Thai Food and Drug Administration

As per the DrugAct, ClinSampleProd, and ClinImprtOrdr, the Thai Food and Drug Administration (Thai FDA) is the regulatory authority responsible for controlling the import of drugs for research purposes, and it 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 set forth in the DrugAct, THA-33, and THA-49, the Thai FDA is a regulatory body under the Ministry of Public Health (MOPH)'s Cluster of Public Health Service Support, and is granted control by the MOPH to protect consumer health. The agency is also authorized to ensure the quality, safety, and efficacy of health products including foods, drugs, cosmetics, and medical devices in Thailand.

In addition, per the DrugAct’s 2019 amendments and according to THA-6, the MOPH has the authority to establish and/or amend drug research-related procedures, regulations, and conditions via Government Gazette announcements. The Thai FDA’s Secretary-General is also permitted to control drug research study activities by issuing temporary suspensions, requesting specific improvements, or completely discontinuing a study that fails to comply with the Minister’s published guidelines.

As indicated in the DrugAct, the Thai FDA’s Medicines Regulation Division is a member of the Drug Board (also referred to as the Drug Committee in the English translation of the DrugAct). Per the DrugAct, the board must consist of MOPH departmental directors-general and representatives from related organizations, as well as five (5) to nine (9) drug experts. Every two (2) years, the Minister of Public Health appoints the Committee, which is chaired by the Permanent Secretary of the MOPH. The DrugAct also indicates that the board should appoint a subcommittee to study the drug review and approval process. The subcommittee should include at least the following: an office representative and Office of Consumer Protection Board representatives including association, foundation, and drug industry representatives whose purpose is to produce, sell, import, or order drugs for use in Thailand.

THA-49 further explains that the Medicines Regulation Division is in charge of reviewing licenses to import or order drugs used for clinical research in Thailand that are exempt from drug registration, issuing licenses to produce drug samples for drug formula registration, and issuing licenses to import or order drug samples for research purposes in Thailand. See THA-49 for additional information on the Medicines Regulation Division’s responsibilities. (See also THA-18 and THA-76 for appendices included in ClinSampleProd and ClinImprtOrdr.)

As described in ClinSampleProd and ClinImprtOrdr, the Thai FDA’s Medicines Regulation Division is responsible for application review and recommendation for approval. Per ClinSampleProd, and according to the Thai FDA’s organizational structure depicted in THA-33, the Secretary-General of the Thai FDA then makes the final decision to approve the application.

Division of Innovative Health Products and Services

As explained in THA-91, the Thai FDA’s Division of Innovative Health Products and Services is a service center that provides advice regarding health product authorization and research and development, product classification, and also accepts requests regarding health products. Its responsibilities include reviewing requests for one-stop service, locally researched and produced health products and innovative products. The Division also develops innovative health product authorization processes through electronic channels; conducts research to develop work systems, creates standards for innovative products as well as the locations and processes for production, import, sale, clinical research, and advertising; and develops policies, regulations, criteria, and practices regarding the licensing of health products. Per THA-66, the Division also houses the agency’s One Stop Service & Consultation Center (OSSC) (THA-35) within the Comprehensive Health Products Service Center. OSSC services include providing preliminary consultations, processing product application submissions (e.g., applications submitted to obtain drug import licenses for clinical research purposes), and handling payment services (e.g., permissions and licensing) for various health products including drugs. See the Submission Process section for more details on the import application submission process.

Contact Information

Per THA-72, the Thai FDA’s contact information is as follows:

Medicines Regulation Division
Food and Drug Administration
Ministry of Public Health
88/24 Tiwanon Road
Talat Khwan Subdistrict
Mueang District, Nonthaburi Province 11000

Email: drug@fda.moph.go.th
Email: saraban@fda.moph.go.th (General FDA Correspondence)
Phone: 0 2590 7000
Phone: 0 2590 1556 (FDA Call Center)
Fax: 0 2590 7116

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.

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.

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.

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.

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.

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.

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.

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.)

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.)

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

In accordance with G-ResEthics, prior to collecting, storing, or using a research participant’s biological specimen(s), written consent must be obtained from the participant or legal representative.

As per G-ResEthics, the investigator(s) are responsible for clarifying to the participant and the legal representative whether the biological materials collected from the study will be destroyed. If the samples will be used, a clear explanation must be provided as to how the samples will be stored, plans for future use, and whether such use is limited. In addition, the investigator(s) must inform the participants whether any products will be derived from the biological materials collected during the study. (See the Required Elements and Participant Rights sections for additional information on informed consent).

G-ResEthics states that written consent should be obtained from the donor or the giver of the tissue samples. The general requirements for consent must be met, including the investigator(s) obtaining institutional ethics committee (EC) review and approval of the research protocol and for complying with ethical guidelines in compliance with the applicable laws and regulations when conducting research using tissue samples. The guidelines should provide procedures for tissue sample collection, processing, distribution, disposal, and storage for the duration of the research or for future use. The participant or the legal representative must be given detailed information about how the samples will be used and stored, and about their right to request the samples be destroyed when the research is complete.

In addition, per G-ResEthics, for retrospective studies using stored human tissue samples, the institution and the EC should establish the rules and regulations to decide when the investigator can waive a donor’s informed consent in order to use stored tissue samples for research. Refer to Section 7.5 of G-ResEthics for detailed information.

G-ResEthics states that the investigator or institution must obtain consent for human genetic research. Investigators and institutions must comply with numerous requirements to ensure participant consent, protection, and privacy rights are upheld with regard to the storage of genetic materials. See Sections 7.6 and 7.7 of G-ResEthics for detailed coverage of genetic research consent requirements.

In addition, as noted in THA-34, the Central Research Ethics Committee (CREC) directs investigators to the broad informed consent form (ICF) template and checklist for storage and use of data and biospecimens for future research and the ICF template and checklist for genetic research provided by the Forum for Ethical Review Committees in Thailand (FERCIT) (see THA-46 for document links). The CREC is one (1) of the ECs approved by the Thai Food and Drug Administration (Thai FDA) to review and approve clinical trial protocols.