast -fed infants of 3% of the maternal weight -adjusted dosage. For this 
reason tramadol should not be used during lactation or alternatively, breast -
feeding should be discontinued during treatment with tramadol. 
Discontinuation of breast -feeding is generally not necessary follow ing a 
single dose of tramadol.  
 
e)  Adverse Effects/Undesirable Effects:  
 
Respiratory depression (rare)  
 
 
Consumer Medication Information Leaflet (RiMUP)  
 
a) Before you use <product name>  
 
When you must not use it:  
- you are less than 12 years old.  
- you have  slow or shallow breathing, or other breathing problems.  
- you are pregnant.  
- you are breastfeeding.  
 
b) While you are using it:  
 
Things to be careful of:  
- Tramadol is not to be used during breast -feeding. Small amounts of 
tramadol is excreted into breast milk. On a single dose it is usually not 
necessary to interrupt breast -feeding. If you have taken <product name> 
when you are breastfeeding, seek immediate medical attention if you 
notice your baby has any changes in their breathing (such as weak, 
difficul t or fast breathing).  
 
 
Reference : Directive No. 20 Year 2017. Ref. BPFK/PPP/07/25 ( 25 ) Jld 1.  Direktif Untuk 
Semua Produk Yang Mengandungi Tra madol Dengan Maklumat Bagi Mengehadkan 
Penggunaan Tramadol Dalam Kalangan Kanak -Kanak Dan Amaran Berkaitan Penggunaan 
Dalam Kalangan Ibu Mengandung Dan Ibu Menyusu  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 597  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
196.  TRETINOIN TOPICAL  
 
The following statement  shall be included in the package inserts  of products 
containing Tretinoin used topically:  
 
USE IN PREGNANCY:  
197.  TRIAZOLAM  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  and BENZODIAZEPINE  
198.  TRIMETAZIDINE  
 
1. Indication of products containing Trimetazidine shall be amended as 
follows:  
a) Indication of Tri metazidine for treatment of pectoris angina is 
limited to second -line add on therapy; and the indication in otology 
and ophthalmology field shall be removed.  
b) Permitted indication is trimetazidine is indicated in adults as 
add-on therapy for the symptomati c treatment of patients with 
stable angina pectoris who are inadequately controlled by or 
intolerant to first -line antianginal therapies.  
2. The following warning statement  shall be included in the package inserts  
of products containing Trimetazidine:  
a) At part of Dosage and method of administration : Studies in animal have shown that oral tretinoin is fetotoxic in rats given 
500 times the topical human dose and teratogenic in rats given 1 ,000 
times the topical human dose. Topica l tretinoin has caused delayed 
ossification in a number of bones in the offspring of rats and rabbits given 
100 to 320 tim es the topical human dose, respectively. There has been 
increasing incidence of foetal malformation following topical administration 
of tretinoi. Use of topical tretinoin is not recommended during pregnancy, 
especially the first trimester.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 598  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
For products containing Trimetazidine 20mg:  
The dose is one tablet of 20mg of trimetazidine three times a 
day during meals.   
The benefit of the treatment should be assessed after three 
months and trimetazidine  should be discontinued if there is no 
treatment response.  
 
Special populations  
Patients with renal impairment:  
In patients with moderate renal impairment (creatinine clearance 
[30-60] ml/min), the recommended dose is 1 tablet of 20mg twice 
daily, i.e., on e in the morning and one in the evening during 
meals.  
 
Elderly patients:  
Elderly patients may have increased trimetazidine exposure due 
to age -related decrease in renal function. In patients with 
moderate renal impairment (creatinine clearance [30 -60] ml/m in), 
the recommended dose is 1 tablet of 20mg twice daily, i.e., one 
in the morning and one in the evening during meals. Dose 
titration in elderly patients should be exercised with caution.  
 
For products containing Trimetazidine 35mg:  
The dose is one table t of 35mg of trimetazidine twice daily 
during meals.   
The benefit of the treatment should be assessed after three 
months and trimetazidine should be discontinued if there is no 
treatment response.  
 
Special populations  
Patients with renal impairment:  
In pat ients with moderate renal impairment (creatinine clearance 
[30-60] ml/min), the recommended dose is 1 tablet of 35mg in the 
morning during breakfast.  
 
Elderly patients:  
Elderly patients may have increased trimetazidine exposure due 
to age -related decrease in renal function. In patients with 
moderate renal impairment (creatinine clearance [30 -60] ml/min), 
the recommended dose is 1 tablet of 35mg in the morning during 
breakfast. Dose titration in elderly patients should be exercised Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 599  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
with caution.  
 
b) At part of Contraindications : 
- Parkinson disease, parkinsonian symptoms, tremors, restless 
leg syndrome, and other related movement disorders  
- Severe renal impairment (creatinine clearance < 30ml/min).  
 
c) At part of Special warnings and precautions for use : 
 
Trimetazidin e can cause or worsen parkinsonian symptoms 
(tremor, akinesia, hypertonia), which should be regularly 
investigated, especially in elderly patients. In doubtful cases, 
patients should be referred to a neurologist for appropriate 
investigations.  
 
The occurre nce of movement disorders such as parkinsonian 
symptoms, restless leg syndrome, tremors, gait instability 
should lead to definitive withdrawal of trimetazidine.  
 
These cases have a low incidence and are usually reversible 
after treatment discontinuation. T he majority of the patients 
recovered within 4 months after trimetazidine withdrawal. If 
parkinsonian symptoms persist more than 4 months after drug 
discontinuation, a neurologist opinion should be sought.  
 
Falls may occur, related to gait instability or h ypotension, in 
particular in patients taking antihypertensive treatment.  
 
Caution should be exercised when prescribing trimetazidine to 
patients in whom an increased exposure is expected:  
-  moderate renal impairment,  
- elderly patients older than 75 years  old. 
 
d) At part of Side effects : 
 
Nervous system disorders:  
Frequency not known:  Parkinsonian symptoms (tremor, 
akinesia, hypertonia), gait instability, 
restless leg syndrome, other related 
movement disorders, usually 
reversible after treatment 
discontinuat ion. 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 600  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Reference: Directive No. 5 Year 2013, (4)dlm.BPFK/PPP/07/25 : Direktif untuk menghadkan 
penggunaan produk mengandungi Tri metazidine dan mengukuhkan amaran berkaitan dengan 
risiko kesan advers simptom parkinson pada sisip bungkusan semua produk Trimetazidine  
 
199.  TRIPROLIDINE  
 
The following statement  shall be included on the label and in the package 
inserts  of liquid oral produ cts containing Triprolidine:  
 
WARNING  
When used for treatment of cough and cold:  
(a) Not to be used in children less than 2 years of age  
(b) To be used with caution and doctor’s/ pharmacist’s advice in 
children 2 to 6 years of age.  
 
Reference:  Circular  Bil (34) dlm. BPFK/PPP/01/03:  Kenyataan Amaran Pada Label dan 
Sisip Bungkusan Produk Persediaan Cecair Oral Untuk Rawatan Batuk dan Selsema (Coug h 
and Cold) yang Mengandungi Antihistamin, Antitusif   dan Dekongestan (Sebagai Bahan Aktif 
Tunggal atau Kombinasi)  
200.  VARENICLINE  
 
The following statement  shall be included in the package inserts  of products 
containing Varenicline:  
 
SPECIAL WARNINGS AND PRE CAUTIONS FOR USE  
 
Effect of smoking cessation:  
Smoking cessation, with or without pharmacotherapy has been associated with 
the exacerbation of underlying psychiatric illness (eg. depression). Care should 
be taken with patients with a history of psychiatric  illness and patients should 
be advised accordingly.  
 
Depression, rarely including suicidal ideation and suicide attempt, has been 
reported in patients undergoing a smoking cessation attempt.  
 
UNDESIRABLE EFFECTS  
 
Post marketing cases of MI, depression and  suicidal ideation have been 
reported in patients taking varenicline.  
 
Reference: Circular Bil (83) dlm. BPFK/17/FV/28:  Maklumat dari pada  European M edicines 
Agency (EMEA) berkaitan penggunaan produk Champix (Varenicline)  untuk rawatan berhenti 
merokok (smoking cessation).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 601  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
201.  VITAMIN K  
 
149.1 The following statement shall be included in the label and package insert 
of health supplement products containi ng Vitamin K as combined 
ingredients with other vitamins and minerals in oral preparation:  
 
 
 
 
 
 
149.2 The following statement  shall be included in the package inserts  of 
products containing Vitamin K1 (phytomenadione) as single ingredient 
used intravenou sly: 
 
WARNING  
Severe reactions, including fatalities, have occurred during and 
immediately after intravenous injection of Vitamin K1. Restrict 
intravenous use to emergency case. When intravenous administration is 
necessary, the rate of injection should not  exceed 1mg per minute . 
 
ADMINISTRATION : 
In severe bleeding, or situations where other routes are not feasible, 
Vitamin K1 may be given by very slow intravenous injection, at a rate 
not exceeding 1mg per minute.  
202.  WARFARIN  
 
a) The following statements  shall be included in the package insert  of products 
containing Warfarin:  
 
 
Caution  
 
Topical preparations containing methyl salicylate should be used with care in 
patients on Warfarin and excessive usage is to be avoided as potentially 
dangerous drug interactio n can occur.  
 
Contraindications  
 
Co-administration with miconazole oral gel (see Interactions).  
 ‘Consult a heal thcare practitioner if you are on anticoagulant/ 
blood thinner products.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 602  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
Special Warnings and Precautions for Use : 
 
• Calciphylaxis is a rare syndrome of vascular calcification with cutaneous 
necrosis, associated with high mortality. The condition is mainly 
observed in patients with end -stage renal disease on dialysis or in 
patients with known risk factors such as protein C or S deficiency, 
hyperphosphatemia, hypercalcaemia or hypoalbuminaemia. Rare cases 
of calciphylaxis have been rep orted in patients taking warfarin, also in 
the absence of renal disease. In case calciphylaxis is diagnosed, 
appropriate treatment should be started and consideration should be 
given to stopping treatment with warfarin.  
• Co-administration with topical micon azole (see Interactions).  
 
 
Interactions  
 
The following drugs have been reported to potentiate the warfarin effect 
(increase INR):  
• Miconazole  
 
 
Adverse Drug Reactions : 
 
Skin and subcutaneous tissue disorders  
 
Frequency ‘not known’: Calciphylaxis  
 
 
b) The following statements  shall be included in the RiMUP  of products 
containing Warfarin:  
 
Possible Side Effects : 
 
Tell your doctor straight away if you have any of the following side effects :  
 
[...] 
 
A painful skin rash. On rare occasions warfarin can cause s erious skin 
conditions, including one called calciphylaxis that can start with a painful skin 
rash but can lead to other serious complications. This adverse reaction occurs 
more frequently in patients with chronic kidney disease.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 603  NO. SPECIFIC LABELLING REQUIREMENTS (SUBSTANCE SPECIFIC)  
 
Before You Use [Product Name]  
 
When you must not use it  
 
Do not take [product name] together with miconazole oral gel  
 
Before you start to use it  
 
Some commonly used medicines and products that may interfere with [product 
name] include:  
• Miconazole  
 
Reference :  
1. Directive No. 15 Year 2016. Rujukan BPFK/PPP/07/25 ( 1 ) Jld 1 . DIREKTIF BAGI 
SEMUA PRODUK YANG MENGANDUN GI WARFARIN DENGAN RISIKO KESAN 
ADVERS CALCIPHYLAXIS  
2. Directive No. 12 Year 2017. Ref. BPFK/PPP/07/25(17)Jld 1.  Direktif Untuk Semua 
Produk Yang Mengandungi Warfarin : Pengemaskinian Sisip Bungkusan Dan Risalah 
Maklumat Ubat Untuk Pengguna (RiMUP) Dengan Maklumat Keselamatan Berkaitan 
Interaksi Ubat  
 
203.  ZIPRASIDONE  
Please refer to ANTIPSYCHOTIC AGENT  
204.  ZOLPIDEM TARTRATE  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  
205.  ZOPICLONE  
Please refer to SEDATIVE – HYPNOTIC PRODUCTS  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 604  APPENDIX 10  : GUIDELINE ON PATIENT DISPENSING PACK 
FOR PHARMACEUTICAL PRODUCTS IN MALAYSIA  
 
 
Outline:  
 
10.1 Purpose  
10.2 Objective  
10.3 Definition  
10.4 Benefits  
10.5 Criteria for I mplementation of Patient Dispensing Pack  
10.6 Products Exempted from this Requirements  
10.7  Other Considerations for Implementation  
10.8 Implementation Timeline  
10.9 Conclusion  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 605  10.1 PURPOSE  
 
To provide guidance on the implementation of patient dispensing  pack  or original 
dispensing pack  for pharmaceutical products in Malaysia.  
 
 
10.2 OBJECTIVE  
 
Improve patient ’s safety by:  
• maintaining product integrity;  
• prevent unnecessary exposure of the product;  
• avoid product contamination due to handling especially in non -GMP premise;  and 
• Fewer  steps in dispensing process hence less possibility for  errors and 
improvement in efficiency.  
 
 
10.3 DEFINITION  
 
Patient dispensing pack or original dispensing pack is  a ready -to-dispense pack with 
sufficient quantity equivalen t to an amount not more than one month  supply  or per 
treatment for one patient’s use.  
 
 
10.4 BENEFITS  
 
Key benefits identified:  
• Ensuring patients on how to take medications and the importance of it, which will 
eventually increase patient’s compliance . 
• Clear identification of the medicine, by whom and where it was manufactured.  
• Providing complete instructions on the use of the medicine.  
• Original packing will maintain the integrity of the pack therefore ensuring  the 
stability of the product.  
• Original packing will carry batch number and expiry date . 
• Prevent mix -ups (or contamination) during repacking and dispensing.  
• Facilitate recall of products since the required information can only be found on 
the original  pack . 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 606  10.5 CRITERIA FOR IMPLEMENTATION O F PATIENT  DISPENSING PACK  
 
• The patient dispensing pack size should be based on the medication, intended 
use, recommended dosage and dosage form sufficient for one mont h supply or 
per treatment for on e patient’s use. 
• This requirement  does not apply for blister or st rip pack . 
• Maximum permitted supply is one month but may be less depending on the 
intended use of the medication.  
• The Product Registration Holder (PR H) is responsible to justify the proposed 
patient dispensing pack size based on these criteria  as the dosing  regimen  for 
certain medication may equate to high numbers of tablets/  capsules. 
Justification should also address the definition of one month i.e. 28, 30 or 31 
days.  
• Blister or strip pack  are strongly recommended  for solid oral dosage forms (e.g. 
tablets and capsules) and bulk loose pac k for supply more than one month are 
not permitted unless justified by the PRH . 
• Oral chemotherapeutics  in tablet or capsule must be packed in blister to reduce 
personnel exposure and presumably risk  which can minimise  the to xic effect of 
the chemotherapeutics .  
 
 
 
10.6 PRODUCTS EXEMPTED FROM TH ESE REQUIREMENTS  
  
 The requirements do not apply to the following products:  
• Injectables, eye, ear and nasal drops, suppositories and pessaries.  
• Products for export only (FEO).  
• Drug whe re the risk of issuing more than the amount required by the patient 
outweigh the benefits of the patient dispensing pack e.g. products containing 
substances with potential for abuse or cytotoxic agents where precise dosing 
are required.  
• Drugs where the dos ing needs to be tailored according to patien t’s body weight 
e.g. drugs used in oncology, HIV etc . 
• Medically critical products and hospital packs for rare diseases with very low 
volumes where it is not  viable to produce special packs for a single market.  
• Products sold with devices with a fixed number of doses  
• Situations where a patient dispensing pack is not appropriate will be considered 
on a case to case basis.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 607  10.7  OTHER CONSIDERATIONS F OR IMPLEMENTATION  
 
VARIATION APPLICATIONS  
 
• Change in patient pack  size with or without involving new pack type shall be 
submitted to Variation Section, Centre for Post Product Registration.  
 
• Supporting documents required are:  
a. Justification for the new pack size and/or type ; 
b. Accelerated stability data (3 or 6 months) and  stability report for new pack 
types; and   
c. Commitment to provide complete real time stability data and report when 
available.  
      
• List of products with recommended pack sizes for oral liquid preparations and 
dermatological are as in Table 1  and Table 2  respectively.  
 
• For tablets and capsules in loose pack, the maximum packing size will depend 
on the highest dosage and frequency per patient’s treatment or one month 
supply.  
 
 
10.8 IMPLEMENTATION TIMELINE  
 
• Implementation of patient dispensing pack has been c onducted in a phased 
manner to ensure smooth transition while ensuring no supply disruption to 
patients. This implementation is effective since 1 March 2008  on a voluntary 
basis and mandated  on 1 September 2008 .  
 
• All products manufactured from 1 September  2008  regardless whether it is 
imported or locally manufactured  will need to conform to the principles of this 
guide.    
 
            
10.9 CONCLUSION  
 
Patient Dispensing Pack is convenient, safe and improves quality of dispensed 
medicines. It will increase efficiency in dispensing and improve safety by reducing 
the risk and possibility of erro r. It will also result in a reduction in drug waste and 
better use of resources.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 608  TABLE 1:  
 
Oral Liquid Preparation Maximum Pack Size Recommendations for Pharmaceutical  
Products  
 
ATC Code  Recommended Pack sizes  
R05      Cough & cold preparation  
R05A    Cold preparation  
R05C    Antitussives  
R05D    Expectorants  Max 120ml  
(except for Pholcodine – Max 90ml)  
R06A   Antihistamines systemic  Max 120ml  
(except for Hydroxyzi ne HCl Syrup - 
200ml)  
R03     Anti -asthma & COPD products  
R03A   Beta2 stimulants  
R03B   Xanthines (theophyllines)  
R03C   Non -steroidal respiratory anti - 
            inflammatory (ketotifen)  Max 120ml  
(except for Procaterol - 250ml)  
N02B    Non -narcoti c analgesics  Max 120ml  
M01A    Antirheumatics non -steroid  Max 120ml  
H02       Systemic corticosteroids  
H02A    Plain corticosteroids  Max 120ml  
M06A    Anti -inflammatory enzymes  Max 500ml  
A02A     Antacid antiflatulents  
A02B     Antiulcerants  Max 250ml  
A06A     Laxatives  Max 120ml  
(except for Lactulose - 500ml)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 609  A03       Functional GI disorder drugs  
A03A     Antispasmodic  
A03E    Other GI combinations (Colimix)  
A03F    Gastroprokinetics   
             (Metoclopramide, Motilium)  
A07      Ant idiarrhoea  Max 120ml  
 
A04A   Antiemetic + Antinauseants  
N07C   Antivertigo products  Max 120ml  
N03A   Antiepileptics  Max 250ml  
(Except for Sodium Valproate Syrup - 
300ml)  
 
N06A   Antidepressant & Mood  
            stabilizer  
 
N06D   Anti Dementia  
N07D   Anti -Alzheimer products  
 
N05A   Antipsychotics   
Max 250ml  
 
 
 
 
 
Max 20ml for drops  
P01B   Antihelmintics  Max 60ml  
N05C   Tranquillizers/ Anxiolytics  Max 250ml  
A05B   Hepatic protector – lipotropics   Max150ml  
J05      Antivirals for systemic use  
J05B   Antivirals excluding Anti -HIV 
J05C   HIV antivirals  Max 250ml  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 610   J01     Antibiotics systemic  
J01A   Tetracyclines & combination  
J01B   Chloramphenicols + combinations  
J01C1 Oral broad spectrum Penicillins  
J01D1 Oral Cephalosporins  
J01E   Trimethop rim combinations  
J01F   Macrolides & similar type  
J01H   Medium & narrow spectrum  
           penicillins  
J01X   Other antibiotics  
J02A  Systemic Antifungals Agents  Max 120ml  
N06D    Nootropics  
N06E    Neurotonics & Miscellaneous  Max 125 ml  
G01A1   Tri chomonacides  Max 120ml  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 611  TABLE 2:  
 
DERMATOLOGICALS PREPARATION MAXIMUM PACK SIZE RECOMMENDATIONS 
FOR PHARMACEUTICAL PRODUCTS  
 
 
ATC Code  Recommended Pack sizes  
D01A    Antifungals for topical use  Liquid preparation - max 250ml  
Others - max 60g  
D02A    E mollients and protectives  Non poisons (liquid preparation) - 
250ml  
Others - 60g (max 500g for 
emollients)  
Except D02AC Soft paraffin and fat 
products and  
D02AX Other emollients and 
protectives (Aq. Cream) - max 500g  
D03     Preparations for treatment of  
            wounds and ulcers  Max 500ml to 1L  
Notes:  
▪ Chlorhexidine gluconate aqueous 
1L 
▪ Povidon 10% 500ml  
▪ Povidon -iodine 1L  
▪ Dermacyn 500ml  
▪ Hydrogen peroxide 1L  
▪ Prontosan 500ml  
▪ Octenisan 500ml  
▪ Acetic acid 500ml  
▪ Cetrimide 500ml  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 612  ATC Code  Recommended Pack sizes  
 
D04A   Antipruritics, anes thetics, etc.  
Except D04AA Antihistamines for topical use (not 
allowed for registration)   
Liquid – max 250ml  
Others – 60g 
D05A   Antipsoriatics for topical use  Liquid – max 500ml (with a 
dispenser).  
Others – max *500g 
Bar – max 100g  
* Notes:  
▪ Tar Preparat ions 
▪ Coal Tar Ointment/ Solution  
▪ Liquor Picis Carbonis (LPC) 500g  
▪ Dithranol Ointment 500g  
▪ Cocois Co Lotion 500ml  
 
D06A    Antibiotics for topical use   
Max 20g  
 Except D06BB Antivirals - Max 10g  
D06B A 01  Silver Sulphadiazine for 
management of burns - 500g Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 613  ATC Code  Recommended Pack sizes  
 
D07A    Corticosteroids, plain  
 
D07AA  Corticosteroids, weak (group I)  
D07AB  Corticosteroids, moderately potent (group 
II) 
D07AC  Corticosteroids, potent  
(group III)  
D07AD  Corticosteroids, very potent  
              (group IV)   
 
 
D07AA – Max 100g  to **500g  
D07AB – Max 50g  to **500g  
 
D07AC – Max 15g to 100g  
 
D07AD – Max 15g to 100g  
 
** Note:  
Pack size of 500g is for hospitals 
and skin specialist clinics  use. 
 
D07C     Corticosteroids, combinations with 
antibiotics  
 
D07CA   Corticosteroids, weak, co mbinations with 
antibiotics  
 
D07CB   Corticosteroids, moderately potent, 
combinations with antibiotics  
 
D07CC   Corticosteroids, potent, combinations with 
antibiotics  
 
D07CD   Corticosteroids, very potent,  
               combinations with antibiotics   
 
 
D07CA - Max 100g  
 
 
D07CB - Max 50g  
 
 
D07CC - Max 15g  
 
D07CD - Max 15g  
D08A     Antiseptics and disinfectants  Liquid antiseptics/ disinfectants - 
1Litre  
Others - max 60g  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 614  ATC Code  Recommended Pack sizes  
D10A    Anti -acne preparations  for topical use  
Except for D10AA Corticosteroids, comb inations for 
treatment of acne  Liquid preparation - max 250ml  
(recommended to be used with a 
dispenser)  
Bar - max 100g  
All others - max 60g  
D11AF   Wart and anti -corn preparations  Max 15ml  
M02A    Topical products for joint and muscular 
pain Liquid – 250ml 
Others, Max – 60g 
D11AX11   Hyperpigmentation  Max 60g  
 
Reference: Circulars  
i) (Bil 16) dlm bpfk02/5/1.3.pdf  
Kawalan Saiz Pek Per sediaan Ubat Batuk Mengandungi Pholcodine (13 October 
2003)  
ii) Bil (22) dlm BPFK/02/5/1.3.pdf  
Lanjutan Tempoh Untuk Menarik Balik Saiz Pek Persediaan Ubat Batuk 
Mengandungi Pholcodeine Yang Melebihi 90mL Dari Pasaran (07 November 2003)  
iii) Bil (21) dlm.BPFK/02/5/1.3.pdf  
Kawalan Penetapan Saiz Pek Maksima Bagi Semua Persediaan Ubat Batuk  
(07 November 2003)  
iv) Bil (24) dlm BPFK/02/5/1.3.pdf  
Pindaan Kepada Kawalan Pe netapan Saiz Maksima Bagi Semua Persediaan Ubat 
Batuk (08 March 2004)  
v) (1) dlm. BPFK/02/5/1.4   
Perlaksanaan Konsep Pek Saiz Pe sakit (Patient Pack Size) bagi Produk 
Farmaseutikal (20 February 2008)  
vi) Bil (4) dlm BPFK/PPP/01/03 Jld 1   
Direktif Justifikasi Untu k Perubahan Pek Saiz Pesakit Untuk Penyakit Kulit Tertentu 
Bagi Produk -produk Dermatologi (14 December 2010)  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 615  APPENDIX 11  : GUIDELINE ON FILLING THE ONLINE 
APPLICATION FORM FOR PRODUCT 
REGISTRATION VIA QUEST SYSTEM  
 
 
 
 
 
 
 
Online application forms are ava ilable for different product categories in the QUEST 
system : 
a) Pharmaceuticals;  
b) Health Supplements  and Natural  Products.  
 
This appendix may not follow the sequence of the  online registration forms . 
  
Applicant shall follow and comply with all requirements i n the online application forms as 
well as any supplementary documentation requested by the Authority, whichever it may 
deems fit.  
 
Applicant shall ensure that you have clicked on the appropriate section of the display panel 
and fill the correct application  form.  
 
Applicants are advised to read the explanatory notes in this appendix, as well as relevant 
ASEAN or ICH guidelines and checklists, for full information on requirement for product 
registration. In order to facilitate the evaluation process the Autho rity, applicants shall 
conform to these guidelines as well as the main guidance document.  
 
The Authority reserves the right to request for supplementary information in certain cases.  
 
  
IMPORTANT NOTES:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 616  Outline:  
 
 
11.1 Product Classification  
11.1.1  Pharmaceuticals  
11.1.2  Health Supple ments  and Natural Products  
 
11.2 Submission of Application  
11.2.1 Step 1: Product Validation  
11.2.2  Step 2: New Registration Application Form  
 
Part I – Administrative Data and Product Information  
 
− Section A: Product Particulars  
 
− Section B: Product Formula  
 
− Section C: Particulars of Packing  
 
− Section D: Label (Mockup) for Immediate Container, Outer 
Carton and Proposed Package Insert  
- Section E/ Section F: Supplementary Documentation  
 
Part II, III & IV – Quality , Nonclinical Document & Clinical 
Document  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 617   
11.1 PRODUCT CLASSIFICATION  
 
Applicant shall ensure  correct product category as listed below  in order to determine the 
method of evaluation i.e. full evaluation (*) or abridged evaluation (**) in which available as 
separate modules for application.  
 
11.1.1  Pharmaceutica ls 
 
i) New Drug Products  *  
ii) Biologicals  * 
iii) Generics (Scheduled Poison)  * 
iv) Generics (Non -Scheduled Poison)  (or known as OTC/ non -prescription) - other 
than listed at v) *  
v) Generics (Non -Scheduled Poison) **, which include , but not limited to  the 
following:  
• Antis eptics/ skin disinfectants;  
• Locally -acting lozenges/ pastilles;  
• Topical analgesic/ counter -irritants;  
• Topical nasal decongestants;  
• Emollient/ demulcent/ skin protectants;  
• Keratolytics;  
• Anti-dandruff;  
• Oral care;  
• Anti-acne;  
• Medicated plasters/ patch/ pad; an d 
• Topical antibacterial.  
 
 
11.1.2  Health Supplements  and Natural Products  ** 
 
• Application form for registration for Health Supplements; and Natural Products (or 
termed as Traditional Products) are available under Abridged module.  
• Do not use the pharmaceuticals mo dule for these product categories.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 618  11.2 SUBMISSION OF APPLICATION  
 
Any application for a product registration shall follow a 2-step process  i.e. Step 1 (Product 
Validation) and Step 2, as described below : 
 
 
11.2.1 STEP 1: PRODUCT VALIDATION  
 
• All fields are compulsory to be entered.  
• Option is given either to accept t he validation result and submit;  or override and 
manually select.  
• Once validation is verified and submitted, the related  application form under Step 2 
will be displayed.  
• Information entered in  Step 1 will be captured in the database and need not be re -
entered at Step 2.  
 
[1] Product Name  
 
1) Product name, dosage form and strength shall be entered.  
(e.g. X Brand Paracetamol Tablet 500mg)  
 
2) Product  name is defined as a name given to a product which m ay be either a 
proprietary name (an invented  name); or a generic name (common name) or 
scientific name, together with a trade mark or the name of the manufacturer . 
3) Product name shall not imply  the following:   
a. Tricky, confusive  and against the law;  
b. Scandal ous and offensive;  
c. Prejudic ial; 
d. Notorious.  
4) Any product name which is the same or similar either in writing/ pronunciation, 
with the product name of an adulterated product or a product that has been  
revoked due to safety concerns is prohibited . 
5) The invented  name shall not be liable to confusion with the common name.  
6) The generic name means the international non -proprietary name recommended 
by WHO (rINN), or if one does not exist, the usual approved name.  
7) The product  name  shall be shown on the product lab elling i.e. immediate  label, 
outer unit carton, package insert and consumer medication information leaflet . Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 619  8) Dosage form and strength of product would need to be entered as part of product 
name to allow for multiple dosage forms (e.g. tablet, capsule) and streng ths (e.g. 
200mg and 400mg) for any particular named (proprietary or generic) product.  
9) If a product name is found similar to another registered product  or any other 
name which deemed  inappropriate by the Authority , NPRA  reserve s the rig hts to 
request for th e change of  the product name.  
10) The generic name cannot be used alone as product name but in combination 
with another name other than generic name.  
 
[2] Dosage Form  
 
• Please select dosage form and further select ‘in the form of’ from the drop -down  
list.  
 
• For example, a  tablet may be in the form of chewable, coated (enteric, film, or 
sugar), uncoated, dispersible, effervescent, extended release, subligual, etc.  
 
• The form that correctly describes it in terms of its product quality control 
speci fications and p erformance shall  be selected.  
 
• A separate application  for registration is required for each dosage form.  
 
 
 
[3] Active Ingredients  
 
i) Name of Active Ingredient : 
  
• Please refer Appendix 8.1  List of Prohibited and Restricte d Active Ingredients 
and Combinations.  
 
• Please select active ingredient from the search database  by clicking button  
‘click here to search ’. If an active ingredient is not listed in the database, 
please click button ‘Not Listed Ingredient’. Automatic e -mail will be send to 
NPRA  for verification.  Please ensure  that the spelling is accurate.  
 
• The actual raw material that is employed in the manufacturing process shall 
be named. For example:  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 620  - Where the raw material used is the salt (e.g. ampicillin trihydrate) wh ich 
will yield an equivalent effective component from its base content (i.e. 
ampicillin), the substance name is the salt and the equivalent base 
comp onent should be indicated in  remarks on substance (if any) field. ***   
- Similarly where a chemical i s a comp onent in the ingredient  (e.g. iron in 
ferrous sulfate; or EPA and DHA in fish oil ), the component details shall  be 
stated in the remarks field if a label claim of the component is made for the 
product, and the actual raw material used declared as the activ e 
ingredient.  
 
• International Non -proprietary Names (INN), approved names, pharmacop oeia 
names of ingredients shall  be used whenever possible.  
 
• After each ingredient entry is correctly made, click the button  ‘add/ save’ . The 
button ‘remove ’ will allow for c orrections to an entry under this heading. To 
remove item, please select item from the listing and click ‘remove ’. 
 
ii) Strength of active ingredient : 
  
• Please enter strength of active ingredient (numerical) and then select unit 
weights and measures from the d rop-down list.  
 
• Content of ingredients shall be expressed as approp riate in the following 
manner :  
a. quantity per dose unit  
(e.g. for unit dose formulations  - tablet, capsule, lozenge, etc.)  
b. percentage composition  - %w/w, %w/v, %v/v, etc.  
(e.g. for produ cts without defined dose unit such as ointments, creams, 
solutions, etc.)  
c. weight per ml.  
(e.g. for solutions, injections, etc.)  
d. quantity (percentage or amount) per measured dose  
(e.g. oral liquids, metered aerosols, drops, etc.)  
 
• Metric weights and measure s shall be used.  
 
• In cases where product contains active ingredient(s) that cannot be definitely 
identified (e.g. certain biological products) state the name of the material to 
which activity is ascribed and, where appropriate, the potency or activity of 
the product.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 621  iii) Remarks on active ingredient (if any) :***  
 
• This field shall  be used  where the raw material in product formulation yields 
an equivalent active component .  
 
After each ingredient entry is correctly made, click the ‘add/ save’  button. The 
remove  button will allow for corrections to an entry under this heading. To remove 
item, select item from the listing and click remove.  
 
 
[4] Excipient  
 
• Please refer Appendix 8.2  List of Prohibited and Restricted Excipients;  and 
Appendix 8.3  Lists of Permitted and Restricted Colouring Agents . 
 
• Details are as for [3] Active Ingredients stated above.  
 
• Please enter  function of excipients,  e.g. sweetener, preservative, thickening 
agent, etc. which can be selected from the drop -down list. 
 
 
[5] Any Animal Origin  
 
• Click the appropriate button ‘Yes’ or ‘No’.  
 
 
[6] Manufacturer  
 
• Click button ‘click here to search’ to select manufacturer listed in the database. 
For a new manufacturer which is not listed in the database search, please cl ick 
‘Not Listed Manufacturer’ button. Automatic e -mail will be send to NPRA  for 
verification.  
 
 
[7] Is The Selected Manufacturer a Contract Manufacturer?  
 
• Status as to whether the declared manufacturer is a contract manufacturer or 
otherwise, has to be ent ered. Click the appropriate button  ‘Yes’ or ‘No’.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 622  [8] Is This Product Second Source?  
 
• Click the appropriate button  ‘Yes’ or ‘No’ . 
 
• If yes, please attach letter of declaration stating that this product is a second 
source product; and provide registration  number and product name of the first 
source.  
 
 
[9] Does This Product Contain Any Premix?  
 
• Click the appropriate button  ‘Yes’ or ‘No’.  
• If yes, please provide the following details:  
i) State your premix form  
j) Manufacturer name  
k) Manufacturer address  
l) Certificate of Good Manufacturing Practice (GMP)  
m) Formulation  
n) Manufacturing Process  
o) Specification of Analysis  
p) Certificate of Analysis (CoA)  
 
 
 
[10] Is This a Replacement Product?  
 
• Click the appropriate button  ‘Yes’ or ‘No’.  
 
• If yes, please attach letter of declaration stating that this product is a replacement 
product; and provide registration number and product name of the replaced 
product.  
 
 
[11] Other Manufacturer (Repacker)  
 
• Click the appropriate button  ‘Yes’ or ‘No’.  
 
• Please enter name of company and click button ‘ search’ to select other 
manufacturer (repacker) listed in the database. For a new other manufacturer 
(repacker) which is not listed in the database search, please click ‘Not Listed 
Manufacturer’ button. Automatic e -mail will be send to NPRA  for verificatio n. 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 623  • Select from processing type drop -down list, e.g. assembly, packing, production, 
labelling, fill and finish, others.  
 
 
[12] Is This an Imported Product?  
 
• Click the appropriate button  ‘Yes’ or ‘No’.  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 624  11.2.2  STEP 2: NEW REGISTRATION APPLICATION FORM  
 
Please click at ‘Section List’ button to display t he application form at Step 2. The 
requirement displayed will depend  on the category  of product being selected for registration 
submission : 
 
• Abridged Evaluation for certain **OTCs, health supplements and natural products;  
• Generic Pharmaceutical Products - Parts I & II ; 
• Existing chemical or biologica l entity(s) in new dosage form - Parts I & II together 
with pharmacokinetic data ; 
• NDP and Biologics - Parts I to Part IV:  
- Part I    - Administrative Data and Produ ct Information  
- Part II   - Quality   
(For details of Part II, please refer Section C: Quality Control  in the 
main DRGD)  
- Part III  -  Nonclinical Document  
- Part IV  - Clinical Document . 
 
Please refer Glossary developed for the ACTD and ACTR . The definitions used in the  
glossary have been developed for the ASEAN Common Technical Dossier (ACTD) and 
Common Technical Requirements (ACTR).  They are not necessarily meaningful outside 
the scope of the specific parts of ACTD and ACTR to which they refer.  
 
 
PART I – ADMINISTRATIVE DATA AND PRODUCT 
INFORMATION  
 
SECTION A: PRODUCT PARTICULARS  
 
Details of the following as entered under Step 1 will  appear automatically  in the application 
form: 
1.   Product name;  
2.  Name and  Strength of Active Ingredients, Name and Strength 
of Excipients; and  
3.   Dosage form.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 625   
Other fields as follow ed, shall be completed:  
 
4.   Product Description:  
 
State, brief ly on  visual and physical characteristics of the product, i ncluding 
(where applicable):  
• Shape, size, superficial markings for identification purposes, colour, odour, taste, 
consistency, type of tablet coating, type of capsule, etc.  
 
• When describing liquid s, state clearly whether it is in the form of a solution 
(clear), suspension, emulsion, etc.  
 
5.  Pharmacodynamics  (for full evaluation only)  
 
Please provide a concise and  comprehensive summary of the pharmacological 
profile : 
• Main and supplementary pharmac ological effects (mechanism of action, actions 
other than the therapeutic effects);  
• Relevant pharmacokinetics (absorption, plasma -protein binding, distribution, 
biotransformati on, metabolism, excretion, etc) ; 
 
• Bioavailability and bioequivalence studies in man.  
 
 
 
6.  Pharmacokinetics  (for full evaluation only)  
 
• Details are as for A5.1 Pharmacodynamics stated above.  
 
 
 
7.  Indication  
 
• State briefly on the recommended clinical use(s) of product, indicating clearly 
whether curative, palliative, adjunctive, dia gnostic, etc.  
 
• Indications should be specific; phrases such as ‘associated conditions’ or ‘allied 
diseases’ would not normally be considered appropriate.  
 
• Indications other than those specified and accepted at the time of registration 
must not be included in any product literature, data sheets, package inserts, 
labels, etc . without  prior permission of the Authority . 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 626  • Should it be desired to include new indications, an application shall be filed to the 
Authority  together with supporting clinical documentatio n on evidence of efficacy 
and safety for the additional uses (indications).  
 
• In the case of pr oducts which are to be used as health supplements , no claims 
shall be made for the prevention and treatment of disease states.  
 
• For natural products , please state  briefly on recommended use(s) of the product, 
starting with the phrase “Traditionally used for...../ Homeopathyically used 
for......”.  
 
 
 
8.  Recommended Dose OR Dose/ Use Instruction  
 
Recommended Dose (for full evaluation only):  
 
• Please s tate the dose (n ormal dose, dose range) and dosage schedule 
(frequency, duration); and route of administration appropriate for each 
therapeutic indication .  
 
• Dosage for adults, and,  children (where appropriate) shall be stated.  
 
• Dosage adjustments for special conditions , e.g. renal, hepatic, cardiac, nutritional 
insufficiencies (where relevant) shall be stated.  
 
• Where appropriate, diluents and instructions for dilution, reconstitution and use or 
admi nistration of the product shall  be clearly stated.  
 
• Distinction shall  be m ade between therapeutic and prophylactic doses, and 
between dosages for different clinical uses , where applicable.  
 
• Ensure that dosage recommendation is relevant and appropriate for the product.  
 
Dose/ Use Instruction (for abridged evaluation only):  
• State the dose (normal dose, dose range) and dosage schedule (frequency, 
duration) [and route of administration appropriate for each therapeutic indication]. 
Dosage for adults, and where appropriate children, should be stated.  
 
• Dosage adjustments for special con ditions e.g. renal, hepatic, cardiac, nutritional 
insuffic iencies, where relevant, shall be stated.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 627   
9.  Route of Administration  (for full evaluation only)  
 
• Details are as for Recommended Dose  stated above.  
 
• Please select route of administration from the drop-down list, e.g. intramuscular, 
oral, rectal, sublingual, etc.  
 
 
10. Contraindication  
 
• Please s tate conditions for which or  under which the product shall not be used.  
 
• Indicate clearly which conditions are :  
- absolutely contraindicated;   
- contraindicate d but may be used under special circumstances and what 
precautions to be taken in such cases.  
 
• Where there is likelihood that additives are added, especially for intravenous 
solutions, foreseeable contraindicated additives shall  be mentioned  (where 
applica ble). 
 
• Concurrent drug therapy which are contraindicated shall  also be included where 
possible  (where applicable) .  
 
 
11. Warnings and Precautions  
 
• Please s tate briefly on warnings  and precautions, where necessary to ensure 
safe use; and efficacious (where  applicable) of the product;  
(e.g. caution against giving to children and elderly; against driving motor vehicles 
or manning heavy machinery after intake of product; use in pregnancy and 
lactation; in infants; etc. ) 
 
 
12. Interactions With Other Medicament s 
 
• Please state interactions which are observed and/or for which there is potential 
clinical significance.  
 
• Interactions may occur with : Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 628  - medicinal products used for the same indication;  
- medicinal products used for other indications;  
- meals, or specific typ es of food.  
 
 
13. Pregnancy and Lactation   
 
 Use in Pregnancy:  
• The following shall  be stated:  
a) conclusions from the animal reproduction/  fertility study and the human 
experience;  
b) the risk in humans at different stages of pregnancy, as assessed from  a); 
c) information on the possibility of using the medical product in fertile and 
pregnant women.  
 
 
Use in L actation:  
• When the active substance(s) or its metabolites are excreted in milk, 
recommendations as to whether to stop  or continue breast feeding, and  the 
likelihood and degree of adver se reaction in infant shall be stated . 
 
For abridged evaluation , please state any effect on pregnancy and lactation, if 
applicable.  
 
 
14. Side Effects/ Adverse Reactions  
 
• Please s tate in order for severity and frequency, the side e ffects, adverse 
reactions, toxic effects, etc. (i.e. reactions, toxic effects, other than those desired 
therapeutically) including reactions such as allergy, hypersensitivity, drug 
dependence, addiction, carcinogenicity, tolerance, liver/  kidney toxicity e tc. 
 
• Indicate also symptoms and sites of effects/  reactions.  
 
• Reactions, w hether minor or serious shall be stated.  
 
• Severity, reversible , frequency of occurrence shall  be indicated , wherever 
possible.  
 
• Clinical tests for detection of ‘sensitive’ patients, measure for management of 
adverse reactions developed shall be described wherever possible.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 629   
15. Signs and Symptoms of Overdose and Treatment  
 
• Please s tate briefly symptoms of overdose/  poisoning, and where possible, 
recommended treatment and antidotes f or overdose/  poisoning.  
 
 
16. Storage Conditions  
 
• Please s tate the recommended storage conditions (temperature, humidity, light 
etc.).  
 
• Information include storage condition before first opening, after reconstitution 
and/or after opening and for all the li sted pack types shall also be provided, 
where applicable. Stability data to suppo rt such storage condition shall  be 
submitted . 
 
 
17. Shelf Life  
 
• Shelf life for all the listed pack types shall  be supported by stability data.  
 
• Information include shelf life before first opening, after reconstitution and/or after 
opening where applicable shall also be provided . Stability data to support such 
shelf life shall be submitted . 
 
• Evidence is required to demonstr ate that the product is stable which meets the 
finished product shelf life specifications thr oughout its proposed shelf -life and  
toxic decomposition products are not produced in significant a mounts during this 
period; potency, sterility and efficacy of preservative, etc . are maintained.  
 
 
18. Therapeutic Code  
 
• Please indicate WHO assigned ATC code for each distinct therapeutic indication 
proposed for a product, if such a code is available. Click button ‘click here to 
search’ to search the code via database  at http://www.w hocc.no/atcddd/ . 
 
• For natural products , please select “Traditional/ Homeopathy” from the listed 
button.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 630   
After completion of Section A has been done, please c lick Section List for display of main 
page of application form and select Section B : Product Form ula, or click button ‘next’ after 
saving the entered data . 
 
SECTION B: PRODUCT FORMULA  
 
a) For full evaluation  requirement, B1.1 and B1.2 as described below is required under 
Section B: Product Formula. Data pertaining to quality of product  is required to be 
submitted under Part I I: Quality of Product . 
 
 B1.1  Batch Manufacturing Formula  
 
• Please state batch size and actual batch manufacturing master formula.  
  
• Data from validation step will be captured in terms of substance name, type 
(active or excipient ingre dient), function and quantity per unit dose.  
• Other information such as overage (where applicable) shall  be entered.  
 
B1.2  Attachment of the Batch Manufacturing Formula D ocumentation   
 
• The attachment shall be submitted.  
 
b) For abridged evaluation  requirement , Batch Manufacturing Formula is required under  
B1.1 and A ttachment of the Batch Manufacturing Formula documentation is required 
under  B4 of the same section i.e. Section B .  
 
Whereas B2.1, B3, B4 and B5 appear as below:  
 
 
 B2.1  Manufacturing process  
 
• Please state a brief description of the manufacturing process.  
 
• Essential points of each stage of manufacturing process and a description of 
the assembling of the product into final containers shall be covered. If the 
product is repacked/ assembled by another  manufacturer, details of 
repacking/assembly and quality control shall be supplied.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 631  • An attachment of the manufacturing process, in the form of a flow chart can 
be submitted under B2.2.  
 
 
B3. In-Process Quality Control  
 
• Please attach document  for In -Proce ss Quality Control to provide a summary 
of the tests performed, stages at which they are done, and the frequency of 
sampling and number of samples taken each time.  
 
• Specifications for quality assurance of the product shall be supplied.  
 
 
B4. Attachment of  Finished Product Specification Documentation  
 
• Please attach document for Finished Product Specification to provide details 
of quality control specifications, including a list of tests for both release and 
shelf life specifications (if they are different) ; and state the limits of 
acceptance.  
 
 B5. Attachment of Stability Data Documentation  
 
• Reports of stability studies shall provide details of :  
- the batches placed under study (a minimum of 2 batches are required);  
- containers/ packaging type;  
- conditions of storage during study (temperature, humidity, etc);  
- duration of study and frequency (interval) of the tests/ observations;  
- the tests performed (including degradation products being monitored) and 
acceptance limits.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 632   
SECTION C: PARTICULARS OF PACKING  
 
• This section is subjected to requirements as stated in  Appendix 10:  Guide for 
Implementation of Patient Dispensing Pack for Pharmaceutical Products in Malaysia. 
Please refer the appendix for details.  
 
• Please enter particulars of packing in the following  sub-sections : 
 
C1 : Pack Size  
 
- Please select pack size by weight  or volume or quantity ; and unit 
 
C2 : Immediate Container Type   
 
- Please select container type , e.g. aluminium, glass, metal, paper, plastic, 
others (if others, ple ase specify)  
- Please enter description of container type  
- Please attach attachment of container type at table appeared after ‘Add’ button 
at the bottom page is clicked  
 
C3 : Barcode/ Serial No.  
 
- Please key in if any (optional)  
 
C4 : Recommended Distributor’s  Price  
 
- Please key in if any (optional)  
 
C5 : Recommended Retail Price  
 
- Please key in  if any  (optional)  
 
and then click button  ‘Add’ to save all the entered informations.  
 
Note:  
To add next particulars, repea t the same process until all  packings are listed  
accordingly. To remove any item from the listing, select item from the listing and click 
the “Remove” button.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 633  SECTION D: LABEL (MOCKUP) FOR IMMEDIATE CONTAINER, OUTER 
CARTON AND PROPOSED PACKAGE INSERT  
 
• This section is subjected to requirements as stated in Appendix 9:  Labelling 
Requirements and other appendices (where applicable).  Please refer the appendices 
for details.  
 
• Please attached label (mock -up) i.e. draft of the actual product label and proposed 
package insert at t he following sub -sections:  
D1. Label (Mock -up) for Immediate Container  
D2. Label (Mock -up) for Outer Carton (Unit Carton)  
D3. Proposed Package Insert  
 
 
SECTION E/ SECTION F: SUPPLEMENTARY DOCUMENTATION  (AND 
PARTICULARS OF PRODUCT OWNER, MANUFACTURER, IMPOR TER 
AND OTHER MANUFACTURER)  
 
a) Product Owner  
 
Please select one of the following for status of product owner:  
- Manufacturer or  
- Product registration holder or  
- Product regi stration holder & manufacturer or  
- Others  (If the product owner is neither of the above st atus) – Please enter name 
and address of the product owner.  
 
 
b) Letter of Authorization from Product Owner  
 
• All applications  for registration shall be accompanied with Letter of Authorization 
from product owner.  
(Not applicable if the Product Registration H older is Product Owner).  
 
• Letters of Authorization (LOA) shall be valid and current at the time of submission.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 634  • The LOA shall be on the product owner’s original letterhead and be dated and 
signed by the Managing Director, President, CEO or an equivalent pe rson who has 
overall responsibility for the company or organization.  
 
• The LOA shall state the name of the product concerned and also the name and 
actual plant address of the manufacturer(s) involved in the manufacture of the 
product .  
 
 
c) Letter of Appointme nt of Contract Manufacturer from Product Owner   
 
• Please attach (if applicable).  
 
• Applicable for product which is contract manufactured by a manufacturer who is not 
the product owner . 
 
 
 
d) Letter of Acceptance from Contract Manufacturer  
 
• Please attach (if app licable).  
 
• The letter of acceptance from the manufacturer shall be on the manufacturer’s 
original letterhead and be dated and signed by the Managing Director, President, 
CEO or an equivalent person who has overall responsibility for the company or 
organiza tion. 
 
• The letter of acceptance  shall state the name of the product concerned and also the 
name and actual plant address of the manufacturer(s) involved in the manufacture of 
the product.  
 
 
e) Is the active ingredients patented in Malaysia?  
 
• Click the appropr iate button  ‘Yes’ or ‘No’.  
• If yes, please attach the related document.  
• Applicants who hold valid patents shall provide documentary evidence of the nature 
and extent of their patents.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 635  f) Certificate of Pharmaceutical Product (CPP) , Certificate of Free Sale (C FS) and 
Certificate of Good Manufacturing Practice (GMP)  
 
• Please attach the certificates.  
 
• Please key in issuing body, date of issue, date of expiry of the certificates. If the 
issuing body is not listed, please select ‘Not Listed’  button. Automatic email will be 
sent to NPRA  for verification.  
 
• The certificate s shall  be valid and current at the time of submission.  
 
• For imported products , the following requirements  shall be furnish ed, either a:  
i) CPP from the competent authority in the country of origin; OR 
(Note: In the event a CPP is not available from the country manufacture, e.g. 
where a product is not licensed for sale in said country because its manufacturer 
is manufacturing under contract only for product owner from another country, the 
following alterna tives may be considered: GMP Certification/ Manufacturing 
License for the manufacturer from the relevant competent authority, together with 
CPP from the country of the product owner; or CPP from country of release, if 
CPP from the country of the product ow ner is not available)  
 
ii) CFS and GMP from the relevant competent authorities is deemed acceptable by 
the Authority for health  supplements and natural products only.  
 
• CPP shall be in the format of the WHO Certification Scheme on the Quality of 
Pharmaceutical Products Moving in International Commerce & be issued by the 
Health Authorities listed in the WHO Certification Scheme ( list is available from 
WHO website : http://www.who.int ).  
 
• CPP which is issued by EMA for products regi stered through the centralized 
procedure in EU will be accepted.  
 
• CPP issued by the manufacturer or other authorities are not acceptable.  
 
• If more than one manufacturer is involved in the manufacture of a product, GMP 
certification sh all be available for a ll the manufacturers.  
 
• The Authority reserves the right to conduct an inspection on any manufacturing site.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 636  • Unless otherwise supported by justifications acceptable to the Authority, the 
following products are unlikely to be registered:  
i) products not licens ed/ certified for sale in the country of manufacture/  product 
owner ; 
ii) products manufactured for export only (imported products) . 
 
g) Is this product licensed to be placed on the market for use in the exporting 
country?  
 
If no, please state the reason . 
 
h) Is the  product on the market in the exporting country?  
 
If no, please state the reason . 
 
 
i) Summary of Product Characteristics (SPC)   
 
Please attach ( where applicable).  
 
 
j) Consumer Medication Information Leaflet  (RiMUP )  
 
Please attach (where applicable) . 
 
 
k) Attachm ent of Protocol Analysis , Analytical Validation  
 
Please attach  (where applicable).  
 
 
l) Certificate of Analysis (CoA)  for Finished Product  
 
• For two (2) batches . 
• Compulsory for imported product.  
• Please attach  the certificate (which must be complete with the p roduct specification 
and results).  
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 637  m) Importer and Store Address  
 
Please key in (where applicable).  
 
 
n) Other Supporting Document  
 
Please attach  (if any) . 
 
 
 
 
PART II, III & IV – QUALITY , NON CLINICAL DOCUMENT & 
CLINICAL DOCUMENT   
 
In order to complete thes e parts, please refer the main DRGD as well as ASEAN Common 
Technical Requirements Guidance Documents,  and the following documents (where 
applicable):  
 
a) Appendix 2:  Requir ements for Product Registration  
b) Appendix 3:  Guidelines on Registration of Biologics  
c) Appendix 4:  Guideline on Registration of Health Supplements  
d) Appendix 5:  Guideline on Registration of Natural Products  
e) Appendix 6: Guideline on Regulatory Control of Active Pharmaceutical  
   Ingredients (API)  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 638  APPENDIX 12 : CONDITIONS AND SUPPORTING DOCU MENTS REQUIRED FOR 
AN APPLICATION OF VARIATION  
 
 
a) VARIATION TYPE I (MINOR VARIATION)  
 
NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
1.  
Change in name of  
manufacturer and/or other 
manufacturers  without 
any change in address of 
site.  
• E13 
(manufacturer)  
• E14 (other 
manufacturers)  
• D1 
• D2 
• D3 
• E6 
• E12 
  
• E2 (manufacturer)  
• E3 (other 
manufacturers)  
• D1 
• D2 
• D3 
• F6 
• F12 
 CONDITIONS  
 
1. The manufacturing/ other manufactur ing s ite of the 
drug product remains unchanged.  
2. No other changes to the label/ package insert 
except for the change of the name of a 
manufacturer/ other manufacturers  of the drug 
product.  
3. The manufacturing site remains the same.  
 
SUPPORTING DOCUMENTS  
 
1. For local  manufacturers/ other manufacturers :  
Certificate of name change i.e. Form 13 Company 
Act 1965.  
(Please attach the supporting document at E12/ 
F12).  
 
2. For foreign manufacturers/ other manufacturers:  
A valid Good Manufacturing Practice (GMP) 
certificate.  
 
3. Official letter from product owner authorizing the Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 639  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
manufacturer with new name to manufacture the 
drug product.  
 
4. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
 
2.  
Replacement, addition or 
deletio n of company logo 
on the packaging  
components (without any 
changes on  
graphic or label content)   
• D1 
• D2 
• D3  
• D1 
• D2 
• D3  
SUPPORTING DOCUMENT  
 
Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 640  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
3.  
Chang e in product owner   
• E1.1 
• E1.2 
• E2.1 
• E2.2 
• E12 
• D1 
• D2 
• D3 
    (if applicable)  
  
• E1 
• F1 
• F2.1 
• F2.2 
• F12 
• D1 
• D2 
• D3 
   (if applicable)  
 
  
CONDITIONS  
 
1. The Product Registration Holder remains the same. 
Submission shall be done by current PRH.  
2. The manufacturing site rem ains the same.  
 
SUPPORTING DOCUMENTS  
 
1. Letter of confirmation for change in product 
ownership countersigned by both old and new 
product owner.  
2. Official letter from the new product owner declaring 
the change, and authorizing the local license holder 
to be r esponsible for the product license.  
3. In the case of a contract manufacturer, new 
product owner to issue Letter Of Appointment to 
contract manufacturer and contract manufacturer to 
issue Letter Of Acceptance.  
4. Revised labels and package insert (if applicabl e).  
 
4.  
Change in importer/ store 
address.  
  
• E13.1  
(importer)  
• E15  
(store address)   
• E2.1 
    (importer)  
• E4  
    (store address)   
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 641  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
5.  
Change or addition of 
imprints, bossing or  
 
 
other markings (except  
scoring/break lines) on 
tablets or printing on 
capsules, including  
replacement, or addition 
of inks used for product  
marking.  
  
• A4 
• P1  
 
 
• P5.1 
• P5.2  
• D3 
• E8 
(if applicable ) 
• E9  
• A2 
• D3 
 
 
• F8  
    (if applicable)  
• B4 
• F9 
  
CONDITIONS  
 
1.  Any new ink must be of oral pharmaceutical/ food 
grade and not a liste d banned substance.  
2. Release and end -of-shelf life specifications of the 
drug product remain unchanged except for 
appearance.  
3. New markings do not cause confusion with other 
registered products.  
 
SUPPORTING DOCUMENTS  
 
1. Revised drafts of the package insert and  labeling 
incorporating the proposed variation (where 
applicable).  
2. Release and end -of-shelf life specifications of the 
drug product with the new product description.  
3. Certificate of analysis (CoA) of new ink.  
4. Details of the proposed new inks (where 
applica ble)  
5. Detailed drawing or written description of the 
current and proposed imprint/ bossing/ markings.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 642  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
6.  
Change in shape or 
dimensions of the 
container or closure 
without any other 
changes.   
• P7 
• C (if applicable)   
• C (if applicable)   
CONDITIONS  
 
1. The prima ry packaging material of container or 
closure remains the same.  
2. Not applicable for sterile products.  
3. No change is made to the product shelf life and/or 
storage conditions.  
4. No change in the qualitative or quantitative 
composition of the container and/or clo sure and the 
change do not affect the delivery, use, safety or 
stability of the drug product.  
 
SUPPORTING DOCUMENTS  
 
Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
 
7.  
• Change in pack size of 
the drug product  
(Finished product), 
without change in 
primary packaging 
material.  (including 
pack size meant as 
samples)  
 
• Change in the number 
or units (e.g. tablets,  
• C 
• D1 
• D2 
• D3 
• E8 
    (if applicable)  
• P7  
• C 
• D1 
• D2 
• D3 
• F8 
    (if applicable)   
CONDITIONS  
 
1. The primary packaging material of container or 
closure remains the same. Primary packaging 
material is the material that is in contact with the 
finished product and may affect the delivery, use , 
safety or stability.  
2. No other changes to the label/ package insert 
except for the pack size.  
3. The new size is consistent with the dosage 
regimen and duration of use as approved in the 
package insert.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 643  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
ampoules) in a pack.  
 
 
• Change in volume of  
non sterile 
preparations   
*The sentence ‘Sample not for sale’ can be added in 
the product label without going through variation 
approval.  
 
 
SUPPORTING DOCUMENTS  
 
Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
 
8.  
Tightening of specification 
limits of drug product 
(finished product ) and/or 
drug substance (active 
ingredient )   
• E9 
• E10 
• E11 
• P5.1 
• P5.2 
• P5.4 
• S4.1 
• S4.2 
• S 4.4   
• B4 
• F9 
• F10 
    (finished product)  
• F11 
   (active ingredient)   
CONDITION  
 
1. Any change should be within the range of currently 
approved limits.  
 
SUPPORTING DOCUME NTS 
 
1. Tabulation of the current and revised release and 
shelf life specifications of the drug product/drug 
substance with changes highlighted.  
2. Certificate of Analysis (CoA) for drug product or 
drug substance.  
3. Protocol analysis for drug product/ drug substan ce. 
4. Revised specification of drug substance.  
5. Specifications of drug product.  
6. Batch analysis of drug product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 644  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
9.  
Change in particular of 
manufacturer of drug  
 
substance (active 
ingredient ) without any 
change in specification  
 
a. Change in 
manufacturer of  drug 
substance  
 
 
b. Addition of 
manufacturer of drug 
substance  
 
c. Change in name and/or 
rephrasing of address 
of a manufacturer of 
drug substance.  
 
  
• S2.1 
• S4.4  
• F11 
  
CONDITIONS  
 
1. Finished product release and end of shelf life 
specification remains the same.  
2. Method of preparation and route of synthesis 
remain the same.  
3. For (c), the manufacturing site of the drug 
substance remains the same.  
 
SUPPORTING DOCUMENTS  
 
For (a) & (b):  
1. Certificate of Analysis (CoA) for drug substance 
(Also include CoA from all of the dru g substance 
manufacturers proposed to be retained) or batch 
analysis of drug substance.  
2. Certificate of Suitability (CEP) for the drug 
substance or Drug Master File; or reference to 
DMF by USFDA, TGA or JFDA  (if applicable) . 
3. Tabulation of the differences co mpared with the 
registered manufacture information (if applicable).  
 
For (c) : 
1. Updated information of the manufacturer of the 
drug substance.  
2. Official document/ evidence when required.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 645  NO. VARIATION TYPE I  
(MINOR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
10.  
Change in secondary  
packaging material (or 
change in any part of  the 
primary packaging 
material that is not in 
contact with the finished 
product  (e.g. colour of flip 
off caps, colour code rings 
on ampoules, change of 
needle shields i.e. 
different plastic used).   
• C 
• D2 
• D3 
• P7 
  
• C 
• D2 
• D3  
CONDITIONS  
 
1. The primary packaging material of container or 
closure remains the same.  
2. The change does not affect the delivery, use, 
safety or stability of the finished product  
 
SUPPORTING DOCUMENT  
 
Revised drafts of the package insert and labeling 
incorporating the proposed variation (where  
applicable).  
 
11.  
Change in testing  
procedure of an excipient   
• P4.2 
• P4.3  
Not applicable   
CONDITION  
 
Specifications of the excipient and drug product 
(finished product) remain the same.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 646  b) VARIATION TYPE II (MAJOR VARIATION ) 
 
NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
1.  
Change of product name.  
  
• A1 
• D1 
• D2 
• D3 
• E4 
 (if applicable)  
• E8 (if applicable)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
• A1 
• D1 
• D2 
• D3  
(if applicable)  
• F4  
(if applicable)  
• F8 (if applicable)  
 
 
  
CONDITIONS  
 
1. No change to product (formulation, specification 
etc) except for the product name  
2. No confusion with other already registered 
product’s name.  
3. The new name does not (1) suggest greater safety 
or efficacy than  supported by clinical data (2) 
imply a therapeutic use (3) imply superiority over 
another similar product (4) imply the presence of 
substance(s) not present in the product.  
4. Health Supplements & Natural Products - Please 
refer Appendix 4  and Appendix 5 , respectively.  
 
SUPPORTING DOCUMENTS  
 
1. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
2. Letter confirming change in na me only issued by 
the product owner or PRH.  
3.  A declaration from the applicant that there is no 
change to the product/ label except name.  
4.   Updated CPP if applicable.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 647  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
2.  
Change in content of 
leaflet or prescribing 
information/ PIL/ SPC.   
• A1 – A17 
• D1 
• D2 
• D3 
• E7  
• E8  
(if applicable)   
• A1 – A13 
• D1 
• D2 
• D3 
• F7 
• F8 
• F12  
CONDITION  
 
As a subsequent change due to revision of datasheet 
approved by regulatory authority e.g. Summary of 
Product Characteristics (SPC), or US Package Insert 
(USPI) or equivalent document . 
 
For natural products:  
Proposed indication shall be within those listed under 
Appendix 5 .  
 
SUPPORTING DOCUMENTS  
 
1. For all types of product please  provide revised 
drafts of the package insert and labeling 
incorp orating the proposed variation with:  
a. Copy with amendments clearly marked.  
b. Clean copy of the proposed new package 
insert.  
 
2. For innovator product please provide:  
a. Datasheet approved by regulatory authority 
e.g. Summary of Product Characteristics 
(SPC), or US Package Insert (USPI) or 
equivalent document.  
b. Conclusion or abstract of recent Periodic 
Safety Update Report where applicable.  
c. Expert Clinical Report (if applicable)  
d. Company Core Datasheet where applicable.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 648  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
3. For generic product please provide supporting 
documents e.g. Martindale or equivalent 
document to support the change.  
 
4. For natural products, please provide:  
a) Justification for the proposed change.  
b) Supporting documents from the clinical 
papers, Chinese Pharmacopoeia and/or 
herbal monograph/ compendium on  the 
therapeutic uses and safety aspect of the 
relevant active ingredient/s.  
 
3.  
Change in content of label 
inclusive of change in 
graphics/ artwork.   
• D1 
• D2 
• D3  
• D1 
• D2 
• D3  
CONDITIONS  
 
For Natural Products Please refer to  (List of 
Prohibited Visuals/ Gra phics On Label of Natural 
Products in Appendix 5 )  
 
SUPPORTING DOCUMENT  
 
Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 649  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
4.  
Change in manufacturing 
process of the finished 
product   
• E11 
• P3.2 
• P3.2.1  
• P3.3 
• P3.4 
• P5.1 
• P5.4 
• P8 
  
• B2.1 
• B2.2 
• B3 
• B4 
• B5 
• F10  
(CoA of  
finished 
product)  
  
CONDITIONS  
 
1. The same currently approved manufacturing site.  
2. The change does not cause a negative impact on 
the quality, safety and e fficacy of the drug product.  
3. Finished product specification is not adversely 
affected.  
 
 
SUPPORTING DOCUMENTS  
 
1. Description of the proposed change in 
manufacturing process.  
2. Comparative batch analysis data between the 
currently approved and proposed manufact uring 
processes OR Certificate of Analysis (CoA), where 
applicable.  
 
3. Stability data of drug product (please refer to 
ASEAN Guideline on Stability Study of Drug 
Product) where applicable.  
4. Comparative dissolution profile data between the 
products manufacture d in the currently approved 
and proposed manufacturing process for oral solid 
dosage forms as per compendium and validation 
batches, where applicable.  
5. Justification for not submitting a new 
bioequivalence study according to ASEAN 
Guidelines for the Conduct  of Bioavailability and 
Bioequivalence Studies, where applicable.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 650  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
For abridged -products, only supporting documents 
(1), (2) and (3) are required.  
 
Process validation report may be requested when 
deemed necessary.  
 
5.  
Change in overage of 
active ingredie nt   
• B1.2 
• E11 
• P5.4 
• E12 
• P8  
• B1.2 
• F10 
• F12 
• B5  
CONDITION  
 
Finished product release and end of shelf life 
specification remains the same.  
 
SUPPORTING DOCUMENTS  
 
1. Certificate of Analysis (CoA) of drug product.  
2. Justification for the change.  
3. Stability data of drug  product (please refer to 
ASEAN Guideline on Stability Study of Drug 
Product) where applicable.  
4. Batch manufacturing formula.  
5. Comparative batch analysis data of drug product.  
6. Table of comparison of proposed and current 
batch manufacturing formula.  
7. Letter of  commitment to undertake the proposed 
change under real time stability study.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 651  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
6.  
Replacement of an 
excipient with a 
comparable excipient 
and/or change in content 
of excipient.   
• A2.1 
• B1.2 
• P1 
• P4.1 
• P4.2 
• P3.2 
• P3.2.1  
 
 
• E11 
• P5.4 
• P8 
• E12 
• D1 
• D2 
• D3 
    (if applic able)  
• A4.2 
• B1.2 
• B2.1 
• B2.2 
• B3 
• B4 
• B5 
 
 
• F10 
• F12 
• D1 
• D2 
• D3 
(if applicable)   
CONDITIONS  
 
1. Finished product release and end of shelf life 
specification remains the same.  
2. There is no change in dissolution profile for oral 
solid dosage forms (where applicable).  
3. Replacement of an excipient with a comparable 
excipient of the same functional characteristics.  
4. No changes on the specification of the excipient 
for product specific requirements (e.g. particle size 
profiles, polymorphic form, etc.), if applicable.  
5. Any new ex cipient does not include the use of 
materials of human or animal origin for which 
assessment is required of viral safety data.  
 
SUPPORTING DOCUMENTS  
 
1. Comparison of new and existing formula.  
2. Batch Manufacturing Formula.  
3. Excipient specification (if applicabl e). 
4. Manufacturing process with amendments.  
5. Certificate of Analysis (CoA) of drug product.  
6. Justification for not submitting a new 
bioequivalence study according to ASEAN 
Guidelines for the Conduct of Bioavailability and 
Bioequivalence Studies (where applica ble). 
7. Comparative dissolution profile data of at least 
one representative pilot/production batch of the 
drug product between the currently approved and 
proposed solid dosage forms formulation (where Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 652  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
applicable).  
8. Stability data of drug product (please refer  to 
ASEAN Guideline On Stability Study of Drug 
Product)  
9. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
10. Batch analysis data.  
11. Product interchangeability/ equivalent evidence (if 
any). 
12. Justification for the change supported by 
appropriate development of pharmaceutics.  
13. New unit formula for coating agent (where 
applicable).  
 
7.  
Change in batch size   
• B1.2 
• E11 
• P5.4 
• P3.4 
• E12 
• P3.2 
• P3.2.1  
(if applicable)   
• B1.2 
• F10 
• F12 
• B2.1 
• B2.2 
      (if applicable)   
COND ITIONS  
 
1. The change does not affect the reproducibility 
and/or consistency of the product.  
2. No change to the manufacturing method nor to the 
in-process controls other that those necessitated 
by the change in batch -size, e.g. use of different 
size equipment.  
3. Finished product release and end of shelf life 
specification remains the same.  
 
SUPPORTING DOCUMENTS  
 
1. Comparative tabulated format of the proposed and 
current manufacturing formula.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 653  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
2. New batch manufacturing formula.  
3. Batch analysis data (in a comparative tab le). 
4. Certificate of analysis for 2 batches of drug 
product.  
5. Process validation report (may be requested when 
deemed necessary).  
6. Justification for the change.  
7. Letter of commitment to undertake the proposed 
batch size under real time stability studies.  
8. Descr iption of the manufacturing process (if 
applicable).  
 
8.  
Change in hard capsule 
shell (colour, size or 
source)   
• A4 
• P1 
• P8 
• E11 
• P4.5 
• P5.4 
• E12 
• P5.1 
• E9  
• D1 
• D2 
• D3  
    (if applicable)   
• A2 
• A3.2 
• B4 
• B5 
• F9 
• F10 
• D1 
• D2 
 
• D3  
      (if applicable)   
CONDITIONS  
 
1. Includes  change of hard gelatin capsule to 
vegetable capsule but does not apply change from 
hard gelatin capsule to soft gel capsule.  
2. Any new coloring agent used must be of oral 
pharmaceutical/ food grade and not a listed 
banned substance.  
3. Same functional characte ristics, no change in 
dissolution profile for solid dosage forms  
4. Finished product release and shelf life 
specifications remain the same except for the 
product description.  
 
SUPPORTING DOCUMENTS  
 
1. Stability data of drug product (please refer to 
ASEAN Guideli ne on Stability Study of Drug Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 654  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
Product) where applicable.  
2. Certificate of analysis (CoA) of drug product with 
the new description.  
3. For empty hard capsule made of ruminants 
source, Transmitting Animal Spongiform 
Encephalopathy (TSE) -free certificate issued f rom 
relevant veterinary authority of the issuing country . 
4. Certificate of analysis of the new capsule shell.  
5. Revised specifications of drug product.  
6. Batch analysis data.  
7. Compa rative dissolution profile data of drug 
product.  
8. Revised drafts of the package ins ert and labeling 
incorporating the proposed variation (where 
applicable).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 655  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
9.  
Change in finished 
product or active 
ingredient specification 
(includes addition of a 
new test parameter)   
• E9 
• E10 
• E11 
• P5.1 
• P5.4 
• P5.6 
• S4.1 
• S4.2 
• S4.3 
• S4.4  
• B4 
• F9 
• F10 
• F11  
CONDITI ONS 
 
The change should not be the result of unexpected 
events arising during manufacture or because of 
stability concerns.  
 
SUPPORTING DOCUMENTS  
 
1.  For change in finished product specifications:  
 
a. Certificate of analysis of drug product as per 
the new spe cifications:  
b. Comparative table of approved and proposed 
specifications with justification  
c. Appropriate analytical validation data  
d. Revised specifications of drug product.  
e. Revised analytical procedures.  
f. Batch analysis data of drug product.  
 
2. For change in act ive ingredient/ drug substance 
specifications:  
 
a. Comparative table of approved and proposed 
specifications with justification  
b. Specification of drug substance,  
c. Analytical procedures of drug substance,  
d. Validation of analytical procedures,  
e. Batch analysis of dr ug substance  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 656  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
10.  
Change to in -process 
tests or limits applied 
during manufacture of the 
product.   
• P3.3 
• P3.4 
• E9 
• E10  
• B3 
• F9  
CONDITIONS  
 
1. Includes tightening of in -process limits and 
addition of new tests  
2. Release and shelf -life specifications of drug 
produ ct remain unchanged  
 
SUPPORTING DOCUMENTS  
 
1. A description of the analytical methodology and 
summary of validation data must be provided for 
all new analytical methods (where applicable).  
2. Revised in -process specifications together with 
justification and rele vant process validation data.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 657  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
11.  
Change or addition in 
primary packaging 
material   
• C 
• D1 
• D2 
• D3 
• P3.2 
• P3.2.1  
• P7 
• P8 
• E8  
(if applicable),  
• E12  
• C 
• D1 
• D2 
• D3  
(if applicable),  
• B5, 
• F8  
(if applicable)  
• F12  
CONDITIONS  
 
Release and shelf life specification remain s 
the same.  
 
 
SUPPORTING DOCUMENTS  
 
1. Assembly process for the new packaging material/ 
revised manufacturing process and revised flow 
chart (if any)  
2. Stability data of drug product (please refer to 
ASEAN Guideline on Stability Study of Drug 
Product) where app licable.  
3. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
4.  Justification for the change in packaging material 
and appropriate scientific studies on the new 
packaging.  
5. For semisolid and liquid dosage  forms, proof must 
be provided that no interaction between the 
content and the packaging material occurs.  
(e.g. no migration of components of the proposed 
material into the content and no loss of 
components of the product into the pack).           
6. Containe r closure system (if applicable).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 658  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
12.  
Change in shelf life of 
finished product: - 
 
a)  As packaged for sale  
 
b)  After first opening  
 
c)  After dilution/  
     reconstitution  
  
• A16 
• P8 
• E12 
• D1 
• D2 
• D3 
  
• A13 
• B5 
• F12 
• D1 
• D2 
• D3 
 
  
CONDITIONS  
 
1. For (a) & (b)  - The studies must show 
conformance to the current shelf life specification.  
2. For (c)  - Studies must show conformance to the 
current shelf life specification for the reconstituted 
product.  
 
SUPPORTING DOCUMENTS  
 
1. Results of appropriate real time stability studies  
covering the duration of proposed shelf -life of at 
least 2 pilot/ production scale batches of the 
product in the authorized packaging material  
• as a package for sale and/or  
• after first opening and/or  
• after the dilution/ reconstitution  
 
In accordance with the ASEAN Guidelines on Stability 
Study of Drug Product; results of appropriate 
microbiological testing should be included (where 
appropriate).  
 
2. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
3. Justification letter for the change of shelf life of the 
drug product (if applicable).  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 659  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
13.  
Change in storage 
conditions   
• A15 
• P8 
• D1 
• D2 
• D3  
• A12 
• B5 
• D1 
• D2 
• D3  
CONDITION  
 
The studies must show conformance to the current 
shelf life specification.  
 
SUPPORTING DOC UMENTS  
 
1. Results of appropriate real time stability studies 
covering the duration of currently approved end -
of-shelf life (at proposed storage condition) of at 
least 2 pilot/ production scale batches of the 
product and in the authorized packaging material 
in accordance with the ASEAN Guidelines on 
Stability Study of Drug Product.  
2. Revised drafts of the package insert and labeling 
incorporating the proposed variation (if 
applicable).  
 
 
14.  
Appointment, deletion or 
change of other 
manufacturers  
  
• D1 
• D2 
• D3 
• E14 
• E12  
  
• E3 
• F12 
• D1 
• D2 
• D3  
  
SUPPORTING DOCUMENTS  
 
1. GMP certificates of the proposed other 
manufacturers.  
2. Description of the manufacturing activity of all 
other manufacturers involved (including 
assembling process).  
3. Letter of appointment and acceptance for c ontract 
of other manufacturers.  
4. Revised drafts of the labeling incorporating the 
proposed variation (where applicable).  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 660  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
 
15.  
Addition or 
deletion of scoring/ 
break line on 
tablet   
• A4 
• P1 
• D1 
• D2  
(if applicable)  
• D3 
• E9 
• E11 
• P5.1 
• P5.4 
• E12 
 
 
  
• A2 
• B4 
• F9 
• F10 
• F12 
• D1  
• D2  
• D3  
(if applicable)  
  
CONDITIONS  
 
Finished product release and shelf life specifications 
remain the same except for the product description.  
 
SUPPORTING DOCUMENTS  
 
1. Certificate of analysis (CoA) FPQC X 1 batch 
(shall include data on the test of unif ormity of 
content of the subdivided parts of tablets at 
release).  
2. Revised drafts of the package insert and labeling 
incorporating the proposed variation (where 
applicable).  
3. Release and end -of-shelf life specifications of the 
drug product with the new produ ct description.  
 
16.  
Change in test procedure 
or analytical protocols of 
finished product.   
• E9 
• E10 
• E11 
• P5.4  
• B4 
• F9 
• F10  
CONDITIONS  
 
1. Finished product specifications are not adversely 
affected.  
2. Appropriate analytical validation or re -validation 
studies hav e been performed in accordance with 
relevant guidelines.  
3. Results of method validation show new test 
procedure to be at least equivalent to the former 
procedure.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 661  NO. VARIATION TYPE II  
(MAJ OR VARIATION)  AFFECTED FIELDS  
SUPPORTING DOCUMENTS REQUIRED AND 
CONDITIONS APPLIED  FULL 
EVALUATION  ABRIDGED 
EVALUATION  
SUPPORTING DOCUMENTS  
 
1. Appropriate verification/ validation data and 
comparative analytical re sults between the 
currently approved and proposed test.  
2. Revised protocol of analysis.  
3. Certificate of analysis of drug product.  
 
 
17.  
Change or addition of fill 
volume and/or change of 
shape or dimension of 
container or closure for a 
sterile solid and liq uid 
drug product  
  
• P3.4 
• P8 
• E12 
• C 
• D1 
• D2 
• D3  
    (if applicable)   
Not applicable   
CONDITIONS  
 
1. Release and end -of-shelf life specifications of the 
drug product are not affected.  
2. The packaging material remains the same.  
 
SUPPORTING DOCUMENTS  
 
1. Justification tha t the proposed pack size is 
consistent with the dosage regimen and duration 
of use as approved in the package insert.  
2. Validation data of the manufacturing process, 
sterilization and container closure system (if 
applicable).  
3. Stability data of drug product ( please refer to 
ASEAN Guideline on Stability Study of Drug 
Product) where applicable.  
4. Revised drafts of the package insert and labeling 
incorporating the proposed variation, where 
applicable.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 662  APPENDIX 13  : SUPPORTING DOCUMENTS REQUIRED FOR 
CHANGE OF MANU FACTURING SITE (COS) APPLICATION  
 
f) Supporting documents required for change of manufacturing site (COS) 
application  
 
No Document To Be Submitted  Type  
I 
(Except 
Natural 
Product)  Type  
II Type  
III Type  
IV Type  
V 
1.  Letter of authori sation/ appointment fr om the 
product owner to authoris e Product 
Registration Holder to submit the change of 
site application.  
 
In case of a contract manufacturer, a letter of 
acceptance from the proposed contract 
manufacturer to manufacture the product.  √ √ √ √ √ 
2.  Letter from the man ufacturer/ product owner 
to clarify/ explain the need to change site of 
manufacture.  √ √ √ √ √ 
3.  Written declaration from the manufacturer to 
certify that the manufacturing process, and the 
release and expiry (check) specifications of 
the product as the sa me as already approved.  
 
OR 
 
If there are minor changes, to declare the 
‘minor changes’ & justify the need for such 
changes.  √ √ √ √ √ 
4.  ‘Release’ and ‘end -of-shelf life’ specifications 
from proposed site . √ √ √ √ √ Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 663  No Document To Be Submitted  Type  
I 
(Except 
Natural 
Product)  Type  
II Type  
III Type  
IV Type  
V 
5.  Original copy of the Certificate of Fr ee Sale 
(CFS) / Certificate of Pharmaceutical Product 
(CPP) and notarised Good Manufacturing 
Practice (GMP) from the source country of the 
new manufacturing site in the case of an 
imported product  
 
OR  
 
Letter of confirmation on GMP status or valid 
manufac turer’s license for the new 
manufacturing site.  √ √ √ √ √ 
6.  Specification of the drug substance  
 √ √ √ √ √ 
7.  Product formula/ Batch Manufacturing 
Formula  √ √ √ √ √ 
8.  Original copy of Certificate of Analysis (CoA) 
from the new manufacturing site.  
 √ √ √ √  
9.  Comparative batch analysis data of drug 
produc t of at least two production batches (or 
one production batch and two pilot batch) from 
the proposed site and last three batches from 
the current site; batch analysis data on the 
next two full production batches should be 
available upon request or reported  if outside 
specifications (with proposed action).  
 √ √ √ √  
10.  “Accelerated” and on -going stability data as 
per ASEAN Guideline on Stability Study of 
Drug Product and a letter of commitment to 
submit real time stability data.  
 √ √ √ √  
11.  Amended immediate label, outer label and 
package insert for the produc t from the 
proposed  site. 
 √ √ √ √ √ 
12.  Process validation report as per ASEAN 
Guideline On Submission Of Manufacturing 
Process Validation Data For Drug 
Registration.  
 √ √ √ √  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 664  No Document To Be Submitted  Type  
I 
(Except 
Natural 
Product)  Type  
II Type  
III Type  
IV Type  
V 
13.  Holding time studies testing of bulk pack 
during storage and transportation be tween the 
bulk production site and primary packager 
(where applicable).  
 √ √ √ √  
14.  Letter of commitment to submit stability data, 
certificate of analysis, process validation 
report (where applicable) and sample for 
laboratory testing within 6 months of a pproval 
of site change.   
    
√ 
15.  A written plan for assessing the effect of the 
change of site on the quality of the product 
with the objective of demonstrating that the 
pre- and post -change products are equivalent.  √ √  √  
16.  Comparative dissolution profi le between the 
proposed and current site for oral solid 
dosage forms that are entitled for “biowaiver”.  
 
For further information, please refer circular:   
Bil (31) dlm. BPFK/PPP/01/03   
 
OR 
 
Report of bioavailability and bioequivalence 
studies for generic products.  
 
OR 
 
Comparative dissolution profile between the 
proposed and current site for oral solid 
dosage forms for innovator produ cts, if 
applicable.  
 
(Please refer to ASEAN Guidelines and list of 
products requiring BA and BE study).  √ √ √  
  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 665  No Document To Be Submitted  Type  
I 
(Except 
Natural 
Product)  Type  
II Type  
III Type  
IV Type  
V 
17.  Letter of commitment to submit comparative 
dissolution profile between the proposed and 
current site for oral solid dosage forms that 
are en titled for “biowaiver”.  
 
For further information, please refer circular:   
Bil (31) dlm. BPFK/PPP/01/03   
 
OR 
 
Letter of commitment t o submit report of 
bioavailability and bioequivalence studies for 
generic products.  
 
OR 
 
Letter of commitment to submit comparative 
dissolution profile between the proposed and 
current site for oral solid dosage forms for 
innovator products, if applicable . 
 
(Please Refer to ASEAN Guidelines and list of 
products requiring BA and BE study).      √ 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 666  b) Supporting documents required for Type I change of manufacturing site (COS) 
application for natural products  
 
No. Documents To Be Submitted  
1.  Letter of authoris ation/ appointment from the product owner to authorise Product 
Registration Holder to submit the change of site application.  
 
In case of a contract manufacturer, a letter of acceptance from the proposed contract 
manufacturer to manufacture the product.  
 
2.  Letter of declaration stating the reason(s) for change of manufacturing site and clearly 
state the proposed and current name and address of manufacturer  
3.  Written declaration from the manufacturer to certify that the manufacturing process, 
and the release and expiry specifications of the product as the same as already 
approved.  
 
OR 
 
If there are minor changes, to declare the ‘minor changes’ & justify the need for such 
changes.  
 
4.  ‘Release’ and ‘end -of-shelf life’ specifications from proposed site.  
 
5.  Letter  of confirmation on GMP status or valid manufacturer’s license for the new 
manufacturing site.  
 
6.  Product formula / Batch Manufacturing Formula  
 
7.  Amended immediate label, outer label and package insert for the product from the 
proposed site.  
 
8.  Declaratio n and commitment that the manufacturer will carry out continuous quality 
monitoring on the post change products  
 
9.  Letter of commi tment to submit stability data and certificate of analysis  after approval 
of site change.  
10.  A written plan for assessing the e ffect of the change of site on the quality of the 
product with the objective of demonstrating that the pre - and post -change products 
are equivalent.  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 667  APPENDIX 14  : GUIDELINES ON SAFETY DATA 
REQUIREMENTS FOR COMPLEMENTARY MEDICINE 
PRODUCTS  
 
 
 
 
Contents  
 
1. Introduction  
 
2. Objectives  
 
3. Safety Data   
 
4. Overview  
 
5. Glossary  
  
6. References   
 
       
       
 
 
 
 
 
 
 
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 668  1. Introduction  
 
Consumer interest in health and self -care has expanded the market for a wide range of 
health supplements and traditional products. These categ ories of products have been used 
since the earliest history of humanity and have formed one of the foundations for 
healthcare in cultures throughout the world. With the increased use of such products and 
the broad spectrum of products classified under this  category, it is important to ensure that 
the products consumed are safe for consumers.  
 
Evaluation of the safety of complementary medicine products (health supplements, herbal 
products and traditional medicine) must be done in a manner that is cost effec tive and 
science -based  within the regulatory environment.  
 
Most ingredients might be  considered as  safe, considering the experience or history of long 
use. When an ingredient is well known for a specific use, the assessment will be limited to 
published da ta (including traditional references). However, under certain conditions, 
additional data will be required to prove the safety of the product , e.g. for  a new active 
ingredient  or a new combination  of ingredients . Even if a product has been in use over a 
long period of time, chronic toxicology risks may have occurred but not recognized.  
 
2. Objectives  
 
This Guideline aims to provide guidance in submitting safety data requirements for 
assessment to facilitate registration  of complementary medicine .   
 
 
3. Safety  Data 
 
Proof that a product is of quality, safe and as efficacious as claimed is a pre -condition for 
marketing of a complementary medicine product. Safety is dependent upon the overall 
product formulation, its intended use, dosage, route of administration, du ration of use and 
targeted group where applicable.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 669   
Each active ingredient shall make a relevant and reasonable contribution to the overall 
therapy and the quantity of each active ingredient shall be safe for the recommended use 
and range of dosage.  
 
3.1 Safety data shall be required to substantiate the safety profile for the following 
complementary medicine product to be marketed but not limited to: 
a. New ingredients  
b. Existing  active  ingredients/products with new combination , new dosage, new delivery 
system , new methods of  manufacturing  or for use in a special target population (e.g. 
pregnant, lactating women, children, etc).  
c. Existing ingredients/products with safety concern. Safety concerns may be newly 
emerging or established, and in some cases may need add itional information to support 
safe usage in complementary medicine. These safety concerns may be addressed by 
including additional cautionary statements.   
 
3.2 Safety substantiation might not be required for complementary medicine  product s that 
do not fal l under items a. - c. as mentioned above. T raditional medicines with documented 
data; health supplements which have been consumed as food or is a food constituent 
within the normal usage limit or for those containing ingredients with well documented and 
established safety profile  may also not require further safety substantiation.  
 
Further e xamples would include:  
i) Product containing the same combination (same nu mber of active ingredients) as 
with another  previously  registered product with the active ingredie nts within limits 
previously registered.  
ii) Combination of vitamins and minerals within permissible limits  
iii) Formulary products  
 
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 670   
3.3 Some general principles on assessing product safety shall  be as follows:  
a) Single ingredient   
For well -known ingredients suc h as vitamins or minerals and herbal ingredients,  
documented  data will be accepted to demonstrate safety of use.  
 
If an ingredient has been used traditionally and documented that it had no safety concerns , 
the submission of toxicology studies will not be required. However, if history of use is used 
to support safety, then the details of use must be consistent with its traditional use.  
 
If toxic effects have been reported or there is insufficient documented safety evidence  and 
there are doubts concerning th e product/active ingredient , submission of toxicological 
reports will be required.  
 
In a case when the anticipated intake of this ingredient is significantly higher than the 
estimated historical intake, or for which the historical intake cannot be assesse d, additional 
safety data/studies will be required . 
 
b) Combination products  
There are no special requirements for combinations of well -known ingredients such as 
vitamins or minerals . Each active ingredient and dosage will be assessed independently 
and acc ording to documented  data.  
 
The intended use/function  of each ingredient must support a logical use of the combination 
in question and if for traditional use must prescribe to the philosophy of that culture. Like 
acting herbal ingredients are considered t o have an additive effect.  
Therefore, the dosage of each active substance may be reduced as compared to its single 
use. The counteracting by one active ingredient to the adverse reaction produced by Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 671  another must be explained.  Illogical combination of herbs  or ingredients having widely 
different therapeutic uses will require justification.  
 
However, for a combination consisting of new active ingredients, toxicological and clinical 
data for finished product may be requested . This will also apply to new combin ations of 
well-known ingredients. Safety data will have to be on the product with information on 
individual ingredients as supportive references.    
 
 
 
c) Target population  
It cannot  be assumed that an ingredient is suitable for pregnant or lactating women unless 
evidence is provided to the contrary. If required,  the product should carry the following 
statement:  
“Pregnancy and breastfeeding: Insufficient reliable data”  
or 
“If you are pregnant /breastfeeding, please consult your doctor/pharmacist before takin g 
this product.”  
 
A product will also be generally assumed not safe for children unless proven otherwise. If 
the product has children dosage instructions, there must be evidence to fully demonstrate 
safety in children of that age.  
 Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 672   
4. Overview  
Information that will be required to substantiate the safe use of a product may include but is 
not limited to:  
 
4.1  Literature search  
A comprehensive literature search which would include both positive and negative reports 
must be submitted. The search criteria used should also be mentioned and references 
cited. Certified translated copies by the recognised  bodies  must also be provided if the 
original articles are not in the English or Malay language.  
 
4.2    Extent of use  
Information on extent of use in other countries may provide insight into the safety profile. 
The maximum amount of the ingredient that is recommended or suggested for use as food 
may be provided as proof of safe use. However, the amount in the product should not 
exceed the recommended level.  
 
If evidenc e is to be based on traditional use, it must be clearly stated that the ingredient 
under review is equivalent to that  used traditionally. Knowledge of chemical components of 
an ingredient will aid in safety evaluation by identifying potentially toxic const ituents or 
constituents known to mimic or modulate endogenous intermediates. Modern extraction 
methods used may in some instances produce a substance that is compositionally different 
from those produced using traditional methodology.  
 
The industry should be able to capture the safety data of any abnormalities and or 
untoward adverse reaction that might be occurred or derived from animal and or human 
study. Efficacy data will also often include information on adverse events that will be useful 
in safety eva luation.  
 
Evidence of the regulatory status of the product in other countries may also be provided as 
supportive evidence to justify safe use of the product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 673   
4.3      Pharmacological properties  
This would include pharmacodynamic and pharmacokinetic studies for medicinal use 
except for traditional products which will be based on the philosophy of its traditional use.  
 
4.4      Toxicology data  
The intended use  and the duration  of use whether it is for short  or long term use  will also 
determine  the type of toxicity  data needed , e.g acute  and/or chronic toxicity . Other toxicity 
data which should be identified would include teratogenicity, carcinogenicity and 
mutagenicity  data, where necessary. All evidence, both favorable and unfavorable should 
be included.  
 
Toxicity  data could be derived from  sources  such as authoritative reference test or from 
animal and/or human study.  The Organisation for Economic Co -operation and 
Development ( OECD ) Guidelines shall be used as a guide to conduct toxicity study on 
animals.  
  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 674   
4.5     Human data  
Safety profile of an ingredient may be obtained from sufficiently powered prospective 
observational studies, clinical trials, dose -escalation studies, systematic reviews, 
retrospective meta -analysis studies or even observation of adverse events  under controlled 
studies.  
 
 
4.6     Post marketing surveillance  
Premarket safety studies are sometimes limited by the number of study subjects. When 
products are in wide use, detection of adverse events provides a strong surrogate for safety 
monitoring in the  general population and in consumers who have chronic conditions. Post 
marketing surveillance also provides valuable information about a product’s safety profile in 
vulnerable populations e.g. in pregnancy, lactation, the elderly etc.  
 
Interaction with ot her medications/ supplementation or even food has significant safety 
implications because of their effects on bioavailability or induction/inhibition of metabolizing 
enzymes. Such interaction may lead to synergism or antagonism of intended effects.  
 
Safet y concerns from existing products may come from the reporting of the adverse 
reaction monitoring mechanism in the market or through post market control.  
 
The industry and regulator may collect those data from post -market reporting and should 
assess the cau sality between the emerging safety concern and the product.  Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 675   
5. Glossary  
 
5.1 New ingredient  
New ingredient refers to complementary medicine  active ingredient/ excipient  that has never 
been listed in the Quest database.  
 
5.2 New delivery s ystem  
New d elivery  system involve s a change in the method of administration and/or the physical 
dosage form of a complementary medicine  product.  
 
5.3 New c ombination  
A combination product, even if it consists of only existing ingredients, is regarded as a New 
Combination , when no product of the same composition (in terms of the constituent 
ingredients and their relative quantities  if higher than documented limits)  had been 
approved for marketing in Malaysia  before.  
 
5.4 New dosage  
New dosage  refers to the quantity of ingre dients/ substances to be used in a daily dose  as 
well as single dose basis, if higher than documented limits.  
 
5.5 Recognised  bodies  (with reference to translation of documents)  
Certified translators , embassies , Malaysia Pharmaceutical Society (MPS), Malaysian 
Organisation of Pharmaceutical Industries (MOPI), Pharmaceutical Association of Malaysia 
(PhAMA), Malaysian Dietary Supplement Association (MADSA), Federation of Chinese 
Physicians & Medicine -Dealers Association of Malaysia (FCPMDAM), Federation of 
Chinese Physicians & Acupuncturists Association of Malaysia (FCPAAM), Malaysian 
Chinese Medical Association (MCMA), Direct Selling Association of Malaysia (DSAM), 
Malaysian Direct Distribution Association (MDDA) , Persatuan Pengeluar Ubat Tradisional 
Malays ia (PURBATAMA), Gabungan Pertubuhan Pengamal Perubatan Tradisional Melayu Drug Registration Guidance Document (DRGD)  
National Pharmaceut ical Regulatory Division, Ministry of Health Malaysia.  
Second Edition, Sept 2016. Revised Ju ly 2018  
 Page | 676  Malaysia (GAPERA), Malaysian Homeopathic Medical Council (MPHM), Malaysian 
Association of Traditional Indian Medicine (PEPTIM), and related industry associations of 
the country of or igin recognized by the local authority . 
 
6. References  
 
1. World Health Organization. General Guidelines for Methodologies on 
Research and Evaluation of Traditional Medicine, 2000.  
2. World Health Organization. Guidelines for the regulation of herbal medicines 
in the South -East Asia Region, 2003.  
3. WHO Research Guideline for The Evaluation of Safety and Efficacy of Herbal 
Medicine 1993 . 
4. Organization for Economic Cooperation and Development ( OECD ) Guideline 
for toxicity studies in animals . Webpage: www.oecd.org   
5. Therapeutic Goods Administration, Australia; Webpage: www.tga.gov.au   
6.  Health Canada; Webpage: www.hc -sc.gc.ca/index -eng.php  
7.  European Medi cines Agency; Webpage: www.emea.eu  
8. Medicines and Healthcare Products Regulatory Agency (MHRA); Webpage: 
www.mhra.gov.uk   
9. ASEAN Traditional medicine and Health supplement Product Working Group (TMHS 
PWG) Meeting minutes