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ADMINISTRATIVE ORDER  
No. ________________  
 
 
SUBJECT:  GUIDELINES ON THE CONDUCT OF CLINICAL  INVESTIGATION OF 
MEDICAL DEVICES  FOR HUMAN SUBJECTS  IN THE PHILIPPINES   
 
I. RATIONALE  
 
The Philippines, as a signatory to the ASEAN Agreement on Medical Device Directive  
(AMDD) , is mandated to institutionalize an appropriate system for the conduct of clinical 
investigation of medical devices, taking into account the Helsinki Declaration adop ted by 
18th World Medical Assembly in Helsinki, Finland, in 1964 and any subsequent amendments 
or revisions to this Declaration by the World Medical Association.   
 
As the regulatory agency for medical devices in the Philippines and pursuant to the 
provisio ns of Republic Act 9711, otherwise known as the “Food and Drug Administration 
(FDA) Act of 2009” , FDA has been tasked to develop policies on the regulation of medical 
devices to ensure public health and safety from the use of these products. In addition, FDA 
is also given the power to conduct, supervise, monitor and audit research studies on health 
and safety is sues of health products undertaken by entities duly approved by the FDA .  
 
To implement the mandate  of FDA and to ensure that all measures relating to the 
protection of human subjects are carried out during the conduct of clinical investigation of  
medical devices, this set of guidelines is hereby issued for strict compliance of all concerned.  
 
II. OBJECTIVES  
 
This Order aims to establish guidelines  on the conduct of clinical investigation of medical 
devices for human subjects in the Philippines . Specifically, it aims to ensure that the medical 
device is suitable for the population for which it is intended  and to ensure the safety and 
well-being of subjects participating  in the clinical investigation.  
 
III. SCOPE  
This Administrative Order shall apply to Contract Research Organization , Sponsors  
and/or other entities engaged in the conduct of clinical investigation of the following medical 
devices  in the Philippines : 
 
1. New medical device that will be marketed in the Philippines  Republic of the Philippines  
Department  of Health 
OFFI CE OF THE SECRETARY  
 
Building I, San Lazaro  Compound , R izal Av·enue, Sta .Cruz, 1003 Mani  la • Trunk  Line  651-7800 • Direct Line: 7 1 1-9501 
Fa x: 743-1829, 743-1786 • URL: http://www.doh.gov.ph  • e-mail: osec@doh.gov.ph   
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 2. Medical devices with corresponding authorization (Certificate of Medical Device 
Registration o r Certificate of Medical Device Notification) that have new intended 
purpose as determined by the product owner  
This guideline shall not cover medical devices that will be studied for thesis or research 
purposes and that the product owner has no intention of marketing/selling the device. It does 
not apply to clinical investigation of in  vitro diagnostic medical devices.  
IV. DEFINITION OF TERMS  
 
For purposes of this Order, the terms below shall be defined as follows:  
 
A. Certificate of Clinical Investigation Approval (CCIA) - a registration document issued 
by the FDA for the purpose of allowing the conduct of clinical investigation of a medical 
device in the country.  
 
B. Class A medical device – low risk medical device  
 
C. Clas s B medical device – low-moderate risk medical device  
 
D. Class C medical device – moderate -high risk medical device  
 
E. Class D medical device – high risk medical device  
 
F. Clinical Investigation - systematic investigation in one or more human subjects, 
undertaken  to assess the safety or performance of a medical device . It is synonymous 
with “Clinical trial” or “clinical study” .  
 
G. Clinical investigation plan  (CIP) - document that state(s) the rationale, objectives, 
design and proposed analysis, methodology, monitoring,  conduct and record -keeping of 
the clinical investigation  
 
H. Conflict of Inter est – a situation created when person s or entities in the public and/or 
private sectors involved in conducting research, making recommendations and decisions 
have personal, financial or any other interest that may influence decision -making in favor 
of the medical device industry.   
 
I. Contract research organization  (CRO ) - person or organization contracted by the 
sponsor to perform one or more of the sponsor's clinical  investigation -related duties and 
functions   
 
J. Investigator  - individual member of the investigation site team designated and 
supervised by the principal investigator at an  investigation site to perform critical 
clinical -investigation -related procedures or to make important clinical  investigation -
related decisions   
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 K. Investigator's brochure (IB) - compilation of the current clinical and non -clinical 
information on the investigational medical device(s), relevant to the clinical investigation  
 
L. Investigational medical device - medical device being assessed for safety or 
performance in a clinical investigation  
 
M. In vitro diagnostic medical device – any reagent, reagent product, calibrator, control 
material, kit, instrument, apparatus, equipment or system, whether used alone or in 
combination with any other reagent, reagent product, calibrator, control material, kit, 
instrument, apparatus, equipment or system, that is intended by its product owner to be 
used in vitro for the examination of any specim en, including any blood or tissue donation, 
derived from the human body, solely or principally for the purpose of providing 
information:  
1. concerning a physiological or pathological state or a congenital abnormality;  
2. to determine the safety and compatibility  of any blood or tissue donation with a 
potential recipient thereof; or  
3. to monitor therapeutic measures and includes a specimen receptacle  
 
N. License to Operate  – authorization issued by the FDA to a licensed research entity to 
conduct clinical investigation  of medical devices or other related activities  delegated by 
the sponsor  
 
O. Medical Device  – any instrument, apparatus, implement, machine, appliance, implant, 
software, material, or other similar or related article intended by the manufacturer to be 
used al one, or in combination, for human beings for one or more of the specific 
purpose(s) of diagnosis, prevention, monitoring, treatment or alleviation of  disease;  
diagnosis, monitoring, treatment, alleviation of , or c ompensation for an injury; 
investigation, replacement, modification, or support of the anatomy or of a physiological 
process; supporting  or sustaining life; preventing infection; control of conception; 
disinfection of medical devices; which does not achieve its primary intended action in or 
on the  human body by pharmacological, immunological or metabolic means but which 
may be assisted in intended function by such means.   
 
P. Monitor – refers to a qualified person responsible for overseeing the progress of a 
clinical investigation and to ensure that it is conducted, recorded, and reported in 
accordance with the CIP, written procedures, PNS ISO 14155:2018 or its subsequent 
amendments and other applicable rules and regulations  
 
Q. Product owner – in relation to a medical device, means any person who:  
1. supplies the medical device under his own name, or under any trade mark, design, 
trade name or other name or mark owned or controlled by him; and  
2. is responsible for designing, manufacturing, assembling, processing, labelling, 
packaging, refurbishing or mod ifying the medical device, or for assigning to tit a 
purpose, whether those tasks are performed by him or on his behalf.  
  
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 R. Principal investigator  – qualified person responsible for conducting the clinical 
investigation at an investigation site   
 
S. Research Et hics Committee (REC) – independent body whose responsibility is to 
review clinical investigations in order to protect the rights, safety and well -being of 
human subjects participating in a clinical investigation.  
 
T. Research entity – refers to sponsor, CRO or principal investigator for principal 
investigator initiated research.  
 
U. Serious adverse event - adverse event that  
1. Led to death  
2. Led to serious deterioration in the health of the subject, that either resulted in  
a. A life -threatening illness or injury, or  
b. A permanent impairment of a body structure or a body function, or  
c. In-patient or prolonged hospitalization, or  
d. Medical or surgical intervention to prevent life -threatening illness or injury or 
permanent impairment to a body structure or a body function  
3. Led t o fetal distress, fetal death or a congenital abnormality or birth defect  
 
Note: Planned hospitalization for a pre -existing  condition, or a procedure required by the CIP, without 
serious deterioration in health, is not considered a serious adverse event.   
 
V. Sponsor  - individual or organization taking responsibility and liability for the initiation 
or implementation of a clinical  investigation  
 
V. GENERAL GUIDELINES  
 
A. Clinical investigations on human subjects shall be carried out in accordance with PNS 
ISO 14155: 2018 Clinical investigation of medical devices for human subjects – Good 
clinical practice or its subsequent revision(s)  and other p ertinent rules and regulations . 
This includes every step in the clinical investigation from first consideration of th e need 
and justification of the study to publication of the results.  
 
B. The conduct of clinical investigation shall demonstrate compliance with relevant 
Essential Principles (including safety, clinical performance and acceptability of 
risk/benefit ratio associated with its use) as stipulated in the ASEAN AMDD and shall 
only be conducted if there are no sufficient data available through other sources (such as 
literature or preclinical testing).  
 
C. The following crucial steps shall be considered in clarifying the need for pre-market 
clinical  investigations:  
 
1. Identi fy relevant clinical Essential Principles  (for example, specifics of safety, 
clinical performance, acceptability of risk/benefit ratio) for the medical device and 
its intended purpose(s) and use(s)   
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 2. Perform risk management activities to help in identifying the clinical data necessary 
to control residual risks and aspects of clinical performance not completely resolved 
by available information e.g. design solutions, preclinical and material/technical 
evaluation, conformity with relevant standards  (ISO 14791) , labelling, etc .; 
3. Conduct a proper clinical evaluation to demonstrate which clinical data are necessary 
and can be adequately contributed to by other methods, such as literature searching, 
prior clinical investigations or clinical experience, and which cli nical data remain to 
be delivered by clinical investigation(s). Available clinical data for comparator 
medical devices shall  be carefully examined for compatibility and adequacy.  
 
D. To avoid unnecessary experimentation on human subjects, the following justi fications 
shall be considered for the need for clinical investigation:  
1. be necessary as assess ed as per sub-section V.C of this guideline ; 
2. be designed properly (see Annex E); 
3. be ethical as approved by REC  
4. follow a proper risk management procedure to avoid undue risks; and  
5. be compliant with all applicable statutory  and regulatory requ irements  
 
E. Trials of Class D medical devices, such as implants which may present a potential serious 
risk to health, safety or welfare of the participant, shall not be conducted on healthy 
volunteers. The current safety data on the medical devices shall be gathered, and the risks 
posed by the device shall be considered and evaluated.  
 
VI. SPECIFIC GUIDELINES  
 
A. License to Operate  
 
1. No CRO and/or sponsors shall be involved in the conduct of clinical investigation of 
a medical device for purposes of product r egistration /notification  without a License 
to Operate (LTO)  from the FDA . For principal  investigator -initiated research , the 
principal investigator shall apply for a License to Operate.  
 
2. No clinical investigation of a foreign sponsor may be conducted in the country unless 
an FDA -license d CRO takes up the responsibility for the foreign sponsor.   
 
3. Other FDA licensed establishments desiring to engage in clinical investigation of 
medical devices for purposes of registration /notification  of the product as either a 
sponsor or CRO shall secure the appropriate LTO.  
 
4. Entities engaged in the following investigatio n related du ties and functions delegated 
by a sponsor are required to secure an LTO as CRO:  
a. Oversight (e.g. ensuring qua lity assurance and/or quality control systems are in 
place to ensure clinical investigation of a medical device are conducted, data are 
gathered, and subsequently reported)  
b. Management of clinical investigation of medical devices  
i. Development of Clinical Investigation Plan/Protocol   
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 ii. Selection of investigator(s) a nd/or site(s)  
iii. Screening and recruitment of subjects  
iv. Data handling (e.g. collection, analysis/evaluation, and record keeping)  
 
5. Entities involved in the procurement/importation, storage, and/or distribution of 
investigational medical device  are not required to secure an LTO as CRO, unless they 
are involved in other activities mentioned above. These entities shall  follow other 
existing licensing requirements.  
 
6. Applicants shall submit the documentary requirements based on the checklist 
specifi ed in Annex A.  
 
7. The LTO shall be valid for three  (3) years for approved initial application and five 
(5) years for approved renewal application.  
 
8. Application for Variation  
 
a. The licensed research entity  shall apply for approval from the FDA of any change 
(major variation or minor variation) in the issued LTO. The types of major and 
minor variation and the documents to be submitted when applying for FDA 
approval are listed in Annex B.  
 
b. The licensed resear ch entity  applying for minor variations may continue 
business operations provided that an application for such variation has already 
been filed.  
 
B. Requirements for Class B, C or D Investigational Medical Devices  
 
1. Certificate of Clinical Investigation Approval (CCIA)  
 
a. The licensed research entity  shall apply for a CCIA with the FDA before 
undertaking clinical investigation of Class B, C or D medical devices.   
 
b. Applicants shall submit the documentary requirements listed in Annex D when 
applying for a CCIA . FDA may issue appropriate issuances to specify details or 
provide clarifications on the list of documentary requirements.  
 
c. The FDA shall  create a Regulatory Experts and Scientific Advisory Committee 
(RESAC) who will review the documents relative to the application for CCIA.  
 
d. Compliance to applicable international or Philippine National Standard(s)  shall 
be considered in the evaluation and approval of the application for CCIA .  
 
2. REC approval . The licensed research entity  shall obtain approval from a Philippine 
Health Research Ethics Board (PHREB) level 3  accredited  REC prior to the conduct 
of the clinical investigation of Class B, C or D medical devices.  The licensed research  
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 entity shall submit to FDA a co py of such REC approval within thirty (30) days after 
receipt of the approval.  
 
C. Requirements for Class A Investigational Medical Devices  
 
1. The licensed research entity  shall obtain only approval from a PHREB level 3 
accredited REC prior to the conduct of the clinical investigation of Class A medical 
devices . The licensed research entity shall present to the REC an explanation why the 
device was classified as Class A .  
 
2. The licens ed research entity shall notify the FDA of the REC approved clinical study 
of Class A medical device by providing a copy of the REC approval fifteen (15) days 
after receipt of the approval. All other provisions of this guideline shall be complied 
with when conducting a clinical investigation of Class A  medical devices.  
 
D. Requirements for Investigational Medical Device for Treatment of a Serious or 
Immediately Life -Threatening Disease or Condition  
 
The FDA shall issue a separate guideline for medical devices that are not yet approved 
for marketing but t hat will under go clinical investigation for a serious or immediately 
life-threatening disease or condition of patients for whom no comparable or satisfactory 
alternative device or other therapy is available.  
 
E. Exemption from LTO and CCIA Requirement  
 
The following categories of clinical investigations are exempted from securing LTO and 
CCIA  from FDA :  
 
1. A medical device undergoing consumer preference testing, testing of a modification, 
or testing of a combination of two or more devices in commercial dis tribution, if the 
testing is not for the purpose of determining safety or effectiveness and does not put 
the subject at risk.  
2. A device intended solely for veterinary use.  
3. A device shipped solely for research on or with laboratory animals and labeled in 
accordance with section VI.F.3 of this guideline.  
4. A custom -made medical device unless the device is being used to determine safety or 
effectiveness for commercial distribution.  
 
F. Labeling of Investigation al Devices  
1. An investigational device or its immediate package shall bear a label with the 
following information: the name and place of business of the manufacturer, importer , 
the quantity of contents, if appropriate, and the following statement: "CAUTION -
Investigational device. Exclusivey for use in a clinical investigation” The label or  
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 other labeling shall describe all relevant contraindications, hazards, adverse effects, 
interfering substances or devices, warnings, and precautions.  
2. The labeling of an investigational device shall not bear any statement that is false or 
misleading in any particular and shall not represent that the device is safe or effective 
for the purposes f or which it is being investigated.  
3. An investigational device shipped solely for research on or with laboratory animals 
shall bear on its label the following statement: "CAUTION -Device for animal testing 
only.”  
 
G. Import Permit  
 
To facilitate the release of the medical device intended for clinical research, the 
applicants shall apply for an Import Permit from the FDA. Documents to be submitted 
are listed in Annex C.  
H. Approval of the Application for Clinical Investigation  
 
1. FDA shall give the final decision to approve or deny an application based on the 
appropriate written recommendation by the RESAC.  
2. A document (CCIA ) granting approval for the conduct of a clinical investigation  shall  
be issued by FDA to the licensed research entity .  
 
I. Amendments  to Clinical Investigation  that need FDA Approval  
 
The following amendments in the clinical investigation shall require FDA approval prior 
to implementation:  
1. Amendment to the CIP   
a. Changes to the study objectives and study endpoints (safety and efficacy 
endpoints)  
b. Changes to inclusion and exclusion criteria  
c. Changes to the study treatment, major and significant study procedures and 
withdrawal criteria  
d. Change in Study Site and main investigator or Principal Investigator  
e. Any change in sp onsorship, contract delegation such as change of Contract 
Research Organization  
f. Increase or decrease in study population  
g. Any other amendment that will affect the safety of the subjects  
2. Amendment to the subject’s informed consent form  if the deviation will affect 
subject’s rights, safety and well -being  
3. Changes in key personnel (principal investigator)  
4. In addition to Sections VI. I.1 through VI. I.3, FDA may issue a separate issuance 
regarding the circumstances and/or amendments in the clinical investigation that 
need FDA approval as may be deemed necessary and appropriate.  
 
  
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 J. Conflict of Interest  
 
All hospitals, personnel, and parties involved in im plementing clinical researches  or 
clinical investigation of medical devices  (including consultants, contractual, project 
based, trainees) shall follow/comply the with the FDA  guidelines on the full disclosure 
and man agement of conflict of interest.    
 
K. Inspection /Audit  by FDA  
 
The FDA shall have the authority to enter any establishment for (1) inspection /audit  of 
compliance and/or (2) verification of submitted documents in relation to any application 
for issuance of appropriate authorization. A separate guideline  shall be issued by FDA 
for the audit /inspection  relative to clinical investigation of medical devices .  
 
L. Termination of the Study  
 
At any time, FDA may terminate all clinical investigation that have failed to comply with 
this guideline, PNS ISO 14155: 2018 Clinical investigation of medical devices for human 
subjects – Good clinical practice or its subsequent revision(s) and/or other pertinent rules 
and regulations; or after careful evaluation of the incident report  involving serious 
adver se event , result of inspection /audit , deviation report, and information and findings 
from other National Regulatory Authority and international bodies . 
 
M. Post-Market Clinical Follow -up Studies  
 
A separate guideline shall be issued by FDA regarding post -mark et clinical follow -up 
studies in accordance with the ASEAN Agreement on Medical Device Dire ctive and 
other pertinent laws.  
 
VII. PROHIBITION OF PROMOTION AND OTHER PRACTICES  
 
A sponsor, CRO or pri ncipal investigator or any person acting for on or behalf of a sponsor, 
CRO or principal investigator shall not:  
A.  Promote or test market an investigational device, until after FDA has approved the device 
for commercial distribution.  
B.  Commercialize an investigational device by charging the subjects or investigators for a 
device a price larger than that necessary to recover costs of manufacture, research, 
development, and handling.  
C.  Unduly prolong an investigation. If data developed by the investigation indicate that 
premarket approval cannot be justi fied or that the device  will not comply with an 
applicable performance standard or an amendment to that standard, the sponsor shall 
promptly terminate the investigation.  
D.  Represent that an investigational device is safe or effective for the purposes for  which 
it is being investigated.   
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VIII.  RESPONSIBILITIES OF LICENSED RESEARCH EN TITY   
In addition to the responsibilities of the sponsor stipulated in PNS ISO 14155: 2018  and/or 
its subsequent amendments and in the National Ethical Guidelines , the sponsor shall be 
responsible for the following:  
A. Upload in the Philippine Health Research Registry ( http://registry.healthresearch.ph ) the 
information related to the clinical investigation of medical devices it is conducting within 
thirty (30) days after receipt of CCIA  and clinical investigation for Class A medical 
devices to conduct the clinical trial/investigation has been granted .  
 
B. Prompt  submission , after awareness,  of adverse device event  or serious adverse device 
event , if any, prepared and signed by the principal investigator. The sponsor shall indicate 
if the same report was received by the monitor  and REC.  
 
C. Prompt submission of deviation report  if any, prepared and signed by the principal  
investigator. The sponsor shall indicate if the same report was received by the monitor  
and REC . 
 
D. Notify  FDA and participating investigators of any withdrawal of approval of an 
investigation or part of an investigation by a reviewing REC within 5 working days after 
receipt of the withdrawal of approval.  
 
E. Notif y the reviewing REC and participating investigators of any withdrawal of FDA 
approval  (CCIA) within 5 working days after receipt of the withdrawal of approval.  
 
F. Prompt notification of any changes in key personnel (principal investigator – requires 
FDA approval) of the on -going clinical study/investigation. The licensed research entity 
shall submit to FDA, at 6 -month intervals, a current list of the names and addresses of all 
investigators participating in the investigation. The sponsor shall submit the first such list 
6 months after FDA approval.  
 
G. Submit to FDA progress report at least yea rly. 
 
H. Notify FDA and the REC of any request tha t an investigator return, repair, or otherwise 
dispose of any units of a device. Such notice shall occur within 30 working days after the 
request is made and shall state why the request was made.  
 
I. Notify FDA within 30 working days of the completion or termination of the investigation  
of Class B, C or D and submit a final report to FDA, REC and participating investigators 
within 6 months after completion or termination. In the case of investigation of Class A 
medical device, notify FDA and REC within 6 months after termination or completion.  
 
J. Prompt  submission of any information  or findings on similar studies from other  countries 
that may have bearing on the health of the subjects.   
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 K. Prompt notification of any a mendments to the approved CIP  
 
L. Report pregnancy and outcome of pregnancy during the conduct of clinical investigation 
of medical device (if applicable)  
 
M. Ensure that essential clinical investigation documents are maintained in the investigation 
site and sponsor files as specified in PNS ISO 14155:2018 or its subsequent 
amendment/s.  
  
IX. RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR  
 
The responsibilities of t he principal investigator shall be those specified in PNS ISO 14155 -
2018: Clinical investigation of medical devices for human subjects – Good clinical pra ctice 
or its subsequent amendment(s)  and those specified in the National Ethical Guidelines for 
Health  and Health -Related Research.  
   
X. RESPONSIBILITIES OF A MONITOR/QUALIFIED PE RSON   
A monitor/ qualified person within the organization of the licensed establishment must be 
identified. The qualified person must be in charge of the overall operations of the 
establishment which shall include:  
A. Monitoring/supervision of all operations of the establishment . 
B. Observance of PNS ISO 14155 :2018  and/or its subsequent amendments and other 
applicable international best practices.   
C. Ensuring that all clinical investigation  have satisfactorily complied with the requirements 
of the research ethics committee, as well as other relevant government agencies.  
D. Ensuring any adverse events experience d by subjects/patients are properly handled, 
documented, and reported to FDA  
E. Ensuring  compliance of the establishment with existing regulations.  
F. The abovementioned responsibilities should be properly translated into a Standard 
Operating Procedure (SOP) which shall be duly validated during post -licensing 
inspection /audit by the FDA.  
 
XI. RESPON SIBILITIES OF FDA  
 
A. Process ing of  application for License to Operate, CCIA and Import Permit relative to the 
conduct of clinical investigation of medical devices.  
B. Coordinating with the REC  on matters relevant to the conduct of the ethical review of 
clinical investigation protocols  
C. Receiving and acting on amendments and other changes to the clinical investigation 
protocol  
D. Monitoring compliance to this guideline and to mandatory requirement f or participation 
in the Philippines Clinical Trial Registry  
E. Conduct on -site inspection /audit  of clinical investigation  and licensed clinical research 
entity  covered by this guideline.   
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 F. Coordination with the RECs as well as PHREB on all matters related to the applications 
under review to resolve whatever issues will arise.  
 
XII. SCHEDULE OF FEES  
The applicant shall be guided by the latest FDA circular on the schedule of fees.  
XIII.  TRANSITORY PROVI SION  
Upon effectivity of this Order, all sponsors, CROs and principal investigator for investigator 
initiated research and all other establishments/research institutions within the scope of this 
Order shall be given six (6) months  from the date of publication of this Order in leading 
newspaper to comply with the provisions  of this guideline.  
XIV. SEPARABILITY CLAUSE  
If any of the provisions of this Administrative Order is found by a court of competent 
jurisdiction to be void or unenforceable, in whole or in part, such provision shall be deemed 
deleted from this Administrative Order but the remaining provisions thereof  not affected 
shall remain in full force and in effect.   
XV. REPEALING CLAUSE  
Sections V.6 and VII.C of DOH Administrative Order No. 2018 -0002, other e xisting 
administrative orders, circular, memoran da and other issuances inconsistent with this 
Administrative  Order are hereby repealed  or amended a ccordingly.  
XVI. EFFECTIVITY  
This Administrative Order shall take effect after fifteen (15) days following the completion 
of its publication in a newspaper of general circulation and filing with the University of the 
Philippines - Office of the National Administrative Register (UP -ONAR).  
 
 
 
                                          FRANCISCO T. DUQUE III, MD, MSc  
                  Secretary of Health  
 
 
 
  
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 ANNEX A  
DOCUMENTARY  REQUIREMENTS  
A. LICEN SE TO OPERATE (LTO) INITIAL APPLICATION  
 
1. Proof of business name registration  (not applicable for principal investigator initiated 
research)  
 For single proprietorship – Certificate of Business Registration issued by the 
Department of Trade and Industry  
 For corporation, partnership and  other juridical person – Certificate of Registration 
issued by the Securities and Exchange Commission (SEC) and Articles of 
Incorporation  
 For government -owned or controlled corporation /university  – the law highlighting 
the provision creating the establish ment /university  
2. For principal investigator initiated research, authority from the president of the research 
institution where the clinical investigation will be conducted  
3. Credentials of monitor/ qualified person  
 The Certificate of Attendance to basic and ad vanced GCP courses or any equivalent 
courses/training for medical devices of the identified qualified person must be 
submitted  
4. Risk management plan (contains details on how to identify, characterize, prevent or 
minimize risk relating to the clinical invest igation project they engage with ) 
 
B. RENEWAL LTO APPLICATION  
 Copy of Certifications issued as a result of LTO Variation  (if applicable)  
 
C. REISSUANCE OF LOST OR DESTROYED LTO  
1. Letter of request  
2. Affidavit of loss or destruction  
 
D. VOLUNTARY CANCELLATION OF LTO  
 Letter of request  
 
 
 
 
 
  
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 ANNEX B  
DOCUMENTARY REQUIREMENTS FOR VARIATION APPLICATION FOR 
SPONSORS AND CONTRACT RESEARCH ORGANIZATION  
A. MAJOR VARIATIONS  (Requires inspection prior to approval of variation)  
1. Change of Ownership  
a. Proof of business name registration  reflecting the name of new owner  
b. Deed of sale or transfer of rights of ownership  
c. Updated delegation of authority (where applicable)  
 
2. Transfer of Location  
 Proof of business name registration reflecting the new address  
 
3. Change of key person  
 Updated delegation of authority  
 
B. MINOR VARIATIONS  – PRIOR APPROVAL  
1. Additional activity (refers to an additional activity engaged by the CRO (e.g. oversight 
with additional development of protocol and/or design activity) or change from the 
initially approv ed activity (e.g. data handling to oversight)  
 Contract agreement to prove activity  
 
2. Expansion of establishment  (refers to the expansion made which is adjacent to the 
existing location of the establishment or inclusion of additional floors where the building 
is occupied)  
 Letter of request  
 
3. Change of Business Name (no transfer of location or change of ownership)  
 Proof of business name registration reflecting the new name of the establishment  
 
4. Zonal Change in Address (refers to change of the name/number  of the street/building 
without physical transfer of the establishment)  
 Document issued by the local municipality as proof of zonal change  
 
5. Change of Delegated Sponsor Activities (refers to addition or deletion of any delegated 
sponsor -clinical activities)  
a. Updated delegation of authority  
b. Contract agreement to prove activity/termination of contract or conformance letter 
(where applicable)  
 
C. MINOR VARIATION – NOTIFICATION  
Change of Monitor/ Qualified Person (there is a change in the initially identi fied qualified 
person with no change of delegated sponsor activity)  
 Credentials of qualified person   
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 ANNEX C  
DOCUMENTARY REQUIREMENTS FOR APPLICATION FOR IMPORT PERMIT 
FOR MEDICAL DEVICE INTENDED FOR CLINICAL INVESTIGATION  
1. Application Form  
2. Letter addressed to the Director of CDRRHR stating that the medical device will be used 
solely for research and is not intended for sale. The letter should contain the following 
information:  
a. Complete list of devices indicating the quantity , brand and the complet e name of the 
manufacturer of the product  
b. Declaration that the organization shall be the sole entity responsible for the medical 
devices and that the FDA will not be held liable for any safety issue concerning th e 
product   
3. Packing list  
4. Proof of payment  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
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 ANNEX D  
DOCUMENTARY REQUIREMENTS FOR APPLICATION FOR CLINICAL 
INVESTIGATION APPROVAL FOR CLASS B, C AND D  MEDICAL DEVICES  
1. Duly accomplished application form  
2. A complete report of prior inve stigations of the device  
3. A description of the methods, facilities, and controls used for the manufacture, 
processing, packing, storage, and, where appropriate, installation of the device  
4. An example of the agreement to be signed by the investigators and a list of the names 
and addresses of all investig ators . The agreement shall include:  
a. The investigator’s curriculum vitae.  
b. Where applicable, a statement of the investigator's relevant experience, including 
the dates, location, extent, and type of experience.  
c. If the investigator was involved in an investigation or other research that was 
terminated, an explanation of the circumstances that led to termination  
d. A statement of the investigator's commitment to:  
i. Conduct the investigation in accordance with the agreem ent, the investigational 
plan, this guideline and other pertinent laws and regulations and conditions of 
approval imposed by the reviewing REC or FDA;  
ii. Supervise all testing of the device involving human subjects; and  
iii. Ensure that the requirements for obtaining informed consent are met.  
e. Disclosure of conflict of interest  
5. Certification that all investigators have signed the agreement, that the list of 
investigators includes all investigators participating in the study, and that new 
investigators will sig n the agreement before being added to the study.  
6. A list of the name s, address es, and chairperson s of all REC s that ha ve or will be asked 
to review the investigation .  
7. The name and address of any institution other than those identified in item 6 at which 
a part of the investigation may be conducted .  
8. Investigator’s brochure  
9. Clinical investigation plan   
10. Sample of labelling attached to investigational device  
11. Insurance certificates  
12. Copies of all informed consent forms and all related information materials to b e 
provided to subjects including translations  
13. Any other relevant information that the FDA may request for review of application  
 
 
 
 
 
 
 
 
  
17 
 ANNEX E 
 
GENERAL PRINCIPLES OF CLINICAL INVESTIGATION DESIGN   
 
The design of the clinical investigation, including the study objectives and statistical 
considerations, should provide the clinical data necessary to address the residual risks, 
including aspects of clinical performance. Some factors that may influence the extent of 
data requirements include, but are not limit ed to, the following:  
1. Type of medical device and/or regulatory experience ; 
2. Novel technology /relevant previous experience ; 
3. Clinical applications/indications ; 
4. Nature of exposure to the medical device, e.g.: surface contact, implantation, 
ingestion ; 
5. Risks inh erent in the use of the medical device, e.g.: risk associated with the 
procedure ; 
6. Performance claims made in the medical device labelling (including  instructions for 
use) and/or promotional materials;  
7. Component materials;  
8. Disease process (including severit y) and patient population being treated;  
9. Demographic, geographic and cultural considerations (e.g.: age, race, gender, etc.);  
10. Potential impact of medical device failure;  
11. Period of exposure to the medical device;  
12. Expected lifetime of the medical device; and  
13. Availability of alternative treatments and current standards of c are and ethical 
considerations