FDA CIRCULAR  
No. ___________  
 
 
TO               :  ALL MANUFACTURERS/ TRADERS/ IMPORTERS OF  
VAPOR PRODUCTS AND HEATED TOBACCO 
PRODUCTS.   
 
 
SUBJECT   :    PROCEDURE FOR PRE -MARKET APPLICATION FOR  
VAPOR PRODUCTS AND HEATED TOBACCO 
PRODUCTS SEEKING REGISTRATION UNDER THE 
CENTER FOR COSMETICS REGULATION AND 
RESEARCH  
 
 
I. BACKGROUND  
 
  Pursuant to Republic Act No. 11467, Republic Act 9711, and Executive Order No. 
106, the Food and Drug Administration (FDA) is mandated to regulate vapor products and 
Heated Tobacco Products (HTPs) consistent with evolving medical, public health, and 
scient ific evidence. To this end, the FDA hereby implements this Circular applicable to 
vapor products with permissible nicotine concentrations above 20 mg/mL but less than 65 
mg/ml with  or without  health claims (such as, but not limited to: for smoking cessation, 
tobacco harm reduction) and HTPs manufactured, distributed, traded, and/or sold by the 
electronic cigarette and tobacco industries.  
 
 
II. OBJECTIVE  
 
  The objective of this Circular is to pro vide the procedural guidelines and 
documentary requirements for the Pre -Market Application pathway for FDA registration 
of Heated Tobacco Products and vapor products that have health claims and permissible 
concentrations above 20mg/mL  but less than 65 mg/m l. 
  
III. SCOPE AND COVERAGE  
 
  This Circular shall cover all manufacturers,  traders, and importers of vapor 
products with health claims or with nicotine concentr ations between 20 and 65 mg/ml. 
This Circular shall also apply to Heated Tobacco Products.  
 
IV. GENERAL PROCEDURE  
 
1. Manufacturers, traders, and importers of vapor products with health claims and 
permissible nicotine concentrations between 20 and 65 mg/ml  shall undergo Pre -Market 
Applic ation (PMA) at least 3 months prior to securing  the License to Ope rate (LTO)  and Certificate of Product Registration (CPR) under the Center for Cosmetics Regulation and 
Research.   
 
2. All HTPs shall undergo PMA prior to securing a CPR under the Center for Cosmetics 
Regulation and Research (CCRR).   Applications should be lodged at least 3 months prior 
to the application of the LTO and CPR.  
 
3. As part of the Pre -Market Application bundle, the following documents are required to be 
submitted to the FDA Action Center (FDAC), in triplicates  including a s oft copy in a 
flashdrive , for each product intended for registration, and upon payment of the required 
fees:  
 
a. For Vapor Products and Heated Tobacco Products:  
i. Complete company information, including:  
1. Company name  
2. Organizational chart  
3. Business addresses and other contact details  
4. Notarized authorized responsible person  to apply in behalf of the 
manufacturer, in case the applicant is a distributor or importer.  
ii. An affidavit signifying the intent of the Manufacturer, Trader, or 
Distributor/Importer to have its products registered under the Philippine 
Food and Drug Administration (FDA)  
iii. Explicit authorization for the FDA  to use, copy, store, and distribute digital 
and physical copies of all documents included in the Pre -Market 
Application bundle for th e purposes of (1) review and evaluation of the 
application by persons internal and external to the Agency, as deemed 
appropriate by the FDA Director -General, (2) medical and public health 
research, (3) enforcement, (4) public policy development, and (5) pu blic 
health programs and communications.  Confidentiality of information and 
documents submitted shall be ensured and as provided under the Data 
Privacy Act . 
iv. An attestation from the manufacturer, trader, or importer that the 
information contained in the bundle is complete, accurate, and unredacted, 
under the penalties of all relevant legislation.  
v. A complete declaration of technical specifications of the product to be 
registered, including at least the following information:  
1. raw material sources  
2. raw mate rial suppliers  
3. countries of origin for all components  
4. physical and chemical characteristics of the components  
5. product design  
6. the complete mechanism of the product’s use and operation as 
known by the manufacturer  
7. tar, nicotine, and carbon monoxide (TNCO)  yield  for HTPs 
including HPHC, additives and other ingredients including trace 
elements  8. aerosol emissions for vapor products  
 
vi. Results of the following in vitro tests on product emissions, as determined 
by ISO-certified government or independent laboratori es not owned, partly 
owned, or otherwise controlled by the electronic cigarette or tobacco 
industries and their agents and/or representatives:  
 
1. Salmonella/microsome fluctuation (Ames) Test following the 
OECD 471 protocol  
2. In vitro dosimetric and cytotoxic assessment by neutral red uptake  
3. Mouse Lymphoma Assay, in accordance with the OECD 490 
protocol  
 
vii. Results of the following in vivo tests on product emissions, as determined 
by ISO-certified government or independent  laboratories not owned, partly 
owned, or otherwise controlled by the electronic cigarette or tobacco 
industries and their agents and/or representatives:  
 
1. 90-day Nose -only Inhalation Studies  
2. 18-month Carcinogenicity Study with A/J mice  
3. Nicotine Pharmacokinetic (PK) Study with Rats  
 
viii. Resul ts of the following systems toxicology studies on product emissions, 
as determined by ISO-certified government or independent laboratories not 
owned, partly owned, or otherwise controlled by the electronic cigarette or 
tobacco industries and their agents a nd/or representatives:  
 
1. Acute and Repeated Exposure Studies with Human Bronchial 
Epithelial Cells  
2. ApoE -/- Mouse Switching Study  
 
ix. A complete list of relevant certifications held by the laboratory conducting 
the in vitro, in vivo, and systems toxicology studies.  
 
x. An attestation from the said laboratory of the exact make, model, and brand 
of the smoking robot used in the conduct of the in vitro studies.  
 
xi. Results of the following studies on clinical behavioral pharmacology, as 
determined by resea rchers not compensated or otherwise controlled by the 
electronic cigarette or tobacco industries and their agents and/or 
representatives:  
1. Pharmacokinetic/Pharmacodynamic (PK/PD) Studies  
2. Intrinsic and Extrinsic Factors Affecting Nicotine Pharmacokinetic 
Data  
3. Nicotine Equivalents (NEQ) in Urine  
4. Use Behavior and Topography  5. Product Use/Consumption  
6. Product Acceptability  
7. Product Abuse Potential  
xii. A complete declaration of interest of all researchers conducting the clinical 
and behavioral pharmaco logy evaluation and their relevant qualifications 
and affiliations.  
 
b. For Vapor Products  
 
i. Certificates of Analysis for the Harmful and Potentially Harmful 
Chemicals in Tobacco Products as listed by the United States Food and 
Drug Administration , European Union or Health Canada , relative to typical 
emissions of the University of Kentucky reference cigarette 3R4F, as 
obtained under established protocols as may be selected by the 
manufacturer, for mainstream and sidestream emissions, as determined by  
laboratories not owned, partly owned, or otherwise controlled by the 
electronic cigarette or tobacco industries and their agents and/or 
representatives.  
ii. A complete, step -by-step description of protocol used by the industry in the 
acquisition of Total Part iculate Matter/Aerosol Condensate for analysis.  
 
c. For Heated Tobacco Products  
 
i. Certificates of Analysis for the panel of Harmful and Potentially Harmful 
Chemicals  (HPHC)  in Tobacco Products as listed by the United States 
Food and Drug Administration , Europe an Union or Health Canada , relative 
to typical emissions of the University of Kentucky reference cigarette 
3R4F, and as obtained under the Health Canada intense smoking protocol 
(55mL puff volume every 30 seconds, with 100% of ventilation 
mechanisms occlud ed, until exhaustion or complete consumption of the 
Heated Tobacco Product cartridge), for mainstream and sidestream 
emissions, as determined by  an ISO-certified government or independent  
laboratories not owned, partly owned, or otherwise controlled by the  
electronic cigarette or tobacco industries and their agents and/or 
representatives.  
 
4. Upon submission of the Pre -Market Application bundle and submission  of proof of 
payment, the FDAC shall be the responsible office to transmit the complete submission to 
the CCRR  within 24 hours from Mondays to Thursdays or within three calendar days if 
the document was received on a Friday . 
5. The FDA  reserves the right to disapprove AL L pre -market application bundles that are 
incomplete or are with deliberately redacted data.  
6. The FDA, through a  corresponding  Personnel Order, shall enlist Expert Panels for 
independent risk assessments of vapor product and HTPs under Non -Disclosure 
Agreem ents, subject to relevant data privacy laws and government procurement 
regulations.  7. The CCRR may request for specific research and journal articles from the applicants in 
aid of a more rigorous evaluation.  
8. The CCRR shall not entertain follow -ups by phone, mail, personal visits or other means, 
electronic or otherwise  during the period of application . 
9. The final disposition on the pre -application evaluations shall lie solely with th e Director 
General of the FDA upon the recommendation of the Director IV of the  CCRR . The 
proposed disposition of the technical staff of the Novel Tobacco Regulatory Unit under 
the CCRR, and concurrence of the Expert Panel shall be deemed recommendatory  at most . 
10. Under no circumstances shall evaluations with favorable dispositions be deemed as an 
imprimatur of FDA approval nor shall they mean that vapor products or HTPs  are 
“appropriate for the protection of public health.” Any industry promotion, advertisement, 
or communication, explicit or implicit, contrary to this p rovision shall be grounds for 
immediate and final denial of active vapor product and HTP  applications associated with 
the offender’s License to Operate.  
11. Criteria for the selection of the expert panel shall be issued in a separate issuance.   A 
corresponding  conflict of interest and confidentiality agreement shall be submitted to the 
FDA.  
 
V. APPROVAL  
 
  Approval of the Pre -Market Application shall mean that the Marketing 
Autho rization Holder may apply for  the LTO and CPR under the licensing and registration 
schemes defined in relevant policy instruments  of the FDA . 
 
VI. PENALTIES  
 
Violation to any provisions of this Circular shall be subject to the 
penalties/sanctions provided under Book III, Article XI of the Rules and Regulations 
Implementing Republic Act No. 9711, Republic Act No. 11467, Executive Order No. 106 
and oth er penalties provided by other applicable laws.  
 
VII. SEPARABILITY CLAUSE  
If any provision in this Circular, or application of such provision to any 
circumstances, is held invalid, the remainder of the provisions in this Circular shall not be 
affected.  
VIII.  EFFECTIVITY  
This Circular shall take effect immediately.   
 
 
 
ROLANDO ENRIQUE D. DOMINGO, MD  
                                                            Director -General