Clinical Research Regulation For Mexico and Thailand

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, NOM-012-SSA3-2012, and COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is the regulatory authority responsible for reviewing, evaluating, and approving all requests for research protocol authorization in human beings and/or their biological samples using registered or unregistered investigational products (IPs). Per NOM-257-SSA1-2014, COFEPRIS requires biotechnological drugs used in clinical research studies to follow the same protocol authorization procedure as is required for all IPs. COFEPRIS-GCP and HlthResRegs specify that the scope of COFEPRIS’s assessment includes all clinical trials (Phases I-IV).

As indicated in HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the health institution’s Research Ethics Committee (REC) and Research Committee where the study is being conducted, and when applicable, the Biosafety Committee. Therefore, the COFEPRIS and EC reviews may not be conducted in parallel. In addition, per NOM-012-SSA3-2012, the REC’s favorable decision is only later submitted to COFEPRIS with the protocol authorization request. Refer to the Ethics Committee section for detailed information on the REC, and the Initiation, Agreements & Registration section for additional information on the Research Committee and Biosafety Committee.

Clinical Trial Review Process

As delineated in Reg-COFEPRIS and MEX-53, COFEPRIS’s Sanitary Authorization Commission (Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on requests for human research protocol authorizations. According to MEX-104, CAS’s work is performed by its protocols area. Per MEX-15, CAS’s technical/protocols area conducts its work via COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services.

As indicated in G-HumResProt and G-ResProtocolAmd, the applicant must submit an application to the CIS (MEX-37) to request protocol authorization or modification/amendment of a protocol authorization, and the application is then forwarded to CAS’s technical/protocols area for evaluation. (Note: COFEPRIS refers to applications as requests or procedures). Per G-HumResProt, the designated evaluator reviews and evaluates the information, comparing the information presented to assess whether it complies with current Mexican legislation on the matter. The information is also evaluated for completeness and accuracy and is reviewed to detect deficiencies or anomalies in the documentation or in the study process. Once the evaluator issues a resolution of authorization or a prevention letter, it is forwarded to the head of CAS for signature.

Following its review of the application documentation, per G-HumResProt and G-ResProtocolAmd, CAS’s technical/protocols area issues an official resolution of authorization or a prevention letter (in which additional or missing information is requested). If authorized, the clinical study may begin. However, if a prevention letter is received, the applicant must respond to what is stated in the letter and resubmit a request for continued processing after addressing all of the issues raised. CAS’s technical/protocols area will issue a final resolution following resubmission of the application for protocol authorization or modification/amendment. G-HumResProt also indicates that for in-person submissions, applicants can go to the CIS (MEX-37) to obtain the resolution.

G-ResProtocolAmd specifies that protocol modifications may be submitted to amend the research protocol, amend the informed consent/assent form, update the clinical and/or preclinical sections of the investigator’s brochure (also known as investigator’s manual in Mexico), remove or add research center(s)/research institution(s), or provide updated clinical and/or preclinical security/safety IP information. Refer to G-ObsrvStdies information on submitting applications to conduct risk-free research (observational studies), and G-BioequivStud for information on submitting applications to conduct bioequivalence studies.

Additionally, as indicated in G-DIGIPRiS-ResProts, once an official authorization from COFEPRIS is obtained, some of the data provided by the applicant via COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86), will be migrated to the CIS (MEX-37) and to the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). According to MEX-109, the G-RNECManual is useful for information on registering with RNEC for clinical trial applications submitted in person at the CIS (MEX-37). See also G-DIGIPRiS-DocComp for instructions on validating and comparing resolutions issued through DIGIPRiS (MEX-86) for research protocols). See Submission Process section for detailed DIGIPRiS (MEX-86) submission requirements.

Reg-HlthProd further explains that applicants must submit a request to COFEPRIS to obtain a sanitary registration for biosimilar biotechnological drug products. The specific requirements for the approval of each biosimilar biotechnological drug (e.g., in vitro studies, preclinical study reports, and comparative pharmacokinetic study reports) will be determined by the Ministry of Health, who will take into consideration the opinion of the Committee of New Molecules. When there is no relevant information in the Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements, nor in national guides or monographs, the Ministry may evaluate biosimilar tests using clinical data obtained from biosimilar biotechnological drug studies conducted in other countries. However, clinical trials are required to be conducted in Mexico when an applicant requests the renewal of an approval for a biosimilar biotechnological drug product. According to MEX-91, COFEPRIS’s acceptance of data produced abroad will accelerate the introduction of biosimilar drug products into Mexico. Additionally, per MEX-120, COFEPRIS has implemented modifications to NOM-177-SSA1-2013, the standard which establishes the tests and procedures to demonstrate that generic drugs or biosimilar biotechnological drugs comply with established interchangeability tests and delineates requirements for the authorized third parties that perform these tests. Pursuant to NOM-177-SSA1-2013-Mod, the modification expands the standard to include studies that are carried out in Mexico as well as in other countries to demonstrate interchangeability and biocomparability. MEX-120 also notes the modifications in NOM-177-SSA1-2013-Mod are designed to expedite the registration of generic and biosimilar biotechnological drugs. See NOM-177-SSA1-2013 and NOM-177-SSA1-2013-Mod for details.(Note: In Mexico, biosimilar is also referred to as biocomparable.)

UHAP Evaluations

Per HlthResRegs, prior to submitting an authorization request, applicants may also obtain a pre-assessment evaluation by an authorized third party that helps to facilitate COFEPRIS’s review. MEX-21 and MEX-10 explain that rather than submitting the application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment (third party) evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). MEX-9 states that the CCINSHAE oversees (12) UHAPs. According to MEX-90, the Faculty of Medicine of the Autonomous University of Nuevo León (Facultad de Medicina de Universidad Autónoma de Nuevo León (UANL)) UHAP is another third-party unit authorized by COFEPRIS to assist in the evaluation and assessment of human research protocols. Refer to MEX-19, MEX-69, and MEX-70 for detailed information on the CCINSHAE, the IMSS, and the UANL UHAP application submission requirements and evaluation process. See also HlthResRegs for information on the third party authorization process by the Secretariat, and MEX-10 and MEX-121 for additional information on authorized third parties. See Timeline of Review section for timeline information on submitting UHAP applications.

According to MEX-10, the UHAP has a maximum of 30 calendar days to respond to an evaluation request. See the Scope of Assessment and Submission Process sections for detailed UHAP information.

1-2

In More Detail

9.2

What is a Comprehensive Service Center?

“Process for handling procedures 04-010 and 09-012 in DIGIPRiS”

XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements and Steps

Requirements (13-15, 26, and 40), Validity, and Steps

Preamble, 1.3, 1.7, and 2

Title II (Chapter II, Article 17 Bis), Title III (Chapter III, Article 41 Bis), Title V (Chapter I, Articles 98 and 102), and Title XVI (Chapter III, Article 391 Bis)

Chapter I (Articles 1-3) and Chapter IV (Article 14)

Article 177

Title II (Chapter I, Article 14), Title III (Chapter I, Article 62) and (Chapter II, Articles 65-66, and 69), and Title V (Chapter I, Articles 99, 102, and 109-111)

2.1-2.2

7

4.2, 5.2, 6.3, 9.2, and 10.3

Last content review/update: March 21, 2024

Overview

In accordance with the DrugAct and ClinImprtOrdr, the Thai Food and Drug Administration (Thai FDA) is responsible for overseeing the import or ordering of drugs for clinical research purposes, and also uses this authority to indirectly regulate drug clinical trials in humans. Per ClinSampleProd and DrugProdReqs, the Thai FDA is also responsible for approving requests for permission to produce drug samples for the registration of drug formulas for human research studies. As per G-ResEthics, the scope of the Thai FDA’s assessment includes Phases I through IV clinical trials for new drugs (also referred to as “modern drugs”), traditional drugs (drugs intended for use in the practice of traditional medicine or to cure animal disease), unregistered drugs, registered drugs being studied in new doses or for indications not previously approved, and locally produced drugs that require efficacy testing.

As indicated in ClinImprtOrdr, ClinSampleProd, and ECRegProc, the Thai FDA’s approvals of a drug import license and of a request for permission to produce sample drugs for human research studies are dependent upon obtaining proof of ethics committee (EC) approval to conduct the clinical trial by a Thai FDA approved EC. ClinSampleProd and ClinImprtOrdr further specify that for both types of approval requests, the application is either submitted to the Thai FDA after the research project and all of the research site(s) have been approved by an EC, or in parallel, pending review by the relevant EC.

Clinical Trial Review Process

As set forth in ClinImprtOrdr, ClinSampleProd, and G-CT-DIPApp, the Thai FDA coordinates the review of applications submitted to obtain drug import licenses for clinical research purposes (N.Y.M.1) and applications submitted to request permission to produce drug samples for human research studies (P.Y.8). Per ClinImprtOrdr and ClinSampleProd, an applicant should submit the application along with supporting documents to the Medicines Regulation Division.

Per G-CT-DIPApp, upon receipt of a drug import license application (N.Y.M.1) package, the Thai FDA’s One Stop Service & Consultation Center (OSSC) (THA-35) sends the application package to an officer in the Thai FDA’s International Affairs and Investigational Drug Section. After administrative processing and troubleshooting, the officer will send the application package to the assigned reviewer to proceed. The reviewer then receives the application package and performs a technical assessment. If the reviewer determines the package is technically correct, then it will be forwarded to the Thai FDA for approval. ClinImprtOrdr specifies that the Secretary-General is responsible for authorizing all drugs to be imported into the country. (See Submission Process and Timeline of Review sections for details on the administrative and technical processing and review timelines.)

According to the DrugAct, the Thai FDA’s approval of a drug import license application for clinical research purposes also serves as an import license that allows the sponsor to import investigational drugs into Thailand. The license will remain valid until December 31^st of the year of issue. The license holder who would like to renew the license must file an application for renewal prior to the license expiration date. (See the Manufacturing & Import section for detailed license renewal instructions).

Per G-CT-DIPApp, after the import license is granted, the applicant must inform or request permission from the Thai FDA prior to initiating the following:

Changes to clinical trial drug supplies
Changes to an approved protocol (protocol amendment) or changes related to or affecting participant safety

In cases where the sponsor is required to immediately make one (1) or more amendments because the clinical trial or the use of investigational products in the trial endangers the health of a clinical trial participant or other person, the applicant may immediately make the amendment without prior review by the Thai FDA. A corresponding notification clearly identifying the change and the rationale for immediate implementation of the change must be filed within 15 working days after the amendment implementation date. A corresponding notification letter referring to the related approved import license along with supplemental documents to be provided in the Form for Requesting Corrections/Additional Clarifications are also required (see ClinImprtOrdr (Appendix 12) and THA-18 (Appendix 12)).

Per G-CT-DIPApp, after the import license is granted, the applicant must also notify the Thai FDA of changes to the protocol that do not affect the safety of the trial participants.

No information is currently available on the review process for P.Y.8 application submissions.

Per ClinImprtOrdr and ClinSampleProd, the Ministry of Public Health (MOPH) may also establish an academic committee or subcommittee for certain drugs requiring special supervision (e.g., the Academic Subcommittee on AIDS Vaccine Trials).

As delineated in ClinImprtOrdr and ClinSampleProd, the Thai FDA has procedures to monitor the research project before, during, and after the trial ends or is terminated. ClinImprtOrdr and ClinSampleProd specify that the authorized Thai FDA officer will contact the licensee to schedule an inspection appointment and provide a letter notifying the licensee at least seven (7) days in advance, except in those cases where the Thai FDA has a special request to carry out an inspection immediately and does not notify the licensee in advance. Refer to ClinImprtOrdr and ClinSampleProd for detailed licensee information on preparing for the inspection. See also THA-18 (Appendix 11) and THA-76 (Appendix 7) for the self-examination form containing the Thai officer’s inspection summary).

Refer to the Submission Process section for submission requirements.

Appendices 1-4, 7-9, and 12

Appendices 2-4, 11-13, and 17

7

2-3 and 15

Section 4, Chapter I (10), Chapter II (12 and 17-18), and Chapter V (46)

Preface, Summary of Changes in this Edition, 1-3, and Appendices 1-4, 7-9, and 12

Preface, 1-3, and Appendices 1-5, 11-13, and 17

5 and 9-10

Appendix 12

Regulatory Fees

Last content review/update: November 8, 2024

Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)

As indicated in G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, MEX-84, G-DIGIPRiS-ResProts, the applicant is responsible for paying a non-refundable fee (also referred to as “Proof of Payment of Rights”) to submit a request for protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)).

According to MEX-37 and MEX-15, applicants may obtain the fee information for a specific procedure or service using COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37). Per MEX-15, CIS is a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services. MEX-15 and MEX-37 indicate that applicants may call CIS (MEX-37) or schedule an appointment for assistance with determining the COFEPRIS procedure code to obtain the correct processing instructions and fees and for help with submitting the payment. See MEX-37 and MEX-15 for information on scheduling an appointment with CIS.

G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, and MEX-11 provide requirements and corresponding costs to submit requests to COFEPRIS for protocol authorizations or amendments/modifications. The costs linked to these procedures are as follows:

Request for authorization of research protocol in humans for medicines, biological, and biotechnological: 7,553.00 Mexican Pesos (G-HumResProt and MEX-11)
Authorization of research protocol in humans (bioequivalence studies): 7,553 Mexican Pesos (G-BioequivStud)

Authorization of research protocol without risk (observational) in humans: 7,553.00 Mexican Pesos (G-ObsrvStdies)
Amendment or modification to the research protocol or inclusions to the protocol: 5,665 Mexican Pesos (G-ResProtocolAmd and MEX-11)

In addition, per G-UnregDrugImprts, the fee to request a health permit to import investigational products for research purposes is 6,727.65 Mexican Pesos.

As indicated in MEX-10, the fee for requesting a pre-assessment application evaluation through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) is 60,000 Mexican Pesos. The cost is the same for obtaining a review from any of the UHAPs within CCINSHAE. In addition, if the applicant selects a scientific committee within an institution that has a UHAP, the cost is 40,000 Mexican Pesos. The cost for each amendment is 3,500 Mexican Pesos, and corrections to the pre-assessment document are free.

Payment Instructions

As explained in MEX-50, G-HumResProt, G-BioequivStud, G-ObsrvStdies, and G-ResProtocolAmd, applicants should make payments for these procedures and services through an authorized credit institution using E5cinco (MEX-52). (See also MEX-52 for a link to participating financial institutions). Per MEX-50 and MEX-52, E5cinco is an electronic scheme created to enable users to submit the Payment of Rights, Products and Benefits (Derechos, Productos y Aprovechamientos (DPAs)) to a participating credit institution through its Internet portal or banking window. See also MEX-51 and MEX-6 for detailed DPA payment instructions via E5cinco (MEX-52).

In addition, G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, and MEX-84 provide a website link, Help Sheet for the Generation of the Fee Payment Format, for users to generate a payment form for fees based on their procedure in order to make a payment at the banking institution of their choice. Refer to G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, MEX-84, and G-DIGIPRiS-ResProts for additional information on this process.

Requirements (32) and Cost

2. General Requirements (2.2 Proof of Payment of Fees)

Other Permits or Authorizations - Supplies for Health (p.10)

Where can I go to submit my paperwork to COFEPRIS? and What is a Comprehensive Service Center?

XIII. Specific Sections of the Procedure on the Platform (III)

Requirements (2) and Cost

Cost

Requirements (2) and Cost

Last content review/update: March 21, 2024

Thai Food and Drug Administration

In accordance with ClinDrugFees, the applicant is required to pay a fee to the Thai Food and Drug Administration (Thai FDA) to submit an application to request permission to import or order drugs for research purposes in Thailand. The ClinDrugFees states that the Thai FDA requires an administrative processing fee of 1,000 Baht to review and verify the correctness of certain application requests related to authorization, including:

Applications to request permission to import or order drugs into the Kingdom for research purposes without registering a drug formula (N.Y.M.1 form) (See ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2) for N.Y.M.1 form)
Applications for drug samples produced for research studies (P.Y.8 form) (See ClinSampleProd (Appendix 1) and THA-76 (Appendix 1) for P.Y.8 form)

In addition, per ClinDrugFees and THA-78, the Thai FDA charges the following fees for the technical evaluation of documents of any application request related to authorization:

Application for permission to import or order drugs for research purposes in the country (N.Y.M.1) or to request permission to register and produce sample drugs for human research studies (P.Y.8): 4,000 Baht
Application to expand the scope of a license to produce drug samples and register new drugs for human research studies (for drugs in bioequivalence studies): 1,000 Baht
New research drug application to expand the scope of a license to produce drug samples and register a new drug for human research studies (for drugs other than those in bioequivalence studies): 4,000 Baht
Application to amend and request specific changes related to the application requests listed in the preceding bullets: 500 Baht
Requesting a certificate of pharmaceutical product (Certificate of Pharmaceutical Product/Certificate of Free Sale): 500 Baht
Request for review of accuracy and translation of Good Manufacturing Practice (GMP) assessment report from Thai version to English version: 1,500 Baht

In addition, per ClinImprtOrdr and ClinSampleProd, in the case of the applicant designating a power of attorney to submit a paper application in person or via PDF file, the Stamp Duty fee is 30 Baht per attorney designation.

Payment Instructions

According to the Thai FDA’s One Stop Service & Consultation Center (OSSC) (THA-35) and THA-66, the OSSC’s finance section provides payment services in cases where expenses need to be paid for various submissions, and accepts multiple payment methods including the cash payment counter, cashier’s check, credit cards, and mobile banking applications for the processing of application fees. However, per THA-79, in order to submit an electronic payment using the Thai FDA’s Skynet E-Submission System (THA-54), the applicant must first submit documentation and supporting evidence to request access as required by the OSSC. Once the OSSC approves e-submission system access, the applicant can submit a payment electronically to request a drug importation waiver via THA-54. See Submission Process section for detailed submission instructions and documentation requirements to access THA-54. Refer to THA-57 for the Skynet e-submission user manual and THA-87 for a guide to request a drug importation waiver via THA-54.

Appendix 1

Appendix 2

Items 2, 11, 33, 34, and 49

1.14 and Appendices 1 and 7

1.16 and Appendices 2 and 11

Preamble and Tables 1 (Item 4.5 and Note) and 2 (Item 10)

Ethics Committee

Last content review/update: November 8, 2024

Overview

As delineated in GenHlthLaw, HlthResRegs, REC-Op, REC-Op-Ref, G-RECs-Op-2018, and NOM-012-SSA3-2012, Mexico has a decentralized process for the ethics review and approval of clinical trial research. Accordingly, every health care institution which carries out research activities in human beings is required to have a Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) that is responsible for evaluating and ruling on research protocols in human beings. RECs are subject to current legislation and the criteria established by the National Bioethics Commission (Comisión Nacional de Bioética (CONBIOÉTICA)).

RECs must also comply with guidelines for the ethical evaluation of research involving human beings as delineated in GenHlthLaw, G-RECs-Op-2018, HlthResRegs and NOM-012-SSA3-2012. Pursuant to G-RECs-Op-2018, RECs must adhere to international guidelines relevant to research with human beings including the Declaration of Helsinki (MEX-76) and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MEX-22)).

In addition, per GenHlthLaw, HlthResRegs, and NOM-012-SSA3-2012, every health institution where research is conducted is required to establish a Research Committee and a Biosafety Committee. Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, REC and Research Committee approval is required for each trial site where a study is being conducted, and when applicable, Biosafety Committee approval is required as well.

GenHlthLaw further notes that in addition to establishing an REC, public, social, or private sector health care establishments of the National Health System must have a Hospital Bioethics Committee for the resolution of problems arising from medical care along with engaging in other bioethical and ethical related activities.

As per HlthResRegs, REC-Op, REC-Op-Ref, G-RECs-Op-2018, and NOM-012-SSA3-2012, Hospital Bioethics Committees also operate through CONBIOÉTICA. MEX-47 specifies that CONBIOÉTICA is responsible for registering RECs and Hospital Bioethics Committees. See the Oversight of Ethics Committees section for details on ethics committee registration.

Ethics Committee Composition

Research Ethics Committee Composition

As indicated in GenHlthLaw, RECs must be interdisciplinary gender-balanced groups composed of medical personnel from different specialties; professionals from psychology, nursing, social work, sociology, anthropology, philosophy, or law fields who have bioethics training; and community representatives affected by the health condition under study or other health services users who may or may not be attached to the health unit or institution. In addition to the previously stated criteria, G-RECs-Op-2018 indicates that these professionals should have a professional license and accredited training and experience in research ethics, good clinical practice, bioethics, and have experience related to the research area they will be evaluating. HlthResRegs further notes that the REC must consist of at least three (3) scientists including both genders and recommends that at least one (1) of them be based outside the health institution. The medical professionals should also represent the moral, cultural, and social values of the research groups. By comparison, NOM-012-SSA3-2012 states that REC health professionals should have expertise in the subjects investigated at the institution, regardless of whether the professionals have experience in the scientific methodology applied to the research. Further, the community representatives should embody the moral, cultural, and social values of the research participants.

Per REC-Op and REC-Op-Ref, the REC members must also be recognized and able to document their professional excellence in research/research bioethics, have personal records that prove ethical suitability and conduct, and advanced knowledge in qualitative and quantitative methodology. Additionally, GenHlthLaw, G-RECs-Op-2018, and NOM-012-SSA3-2012 state that REC members may or may not be based at the associated institution where the study is being conducted.

Additionally, NOM-012-SSA3-2012 specifies that the REC should be composed of a minimum of three (3) scientists, plus community representatives, as deemed necessary, with a total of at least six (6) members and a maximum of 20. G-RECs-Op-2018, REC-Op, and REC-Op-Ref note that the REC should comprise a president, at least four (4) members, one (1) of whom will serve as secretary, a representative from the affected study group or other health services users, with at least one (1) member who has expertise in bioethics and research ethics, and internal or external specialists to be included on an as needed basis. G-RECs-Op-2018 also notes that the member acting as a representative is not required to have a professional license in research or medical care and may include individuals with basic education or technical training.

Hospital Bioethics Committee Composition

Per GenHlthLaw and G-CHBs-Op, Hospital Bioethics Committees must be multidisciplinary, diverse, gender-balanced groups composed of medical personnel from different specialties and the health team; professionals from psychology, nursing, social work, sociology, anthropology, and philosophy fields; lawyers with knowledge in health matters, and community representatives affected by the health condition under study or other health services users who may or may not be attached to the health unit or institution. G-CHBs-Op notes that the members must have previous bioethics training or receive the training within the six (6) months after joining the Committee. Administrative personnel, directors of institutions, or people who occupy managerial positions in the institution should not be included, in order to promote an environment of equity.

In addition, per G-CHBs-Op, the Hospital Bioethics Committee should be composed of a president and a minimum of four (4) members with assistance from a secretary, to be appointed from among the members by the president. At least one (1) member not assigned to the health establishment must be included.

Terms of Reference, Review Procedures, and Meeting Schedule

Research Ethics Committees

Per NOM-012-SSA3-2012, the constitution and operation of the REC will be subject to the provisions of current legislation and, where appropriate, to the criteria referred to in article 41 Bis of the GenHlthLaw. REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP specify that RECs should operate within written standard operating procedures (SOPs) to conduct their reviews. REC-Op and G-RECs-Op-2018 indicate that the health institution owner must approve the SOPs and issue a certificate of appointment to each of the REC members. HlthResRegs, G-RECs-Op-2018, and NOM-012-SSA3-2012 note that members must hold office for three (3) years and may be approved for an equal period.

Per REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP, the following minimum requirements must be met (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

RECs must meet at least six (6) times a year, and at least once every two (2) months
The minimum number of members required to complete a quorum must be greater than 50% of the members, and the president and/or secretary must be present to form a quorum
In the evaluation of multicenter studies and when otherwise warranted, the REC may meet jointly with other RECs that belong to other establishments in the country, for the assessment and opinion for these protocols
Minutes must be prepared for legal and administrative purposes in meetings
An annual report of activities should be presented to the institutional head in the first 30 calendar days of the year
Avoid conflicts of interest in protocol evaluations or be declared disqualified for that particular review
Participation is required in initial training and bioethics continuing education
Liaisons with other RECs within and outside the country to better carry out its functions
A general policy on the confidentiality of information for protocols reviewed must be established and implemented
A code of conduct for REC members must be established and implemented
Members must refrain from participating in the evaluation and opinion of their own research
Members will remain in office for the time established in each committee’s installation act and may be ratified at the end of each period, if applicable. Members may be replaced in a staggered manner, for which documentary evidence must be kept
The committee will designate the person who will occupy the position of president and who will be responsible to the head of the institution or establishment and for the committee’s activities
In the committee sessions, members of external committees may participate or have the support of external advisors, who will have a voice but no vote. In these cases, researchers from the institution or establishment itself may also participate as long as they work in areas related to the subject of the project or research protocol in the opinion phase
It is the responsibility of the committee to issue the technical opinion on ethics, according to the nature of the proposed investigations

For detailed REC procedures and information on other administrative processes, see REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP. See also MEX-72 for information on CONBIOÉTICA’s REC follow-up monitoring reports.

As per G-RECs-Op-2018, the REC should also keep documentation related to its integration, operation, and registration activities for up to three (3) years after the conclusion of the committee’s activities. The committee should also define the procedure for transferring the files and appoint the responsible person at the institution where the REC registration was granted. In addition, the REC will keep all the essential documents reviewed and related to each evaluated investigation, up to five (5) years following the end of the investigation or during the period established in the applicable provisions.

See G-RECs-Op-2018 for additional REC recordkeeping requirements.

Hospital Bioethics Committees

As indicated in G-CHBs-Op, Hospital Bioethics Committees must establish operating rules, which specify member functions as well as the internal mechanisms and procedures for operations during the sessions. In newly created Committees and during the first six (6) months, the members must be trained in bioethics on an ongoing basis. Per G-CHBs-Op and GenHlthLaw, the Committee will also promote, with the head of the hospital, the dissemination, elaboration and implementation of institutional bioethical guidelines and guides for medical care and teaching. It will also promote the ongoing the bioethical education of its members and hospital staff. GenHlthLaw also notes the Hospital Bioethics Committees must comply with current legislation and CONBIOÉTICA guidelines.

G-CHBs-Op further explains that Hospital Bioethics Committees must meet in an ordinary manner, at least six (6) times a year, and in an extraordinary way, at any time, at the President’s request, or when requested by the majority of its members. Quorum requirements to review and decide on a request must include attendance of at least half the number of committee members and the president. Minutes will also be prepared for each of the Committee sessions. The resolutions issued by the Committee are the result of the analysis and deliberation of the members present at the session and must be communicated through a letter addressed to the applicant who presented the case. The recommendations issued by the Committee must not be incorporated into the clinical file. The Committee President is responsible for safeguarding the files. For detailed Hospital Bioethics Committee procedures and information on other administrative processes, see G-CHBs-Op.

9.2

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11)

2

1.2-1.3, 2-3, 3.1, 3.3, 4.1, 4.3, 5.1-5.2, 6.1-6.2, 8.1, 9, 11, and Annexes 1 and 2

Integration, Operation, Sessions, Minutes, Quorum, Issuance of Recommendations, and Information and Files

Title III (Chapter III, Article 41 Bis) and Title V (Chapter I, Articles 98 and 100)

Preamble, Fourth, Sixth-Tenth, and Twelfth

Preamble, Article One (Twelfth, Twelfth Bis 1, Twelfth Bis 2, and Sixteenth)

Title II (Chapter I, Articles 13-14), Title V (Chapter I, Articles 99-102, 104, and 108-109)

0-1 and 9

Last content review/update: March 21, 2024

New Info (Not Yet in Profile)

Version 5.1 of the CREC’s Standard Operating Procedures for the Operations of the CREC and Office Staff took effect on July 24, 2024 and replaces THA-37. (Google Translation of SOPs)

Overview

As per ClinImprtOrdr, ClinSampleProd, and ECRegProc, clinical trials require ethics committee (EC) approval for each trial site from an EC recognized by the Thai Food and Drug Administration (Thai FDA). ECRegProc indicates that an EC may function as a committee under a government agency (e.g., the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH)); as a committee affiliated with a private hospital/institution licensed to comply with the HospitalAct; or, as a committee operating as a part of a non-profit partnership between a government agency and a private organization(s) (e.g., the Central Research Ethics Committee (CREC)). ECRegProc states that the Thai FDA posts a list of the approved/renewed ECs on its website (see THA-90), and as noted in THA-3, this usually occurs every two (2) years. According to THA-4, the ECMOPH and the CREC are both government ECs whose approvals are still active. As discussed in THA-63, the ECMOPH and the CREC are also collaborating on a multi-institutional clinical research project to reduce redundancy during the review process and to develop joint human research ethics guidelines. (See THA-18 and THA-76 for the forms included in the appendices in ClinSampleProd and ClinImprtOrdr.) (Note: The ECMOPH website is not accessible to users residing outside of Thailand.)

Per THA-1, the ECMOPH and the CREC represent the two (2) central ECs recognized by the Thai FDA to review and approve clinical research protocols involving humans. THA-1 further explains that both the ECMOPH and the CREC are categorized as central ECs because they can accept all clinical research studies for review, regardless of the trial sites involved.

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health

Per THA-39, the ECMOPH is responsible for controlling, supervising, and monitoring research in accordance with international ethical principles; developing research policies; suspending unethical research programs; creating a national database of clinical research; establishing a regional/international committee network system; developing personnel capacity to support clinical research in Thailand; and other related or assigned academic projects. See THA-13 for additional details about the ECMOPH, and THA-13 and THA-39 for requirements specifically related to studies approved by the ECMOPH.

Central Research Ethics Committee

Per THA-1, the CREC was formed in 2014 through the cooperative efforts of 26 public and private institutions in Thailand, including the Thai FDA. THA-44 explains that the focus of the CREC is on reviewing multi-center clinical research projects to improve the efficiency of the EC review and to reduce the duplicative review of multi-institutional studies. See THA-44 for additional information on the CREC, and the Submission Process and Submission Content sections for detailed CREC submission requirements.

Ethics Committee Composition

As per G-ResEthics, institutional ECs should consist of at least five (5) members, both male and female, with the following qualifications:

At least one (1) member with knowledge and experience in research fields regularly reviewed (e.g., medicine, public health, social science, etc.)
At least one (1) member who is a lawyer or has legal expertise
At least one (1) member who is unaffiliated with the institution, and, if possible, that member should be selected from the community where the institution is based
At least two (2) members who have patient care, counseling, and treatment knowledge and experience
At least one-third of the total EC should be knowledgeable or trained in human research ethics

ECRegProc, by comparison, also requires institutional ECs to have at least five (5) members who are experts on science, medicine, and ethics. In addition, the committee must include members representing the following qualifications:

At least three (3) members who are medical professionals
At least one (1) member must be an expert in a non-scientific category
At least one (1) member from outside of the institution where the trial is taking place

The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28) similarly indicates that ECs should be composed of medical personnel, scientists, and non-scientists, and also notes that while these committees may have differences in legal status, composition, and function, the duties of an EC should be consistent with THA-28. Per an in-country subject matter expert, Thailand is implementing THA-28.

Because each EC has its own requirements, it is recommended that the individual ECs be contacted to confirm their specific requirements.

No information is available on ECMOPH and CREC composition requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in G-ResEthics and ECRegProc, ECs must conduct clinical protocol reviews according to THA-28 using written standard operating procedures (SOPs) that are periodically updated, and develop a process for conducting reviews. The SOPs should include information on EC composition, meeting schedules, timeframes for protocol reviews, quorum requirements, decision-making procedures, channels of communicating the decision(s), complaint processes, reviewing fees (if any), protection of protocol confidentiality, and prevention of possible conflicts of interests. The G-ResEthics also states that each EC must establish the composition, member terms of service, and criteria for selecting the committee members, as appropriate. The members must also be appointed officially as evidenced by a written document.

Additionally, per ECRegProc, ECs must meet the following requirements:

Have the legal qualifications or comply with the government regulations related to providing research or research-related services
Have a clearly defined structure with proof of appropriately appointed members, including the secretary and secretariat
Have voting rights and the right to issue independent research opinions without investigator/sponsor involvement, and with no direct or indirect interest or conflict of interest with the investigator or clinical research study
Have members who are trained in conducting research and clinical trials in human participants, and who participate in ethics training or other related training at least once every two (2) years while serving on the committee
Have experience in reviewing human research involving experimental drugs for at least 10 studies

For detailed EC requirements and information on other administrative processes, see G-ResEthics and ECRegProc.

Also, refer to THA-47 for a list of CREC forms needed to prepare for initial protocol submission, and THA-37 for a complete list of CREC SOPs.

No information is available on the ECMOPH’s terms of reference, review procedures, and meeting schedule.

Which EC? And CREC

Important Modifications in the New List

Important Updates in the New List and Saving Time…and Cost!

Appendices 3-4, 7, and 9

Appendices 1-5, 11, and 13

1.27 and 3.3

Chapter 6

Preface, 1, 3, and Appendices 3-4, 7, and 9

1, 3, and Appendices 1-5, 11, and 13

4-6 and 9-10

Scope of Review

Last content review/update: November 8, 2024

Overview

According to HlthResRegs, REC-Op, and G-RECs-Op-2018, the primary scope of information assessed by the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. Per HlthResRegs and G-RECs-Op-2018, RECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable. (See Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations.)

HlthResRegs and G-RECs-Op-2018 also state that RECs must ensure an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. See HlthResRegs and G-RECs-Op-2018 for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must obtain a favorable decision from the REC and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. As per COFEPRIS-GCP, HlthResRegs, and NOM-012-SSA3-2012, the REC must provide a favorable decision for the research protocol and informed consent form prior to the applicant submitting a request for protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Consequently, the REC and COFEPRIS reviews may not be conducted in parallel.

HlthResRegs, GenHlthLaw, and G-HumResProt explain that the REC provides ethics recommendations on protocols for research in human beings, including a review of the research risks and benefits, and per G-HumResProt, assesses the technical quality and scientific merit of the protocol. HlthResRegs further notes that RECs also prepare ethics guidelines for conducting research in humans.

As delineated in G-RECs-Op-2018, the REC agenda and documents corresponding to each session should be delivered at least seven (7) days prior to the meeting. It is then recommended that the REC’s decision be sent within a period not exceeding five (5) working days after the committee has met, or if applicable, not to exceed 30 calendar days from the review request date. G-RECs-Op-2018 and G-DIGIPRiS-ResProts also state that the approval of a new application is valid for one (1) year.

After obtaining a favorable opinion from the REC that validated the initial project or protocol, per NOM-012-SSA3-2012, the principal investigator (PI) must submit an amended protocol to the Ministry of Health (Secretaría de Salud) to request a new authorization for any amendments to be made to the methodological design of the initial research project. In those cases where the lives of research participants are endangered, amendments can be applied immediately, prior to approval by the REC and authorization by the Ministry of Health. However, in these situations, it will be necessary for the PI to provide documentary evidence following the event to the REC and the Ministry.

In addition, G-RECs-Op-2018 indicates that the REC should establish procedures for monitoring approved studies, from the point at which the decision was made until the completion of the investigation and reporting of results. Per NOM-012-SSA3-2012 and G-RECs-Op-2018, the REC must assess and approve the research protocol at the beginning of the project, and periodically throughout the project’s duration to ensure conformance with ethical principles and applicable regulations. NOM-012-SSA3-2012 further specifies that the REC must propose to the head of the institution or establishment where health research is carried out that the research be suspended or cancelled in the presence of any adverse effect that is an impediment from an ethical or technical point of view to continue with the study.

(See Submission Process and Timeline of Review sections for detailed REC submission process and timeline details.)

9.2

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11)

2

3.1-3.3, 4.3-4.4, 7.2, 8.1-8.2, 11, and Annexes 5 and 6

Title V (Chapter I, Article 100)

Preamble and Fifth

Preamble, Title II (Chapter I, Article 13 and Chapter II, Article 29), Title III (Chapter I, Article 61-62), and Title V (Chapter I, Articles 99-102, 104, and 108-109)

0, 6.3, 8.4, 9.2, and 10.3

Last content review/update: March 21, 2024

Overview

As delineated in G-ResEthics, ECRegProc, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28), the primary scope of information assessed by Thai Food and Drug Administration (Thai FDA) recognized ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. According to THA-10, clinical research and trials (i.e., research studies and experiments on humans) are subject to the medical ethics standards delineated in the Regulations of the Medical Council on Maintaining the Ethics of the Medical Profession (B.E. 2549) (MCEthics), the Declaration of Rights and Code of Conduct for Patients (THA-11), and the Researcher’s Code of Ethics (THA-14).

MCEthics explains that ECs are established to review the ethical aspects of research studies and human trials to protect the rights, safety, and well-being of participants in research studies and human trials. THA-14 further states that researchers should treat all research participants, whether animate or inanimate, with appropriate respect and consideration and should take full responsibility for the impact and consequences of their research. Researchers should also have respect for the dignity and rights of their human participants. THA-11 indicates that every patient has the fundamental right to receive professional medical and health care from health professionals without discrimination as provided for in the Constitution of the Kingdom of Thailand (B.E. 2560). Per G-ResEthics, ECRegProc, and THA-28, ECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed to be vulnerable. Per an in-country subject matter expert, Thailand is implementing THA-28. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses, and Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

In addition, per G-ResEthics, ECRegProc, and THA-28, ECs are also responsible for ensuring an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. ECs must act in the interests of the potential research participants and the communities involved, evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, and methods; and verifying the adequacy of confidentiality and privacy safeguards. G-ResEthics further states that ECs should review the ethical aspects of the protocol in compliance with current international ethical guidelines while taking into account local or national laws, religions, traditions, and cultures. Per G-ResEthics, the appointed EC is also responsible for ensuring that research conducted within the institution adheres to ethical principles including those established in the Declaration of Helsinki (THA-45), the Council for International Organizations of Medical Science (CIOMS)’ International Ethical Guidelines for Biomedical Research Involving Human Subjects (THA-7), and the World Health Organization (WHO)’s Operational Guidelines for Ethics Committees that Review Biomedical Research (THA-64). See G-ResEthics, ECRegProc, and THA-28 for detailed ethical review guidelines. MCEthics further states that the medical practitioner who conducts or participates in the research study on humans must only undertake such study or experiment after it is approved by the EC responsible for the study. The medical practitioner must also conform to G-ResEthics and THA-14 when conducting the research study.

Role in Clinical Trial Approval Process

Pursuant to ClinImprtOrdr and ECRegProc, Thai FDA-recognized ECs are responsible for reviewing and approving protocols for clinical research related to drugs to be imported into Thailand. Per ClinSampleProd and DrugProdReqs, the Thai FDA is also responsible for approving requests for permission to produce drug samples for the registration of drug formulas for human research studies. As stated in ClinImprtOrdr, ClinSampleProd, and ECRegProc, the Thai FDA’s approvals of a drug import license and of a request for permission to produce sample drugs for human research studies are dependent upon obtaining approval by a Thai FDA approved EC. ClinImprtOrdr and ClinSampleProd further specify that for both types of approval requests, the application is either submitted to the Thai FDA after the research project and all the research sites have been approved by an EC, or in parallel, pending review by at least one (1) EC involved in the study. THA-5 further notes that if an approval is obtained from the EC of the research institute or university conducting the trial, an approval from the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) is usually optional (unless it is further required by the internal rules and regulations of that research facility).

In the instance of a multicenter clinical trial, G-ResEthics indicates that protocols submitted to each institution’s EC should contain the same content substance and details, and should specify the quality control techniques to ensure that research practices are the same in each institution. Although each institutional EC may independently approve or disapprove an application, G-ResEthics advises the committees from each participating institution to consult with one another to reach a clearly agreed upon decision.

There is no stated expiration date for an EC approval in G-ResEthics, in the ECMOPH guidelines (THA-13), or on the Central Research Ethics Committee (CREC) website (THA-36). Per ECRegProc, ECs must provide continuous supervision and monitoring, and conduct inspections to ensure that clinical trial operations are carried out in compliance with all approved research projects and research sites without any deviations or changes from those approved by the committee, unless otherwise specified according to THA-28. ECs must also supervise and monitor research projects to ensure that participants’ rights, safety, and well-being are protected (e.g., in the case of an adverse event, etc.).

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health

According to THA-13, an application submitted to the ECMOPH is initially reviewed by at least two (2) advisors, followed by a final review by the ECMOPH at its regular meeting. At this meeting, the advisors present a summary of the proposal to the committee along with their recommendations. The committee discusses the proposal and sends a list of comments to the principal investigator (PI) for clarification. Once the PI provides the requested information, the committee makes a final decision, and this is reported to the ECMOPH Chairman and the Permanent Secretary for Public Health respectively. A letter of notification signed by the Permanent Secretary for Public Health is then forwarded to the PI and the responsible organization. As earlier stated, this review and approval process is specific to the ECMOPH. However, it can be used to obtain a better understanding of the EC process within Thailand.

Central Research Ethics Committee

As indicated in THA-44 and THA-24, a research project is eligible to apply for CREC review when it meets one (1) of the following criteria:

It is a pharmaceutical-sponsored multi-center clinical trial
It is an investigator-initiated multi-site study granted by a research funding organization (e.g., the National Research Council of Thailand (NRCT), the Thai Health Promotion Foundation, the Health Systems Research Institute (HSRI), etc.)
It is assigned by the Thai Health Board of Directors for review
It is a single center, multi-site study of researchers at partner institutions with co-researchers from each site (THA-24)

Per THA-44, when a research proposal is submitted to the CREC for review, the committee will cooperate with all the participating ECs to confirm the researchers are qualified, the institution has adequate facilities, and the proposed research is compliant with institutional regulations, applicable laws, local contexts, and standards of professional conduct and practice. The CREC will also consider the concerns and attitudes of the various communities participating in the project. Once the review process is completed, the decision will be documented in a formal letter. The issued decision letter will be sent to the PI, the contract research organization, and all of the participating ECs. Refer to THA-44 and THA-24 for additional CREC requirements.

Clinical Trials

2

Instruction for the Submission of a Study/Research Proposal to be Reviewed by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (p.63)

4-5

1.27 and 3.3

1.1, and Chapters 2, 4, and 6

Preface, Summary of Changes in this Edition, 1, 3, and Appendices 3-4, and 9

1, 3, and Appendices 1-5 and 13

Chapter 1 (Article 5) and Chapter 9 (Articles 50-51)

5-6

Appendix 12

Ethics Committee Fees

Last content review/update: November 8, 2024

As set forth in G-RECs-Op-2018, COFEPRIS-GCP, and REC-Op, Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) do not charge sponsors/investigators for their review. Rather, the health institution must finance REC operating expenses, without this causing any conflict of interest in the committee’s functions.

G-RECs-Op-2018 further states that the institution may also receive support from external sources for evaluating protocols. However, this funding should not be given directly to any of the REC members, and the contributions should not lead to a conflict of interest between the funding source and the REC’s functions. Similarly, the committee’s evaluations should not result in financial gains as a result of these contributions.

Per G-RECs-Op-2018, REC financial support should not be used for purposes other than for its operation, and all activities should be handled with full transparency. Support is provided for the following activities:

Time for participation in committee meetings
Work recognition for their performance in the REC
Support for training in bioethics and research ethics inside and outside the institution
Physical space for the REC headquarters, both for meetings and receipt of documents, and safeguarding of documentation protocols, opinions, and minutes
Administrative assistance for REC activities

No information is available on Hospital Bioethics Committee fees.

2.7

4.2

Seventh, Ninth, and Eleventh

Last content review/update: March 21, 2024

As explained in G-ResEthics, Thai Food and Drug Administration (Thai FDA)-recognized ethics committees (ECs) should review their research budgets to ensure that fee information is addressed. In general, the sponsor will pay the investigator based on the number of research participants. The Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) and the Central Research Ethics Committee (CREC) are both ECs recognized by the Thai FDA to review and approve clinical trial protocols.

G-ResEthics further states that research conducted in public hospitals or public health care facilities involves expenditures such as laboratory tests and lump sum fees determined by the institution. The disclosure of these payments and other budget items enables the EC to evaluate any conflict of interest and helps the investigator to decide whether to conduct the trial.

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health

No information is currently available on ECMOPH fees.

Central Research Ethics Committee

As set forth in CRECFees, the CREC requires investigators to pay a nonrefundable fee to submit a clinical trial research protocol for ethical review and approval.

CRECFees and THA-50 specify the following fees for the ethical review of research projects funded by private capital (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

New research project: 50,000 Baht

· Request for certification renewal of old research project: 20,000 Baht

Amendments to the research project (research outline amendments/adding a research location): 10,000 Baht
Report requesting amendments to the research outline: Amendment certified by the local EC of the joint research institute in the CREC-certified research project, followed by a report submitted for CREC consideration (site-specific amendment): No fees charged
Reporting adverse events, reporting non-compliance, notifying the CREC of a research project closure, and various other reports: No fees charged
Edit the Certificate of Approval (COA) document: 1,000 Baht
Edit certification/acknowledgement: 500 Baht
Edit document with certified seal: 500 Baht

For research projects funded by government agencies, royal colleges, medical professional associations, or personal capital, CRECFees and THA-50 delineates the following fees:

New research project: 25,000 Baht
Request for certification renewal of old research project: 10,000 Baht
Amendments to the research project (research outline amendments/adding a research location): 5,000 Baht
Report requesting amendments to the research outline: Amendment certified by the local EC of the joint research institute in the CREC-certified research project, followed by a report submitted for CREC consideration (site-specific amendment): No fees charged
Reporting adverse events, reporting non-compliance, notifying the CREC of a research project closure, and various other reports: No fees charged
Edit the Certificate of Approval (COA) document: 500 Baht
Edit the certification/acknowledgement: 250 Baht
Edit document with certified seal: 250 Baht

Payment Instructions

THA-42 explains that investigators should submit ethics application fee payments to the following bank:

Bank Name: Krungthai Bank
Bank Address: 2/1 SOI Phahonyothin, Phahonyothin Road 40, Sena Nikhom, Jatujak, Bangkok 10900
Swift Code: KRTHTHBK
Branch: Phahonyothin 39
Account Type: Savings Account
Account Name: Foundation for Human Research Promotion in Thailand
Account number: 981-2-84782-0

Per CRECFees and THA-25, the investigators must submit proof of payment with the application submission. CRECFees indicates that the investigators and research sponsor are responsible for paying the fees and preparing the documentation to submit to the research institute. In the case of an investigator having transferred fees for a project that has been cancelled, the investigator may request a refund. The Foundation will deduct 20% of the transferred fee. The investigator should contact the bank for any service fee applied.

THA-50 and THA-25 indicate that any questions regarding the payment submission process may be directed to the following contact:

Miss Netdao Kanseecha
Financial Officer
Phone: 061-089-9966
Email: natdown@crecthailand.org

Per THA-25, if the CREC has no evidence of payment, the application submission will be considered incomplete. See THA-50 for additional information on fee rate based on funding source and fee receipts.

Type of Funding Source, Fee Rate, and Notes

7.1.5

Oversight of Ethics Committees

Last content review/update: November 8, 2024

Overview

The National Bioethics Commission (Comisión Nacional de Bioética (CONBIOÉTICA)) was established as a decentralized entity of the Ministry of Health (Secretaría de Salud) in 2005, as specified in D-CONBIOETICA. According to D-CONBIOETICA and MEX-55, the agency has technical and operational autonomy in defining and establishing national bioethics policies in medical care and health research. Per D-CONBIOETICA, GenHlthLaw, G-RECs-Op-2018, and MEX-57, CONBIOÉTICA is also responsible for promoting the organization and operation of Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) and Hospital Bioethics Committees in public and private health institutions, for establishing and disseminating criteria to support development of REC activities, and for providing committee member training support.

In addition, per D-CONBIOETICA, CONBIOÉTICA’s other roles include:

Exercising the Commission’s legal authority and head Commission operations
Presiding over the Commission’s Advisory Council
Issuing positions on bioethical issues relevant to society
Establishing links with federal entities to promote the creation and operation of state bioethics commissions
Signing and implementing collaborative agreements with organizations and opportunities that favor the development and consolidation of bioethical culture
Carrying out activities assigned by the Secretary of Health
Providing information and technical cooperation required by the Ministry of Health’s administrative units and other dependencies/entities within the Federal Public Administration

Registration, Auditing, and Accreditation

Research Ethics Committees

As delineated in HlthResRegs, REC-Op, REC-Op-Ref, REC-Op-Amd, G-RECs-Op-2018, G-RECReg, and MEX-57, all RECs are required to register with CONBIOÉTICA in order to conduct health research in humans.

G-RECs-Op-2018, and G-RECReg further state that CONBIOÉTICA has 10 working days from the business day following application receipt to accept the application, or require the applicant to correct omissions in the application within 15 working days from the business day following the date when the applicant is notified. If the applicant fails to respond within this timeframe, the application must be deemed not filed. Once the application has been admitted for processing, the Commission has 30 working days to notify the applicant of receipt, and if appropriate, to issue the corresponding registration certificate, which will be valid for three (3) years. The registration record must also be visibly displayed in the institution where REC operations occur and on its website, if applicable. Additionally, the registration number must be included in all official committee communications.

Per REC-Op-Amd, MEX-58, and G-RECReg, the REC registration form (MEX-29) is available for completion or download via MEX-58 or G-RECReg, and should be submitted in person according to the requirements outlined in REC-Op-Amd, MEX-58, and G-RECReg. The application must include the REC’s health institution identification data, an email address in order to receive Commission notifications, and the name and signature of the responsible person heading the REC. G-RECReg specifies that the applicant may request an appointment by phone or email to deliver all the documentation in printed form to CONBIOÉTICA, or send the application documentation via certified mail.

Refer to REC-Op-Amd, G-RECs-Op-2018, MEX-58, and G-RECReg for detailed registration application instructions and documentation requirements. See also MEX-57 for a list of registered RECs.

As delineated in REC-Op-Amd, G-RECs-Op-2018, and G-RECRegRenew, a registration renewal application must be submitted by the principal or owner of the health establishment or by the legal representative to CONBIOÉTICA within 45 working days prior to the expiration of the validation period covered by the registration certificate. From this point, the timing requirements are the same as for the initial application. See REC-Op-Amd, G-RECs-Op-2018, and G-RECRegRenew for detailed registration renewal application requirements and the application form.

In addition to CONBIOÉTICA’s REC registration requirement, per GenHlthLaw, G-RECs-Op-2018, REC-Op, and REC-Op-Ref, RECs must be installed under the responsibility of the head of the health institution where the study is taking place. They are required to sign a REC Installation Certificate (MEX-27), which stipulates its characteristics and functions. Refer to G-RECs-Op-2018 for detailed certificate requirements. See also MEX-72 for information on CONBIOÉTICA’s REC follow-up monitoring reports.

According to NOM-012-SSA3-2012, the research institution owner must also register the REC with the Ministry of Health (Secretaría de Salud), and report on the modification, designation, or substitution of any of its members. Additionally, an annual report documenting the integration and activities of these committees must be submitted to the Ministry during the first 10 business days of June each year.

Hospital Bioethics Committees

G-CHBs-Op and G-CHBReg indicate that Hospital Bioethics Committees must also register with CONBIOÉTICA, who is, in turn, required to issue a registration record within a maximum of 15 business days. CONBIOÉTICA’s registration is valid for three (3) years. Per G-CHBs-Op, the Hospital Bioethics Committee registration form must be submitted electronically through CONBIOÉTICA’s website. The application for registration renewal can be submitted one (1) month prior to the registration’s expiration date. Refer to G-CHBs-Op, MEX-56, MEX-59, and G-CHBReg for additional Hospital Bioethics Committee registration information.

Registration Process of Research Ethics Committees (CEI) and List of Registered CEI

Preamble, Articles One-Three, and Seven

Requirements, Who Can Apply?, Legal Basis, Steps, Response Time, Validity, and Additional Information

5.3, 11, and Annex 4

Registry of the Hospital Bioethics Committees, Proof of Registration, Validity of the Registration, Renewal of the Registration, and Appendix 1

Title III (Chapter III, Article 41 Bis) and Title V (Chapter I, Article 98)

Preamble, Article One (Twelfth and Twelfth Bis 1), and Transients (Third)

Preamble, Fourth, Sixth-Tenth, Twelfth, and Annex 1

Article One (Seventh, Twelfth, Twelfth Bis 2, and Sixteenth), and Annex 1

Title V (Chapter I, Articles 99-102, 104, and 108-109)

4.8 and 9.1.4

Last content review/update: March 21, 2024

Overview

As indicated in ECRegProc, ClinImprtOrdr, and ClinSampleProd, institutional ethics committees (ECs) and other types of ECs, including the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) and the Central Research Ethics Committee (CREC), must be authorized by the Thai Food and Drug Administration (Thai FDA) to conduct ethical reviews of drug clinical trial protocols. ClinImprtOrdr and ECRegProc specify that authorized ECs are responsible for reviewing and approving protocols for clinical research involving drugs to be imported into Thailand. (See also THA-18 and THA-76 for the forms included in the appendices relating to EC authorization in ClinImprtOrdr and ClinSampleProd.)

As per ECRegProc, an acceptance letter issued to the ECs by the Thai FDA is valid for two (2) years and may be obtained by applying to the agency using the Jor Thor Form EC-1 (THA-23). Each EC is also required to submit an annual report (THA-21) to the Thai FDA, and to apply for an acceptance extension no later than 60 days before the expiration date.

ECRegProc states that the Thai FDA posts a list of the approved/renewed ECs on its website (see THA-90) and as noted in THA-3, this usually occurs every two (2) years. These ECs are approved in addition to the centralized ECMOPH and the CREC.

Registration, Auditing, and Accreditation

Pursuant to EC-QualAccredReq, in addition to the ECRegProc approval and renewal of approval documentation requirements, the Thai FDA requires ECs to submit proof of accreditation based on an evaluation by a quality accreditation agency in compliance with international accreditation standards. The following organizations are approved by the Thai FDA to provide quality accreditation reviews:

National Ethics Committee Accreditation System of Thailand (NECAST)
The Strategic Initiative for Developing Capacity in Ethical Review (SIDCER)/The Forum for Ethical Review Committees in Asian and Western Pacific Region (FERCAP)
The Association for the Accreditation of Human Research Protection Programs (AAHRPP)
Other Thai FDA-approved quality accreditation agencies

Per EC-QualAccredReq, EC submissions will be reviewed and completed within one (1) business day.

Important Modifications in the New List

Appendices 3-4 and 9

Appendices 2-5 and 13

Preface, 1, 3, and Appendices 3-4 and 9

1 and Appendices 1-5, and 13

Preface, 4-6, 9, and 11

Submission Process

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, and NOM-012-SSA3-2012, Mexico requires the applicant to obtain research protocol authorization from the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. Because COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the REC and Research Committee, the COFEPRIS and ethics committee (REC and Research Committee) reviews may not be conducted in parallel.

Regulatory Submission

MEX-15 states that applicants may submit research authorization requests or protocol modification/amendment requests in person or by mail to COFEPRIS at the Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services. According to G-HumResProt, G-ResProtocolAmd, MEX-109, and MEX-37, however, requests should be submitted to the CIS (MEX-37) in person or electronically via COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86). (Note: COFEPRIS refers to applications as requests or procedures).

Pre-submission Registrations

As delineated in G-DIGIPRiS-Regis and G-DIGIPRiS-SystAccess, prior to submitting a request for research protocol authorization via DIGIPRiS (MEX-86), an applicant must first register in (MEX-86) using an e.signature (also known as e.firma) digital certificate. MEX-49 explains that the signature is a secure, encrypted digital file that identifies an applicant, and can be used to carry out procedures electronically with various government agencies. An e.signature can be obtained from the Tax Administration Service (Servicio de administración tributaria (SAT)) as described in MEX-105. G-DIGIPRiS-Regis and G-DIGIPRiS-SystAccess further explain that an e.signature is used to validate the natural person or legal entity registering in MEX-86. DIGIPRiS’s Terms of Use, which is accessible via MEX-86, also notes that the applicant is required to be registered with the Federal Taxpayer Registry (Registro Federal de Contribuyentes (RFC)). See G-DIGIPRiS-Regis, G-DIGIPRiS-SystAccess, and DIGIPRiS’s Terms of Use for details on registering in MEX-86. See also MEX-106 for an instructional tutorial on registering in MEX-86, and see G-DIGIPRiS-FAQs for frequently asked questions on using MEX-86.

DIGIPRiS Submissions

DIGIPRiS’s Terms of Use further explains that the application process is carried out entirely electronically via DIGIPRiS (MEX-86), unless the user is required to present printed documents with a handwritten signature or a physical inspection is required. The application request will be considered active when the documentation is signed and submitted, otherwise it will only remain in the system for 90 calendar days. When the request is active, the user receives a “Procedure Entry Receipt” through which COFEPRIS assigns a procedure number and the entry date and time is recorded. Once the procedure has begun, the user will be notified in MEX-86 of all request related administrative acts (e.g., requirements, actions, preventions or missing information, and resolutions). Authorizations issued via MEX-86 will take effect on the date and time indicated in the corresponding document. The email address the user provides during registration will be used to send notices of notification availability related to submitted applications. Refer to DIGIPRiS’s Terms of Use for detailed information on the administrative act notification process via MEX-86. See also G-DIGIPRiS-SystAccess for instructions on registering and updating emails in MEX-86.

Pursuant to G-DIGIPRiS-SystAccess and G-DIGIPRiS-ResProts, users can view the flow and status of the entire application process (application, evaluation, verification, signature and resolution) in DIGIPRiS (MEX-86), as well as view previously authorized applications. Additionally, multiple requests and procedures can be in process simultaneously in MEX-86. See also G-DIGIPRiS-DocComp for instructions on validating and comparing documents issued through MEX-86 for research protocols. Refer to MEX-96, MEX-97, and MEX-108 for additional background information on MEX-86. Per G-HumResProt, electronic submissions via MEX-86 are tracked via the applicant’s e.signature (MEX-105). See also G-DIGIPRiS-Reqs&Amdts for instructions on submitting requests for protocol amendment/modification via MEX-86.

CIS Submissions

As indicated in MEX-37 and MEX-15, applications submitted in person at the CIS (MEX-37) can be tracked via a CIS assigned reference number in the COFEPRIS Electronic Procedures Portal (MEX-103). MEX-109 specifies that the Electronic Procedures Portal (MEX-103) is only to be used for procedures submitted in person at the CIS (MEX-37) while procedures submitted via DIGIPRiS (MEX-86) should be tracked through the DIGIPRiS platform.

As per MEX-15, and MEX-71, applications as well as technical inquiries, or those inquiries requiring an official response, should be submitted to the CIS (MEX-37) at:

COFEPRIS
Centro Integral de Servicios
Oklahoma No. 14
Colonia Nápoles
Del. Benito Juárez
CP 03810, Ciudad de México

COFEPRIS Call Center Phone: 01-800-033-5050 (toll free within Mexico) or 55 53 40 09 96 (international calls) (per MEX-37)
Foreign Processing Area Phone (for entry and/or tracking number of procedure): 01-800-420-4224 (toll free within Mexico) (per MEX-25)
Email: contactociudadano@cofepris.gob.mx (per MEX-71 and MEX-37)

Per G-DIGIPRiS-ResProts, all documents uploaded to DIGIPRiS (MEX-86) must be in “.pdf” format (unrestricted text file), unless another format is specified.

Per G-HumResProt, G-ResProtocolAmd, and MEX-18, the Authorizations, Certificates and Visits form (MEX-25) should also be included in the application submission, as well as the original proof of payment of rights with two (2) copies of the receipt for protocol authorization and protocol modification/amendment requests. See the Submission Content section for detailed submission documentation requirements.

G-HumResProt and G-ResProtocolAmd state that all documentation related to submitting applications for research protocol authorization and protocol modification/amendment is required to be in Spanish. MEX-84 also specifies that the protocol, investigator’s brochure (known as the researcher’s manual in Mexico), and the informed consent forms should be in Spanish.

Enabled Pre-Assessment Support Unit (UHAP) Evaluation Submissions

Per MEX-21 and MEX-10, rather than submitting the application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). See Scope of Assessment section for detailed information on UHAPs.

Ethics Review Submission

As earlier stated, per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, all requests for research protocol authorization in human beings and/or their biological samples in Mexico require the applicant to obtain a favorable decision from the REC and the Research Committee, and when applicable, a favorable decision from the Biosafety Committee. Because the submission process at individual institutional RECs will vary, applicants should review and follow their institution’s specific requirements.

9.2

1. Homoclave, name and modality of procedure (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)

Access with Electronic Signature of the SAT and Terms of Use

Introduction, Access to the system creation of the profile, Register an email to receive notifications from the platform, and Abbreviations

Introduction, XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements (31-32 and 11) and Additional Information

Requirements (1-2) and Additional Information

Title II (Chapter II, Article 17 Bis) and Title III (Chapter III, Article 41 Bis), and Title V (Chapter I, Article 98)

Chapter I (Articles 1 and 3) and Chapter IV (Article 14)

Title III (Chapter II, Article 65) and Title V (Chapter I, Articles 99, and 109-111)

5.2, 6.3, and 9.2

Last content review/update: March 21, 2024

New Info (Not Yet in Profile)

As of November 20, 2024, CREC’s online submission system is suspended. All research project documents should be submitted via email to official@crecthailand.org. See the announcement on CREC’s website.

Overview

In accordance with ClinImprtOrdr and G-CT-DIPApp, the sponsor or the contract research organization (CRO) is responsible for submitting a drug import license application for clinical research purposes to the Thai Food and Drug Administration (Thai FDA). Per ClinSampleProd and DrugProdReqs, the Thai FDA is also responsible for approving requests for permission to produce drug samples for the registration of drug formulas for human research studies.

As set forth in ClinImprtOrdr, ClinSampleProd, and ECRegProc, the Thai FDA’s approvals of a drug import license and of a request for permission to produce drug samples for human research studies are dependent upon obtaining proof of ethics committee (EC) approval from the Thai FDA to conduct the clinical trial. ClinImprtOrdr and ClinSampleProd further specify that for both types of approval requests, the application is either submitted to the Thai FDA after the research project and all the research sites have been approved by an EC, or in parallel, pending review by at least one (1) EC involved in the study. (Note: Per ClinImprtOrdr, the sponsor is also referred to as the applicant or importer.)

Regulatory Submission

OSSC Pre-Submission Permission

According to THA-77 and THA-75, prior to submitting a drug import license application (N.Y.M.1 form), an applicant must first request permission from the Thai FDA’s One Stop Service & Consultation Center (OSSC) (THA-35) to use the OSSC’s online consultation system (E-Consult) (THA-77). Per THA-65, requesting E-Consult permission is a two-part process that initially requires applicants who are Thai citizens to create a user account and register via Digital ID (THA-89) which enables Thai citizens to access all government agency electronic services using a single user account/password. The user account can then be used to submit applications and supporting documentation to the Thai FDA’s Medicines Regulation Division via the Skynet E-Submission System (THA-54).

Per THA-65 and THA-77, once registered in THA-89, Thai applicants (i.e., the general public, entrepreneurs, or researchers) are subsequently required to provide documentation to E-Consult (THA-77) to confirm that they, or representatives authorized to act on their behalf, are authorized to use the FDA’s Skynet E-Submission System (THA-54). Although non-citizens cannot register directly with THA-89, they can request permission to authorize a juristic person who receives power of attorney (i.e., agency representatives, registration agents, or researchers who submit applications on behalf of an agency). Documentation should be submitted to E-Consult (THA-77) either in person or via email (econsultcenter@fda.moph.go.th) specifying in the subject line: “Request to open the right to use the information system.”

Per THA-77, for Thai applicants, this documentation includes:

Form for Requesting Permission to Use the Health Product Consultation Information System (E-Consult) (THA-80)
Copy of identity card

Per THA-77, for juristic applicants with power of attorney, this documentation includes:

Form Requesting Power of Attorney Permission to Use the Health Product Consultation Information System (E-Consult) (THA-81)
Copy of juristic person certificate (if any)
Power of attorney form
Copy of identity card of grantor (the national identity card issued to Thai citizens)
Copy of identity card of attorney-in-fact (refers to a passport)

THA-66 indicates that when an applicant completes the process of submitting an in-person request within one (1) day at the service center, a service provider can then forward the request for review and may receive a response within one (1) day. For requests that take more than one (1) day to be reviewed, the service center will forward the application to the Product Division for consideration. See also THA-51 for additional information on services provided by the OSSC’s E-Consult Service.

Import and Export Division Pre-Submission Permission

Per THA-79, the Thai FDA’s Import and Export Inspection Division also requires applicants to request permission to access the Skynet E-Submission System (THA-54) prior to being permitted to submit a drug import waiver application for clinical trial purposes. Applicants requesting access may submit documentation via email to bie.thaifda@gmail.com to open temporary rights first. After reviewing the emailed documentation for correctness/completeness, the officer will reply to the email and request original copies of the documents. A request for permission can also be mailed to the OSSC (THA-35), 4th floor. Also, per THA-87, Thai applicants may register and submit authorization documentation via THA-54 once they have obtained access.

THA-79 states that for Thai applicants, the required authorization documentation includes:

Copy of the registration certificate of the company or partnership, or a copy of the commercial registration (which has been issued no more than six (6) months and has a grantor to sign)
Copy of grantor’s identity card (which has not expired on the date of document submission along with a signature to certify the copy)
Copy of the identity card of the attorney-in-fact (which has not expired on the date of document submission along with a signature to certify the copy)

THA-79 further notes that the applicant has the right to use the Skynet E-Submission System (THA-54) for import/export purposes for no more than one (1) year. The following forms are also provided on the Import and Export Inspection Division webpage (THA-85) to complete these requests: Form Requesting Access to the FDA E-Submission System for Permission to Import Drugs for Other Purposes (THA-83), Form Requesting Power of Attorney Access to the FDA E-Submission System for Permission to Import Drugs for Other Purposes (THA-82), and Application Form for Medicine Importation (THA-84). See also THA-85 for additional related forms that may be useful.

Submissions

N.Y.M.1

As delineated in ClinImprtOrdr, the Thai FDA accepts paper and electronic clinical trial application submission packages for requests to import or order drugs for clinical research. However, paper applications are only to be submitted at the discretion of an agency officer when it is determined that the application process cannot be completed electronically via the Skynet E-Submission System (THA-54) for Medicines Regulation Division review and approval (see Submission Content section for content details).

As per ClinImprtOrdr, for paper submissions, sponsors must submit two (2) original sets with real signatures of the completed N.Y.M.1 form (ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2)) with the required attachments to the Thai FDA. For paper submissions, the applicant must also submit an MS Word template file for importing the data electronically, so that the file can be connected to the information in the drug importation and clinical research sections in the information system. A copy of all the submitted documents should also be provided in PDF format. G-CT-DIPApp also states that two (2) sets of the application package must be submitted to the Thai FDA. Per ClinImprtOrdr, if the Thai FDA reviewer determines that submitted documents require correction or additional documentation needs to be submitted, the applicant must make corrections/clarifications based on the evaluation results within the specified time by submitting a correction/clarification request form (see ClinImprtOrdr (Appendix 12) and THA-18 (Appendix 12)).

Additionally, per ClinImprtOrdr, the non-local applicant must authorize a qualified person through a power of attorney to submit an application and respond to requests to provide clarification, amend, and/or receive documents related to the submission. The attorney-in-fact should be someone who has knowledge in pharmacy or a related medical field as well as an understanding of requests, permissions, etc. relating to the application submission and associated documentation. The scope and responsibilities of the attorney-in-fact must be specified in the authorization to include filing application submission clarifications and corrections. The authorization documentation should be submitted with the paper application. ClinImprtOrdr further notes that one (1) set of power of attorney submission documentation may only be used for one (1) application submission request.

ClinImprtOrdr also states that the application submission should include documentary evidence for quality control and drug production separated by drug. The identification of the manufacturer of each drug included in the submission must match the one specified in the Microsoft Excel files for the Logistics System (See ClinImprtOrdr (Appendix 7) and THA-18 (Appendix 7) for the manufacturer’s form).

As indicated in ClinImprtOrdr and G-CT-DIPApp, Thai and English are the preferred languages for use in preparing an application package for requests to import or order drugs for clinical research. The following requirements are specified (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Research project name and summary of research project in Thai
Drug packaging documents for already registered drugs presented in Thai or English (Note: if drug formula documentation from abroad is in a foreign language other than English, then it should be translated into Thai or English and certified that the text matches the Thai/English language version)
Protocol synopsis in Thai
Detailed study protocol specification (completed version of study protocol) in Thai or English
Patient information sheet in Thai or translated to an appropriate language and certified the text matches the Thai version
Drug labels for every package size in Thai or English
EC approval document in Thai
Certificate of Free Sale in English and translated by a trusted certification authority and any other language in which it has been originally issued
Progress report in Thai

Additionally, as explained in THA-79, once the applicant has obtained permission from the Import and Export Inspection Division to access the Skynet E-Submission System (THA-54), a drug import waiver application (N.Y.M.1) may be submitted electronically. Per THA-87, following official review of the submitted documentation, a response will sent within one (1) business day. THA-87 and THA-79 indicate that once the request is approved, a License Per Invoice (LPI) number will be used in making a goods declaration with the Thai Customs Department. See THA-48, THA-86, and THA-88 for additional information and instructions on submitting an LPI to Customs). Refer to THA-57 and THA-87 for detailed instructions on submitting a drug importation waiver request via the Skynet E-Submission System (THA-54).

P.Y.8

As indicated in ClinSampleProd, the Thai FDA also accepts paper and electronic clinical trial application submission packages for requests for permission to produce sample drugs for human research studies. However, if the electronic system is not available, the application must be submitted in paper form, along with the appropriate supporting documentation (see Submission Content section for content details). In the case of filing via the Skynet E-Submission System (THA-54), information will be filled in the system in a P.Y.8. form, and the research project information will be created automatically. If the Thai FDA reviewer determines that submitted documents require correction or additional documentation needs to be submitted, the applicant must make corrections/clarifications based on the evaluation results within the specified time by submitting a correction/clarification request form (see ClinSampleProd (Appendix 8) and THA-76 (Appendix 8)). The paper documentation should be submitted to the New Drugs and Drug Research Promotion Group within the Medicines Regulation Division or submitted electronically via THA-54. When submitting a paper application, the applicant must also submit a template file for importing the data via THA-54 to serve as a starting point for operators in the electronic process and for use in overseeing the trial. A copy of all the submitted documents should also be provided in PDF format.

Additionally, per ClinSampleProd, the non-local applicant must authorize a qualified person through a power of attorney to submit an application and respond to requests to provide clarification, amend, and/or receive documents related to the submission. The attorney-in-fact should be someone who has knowledge in pharmacy or a related medical field as well as an understanding of requests, permissions, etc. relating to the application submission and associated documentation. The scope and responsibilities of the attorney-in-fact must be specified in the authorization to include filing application submission clarifications and corrections. The authorization documentation should be submitted with the paper application, or via the Skynet E-Submission System (THA-54), if the application is being submitted electronically. ClinSampleProd further notes that one (1) set of power of attorney submission documentation may only be used for one (1) application submission request.

As indicated in ClinSampleProd, Thai and English are the preferred languages for use in preparing an application package to request permission to produce investigational drugs for clinical research. The following requirements are specified:

Research project name in Thai and English
Summary of research project in Thai
Drug labels for every package size in Thai or English
Patient Information Sheet in Thai
EC approval document in Thai
Complete research project details in Thai or English

OSSC Contact Information for Application Submissions

Per THA-74, THA-65, and THA-77, the following is contact information for submitting an application to the OSSC (THA-35) in person or via email, and for requesting permission to access the Skynet E-Submission System (THA-54):

One Stop Service Center (OSSC)
Building 6, 5^th Floor
Food and Drug Administration Building
Ministry of Public Health
88/24 Tiwanon Road
Talat Khwan Subdistrict
Mueang District, Nonthaburi Province 11000

Email (E-Consult): econsultcenter@fda.moph.go.th
Phone: 02 590 7614 (Consultation E-service for general inquiries, reporting usage problems, and issues related to requesting permissions)

See also THA-52 for the Medicines Regulation Division staff list.

Ethics Review Submission

Per G-ResEthics, each institutional EC should establish its own requirements for protocol submission along with the required documents including the application, number of research protocol copies to be submitted, the patient information sheet, the informed consent form, and the case report form. Each EC should also communicate these requirements to personnel or staff within the institution.

According to THA-4, if a trial site is not affiliated with a Thai FDA-recognized EC, the investigator(s) usually needs to apply to two (2) ECs for approval—the unaffiliated local EC and a central EC approved by the Thai FDA. THA-1 further explains that both the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) and the Central Research Ethics Committee (CREC) are categorized as central ECs because they can accept all clinical research studies for review, regardless of the trial sites involved.

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health

According to THA-13, the ECMOPH requires one (1) original and 20 copies of the protocol submitted in Thai, and one (1) copy submitted in English for review purposes.

Per THA-41, investigators can electronically submit applications to the ECMOPH to obtain approval for new research projects or to request other services via the ECMOPH e-submission login page (THA-40).

Central Research Ethics Committee

THA-36 and THA-29 indicate that investigators applying for a new research project should submit an application to the CREC for review via its Online Submission System (THA-43).

THA-29 further explains that in some cases, hard copies may be requested by the CREC officer, with the number of additional hard copies requested subject to the reviewer’s requirements. Per THA-29, one (1) set of hard copy documents, consisting of a project folder and a CD with project information should be submitted. Documents should be placed in a folder indicating the correct number of files in order to avoid processing delays.

THA-29 also states that if a local EC requires a hard copy for the local assessment, the CREC will prepare an introduction letter and local issue assessment form. These documents will be sent to every local EC by email; the researcher/coordinator will be copied on this email. The researcher/coordinator will attach the local CREC introductory letter and assessment form to the hard copy submission package for the local EC.

See also THA-34 for detailed application package documentation submission requirements, and THA-37 for a comprehensive list of all the CREC Standard Operating Procedures (SOPs).

Per THA-34 and THA-38, in the case where the research project is in English, a brief research outline should be provided in Thai as well. In addition, an explanation about the research participants and letter of intent to consent should be provided, if the master version of the informed consent documents are written in English.

Which EC?

Saving time...and cost!

Guidelines for the preparation of a research proposal submitted to the Ethical Review Committee for Research on Human Subjects, Ministry of Public Health (p. 67)

Chapters 1-2

Requirements before using the E-consult system, Applying for service, Requesting Permissions, and Form

1 and 3

4-5

Appendices 1-4 and 7-9

Appendices 1-13, 15, and 17

Online Submission – For Researchers/Research Coordinators

1. Introduce the Ethics Request System (E-Submission)

6.1

3, 11-13, and 15

1-2 and Appendices 1-4 and 7-9

Preface; Summary of Changes in this Edition; 1-3; and Appendices 1-13, 15, and 17

5 and Form EC-1

Appendix 12

Submission Content

Last content review/update: November 8, 2024

Regulatory Authority Requirements

As specified in GenHlthLaw, HlthResRegs, NOM-012-SSA3-2012, COFEPRIS-GCP, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the following documentation must be submitted to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) as part of the approval process (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Authorizations, Certificates and Visits form (original and two (2) copies) (MEX-25)
Proof of payment of rights (original and two (2) copies)
Request letter (in editable format (.docx) containing study data (title, investigator’s name, etc.), description of study risk level and duration (including estimated start and end dates (DD/MM/YYYY), and documents submitted for research protocol authorization (original)
Response to COFEPRIS prevention letter requesting missing or additional information should be submitted in a new request letter
Research protocol (original and one (1) copy)
Acceptance letter from research institution head and responsible principal investigator (PI)
Sponsor letter of acceptance of position and delegation of responsibilities (must include at least sponsor contact information, description of obligations and protocol rights, sponsor legal representative/authorized person signature, protocol number, when applicable, a certified copy of the apostilled, notarized, and translated power of attorney) (one (1) copy)
Letter of No Conflict of Interest from the sponsor (one (1) copy)
Document proving applicant’s legal identity (e.g., health license, operating notice or, where appropriate, the Federal Taxpayer Registry (Registro Federal de Contribuyentes (RFC)) (one (1) copy)
Follow-up letter from sponsor providing monitoring/auditing plan
Model letter of informed consent in Spanish
Informed consent of the research participant or, where appropriate, the legal representative (original and one (1) copy)
Study schedule (original and one (1) copy)
Health warehouse license for operation of storage and distribution warehouse for biological products for human use, with handling of medications: narcotics, psychotropics, vaccines, toxoids, serums and antitoxins of animal origin and/or blood derivatives (one (1) copy)
Letter of acceptance of responsibility from the importer (signed by legal representative of the importer)
Importer name, license number, and address
Sanitary license of the warehouse for storage and distribution of the research product (only narcotics, psychotropics, biologicals, radiopharmaceuticals, and vaccines)
Letter of import supplies providing approximate total quantity and description of investigational products (IPs) requiring importation at each stage of the study; letter serves as acknowledgement of information, not authorization (original and one (1) copy)
IP route of administration
Insurance policy or current document from the financial fund that covers all study participants at the local level (one (1) copy)
Current Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and Research Committee registration and Biosafety Committee registration, where applicable (one (1) copy)
Favorable opinion of REC, Research Committee, and where appropriate, Biosafety Committee (original and one (1) copy)
REC member list
REC member letters recusing themselves if on research team (one (1) copy)
REC letter describing study follow-up monitoring process (one (1) copy)
Letter of No Conflict of Interest and Confidentiality signed by REC members (one (1) copy)
Institution’s or establishment’s sanitary license or notice of operation (one (1) copy)
Letter of authorization to carry out the research, signed by institutional head or health institution owner (must include protocol title/number, PI name, institution/establishment head signature and position, research center name/address) (original and one (1) copy)
Where applicable, copy of agreement between research centers that have agreements for emergency medical care with other institutions
Acceptance letter from the head of the institution or establishment describing resources available for emergency management (original and one (1) copy)
Health license of the establishment to carry out medical emergency care
Agreement or contract of the establishment for the care of medical emergencies of the research (must include at least title/protocol number; PI name; scope, clauses, and validity; signature of holders and legal representatives of both institutions; statement establishing the care of medical emergencies)
Agreement or contract with institution or establishment to provide care for research related medical emergencies (one (1) copy)
Letter of acceptance, confidentiality, and commitment to report suspected adverse reactions and events signed by the PI (original and one (1) copy)
Summary of PI’s professional record/official professional documentation issued and registered by competent educational authorities (original and one (1) copy)
Professional background of the PI (one (1) copy)
Summary of academic preparation and experience of medical personnel, paramedics, and other experts involved in study (include updated Curriculum Vitae (CV), dated and signed, for each member; include a copy of documentation issued and registered by competent educational authorities accrediting academic preparation) (original and one (1) copy)
Express letter of No Conflict of Interest to conduct the research, signed by the PI and research team
PI letter describing research team’s delegation of responsibilities (must including protocol title/number, detailed description of activities, PI name/signature, team member signatures) (one (1) copy)
Investigator’s Brochure (IB) (original and one (1) copy) (also known as investigator’s manual in Mexico)
Letter describing the sponsoring institution’s or establishment’s resources for the study’s development (include institution/establishment name, PI name, protocol title/number, type of support required (e.g., human, material, financial, advisory information, equipment, auxiliary laboratory services, cabinets, and other resources), and how support will be provided and distributed) (original and one (1) copy)
Document indicating drugs used in study comply with Good Manufacturing Practices (GMPs) and have the expected quality characteristics for IPs to be used in study, or letter documenting GMPs (one (1) copy)
Status of stability studies, or letter documenting IP stability studies comply with applicable regulations (one (1) copy)
Basic pharmacological and preclinical product information
Additional study information (countries where research will be conducted, health conditions/problems, public consultation contact, scientific consultations contact)
Optional pre-assessment evaluation opinion (See Scope of Assessment and Submission Process sections for details on pre-assessment evaluations)

See also Scope of Assessment and Timeline of Review sections for additional COFEPRIS review process and timeline information.

Refer to GenHlthLaw, HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, G-DIGIPRiS-ResProts, and MEX-18 for more detailed submission information. See also MEX-36 for information on obtaining a certificate of GMPs.

Ethics Committee Requirements

As indicated in MEX-84 and G-DIGIPRiS-ResProts, the following documentation should be submitted to obtain the favorable opinion of the REC, the Research Committee, and where appropriate, the Biosafety Committee:

Full title and number of the research protocol
Research protocol with the version and date in Spanish
IB with the version and date in Spanish
Full name of the IP corresponding to the research center
Research center company name and address
Informed consent forms with the version and date in Spanish
Protocol summary
Detailed description of the documents evaluated and approved in Spanish, citing version and date
Validity of the approval opinion (not greater than one (1) year)
Name, position, and signature of the person responsible who supports the opinion
Confirmation of the evaluation of aspects of a scientific nature, the risk/benefit of the protocol as well as the guarantee and well-being of the participants

Additionally, a signed opinion issued on letterhead should be submitted that includes:

Committee name and address (in accordance with its current registration)
Date the opinion was issued
PI name
Company name and address of the research center
Title of the study and protocol number
Status/result of the evaluation of the documents (must be approved)
Date of issue of the opinion (day, month, and year)
Name and position of the signatory who supports the opinion (must be the President or the Secretary Member)

G-DIGIPRiS-ResProts, also notes that only the opinions with the signature of the President of the REC (or, where appropriate, the Secretary-Vocal) will be accepted with a letter attached stating “NO VOTE” or a justification for the absence of the president. See MEX-84 and G-DIGIPRiS-ResProts for additional ethics committee requirements.

Clinical Protocol

As set forth in MEX-84 and G-DIGIPRiS-ResProts, which are in compliance with the Guideline for Good Clinical Practice E6 (R2) (MEX-22), and NOM-012-SSA3-2012, the research protocol should include the following elements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title, acronym, and protocol number (corresponds to the opinion of the committee(s) evaluators)
Document version and date, and amendments (if applicable) (corresponds to the opinion of the committee(s) evaluators)
Sponsor name/address and monitor, if different from sponsor
Theoretical framework (IP name/description, preclinical findings summary, etc.)
Definition of problem
Participant selection and withdrawal criteria
Statement that the clinical trial will be conducted in accordance with the protocol, good clinical practices, and local regulatory requirements
Background
Rationale
Hypotheses (if applicable, includes statistical hypotheses)
General objective (if applicable, includes specific, primary, secondary, or exploratory objectives)
specific objectives)
Materials and methods
Study design (e.g., inclusion/exclusion and elimination criteria; information input, processing, analysis, and interpretation)
Phase and type of study
Study duration
Sample size (global and local, as appropriate)
Countries where the research will be carried out
Health conditions or problems studied
Capture, processing, analysis, and interpretation of the information obtained
Route of administration, dose, dosing regimen, and treatment period(s) and justification
Accountability procedure for handling the IP and placebo (if applicable)
Mechanisms for maintaining randomization and blinding (if applicable), and codes for breaking them (e.g., criteria for premature unblinding, etc.)
Statistical considerations
Ethical considerations
Efficacy and safety assessments
Study schedule (document detailing activities to be carried out during the investigation)
Bibliographic references and relevant trial data
Names and signatures of PI and associate researchers (no more than five (5), classified according to their involvement in the research project)
Other documents related to the research project or protocol
Optional pre-assessment evaluation opinion (See Scope of Assessment and Submission Process sections for details on pre-assessment evaluations)

In addition to the protocol submission, per NOM-012-SSA3-2012, an additional letter should accompany the application. Please refer to NOM-012-SSA3-2012 for more specific letter instructions. See also MEX-84 and G-DIGIPRiS-ResProts for more detailed protocol requirements.

2-10

1. Homoclave, name and modality of procedure (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)

6. Clinical Trial Protocol and Protocol Amendment(s)

Change Control, V, X. Sections that Make Up a Request for Protocols of Research in Human Beings, and XIII. Specific Sections of the Procedure on the Platform (I - XV)

Requirements

2 and 10.1

Title V (Chapter I, Article 102)

Title III (Chapter I, Article 62) and (Chapter II, Article 69)

6.1-6.3

Last content review/update: March 21, 2024

Regulatory Authority Requirements

N.Y.M.1

As per ClinImprtOrdr and G-CT-DIPApp, sponsors must submit the following documents to the Thai Food and Drug Administration (Thai FDA) to request a drug import waiver request (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Cover letter
Application for Permission to Import or Order Drugs for Research Purposes in the Kingdom (N.Y.M.1 form) (see ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2))
Checklists and Attached Documents for N.Y.M.1 form (see appendices in ClinImprtOrdr and THA-18)
Drug labels for every package size in Thai or English
Package inserts (for registered drugs)
Prescriptions (for registered drugs)
Investigator’s Brochure (IB) (for unregistered drugs)
Informed Consent Form in Thai
Patient Information Sheet in Thai
Research project summary in Thai
Completed version of study protocol in Thai or English
Chemistry, manufacturing, and control (CMC) information
Ethics Committee (EC) approval from a Thai FDA-recognized institutionally-based EC and/or an independent EC. If waiting for approval from the relevant EC, instead submit the latest protocol version under consideration.
Estimates of the amount of study drug, comparators, or other goods to be imported
Certificate of Analysis
Certificate of Free Sale in English and other language used
Drug registration authorization document
Summary of product characteristics
Literature review
Description (name and content) and pictures of lab/materials to be imported
Power of attorney
Investigational medicinal product (IMP) information

Per ClinImprtOrdr, when an applicant authorizes a qualified person through a power of attorney to submit an application package, the following documents must also be included with the submission:

Copy of identity card of the grantor and the attorney-in-fact with signatures to certify that they are true copies
Stamp duty in the amount of 30 Baht per one (1) power of attorney designation

As delineated in G-CT-DIPApp, applicants are also required to submit the following documents to the Thai FDA regarding EC approval:

Protocol title
List of principal investigator(s) (PIs)
Proposed study site
List of documents reviewed and approved by the EC, including the document version
Period of approval and/or date of expired approval

As noted in ClinImprtOrdr, the Ministry of Public Health (MOPH) may also establish an academic committee or subcommittee for certain drugs requiring special supervision (e.g., the Academic Subcommittee on AIDS Vaccine Trials to review AIDS vaccines, etc.). Therefore, when submitting an application to request permission to import or order a specialized drug for clinical research requiring this type of oversight, an additional approval letter from the relevant committee is also required. Additional information on obtaining the approval for the committee is not available.

P.Y.8

Per ClinSampleProd, applicants must submit the following documents to the Thai FDA to request permission to produce drug samples for the registration of drug formulas for human research studies:

Application for Permission to Produce Drug Samples for Drug Formula Registration (P.Y.8. Form) (see ClinSampleProd (Appendix 1) and THA-76 (Appendix 1))
Research project summary in Thai
Certification of compliance with the terms and conditions related to the production of drug samples for use in human research studies
Certificate of Compliance for Principal Investigators
Evidence of insurance or compensation
Power of attorney (for paper submissions)
A copy of the license to produce modern drugs (for paper submissions)
Drug labels for every package size in Thai or English
Copy of Good Manufacturing Practice (GMP) Certificate
Drug leaflet (for bioequivalence study drugs)
IB (for research drugs)
Patient Information Sheet in Thai
EC approval from a Thai FDA-recognized institutionally-based EC and/or an independent EC, except in the case of waiting for approval from the relevant EC
Drug quality control and pharmaceutical production documentation
Documents approved by relevant technical committees (if any)
Complete research proposal in Thai or English
Document self-verification form (see ClinSampleProd (Appendix 7) and THA-76 (Appendix 7))

Per ClinSampleProd, when an applicant authorizes a qualified person through a power of attorney to submit an application package, the following documents must also be included with the submission:

Copy of identity card of the grantor and the attorney-in-fact with signatures to certify that they are true copies
Stamp duty in the amount of 30 Baht per one (1) power of attorney designation

As noted in ClinSampleProd, the MOPH may also establish an academic committee or subcommittee for certain drugs requiring special supervision (e.g., the Academic Subcommittee on AIDS Vaccine Trials to review AIDS vaccines, etc.). Therefore, when submitting an application to request permission to import or order a specialized drug for clinical research requiring this type of oversight, an additional approval letter from the relevant committee is also required. Additional information on obtaining the approval for the committee is not available.

Ethics Committee Requirements

Per G-ResEthics, each institutional EC should establish its own requirements for protocol submission along with the required documents including the application, number of research protocol copies to be submitted, the patient information sheet, the informed consent form, and the case report form. Each EC should also communicate to personnel or staff within the institution.

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health

Per THA-13, the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) requires investigators (applicants) to submit the following documentation for ethics approval:

One (1) original set and 20 copies of the protocol in Thai and one (1) copy in English for review
Ethical considerations
Combined information sheet and informed consent certificate for research participants
Budget details and funding source
Curriculum Vitae (CV) for each research team member
Letter of approval from implementing institution
Results of ethical review by EC of implementing institution, if available
Data collection/questionnaire tools
Letter signed by PI’s supervisor
For an international project, Thai and foreign PIs required for each side
Material transfer agreement for transfer of blood or biomedical samples
References

Refer to THA-13 for detailed ECMOPH submission requirements respectively.

Central Research Ethics Committee

According to THA-34 and THA-38, investigators applying for an initial research project review by the Central Research Ethics Committee (CREC) should submit the following:

Books/memorandum for research presentation signed by investigator (Word and PDF files required)
Ethics Consideration Proposal Form for Biomedical Research Projects (CREC form AP 04-S04) signed by investigator (Word and PDF files required)
Complete research proposal
Brief research proposal in Thai
Documents clarifying information about research participants and letter of intent to consent (in the case of a master informed consent form (ICF) version, single document in English is used for all institutions; alternatively, each institution may also use their own documents) (See also THA-46 for ICF template and checklist links)
Case report form
IB (including Investigator’s Guide; a certificate that the drug has been approved by the Thai FDA; invoice in the case of a drug that has been registered with the Thai FDA; and a drug leaflet)
Other documents (including questionnaire or interview form; notebook; documents for invitation to participate in the research, such as brochures, posters, public relations scripts; other documents applicable to volunteers/research participants; documents requiring issuance of a certificate)
Research injury compensation insurance documents
Material transfer agreement (MTA) (must be uploaded according to each institution’s form)
(Draft) Research project budget
Letter of approval from the junior supervisor (separate documents by institution) (including a list of researchers at all data collection institutes in Thailand)
Investigator CVs and evidence of good clinical practice (GCP) training or research ethics training
Conflict of Interest Form completed by PIs/co-investigators (CREC form AP 06-S04) (separate documents by institution)
Research Outline Completeness Check Form (CREC form AO 01-S04)
PI for clinical trial phase I/II research projects (CREC form AP02-S04)
Proof of fee payment

Refer to THA-34 and THA-38 for detailed CREC submission requirements.

Clinical Protocol

As delineated in ClinImprtOrdr, ClinSampleProd, G-ResEthics, and G-CT-DIPApp, the clinical protocol should include the following elements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Protocol summary/synopsis
General information (e.g., sponsor and investigator(s) name(s) and address(es))
Background information (e.g., investigational product name and description)
Trial objectives and purpose
Trial design
Number of trial participants
Participant selection/withdrawal criteria
Participant treatment
Safety and efficacy assessments
Quality control/quality assurance
Adverse event reporting requirements (See the Safety Reporting section for additional information)
Statistics and methods to track trial data
Sponsor specifications for direct access to source data/documents
Ethical considerations
Data management and recordkeeping
Financing and insurance details
Publication policy
Supplements
Information about each research facility in Thailand
Number of institutions participating in the research in Thailand
Other countries where the research project is being conducted
IMPs to be used

For complete protocol requirements, refer to ClinImprtOrdr and Annex 6 of G-ResEthics, which is directly based upon the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (THA-28) and the ICH guideline Structure and Content of Clinical Study Reports (E3) (THA-27). Per an in-country subject matter expert, Thailand is implementing THA-28. Both of these ICH guidelines are also referenced in G-ResEthics.

G-CT-DIPApp also provides protocol synopsis requirements for submission to the Thai FDA. Please refer to G-CT-DIPApp for detailed information.

In the instance of a multicenter clinical trial, G-ResEthics indicates that protocols submitted to each institutional EC should contain the same content and should specify the quality control techniques to ensure that the research practices are the same in each institution.

Also, see THA-13 for ECMOPH and THA-29 for CREC protocol submission requirements. (See also THA-18 and THA-76 for the forms included in the appendices in ClinSampleProd and ClinImprtOrdr.)

Guidelines for the preparation of a research proposal submitted to the Ethical Review Committee for Research on Human Subjects, Ministry of Public Health (p.67); Ethical Criteria

Appendices 1-2 and 7

Appendix 2-11 and 13

6

Annex 6

3, 12-13, and 15

Preface, 1, 4, and Appendices 1-2, and 7

Summary of Changes in this Edition, 1, 3, and Appendices 1-11, and 13

Timeline of Review

Last content review/update: November 8, 2024

Overview

As delineated in HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS))’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the health institution’s Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and where applicable, the Biosafety Committee. Therefore, COFEPRIS and ethics committee (REC, Research Committee, and Biosafety Committee) reviews may not be conducted in parallel. However, per HlthResRegs, the REC, the Research Committee, and the Biosafety Committee may meet together to decide whether to authorize a protocol to conduct research on humans, as appropriate.

Regulatory Authority Approval

Pursuant to HlthResRegs, COFEPRIS must approve a request for research protocol authorization within 30 working days from the day following an application’s filing. However, according to G-HumResProt, COFEPRIS is required to complete its review of a research protocol authorization request and notify the applicant within three (3) months.

According to Reg-COFEPRIS and MEX-53, COFEPRIS’s Sanitary Authorization Commission (Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on requests for human research protocol authorizations. Per G-HumResProt, the evaluator in CAS issues a resolution of authorization or a prevention letter, and it is forwarded to the head of the area (CAS) for signature. If a prevention letter is issued in which additional or missing information is requested, the applicant is required to address the issues within 30 calendar days. See Submission Process section for details on tracking submitted procedures via the Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) or COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86).

Per G-ResProtocolAmd, G-ObsrvStdies, and G-BioequivStud, COFEPRIS’s review deadlines (three (3) months or 90 calendar days) to notify applicants are also applicable to requests for authorization of protocol amendments or modifications and requests for authorization to conduct risk-free research (observational studies) and bioequivalence studies. Refer to G-ResProtocolAmd, G-ObsrvStdies, and G-BioequivStud for details. See Submission Process section for detailed submission requirements.

Additionally, per Reg-HlthProd and G-UnregDrugImprts, COFEPRIS has 10 days to approve import requests for investigational drug products. If COFEPRIS does not respond within this timeframe, the request is deemed approved. G-UnregDrugImprts also notes that COFEPRIS has four (4) business days to send the applicant a prevention notification regarding missing or additional information required. The applicant, in turn, has five (5) business days to respond.

Per HlthResRegs and G-RNECManual, once the applicant obtains an official authorization from COFEPRIS, the applicant has a maximum of five (5) working days to enter this information into the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). The RNEC is in charge of the CAS’s Clinical Trials technical area and serves as the interface through which applicants are required to submit their application documentation in order to maintain an updated national inventory of clinical studies involving humans and/or their biological samples.

Enabled Pre-Assessment Support Unit (UHAP) Evaluations

Per HlthResRegs, prior to submitting an authorization request, applicants may also obtain a pre-assessment evaluation by an authorized third party that helps to facilitate COFEPRIS’s review. MEX-21 and MEX-10 explain that rather than submitting an application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment (third party) evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Specialty Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). According to MEX-10, the UHAP has a maximum of 30 calendar days to respond to an evaluation request. See MEX-10 and MEX-121 for additional information on authorized third parties. See the Scope of Assessment and Submission Process sections for detailed UHAP information.

Ethics Committee Approval

As delineated in G-RECs-Op-2018, the REC agenda and documents corresponding to each session should be delivered at least seven (7) days prior to the meeting. It is then recommended that the REC’s decision be sent within a period not exceeding five (5) working days after the committee has met, or if applicable, not to exceed 30 calendar days from the date of request for its review. G-RECs-Op-2018 and G-DIGIPRiS-ResProts also state that the approval of a new application is valid for one (1) year.

In addition, G-RECs-Op-2018 indicates that the REC should establish procedures for monitoring approved studies, from the point at which the decision was made until the completion of the investigation and reporting of results. RECs should conduct at least one (1) review a year.

9.2

10

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11), Response Time, and Steps

Response Time and Steps

Validity of the Resolution

3.3, 6.2, 8.1, and 8.2

Response Time and Steps

Chapter IV (Article 14)

Title VI (Chapter IV, Article 196)

Title III (Chapter I, Articles 62 and 74a) and (Chapter II, Articles 65 and 69) and Title III bis

5.2, 6.3, 9.2, and 10.3

Last content review/update: March 21, 2024

Overview

ClinImprtOrdr specifies that a drug import license application for clinical research purposes is submitted to the Thai Food and Drug Administration (Thai FDA) after the research project and all the research sites have been approved by the ethics committee (EC), or in parallel, pending review by at least one (1) EC involved in the study. Per ClinSampleProd and DrugProdReqs, the application to produce drug samples for the registration of drug formulas for human research studies must also be submitted to the Thai FDA either after the research project and all the research sites have been approved by an EC, or in parallel, pending review by at least one (1) EC involved in the study.

Regulatory Authority Approval

As specified in THA-78, the Thai FDA has 60 working days to evaluate an application to import or order drugs in the country for clinical research (N.Y.M.1); 60 working days to evaluate an application to produce drug samples to request modern drug registration for human research studies (P.Y.8); 20 working days to review an application to amend a N.Y.M.1 or P.Y.8 submission; one (1) working day to review an application for a certificate of pharmaceutical product (Certificate of Pharmaceutical Product/Certificate of Free Sale); and 30 working days to evaluate the accuracy and translation of a Good Manufacturing Practice (GMP) assessment report from a Thai version to an English version.

Per G-CT-DIPApp, upon receipt of an application package, the Thai FDA’s One Stop Service & Consultation Center (OSSC) (THA-35) sends the application package to an officer in the Thai FDA’s International Affairs and Investigational Drug Section. The officer then screens the package for completeness and informs the eligible sponsor of the results within five (5) working days from the date the application was received. If deemed complete, the officer sends the package to the assigned technical reviewer to proceed. If the officer finds the package to be incomplete, a “Screening Result Notification form” will be sent to the applicant or the applicant’s attorney for correction. If the applicant or the applicant’s attorney fails to fully correct the package within five (5) working days, then the Thai FDA will send a rejection letter and return all the documents to the applicant. However, the applicant may later correct or amend the application package and resubmit it to the OSSC. Once the correction is completed, the officer will send the application package to the assigned reviewer to proceed.

Per G-CT-DIPApp, the reviewer then receives the application package and performs a technical assessment. If the reviewer determines the package is technically correct, then it will be forwarded to the Thai FDA’s Secretary-General for approval. If the reviewer finds the application package technically incorrect, then it will be forwarded to the Thai FDA’s Secretary-General for rejection. If the reviewer finds the technical information to be incomplete, then the applicant or the applicant’s attorney will be asked to clarify and/or submit additional documents/information. If the documentation or amended information is not submitted within five (5) working days, the Thai FDA will issue a rejection letter and return the package to the applicant. However, the applicant may resubmit a corrected package to THA-35 (timeline not specified in G-CT-DIPApp). If the applicant can completely correct the application package, the officer will forward the package to the assigned reviewer for re-assessment.

In addition, ClinImprtOrdr and ClinSampleProd further specify that once the Thai FDA receives the EC approval documentation, the agency will complete its review within 15 days. See also THA-18 (Appendix 13) and THA-76 (Appendix 9) for the form to submit results of EC review to the Thai FDA. Refer to the Submission Process and Submission Content sections for detailed submission requirements.

Ethics Committee Approval

The review and approval process by a Thai FDA recognized EC will vary by institution. However, according to THA-13, which provides the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) requirements, and THA-5, which provides more general EC requirements, the EC review and approval process can take between two (2) and three (3) months.

Per G-ResEthics, each EC should establish its own requirements for protocol submission and timeline of review.

Clinical Trials

Instruction for the Submission of a Study/Research Proposal to be Reviewed by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (p. 63)

Appendices 1-3, 7, and 9

Appendices 2-4, 11, and 13

Items 2, 11, 33, 34, and 49

Annex 6

2-3 and 15

1-3, and Appendices 1-3, 7, and 9

1, 3, and Appendices 1-4, 11, and 13

Appendix 12

Initiation, Agreements & Registration

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, NOM-012-SSA3-2012, COFEPRIS-GCP, G-HumResProt, and MEX-84, a clinical trial can only commence after an applicant receives authorization from Mexico’s Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Per HlthResRegs, G-HumResProt, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. No waiting period is required following the applicant’s receipt of these approvals.

As per GenHlthLaw, an applicant must be a resident of Mexico and is required to obtain an import license from COFEPRIS for the shipment of an investigational product to be used in the trial. The applicant must be a resident of Mexico or have a legal representative submit the application on their behalf. (See the Manufacturing & Import section for additional information).

As set forth in NOM-220-SSA1-2016, the health record holder, principal investigator (PI), sponsor, or person responsible for a study authorized by COFEPRIS must also issue a notice of a study’s commencement (e.g., first visit of the first patient) and a notice of its completion (e.g., last visit of the last patient).

Clinical Trial Agreement

Prior to initiating the trial, as set forth in NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, if applicable, the sponsor must sign a letter of acceptance that serves as an agreement to assume the project obligations and rights stated in the letter. G-DIGIPRiS-ResProts also notes that the letter must include the sponsor’s delegation of activities to other institutions and/or companies duly authorized to accept the obligations, responsibilities, and rights imposed by the development and conduct of the study. Per G-DIGIPRiS-ResProts and NOM-012-SSA3-2012, in the case of corporate entities, this position must be accepted by an individual authorized to do so or by a corporation’s legal representative, according to its organizational structure or incorporation regime.

Additionally, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts state that the sponsor must sign a letter to ensure there are no conflicts of interest that could lead to the interruption of treatment for the research participant. NOM-012-SSA3-2012, further specifies that when the research is sponsored by a public or private organization, that it must be guaranteed that this will not generate conflicts of interest that could cause the interruption of treatment for the research participant. A detailed explanation of the resources available and the way in which they will be provided and distributed must also be attached in the research protocol.

According to COFEPRIS-GCP, COFEPRIS requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. COFEPRIS-GCP indicates that the sponsor must establish in writing each of the research team member functions and responsibilities, and the financial agreement with the PI. The sponsor or the CRO must also establish a declaration of financing, sponsorship, affiliations, contracts of agreements with other institutions involved, and procedures for handling any conflict(s) of interest, and a system for providing incentives and quantity/payments to research participants. MEX-32 specifies that the financial aspects of the trial should be documented in an agreement between the sponsor and the investigator and the institution.

Further, per MEX-32, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure and should provide sufficient time for the investigator and institution to review the protocol and the information provided.

COFEPRIS-GCP further states that in the case of delegating investigation-related activities to a CRO, the sponsor must also establish in writing each of the activities that are delegated. However, the ultimate responsibility for all CRO activities remains with the sponsor. Additionally, COFEPRIS-GCP indicates that the sponsor or the CRO must establish a declaration of financing, sponsorship, affiliations, contracts, or agreements with other institutions involved, handling of any conflict of interest, incentives, and quantity and payments to the research participants.

According to MEX-32, the sponsor or the CRO must also obtain the investigator(s)’s and the institution(s)’s agreement to:

Conduct the trial in compliance with MEX-32 and the protocol agreed to by the sponsor and approved by the ethics committee
Comply with data recording and reporting procedures
Permit monitoring, auditing, and inspection
Retain essential documents until the sponsor informs them that they are no longer needed

Per MEX-32, the sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

Per G-DIGIPRiS-ResProts, once an official authorization from COFEPRIS is obtained, some of the data provided by the applicant in COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86), will be migrated to COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) and to the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). According to MEX-109, the G-RNECManual is useful for information on registering with RNEC for clinical trial applications submitted in person at the CIS (MEX-37).

Governance

Per GenHlthLaw, HlthResRegs, and NOM-012-SSA3-2012, every health institution where research is conducted is required to establish a Research Committee and a Biosafety Committee. Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, REC and Research Committee approval is also required for each trial site where a study is being conducted, and when applicable, Biosafety Committee approval is required as well.

HlthResRegs explains that the Research Committee evaluates the technical quality and scientific merit of the proposed research, and its opinion must contain the REC opinion and, where applicable, the Biosafety Committee opinion. The Biosafety Committee, in turn, is responsible for determining and regulating the use of ionizing radiation or genetic engineering techniques within the health institution as indicated in HlthResRegs, GenHlthLaw, and NOM-012-SSA3-2012. Pursuant to HlthResRegs, NOM-012-SSA3-2012, and G-HumResProt, the Biosafety Committee issues a technical opinion on the biosafety aspects of the proposed research and ensures that research study staff, research participants, the community, and the environment are protected against radiological risks.

Additionally, per MEX-47, COFEPRIS is responsible for registering Research Committees and Biosafety Committees. Refer to MEX-47, G-BiosafetyReg, and G-ResCommReg for detailed Research Committee and Biosafety Committee registration requirements. See MEX-26 for COFEPRIS’s Research Committee and Biosafety Committee registration form.

2, 4.1, 4.5, and 9.2

4.9, 5.6, and 5.9

XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements (2-3 and 11)

Preamble, 2, 4.1, 4.9-4.11, 4.13, and 5.7

Title V (Chapter I, Article 98), Title XII (Chapter I, Articles 194 and 194 bis) and (Chapter XIII, Articles 238-239 and 283-285), and Title XVI (Chapter I, Articles 368-369 and 371-372)

Chapter I (Articles 1 and 3) and Chapter IV (Article 14)

Title I (Chapter I, Articles 9 and 10), Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69), Title V (Chapter I, Articles 99-102 and 110-111), and Title VI (Chapter I, Articles 113 and 117)

7.4

5.2, 6.3, 7.4, and 9.1-9.2

Last content review/update: March 21, 2024

Overview

In accordance with ClinSampleProd, ClinImprtOrdr, and ECRegProc, a clinical trial can only commence after a sponsor receives approval of a drug import application for clinical research purposes or of a request to produce drug samples for human research studies from the Thai Food and Drug Administration (Thai FDA), as well as approval to conduct the clinical trial from a Thai FDA recognized ethics committee (EC). No waiting period is required following the sponsor’s receipt of these approvals. (See also THA-18 and THA-76 for the forms included in the appendices in ClinImprtOrdr and ClinSampleProd.)

Additionally, the clinical trial should be conducted in compliance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28). Per an in-country subject matter expert, Thailand is now implementing THA-28.

Clinical Trial Agreement

G-ResEthics and THA-28 require the sponsor to sign a letter of agreement with the participating institution(s) before the trial begins. THA-28 also notes that any agreements between the sponsor and the investigator(s)/institution(s) and any other parties involved with the trial should be in writing either as part of the protocol or in a separate agreement.

Per THA-14, researchers should also abide by research obligations and agreements specified by and entered into with fellow researchers, funding agencies, and their affiliates.

Clinical Trial Registration

The ClinImprtOrdr application document checklist (Appendix 3) includes clinical trial registry information as one (1) of the items to be included in the application submission package, specifying that sponsors may register with either the Thai Clinical Trials Registry (TCTR) (THA-31) or a foreign registry. Sponsors may register in more than one (1) location.

2

Appendices 1-3, 7, and 9

Appendices 2-4, 11, and 13

1.25, 2.8, 4.1, 5.1, and 5.5

Annex 5 (6)

Preface, 1-3, and Appendices 1-4, 7, and 9

Preface, 1-3, and Appendices 1-4, 11, and 13

4-5 and 9-10

Safety Reporting

Last content review/update: November 8, 2024

Safety Reporting Definitions

In accordance with NOM-220-SSA1-2016, NOM-012-SSA3-2012, G-ClinResPV, and G-PharmPerSafRpt, the following definitions provide a basis for a common understanding of Mexico’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Adverse Event/Experience (AE) – Any undesirable medical event that may occur in a research participant during the clinical investigation stage of a drug/vaccine, but does not necessarily have a causal relationship to it
Adverse Drug Reaction or Adverse Reaction (ADR) – An unwanted response to a drug, in which the causal relationship with it is, at least, reasonably attributable
Unexpected Adverse Drug Reaction – One whose nature or severity is inconsistent with the applicable product information, or in the documentation presented for its sanitary registration
Suspected Adverse Drug Reaction (SRAM) – Any clinical or laboratory manifestation that occurs after administration of one (1) or more drugs

Safety Reporting Requirements

As specified in NOM-220-SSA1-2016-Mod, for clinical study related incidents involving health professionals (public and private) or institutions conducting health research, notifications to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS))’s National Pharmacovigilance Center (CNFV) must be submitted according to the following timelines:

Serious SRAMs or serious AEs/ADRs must be reported within a maximum of seven (7) calendar days, if fatal, and within a maximum of 15 days, if not fatal (severe cases from abroad should only be included in the final study safety report, if the study has a research center in Mexico)
Not serious SRAMs or AEs/ADRs must be reported at the end of the study
Two (2) or more serious cases, in the same place with the same drug and the same batch, must be reported immediately, and no later than 48 hours
When a review of scientific literature shows a safety issue, it should be reported within a maximum of 30 calendar days from first knowledge of the AE/ADR

HlthResRegs and NOM-012-SSA3-2012 state that the institution must notify and provide a report to the Ministry of Health (Secretaría de Salud) within a period of 15 days after the suspension or cancellation of the research has been agreed upon. The report should specify the effect(s) detected, all medical care steps adopted, and the consequences produced. A detailed report on the research participant(s) physical condition should also be included. NOM-012-SSA3-2012 indicates that all serious or deadly adverse reactions or effects must be immediately reported to the Ministry. Per NOM-012-SSA3-2012, the principal investigator (PI), the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), the institutional head(s), or the Ministry of Health must also suspend or cancel the research as soon as any AE representing an ethical impediment to research is identified.

Additionally, per NOM-220-SSA1-2016, institutions must notify the CNFV of a study’s suspension or cancellation within a maximum of 15 days. If the study is resumed, the CNFV must also be notified within a maximum of 15 working days following the study’s recommencement.

Per MEX-2, COFEPRIS has also implemented the following International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines:

Guideline E2B (R3) on Electronic Transmission of Individual Case Safety Reports (ICSRs) – Data Elements and Message Specification – Implementation Guide (MEX-79)
ICH Harmonised Tripartite Guideline: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (MEX-80)
ICH Harmonised Tripartite Guideline: Pharmacovigilance Planning (E2E) (MEX-82)

Investigator Responsibilities

As specified in HlthResRegs, NOM-012-SSA3-2012, and COFEPRIS-GCP, the PI must report to the REC all probable AEs or any AEs directly related to the research study. Per NOM-012-SSA3-2012, the investigator is also responsible for submitting safety reports to the CNFV.

Other Safety Reports

As indicated in NOM-220-SSA1-2016, a pharmacovigilance study protocol should be prepared and submitted to the Executive Director of Pharmacopeia and Pharmacovigilance through COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37).

Per NOM-220-SSA1-2016, a clinical safety report is also required to be submitted to the CNFV for all trials, sponsored or not, that have at least one (1) site or research center in Mexico. In addition, G-ClinResPV explains that a final safety report must be submitted to the CNFV in the following circumstances:

A study is completed that has included at least one (1) research center in Mexico
A study has been cancelled, discontinued, or definitively suspended
A bioequivalence, bioavailability, and pharmacokinetics study is concluded

Refer to G-ClinResPV and G-PharmPerSafRpt for additional report writing instructions and criteria that align with the safety reporting requirements delineated in NOM-220-SSA1-2016 and NOM-220-SSA1-2016-Mod. See also G-PharmRptReq for detailed pharmacovigilance reporting guidelines and to extend sanitary registrations for drug products.

Form Completion & Delivery Requirements

G-ClinResPV specifies that clinical safety reports must be written in Spanish and submitted electronically (in PDF format) to the CNFV. In addition, reports should be submitted by either the health record holder or the sponsor or the legal representative to avoid sending duplicate information to the CNFV. G-PharmPerSafRpt states, in turn, that the safety report must be written in Spanish in the sections delineated in Annex 1 of G-PharmPerSafRpt and submitted electronically via CD or USB in editable PDF format. As indicated in G-ClinResPV and G-PharmPerSafRpt, the annual safety report submission date is determined by the date of the study’s first national authorization by COFEPRIS.

As per MEX-117, the E-Reporting Industry platform, which is linked to VigiFlow (MEX-43), was developed by the World Health Organization (WHO)’s Uppsala Monitoring Centre for the pharmaceutical industry to manage individual case safety reports at the national level. Reports are submitted by pharmaceutical industry professionals including health registration holders or their legal representatives and institutions/establishments where research is conducted as well as contract research organizations, distributors, and marketers. MEX-117 also specifies the CNFV is responsible for granting access to the E-Reporting Industry tool, and requests can be made via email: xmlvigiflow@cofepris.gob.mx. Refer to MEX-117 for details. Additionally, per MEX-77, state centers, institutional coordinating centers, institutional centers, and pharmacovigilance units of the National Health System should also report AE/ADRs, SRAMs, ESAVIs, and other safety issues via MEX-43.

MEX-78, in turn, provides patients, consumers, and health professionals instructions on reporting ADRs via VIGIRAM (MEX-118). See MEX-12 for instructions on using MEX-118, see MEX-30 for the form to be completed via MEX-118, and see MEX-119 for additional information on MEX-118. See also G-ADR-PatientRpt for information on how patients, consumers, and/or family members report suspected ADRs.

Refer to NOM-220-SSA1-2016 for detailed reporting requirements, and the G-AENotif, MEX-44, and MEX-117 for submitting safety reports via VigiFlow (MEX-43). See also MEX-54 for additional CNFV issued pharmacovigilance guidelines and requirements.

1. Generalities, 3. Content Development (3.1), and 5. Annex A

XIII. Specific Sections of the Procedure on the Platform (IX)

3.6

2-6

1-5

1, 4, 6, Table 1, and Annex 1

Title III (Chapter I (Article 64))

4.21, 4.44-4.45, 4.53, 4.55-4.56, 4.59, 4.72, 7.5, 7.7, and 8.1-8.3

8.1.2, 8.1.11, and 8.2.1-8.2.10

4.5, 8.7-8.10, and 10.9

Last content review/update: March 21, 2024

Safety Reporting Definitions

In accordance with ClinImprtOrdr, ClinSampleProd, G-AEReptReqs, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28), the following definitions provide a basis for a common understanding of Thailand’s safety reporting requirements:

Adverse Event (AE) – Any untoward or unfavorable medical occurrence in a research participant to whom a drug product was administered, and which does not necessarily bear a causal relationship to the treatment
Adverse Drug Reaction (ADR) – All dangerous and adverse reactions resulting from any dose of an investigational drug, for which it is at least reasonably likely that the adverse reaction is attributable to the drug being studied, that is, a relationship cannot be ruled out
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Suspected Unexpected Serious Adverse Reaction (SUSAR) – An unexpected SAE/SADR given the nature of the research procedures and the population being studied
Unexpected Adverse Event/Adverse Drug Reaction – A reaction where the nature or severity is inconsistent with the applicable product information

Per an in-country subject matter expert, Thailand is implementing THA-28. THA-28 also notes that the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (THA-26) should be referenced for additional safety terms not defined in this list.

Safety Reporting Requirements

Investigator Responsibilities

As stated in G-AEReptReqs, the principal investigator (PI) is responsible for reporting all SAEs/SADRs to the sponsor and the ethics committee (EC) no later than 24 hours after the PI becomes aware of the event. The PI must also report all AEs/ADRs to the sponsor and the EC no later than seven (7) calendar days following first knowledge.

For safety reporting requirements specific to the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) and the Central Research Ethics Committee (CREC), please see THA-13 and THA-37 respectively.

Sponsor Responsibilities

As delineated in THA-28, sponsors who are permitted to import or order drugs for research in Thailand and those who are licensed to produce drug samples for human research studies, must comply with the Thai Food and Drug Administration (Thai FDA)’s safety monitoring and reporting requirements. ClinImprtOrdr and ClinSampleProd state that the following information is viewed as urgent and is required to be reported:

SAEs/SADRs that never occurred before because the research team used safety reporting information from other countries to substantiate investigational product (IP) use
Other safety and security information useful to evaluating IP risk-benefit assessment, IP changes to the method of administration, or changes required to the overall research process
Unexpected SAE/SADR incidents that never occurred before, with an increased incidence or severity and considered to be of clinical importance
Significant harm to the participant, such as the ineffectiveness of an IP used to treat a life-threatening disease
Significant new information about experimental animal safety studies, such as carcinogenicity

Per ClinImprtOrdr and ClinSampleProd, an ADR report must be filed in the following specified timelines:

Unexpected SAEs/SADRs that are fatal or life-threatening must be reported to the Thai FDA within seven (7) days from the first knowledge of the incident’s occurrence. Any additional relevant information should be sent within eight (8) days of the initial report
Unexpected SAEs/SADRs that are not fatal or life-threatening must be reported to the Thai FDA within 15 days from the date of SAE/SADR notification. A report must also be submitted periodically with any additional information.
AEs/ADRs that occur following the research participant’s participation in the study or after the study has been completed must be reported within 15 days from first knowledge of the event

According to G-AEReptReqs and G-ResEthics, the sponsor is also required to report all SUSARs to the EC as soon as possible, but no later than seven (7) calendar days for all fatal or life-threatening events, and no later than 15 calendar days for any non-fatal or non-life-threatening events. The sponsor must include the main points of concern. In addition, the sponsor must report to the EC any other non-local adverse reactions that may increase risks to participants within 15 days. Additionally, the sponsor must report any non-local SAEs/SADRs including SUSARs at least every six (6) months to the EC.

G-ResEthics and THA-28 state that the sponsor is responsible for expediting the reporting of all SUSARs to the investigator(s)/institution(s) participating in the trial, the EC(s), and to the Thai FDA. These reports should comply with G-AEReptReqs and the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (THA-26). See G-AEReptReqs for detailed reporting requirements for the investigator and sponsor.

Other Safety Reports

THA-28 indicates that the sponsor should submit to the Thai FDA all safety updates and periodic reports as required by applicable regulatory requirements. The sponsor is also responsible for the ongoing safety evaluation of investigational drug(s) and should promptly notify all concerned parties of findings that could adversely impact the safety of research participants, the conduct of the trial, or alter the EC’s approval or favorable opinion to continue the trial.

Per ClinImprtOrdr and ClinSampleProd, annual and end of study safety reports must be provided to the New Drugs and Drug Research Promotion Group within the Thai FDA’s Medicines Regulation Division. The annual report must be submitted as a document within three (3) months of the one (1) year anniversary of the study, and the final safety report must be submitted as a document within six (6) months after the study has concluded. In addition, a list of all SAE/SADR incidents involving research participant(s) should be included in the annual report. A detailed summary table with the number of SAEs/SADRs organized by terminology (symptoms and diagnosis) should be provided. See Appendix 21 in ClinImprtOrdr (Appendix 21 in THA-18) and Appendix 17 in ClinSampleProd (Appendix 17 in THA-76) for an example of the reporting form.

ClinImprtOrdr and ClinSampleProd further notes that other reports must be made in writing with information such as summary of risk assessment issues and related details for submission to the New Drugs and Drug Research Promotion Group.

Form Completion & Delivery Requirements

As per G-AEReptReqs, all SAEs/SADRs and SUSARs must be reported on the Thai FDA’s Health Product Vigilance Center (HPVC) (THA-30) SAE reporting form (THA-22) or the Council for International Organizations of Medical Sciences (CIOMS)’ form (THA-20). According to THA-37 and THA-20, AEs/ADRs and SAEs/SADRs must be reported to the Thai FDA. THA-22 indicates that the SAE form should be sent to the HPVC via mail, fax, or email at:

Health Product Vigilance Center
Food and Drug Administration
Ministry of Public Health
88/24 Tiwanon Road
Nonthaburi 11000
Thailand

Fax: 02 590 7253 or 02 591 8457
Email: adr@fda.moph.go.th

Pursuant to ClinImprtOrdr and ClinSampleProd, individual reports should be submitted electronically via the Thai FDA’s HPVC (THA-30), unless the system is unavailable. The report may also be submitted as a document to the New Drugs and Drug Research Promotion Group within the Thai FDA’s Medicines Regulation Division.

Individual report data should include at minimum the following information:

Research participant information for those that can be identified (e.g., participant codes)
Investigational drugs used in research study
AE/ADR symptoms or results suspected of being connected to the drugs
Source of follow-up reports
Research project code or name
Reporting numbers (e.g., report number specified by sponsor)

Per ClinImprtOrdr and ClinSampleProd, for research studies involving participants whose identities are disclosed, submitted AE/ADR reports should include the participant codes unless the Thai FDA’s Office of the Board of Directors deems it necessary to reveal the code immediately.

Ethical Criteria

Appendix 17

Appendix 21

II

1.1-1.2, 1.50, 1.60, 5.5, and 5.17

CREC 11 / v.4.0 Review of Adverse Event Reports

Annex 5 (17)

Descriptions and Definitions, 1, 2, 4, and Appendices 1-4

4.6 and Appendix 17

4.6 and Appendix 21

Progress Reporting

Last content review/update: November 8, 2024

Interim and Annual Progress Reports

Per HlthResRegs, NOM-012-SSA3-2012, and MEX-28, the principal investigator (PI) must prepare and submit a progress report (also referred to as a partial technical or technical-descriptive report) (MEX-31) to the Ministry of Health (Secretaría de Salud) at any time, but at least once a year, to communicate progress and partial research study results. In addition, per NOM-012-SSA3-2012, information related to any investigation that the PI submits to the Ministry of Health must be classified as confidential. NOM-012-SSA3-2012 further states that the PI must also provide a copy of every report to the head of the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and if applicable, the Biosafety Committee of the institution where the research takes place.

NOM-012-SSA3-2012 specifies that the progress reports should describe the results obtained and at a minimum should include the following elements:

Identification data
Materials and methods
Results
Conclusions
Bibliographic references
Any relevant exhibits

In accordance with NOM-012-SSA3-2012, a report should be submitted annually to the Ministry of Health on the integration and activities of the REC, the Research Committee, and, if applicable, the Biosafety Committee, during the first 10 business days of June.

Final Report

As set forth in HlthResRegs, NOM-012-SSA3-2012, and MEX-28, the PI is also required to submit a final report to the Ministry of Health in order to communicate the final results of a research protocol or project as well as the major findings obtained throughout the course of the study. Additionally, per NOM-012-SSA3-2012, the PI must deliver a copy of this report to the research team members, the REC, the Research Committee, and the Biosafety Committee, as applicable, where the study was conducted.

As per NOM-012-SSA3-2012, the final reports should describe the results obtained and at a minimum should include the following elements:

Identification data
Summary
Introduction
Materials and methods
Results
Discussion
Conclusions
Bibliographic references
Any relevant exhibits/Annexes

See section 7.4 of NOM-012-SSA3-2012 for additional required report information.

HlthResRegs further states that the PI is also required to submit a final report to the Research Committee at the institution where the study was conducted. Refer to MEX-31 for the reporting form.

Title VI (Chapter I (Articles 116 and 119-120))

4.8-4.10, 7.1, 7.4, 10.10, and 12.1

Last content review/update: March 21, 2024

Interim and Annual Progress Reports

As delineated in G-ResEthics, the investigator(s) must submit progress reports on the status of the trial to the ethics committee (EC) at the designated interval (not specified). For high-risk research protocols, investigator(s) should report the progress more frequently than for a low-risk protocol. The investigator should also provide a proposed schedule to submit a progress report to the EC from the date of protocol submission for ethical review, which should be at least once a year.

The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28) further notes that investigator(s) should submit a research summary report in writing to the EC once a year, or more often, as required by the EC. Investigator(s) should send a written report to the EC and the institution, if applicable, regarding any changes that may impact the research process and/or cause increased risk to the research participants. Per an in-country subject matter expert, Thailand is implementing THA-28.

In addition, according to ClinImprtOrdr and ClinSampleProd, the sponsor must submit a study progress report annually to the Director of the Thai Food and Drug Administration (Thai FDA)'s Medicines Regulation Division between October 1 and 31 every year until the study ends. Per ClinImprtOrdr, for N.Y.M.1/investigational product (IP) import applications, this report should be submitted using the progress report form in Appendix 15 in THA-18, and accompanied by a delivery letter to the Thai FDA’s Director of the Bureau of Medicine using the format in Appendix 14 in THA-18. Per ClinSampleProd, for P.Y.8/IP sample production applications, the report should be submitted using the progress report form in Appendix 11 in THA-76, and accompanied by a delivery letter to the Thai FDA’s Director of the Bureau of Medicine using the format in Appendix 10 in THA-76.

Requests that already have information in the FDA’s Skynet E-Submission System (THA-54) must submit documents according to the system’s procedures. See Submission Process section for detailed information on submitting information via the FDA’s Skynet E-Submission System (THA-54).

Final Report

As specified in ClinImprtOrdr, in the event of early termination of the research study, the sponsor must submit a summary report (Appendix 19 of ClinImprtOrdr) to the Thai FDA within 60 days after the closeout of the last study site.

G-ResEthics also requires investigator(s) to submit a final report to the EC upon the trial’s termination.

For reporting requirements specific to the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH), please see THA-13. Also, refer to THA-37 for Central Research Ethics Committee (CREC) reporting requirements. The ECMOPH and the CREC are both ECs recognized by the Thai FDA to review and approve clinical trial protocols.

Individual ECs should be contacted to confirm their specific requirements.

Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (Revised 2007) (p. 72); Additional Resolution of the Committee (2005) (p. 76); Additional Resolution of the Committee (2006) (p. 80)

Appendices 10-11

Appendices 14-15 and 19

4.10

CREC 12 / v.4.0 Review of Close Study Reports; CREC 13 / v.4.0 Management of Study Termination Report

6.6

4.1 and Appendices 10-11

4.1 and Appendices 14-15 and 19

Definition of Sponsor

Last content review/update: November 8, 2024

As set forth in NOM-012-SSA3-2012, COFEPRIS-GCP, and MEX-84, a sponsor is defined as an individual or corporation willing to undertake responsibilities to participate and finance a research project or protocol, in full or in part.

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. Per COFEPRIS-GCP and MEX-32, a sponsor is an individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial. A sponsor may also hire a CRO to conduct one (1) or more of the activities related to health research that are sponsored in the country. The sponsor must specify in writing any trial-related duty and function that is transferred to and assumed by a CRO. However, the ultimate responsibility for all CRO activities remains with the sponsor. Additionally, MEX-32 notes the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor, and any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor. COFEPRIS-GCP also indicates that CROs of foreign origin must also have a registered address in Mexico, and an authorization to carry out clinical research activities in the country.

4.1

1.53 and 5.2

1.5-1.6, 4.1-4.2, and 4.15

4.18

Last content review/update: March 21, 2024

In accordance with G-ResEthics, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28), a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. Per an in-country subject matter expert, Thailand is implementing THA-28.

Per G-ResEthics and THA-28, the Thai government also permits a sponsor to authorize a contract research organization (CRO) to perform one (1) or more of a sponsor’s trial-related duties and functions. However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities to be transferred and assumed by a CRO should be specified in a written agreement or contract. A sponsor may be domestic or foreign.

Per THA-65 and THA-77, although applicants residing outside Thailand cannot register directly with Digital ID (THA-89), they can request permission to authorize a juristic person who receives power of attorney to use the OSSC’s online consultation system (E-Consult) (THA-77) and to submit applications to the FDA’s Skynet E-Submission System (THA-54).

THA-28 also states that the sponsor may be a sponsor-investigator if the individual both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered or dispensed. The sponsor-investigator’s obligations include both those of a sponsor and those of an investigator.

According to THA-13, the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) requires the sponsor and/or CRO to be legally registered in Thailand. The ECMOPH is one (1) of the ethics committees approved by the Thai Food and Drug Administration (Thai FDA) to approve clinical research protocols. See THA-13 for additional ECMOPH sponsor requirements.

Per ClinImprtOrdr, the sponsor is also referred to as the applicant or importer, and in ClinSampleProd, the sponsor is also referred to as applicant.

Additional Resolution of the Committee (2005) (p. 76) and Additional Resolution of the Committee (2006) (p. 77)

Requirements before using the E-consult system, Applying for service

1.20, 1.53-1.54, and 5.2

Annex 5

Site/Investigator Selection

Last content review/update: November 8, 2024

Overview

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. COFEPRIS-GCP states the sponsor or the CRO is responsible for selecting each research center and ensuring that COFEPRIS has authorized its operation as well as the human and material resources needed to conduct research. MEX-32 indicates the sponsor should ensure the investigator(s) have adequate resources to properly conduct the trial for which they are selected. Additionally, MEX-32, explains the investigator should have available an adequate number of qualified staff and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely.

Per COFEPRIS-GCP, the sponsor must establish in writing each of the research team member functions and responsibilities, and the financial agreement with the principal investigator (PI). G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also note the sponsor or the CRO must specify in a letter the human and material resources that will be allocated for the research and the way in which they will be provided and distributed to the research sites.

As stated in the HlthResRegs and NOM-012-SSA3-2012, all investigators must possess appropriate qualifications, training, and experience. Per COFEPRIS-GCP, the PI is also responsible for selecting a research team with knowledge, education, and training in MEX-32, and in the process of the investigation in which the investigator is involved. Per MEX-32, the sponsor must ensure each investigator is qualified by education, training, and experience to assume responsibility for the proper conduct of the trial; meets all the qualifications specified by the applicable regulatory requirement(s); and provides evidence of such qualifications through updated curriculum vitae (CV) and/or other relevant documentation requested by the sponsor, the ethics committee (EC), and/or COFEPRIS. G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also indicate the PI should provide legally issued and registered documentation delineating appropriate academic training and experience appropriate to the research to be conducted, which includes academic preparation, representative scientific production, and clinical practice.

G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also indicate that institutions in charge of providing medical care for study related medical emergencies are required to sign an agreement or contract to provide these services, and a provide letter stating the institution’s acceptance, authorization, and description of the available resources.

Foreign Sponsor Responsibilities

COFEPRIS-GCP indicates that foreign CROs must have a registered address in Mexico, and an authorization or notice specifying the activities to be carried out in the country.

Data Safety Monitoring Board

According to COFEPRIS-GCP, the sponsor or the CRO is responsible for the continuous monitoring of the study which should be established based on the nature of the study, and must ensure study monitoring is carried out in compliance with MEX-32. Per MEX-32, the sponsor or the CRO may consider establishing an independent data monitoring committee to assess the progress of a clinical trial, the safety data, the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. The committee should have written operating procedures and maintain written records of its meetings.

Multicenter Studies

As delineated in MEX-32, in the event of a multicenter clinical trial, the sponsor or the CRO must ensure that:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and, if required, by COFEPRIS, and given ethics committee approval
The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
Investigator responsibilities are documented prior to the start of the trial
All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
Communication between investigators is facilitated

4.6, 7.2-7.3, and 8.2

1.25, 4.1-4.2., 5.5-5.7, and 5.23

XIII. Specific Sections of the Procedure on the Platform (IV, VIII, and IX)

Requirements (4, 19-20, and 24)

Preamble, 3.8, 4.14.7, 4.10-4.11, 4.13, and 4.15

Title III (Chapter I, Article 62) and Title VI (Chapter I, Articles 113 and 117)

10.1

0 and 1

Last content review/update: March 21, 2024

Overview

In accordance with G-ResEthics and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial, and for ensuring that the investigator(s) are qualified by training and experience. Per an in-country subject matter expert, Thailand is implementing THA-28. THA-14 also states that researchers must have basic knowledge in the field of research.

Additionally, per THA-28 and G-ResEthics, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure.

Foreign Sponsor Responsibilities

No information is available regarding foreign sponsor regulatory requirements.

Data Safety Monitoring Board

Although not specified as a sponsor requirement, G-ResEthics, G-AEReptReqs, and THA-28 encourage the establishment of a Data Safety Monitoring Board.

Multicenter Studies

As delineated in G-ResEthics and THA-28, in the event of a multicenter clinical trial, the sponsor must ensure that:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and if required, by the Thai Food and Drug Administration (Thai FDA), and are given ethics committee approval
The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
Investigator responsibilities are documented prior to the start of the trial
All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
Communication between investigators is facilitated

3

1.25, 4.1, 5.1, 5.5, and 5.7

Annex 5 (5, 6, 7, and 23)

Descriptions and Definitions and Appendix 3

Insurance & Compensation

Last content review/update: November 8, 2024

Insurance

As set forth in COFEPRIS-GCP, the sponsor or the contract research organization (CRO) must establish a financial fund or have insurance to cover serious adverse events that result from the medication or the research study.

Additionally, per COFEPRIS-GCP, which requires the sponsor or the CRO to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/institution against claims arising from the trial, except for those claims arising from malpractice and/or negligence. Per MEX-32, if required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator and the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

Compensation

As specified in COFEPRIS-GCP, the sponsor or the designated CRO must establish a statement of funding and describe the quantity and payments to be allocated for research participants.

Per MEX-32, the ethics committee (EC) should review both the amount and method of payment to participants to ensure that neither presents problems of coercion or undue influence on the trial participants. Payments to a participant should be prorated and not wholly contingent on the completion of the trial by the participant.

Injury or Death

Although NOM-012-SSA3-2012 does not specifically ascribe responsibility to the sponsor, it indicates that the research budget must include the availability of a financial fund as well as mechanisms to guarantee continuity of medical treatment and indemnity of the research participant, in the event of trial-related injuries. Additionally, the head of the institution or establishment, the, Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), Research Committee, or Biosafety Committee, the PI, and, where applicable, the sponsor, must be responsible, in accordance with their area of competence, for the damage to health resulting from the development of the research as well as damage resulting from the interruption or early suspension of treatment for reasons not attributable to the research participant.

Per HlthResRegs and GenHlthLaw, the health care institution and the sponsor or the CRO must provide medical attention to injured participants, and where appropriate, legally required compensation, if the injuries are directly related to the study. Medical attention that is provided to such participants will not prejudice the compensation that may be legally due from the study.

In addition, per COFEPRIS-GCP, the sponsor or the CRO is also responsible for ensuring that research institutions provide urgent care resources, or where appropriate, have a written agreement with the health institution that will handle the emergencies. The agreement must comply with NOM-206-SSA1-2002, which establishes the criteria for the operation and attention in providing emergency services in health care institutions

MEX-32 explains the sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable regulatory requirement(s). In addition, when study participants receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s).

In addition, per G-DIGIPRiS-ResProts and G-HumResProt, the sponsor should provide the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) with a copy of the financial fund or current insurance policy, which guarantees the continuity of the medical treatment and the compensation to which the participant will be legally entitled in the event of suffering damages directly related to the development of the research. MEX-84 specifies that the insurance policy or current document from the financial fund should cover all study participants at the local level. The document guarantees coverage to the participant in case of any injury or damage related to the research. The insurance policy and certificate must indicate the number of participants that will be covered, study title, protocol number, and must be on behalf of the license holder and the sponsor.

Trial Participation

Per COFEPRIS-GCP, the sponsor or the CRO must ensure that each and every treatment, clinical analysis procedure, and other study procedures are delivered in a timely manner, in good condition, and free of charge to the research participant.

4.3

3.1 and 5.8

XIII. Specific Sections of the Procedure on the Platform (IV)

Requirements (6)

Preamble, 4.1, 4.8, and 4.13-4.14

Title V (Chapter I, Article 100)

Title II (Chapter I, Article 14) (Chapter II, Article 21), and (Chapter V, Article 58)

5.14 and 7.2

Last content review/update: March 21, 2024

Insurance

ClinImprtOrdr and ClinSampleProd specify that financing and insurance information should be included in the study protocol and protocol summary. If not included in the protocol and research project summary, a financial/insurance agreement should be attached separately in the application package as one (1) of the documents that the ethics committee (EC) considers approved or certified (e.g., Patient Information Sheets, etc.). G-ResEthics also states that the sponsor should provide insurance or indemnify the investigator/institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence, if required by applicable regulatory requirements.

Compensation

Injury or Death

As specified in ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28), the sponsor or the designated contract research organization (CRO) is responsible for providing information related to compensation in the event of trial-related injuries or death to research participants and/or their legal heirs. ClinImprtOrdr further states that payment of compensation (if any) will be determined on a monthly basis to participants involved in the research. (See THA-18 and THA-76 for the forms included in the appendices in ClinSampleProd and ClinImprtOrdr.)

Per an in-country subject matter expert, Thailand is implementing THA-28. The sponsor must also inform the participants of any available medical treatment in the event of trial-related injuries. MCEthics further indicates that medical practitioners are responsible for harm or damage because the research studies involving the participant were not the fault of the participant.

Trial Participation

As per G-ResEthics, Phase I trial participants should be compensated for travel, loss of work, or other expenses incurred while participating in the trial.

Appendices 2 and 7

Appendices 3 and 11

4.8

3.2 and Annex 5 (8)

11

1.5, 1.10, and Appendices 2 and 7

1.3, 1.9-1.10, and Appendices 3 and 11

Chapter 9 (Article 49)

Risk & Quality Management

Last content review/update: November 8, 2024

Quality Assurance/Quality Control

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), and to ensure and control the quality of the research during a study. Per COFEPRIS-GCP and MEX-32, the sponsor or the CRO is also responsible for establishing written standard operating procedures (SOPs) for each stage of the investigation. In addition, the sponsor or the CRO must implement and maintain quality assurance (QA) and quality control (QC) systems to make certain the trial is conducted, and data are generated, recorded, and reported in compliance with the protocol.

MEX-32 further delineates the sponsor or the CRO is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. The sponsor and investigator(s) agreement should be confirmed in writing prior to the trial. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

Monitoring Requirements

According to COFEPRIS-GCP, the sponsor or the CRO must ensure and control the quality of the research through periodic monitoring visits and audits to ensure compliance with the protocol and the SOPs, and if necessary, compliance with reports derived from inspections or verifications by COFEPRIS. The principal investigator (PI) is responsible for reporting and guaranteeing the quality and validity of the data obtained during the investigation. MEX-32 indicates the sponsor should ensure that the trials are adequately monitored and determine the appropriate extent and nature of monitoring, which should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial.

Additionally, per MEX-32, the sponsor should also appoint the monitors who should be appropriately trained, and have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented. Monitors should also be thoroughly familiar with the investigational product(s), the protocol, written informed consent form, and any other written information to be provided to research participants, the sponsor’s SOPs, COFEPRIS-GCP, and the applicable regulatory requirement(s).

MEX-32 further indicates the sponsor should appoint individuals, who are independent of the clinical trials/systems, to conduct audits and ensure the auditors are qualified by training and experience to conduct audits properly. An auditor’s qualifications should be documented. The sponsor should also ensure the auditing of clinical trials/systems is conducted in accordance with the sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The sponsor's audit plan and procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of study participants, the type and complexity of the trial, the level of risks to the study participants, and any identified problem(s). Auditor(s) observations and findings of the auditor should be documented.

Pursuant to MEX-32, noncompliance with the protocol, SOPs, good clinical practice, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor's staff should lead to prompt action by the sponsor to secure compliance. If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigator's/institution’s participation in the trial and notify promptly the regulatory authority(ies). Also, upon the request of the monitor, auditor, ethics committee (EC), or COFEPRIS, the investigator/institution should also make available for direct access all requested trial-related records. See MEX-32 for detailed monitoring and auditing requirements.

Per NOM-012-SSA3-2012, the institutional head, the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), Research Committee, or Biosafety Committees, the PI, and, where applicable, the sponsor, must be responsible, in accordance with their area of competence, for monitoring the research. NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts further require the sponsor or the CRO to provide a follow-up letter to COFEPRIS describing the monitoring and auditing plan to be carried out during the investigation. G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts specify the letter must contain the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Type of plan: audit or monitoring
Frequency of application
Responsibility for monitoring, and where appropriate, cite the third party to carry out the activity
Objective and scope of monitoring
Evaluation tools and methodology implemented
Methodology to carry out the scientific, technical, and ethical monitoring
Communication and notification strategies between investigator, sponsor, ECs, and COFEPRIS
Profile of the monitor or auditor
Classification of findings and decision-making
Decision-making derived based on severity classification
Notification mechanism to the PI, ECs, and COFEPRIS
Design of the Action Plan: Corrective, Improvement, or Preventive
Reporting results through the partial and annual technical report (See MEX-31 for the partial reporting form)

COFEPRIS-GCP also states that the PI is responsible for reporting and guaranteeing the quality and validity of the data obtained during the investigation.

Premature Study Termination/Suspension

Per HlthResRegs the PI, the REC, the institutional head or other authorized institutional officers, or the Ministry of Health (Secretaría de Salud) must order the immediate suspension or cancellation of a research study as soon as any adverse effect is identified that might become an ethical or technical impediment to continuing with the study. The health care institution will submit a report to the Secretariat within 15 business days following the day in which the suspension or cancellation of the study was agreed, specifying the effect noticed, the measures adopted, and consequences produced. NOM-012-SSA3-2012 similarly states the head of the institution or establishment, the REC, the Research Committee, the Biosafety Committee, or PI must order the immediate suspension or cancellation of research, in the presence of any severe adverse effects, which become an ethical or technical impediment to continue with the study and notify the Secretariat in detail. The institutional head must notify the Secretariat of any adverse effect resulting from the experimental research within a maximum period of 15 working days from the event occurrence, including the care measures adopted, the identified sequelae, as well as a detailed report on the physical condition of the patient, which mentions whether the patient is free of any risk at the time of notification. In such case, the resumption of the research will require a new authorization. The investigator is also responsible for suspending the investigation if there is a risk of serious injury, disability, or death of the research subject in accordance with GenHlthLaw. Additionally, per NOM-220-SSA1-2016, institutions must notify the National Pharmacovigilance Center (CNFV) of a study’s suspension or cancellation within a maximum of 15 days. If the study is resumed, the CNFV must also be notified within a maximum of 15 working days following the study’s recommencement. The investigator is responsible for submitting safety reports to the CNFV.

MEX-32 delineates if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigators/institutions and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s). The EC should also be provided with a detailed written explanation of the termination or suspension.

MEX-32 further indicates that if the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial participants, ensure appropriate therapy and follow-up for the participants, and, where required by the applicable regulatory requirement(s), inform the regulatory authority(ies). If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the EC and provide the sponsor and the EC with a detailed written explanation of the termination or suspension. If the EC terminates or suspends its approval/favorable opinion of a trial, the investigator should inform the institution where applicable, and the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.

4.2

4.9, 4.12, 5.1, 5.12, and 5.18-5.21

XIII. Specific Sections of the Procedure on the Platform (IV)

Requirements (5)

Preamble, 3.5, 4.1, 4.6, 4.9, and 4.13

Title V (Chapter I, Article 100)

Title III (Chapter I, Article 64)

7.5

7.2, 8.7-8.8, 9.2, and 10.5

Last content review/update: March 21, 2024

Quality Assurance/Quality Control

As stated in ClinImprtOrdr, ClinSampleProd, and G-ResEthics, the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol and the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (THA-28). Per an in-country subject matter expert, Thailand is implementing THA-28.

G-ResEthics and THA-28 explain that the sponsor is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities.

G-ResEthics and THA-28 further specify that the sponsor must also obtain the investigator(s) and the institution(s) agreement to:

Conduct the trial in compliance with THA-28, applicable regulatory requirement(s), and the protocol agreed to by the sponsor and approved by the ethics committee (EC)
Comply with data recording and reporting procedures
License monitoring, auditing, and inspection
Retain essential documents until the sponsor informs them that they are no longer needed

Any agreements should be made in writing and the sponsor should sign the protocol, or a separate agreement.

Pursuant to G-ResEthics and THA-28, QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. In addition, per THA-28, the sponsor should focus on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should also use a risk-based approach that includes:

During protocol development, identify processes and data that are critical to ensure participant protection and the reliability of trial results (Critical Process and Data Identification)
Identify risks to critical trial processes and data (Risk Identification)
Evaluate the identified risks against existing risk controls (Risk Evaluation)
Decide which risks to reduce and/or which risks to accept (Risk Control)
Document quality management activities and communicate to those involved in or affected by these activities (Risk Communication)
Periodically review risk control measures to ascertain whether the implemented quality management activities are effective and relevant (Risk Review)
In the clinical study report, describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken (Risk Reporting)

ClinImprtOrdr states that the trial must be conducted in accordance with the Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) principles.

Monitoring Requirements

G-ResEthics and THA-28 note that the sponsor may choose to perform a clinical trial audit as part of its QA system. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, and other applicable regulatory requirements. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with the SOPs, the auditor observations are documented, and data are available as needed for the Thai Food and Drug Administration (Thai FDA). No specific timeframe is provided for the audit process.

Per ClinImprtOrdr, the sponsor and investigator must facilitate the Thai FDA’s monitoring of the clinical trial to ensure compliance with GCP and GLP, safety reporting, and progress reporting requirements.

In addition, per THA-28, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose onsite monitoring, a combination of onsite and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan). See THA-28 for detailed information on the sponsor’s role in developing monitoring systems.

Premature Study Termination/Suspension

G-ResEthics and THA-28 state that if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigators/institutions and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The sponsor or the investigator/institution should also promptly inform the EC and provide the reasons for the study’s termination or suspension.

G-CT-DIPApp also specifies that in the event of the premature discontinuance of a trial, the Thai FDA must be notified no later than 30 working days after the date of discontinuance. G-CT-DIPApp further notes that a corresponding notification letter referring to the related approved import license along with supplemental documents as indicated in Appendix 13 is needed, and a corresponding notification letter along with supplement documents as indicated in Appendix 14 is needed. (Note: Appendices 13 and 14 as referenced in G-CT-DIPApp are only available in the ClinImprtOrdr.) As stated in ClinImprtOrdr and ClinSampleProd, at the conclusion or termination of a clinical trial, a summary report must also be submitted within 60 days after the closeout of the last study site. ClinImprtOrdr and ClinSampleProd further explain that details of remaining medicines to be destroyed and evidence supporting the destruction or return of the study drugs should also be included (Appendix 20 in ClinImprtOrdr and Appendix 16 in ClinSampleProd each contain a sample notification form required to be completed when terminating a research project). (See also THA-18 and THA-76 for the forms included in the appendices in ClinSampleProd and ClinImprtOrdr.)

Per G-CT-DIPApp, after the import license is granted, the applicant must also notify the Thai FDA when the clinical trial has been discontinued in its entirety or at any clinical trial site for reasons not related to the safety of clinical trial, or if the trial has been discontinued prematurely.

Appendices 7 and 16

Appendices 2, 5, 7-11, 13-14, 16-18, and 20

1.65, 4.9, 4.12, 5.0-5.1, 5.5-5.6, 5.18-5.19, 5.21, 5.23, and 6.10

Annex 5 (1, 5, 6, 19, and 21)

16.2

1.8-1.10, 2, 4.5, and Appendices 7 and 16

1.6-1.7, 1.10-1.11, 4.2, and Appendices 2, 5, 7-11, 13-14, 16-18, and 20

Data & Records Management

Last content review/update: November 8, 2024

Electronic Data Processing System

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. Per MEX-32, the sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.

In addition, per MEX-32, when using electronic trial data processing or handling systems or remote electronic trial data systems, the sponsor should:

Ensure and document that the electronic data processing system(s) conform(s) to the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance
Maintain standard operating procedures (SOPs) for using these systems
Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data
Maintain a security system that prevents unauthorized access to the data
Maintain a list of the individuals who are authorized to make data changes
Maintain adequate backup of the data
Safeguard the blinding, if any

See MEX-32 for additional data processing requirements.

Records Management

As indicated in MEX-32, the sponsor, or other owners of the data, should retain all of the sponsor-specific essential documents pertaining to the trial (see section 8 of MEX-32). The sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the investigational product (IP) is approved, and/or where the sponsor intends to apply for approval(s). If the sponsor discontinues the clinical development of an IP (i.e., for any or all indications, routes of administration, or dosage forms), the sponsor should maintain all sponsor-specific essential documents for at least two (2) years after formal discontinuation or in conformance with the applicable regulatory requirement(s).

MEX-32 also states the essential documents should be retained until at least two (2) years after the last marketing approval or at least two (2) years have elapsed since the formal discontinuation of clinical development of the IP. These documents should be retained for a longer period, however, if required by the applicable regulatory requirement(s) or if needed by the sponsor. The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) when trial-related records are no longer needed.

In addition, as delineated in COFEPRIS-GCP, the principal investigator (PI) is responsible for preparing, integrating, using, filing, and ensuring the safekeeping of the research participant’s clinical file for a minimum of five (5) years in accordance with NOM-004-SSA3-2012, MEX-32, and Good Documentation Practices per NOM-164-SSA1-2015.

Per NOM-004-SSA3-2012, clinical records are the property of the institution or the medical services provider that generates them. However, the patient/participant has ultimate ownership rights over this information to protect their health and the confidentiality of their data. Consequently, because the documents are prepared in the interest and benefit of the patient/participant, they must be kept for a minimum period of five (5) years, which is calculated from the date of the last medical procedure/visit.

4.9, 5.5, and 8

3.7 and 4.1

4.1, 5.1, and 5.2

5.4

Last content review/update: March 21, 2024

Electronic Data Processing System

Per G-ResEthics and THA-28, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that standard operating procedures are maintained for using these systems. Per THA-28, the sponsor’s approach to validate such systems should be based on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. Refer to G-ResEthics and THA-28 for detailed information on electronic trial data systems. ClinImprtOrdr and ClinSampleProd also note that sponsors should ensure that research facilities are prepared for inspections by the Thai Food and Drug Administration (Thai FDA) by ensuring that research participant source data and case report forms are stored in electronically based data collection systems.

Records Management

As set forth in G-ResEthics and THA-28, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application in an International Council for Harmonisation (ICH) region, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of an investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, THA-28 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

5.5 and 8

Annex 5 (5)

4.7

Personal Data Protection

Last content review/update: November 8, 2024

New Info (Not Yet in Profile)

Effective March 21, 2025, the new Federal Law on the Protection of Personal Data Held by Private Parties repeals PDP-PrivateLaw. The law provides some revisions to key definitions, data controllers’ obligations, and data subjects’ rights, amongst other things.

Responsible Parties

According to the PDP-PrivateLaw, the PDP-Reg, the PDP-Public, and MEX-4, a private entity that processes personal data is called the “responsible person or entity” or “controller.” Federal, state, or local authorities are referred to as “obliged subjects” and make decisions about the processing of personal data. The private and public entities must protect personal data in accordance with the above laws and regulations.

Data Protection

PDP-PrivateLaw, PDP-Reg, and PDP-Public provide the requirements, responsibilities, and restrictions for handling personal data in the public and private sectors. The PDP-Public regulates the processing of personal information in the public sector by “obliged subjects”. The PDP-PrivateLaw and the PDP-Reg regulate the processing of personal information in the private sector by an individual or legal entity of a private nature.

Per the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, the sponsor or the sponsor’s representative(s) must comply with the principles of data protection: legality, purpose, loyalty, consent, quality, proportionality, information, and responsibility in the processing of personal data.

According to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, the sponsor is also required to protect the confidentiality of the owner of the personal data and their background. The PDP-PrivateLaw further notes that this obligation will remain in place even after the data processing activities have been completed and the relationship between the sponsor or the sponsor’s representative(s) and the data owner has concluded.

Additionally, the PDP-PrivateLaw and the PDP-Public provide definitions to address health related data. Sensitive personal data refers to the most intimate sphere of its owner, whose improper use may result in discrimination, or carries a serious risk of resulting in discriminatory activities. More specifically, data considered to be sensitive may reveal personal information such as racial or ethnic origin, present or future health status, genetic information, religious, philosophical, and moral beliefs, political opinions, and sexual preferences.

Per the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, data owners have the right to be informed about the collection and use of their personal data. Per the PDP-Reg, the person responsible must also inform the information owner regarding the existence and main characteristics of the treatment to which their personal data will be subjected through the consent document, known as the “privacy notice,” in accordance with the provisions of the PDP-PrivateLaw and the PDP-Reg.

Please refer to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public for detailed information on the principles guiding the protection and handling of personal data. See also MEX-3 and MEX-4 for additional information on data protection requirements.

Consent for Processing Personal Data

As explained in the PDP-PrivateLaw and the PDP-Public, the consent document or “privacy notice” is a physical document, electronic, or any format generated by the sponsor, that is made available to the data owner prior to processing the owner’s personal data. The PDP-Reg further explains that the privacy notice must be characterized as simple, with necessary information expressed in clear and understandable language, and with a structure and design that facilitates the owner’s understanding.

The PDP-PrivateLaw states that in the case of sensitive data, the sponsor is required to obtain the express and written consent of the data owner for the sponsor’s use, through a written or electronic signature, or any authentication mechanism established for that purpose. In cases where sensitive personal data is being processed, the sponsor must make reasonable efforts to limit processing to the minimum period necessary to complete the goal as delineated in the privacy notice. Moreover, databases containing sensitive personal data may not be created without justifying their creation for legitimate, concrete purposes, and if they are not in accordance with the specified activities delineated and pursued by the sponsor. The PDP-Reg also notes that sponsors may only create databases containing sensitive personal data when they obey a legal mandate; are justified pursuant to the territorial scope of the regulation; or are required by the sponsor for legitimate, concrete purposes, and in accordance with the activities or explicit purposes indicated in the privacy notice.

The PDP-Reg, whose focus is on regulating the process of personal data held in physical or electronic media, further indicates that the sponsor must obtain prior consent to process the data when acquired personally or directly from its owner. Whether tacit or express, the consent process must be:

Free: without error, bad faith, violence, or intent, which may affect the manifestation of the owner’s will
Specific: referring to one (1) or more specific purposes that justify the treatment, and
Informed: the owner has knowledge of the privacy notice prior to granting consent to the processing of their data

The sponsor must obtain the owner’s express consent when their data is deemed sensitive. The express consent must also be unequivocal; that is, there are elements that indisputably demonstrate its granting.

As delineated in the PDP-Public, the sponsor will not be required to obtain consent when processing sensitive data in the following cases:

When an applicable law authorizes such processing, and is consistent with and does not contravene the bases, principles, and provisions set forth in the PDP-Public
When sensitive personal data transfers are made between those responsible, the transfers are compatible with the original purpose that motivated the processing of personal data
When there is a judicial order, resolution, or well-founded and motivated mandate of the competent authority
For the recognition or defense of the owner's rights before the competent authority
When personal data is required to exercise a right or fulfill obligations derived from a legal relationship between the owner and the person in charge
When there is an emergency that could potentially harm an individual or the individual’s property
When personal data is necessary to carry out a treatment for the prevention, diagnosis, or provision of health care
When the personal data appear in publicly accessible sources
When personal data is subject to a prior dissociation procedure
When the owner of the personal data is a person reported missing under the terms of the law on the matter

Please refer to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public for detailed consent and privacy notice requirements.

Consent for Processing Personal Data of Minors

Per the PDP-Public, in processing the personal data of minors, the best interest of the children and adolescents must be prioritized in accordance with the applicable legal provisions. MEX-4 further states legal guardians must always give consent when processing children’s personal data. This applies to any individual younger than 18 years of age.

(See the Children/Minors section for additional information on consent requirements for children/minors.)

2.1, 6.1, and 8.2

Articles 1-3, 6, 8-9, 12-17, 21, and 23-25

Articles 1, 3, 7, 16, 22-23, 26, 31, and 59

Articles 1-4, 9-12, 15, 23-24, 36, and 56-57

Last content review/update: March 21, 2024

Responsible Parties

The PDPA defines the “data controller” as the person or juristic person having the power and duties to make decisions regarding the collection, use, or disclosure of the personal data.

Data Protection

Per the PDPA, the data controller must ensure that collected personal data remains accurate, up-to-date, complete, and not misleading. Personal data collection must be limited to the extent necessary in relation to the lawful purpose of the data controller. The data controller’s purpose for collecting data must meet one (1) of the purposes specified in the PDPA in order to be permitted to collect personal data, with the data subject’s explicit consent (see Section 23 of PDPA for details).

PDPA further specifies that personal data includes health and genetic data and requires the data subject’s explicit consent. Permissible personal data collection includes data collected in the interest of public health, such as protecting against cross-border dangerous contagious diseases or epidemics which may be contagious or pestilent, or ensuring standards or quality of medicines, medicinal products, or medical devices, provided there are measures to safeguard the rights and freedom of the data subject, including the confidentiality of personal data. Additionally, in the event that the data controller sends or transfers personal data to a foreign country, the destination country or international organization that receives such personal data must have an adequate data protection standard, and must be carried out in accordance with the rules for personal data protection as prescribed by the Personal Data Protection Commission (PDPC). See PDPC-Estab and THA-62 for additional information on the PDPC. Refer to the PDPA for a detailed list of permissible data collection purposes.

As set forth in the PDPA, the data controller is responsible for the following duties:

To provide appropriate security measures for preventing the unauthorized or unlawful loss, access to, use, alteration, correction, or disclosure of personal data; such measures must be reviewed when necessary, or when technology has changed in order to efficiently maintain proper security and safety, and also comply with the minimum standard specified by the PDPC
In the case of personal data being provided to other persons or legal persons other than the data controller, the data controller must take action to prevent such person(s) from using or disclosing the personal data unlawfully or without authorization
Establish an examination system for personal data erasure or destruction when the retention period ends, when the personal data is irrelevant or beyond the purpose necessary for which it has been collected, when the data subject has requested to do so, or when the data subject withdraws consent, except where the retention of such personal data is for the purpose of freedom of expression
Notify the PDPC of any personal data breach without delay and, where feasible, within 72 hours after having become aware of it, unless such breach is unlikely to result in a risk to the rights and freedoms of the persons whose data have been breached

Refer to the PDPA for additional information on data controller responsibilities. See also PDPC-Breach, G-PDPBreaches, THA-15, THA-10, and THA-17 for data controller guidelines on assessing data breach risks and applicable PDPC reporting requirements.

As described in the PDPA, with regard to personal data record management, the data controller must maintain, at least, the following records in order to enable the data subject and the PDPC to monitor in either written or electronic form the following: the collected personal data; the purpose of the collection of personal data; data controller details; personal data retention period; rights and methods for access to the personal data, including the conditions regarding the person’s right to access their personal data and the conditions to access such data; personal data use or disclosure; rejection of or objection to a request for personal data; and details of the appropriate personal data security measures.

Per the PDPA, the data protection legislation states that a data protection officer must be designated in the event the data controller/data processor is deemed a public authority per the PDPC; if the activities of the data controller/data processor in the collection, use, or disclosure of personal data, or the system itself, requires regular monitoring, due to the large quantity of personal data; or, if the core activity of the data controller/data processor is the collection, use, or disclosure of personal data for which the explicit consent of the data subject has not been obtained. See the PDPA for guidance related to data protection officers. See also THA-61 for a detailed guidance on the PDPA.

Consent for Processing Personal Data

The PDPA states that the data controller must not collect, use, or disclose personal data, unless the data subject has given consent prior to or at the time of such collection, use, or disclosure, except in the case where the data controller is permitted to do so by the provisions of the PDPA or any other laws. These cases may include the preparation of historical documents or public interest archives, research, or statistics, or preventing or suppressing a danger to a person’s life, body, or health.

The PDPA specifies that a request for consent must be made explicitly in a written statement or via electronic means unless consent cannot be done by those means. In addition, the data controller must inform the data subject of the purpose for collecting, using, or disclosing the subject’s personal data. The request for consent must be presented in an easily accessible and intelligible form and with statements using clear and plain language that is neither deceptive nor misleading to the data subject. The data controller must also ensure that the data subject’s consent is freely given.

The PDPA further explains that the data subject may withdraw consent at any time. The withdrawal of consent must be as easy as giving consent, unless there is a restriction of the withdrawal of consent by law, or the contract which gives benefits to the data subject. However, the withdrawal of consent must not affect the collection, use, or disclosure of personal data that the data subject has already legally consented to. If the withdrawal of consent will affect the data subject in any manner, the data controller must inform the data subject of the consequences of withdrawal.

In the event that the data subject is a minor who is not sui juris by marriage or has no capacity as a sui juris person under the PDPA, the request for consent from such a data subject must be made as follows:

In the event that giving consent is not an action that the minor is entitled to exercise independently, the consent of the holder of parental responsibility over the child must be obtained
Where the minor is below the age of 10 years, the consent must be obtained from the holder of parental responsibility over the child
In the event that the data subject is incompetent, the consent must be obtained from the custodian who has the power to act on behalf of the incompetent person
In the event that the data subject is quasi-incompetent, the consent must be obtained from the curator who has the power to act on behalf of the quasi-incompetent person

The above stated provisions also apply to the withdrawal of data consent of the data subject, the notice given to the data subject, the exercise of rights of the data subject, the complaint of the data subject, and any other acts under the PDPA for the data subject who is a minor, an incompetent person, or a quasi-incompetent person.

Refer to the G-PDPConsent for detailed data controller guidance on obtaining consent, and the G-PDPNotif for data controller guidelines on the conditions to be assessed when notifying a data subject of the purpose and details related to collecting their personal data. THA-16 also provides useful information on these guidelines.

Section 6, Chapter II (Sections 19-24 and 26), Chapter III (Sections 28, 35, 37, 39, 41-42)

Documentation Requirements

Last content review/update: November 8, 2024

Obtaining Consent

In all Mexican clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in HlthResRegs, GenHlthLaw, NOM-004-SSA3-2012, and COFEPRIS-GCP. Per COFEPRIS-GCP, the principal investigator (PI) is required to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) in obtaining and documenting informed consent, and per G-RECs-Op-2018, the PI must also comply with consent requirements as delineated in the Declaration of Helsinki (MEX-76). (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MEX-22)).

As per HlthResRegs and G-RECs-Op-2018, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and provided to COEFPRIS with the request for research protocol authorization. (See the Required Elements section for details on what should be included in the form.)

HlthResRegs, COFEPRIS-GCP, and NOM-012-SSA3-2012 state that the PI must provide detailed research study information to the participant or legal representative/guardian. As delineated in HlthResRegs, G-RECs-Op-2018, NOM-012-SSA3-2012, MEX-32, and MEX-84, the ICF content should be presented with a clear explanation and provided in a format that facilitates understanding. Per NOM-012-SSA3-2012 and MEX-32, the participant or legal representative/guardian should also be given adequate time to consider whether to participate. GenHlthLaw and MEX-84 further note the ICF should be expressed in writing in an accessible, timely manner and in understandable language, using accurate and complete information, including the possible benefits and expected risks, and the treatment alternatives, to ensure that services are provided on the basis of free and informed consent. Once comprehension of the information is guaranteed through the necessary means and supports, individuals have the right to accept or reject consent. G-DIGIPRiS-ResProts, MEX-84, and G-HumResProt indicate the ICF and/or assent form, as applicable, is a document through which the research participant agrees to voluntarily participate in a research study and to undergo experimental procedures when the information is presented in a sufficient, timely, clear and truthful manner regarding the expected risk and benefits.

As per HlthResRegs, G-RECs-Op-2018, and MEX-32, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Re-Consent

According to G-RECs-Op-2018 and MEX-32, any change in the ICF that is relevant to the participant’s consent should be approved by the REC prior to implementing any changes. Per G-RECs-Op-2018 and MEX-32, the participant or legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participating in the trial. MEX-32 further states the communication of this information should be documented.

Language Requirements

G-HumResProt states that the applicant must submit the request for protocol authorization application and all associated documentation (including the protocol and the ICF) in Spanish.

Documenting Consent

As delineated in HlthResRegs, G-RECs-Op-2018, and MEX-32, the participant or legal representative/guardian, as well as two (2) witnesses, must sign the ICF. MEX-32 specifies that the ICF should be dated, and any updates must also be signed, and a copy of the amendments provided to the participant or legal representative/guardian. If the participant does not know how to sign, the participant will provide a fingerprint and will also need to designate someone to sign the participant’s name on their behalf. A copy of the signed ICF will be provided to the participant or legal representative/guardian. Per G-DIGIPRiS-ResProts, which complies with MEX-22, the ICF version and date must coincide with what is recorded as approved in the opinions of the ethics committees (ECs). G-HumResProt further specifies the ICF should be signed by the PI, the participant and the participant’s family, or a legal representative and two (2) witnesses. The names of the witnesses, the addresses, and the relationships the witnesses have with the research participant must be indicated. MEX-84 also notes a section in the ICF should be provided for the participant or the legal representative to sign the document to indicate express acceptance. The section must include general data (full name, address, relationship with the participant) and signatures of two (2) witnesses.

Waiver of Consent

No information is currently available regarding waiver requirements.

3.3

25-32

1.28, 2.9, and 4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

XIII. Specific Sections of the Procedure on the Platform (V)

Requirements (9) and Additional Information

3.1 and 3.9

1.2, 3.3, 10, Annexes 5 and 6, and Glossary

Title III (Chapter IV, Article 51 Bis 2) and Title V (Chapter I, Article 100)

Title II (Chapter I, Articles 20-22)

0 (Introduction)

4.3 and 10.6

Last content review/update: March 21, 2024

Obtaining Consent

In all Thai clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (THA-28). Per an in-country subject matter expert, Thailand is implementing THA-28. MCEthics further states that a medical practitioner who conducts research studies and human experiments must obtain the consent of the participant and must be ready to protect the participant from harm arising from that experiment.

As per ClinImprtOrdr, ClinSampleProd, G-ResEthics, and THA-28, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) recognized by the Thai Food and Drug Administration (Thai FDA), and provided to the Thai FDA with the drug import license application to conduct a clinical trial. (See the Required Elements section for details on what should be included in the form.) (Note: The ICF is referred to as the Patient Information Sheet in G-CT-DIPApp.) (See also THA-18 and THA-76 for the forms included in the appendices in ClinSampleProd and ClinImprtOrdr.)

G-ResEthics and THA-28 state that the investigator(s) or the representative(s) must provide detailed research study information to the participant or legal representative/guardian. G-ResEthics and THA-28 also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant and legal representative/guardian, should also be given adequate time to consider whether to participate. THA-11 also explains that patients who seek medical treatment have the right to receive truthful and adequate information about their illness, examination, treatment, advantages and disadvantages from the examination, and treatment from health professionals, in a language that patients can easily understand. Patients can then choose to make decisions about consenting or not consenting to the health professionals treating them, except in cases of urgent and life-threatening emergencies. THA-14 further states that researchers should take pains to explain the objectives and scope of their research to the human participants without deceiving or coercing them and they should not violate their participants’ rights as private individuals. Researchers should respect the rights and dignity of their human participants and enlist their consent prior to any research experiments involving human participants.

As per G-ResEthics and THA-28, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

THA-13 provides informed consent documentation guidelines required by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH), which is one (1) of the institutional ECs approved by the Thai FDA.

As noted in THA-34, the Central Research Ethics Committee (CREC) does not have its own informed consent documentation guidelines and directs investigators to the ICF template and checklist provided by the Forum for Ethical Review Committees in Thailand (FERCIT) (see THA-46 for document links).

Re-Consent

No information is currently available regarding re-consent requirements.

Language Requirements

As stated in ClinImprtOrdr and ClinSampleProd, the ICF content and accompanying information (Patient Information Sheet) should be presented in the participant’s language, must be submitted in Thai and translated to English, and certify that the text in other languages aligns with the Thai translation. G-CT-DIPApp also indicates that the Patient Information Sheet should be presented in Thai.

Documenting Consent

G-ResEthics and THA-28 state that the participant or legal representative/guardian, and the investigator(s) must sign and date the ICF. Where the participant is illiterate, or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. The NatHlthAct also indicates that the participant’s consent must be obtained in writing prior to conducting the trial.

Waiver of Consent

As per G-ResEthics, the EC should establish the conditions under which an informed consent discussion and/or signing the ICF can be waived. In these cases, the investigator must explore other means to protect the participant’s confidentiality. For example, if the investigator uses information from a participant’s medical records, the investigator must also ensure that the ICF is kept in the medical record by having the participant sign the form in advance and keep it in the records, or by having the participant sign the ICF later. The EC will then consider waiving the informed consent as long as the investigator provides proof that the participant is informed about the method for collecting the data, and that the participant’s privacy is protected.

Information Sheet (p.70)

Approval documents - Informed Consent

5

Appendix 7

Appendix 11

1.27-1.28, 2.9, 3.1, 4.8, and 8.2-8.3

1. Informed consent form for clinical trials

2.2 and 3.1-3.3

11

Section 9

Preface, 1.9, and Appendix 7

1.9 and Appendix 11

Chapter 9 (Article 47)

Required Elements

Last content review/update: November 8, 2024

As delineated in G-RECs-Op-2018 and MEX-84, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Identification data (Title, protocol number, version, version date, research institution data, principal investigator (PI) name, medical emergency establishment data, and Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), and this data must coincide with the opinions of the ethics committees)
The study rationale and objectives
Purpose and procedures, including all invasive procedures
Identification of experimental aspects of the study
Trial duration
Participant’s responsibilities
Investigator responsibilities
Approximate number of participants
Circumstances that may terminate the study
Duration of study
Any expected risks or discomforts to the participant
Any expected benefits to the participant; if no benefit is expected, the participant should be informed of this point (physical examination, laboratory tests and imaging should not be considered as benefits to the participant)
Alternative treatments that may be beneficial to the participant
Trial treatment(s) and the probability for random assignment to each treatment
Explains the blinding of the study (if applicable) and what it consists of
Allocation method
Compensation and/or treatment available for the participant by the health care institution in the case of trial-related injury
All drugs, products, and procedures are free
That participation is voluntary, and that the participant can withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
Assurance that the participant will not be identified and that their confidential information relating to their privacy will be maintained
Confidentiality of records identifying the participant will be maintained (including sensitive personal data and data derived from the study), and permission given to monitors, auditors, the REC, and the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) to access the participant’s medical records to verify the procedures or trial data, without violating the participant’s confidentiality, insofar as the applicable laws and regulations permit
Contact information for the sponsor and PI in the event of participant problems or trial-related injuries
Communication channels and data to request clarification and to guarantee a response to questions and clarification of concerns about procedures, risks, benefits, and other matters related to the investigation and treatment of the participant
Foreseeable circumstances under which the PI(s) may remove the participant without their consent
Commitment to provide updated information throughout the study although this may affect the participant’s willingness to continue
Notification that any additional research study expenses will be absorbed by the research budget

The Guideline for Good Clinical Practice E6 (R1) (MEX-32) also mentions the following required elements:

Any expected risks or discomforts, when applicable, to the embryo, fetus, or nursing infant
Any anticipated prorated payment to the participant for participating in the trial
Any expenses the participant needs to pay to participate in the trial

Additionally, per NOM-012-SSA3-2012, the investigator must ensure that the ICF explicitly states the compensation to which the research participant is entitled in the event of suffering damage to their health directly attributable to the research, and the availability of free medical treatment, even in the event the participant decides to withdraw from the study before it is concluded.

See HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, and MEX-32 for additional details related to ICF requirements. (Note: Per MEX-2, COFEPRIS is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

Also, see the Vulnerable Populations and Consent for Specimen sections for further information.

3.3

4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

Annex 5

Title II (Chapter I, Article 21)

4.3, 4.6, 9.29, 10.6-10.7, 11.2-11.3

Last content review/update: March 21, 2024

Based on ClinImprtOrdr, ClinSampleProd, the G-ResEthics, and the G-CT-DIPApp, the informed consent form (ICF) (also referred to as the Patient Information Sheet in G-CT-DIPApp) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The study purpose and objectives
The expected duration of research participant’s involvement in the trial
Experimental aspects of the study
The participant’s responsibilities in participating in the trial
Any expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
Disclosure of alternate procedures or treatments available to participants, including the benefits and risks
The trial treatment(s) and the probability for random assignment to each treatment
The research procedures to be followed, including all invasive procedures
The expected benefits that can be obtained from the study; if no benefit is expected, the participant should be made aware of this
Compensation and/or treatment available for the participant in the case of trial-related injury
Payment of compensation (if any) determined on a monthly basis to research participants
Various expenses (if any) for research participants
That participation is voluntary, and that the participant may refuse to participate or withdraw from the study at any time without guilt or loss of benefits to which the participant is otherwise entitled
That the Thai Food and Drug Administration (Thai FDA), research investigators, the ethics committee (EC), and regulatory agencies are permitted to directly inspect participant’s original medical records to validate the accuracy of clinical research procedures and/or other information without violating the participant's right to maintain confidentiality beyond the limits allowed by laws and regulations, and that, by signing a written ICF, the participant or legal representative/guardian is authorizing such access.
The extent to which confidentiality of records identifying the participant will be maintained
That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
Individuals to contact for further information regarding the trial, the rights of trial participants, and whom to contact in the event of trial-related injury
Foreseeable circumstances under which the investigator(s) may remove the participant without consent
Estimated number of participants participating in research for the entire project, and the number of participants at each institution in Thailand

THA-13 provides information sheet guidelines required by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH), which is one (1) of the institutional ethics committees approved by the Thai FDA.

As noted in THA-34, the Central Research Ethics Committee (CREC) does not have its own informed consent documentation guidelines and directs investigators to the ICF template and checklist provided by the Forum for Ethical Review Committees in Thailand (FERCIT) (see THA-46 for document links).

See the Vulnerable Populations and Consent for Specimen sections for further information. See also Appendix 11 (Part 4) in THA-18 and Appendix 7 (Part 4) in THA-76 for a checklist of items to be included in the ICF.

Information Sheet (p.70)

Approval documents - Informed Consent

Appendix 7

Appendix 11

1. Informed consent form for clinical trials

3.1.1 and 3.2

11

1.9 and Appendix 7

1.9 and Appendix 11

Participant Rights

Last content review/update: November 8, 2024

Overview

In accordance with HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, and the Guideline for Good Clinical Practice E6 (R1) (MEX-32), Mexico’s ethical standards promote respect for all human beings and safeguard the rights of research participants. (COFEPRIS-GCP requires the principal investigator (PI) to comply with MEX-32). HlthResRegs and MEX-32 state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

The Right to Participate, Abstain, or Withdraw

As stated in HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, MEX-32, and MEX-84, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, MEX-32, and MEX-84, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to G-RECs-Op-2018, MEX-32, and MEX-84, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. In addition, per NOM-004-SSA3-2012, although clinical records are the property of the institution or the medical services provider that generates them, the participant has ultimate ownership rights over this information to protect their health and the confidentiality of their data.

The Right of Inquiry/Appeal

MEX-32 states that the research participant or legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or their rights. G-RECs-Op-2018 further specifies that the names and contact information of the PI and the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI))’s president, including a 24-hour telephone number in case of emergency, should be provided.

The Right to Safety and Welfare

HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, COFEPRIS-GCP, and MEX-32 that upholds the Declaration of Helsinki (MEX-76), clearly state that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

3.3

Introduction and 4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

Preamble and 3.1

1.1, 1.2, 3.2, and Annex 5

Title II (Chapter I, Articles 13 and 21)

5.4

0, 5.3, and 11.3

Last content review/update: March 21, 2024

Overview

In accordance with G-ResEthics and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), Thailand’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The Declaration of Rights and Code of Conduct for Patients (THA-11) also states that every patient has the fundamental right to receive professional medical care and health care from health professionals without discrimination as provided for in the Constitution of the Kingdom of Thailand (B.E. 2560). Per an in-country subject matter expert, Thailand is implementing THA-28. ClinImprtOrdr, ClinSampleProd, G-ResEthics, THA-28, the NatHlthAct, and G-CT-DIPApp, state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) (also referred to as the Patient Information Sheet) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As set forth in ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and THA-28, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled. NatHlthAct also states that the participant may withdraw consent at any time. THA-11 similarly states that the patient has the right to be fully informed in order to make a decision to participate or withdraw from being a participant in a health practitioner’s research.

The Right to Information

As delineated in ClinImprtOrdr, ClinSampleProd, G-ResEthics, the NatHlthAct, G-CT-DIPApp, and THA-28, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. THA-11 states that patients who seek medical treatment have the right to receive truthful and adequate information about their illness, examination, treatment, advantages and disadvantages from the examination, and treatment from health professionals, in a language that patients can easily understand. Patients can then choose to make decisions about consenting or not consenting to the health professionals treating them, except in cases of urgent and life-threatening emergency.

The Right to Privacy and Confidentiality

As per ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and THA-28, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. In addition, per G-ResEthics, which incorporates the principles of the Declaration of Helsinki (THA-45), every precaution should be taken to respect the privacy of the participant, the confidentiality of the participant’s information, and to minimize the impacts of the study on the participant. THA-11 further states that unless the patient’s permission or approved legal authorization is obtained, healthcare personnel cannot disclose the patient’s information.

The Right of Inquiry/Appeal

ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and THA-28 state that the research participant or the legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries. THA-11 similarly indicates that every patient has the right to know the name, surname, and profession of the healthcare personnel in charge.

The Right to Safety and Welfare

G-ResEthics states that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society. THA-14 explains that researchers should take full responsibility for the impact and consequences of their research regarding themselves, their research participants, and society at large.

(See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

4

1.28, 4.8, and 8.2

2.2, 3.1-3.3, and 4.1

11

Section 9

1.9

Emergencies

Last content review/update: November 8, 2024

The HlthResRegs and the Guideline for Good Clinical Practice E6 (R1) (MEX-32) make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies (COFEPRIS-GCP requires the principal investigator (PI) to comply with MEX-32). (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation’s Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

According to HlthResRegs, in an emergency, when it is deemed necessary to use an investigational drug, or a known drug with indications, doses, or routes of administration other than the established uses, the treating physician must obtain the favorable opinion of the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and an informed consent form (ICF) signed by the research participant or legal representative/guardian. The terms under which this documentation is obtained must meet the following requirements:

The REC and Research Committee will be informed of the use of the investigational drug in advance if the researcher can anticipate the need for use in emergency situations. If this is not possible, an opinion must be obtained after the situation occurs. In both cases, the committees will issue an opinion in favor or against approving the planned or recurring unintended use of the drug.
A signed ICF must be obtained from the participant or legal representative/guardian unless the participant’s condition prevents them from signing the form, the legal representative/guardian are not available to sign the form, or stopping use of the drug constitutes an almost absolute risk of death to the participant.

Per MEX-32, in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative/guardian, if present, should be requested. When prior consent of the participant or legal representative/guardian cannot be obtained, the ethics committee must provide documented approval in order to protect the participant’s rights, safety, and well-being, pursuant to the applicable regulations. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

In addition, per GenHlthLaw, in cases of medical emergency, and when the terminally ill patient is unable to express their consent, and in the absence of family members, a legal representative, guardian or trusted person, the specialist doctor and/or the institution’s Bioethics Committee will make the decision to apply a necessary surgical medical procedure or treatment.

4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

3.1

Title V (Chapter I, Article 100) and Title VI (Chapter II, Article 166 Bis 8)

Title III (Chapter II, Article 71)

Last content review/update: March 21, 2024

Per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), research participants involved in clinical research under emergency circumstances are viewed as vulnerable and should be provided additional protections to ensure their safety and well-being. Per an in-country subject matter expert, Thailand is implementing THA-28. In addition, per the Declaration of Rights and Code of Conduct for Patients (THA-11), patients who are in a life-threatening condition are entitled to immediate, urgent assistance from a healthcare practitioner as required, regardless of whether the patient requests assistance.

THA-28 explains that in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If prior consent cannot be obtained from the legal representative/guardian, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, to ensure compliance with ethics committee (EC) and other applicable regulatory requirements. Documented EC approval to protect the participant’s rights, safety, and well-being must also be obtained. The participant or the legal representative/guardian should be informed about the trial as soon as possible and provide consent. Consent should also continue to be obtained throughout the trial as appropriate per THA-28. However, THA-11 further notes that except in an emergency, every patient has the right to obtain sufficient information regarding their illness from healthcare personnel prior to deciding to allow any treatment.

1.61, 3.17, and 4.8.15

Vulnerable Populations

Last content review/update: November 8, 2024

Overview

As delineated in G-RECs-Op-2018, in all Mexican clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. G-RECs-Op-2018 characterizes vulnerable populations as individuals or groups experiencing diminished autonomy due to imposing social, political, and/or economic situations that prevent them from having control over their quality of life. Populations traditionally viewed as vulnerable include minors, women, persons with disabilities, the elderly, those suffering from mental illness, immigrants, those who are illiterate, those belonging to ethnic or racial minorities, the unemployed, the homeless, and reclusive individuals.

As per COFEPRIS-GCP, the principal investigator (PI) is required to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), which similarly characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation’s Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

G-RECs-Op-2018 specifies that Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) should ensure that additional security mechanisms are implemented to minimize the specific risks for each group. MEX-32 similarly states that ethics committees must pay special attention to protecting participants who are from vulnerable populations.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations. Information on the other vulnerable populations specified in HlthResRegs is provided below.

Persons in Dependent Groups

As indicated in HlthResRegs, for clinical trials involving participants who are involved in subordinate or dependent relationships, the REC must ensure the following:

Participation or refusal of individuals to participate or withdrawal of consent during the study, will not affect their school, work, military status, or that which is related to the judicial process and any conditions of compliance with a sentence, if applicable
Research results are not used to the detriment of the individuals involved
The health institution and sponsors take responsibility for dangers associated with medical treatment, and where appropriate, provide legally required compensation for the harmful consequences of the investigation

Per G-RECs-Op-2018, the following criteria must also be met to conduct a study with a subordinate population:

The PI must clearly define the reasons for planning to recruit a subordinate population
Protocol approval must also be obtained in which a written statement from the immediate boss or corresponding authority of the subordinate participant(s) verifying that no coercion has existed
If resident doctors or partners are recruited for the study, the program director must provide the REC with a letter of support issued by a person without ties to the study
Confidentiality of research data for the group of subordinate and student participants is important to consider to avoid negatively impacting the participants’ employment possibilities, professional development, study plans, or social relationships. The REC will also need to pay special attention to the PI’s plans to safeguard data security

The HlthResRegs and G-RECs-Op-2018 further specify that these relationships include participants who are in junior or subordinate positions in hierarchically structured groups, such as students, employees, workers in laboratories and hospitals, members of the armed forces, prisoners, social rehabilitation centers, and other members of special population groups in which informed consent can be influenced by some authority.

Persons in Local Communities

As per HlthResRegs, clinical trials involving participants in local communities must meet the following requirements:

Research will be permitted when the expected benefit is reasonably assured, and when previous studies carried out on a small scale have not produced conclusive results
The PI must obtain the approval of the health authorities and other civil authorities of the community to be studied, in addition to obtaining informed consent from individuals who are included in the trial
In the case of vulnerable communities due to their economic or social conditions, such as indigenous communities, the REC is also required to issue a favorable opinion
Experimental investigations in communities may only be carried out by establishments that have the Ministry of Health (Secretaría de Salud)’s prior authorization
The experimental design should offer practical measures of protection for research participants, and ensure that valid results will be obtained, involving the minimum number of participants
The most pertinent ethical considerations applicable to research on participants must be extrapolated to the communal context

Terminally Ill Persons

As stated in GenHlthLaw, if a terminally ill patient is a minor, or is incapable of expressing their consent, consent should be provided by the patient’s parent(s) or guardian(s), and in their absence, by their legal representative(s).

1.61

Search for the Status of Implementation of ICH Guidelines by ICH Members

3.1

Annex 5

Title VI Chapter II (Article 166 Bis 8)

Title II (Chapters II and V)

Last content review/update: March 21, 2024

Overview

As per G-ResEthics and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), in all Thai clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Per an in-country subject matter expert, Thailand is implementing THA-28.

G-ResEthics characterizes vulnerable populations as those who are dependent on others and are unable to express their opinion freely or make their own decisions. THA-28 adds that, whether reasonable or not, the participant may also consent to participate out of fear that they will be penalized for not participating. This may apply, for example, to members of a hierarchical organization such as medical, pharmacy, dental, or nursing students and lower-level hospital personnel and staff rooms. THA-28 also notes that participants in this study population may be persuaded to enter a trial with the hope of obtaining benefits from their participation in the research. Per G-ResEthics, these participants may include hospitalized patients, prisoners, children, the mentally impaired, critically ill and psychotic patients, pregnant women, and the disadvantaged. Per THA-28, other vulnerable participants may include drug company employees, soldiers, prisoners, patients with incurable diseases, emergency patients, unemployed or poor people, members of minority groups, the homeless, immigrants, and young people who are unable to give consent on their own.

The G-ResEthics specifies that trials involving vulnerable persons must meet the following requirements:

Irrefutable rationale for conducting research clearly explained in the protocol
Precautions against possible physical and mental harms exercised
Appropriate research procedures used
Ensure that, as applicable, the participant’s parents or legal representative/guardian are fully informed about the study
Proof that the participants are voluntarily participating in the study
Ensure that the possible risks should not be greater than minimal when a study will not have a direct health benefit to the vulnerable group, unless the ethics committee permits a greater than minimal risk study to be conducted

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.

1.61

2.2.2 and 3.4

Children/Minors

Last content review/update: November 8, 2024

Per ChildRts, a child is defined as under 12 years of age, and adolescents are those between 12 and 18 years of age. When there is doubt as to whether the person is over 18 years of age, it should be presumed that the person is an adolescent. When there is doubt as to whether the person is over or under 12 years of age, it should be presumed that the person is a child.

Additionally, per HlthResRegs, in all cases, a written informed consent must be obtained from those exercising parental authority, or the legal guardian(s) of the minor, except in the case of emancipated minors over 16 years of age. Moreover, when the mental capacity or psychological state of the minor or incapacitated person permits, their acceptance must also be obtained after the investigator(s) have explained what they intend to do in the study. However, the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) may waive compliance with these requirements for justified reasons.

As set forth in G-RECs-Op-2018 and HlthResRegs, a research study involving minors must ensure that similar studies have been previously done in older people and in immature animals, except when it comes to studying conditions that are specific to the neonatal stage or specific conditions associated with certain ages.

Per G-RECs-Op-2018, research studies classified as risky and likely to benefit the minor directly, will be admissible when the following requirements are met:

The risk is justified by the importance of the benefit that the minor will receive
The benefit is equal to or greater than other alternatives already established for its diagnosis and treatment
When the mental capacity and psychological state of the minor allow, the informed assent must also be obtained, after explaining what is intended to be done. The REC may waive compliance with these requirements for justified reasons
The informed consent information provided is appropriate for the understanding of minors

Per G-RECs-Op-2018 and HlthResRegs, when two (2) persons exercise the parental authority of a minor, only the consent of one (1) of them must be permitted if there is irrefutable or manifest proof that the other is unable to provide it, proof of the parental authority’s negligence, or imminent risk to the minor’s health or life.

HlthResRegs indicates that investigations classified as risky, and with a probability of direct benefit for the minor, will be permitted in the following circumstances:

The risk is justified by the importance of the benefit that the minor will receive, and
The benefit is equal to or greater than other alternatives already established for diagnosis and treatment

Per HlthResRegs, investigations classified as risky and without direct benefit to the minor, will be allowed in the following circumstances:

When the risk is minimal: The intervention or procedure must represent a reasonable experience for minors, and comparable with those characteristics of their current or expected medical, psychological, social, or educational situation. Also, the intervention or procedure should have high probability of obtaining generalizable knowledge about the condition or illness of the minor to benefit others with this disorder as well
When the risk is greater than the minimum: The research should offer a good chance of understanding, preventing, or alleviating a serious problem affecting the health and well-being of children. Also, the head of the health institution should establish strict supervision to evaluate the magnitude of the risks anticipated or others that may arise, and immediately suspend the investigation when the risk could affect the biological, psychological, or social welfare of the minor

Assent Requirements

The applicable regulatory requirements do not specify the age of assent required for minors.

Per G-RECs-Op-2018, assent must also be obtained from a minor who is deemed capable of providing assent, and the minor must be informed about the study in a manner tailored to their emotional and intellectual maturity level, considering at all times the seriousness of the decision.

Article 5

Annex 5

Title II (Chapter III)

Last content review/update: March 21, 2024

According to the ThaiCode, a minor is someone under 20 years of age or unmarried. The Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH) guidelines (THA-13) specifies that the age suitable to give consent is 18 years or older. The Declaration of Rights and Code of Conduct for Patients (THA-11) also indicates that a child is someone under 18 years of age.

As set forth in G-ResEthics, when the research participant is a minor, informed consent should be obtained from the parents, guardians, or legal representatives. Additionally, precautions against possible physical and mental harms should be exercised. Furthermore, the rights of the minors should be respected for their voluntary decision to participate in a clinical study. THA-11 similarly indicates that parents or legal guardians may exercise their rights on behalf of a child patient who is not over 18 years of age.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28) states that when a clinical trial includes minors, the minor should be informed about the trial to the extent compatible with the minor’s understanding and, if capable, the minor should sign and personally date the written informed consent. Per an in-country subject matter expert, Thailand is implementing THA-28.

Assent Requirements

THA-13 specifies that assent is required for minors seven (7) through 18 years of age. Different assent forms should be created for the following age groups: seven (7) to 13 and over 13 until 18.

Additional Suggestion of the Committee (2004) (p. 75) and Additional Resolution of the Committee (2006) (p.77)

4.8.12

2.2.2 and 3.4

Part II (Sections 19 and 20)

Pregnant Women, Fetuses & Neonates

Last content review/update: November 8, 2024

As per HlthResRegs, studies involving women of childbearing age; women who are in any stage of pregnancy or are postpartum; or studies involving treatments or procedures using embryos, fetuses, or newborns, are required to obtain an informed consent form (ICF) from the woman and her spouse or partner. In addition, HlthResRegs and G-RECs-Op-2018 note that consent from the spouse or partner may only be waived in the case of their incapacity (or irrefutable or manifest inability) to provide it, or when there is imminent risk to the health or life of the woman, embryo, fetus, or newborn. All studies must also comply with the general ethics requirements that must be fulfilled prior to research involving humans as delineated in HlthResRegs.

HlthResRegs and G-RECs-Op-2018 further state that research in pregnant women will only be permitted if it is for therapeutic benefit, and represents an opportunity to understand, prevent, or alleviate any serious pathology. HlthResRegs and G-RECs-Op-2018 indicate that these studies are allowed when they are aimed at improving a pregnant woman’s health with minimal risk to the embryo or fetus, or per HlthResRegs, seek to increase the fetus’s viability, with minimal risk to a pregnant woman. G-RECs-Op-2018 adds that the ICF should mention the possible risk to the fetus.

According to HlthResRegs, investigations to be carried out on pregnant women should be preceded by studies carried out on non-pregnant woman to demonstrate the study’s safety, with the exception of studies requiring the specific condition. Those investigations classified as higher than minimum risk and will be conducted using women of childbearing age should implement the following measures:

Certify the women are not pregnant prior to their acceptance as research participants, and
Decrease the chances of pregnancy as much as possible during the development of the investigation

Per HlthResRegs and G-RECs-Op-2018, during studies conducted with pregnant women, the following requirements must be met:

The investigators will not have the authority to decide on the time, method, or procedure used to terminate the pregnancy, nor will they participate in decisions regarding the viability of the fetus
The Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI))’s authorization is required prior to any modification of the method used to terminate the pregnancy. These modifications mean that there will be minimal risk to the mother’s health and do not represent any risk to the survival of the fetus, and
In any case, it is strictly forbidden to grant monetary or other incentives to interrupt the pregnancy, for the interest of the investigation or for other reasons

As set forth in HlthResRegs and G-RECs-Op-2018, investigators must comply with the following additional criteria when conducting studies with women who are in any stage of pregnancy or are postpartum:

Research without therapeutic benefit in pregnant women, whose objective is to obtain general knowledge about pregnancy, should not represent a risk greater than the minimum for the woman, the embryo, or the fetus
Investigations in pregnant women that imply an intervention or experimental procedure not related to pregnancy, but with therapeutic benefit for women (e.g., cases of toxemia gravidarum, diabetes, hypertension, and neoplasms, etc.) should not expose the embryo or the fetus to a greater than minimum risk, except when the use of the intervention or procedure is justified to save the life of the woman
For investigations during labor, the informed consent must be obtained prior to initiating the study and must expressly state that consent may be withdrawn at any time during labor
Investigations in women during the puerperium will be allowed when they do not interfere with the health of the mother and the newborn
Research on women during lactation will be authorized when there is no risk for the infant, or when the mother decides not to breastfeed, she ensures her feeding by another method and provides informed consent

Per HlthResRegs, studies involving treatments or procedures using embryos, fetuses, or newborns must meet the following requirements:

Fetuses will be permitted to be subjects of investigation only if the techniques and means used provide maximum security for them and the pregnant woman
Newborns will not be used as subjects of investigation until it has been established with certainty whether or not they are live births, except when the research is aimed at increasing their probability of survival until the viability phase, the study procedures do not cause the cessation of their vital functions or when, without adding any risk, they seek to obtain important generalizable knowledge that cannot be obtained in any other way
Live births may be used as subjects of investigation if the investigator(s) obtain consent from the woman and her spouse or partner

In addition, HlthResRegs indicates that investigations involving embryos, deaths, fetuses, still births, macerated fetal matter, cells, tissues and the use of biological materials extracted from them, must comply with GenHlthLaw. GenHlthLaw specifically prohibits the use, for any purpose, of embryonic or fetal tissues caused by induced abortions. G-RECs-Op-2018, by comparison, states that for investigators to use biological materials derived from abortions, the informed consent must be independent from the consent granted for an abortion, and will not include financial compensation.

Annex 5

Title XIV (Chapter I, Article 318 and Chapter III, Article 330)

Title II (Chapter IV, Articles 41-55)

Last content review/update: March 21, 2024

As per G-ResEthics, any Thai clinical studies involving pregnant women and fetuses require additional safeguards to ensure that the research conforms to appropriate ethical standards and upholds societal values. Adequate information on the safety and impacts to the fetus should also be made available.

In addition, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28) indicates that the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant. Per an in-country subject matter expert, Thailand is implementing THA-28.

4.8.10

2.2 and 3.4

Prisoners

Last content review/update: November 8, 2024

No applicable requirements

Last content review/update: March 21, 2024

According to G-ResEthics, prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study involving prisoners should ensure that these prospective participants are informed and are given the opportunity to make their own decisions without any interference from a higher authority.

2.2, 3.2, and 3.4

Mentally Impaired

Last content review/update: November 8, 2024

The Mexican government has updated the GenHlthLaw to prioritize mental health with the development of health policies required to be in accordance with the provisions of the MexConstitution and international treaties on human rights. For the purposes of this law, mental health is understood as a state of physical, mental, emotional, and social well-being determined by the individual's interaction with society and linked to the full exercise of human rights. Refer to GenHlthLaw for details on consent requirements for the treatment of the mental health services user population.

Per HlthResRegs, when the mental capacity and psychological state of the participant permits, their acceptance must also be obtained after the investigator(s) explain what they intend to do during a clinical study. The Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) may waive compliance with these requirements for justified reasons. All studies must also comply with the general ethics requirements that must be fulfilled prior to research involving humans as delineated in HlthResRegs.

As indicated in HlthResRegs, investigations classified as risky, but with a probability of direct benefit for the mentally incompetent participant, will be allowed when:

The risk is justified by the importance of the benefit that the incompetent participant will receive, and
The benefit is equal to or greater than other alternatives already established for diagnosis and treatment

In addition, per HlthResRegs, investigations classified as risky and without direct benefit to the mentally incompetent, will be allowed in the following circumstances:

When the risk is minimal: The intervention or procedure must represent a reasonable experience for the incompetent participant and be comparable with those characteristics of their current or expected medical, psychological, social, or educational situation. The intervention or procedure should also have a high probability of obtaining generalizable knowledge about the condition or illness of the mentally incompetent participant to benefit others with this disorder
When the risk is greater than the minimum: The research should offer a good chance of understanding, preventing, or alleviating a serious problem affecting the health and well-being of the mentally incapacitated. In addition, the head of the health institution should establish strict supervision to evaluate the magnitude of the risks anticipated or others that may arise, and immediately suspend the investigation when the risk could affect the biological, psychological, or social welfare of the mentally incompetent participant.

Title III (Chapter VII, Articles 72 and 75)

Title I (Chapter I, Article 1)

Title II (Chapter I, Article 14 and Chapter III, Articles 34, 36-39)

Last content review/update: March 21, 2024

Per G-ResEthics, informed consent should be obtained from the legal representatives or guardians of participants for studies involving psychiatric or mentally incapacitated patients. The Declaration of Rights and Code of Conduct for Patients (THA-11) also states that parents or legal representatives may exercise their rights on behalf of a physically or mentally handicapped child patient who cannot exercise their rights on their own.

As further explained in MentalHlthAct, any research to be conducted with patients who are mentally impaired have the right to:

Receive treatment according to medical standards that protect human dignity
Have information about their illness and treatment kept confidential other than what is required to be disclosed by law
Sign an ethics committee (EC) approved consent form prior to participation
Receive equal access to state health insurance and social security systems

In addition, MentalHlthAct prohibits disclosure of health information of mentally impaired participants in a manner that may damage the individual, except in the event that the patient or others may be in danger, for public safety, or specific laws require this information to be disclosed.

MentalHlthAct also states that any research involving patients who are mentally impaired can only be performed after obtaining their consent as well as EC approval and approval from other relevant authorities to conduct the study. The patient’s approval may be revoked at any time. Treatment may only be administered once the patient has been informed as to why the treatment is necessary and provided with the details and benefits prior to giving consent. In the case of a patient under 18 years old, or one who lacks the ability to make decisions, the patient’s parent or legal guardian should provide consent. If the patient is to be admitted to a public hospital or treatment facility, signed consent is necessary. Research is permitted in the case of patients with mental impairments who are either facing dangerous conditions or compulsory treatment is required.

3.4.5

Sections 3, 17, and 20-22

Definition of Investigational Product

Last content review/update: November 8, 2024

As delineated in COFEPRIS-GCP and the Guideline for Good Clinical Practice E6 (R1) (MEX-32), an investigational product (IP) is defined as any pharmaceutical form containing an active ingredient or placebo, or a product of biological or biotechnological origin that is used or tested in a clinical trial, including a registered product when used or packaged in a different way with for which it was authorized, or when it is tested for indications that have not been authorized, or when it is used to obtain more information about its authorized use. COFEPRIS-GCP also notes this definition also applies to new chemical and biological entities, generics, new formulations, combination products, and biosimilars, and medical devices with or without the release of some active ingredient.

NOM-012-SSA3-2012 similarly states that investigational medicines or devices are used or applied to humans for scientific research purposes, for which there is insufficient scientific evidence to demonstrate its preventative, therapeutic, or rehabilitative effectiveness, or is intended to modify the therapeutic indications of already known products.

NOM-059-SSA1-2015 further defines an IP as a drug or biological product for which there is no previous experience in the country, has not been registered by the Ministry of Health (Secretaría de Salud), and therefore, has not been distributed commercially. This definition also encompasses medicines registered and approved for sale, when they are being investigated for an unapproved indication, dose, or route of administration, including their use in combination with other products that are different from the approved use.

(Note: In Mexico, IPs are also referred to as “drugs/products in research”).

1.33

1.7

1 and 4.16

3.77

Last content review/update: March 21, 2024

In accordance with G-ResEthics and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use. Per an in-country subject matter expert, Thailand is implementing THA-28.

G-ResEthics states that an investigational drug used in a clinical trial falls into one (1) of four (4) categories:

New drugs
Unregistered drugs in Thailand
Drugs registered by the national drug authority, but being studied in new doses or indications not previously approved
Locally produced drugs that require efficacy testing

1.33

7.1 and Annex 5

Manufacturing & Import

Last content review/update: November 8, 2024

Manufacturing

According to GenHlthLaw, Reg-COFEPRIS, and Reg-HlthProd, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is responsible for authorizing the manufacture of all drug products for human use, including investigational products (IPs), in Mexico. Pursuant to GenHlthLaw, COFEPRIS, acting on behalf of the Ministry of Health (Secretaría de Salud), also issued NOM-059-SSA1-2015 and NOM-164-SSA1-2015 to provide standards delineating the minimum requirements necessary for the manufacture of drugs or active ingredients to be marketed in the country or used in clinical research. See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

As indicated in GenHlthLaw and Reg-HlthProd, drug manufacturers must submit a request to COFEPRIS to obtain a sanitary registration prior to initiating any drug manufacturing activities. Reg-HlthProd states that COFEPRIS must complete its review in 60 days, or the application will be deemed approved. Per GenHlthLaw, the sanitary registration is valid for five (5) years. The sanitary registration may be extended for an additional five (5) years if the extension is requested prior to the expiration of the current authorization, or the registration will be cancelled or revoked. See also GenHlthLaw and Reg-HlthProd, for detailed drug manufacturer registration submission requirements. In addition, per MEX-110, COFEPRIS is recognized as a National Regulatory Authority of Regional Reference of Medicines and Biological Products by the Pan American Health Organization (PAHO)/World Health Organization (WHO), and per MEX-111, is also a member of Pharmaceutical Inspection Co-operation Scheme (PIC/S). Per MEX-2, COFEPRIS has also implemented the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)’s Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Q7) (MEX-81).

Import

As delineated in GenHlthLaw, Reg-COFEPRIS, Reg-HlthProd, and G-UnregDrugImprts, COFEPRIS is also responsible for authorizing the import of IPs. According to Reg-HlthProd, G-UnregDrugImprts, and G-UnregDrugImprts, an applicant or the legal representative may submit a request to import an IP after COFEPRIS has approved the sanitary authorization request for those drugs that are neither narcotic nor psychotropic, that do not have sanitary registrations, and that are intended to be used for human research. As per GenHlthLaw, the applicant must be a resident of Mexico or have a legal representative submit an import request on the applicant’s behalf. Additionally, per MEX-84 and G-DIGIPRiS-ResProts, the following documentation is required for submission to COFEPRIS:

Letter of delegation of responsibility to the importer signed by the sponsor
Letter of acceptance of responsibility from the importer signed by the importer’s legal representative

Per Reg-HlthProd, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, foreign manufacturers must submit a license, a good manufacturing practices (GMP) certificate, or a document issued by the competent authority in the country of origin that proves the company has permission to manufacture drugs. See MEX-36 for additional information on obtaining a GMP certificate.

Reg-HlthProd further states that COFEPRIS may grant permission to import raw materials or finished products without sanitary registration only in the following cases:

When a contingency arises
When required by health policy
For purposes of scientific research, registration, or personal use, or
For laboratory tests

In addition, Reg-HlthProd indicates that three (3) types of sanitary import permits may be issued:

Definitive import – authorizes the entry of products to remain in the national territory for an unlimited time
Temporary import – authorizes the entry of products for a limited time and with a specific purpose, with the understanding that they must return to the country of origin in a period not exceeding one (1) year
Import in transit – authorizes the entry of products for their transfer from one (1) national office to another, for their departure to leave the country, within a period not exceeding 30 days, and for sale or temporary distribution. The sale or distribution is authorized exclusively for medicines to be used for strategic purposes

Reg-HlthProd, G-UnregDrugImprts, and G-UnregDrugImprts state that an import request may be submitted to COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) once the agency has authorized the protocol for research to be conducted on human beings. The following documentation should be included (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Authorizations, Certificates and Visits Form (see MEX-25) (Original)
Proof of payment of fees (original and two (2) copies)
Health License
Notice of Operation (original and one (1) copy)
Approval from the research protocol office authorized by COFEPRIS and its amendments, (only in the case of research on human beings) (original and one (1) copy)
Technical and scientific information demonstrating the identity and purity of its components in accordance with Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements; the stability of the finished product in accordance with the corresponding standards, and; therapeutic efficacy and safety according to the corresponding scientific information
Prescribing information (broad and reduced versions)
Sample label
Free sale certificate issued by the health authority of the country of origin
Certificate that the company has permission to manufacture medicines and proof of good manufacturing practices issued by the corresponding authority of the country of origin
Letter of representation, when the laboratory that manufactures import product abroad is not a subsidiary or parent company of the laboratory requesting the registration

In addition, Reg-HlthProd requires documents originating from a foreign country to be presented in Spanish, or if in another language, with a Spanish translation made by an expert translator.

Per Reg-HlthProd and G-UnregDrugImprts, COFEPRIS has 10 days to approve the request. If COFEPRIS does not respond within this timeframe, the request is deemed approved. G-UnregDrugImprts also notes that COFEPRIS has four (4) business days to send the applicant a prevention notification regarding missing or additional information required. The applicant, in turn, has five (5) business days to respond. Reg-HlthProd and G-UnregDrugImprts further states that the maximum validity of import authorizations is 180 days, which may be extended for an equal period, provided the conditions in which they have been granted have not changed.

As set forth in Agrmnt_RegHlthSup, COFEPRIS published an agreement that recognizes the requirements, tests, and evaluation procedures carried out by an approved list of regulatory authorities specified in this agreement to be equivalent to those conducted in Mexico for the purposes of evaluating and approving allopathic drug products for sale, distribution, and use. Per Agrmnt_RegHlthSup, COFEPRIS will also permit the regulatory authorities referenced in this agreement to import raw materials or finished drug products, aimed at any disease or condition, whether the products are registered or unregistered in Mexico, and even if the products do not meet COFEPRIS’s quality, safety, efficacy, and GMP standards. The imported products or raw materials must be registered by the approved regulatory authorities, be prequalified by the WHO, or be registered with a regulatory agency that is a PIC/S member like COFEPRIS. See NOM-059-SSA1-2015-Annexes for additional information on COFEPRIS’s compliance with PIC quality risk management and master file preparation requirements that are included as annexes to NOM-059-SSA1-2015.

Per Agrmnt_RegHlthSup, the Ministry of Health may only grant permission for these unregistered drug products to be imported from regulatory authorities approved by COFEPRIS if the drugs are required by necessity in accordance with Reg-HlthProd, as described earlier in this section. Agrmnt_RegHlthSup requires the manufacturer to initiate the sanitary registration process with COFEPRIS within five (5) business days following the import of an unregistered drug product. COFEPRIS will then have a maximum of 60 business days to issue its decision.

As discussed in detail in Agrmnt_RegHlthSup, imported drugs must comply with the legal and technical provisions laid down in GenHlthLaw and Reg-HlthProd. MEX-13 further notes that COFEPRIS is allowed to purchase medicines anywhere in the world with the fundamental goal of avoiding a drug shortage in Mexico. The agreement also guarantees the quality of imported drugs through the regulatory measures COFEPRIS established mandating the analysis of all drug batches that enter the country to go through the Analytical Control and Coverage Expansion Commission, the laboratory that will then carry out a corresponding analysis. The imported drugs must also originate from countries with a regulatory standard equivalent to COFEPRIS and from those manufacturers that can provide health records from the country of origin demonstrating that the drugs have already been used in their population.

Refer to Agrmnt_RegHlthSup for detailed information and documentation requirements to register drugs and biological products. See also MEX-42 for additional background information on this agreement.

D-CargoTransprt bars exclusive cargo shipments to the Mexico City International Airport (AICM). See D-CargoTransprt and D-ModCargoTransprt for more details regarding the relocation of cargo shipments to other airports in Mexico.

Please note: Mexico is party to the Nagoya Protocol on Access and Benefit-sharing (MEX-5), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see MEX-35.

4.4, 5.1, and 10.1

Introduction (Box 1)

XIII. Specific Sections of the Procedure on the Platform (VI and XIV)

Requirements (29)

Requirements, Response time, Validity of the Resolution, and Steps

Title V (Chapter I, Article 102), Title XII ((Chapter I, Articles 194, 194 Bi., 195, 197, 198, and 200-204), (Chapter IV, Articles 221-222), (Chapter VII, Articles 257-258), and (Chapter XIII, Articles 285 and 295)), and Title XVI ((Chapter I, Articles 368-376, 376 Bis, and 378) and (Chapter III, Article 391 Bis))

Preamble, First-Third, Section II (Second, Third, Fourth, and Fifteenth), and Section IV

Chapter I (Article 3)

Title IV ((Chapter I, Articles 99-100) and (Chapter II, Article 113)), Title V (Chapter I, Article 132), Title VI ((Chapter I, Articles 160-161), (Chapter II, Articles 162-163), (Chapter III, 167-171, 185-186, 190-bis 1, 190-bis 2, 190-bis 5, 190-bis 6), and (Chapter IV, Articles 193-194 and 196)), and Title VII

1 and 16

1 and 10.9

Last content review/update: March 21, 2024

Manufacturing

According to the DrugAct, ClinSampleProd, and ClinImprtOrdr, the Thai Food and Drug Administration (Thai FDA) is responsible for authorizing the manufacture of investigational products (IPs) in Thailand. The Thai FDA will approve the manufacture of an IP after the clinical trial application has been approved.

As explained in ClinSampleProd, the Thai FDA’s approval of a request to manufacture drug samples for investigational purposes is obtained using the P.Y.8 form (ClinSampleProd (Appendix 1) or THA-76 (Appendix 1)).

ClinSampleProd specifies that the following information must be included with the P.Y.8 form (Appendix 1):

Detailed list of manufactured drugs
Appearance and color of medicine
Number or quantity to be produced
Quantity of drug ingredients (must be reported in metric units or in a percentage)
Packaging size (packaging details)
Specifying if drug samples are for human research studies or cases other than human research studies
Drug label (two (2) copies)
Medicine package document (two (2) copies)
Other documents in the case of producing drug samples for human research studies

See also the Appendix 6 (Evidence of Drug Quality Information) in ClinSampleProd and (THA-76 (Appendix 6)) for additional requirements included on this form.

ClinSampleProd and ClinImprtOrdr, also state that the IP must be manufactured in accordance with good manufacturing practice (GMP) guidelines.

In addition, per ClinSampleProd, following the Thai FDA’s approval to manufacture IP samples, the applicant must also obtain approval prior to implementing changes in the following categories:

Changes that must be notified
Changes that require a change request to be submitted before proceeding, and
Changes that require a new production permit request to be submitted

ClinSampleProd indicates that when the change complies with one (1) of the listed categories, the applicant should:

Prepare documents and evidence according to the document self-check form for requesting changes using the Appendix 13 form or (THA-76 (Appendix 13))
Submit a request to amend the details regarding permission using the Appendix 14 form or (THA-76 (Appendix 14)) (1 set)

Per ClinSampleProd, along with the Appendix 14 form, the applicant should attach relevant documents showing the revised section(s) and one (1) set of power of attorney documentation for each paper submission. ClinSampleProd notes that one (1) request can only change one (1) main issue. For example, in the case of requesting to extend the validity of medicines, this is a change in quality and results in a new expiration date label) to be submitted in one (1) request. Additionally, for amendment requests that refer to information already submitted via the FDA’s Skynet E-Submission System (THA-54), the applicant must submit documents according to the system's procedures.

For changes that require the Thai FDA’s Medicines Regulation Division to be notified, ClinSampleProd states that the applicant should submit a letter of explanation, refer to the sample drug production license for human research studies that has been received, and attach related documents showing the revised sections or other information that needs to be notified as detailed in the Appendix 15 form or (THA-76 (Appendix 15)).

Import

As delineated in ClinImprtOrdr, the Thai FDA is also responsible for authorizing the import of IPs. The Thai FDA’s approval of a drug import license application for clinical research purposes serves as the import license using the N.Y.M.1 form (ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2)). Per DrugImprtRules-1989 and DrugImprtRules-2009, all requests approved by the Thai FDA to order or import drugs into the country for research purposes are exempt from registration.

According to ClinImprtOrdr and THA-18, the following documents are also required to be submitted to the Thai FDA:

Import license application/N.Y.M.1 (ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2))
Summary of research project (Thai)
Ethics committee (EC) approval letter
Patient Information Sheet (in Thai)
Complete research project details (in Thai or English)
Drug labels for every package size (in Thai or English)
Drug documentation (for drug formulas that have already been registered)
Investigator’s brochure (IB) (for drugs not yet registered)
Pharmaceutical quality control and production documents
Drug name(s) (including dosage form, quantity, and details of every packaging size)

ClinImprtOrdr also states that the quantity of the IP must be calculated based on the number of study participants of each institute for the whole study duration in accordance with the information in the study protocol. The amount of the IP cannot exceed 20% to cover drug damage. Please refer to ClinImprtOrdr for more detailed IP supply requirements.

In addition, per G-CT-DIPApp, after the import license is granted, the applicant must inform or request permission from the Thai FDA prior to initiating the following:

Changes to clinical trial drug supplies
Changes to an approved protocol (protocol amendment) or changes related to or affecting participant safety
In cases where the sponsor is required to immediately make one (1) or more amendments because the clinical trial or the use of IP in the trial endangers the health of a clinical trial participant or other person, the applicant may immediately make the amendment without prior review by the Thai FDA. A corresponding notification clearly identifying the change and the rationale for immediate implementation of the change must be filed within 15 working days after the amendment implementation date. A corresponding notification letter referring to the related approved import license (see ClinImprtOrdr (Appendix 2) and THA-18 (Appendix 2) for N.Y.M.1 form), along with supplemental documents as stated in Appendix 12, are also required. (Note: The Additional Amendment/Clarification Request Form referenced in G-CT-DIPApp as Appendix 12 is only available in ClinImprtOrdr and THA-18 (Appendix 12))

Furthermore, per G-CT-DIPApp, after the import license is granted, the applicant must also notify the Thai FDA in the following cases:

Changes to the protocol that do not affect the safety of the trial participants
When the clinical trial has been discontinued in its entirety or at any clinical trial site for reasons not related to the safety of clinical trial participants
IB changes
Chemistry and manufacturing or quality changes that do not affect drug quality or safety
Premature discontinuation of a trial (See the Risk & Quality Management section for detailed notification requirements)

Per THA-19, a request for an expedited license to order or import IPs may also be submitted to the Thai FDA for the following:

Clinical research purposes
To produce sample IPs for human research
To expand the scope of drug results for human research to include a new research project
To address a public health emergency
To address an urgent clinical research need, in the event a facility runs out of an IP (an EC waiver may be required)

See the Regulatory Fees section for information on IP import fees. See also the Submission Process section for instructions on submitting a drug import waiver request to the Thai FDA.

The DrugAct states that a license will remain valid until December 31st of the year of issue. The license holder who would like to renew the license must file an application for renewal prior to the license expiration date. Once the renewal application has been filed, the license holder may continue to conduct business unless the renewal request is denied. A license holder whose license has expired for not more than one (1) month may file an exemption indicating the reason for obtaining a license extension. However, an application renewal request submitted after one (1) month from the date of license expiration is not permitted. In the event that the Thai FDA does not issue or grant a license renewal request, the applicant may appeal in writing to the Minister within 30 days from the date of receiving the notice rejecting the request. The applicant may obtain a temporary license to operate the business until a final decision is issued by the Minister.

Appendices 1-3, 6-7, and 12-15

Appendices 2-4, 7-8, 11-12, and 17-19

14.2 and 16.2

Chapter I (10), Chapter II (12), Chapter III (25 and 27), and Chapter V (46)

Preface, 1.1-1.3, 1.6, 1.10-1.12, 4.2, and Appendices 1-3, 6-7, and 12-15

Preface, 1.1-1.4, 1.10-1.12, 1.15, and Appendices 1-4, 7-12, and 17-19

Articles 2 and 3

Articles 2 and 3, and Letter 1

Quality Requirements

Last content review/update: November 8, 2024

Investigator’s Brochure

As indicated in MEX-2, COFEPRIS is in the process of implementing the ICH Guideline for Good Clinical Practice E6 (R2) (MEX-22). G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts are in compliance with the Guideline for Good Clinical Practice E6 (R2) (MEX-22), regarding investigational product (IP) quality/manufacturing and investigator’s brochure (IB) requirements (also known as investigator’s manual in Mexico), while COFEPRIS-GCP complies with the Guideline for Good Clinical Practice E6 (R1) (MEX-32).

As set forth in GenHlthLaw, and G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, which are in compliance with (MEX-22), the applicant or sponsor is responsible for providing the investigators with an investigator’s brochure (IB). MEX-22 specifies that the sponsor is generally responsible for ensuring that an updated IB is made available to the investigator(s), and the investigators are responsible for providing the updated IB to the responsible ethics committees (ECs). The sponsor should also update the IB as relevant new information becomes available. According to MEX-84, G-DIGIPRiS-ResProts, and MEX-22, the IB should include the following elements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title
Confidentiality statement
Table of Contents
Summary
Introduction
Investigational product (IP) identification data (IP number, generic name of the drug or device, international nonproprietary name, trade name, if applicable)
Collection of clinical and preclinical IP data relevant to the study of IP(s) in human participants
Preclinical information (includes non-clinical pharmacology, pharmacokinetics and metabolism in animals, toxicology)
Clinical information (includes pharmacokinetics and metabolism in humans, safety and efficacy, experience during commercialization)
Data summary and guide for the investigator
Document version and version date (coinciding with the approving opinions of the ECs)
For drug authorization requests: (include IP physicochemical and pharmaceutical properties, formulation, presentation, manufacturing, labeling, storage, packaging and stability, when applicable, etc.)
For COFEPRIS-04-010-D modality (risk-free research (observational studies)) authorization requests: include prescribing information

MEX-84 further notes the purpose of the IB is to provide researchers and others involved in the trial with information to facilitate their understanding of the rationale for and compliance with key protocol features such as: dose, dose frequency/interval, administration methods, and safety monitoring. The IB also provides information to support the design of the clinical phase of the study subjects over the course of the clinical trial. The information in this document must be presented in a concise, objective, and balanced manner which allows the principal investigator, as well as the other parties involved in the trial, to assess the suitability of the proposed trial, emphasizing the relevant and updated scientific information on the IP to monitor participant safety.

See MEX-84, G-DIGIPRiS-ResProts, and MEX-22 for detailed IB guidelines.

Quality Management

As specified in COFEPRIS-GCP, GenHlthLaw, Reg-HlthProd, NOM-059-SSA1-2015, NOM-164-SSA1-2015, NOM-176-SSA1-1998, NOM-073-SSA1-2015, G-HumResProt, MEX-84, G-DIGIPRiS-ResProts, and MEX-22, the sponsor must verify that the products are manufactured in accordance with the current codes of Good Manufacturing Practices (GMPs). See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

In accordance with the GenHlthLaw, Reg-HlthProd, NOM-059-SSA1-2015, NOM-164-SSA1-2015, NOM-176-SSA1-1998, G-HumResProt, G-DIGIPRiS-ResProts, and MEX-22, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires that drug manufacturers ensure IPs meet the required safety, efficacy, and quality characteristics and are manufactured, handled, and stored in accordance with applicable GMPs and provide the following additional information (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Issue the corresponding certificate of analysis signed by the health officer to verify the drugs comply with the quality specifications indicated in the current edition of the Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements, or those specified in the pharmacopeias from other countries, if applicable (per NOM-176-SSA1-1998)
In case of foreign manufacture, the manufacturer must have a GMP certification, license, or document proving that the manufacturer has permission to manufacture medicines, issued by the competent authority in the country of origin (per Reg-HlthProd)

MEX-84 further specifies that the following IP documentation is required to demonstrate compliance with GMPs:

Letter under oath, declaring that the IP and placebo are manufactured under standards that ensure a product is safe for use and that it has the ingredients and potency it claims to have in accordance with established quality requirements, or
Certificate of good practices for the IP, or
Certificate of pharmaceutical product

Additionally, per GenHlthLaw, verification of GMP compliance must be conducted by the Ministry of Health (Secretaría de Salud) or the Ministry’s authorized third parties, or if necessary, recognition of the respective certificate issued by the competent authority of the country of origin, provided there are recognition agreements in place between the competent authorities from both countries. See MEX-36 for additional information on obtaining a GMP certificate.

NOM-059-SSA1-2015 also notes that the manufacture of IPs for use in clinical studies presents greater complexity than marketed drug products due to the lack of systematic procedures resulting from the variety of clinical trial designs. In addition to applying basic GMP principles, drugs for research use in Mexico must also be released in accordance with good clinical practices, and the personnel involved in IP production and control must be experienced in handling drugs in the clinical research phase and be familiar with GMPs.

In addition, per MEX-110, COFEPRIS is recognized as a National Regulatory Authority of Regional Reference of Medicines and Biological Products by the Pan American Health Organization (PAHO)/World Health Organization (WHO), and per MEX-111, is also a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S).

3.2 and 10.1

2.12, 5.6, 7, and 8.2-8.3

XIII. Specific Sections of the Procedure on the Platform (V-VI)

Requirements (28-29)

4.3

Title V (Chapter I, Article 102) and Title XII (Chapter IV, Article 222)

Title II (Chapter I, Articles 7-9), Title IV (Chapter II, Article 113), Title V (Chapter II, Article 168 and 170), and Title VII

0, 1.2, 3.14, and 16

1

4.1

1-3, 6.1, and 9

Last content review/update: March 21, 2024

Investigator's Brochure

In accordance with ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), the sponsor or the designated contract research organization (CRO) is responsible for providing the investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse events data. The sponsor should also update the IB as significant new information becomes available. Per an in-country subject matter expert, Thailand is implementing THA-28. ClinImprtOrdr and ClinSampleProd further state that the IB should comply with the current version of THA-28. Per ClinImprtOrdr, the sponsor is also referred to as the applicant or importer.

As specified in G-ResEthics, ClinImprtOrdr, and ClinSampleProd, and in accordance with THA-28, the IB must provide coverage of the following areas:

Physical, chemical, and pharmaceutical properties and formulation parameters
Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post marketing experiences)
Summary of data and guidance for the investigator(s)
Bibliography

See Section 7 of THA-28 for detailed content guidelines.

ClinImprtOrdr and ClinSampleProd also indicate that evidence must be provided that the IB has been submitted to the ethics committee. In addition, per G-CT-DIPApp, the applicant must notify the Thai Food and Drug Administration (Thai FDA) of changes to the IB after the import license is granted.

Quality Management

ClinImprtOrdr and ClinSampleProd also state that the IP must be manufactured in accordance with Good Manufacturing Practice (GMP) guidelines.

As stated in ClinImprtOrdr, ClinSampleProd, and the DrugAct, the Thai FDA requires the manufacturer to provide the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Evidence of manufacture under conditions compliant with current GMPs
A Certificate of Analysis for each batch of IPs (must be in Thai if the manufacturer is foreign)
A drug registered in a foreign country is required to have a Certificate of Product (CPP)/Certificate of Free Sale (CFS)/evidence of registration from the Drug Control Department from that country and certified by a qualified translator
A Certificate of Free Sale
In the case that the product is approved for marketing authorization in Thailand, provide a copy of certificate of drug registration and evidence that the imported drug and the registered drug are produced by the same manufacturer

Per G-CT-DIPApp, the chemistry, manufacturing and control (CMC) information for an IP submission to the Thai FDA must comply with specific requirements for a new chemical entity. Depending on the phase of the clinical trial, the completed CMC template, as well as the following additional quality information as outlined in the template, must be submitted (Note: The appendices referenced in G-CT-DIPApp are only available as Appendices 7 and 8 in the ClinImprtOrdr and Appendices 7 and 8 in THA-18.)

Additionally, per ClinImprtOrdr, in cases where an applicant submits “Drug quality control and production documents” for drug formulas registered in Thailand, the drug documentation approved by the Thai FDA must be used. When the “Drug quality control and production documents” are for drug formulas registered in other countries, the drug documentation of the specific country should be used. If the documentation is in a language other than English, it should be translated to Thai or English, and certified that the text in other languages matches the Thai/English language. See Appendix 7 of ClinImprtOrdr or THA-18 (Appendix 7) for additional information.

Per G-CT-DIPApp, after the import license is granted, the applicant must also notify the Thai FDA of chemistry and manufacturing or quality changes that do not affect drug quality or safety.

See also THA-18 and THA-76 for the forms included in the appendices in ClinImprtOrdr and ClinSampleProd.

Refer to the Product Management section for additional information on IP supply, storage, and handling requirements, and the Submission Process and Submission Content sections for detailed application requirements.

Appendices 1, 6-7, and 12

Appendices 2, 7-8, 11, and 18

1.36, 5.14, and 7

Annex 5 (6.2, 12.2, and 13)

3, 6, 10, and 14.1

Chapter III (25 and 27)

Preface, 1.6, 1.8, 1.10-1.11, and Appendices 1, 6-7, and 12

1.7-1.8, 1.11, and Appendices 2, 7-11, and 16

Labeling

Last content review/update: November 8, 2024

Investigational product (IP) labeling in Mexico must comply with the requirements set forth in COFEPRIS-GCP, NOM-164-SSA1-2015, NOM-059-SSA1-2015, and the Guideline for Good Clinical Practice E6 (R1) (MEX-32).

As delineated in COFEPRIS-GCP and NOM-059-SSA1-2015, the IP label must be written in Spanish and contain, at a minimum, the following information (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Name, address, and telephone number of the sponsor or main contact
Protocol identification number
Pharmaceutical form and route of administration
Manufacturer name and address
Lot number, identification code, and dosage form
Statements: “For clinical studies only” or "Permitted use only investigation ", "Forbidden marketing", and "Keep away from the reach of children"
Symbol or pictograms warning, if applicable
Expiration date
Storage conditions

NOM-164-SSA1-2015 also states that the IP label must indicate it is material under investigation.

In addition, MEX-22 indicates the sponsor should verify the IPs are coded and labeled in a manner that protects the blinding, if appropriate. In blinded trials, the IP coding system should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding. A sample of the attached IP container label(s) should also be provided to document compliance with applicable labelling regulations and appropriateness of instructions provided to the study participants.

Per NOM-164-SSA1-2015 and NOM-059-SSA1-2015, IPs for use in clinical trials should be packaged in a way that protects the products from alteration, contamination, and damage during storage and shipment. Additionally, procedures or instructions for the control of packaging, labeling, and distribution operations should be prepared.

Per NOM-059-SSA1-2015, in the case of products packaged for blinded clinical studies, manufacturers must ensure that the unused products and supplies are completely (100%) retrieved.

5.13, 8.2.13 and 8.2.17

4.4

5.2

10.9.8

Last content review/update: March 21, 2024

Investigational product (IP) labeling in Thailand must comply with the requirements set forth in ClinImprtOrdr, ClinSampleProd, G-ResEthics, G-CT-DIPApp, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28). Per an in-country subject matter expert, Thailand is implementing THA-28. G-ResEthics and THA-28 state that the IP must be coded and labeled in a manner that protects blinding, if applicable. In addition, per G-CT-DIPApp, if a drug product is registered in Thailand, a certified copy of a certificate(s) of drug registration by the Thai Food and Drug Administration (Thai FDA) must be submitted.

ClinImprtOrdr, ClinSampleProd, and G-CT-DIPApp specify that in general, primary and secondary labels must contain (at least) the following requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

All containers and packaging of all sizes are to use the same format as the actual label
Thai language should be used, except for the drug name/drug code and research project sponsor information, where Thai or English language may be used; in the case of drugs administered by medical study personnel, the label information may be submitted in Thai or English
Drug name/drug code, strength, pharmaceutical form, drug delivery system, unit quantity; in the case of a blind treatment study, the label must specify: “Placebo or [Drug Name/Drug Code] + [Strength]”
Research project code or name
Production model and/or code number to identify components and packaging process
Participant number or treatment number and appointment number (if applicable)
Methods of drug use may refer to documentation specifically describing participants (such as drug use records) or to communicate how medical study personnel can correctly administer the drug product
Name, address, and telephone of the sponsor, contract research organization (CRO), or the investigator (main point of contact for clinical research product information and emergency treatment disclosure), unless the participant receives an identification card displaying this information (with attached documents) and is advised to keep this document in their possession at all times
Statement indicating “for clinical research purposes only” or in other words with the same meaning in the Thai language
Drug storage conditions
Period of use (use as appropriate within the expiration date or retest date) in months/years and in a manner that avoids ambiguity
Statement indicating “keep out of the reach of children” in Thai or in other words meaning the same in Thai, unless the participant is not going to take home the medicine

As described in ClinImprtOrdr and ClinSampleProd, primary labels where the primary packaging is always combined with the secondary packaging, should consist of (at least) the following:

Drug name/drug code, strength, pharmaceutical form, drug delivery system (the dosing route may not be established for the oral solid dosage form), unit quantity, in the case of blind treatment study, specify: “placebo or [drug name/drug code] + [strength]"
Research project code or name
Production model and/or code number to identify the components and packaging procedure
Participant number or treatment number and appointment number (if applicable)
Sponsor/CRO/investigator name

Refer to ClinImprtOrdr and ClinSampleProd for additional primary label requirements.

Per ClinImprtOrdr and ClinSampleProd, drug labeling must be carried out in a facility licensed to manufacture drugs and in accordance with the DrugProdReqs (see Appendix 12). As indicated in ClinImprtOrdr and ClinSampleProd, in the case of drug preparation for administration at the research site, new labels must be attached to the drug package to be used (e.g., injectable drug preparations, preparing to dispense drugs to be taken immediately, etc.). The applicant must ensure that the principal investigator (PI) or designee:

Prepare label(s) or label image(s) with appropriate and accurate information for the purposes of the research project
Prepare a standard operating procedure (SOP) manual or a standardized method for preparing drugs and labeling drugs in accordance with the rules and methods for producing modern drugs
Ensure the SOPs are administered by a pharmacist or other health professional at the research site who has received appropriate training
Provide evidence to document that practices have been inspected by a second party under strict labeling control
Preserve evidence and record various related documents to support inspection by the authorized person or the Medicines Regulation Division

The applicant does not need to submit a label in this case along with the request, but must ensure that the PI or designee complies with these requirements and is always available for inspection or inspection of the research.

Per ClinImprtOrdr, for labels on drugs authorized for importation or ordering into Thailand for research purposes and that have been submitted to the Medicines Regulation Division, the applicant may refer to the original application document if there is no change from the original submission. As described in ClinImprtOrdr, in the case of a request to change the information on the duration of drug use, an additional label indicating the new date and using the original production version should be added. The new label(s) or label image(s) should be submitted in the same format as the original label used, which may cover the original date. However, the new label must not cover the original production version for quality control reasons, and the labeling must be performed at a facility licensed to manufacture the drugs. If necessary, the on-site labeling requirement may be waived. In such cases, the drug must be labeled by a pharmacist or other health professional at the site, or an appropriately trained research supervisor.

Similarly, per ClinSampleProd, for drug labels previously submitted to the Medicines Regulation Division to produce drug samples for human research studies, the applicant may refer to the original document, if it has not been amended. Additionally, the requirements for requesting a change to the period of use on the drug label also follow the same requirements as those delineated for ClinImprtOrdr.

Per ClinImprtOrdr and ClinSampleProd, if necessary, the applicant may request that the Medicines Regulation Division consider a waiver of drug label requirements in the following cases:

Information on drug labels for clinical drug research projects that are conducted in many countries and cannot be changed in a timely manner upon submission of the first authorization request (passing the application review and entry into the system)
Information on the label that may refer to other documents (e.g., reference method of dosage administration, record of drug use, etc.) should be attached to the reference document with an explanation
Additional labeling after the drug is brought into Thailand in order to comply with the requirements for research drug labels: a label(s) or label image(s) must appear in the same format as the actual label; information on the label that may refer to other documents, such as how to give medicine, reference to medication records, etc., by attaching the reference document with an explanation; the place of labeling is a licensed facility to produce the correct drug, or, if necessary, a waiver may be requested for the labeling operation to be in a controlled location instead. In such cases, labeling procedures must be performed by a pharmacist or other research site health professional, or by an appropriately trained research supervisor. Operational procedures and a record of practices should be prepared, and these documents should be checked by a second person. The labeling should be strictly controlled, and operations must be consistent with modern drug production manufacturing guidelines and procedures.

In addition to completing the Request for Drug Waiver in Specific Cases Form (see Appendix 6 of ClinImprtOrdr, Appendix 6 of THA-18, Appendix 5 of ClinSampleProd, or Appendix 5 of THA-76), the reasons should be stated, and the SOPs should be attached.

ClinImprtOrdr and ClinSampleProd state that recommendations for how the drug is to be used should be identified in the protocol for use in accordance with the established indications. If the drug is registered in Thailand as a drug procured from the market in Thailand, there is no need to obtain approval for another production process or packing process. The following should be added to the original container, but not over the original label:

Sponsor, CRO, or investigator name
Research project code
Statements "for clinical research purposes only" or other words synonymous with the Thai language

Appendices 1, 5, 7, and 14

Appendix 2, 6-7, 11, and 18

5.13

Annex 5 (13.1)

3 and 8

1.7 and Appendices 1, 5, 7, and 14

1.6 and Appendices 2, 6-7, 11, and 18

Appendix 12

Product Management

Last content review/update: November 8, 2024

Supply, Storage, and Handling Requirements

COFEPRIS-GCP and the Guideline for Good Clinical Practice E6 (R2) (MEX-22) state the sponsor is responsible for supplying investigators with the investigational products (IP(s)) while ensuring that only the quantity of products necessary to carry out the study is provided, and that none of the products will be marketed or used for purposes unrelated to the investigation.

MEX-22 further specifies that the sponsor is responsible for supplying the investigator(s)/institution(s) with the IP(s) and for ensuring the timely delivery of the IPs. However, the sponsor should not supply an investigator/institution with the IP(s)) until all the required documentation is obtained, such as the favorable opinion of the ethics committee (EC) and approval from the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)).

The sponsor should ensure written procedures include instructions that the investigator/institution should follow for the handling and storage of IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)).

Additionally, MEX-22 indicates the IP should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). The sponsor should determine acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any, for the IPs, and inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations. Additionally, the sponsor should:

Take steps to ensure that the IP(s) are stable over the period of use
Maintain sufficient quantities of the IP(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period

Refer to MEX-22 for detailed sponsor-related IP requirements and MEX-36 for additional information on obtaining a GMP certificate.

COFEPRIS-GCP also delineates the sponsor is responsible for ensuring that IP manufacturing complies with NOM-073-SSA1-2015, which states that during the clinical trial, the manufacturer must validate the stability of the IP until the date of the last administration. The sponsor and the contract research organization (CRO) are responsible for ensuring that the research institution has a restricted storage area to protect the IPs and other products required for the investigation, including adequate temperature controls, humidity, and other conditions according to the manufacturer’s provisions. Additionally, the principal investigator is required to keep track of the receipt, storage, distribution, administration, destruction, or retrieval of the IP and other products required for the clinical study, in accordance with the research protocol provisions.

In addition, NOM-164-SSA1-2015 and NOM-059-SSA1-2015 indicate that there must be a procedure for the retrieval of IPs for clinical use that describes the responsibilities of all the members of the supply chain using the drug to include the manufacturer, the sponsor, the investigator, the clinical monitor, and the head of the research unit. NOM-164-SSA1-2015 further states that a system must be in place for the release of each lot of manufactured IPs and that a qualified person must approve the release. See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

According to MEX-84, the following IP documentation is also required to be submitted to COFEPRIS:

Letter under oath guaranteeing the shelf life (stability) of the IP from the date of manufacture to the date of the last administration that will be carried out as part of the investigational protocol, or a protocol and report of results of the accelerated and long-term stability study of the IP and placebo, guaranteeing its stability from the date of manufacture to the date of the last administration in the research protocol
Letter under oath, declaring that the IP and placebo are manufactured under standards that ensure a product is safe for use and that it has the ingredients and potency it claims to have in accordance with established quality requirements; a certificate of good practices for the IP; or a certificate of pharmaceutical product
Letter of description of import inputs that expresses the approximate quantity of the IP

MEX-84 further notes that compliance with GMP and product stability are not equivalent. In the case of a letter under oath, it is valid to declare together compliance with GMP and that the shelf life of the IP is guaranteed at least until the date of the last administration of the IP and/or placebo.

In addition, per G-DIGIPRiS-ResProts, a letter of import supplies should be provided to COFEPRIS that clearly establishes the quantity and description of supplies that will be imported during each stage of the study. The letter should include the IP or placebo (when applicable), pharmaceutical form, presentation, concentration, and number of participants to be enrolled in Mexico. A letter of the stability studies should also be provided to support the IP and the placebo comply with the physical, chemical, and biological parameters which must be complied with throughout its useful life, and to maintain established quality specifications during storage and use.

Record Requirements

As indicated in the MEX-22, the sponsor should:

Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
Maintain a system for retrieving IPs and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim)
Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

MEX-22 further states the investigator/institution and/or a pharmacist, or other appropriate individual who is designated by the investigator/institution, should maintain records of the IP's delivery to the trial site, the inventory at the site, the use by each participant, and the return to the sponsor or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the IP(s) and trial participants. Investigators should maintain records that document adequately that the participants were provided the doses specified by the protocol and reconcile all IP(s) received from the sponsor.

Per NOM-059-SSA1-2015, the sponsor is also responsible for storing files related to the manufacture and control of the IP for at least five (5) years after product registration has been granted. Additionally, the sponsor must ensure that this documentation is safeguarded, and that the files are stored at the sponsor’s facilities or in specific facilities contracted for this purpose.

4.7 and 10.1-10.2

2.12, 4.6, 5.13-5.14, and 8.2.14-8.2.15

XIII. Specific Sections of the Procedure on the Platform (VI)

3.4, 4.3, 4.5, and 4.12

3.24, 10.2, and 16.10

10.9

10.27

Last content review/update: March 21, 2024

Supply, Storage, and Handling Requirements

As defined in G-ResEthics and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (THA-28), the sponsor or the designated contract research organization (CRO) must supply the investigator(s)/institution(s) with the investigational products (IPs), including the comparator(s) and placebo, if applicable. The sponsor or the designated CRO should not supply either party with the IP(s) until approval is obtained from the Thai Food and Drug Administration (Thai FDA) and the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH), another ethics committee (EC) (e.g., the Central Research Ethics Committee (CREC)), and/or the local EC. The ECMOPH and the CREC are both ECs recognized by the Thai FDA. Per an in-country subject matter expert, Thailand is implementing THA-28.

G-ResEthics and THA-28 specify that the sponsor or the designated CRO must ensure the following:

Timely delivery of the IP(s)
Records maintained for document shipment of the IP(s)
Written procedures including instructions for handling and storage of the IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
IP product quality and stability over the period of use
IP manufactured according to any applicable Good Manufacturing Practices (GMPs)
Proper coding, packaging, and labeling of the IP(s)
Acceptable IP handling and storage conditions and shelf life

Refer to the G-ResEthics and THA-28 for detailed, sponsor-related IP requirements. As defined in G-ResEthics and THA-28, the sponsor is also accountable for supplying the IP, including the comparator(s) and placebo, if applicable.

Record Requirements

As per G-ResEthics and THA-28, the sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial related records are no longer needed. Additionally, the sponsor must ensure sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary, and should maintain records of batch sample analyses and characteristics. All sponsor-specific essential documents should be retained for at least two (2) years after formal discontinuation of the trial or in conformance with applicable regulatory requirements.

1.33, 4.9, 5.5, 5.13-5.14, and 7

Annex 5 (5.11, 6.2, 13, and 14)

Definition of Specimen

Last content review/update: November 8, 2024

In Mexico, a specimen is referred to as a “product of human beings.” According to GenHlthLaw and Reg-HumSpecDisp, products of human beings include any tissues or substances, excreted or expelled by the human body as a result of normal physiological processes.

GenHlthLaw and Reg-HumSpecDisp also provide more specific definitions for specimens including germ cells, stem cells, blood and derivatives, plasma, tissue, cellular concentrates, and organs. Please refer to these sources for more detailed information.

Additionally, G-RECs-Op-2018 states that human biological material includes organs, tissues, tissue components, cells, and products and cadavers of human beings.

Chapter I (Article 6)

14

Title XIV (Chapter I, Article 314)

Last content review/update: March 21, 2024

In Thailand, a specimen is generally referred to as biological material. As delineated in G-ResEthics, biological material is defined as original material, progeny, and unmodified derivatives. In the Material Transfer Agreement template provided in G-ResEthics, material covered by the agreement includes all living or dead biological materials and any replicated or derived cells or DNA molecules.

G-ResEthics collectively classifies biomedical research as those studies that include information from a participant’s medical records or databases; laboratory specimens; bodily fluids; human tissues; and studies about the physiology, biochemistry, pathology, biochemistry, and psychology of typical participants.

In addition, G-ResEthics specifically defines human tissue samples as anything being taken out or excreted from a human body or a corpse. These samples may also include other tissues, blood, secretions, and excretions from all organ systems to be used for the diagnosis of a disease or for other purposes.

Please refer to G-ResEthics for more specific definitions for selected terms including progeny and unmodified derivatives.

1.4, 7.5-7.7, and Annex 8

Specimen Import & Export

Last content review/update: November 8, 2024

Import

As delineated in GenHlthLaw, Reg-COFEPRIS, and Reg-HumSpecDisp, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is responsible for authorizing the import of specimens (referred to as “products of human beings” in Mexico).

According to G-ImprtPermit, institutions that import products of human beings including tissues, cells, blood and its components or derivatives intended for research, diagnosis, teaching, or treatment for therapeutic purposes, must comply with specific COFEPRIS documentation submission requirements to apply for an import permit. The documentation required to obtain an import permit specifically for research purposes is as follows (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Import or Export of Products of Human Beings form (original) (see MEX-24)
Proof of payment of rights (one (1) original; G-ImprtPermit also specifies that in terms of the Federal Rights Law, proof of payment of rights is applicable only to the application for a permit for the hospitalization of blood units, their components, and hematopoietic progenitor cells)
Document certifying the operation of the foreign establishment issued by the health authority of the country of origin (original)
Health license for the corresponding line of business (original)
Notice of operation for the corresponding line of business (original)
Authorization document issued by COFEPRIS for the protocol when it is intended for humans, or a summary of the study when in vitro is being carried out, where appropriate (original)
Letter of acceptance in which the establishment that will receive the samples indicates the reason and use of the samples (original)
Shipping letter in which the foreign establishment indicates the reason and use of sending the samples (original)
Power of attorney (accreditation of the legal representative)

G-ImprtPermit further notes that COFEPRIS has 45 business days to respond to the import request, and 15 business day to notify the applicant of missing or additional information required in a prevention letter. The applicant, in turn, has five (5) business days to respond COFEPRIS’s prevention letter. The import permit approval is valid for 180 business days. Refer to G-ImprtPermit for detailed information necessary to obtain import permits for teaching, diagnosis, and therapeutic purposes including the use of human blood (i.e., umbilical cord blood or hematopoietic progenitor cells) and corneas.

D-CargoTransprt bars exclusive cargo shipments to the Mexico City International Airport (AICM). See D-CargoTransprt and D-ModCargoTransprt for more details regarding the relocation of cargo shipments to other airports in Mexico.

Export

According to G-ExprtPermit, institutions that dispose of or export products of human beings including tissues, cells, blood and its components or derivatives that are intended for diagnosis, treatment, research, or teaching purposes must also submit documentation to COFEPRIS to apply for an export permit.

G-ExprtPermit indicates the following general documentation must be provided to export cells, tissues, and products of human beings and their components (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Import or Export of Products of Human Beings form (see MEX-24)
*Proof of payment of fees (original and two (2) legible copies)
*Letter of acceptance of the establishment abroad (original)
Authorization letter issued by COFEPRIS for the protocol when it is intended for humans, or a summary of the study when in vitro is being carried out, where appropriate (original)
Notice of operation of health establishment (original)
Health license (original)
Power of attorney (original)

*G-ExprtPermit indicates this requirement is only applicable to exports for blood units, their components and hematopoietic progenitor cells.

G-ExprtPermit further notes that COFEPRIS has 45 business days to respond to the export request, and 15 business days to notify the applicant of missing or additional information required in a prevention letter. The applicant, in turn, has five (5) business days to respond to COFEPRIS’s prevention letter. The permit approval is valid for 180 business days.

In addition, G-ExprtPermit outlines the following required documentation to be submitted to COFEPRIS to export umbilical cord blood or hematopoietic progenitor cells, for cryopreservation, research, or therapeutic purposes:

Import or Export of Products of Human Beings form (original) (see MEX-24)
Proof of payment of fees (one (1) original and two (2) legible copies (per G-ExprtPermit); G-ExprtPermit also specifies that in terms of the Federal Rights Law, proof of payment of rights is applicable only to the application for a permit for the hospitalization of blood units, their components and hematopoietic progenitor cells)
Letter of acceptance of the establishment abroad (original)
Health license (original)
Notice of operation of health establishment (original); G-ExprtPermit indicates this is only applicable to permits to export cells, tissues, products of human beings and their components
Document issued by the health authority of the destination country that certifies the operation of the establishment (original)
Power of attorney (original)

See also G-ExprtPermit for detailed documentation to be submitted to export cells, tissues, and products of human beings and their components intended for scientific research.

Import/Export Permit Submission Procedures

MEX-24 indicates that an applicant may submit a request to obtain a permit to import or export specimens in print, in person via COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), or electronically via the Mexican Digital Window for Foreign Trade (Ventanilla Única de Comercio Exterior Mexicano (VUCEM)) (MEX-114). Per G-ImprtPermit and G-ExprtPermit, the application should be submitted electronically via MEX-114 (Refer to MEX-114 for submission instructions). G-ImprtPermit and G-ExprtPermit state that to submit an application online, it is necessary to obtain an e.signature (also known as e.firma). MEX-49 explains that the e.signature is a secure, encrypted digital file that identifies an applicant, and can be used to carry out procedures electronically with various government agencies. An e.signature can be obtained from the Tax Administration Service (Servicio de administración tributaria (SAT)) as described in MEX-105.

See MEX-116 for instructions on completing MEX-24. See also G-ImprtPermitMod for the required documentation and submission procedures to modify an import/export permit for products of human beings including tissues, cells, and blood and its components or derivatives.

Chapter VI (Articles 89 and 100)

Requirements, Form, Term, Validity of Resolution, and Steps

Title I (Chapter I, Article 3), Title II (Chapter II, Articles 17 Bis), Title XII (Chapter XIII, Articles 283-286 Bis), and Title XVI (Chapter I, Article 375)

Chapter I (Article 3)

Last content review/update: March 21, 2024

Import/Export

No information is currently available regarding the Thai Food and Drug Administration (Thai FDA)’s role in approving the import and export of biological specimens.

Material Transfer Agreement

G-ResEthics states that in the case of the transfer of biological materials, the sponsor must complete the Material Transfer Agreement (MTA) form (Annex 8) to obtain or transfer biological materials for research purposes. An MTA form must also be used to transfer human tissue samples to other institutions.

See also THA-13 for the Material Transfer Agreement and Material Transfer Record forms provided by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health (ECMOPH).

Per THA-34, the Central Research Ethics Committee (CREC) requires investigators to include an MTA in the initial protocol submission package in cases where specimens are sent to an outside research institute. The MTA must be uploaded to the CREC online submission system (THA-43) using the form required by each institute. This document will be used by the CREC for consideration, but it is not endorsed.

The ECMOPH and the CREC are both ethics committees approved by the Thai FDA to review and approve clinical trial protocols.

Material Transfer Agreement (p. 83) and Material Transfer Record (p. 87)

Supporting Documents - 22. Material Transfer Agreement

7.5 and Annex 8

Consent for Specimen