Clinical Research Regulation For Malawi and Thailand

Last content review/update: August 29, 2024

Overview

In accordance with the PMRAAct, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for reviewing and approving clinical trial applications for new drugs, generic drugs, and imported drugs to be registered in Malawi. The PMRA has replaced the Pharmacy, Medicines and Poisons Board (PMPB).

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

As per the SciTechOrder, an NCST-issued license is required for research activities involving humans; research involving clinical trials; and research activities of multicentered research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC and COMREC approvals. See the Scope of Review section for information on NHSRC and COMREC approvals of the aforementioned research activities.

Clinical Trial Review Process

According to MWI-50, the PMRA receives clinical trial applications through the office of the Director General, and the applicant must submit evidence of ethical clearance from either the NHSRC or COMREC.

Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs. The G-CTARevVacBiol and the G-CTAProcsVacBiol indicate that upon receipt of a clinical trial application, the PMRA initially screens the application for completeness and assigns a PMRA reference number to the application. According to the G-CTARevVacBiol, the result of the screening will be communicated, and the screening form will be forwarded by fax, to the applicant. The applicant will forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert, or to an evaluator for scientific review.

The G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection.

MWI-50 further specifies that the PMRA may grant full or conditional approval depending on the nature of the CTRC’s findings. Depending on the study’s risk profile, the PMRA may conduct post-authorization good clinical practice (GCP) inspections for select clinical trials. Per the G-CTARevVacBiol, if the application is neither approved nor rejected, the PMRA’s technical staff will communicate its recommendation to the applicant. The response from the applicant will be considered at the PMRA’s subsequent scheduled meeting, and the subsequent decision will be communicated to the applicant. If changes must be made to the protocol, investigator’s brochure, or any other document, the amended document should be submitted with the applicant’s response.

The G-CTAProcsVacBiol states that the applicant may appeal a rejection decision, providing additional information, or amending the application to meet the PMRA’s requirements. The appeal will be referred to the CTRC for a final recommendation to the PMRA.

Per MWI-61, the PMRA may conduct GCP inspections during ongoing clinical trials to provide real-time assessment of the investigator’s conduct of the trial and protection of participants. Clinical trial sites may be inspected before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. See MWI-61 for more information.

(See the Submission Process and Timeline of Review sections for details on the administrative and technical processing and review timelines. See also the G-CTARevVacBiol and the G-CTAProcsVacBiol for more information on the PMRA’s review procedures.)

1-6

2 and 3

Part II (Sections 4-5) and Part XIII (Section 131)

2.0 and 8.0-8.3

Last content review/update: March 21, 2024

Overview

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

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

Clinical Trial Review Process

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

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

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

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

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

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

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

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

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

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

Refer to the Submission Process section for submission requirements.

Appendices 1-4, 7-9, and 12

Appendices 2-4, 11-13, and 17

7

2-3 and 15

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

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

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

5 and 9-10

Appendix 12

Regulatory Fees

Last content review/update: August 29, 2024

Pharmacy and Medicines Regulatory Authority

According to the PMRAAct, a person who intends to conduct a clinical trial must apply to the Pharmacy and Medicines Regulatory Authority (PMRA) for a clinical trial certificate upon payment of the prescribed fee.

Per the PMRAFeesRegs, the following fees apply to clinical trials:

Application, review, and registration: 5% of total budget
Annual renewal: $2,200 USD
Amendments: $300 USD

As delineated in the PMRAFeesRegs, a fee equaling 6% of the total invoice value must also be paid for the importation of unregistered medicines or allied substances from authorized sources. The G-ImpExpMP further indicates that this fee is subject to change from time to time.

Payment Instructions

No information is available regarding payment instructions.

National Commission for Science and Technology

No information is available regarding fees for the National Commission for Science and Technology (NCST).

Part VII (Section 75)

10 and 11

3.3

Last content review/update: March 21, 2024

Thai Food and Drug Administration

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

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

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

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

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

Payment Instructions

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

Appendix 1

Appendix 2

Items 2, 11, 33, 34, and 49

1.14 and Appendices 1 and 7

1.16 and Appendices 2 and 11

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

Ethics Committee

Last content review/update: August 29, 2024

Overview

Malawi has a centralized registration process for ethics committees (ECs) and EC review. As mandated by the SciTechAct, the National Commission for Science and Technology (NCST) is the governmental body responsible for EC oversight, and for the promotion and coordination of research in Malawi.

As per the G-NHSRC, the G-COMREC, MWI-5, and MWI-50, the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC) are the two (2) NCST-approved ECs responsible for monitoring and evaluating health research studies involving humans. The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of the NHSRC, only reviews and approves studies involving or originating from College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions. Per the R-HlthResCoord, each EC has members representing the other committee in order to facilitate the transfer of information between the ECs. The NHSRC and COMREC report to and are centrally monitored by the NCST.

MWI-25 indicates that as of August 2024, COMREC is operating under KUHeS and will be changing its name to Kamuzu University of Health Sciences Research Committee (KUREC), following approval from the NCST. The COMREC guidance and forms provided in the Malawi profile are still being used.

Ethics Committee Composition

National Health Sciences Research Committee

As per the G-NHSRC, NHSRC must consist of members with varying backgrounds, including the social sciences, to promote complete and adequate research proposal review. The committee should include one (1) lay person, as well as members from the following organizations:

National Research Council of Malawi (one (1) member)
Ministry of Health (MOH) headquarters (two (2) members)
COMREC (two (2) members)
Community Health Sciences Unit (one (1) member)
National AIDS Commission (one (1) member)
Center for Social Research (one (1) member)
Queen Elizabeth Central Hospital (one (1) member)
Zomba Central Hospital (one (1) member)
Lilongwe Central Hospital (one (1) member)
Christian Health Association of Malawi (one (1) member)
Mzuzu University (one (1) member)
Mzuzu Central Hospital (one (1) member)
Nurses and Midwives Council of Malawi (one (1) member)
Ministry of Justice (one (1) member)

The members elect the chairperson and the vice-chairperson.

College of Medicine Research and Ethics Committee

The G-COMREC specifies that COMREC should be multidisciplinary, and its members must have the basic qualifications, experience, and expertise to conduct fair scientific and ethical proposal reviews. The committee must have a maximum membership of 15, and include representatives from the biomedical sciences, research methods, behavioral science, and research ethics areas. Additionally, there must also be representatives from the NCST, the NHSRC, the KCN, and the lay community.

Furthermore, the committee must be diverse, have balanced gender representation, and embody community interests and concerns. Members are also required to sign a confidentiality agreement and refuse projects in which they have a conflict of interest. Members from the COM staff serving on the committee must be a minimum grade of senior lecturer, and preferably have peer reviewed publications.

See the G-NHSRC and the G-COMREC for additional EC membership criteria and qualification requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

National Health Sciences Research Committee

The G-NHSRC states that the MOH’s Research Unit serves as a secretariat for NHSRC, and is responsible for preparing materials and meeting logistics. Research proposals must be distributed to NHSRC members two (2) weeks before the scheduled meetings to allow members time to adequately review the submitted proposals. Half of the NHSRC’s membership constitutes a quorum of any meeting, and the meeting is rescheduled within the following two (2) weeks if a quorum is not reached. Half of the ordinary quorum forms a quorum for the rescheduled meeting if no ordinary quorum is reached. Otherwise, the meeting must be rescheduled.

As delineated by the G-NHSRC, NHSRC decisions are reached by consensus. If there is no consensus, a decision is made by simple majority of members present through an open ballot. In the event of a tie, the chairperson casts a vote.

According to the G-NHSRC, when new NHSRC members have been appointed, they may attend the first one (1) or two (2) meetings as an observer in order to learn about the workings of the NHSRC before being assigned reviewer responsibility. Such members will undergo NHSRC orientation sessions covering guidelines and standard operating procedures (SOPs) of the committee and any practical matters with the secretariat and chairperson. Continuing education for all members in matters of health research ethics and related disciplines in human research protections is also essential, and the chairperson is responsible for fostering local and international networks, links, and partnerships for the purposes of continuing the NHSRC’s education and development.

Per the G-NHSRC, NHSRC members must serve on the committee for three (3) years and are required to renew their appointments if requested by their organizations. The G-NHSRC and the G-HlthResConduct also indicate that the NHSRC meets once every two (2) months.

College of Medicine Research and Ethics Committee

COMREC requires written SOPs to be maintained, and all relevant records (e.g., SOPs, reports, curriculum vitaes (CVs), meeting minutes, and correspondence) to be archived for three (3) years following the study’s completion, as delineated in the G-COMREC. The COMREC secretariat must compile all the relevant documents and materials required for review of a proposal and circulate them to the members at least 14 days before the date of the scheduled meeting. Quorum of any meeting is achieved when a majority of the members attend. The quorum should preferably include members of both genders, a member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the COM. If the quorum cannot be achieved, the meeting must be rescheduled within two (2) weeks of the failed meeting. If the subsequent meeting does not achieve quorum, then the chairperson must make a decision based on the expertise and number of members present.

The G-COMREC further states that COMREC’s final decision will be reached through a consensus. If there is no consensus, a decision is made through a majority vote.

Per the G-COMREC, COMREC members must receive initial and continuing training regarding the ethics and science of research. The appointment of committee members is valid for three (3) years, and a member may be reappointed to serve another three (3) year term. According to the G-COMREC and the G-HlthResConduct, COMREC meets every month.

1.0, 2.0, 3.1-3.3, 4.0, 5.7-5.8, and 8.0

1 and 7

1.0, 3.1-3.3, and 4.0

Part IV

2.0 and 8.0

Last content review/update: March 21, 2024

New Info (Not Yet in Profile)

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

Overview

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

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

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

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

Central Research Ethics Committee

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

Ethics Committee Composition

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

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

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

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

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

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

No information is available on ECMOPH and CREC composition requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

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

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

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

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

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

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

Which EC? And CREC

Important Modifications in the New List

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

Appendices 3-4, 7, and 9

Appendices 1-5, 11, and 13

1.27 and 3.3

Chapter 6

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

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

4-6 and 9-10

Scope of Review

Last content review/update: August 29, 2024

Overview

According to the G-NHSRC and the G-COMREC, the primary scope of information assessed by the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial.

The G-HlthResConduct states that scientific design; recruitment of research participants; care and protection of research participants; ethical consideration; and community consideration are essential elements that the NHSRC and COMREC must review in a clinical trial application. Per the G-NHSRC, the NHSRC must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of NHSRC, only reviews and approves studies involving or originating from the College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions.

Role in Clinical Trial Approval Process

The R-HlthResCoord indicates that before submitting a clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA), the sponsor or principal investigator (PI) must obtain full ethical approval from either the NHSRC or COMREC. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Moreover, as specified in the R-HlthResCoord, for all studies originating outside Malawi, the sponsor or the PI is required to obtain approval from an EC based in their country prior to submitting an application to the NHSRC or COMREC for ethical review and approval.

Per the G-NHSRC and the G-COMREC, the applicable EC will screen submitted applications for completeness, and help determine the type of review to be conducted.

The G-NHSRC states that new studies submitted to the NHSRC are generally reviewed by a fully convened NHSRC meeting. The following studies will be reviewed by the full NHSRC:

All high-risk studies
Studies involving vulnerable populations (including pregnant women, prisoners, mentally incompetent patients, etc.)
Any clinical interventional study that randomly assigns human participants to alternative experimental or placebo groups
Studies involving sensitive information connected to personal identifiers
Studies previously reviewed that require major issues to be addressed

The G-NHSRC and the G-COMREC indicate that following the NHSRC’s or COMREC’s review, the EC will decide to approve the research, stipulate minor changes for approval, or not approve the research. A negative decision on an application must be supported by clearly stated reasons. In addition, the G-NHSRC states that if the NHSRC determines that substantive changes/clarifications must be made before approval may be granted, the study will be deferred for a full NHSRC meeting.

The G-COMREC specifies that the COMREC’s approval of a new application is valid for one (1) year. However, the R-HlthResCoord indicates that EC approval of a study is valid for the period of the study as described in the protocol, which is effective from the date of approval as indicated in the approval letter.

The R-HlthResCoord, the G-NHSRC, and the G-COMREC state that the EC must review and approve any protocol amendments prior to those changes being implemented. See MWI-52 and MWI-44 for the NHSRC and COMREC amendment request forms, respectively. Any changes cannot be implemented until approved by the EC.

The G-COMREC requires that COMREC follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. The follow-up review intervals are determined by the nature of the research project. However, each protocol should undergo a follow-up review at least once a year. As part of its monitoring process, COMREC conducts inspections of institutions and study sites.

Studies of National Interest

All studies of national interest, as defined in the G-NHSRC, the G-COMREC, and the R-HlthResCoord to include all vaccine trials and stem cell research, should be referred to the NHSRC, regardless of the origin of the protocol. The NHSRC may form a standing committee for that specific project, which will monitor the project through to its conclusion, composed of members to be drawn on the basis of their expertise.

Multicenter Studies

As delineated in the R-HlthResCoord, the NHSRC is designated and mandated to review and approve multicenter clinical trials, including those originating outside Malawi. The NHSRC will conduct a full initial review of the same protocols for a multicenter study submitted by different investigators provided that such protocols are submitted simultaneously. Protocols for the same multicenter trial to be implemented at different institutions may also be merged into one (1) protocol that the NHSRC will treat as a joint submission for review.

Continuing Review

According to the G-NHSRC and the G-COMREC, all approved studies running for more than one (1) year are subject to continuing annual review by the approving EC (the NHSRC or COMREC). If the materials for continuing EC review are not received within one (1) month following the expiration date of the previous approval, then the study will be classified as lapsed and inactive. If a study has lapsed, the EC will order that all study-related operations cease, except those necessary for the welfare of the participants. Per the G-NHSRC, if the PI wants to continue an NHSRC-reviewed study that has lapsed for two (2) months, the PI must submit a new application for NHSRC review and wait for approval before resuming research under the protocol. MWI-53 indicates that the NHSRC follows, at a minimum, the regulations set forth in the Declaration of Helsinki (MWI-42) and the Council for International Organizations of Medical Sciences (CIOMS) guidelines as the criteria for continuing review of a study. The PI is responsible for timely submission of a continuing review application to prevent any lapse in NHSRC approval. NHSRC regulations do not provide for exceptions to the requirement for continuing review. The NHSRC’s continuing review application form is available at MWI-53.

Expedited Review

Per the G-NHSRC and the G-COMREC, research studies that have previously been reviewed by a fully convened committee and require the PI to address minor issues, may be approved through the NHSRC’s or COMREC’s expedited processes. Studies by students may also be considered for expedited review. Expedited review can be considered for continuing review of research previously approved by the NHSRC or COMREC, where the research is permanently closed to the enrollment of new subjects, and all subjects have completed all research related interventions.

Per the G-COMREC, COMREC’s review period for such a resubmission must not exceed 14 days from the date of the resubmission. The G-NHSRC further indicates that the NHSRC will also consider expedited review for continuing review of research previously approved by NHSRC where no subjects have been enrolled and no additional risks have been identified, or where the remaining research activities are limited to data analysis and report writing.

For more information on each EC’s expedited review procedures, see the G-NHSRC and the G-COMREC.

Exemption from Review

As delineated in the G-NHSRC and the G-COMREC, certain types of human participants research may be exempted from NHSRC or COMREC review. Exemption may be considered for research involving the collection or study of existing data, documents, records, program evaluation, pathological specimens, or diagnostic specimens, if the sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects.

Suspension or Termination of Study/Approval

Per the G-NHSRC, the NHSRC chairperson or the convened NHSRC may suspend a study at any time if it is determined that the study requires further review or evaluation. This determination may be made in the event of an adverse event, non-compliance, or other danger to human participants. The study will be reviewed at the next convened meeting to determine if it requires changes. The NHSRC must notify the PI and the sponsor in writing specifying reasons for suspension or termination with a copy to the National Research Council of Malawi (NRCM). The NRCM must be informed of all the suspended or terminated studies with detailed reasons for the decision. In the event of documented serious adverse events and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. In the case of any officially or unofficially reported noncompliance, protocol violation, or deviation by the researcher, the NHSRC must suspend the study to ensure safety of the study participants and carry out an investigation. Upon investigation of the problem prompting the suspension of the study, the convened NHSRC must terminate the study if convinced beyond any reasonable doubt that there was noncompliance, deviation, or violation of the protocol.

The G-COMREC states that COMREC may recommend to COM management suspension or termination of approval of research that is not being conducted in accordance with the guidelines, or that has been associated with unexpected serious harm to participants. Any suspension or termination of approval must include a statement of the reasons for COMREC's action and must be reported promptly to the investigator, appropriate institutional officials, Dean of Postgraduate Studies and Research, and the Principal of the COM. The Principal of the COM must then send a report of suspended or terminated studies with the reasons contained therein to the NCST and the PMRA, or any other government agency responsible for research policy matters.

1.0, 3.2, 3.3, 5.1, 5.4-5.9, 6.0, and 7.0

1, 7, and 9

1.0, 2.0, 3.1, 5.1-5.4, 5.7, 6.2, and 9.2

2.0, 6.0, 7.0, 7.2, 8.1-8.4, 8.6, and 9.0

Last content review/update: March 21, 2024

Overview

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

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

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

Role in Clinical Trial Approval Process

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

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

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

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

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

Central Research Ethics Committee

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

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

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

Clinical Trials

2

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

4-5

1.27 and 3.3

1.1, and Chapters 2, 4, and 6

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

1, 3, and Appendices 1-5 and 13

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

5-6

Appendix 12

Ethics Committee Fees

Last content review/update: August 29, 2024

National Health Sciences Research Committee

According to MWI-4 and MWI-15, non-Malawian researchers must pay $150 USD or its equivalent in Malawian Kwacha to the National Health Sciences Research Committee (NHSRC) upon submission of a research proposal. Malawian students (Masters and below) are required to pay 5000 Malawian Kwacha.

The G-NHSRC and MWI-5 indicate that following the protocol’s approval, the principal investigator must also pay the Ministry of Health (MOH) a fee of 10% of the total budget indicated in the proposal to cover NHSRC institutional capacity strengthening and administrative operating expenses. MWI-15 further specifies that the fee, referred to as a 10% NHSRC Human Subject Protection (HSP) fee, must be paid by PhD students and above.

MWI-5 clarifies that the NHSRC fee and the Pharmacy and Medicines Regulatory Authority (PMRA)’s Clinical Trial Review Committee (CTRC) fees are included in the 10%. Payment of the 10% fee must be made for all NHSRC-approved research projects prior to commencement of the research study.

Payment Instructions

Per MWI-15, the application fee and the 10% HSP fee may be paid at the MOH Headquarters Cash Office or through the following bank details:

Account Name: NHSRC NCST Review Fees
Account Number: 1010759176
Bank Name: National Bank of Malawi
Bank Address: Capital City Branch, Lilongwe 3, Malawi
Swift Code: NBMAMWMW008

College of Medicine Research and Ethics Committee

As per MWI-5, non-Malawian researchers must pay $150 USD and Malawian researchers must pay 500 Malawian Kwacha to the College of Medicine Research and Ethics Committee (COMREC) upon the submission of a research proposal. COMREC is also mandated to charge a College of Medicine (COM) fee of 10% of the total budget indicated in the proposal. As delineated in MWI-1, the COM’s Dean of Postgraduate Studies and Research can grant waivers for the 10% fee.

However, the G-COMREC states that the COM’s processing fee is $100 USD for each new protocol submission and resubmission for the fourth time, and that eligible investigators may apply to management for exemption from paying the fee.

Payment Instructions

No information is currently available regarding payment instructions for COMREC.

3.3.10

8.0

Last content review/update: March 21, 2024

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

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

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

No information is currently available on ECMOPH fees.

Central Research Ethics Committee

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

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

New research project: 50,000 Baht

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

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

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

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

Payment Instructions

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

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

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

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

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

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

Type of Funding Source, Fee Rate, and Notes

7.1.5

Oversight of Ethics Committees

Last content review/update: August 29, 2024

Overview

The R-HlthResCoord indicates that the National Commission for Science and Technology (NCST) is the central statutory body responsible for coordinating and regulating all research, science, and technology related activities in Malawi, as mandated by the SciTechAct.

The R-HlthResCoord further specifies that the NCST provides oversight to the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC). The NCST’s core responsibilities in this capacity include:

Participating as an ex-officio member for the NHSRC and COMREC by having a voting representative from the NCST sit on both committees
Reviewing and approving the ethics committees’ (EC) guidelines and standard operating procedures
Monitoring the ECs’ performance and adherence to relevant national policies, laws, regulations, and guidelines

Registration, Auditing, and Accreditation

As stated in the SciTechOrder, an NCST-issued license is required for the accreditation of research institutions and the establishment of an institutional EC. Additional information regarding the NCST-issued license is not available at this time.

Part IV

2.0 and 2.2

Last content review/update: March 21, 2024

Overview

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

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

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

Registration, Auditing, and Accreditation

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

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

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

Important Modifications in the New List

Appendices 3-4 and 9

Appendices 2-5 and 13

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

1 and Appendices 1-5, and 13

Preface, 4-6, 9, and 11

Submission Process

Last content review/update: August 29, 2024

Overview

According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval of a clinical trial application.

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Regulatory Submission

According to MWI-60, an electronic or soft copy of the clinical trial application dossier must be sent to registration@pmra.mw and info@pmra.mw.

As per the G-CTARevVacBiol and MWI-9, applicants must submit three (3) copies of the clinical trial application to the PMRA. MWI-60 further requires that the three (3) dossier hard copies be submitted in a lever arch file to the Director General. Each section of the dossier must be well demarcated for ease of reference by PMRA reviewers. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent.

There is no specified language requirement for the clinical trial documents to be submitted to the PMRA.

Ethics Review Submission

National Health Sciences Research Committee

As stated in the G-HlthResConduct and MWI-15, the applicant is required to bind and submit application materials (plus an electronic copy, per MWI-15) to the NHSRC at least three (3) weeks before the date of the review meeting.

MWI-15 states that applications should be submitted to the NHSRC at the following address:

The Chairperson
National Health Sciences Research Committee
Ministry of Health Research Department Area 2/124
P.O. Box 30377
Lilongwe 3, Malawi
Tel: +265 1 789 400

The electronic copy should be submitted at the same time to research@health.gov.mw and mohdoccentre@gmail.com.

MWI-15 indicates that three (3) copies of each item indicated in the NHSRC Checklist (MWI-4) must be submitted in the research proposal package to the NHSRC (See the Submission Content section for a list of these items). Three (3) copies for Malawian student proposals (up to master’s level) must also be submitted to the NHSRC secretariat for expedited review. The submission must be bound in the order indicated by MWI-4 as one (1) PDF document. (See the Submission Content section for more details on the individual elements of the NHSRC research proposal submission.)

According to MWI-15 and MWI-4, the data collection tools and informed consent forms must be provided to the NHSRC in both English and Chichewa (or the appropriate local language).

The R-HlthResCoord indicates that for multicenter trials, sponsors and PIs may plan to hold a pre-clinical trial submission and authorization meeting with the NHSRC, at their own choice and cost. The sponsor or PI must write to the NHSRC secretariat of the review committee to request the meeting’s arrangement at least four (4) weeks in advance of the suggested meeting date. For more information, see the R-HlthResCoord.

College of Medicine Research and Ethics Committee

Per the R-HlthResCoord, COMREC may at its own discretion allow a pre-clinical trial application procedure, where applicable, at the request and cost of the sponsor. As stated in the G-HlthResConduct, the applicant is required to submit application materials to COMREC at least three (3) weeks before the date of the review meeting.

According to MWI-10, protocol submissions to COMREC may be made through the Research Ethics Information Management System (REIMS) (MWI-19). Following submission, the protocol will be reviewed, and feedback will be given through the applicant’s registered email address. All file attachments should be in PDF format with clear, descriptive names. Per MWI-19, ECs in Tanzania, Rwanda, and Kenya also participate in REIMS. See MWI-10 for more information on the REIMS submission portal.

MWI-19 provides the following additional contact information for COMREC:

Tel: +265 888 118 993
Email: comrec@medcol.mw

However, MWI-1 indicates that all documents should be submitted to COMREC by email to comrec@medcol.mw in one (1) PDF file, if the file size does not exceed 5MB. If the file size is over 5MB, then the file should be sent as a compressed zipped file. The data collection tools and informed consent forms must be provided in both English and Chichewa (or the appropriate local language).

3.2

1 and 8

2.0, 7.1, and 8.0-8.3

Last content review/update: March 21, 2024

New Info (Not Yet in Profile)

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

Overview

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

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

Regulatory Submission

OSSC Pre-Submission Permission

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

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

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

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

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

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

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

Import and Export Division Pre-Submission Permission

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

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

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

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

Submissions

N.Y.M.1

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

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

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

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

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

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

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

P.Y.8

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

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

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

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

OSSC Contact Information for Application Submissions

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

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

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

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

Ethics Review Submission

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

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

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

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

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

Central Research Ethics Committee

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

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

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

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

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

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

Chapters 1-2

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

1 and 3

4-5

Appendices 1-4 and 7-9

Appendices 1-13, 15, and 17

Online Submission – For Researchers/Research Coordinators

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

6.1

3, 11-13, and 15

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

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

5 and Form EC-1

Appendix 12

Submission Content

Last content review/update: August 29, 2024

Regulatory Authority Requirements

As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and MWI-60, the following documentation must be submitted to the Pharmacy and Medicines Regulatory Authority (PMRA) in an application to conduct a clinical trial (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Comprehensive table of contents for the entire application, including a complete list of all documents provided in the application. The location of each document should be identified by tab identifiers. In general, the name for the tab identifier should be the name of the document
Cover letter signed by the principal investigator (PI) or sponsor
Proof of payment of the application and registration fees
Signed and stamped Clinical Trial Application (Form CT 8) (MWI-9)
Current version of the study protocol signed and dated by the sponsor and investigator (in the format provided in the International Council for Harmonisation’s (ICH) good clinical practice (GCP) guidelines and/or in line with Attachment 1 of MWI-60)
Investigator’s Brochure (IB), where applicable (in the format provided in the ICH GCP guidelines)
Certificate of Good Manufacturing Practice (GMP) of the investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) and/or placebo, or evidence of manufacture quality, safety, and consistency
Mock-up labels for the IP
Blank case report forms (CRFs) and serious adverse events (SAEs) reporting form to be used in the study
Investigational Medicinal Product Dossier (IMPD) or alternative as provided in Attachment 2 of MWI-60
Stability data of the IP and auxiliary medicine(s) for climatic zone IVa if not registered in Malawi by the PMRA
Evidence of registration of the IP or auxiliary medicines in a country with Stringent Regulatory Authority (SRA) and/or Certificate of Pharmaceutical Product (CoPP), i.e., if IP/auxiliary medicines are not registered by the PMRA
Summary of Product Characteristics (SmPC) for IP and auxiliary medicines
Pharmacy plan
Report summaries of prior clinical trials with the IP (part of IB if it is in the ICH format)
Capacity building plans including training and updating of staff involved in the trial
Informed consent form (ICF) (in ICH format)
Declaration of intent by the national PI or contact person (MWI-31)
Signed and completed declaration by investigators (MWI-32)
Investigator(s) Curriculum Vitae(s) (CVs), including that of pharmacist(s)
Financial declaration by sponsor and PI (MWI-59)
Ethical clearance certificate from an independent ethics committee (EC) recognized by the laws of Malawi
Certified copy of clinical trial insurance for study participants endorsed by the National Commission for Science and Technology (NCST)
Malpractice insurance for investigators and associated staff endorsed by the NCST
Evidence of accreditation or equivalent of the designated laboratories (see the World Health Organization (WHO)’s guidance on Good Clinical Laboratory Practice (MWI-30))
Completed PMRA Material Transfer Agreement Form on Shipping of Samples (MWI-14)
Description of the site facilities (pictorial presentations may be included)
Evidence of registration of investigators with appropriate bodies
Evidence of registration of pharmacists with the PMRA
Evidence of GCP training by investigators and pharmacists in the last three (3) years
Batch release certificate
Authorization of the clinical trial from the country of origin, if applicable
Full, legible copies of key, peer-reviewed published articles supporting the application
Any other requirement as may be determined by the PMRA

If any above items are not submitted, justification for not submitting the document must be provided. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent. See MWI-60 for more details. According to MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.

Ethics Committee Requirements

National Health Sciences Research Committee

According to the G-NHSRC, MWI-4, and MWI-15, any proposals submitted to the National Health Sciences Research Committee (NHSRC) must be accompanied by the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The NHSRC checklist (MWI-4)
Cover letter from the PI
The NHSRC application form (MWI-15)
Research proposal summary, maximum four (4) pages
Full/main research proposal (see the G-NHSRC, MWI-4, and MWI-15 for details)
Data collection instruments in both English and Chichewa (or other appropriate local language)
Informed consent in both English and Chichewa (or other appropriate local language)
Letter of approval from foreign EC, where applicable (for all students studying in foreign universities)
Support letters from affiliating institutions (e.g., universities, hospitals, research institutions, or companies where the study is going to take place)
A copy of the receipt for the paid application fee
CVs for all the investigators
Proof of funding from the sponsor/funder (where applicable)

MWI-4 requires that if any of the above items are not included in the submission to the NHSRC, an explanation must be provided.

College of Medicine Research and Ethics Committee

MWI-1 indicates that for submissions to the College of Medicine Research and Ethics Committee (COMREC), a single PDF file should include the following information in the following order:

Completed copy of the COMREC checklist (MWI-1)
Cover letter from the PI
Protocol
ICFs in both English and Chichewa for adult participants ages 18 and above, parental consent forms for all minors, and assent forms (in addition to the parental consent forms) for all minors between the ages of 7 and 17
Data collection tools (those that will involve obtaining information from research participants should be translated into Chichewa)
Material transfer agreement forms and documents
Waiver letter for the 10% College of Medicine (COM) overhead fee, if applicable
Information regarding whether the research proposal has been submitted to another EC
Letter of support from COM head of the principal department hosting the research
Letter(s) of support from heads of all other departments and institutions in which any research work will be done
Evidence of current active registration with the Medical Council of Malawi for the PI and other investigators
Investigator(s) CV(s)

MWI-1 further indicates that the proposal should not be submitted unless every item on the checklist is included, or unless a reason can be provided for the absence of any item. The completed checklist must be attached to the front of the submission. See the G-COMREC and MWI-1 for more information.

Clinical Protocol

As delineated in the G-CTAProcsVacBiol, the clinical protocol should comply with the format provided in the ICH's GCP guidelines. Per MWI-25, clinical trials in Malawi are required to follow the ICH's Guideline for Good Clinical Practice E6(R2) (MWI-22). In addition, MWI-60 provides recommended items to address in a clinical trial protocol and related documents, based on SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidance.

Per the G-HlthResConduct, MWI-60, MWI-1, and MWI-22, the following elements should be included in the protocol (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Cover page
General information (protocol title, identifying number, and date; registry name; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study, along with role responsibilities)
Protocol summary/abstract
Background and justification
Investigator(s) CV(s) and contact information
IP description (See the Investigational Products topic for detailed coverage of this subject)
Form, dosage, route, method, and frequency of administration and treatment period
Summary of potential risks and known benefits to research participants
Hypothesis
Trial objectives and purpose
Study setting
Trial design, random selection method, and blinding level
Work plan/Gantt chart
Participant selection/withdrawal, timeline, and sample size
Participant treatment
Safety and efficacy assessments
Literature review
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
Quality control/quality assurance procedures and practices
Data monitoring, including composition of a data monitoring committee, and auditing
Ethical considerations, including confidentiality, and plans for seeking EC approval
Plans for communicating important protocol modifications to relevant parties
Data management and recordkeeping
Dissemination of findings
Financing and insurance details
Publication policy
Consent form, and information on who will obtain consent
Plans for collection, laboratory evaluation, and storage of biological specimens

For more detailed protocol requirements and recommendations, refer to MWI-60, MWI-22, MWI-1, and the G-HlthResConduct.

5.0

7 (Checklist of Required Documents)

1, 2, 3.2, and Screening Form

5 and 7

5.1

6

Last content review/update: March 21, 2024

Regulatory Authority Requirements

N.Y.M.1

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

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

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

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

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

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

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

P.Y.8

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

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

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

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

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

Ethics Committee Requirements

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

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

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

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

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

Central Research Ethics Committee

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

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

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

Clinical Protocol

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

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

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

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

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

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

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

Appendices 1-2 and 7

Appendix 2-11 and 13

6

Annex 6

3, 12-13, and 15

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

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

Timeline of Review

Last content review/update: August 29, 2024

Overview

As stated in the R-HlthResCoord, one (1) of the two (2) government approved ethics committees (ECs), the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC), must review and approve a clinical trial application prior to the Pharmacy and Medicines Regulatory Authority (PMRA) initiating its review and approval process. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

Regulatory Authority Approval

According to the G-CTARevVacBiol, the PMRA review process takes approximately six (6) weeks.

As per the G-CTARevVacBiol and the G-CTAProcsVacBiol, once the dossier is submitted to the PMRA, the application is screened for completeness. According to the G-CTARevVacBiol, the result of the screening will be communicated to the applicant within 10 working days after receipt of the application, and the screening form will be forwarded by fax. The applicant will have 10 working days to forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert or evaluator for scientific review, with an allocated review period of three (3) weeks.

However, the G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report within 14 days to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection. (Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.)

As stated in the G-ImpExpMP, the PMRA’s processing time for an import permit application is 10 working days.

Ethics Committee Approval

National Health Sciences Research Committee

The G-NHSRC indicates that in the case of an approval with no changes, the chairperson must inform the investigator in writing within seven (7) days. The NHSRC’s timeline for review of research proposals is not otherwise specified in the requirements.

College of Medicine Research and Ethics Committee

According to the G-COMREC, COMREC must ensure that submitted complete proposals are reviewed in a timely manner, i.e., within the month of submission. A written decision is provided to the applicant within two (2) weeks of the meeting at which the decision was made.

5.1 and 5.9

2-6

1-3

5.4

7.0, 7.2, 8.0-8.2

3.5

Last content review/update: March 21, 2024

Overview

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

Regulatory Authority Approval

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

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

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

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

Ethics Committee Approval

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

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

Clinical Trials

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

Appendices 1-3, 7, and 9

Appendices 2-4, 11, and 13

Items 2, 11, 33, 34, and 49

Annex 6

2-3 and 15

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

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

Appendix 12

Initiation, Agreements & Registration

Last content review/update: August 29, 2024

Overview

According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval before initiating a clinical trial.

The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC).

In addition, as per the D-ImprtRelIMPs, the sponsor should not supply the investigational product (IP) to be used in the clinical trial until the sponsor obtains all required documentation. As stated in the G-ImpExpMP, IP import permit applications should be made by the pharmacist of record for the trial. (See the Manufacturing & Import section for additional information.)

Clinical Trial Agreement

The G-CTAProcsVacBiol requires the sponsor to sign a letter of agreement with the participating institution(s) before the trial begins. In addition, the investigators and the sponsor or the contract research organization must sign an agreement specific to the clinical trial.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 indicates that the sponsor should obtain the investigator’s/institution’s agreement to:

Conduct the trial in compliance with good clinical practice (GCP), with the applicable regulatory requirement(s), and with the approved protocol
Comply with procedures for data recording/reporting
Permit monitoring, auditing, and inspection
Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

No clinical trials registry exists at this time and there is no stated requirement to register in an international registry.

3

7 (Checklist of Required Documents (Appendices 1, 8, and 10) and CTA Sections 4 and 8)

1, 3.2, and Screening Form

8.0-8.2

3.7

5.6

Last content review/update: March 21, 2024

Overview

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

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

Clinical Trial Agreement

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

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

Clinical Trial Registration

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

2

Appendices 1-3, 7, and 9

Appendices 2-4, 11, and 13

1.25, 2.8, 4.1, 5.1, and 5.5

Annex 5 (6)

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

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

4-5 and 9-10

Safety Reporting

Last content review/update: August 29, 2024

Safety Reporting Definitions

In accordance with the G-SAEs-PMRA, the following definitions provide a basis for a common understanding of Malawi’s safety reporting requirements:

Adverse Event (AE) – Any AE associated with the use of a medicine in humans, and which does not necessarily bear a causal relationship to the treatment. This may include an AE occurring in the following circumstances: during use in professional practice; from an overdose, whether accidental or intentional; from drug abuse; from drug withdrawal; and as a result of any failure of expected pharmacological action.
Adverse Drug Reaction (ADR) – A reaction characterized by the suspicion of a causal relationship between the drug and the occurrence.
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – An adverse experience occurring at any dose that results in death, is life-threatening, requires or extends patient hospitalization, results in persistent or significant disability, is a birth defect or congenital anomaly; or is an important medical event that, based upon appropriate medical judgment, may jeopardize the participant, and may require intervention to prevent one (1) of the listed outcomes.

Safety Reporting Requirements

As stated in the G-SAEs-PMRA, the sponsor or the investigator(s) is required to report all SAEs that meet the Pharmacy and Medicines Regulatory Authority (PMRA)’s reporting requirements as soon as possible (within 24-72 hours) following site awareness using the SAE Form (MWI-12). All deaths that are assessed as definitely, probably, or possibly related must be reported to the PMRA within 24 hours of site awareness, and the SAE Form (MWI-12) must be submitted within three (3) working days of site awareness. See the G-SAEs-PMRA for additional details on reporting timelines for different reportable SAE situations.

The G-NHSRC indicates that the National Health Sciences Research Committee (NHSRC) requires the investigator to submit a written report for any occurrence of an AE. In the event of documented SAEs and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. Per the G-COMREC, AE and SAE reports must also be submitted to the College of Medicine Research and Ethics Committee (COMREC).

Form Completion & Delivery Requirements

As per the G-SAEs-PMRA, all SAEs that meet reporting requirements must be reported to the PMRA on an SAE Form (MWI-12). The G-SAEs-PMRA indicates that the form must be submitted to the PMRA office by email or hand delivered to the offices at the following address:

The Director General
Pharmacy and Medicines Regulatory Authority
P.O. Box 30241
Lilongwe 3, Malawi
Tel: 265-1755166/165
Email: info@pmra.mw, registration@pmra.mw

According to the G-NHSRC, AE reports submitted to the NHSRC must provide the following details:

Title of protocol
NHSRC assigned reference number
Name of investigator
Local affiliating institution for studies originating from outside Malawi
Subject identifier
Date and site/place of event
Description of event (i.e., nature of injury or other adverse occurrence, assessment of severity, and assessment of relationship of the event to the study)
Action taken by the researcher
Signature of the principal investigator (PI)

See MWI-2 for the NHSRC SAE Reporting Form.

6.0

5.7-5.8

1 and 2

Last content review/update: March 21, 2024

Safety Reporting Definitions

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

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

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

Safety Reporting Requirements

Investigator Responsibilities

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

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

Sponsor Responsibilities

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

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

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

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

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

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

Other Safety Reports

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

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

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

Form Completion & Delivery Requirements

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

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

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

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

Individual report data should include at minimum the following information:

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

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

Ethical Criteria

Appendix 17

Appendix 21

II

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

CREC 11 / v.4.0 Review of Adverse Event Reports

Annex 5 (17)

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

4.6 and Appendix 17

4.6 and Appendix 21

Progress Reporting

Last content review/update: August 29, 2024

Interim and Annual Progress Reports

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 notes that the investigator should promptly provide written reports to the sponsor and the institutional ethics committee (EC) on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-NHSRC, the National Health Sciences Research Committee (NHSRC) requires an initial submission of a progress report within three (3) months of approval of the study, and an annual report for medium to long-term studies.

The G-COMREC requires that the College of Medicine Research and Ethics Committee (COMREC) follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. As part of the monitoring process, every approved study must submit annual reports by November 30, regardless of the date of its approval.

As required in MWI-58, the principal investigator (PI) must submit an annual progress report to the Pharmacy and Medicines Regulatory Authority (PMRA). All sections of the Clinical Trial Annual Progress Reporting Form for Investigators (MWI-58) must be completed in typescript and submitted together with accompanying documents to the PMRA Director General at info@pmra.mw. Both hard and soft (electronic) copies must be submitted.

The G-NHSRC and the G-COMREC further state that all approved studies continuing for more than one (1) year are subject to continuing review by the approving EC. As part of this review, applicant(s) are required to submit a progress report describing the number of participants enrolled, any problems that occurred during the prior approval period, any new knowledge regarding the study, and any procedural changes.

See MWI-54 and MWI-8 for the NHSRC and COMREC report forms, respectively.

Final Report

As required by the G-NHSRC and the G-COMREC, the applicant is required to submit a final report to the approving EC when a study is completed.

According to the G-NHSRC, the investigator must submit three (3) copies of the final technical report when submitting written notice of the completion of the study to NHSRC.

Other Considerations

The G-NHSRC states that all data originating from a research study conducted in Malawi are the property of the Malawi Government irrespective of the source of funds for carrying out the study. Therefore, investigators are required to submit copies of their reports to NHSRC for review prior to submitting for publication within or outside of Malawi. Investigators are expected to have plans for disseminating research findings in Malawi.

5.5 and 6.0

5.1, 5.6, and 11

4.10 and 4.13

Last content review/update: March 21, 2024

Interim and Annual Progress Reports

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

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

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

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

Final Report

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

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

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

Individual ECs should be contacted to confirm their specific requirements.

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

Appendices 10-11

Appendices 14-15 and 19

4.10

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

6.6

4.1 and Appendices 10-11

4.1 and Appendices 14-15 and 19

Definition of Sponsor

Last content review/update: August 29, 2024

As per the D-ImprtRelIMPs and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22), 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 MWI-25, clinical trials in Malawi are required to follow MWI-22. MWI-22 goes on to specify that a sponsor-investigator is an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

In accordance with MWI-22, a sponsor may transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.

A sponsor may be domestic or foreign. As specified in the R-HlthResCoord, a sponsor that is a foreign company, organization, or individual(s), must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.

7

10.0

1.53, 1.54, 5.1, and 5.2

Last content review/update: March 21, 2024

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

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

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

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

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

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

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

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

1.20, 1.53-1.54, and 5.2

Annex 5

Site/Investigator Selection

Last content review/update: August 29, 2024

Overview

The G-CTAProcsVacBiol specifies that the investigator(s) must be qualified, experienced, and have specific good clinical practice (GCP) training. The principal investigator (PI) should have acted as a sub-investigator in at least one (1) prior clinical study. The investigator must also commit to complying with the clinical trial protocol, have no conflicts of interest, and have no history of GCP noncompliance.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides the following guidance to sponsors on investigator and site selection:

The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicenter trials, their organization and/or selection are the sponsor’s responsibility.
Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and should provide sufficient time for the investigator/institution to review the protocol and the information provided.

As stated in the G-CTAProcsVacBiol, all clinical trials must also be conducted in a laboratory that can provide evidence of accreditation with a recognized control authority to conduct the specified test. In the absence of an accreditation authority, proof of Good Laboratory Practice compliance and validation of assay methods should be provided.

Foreign Sponsor Responsibilities

According to the G-NHSRC, foreign researchers must be affiliated to a local institution and provide a supporting letter from the institution as evidence. Additionally, they must have a local collaborator. The R-HlthResCoord further indicates that any foreign-based institution or organization must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.

Data and Safety Monitoring Board

Although not specified as a sponsor requirement, the G-CTAProcsVacBiol states that a Data Safety Monitoring Board (DSMB) or a similar body must be established and empowered to regularly assess the trial and to recommend a pause or termination of the trial for safety reasons. MWI-22 notes that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Multicenter Studies

As delineated in MWI-22, 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 given ethics committee (EC) 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 among investigators is facilitated

7 (Checklist of Required Documents (Appendices 8 and 10) and CTA Sections 4 and 8)

5.1

10

1.25, 5.5, 5.6, and 5.23

Last content review/update: March 21, 2024

Overview

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

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

Foreign Sponsor Responsibilities

No information is available regarding foreign sponsor regulatory requirements.

Data Safety Monitoring Board

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

Multicenter Studies

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

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

3

1.25, 4.1, 5.1, 5.5, and 5.7

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

Descriptions and Definitions and Appendix 3

Insurance & Compensation

Last content review/update: August 29, 2024

Insurance

As set forth in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC, the sponsor or the investigator(s) are responsible for providing insurance coverage for any unforeseen injury to research participants. Before a clinical trial begins, the sponsor should also provide insurance or indemnify the investigator and the institution against claims arising from malpractice or negligence. See the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC for detailed information on when insurance is required.

As per the G-CTInsurance-MWI, the sponsor or the investigator(s) must provide the participants with a no-fault insurance policy and certificate for the duration of the trial, and for five (5) years following the trial’s completion. “No-fault” is defined as insurance for which proof of negligence or other wrongful conduct need not be established. However, the causal connection between the trial and harm, bodily injury, or death must be proven to trigger the obligation to make a compensation payment. The National Health Sciences Research Committee (NHSRC), the College of Medicine Research and Ethics Committee (COMREC), or the Pharmacy and Medicines Regulatory Authority (PMRA)'s Clinical Trial Review Committee are responsible for determining which clinical trials fall within the scope of this requirement.

Per the G-CTInsurance-MWI, obtaining and submitting insurance is a requirement and a prerequisite to obtaining clinical trial ethics and regulatory approval. The insurance documentation must be included as part of the application package submitted to either the NHSRC or COMREC, and the PMRA. As specified in the G-CTAProcsVacBiol, the sponsor or the investigator(s) must also comply with the insurance and compensation requirements delineated in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20).

The PMRA’s Indemnity Form for Conducting Clinical Trials (Form CT 10) is available at MWI-18.

Compensation

Injury or Death

As specified in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, and the G-COMREC, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

As per the G-CTAProcsVacBiol, the sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20) to comply with Malawi’s participant compensation and treatment requirements due to trial-related injuries. The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or the legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committees (ECs).

MWI-21 provides several basic principles to guide sponsors in fulfilling their compensation obligations. Compensation should be paid as follows:

When it can be demonstrated that a causal relationship exists between a participant’s injury and participation in a trial
When a child is injured in utero through participation by the child’s mother in a clinical trial
When the injury results in permanent injury or disability to the participant
When there is an adverse reaction to a medicinal product under trial, and injury is caused by a procedure adopted to deal with that adverse reaction

MWI-21 states that the likelihood of an adverse reaction, or the fact that the participant has freely consented (whether in writing or otherwise) to participate in the trial should not exclude the participant from being eligible for compensation. The amount of compensation paid to the participant should be appropriate to the nature, severity, and persistence of the injury. The compensation should also be generally consistent with the amount of damages commonly awarded for similar injuries.

According to MWI-21, the amount paid in compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):

The seriousness of the disease being treated
The degree of probability that adverse reactions will occur and any warning given
The risks and benefits of the established treatments relative to those known or suspected of the trial medicines

Per MWI-21, in any case where the sponsor agrees to pay the participant, but the two (2) parties differ on what is the appropriate level of compensation, it is recommended that the sponsor agree to seek the opinion of a mutually acceptable independent expert at the sponsor’s own cost. This opinion should then be made available to the participant(s), and the expert’s opinion should be given substantial weight by the sponsor in reaching a decision on the payment amount.

Additionally, any participant claims pursuant to MWI-21, should be made to the sponsor, preferably via the investigator. The participant should include details on the nature and background of the claim, which the sponsor should review expeditiously. The review process may be delayed if the participant requests an authority to examine any medical records relevant to the claim.

Trial Participation

Per G-BioSampCompense, participants may also be reimbursed for trial-related expenses, if allowed by the EC. However, payments to participants that are construed to affect the voluntary participation of the subjects are not allowed. Furthermore, lump sum payments for research participation are not allowed. Participants who incur direct costs from trial participation must be reimbursed if required by the EC. Such reimbursable expenses include travel and communications costs associated with routine clinical trial evaluations. During review of the protocol, the EC will make a case-by-case determination if the study should provide any form of acceptable recompense.

(b)(ii) and (b)(iii)

9.0

7 (Checklist of Required Documents (Appendix 9), CTA Section 5, CTA Section 9, and Check of Appended Documents (Appendix 9))

1, 2, 3.2, and Screening Form

1.0-3.0 and 7.0

3 and 4

4.8 and 5.8

Last content review/update: March 21, 2024

Insurance

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

Compensation

Injury or Death

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

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

Trial Participation

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

Appendices 2 and 7

Appendices 3 and 11

4.8

3.2 and Annex 5 (8)

11

1.5, 1.10, and Appendices 2 and 7

1.3, 1.9-1.10, and Appendices 3 and 11

Chapter 9 (Article 49)

Risk & Quality Management

Last content review/update: August 29, 2024

Quality Assurance/Quality Control

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 guides sponsors on quality, data, and records management.

Per MWI-22, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

During protocol development, identification of processes and data that are critical to ensure participant protection and the reliability of trial results
Identification of risks to critical trial processes and data
Evaluation of the identified risks against existing risk controls
Decisions on which risks to reduce and/or which risks to accept
Documentation of quality management activities and communication to those involved in or affected by these activities
Periodic review of risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, a description of the quality management approach implemented in the trial and a summary of important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

As part of its quality assurance system, the G-CTAProcsVacBiol notes that the sponsor should perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, standard operating procedures (SOPs), and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. 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 sponsor’s own SOPs, the auditor observations are documented, and data are available as needed for the Pharmacy and Medicines Regulatory Authority (PMRA) to review. No specific timeframe is provided for the audit process.

Per MWI-22, 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 on-site monitoring, a combination of on-site 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).

Per MWI-61, the PMRA may conduct good clinical practice (GCP) inspections of clinical trial sites before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. In general, the inspectee will be notified one (1) to four (4) weeks prior to the proposed announced inspection date and asked to confirm availability. The notification will identify the study and the proposed sites to be inspected. In relation to triggered inspections, the PMRA may provide a shorter notice period. The inspection dates will be confirmed with the inspectee, who may be required to submit information to the PMRA within 14 days of the receipt of the notice of GCP inspection. The inspection plan is finalized by the PMRA before the inspection. See MWI-61 for more information on PMRA GCP inspections.

Premature Study Termination/Suspension

According to MWI-22, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor. Refer to MWI-17 for the National Health Sciences Research Committee (NHSRC)’s protocol termination form.

The G-COMREC states that if a study is prematurely suspended/terminated, the applicant should notify the College of Medicine Research and Ethics Committee (COMREC) of the reasons for suspension/termination, and a summary of the results obtained should be communicated to the committee.

6.0

7 (CTA Section 8)

4.0 and 6.2-6.3

5.0-5.2, 5.18-5.19, 5.21, and 6.10

Last content review/update: March 21, 2024

Quality Assurance/Quality Control

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

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

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

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

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

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

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

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

Monitoring Requirements

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

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

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

Premature Study Termination/Suspension

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

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

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

Appendices 7 and 16

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

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

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

16.2

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

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

Data & Records Management

Last content review/update: August 29, 2024

Electronic Data Processing System

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). As per MWI-22, 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. The sponsor should base their approach to validate such systems 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. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to MWI-22 for additional information.

Records Management

As set forth in MWI-22, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the 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, MWI-22 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.

According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the National Health Sciences Research Committee (NHSRC).

1.65, 5.5, and 8

Last content review/update: March 21, 2024

Electronic Data Processing System

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

Records Management

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

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

5.5 and 8

Annex 5 (5)

4.7

Personal Data Protection

Last content review/update: August 29, 2024

Responsible Parties

For the purposes of data protection requirements, as stated in the G-DataPrtct-MWI, the data controller means a natural or legal person who, alone or jointly with another natural or legal person, determines the purpose and means of processing personal data. The data processor means a natural or legal person who processes personal data on behalf of a data controller. The Malawi Communications Regulatory Authority (MACRA) regulates the processing of personal data and is responsible for the enforcement of the G-DataPrtct-MWI.

Data Protection

A data controller and data processor must process personal data lawfully, fairly, and in a transparent manner, as described in the G-DataPrtct-MWI. Additionally, a data controller and data processor must collect personal data for a specific and legitimate purpose and must not process the data in a manner that is incompatible with the purpose for which it was collected. They also must not store personal data for a period that is longer than necessary to achieve the purpose for which the data is processed, except where the data is stored for the purpose of archiving for public interest or for research or statistical purposes. The appropriate technical or organizational security measures must be implemented to guarantee the security of personal data, including protection against unauthorized or unlawful processing and accidental loss, destruction, or damage of the data.

See the G-DataPrtct-MWI for more details on the duties of a data controller and data processor.

Consent for Processing Personal Data

The G-DataPrtct-MWI indicates that a data controller must obtain the consent of a data subject before processing the personal data of the data subject. Where a data controller seeks consent from a data subject on several matters in the form of a written declaration, each matter on which consent is sought must be presented in a clearly distinguishable manner. A data subject may, at any time, withdraw consent given to a data controller and the withdrawal of the consent shall, where practicable, be in the same manner the consent was provided. The withdrawal must not affect the legality of the data processing that occurred before the withdrawal of the consent. Where a question arises on whether consent was freely provided, consideration must be taken of whether the performance of a contract between the data controller and the data subject, or the delivery of a good or a service by the data controller to the data subject, is conditional on provision of the consent.

According to the G-DataPrtct-MWI, a data controller must, at the time of collecting personal data from a data subject, provide the following information to the data subject:

The identity and contact details of the data controller or representative of the data controller
The legal basis for processing the personal data
The purpose for processing the personal data
Where possible, the storage period for the personal data
The existence of automated decision-making, including profiling
The rights of the data subject provided in the G-DataPrtct-MWI (described below)
The right to lodge a complaint with the MACRA
Whether the data controller intends to transfer the personal data to a place outside Malawi

As per the G-DataPrtct-MWI, a data subject has the right to obtain confirmation of whether personal data concerning the data subject is being processed by the data controller or data processor. Where the data controller or data processor confirms the processing of the personal data of the data subject, the data controller or data processor must provide the data subject with a copy of the personal data being processed (i) in a commonly used electronic format; (ii) within 30 days of receipt of the request; and (iii) where practicable, at no expense to the data subject. The data subject also has a right to data portability, rectification of personal data, erasure of personal data, restriction of processing personal data, object to the processing of personal data, and not to be subject to a decision based solely on automated processing. See the G-DataPrtct-MWI for more information on these rights.

Children and Incapacitated Persons

The G-DataPrtct-MWI delineates that where a data subject is a child or any other natural person lacking the legal capacity to exercise the rights of the data subject, a parent or legal representative/guardian of the data subject must exercise the rights of the data subject on behalf of the data subject. A data controller or data processor who intends to process personal data of a data subject who is a child or any other natural person lacking legal capacity to provide consent must obtain the consent from a parent or legal representative/guardian of the data subject. Additionally, the data controller or data processor who obtains such consent must put in place appropriate mechanisms to verify the age of the child or the mental capacity of the other natural person, as well as the identity of the parent or legal representative/guardian providing the consent.

Parts I (2), II (4-5), III (8-17), IV, and V

Last content review/update: March 21, 2024

Responsible Parties

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

Data Protection

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

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

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

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

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

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

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

Consent for Processing Personal Data

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

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

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

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

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

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

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

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

Documentation Requirements

Last content review/update: August 29, 2024

Obtaining Consent

In all Malawian clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the G-NHSRC and G-COMREC-IC. The G-BioSampCompense also confirms that a participant’s voluntary informed consent is required. Also, per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22).

As per the G-NHSRC, the G-CTAProcsVacBiol, the G-CTARevVacBiol, the G-COMREC, and MWI-22, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by one (1) of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—and provided to the Pharmacy and Medicines Regulatory Authority (PMRA) with the clinical trial application. (See the Required Elements section for details on the contents to be included in the form.)

The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the participant or legal representative/guardian must be provided with detailed research study information. Per the G-NHSRC, the ICF content should be presented orally and in writing, in a manner that is easy to understand, commensurate with the comprehension level of the research participants, and without coercion. When drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education.

As per the G-NHSRC and MWI-22, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or appear to waive the participant’s 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. The G-BioSampCompense also confirms that researchers must not duly induce participants to participate in any proposed research. Rather, they must design and implement their studies in a manner that calls for the participants’ informed voluntary consent to participate.

Re-Consent

According to MWI-22, the written ICF and any other written information to be provided to participants should be revised whenever important new information becomes available that may be relevant to the participant’s consent. Any revised written ICF and written information should receive the EC's approval/favorable opinion in advance of use. The participant or legal representative/guardian should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant or legal representative/guardian should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.

Language Requirements

As stated in the G-NHSRC, the G-COMREC, and the G-COMREC-IC, the ICF should be written in English and any other relevant local languages that the participant is able to understand.

Documenting Consent

The G-NHSRC and MWI-22 specify that the participant or legal representative/guardian must sign the ICF. The G-NHSRC indicates that where the participant is illiterate, the NHSRC will permit the participant to provide a thumbprint in the presence of a witness, who must also sign the ICF. NHSRC also permits the participant to provide verbal consent in cases where the participant is illiterate. However, the script or information sheet to be read to the potential participant must be approved by NHSRC and signed for by the participant’s legal representative/guardian.

MWI-22 states that where the participant is illiterate or legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

The written ICF and any other written information provided to the participant is read and explained to the participant and the legal representative/guardian
The participant and the legal representative/guardian, have orally consented to the participant’s involvement in the trial, and has signed and dated the ICF, if capable of doing so

Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the NHSRC.

Waiver of Consent

Per the G-NHSRC, the NHSRC may waive the requirement for the investigator to obtain a signed ICF in cases where circumstances warrant such a waiver. The following conditions may be considered for a waiver:

The research presents no more than a minimal risk of harm to the participants and involves no procedures for which written consent is normally required outside of the research context
The research could not practically be carried out without the consent waiver and obtaining informed consent is not practicable
The consent document is the only link between the participant and the research and the principal risk of harm would come from a breach of confidentiality
Waiver is consistent with the individual’s rights

The G-NHSRC indicates that in lieu of a signed ICF, the NHSRC may require the investigator to provide participants with a written statement regarding the research in the form of an information or fact sheet. This statement should contain, at a minimum:

A statement verifying that the project involves research
A description of the level of involvement and amount of time expected from participants
A description of the study
A description of the risks and benefits to the participants
A statement describing the participant’s rights
A description of the compensation to be provided to participants
Contact information for both the investigator and NHSRC chairperson

(b)(i)

5.0

7 (Checklist of Required Documents (Appendix 4), CTA Section 10, and Check of Appended Documents (Appendix 4))

Screening Form

5.1, 6.2, 7.0, and 7.4

2, 4.4, 4.8, 8.2, and 8.3

Last content review/update: March 21, 2024

Obtaining Consent

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

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

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

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

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

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

Re-Consent

No information is currently available regarding re-consent requirements.

Language Requirements

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

Documenting Consent

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

Waiver of Consent

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

Information Sheet (p.70)

Approval documents - Informed Consent

5

Appendix 7

Appendix 11

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

1. Informed consent form for clinical trials

2.2 and 3.1-3.3

11

Section 9

Preface, 1.9, and Appendix 7

1.9 and Appendix 11

Chapter 9 (Article 47)

Required Elements

Last content review/update: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides guidance on the elements to include in the informed consent form (ICF). The G-NHSRC and MWI-22 state that information about the research study should be clearly presented in both written and oral form.

Based on the G-NHSRC, the G-COMREC-IC, the G-NHSRC-ICF, MWI-22, and MWI-13, the ICF 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 title, purpose, procedures, and duration
Experimental aspects of the study
The responsibilities and expected duration of the participant's participation
The trial treatment(s) and the probability for random assignment to each treatment
Any expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
Any expected benefits to the participant, others, or to the country as a whole that may reasonably be expected from the research
Description of procedures, including data collection, that will be followed
Identification of any experimental procedures
Disclosure of alternate procedures or treatments available to participants that might be advantageous to the participant
Compensation and/or treatment available for the participant in the case of trial-related injury
The anticipated prorated payment, if any, to the participant for participating in the trial
The anticipated expenses, if any, to the participant for participating in the trial
That participation is voluntary, and that the participant can refuse to participate or withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
That the monitor(s), the auditor(s), the ethics committee (EC), and the regulatory authority(ies) will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written ICF, the participant or the participant's legally acceptable representative is authorizing such access
The extent to which confidentiality of records identifying the participant will be maintained
Name and contact details of institutions that have approved the study
Contact information for the sponsor and investigator in the event of participant problems or trial-related injuries
EC contact information
Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
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
Any additional costs to the participant that may result from participation in the research
The site of the study
Consent and signature or thumb print, including the last sentence, which should explicitly read “I voluntarily agree”

See the Vulnerable Populations and Consent for Specimen sections for further information.

5.1, 6.2, 7.0, and 7.1

4.4 and 4.8

Last content review/update: March 21, 2024

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

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

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

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

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

Information Sheet (p.70)

Approval documents - Informed Consent

Appendix 7

Appendix 11

1. Informed consent form for clinical trials

3.1.1 and 3.2

11

1.9 and Appendix 7

1.9 and Appendix 11

Participant Rights

Last content review/update: August 29, 2024

Overview

Per the G-NHSRC, Malawi’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), which addresses participant rights.

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

The Right to Participate, Abstain, or Withdraw

As set forth in the G-NHSRC, the G-COMREC-IC, and MWI-22, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the G-NHSRC, the G-COMREC-IC, and MWI-22, 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. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

As per the G-NHSRC, the G-COMREC-IC, and MWI-22, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. It is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The Malawi government complies with MWI-22 principles that state 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.

2, 6.2, and 7.1

2, 3.1, and 4.8

Last content review/update: March 21, 2024

Overview

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

The Right to Participate, Abstain, or Withdraw

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

The Right to Information

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

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

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

The Right to Safety and Welfare

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

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

4

1.28, 4.8, and 8.2

2.2, 3.1-3.3, and 4.1

11

Section 9

1.9

Emergencies

Last content review/update: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies.

Per MWI-22, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee (EC) must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

As per the G-NHSRC, a waiver of consent may be justified if the research being conducted could not practically be carried out without the consent waiver, and obtaining informed consent is not practicable. See the Documentation Requirements section for more information on waiver of consent.

7.4

4.8

Last content review/update: March 21, 2024

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

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

1.61, 3.17, and 4.8.15

Vulnerable Populations

Last content review/update: August 29, 2024

Overview

As per the G-NHSRC, in all Malawian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The G-NHSRC characterizes vulnerable populations as those who are relatively or absolutely incapable of protecting their own interests due to illiteracy, a lack of education, autonomy, resources, or other necessary attributes. These participants may include children, pregnant women, prisoners, refugees, orphans, sex workers, people living with HIV and AIDS, persons with mental disabilities, and persons in dependent relationships (e.g., some women who culturally must ask their husbands before consenting to participate in a research study).

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 includes the following as vulnerable populations: members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable populations include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

The G-NHSRC specifies that National Health Sciences Research Committee (NHSRC) members must pay special attention to protecting participants who are from vulnerable populations. Consent for those who are not legally, mentally, and physically able should be sought from their legal representative/guardian in the form of a signature or thumbprint.

As per the G-NHSRC, trials involving vulnerable persons require the research to be directly related to the specific conditions of the vulnerable population involved, and that the participants should personally benefit from the research. In addition, the following elements must be considered when studies are conducted using vulnerable populations:

The methods of recruitment, selection, and inclusion/exclusion criteria, as well as informed consent, data confidentiality, and the participant’s willingness to volunteer
Group characteristics such as economic, social, physical, environmental, and cultural conditions
Applicable local laws that bear on the decision-making abilities of potentially vulnerable participants
Research studies involving potentially vulnerable population groups should have adequate procedures in place for assessing and ensuring participants’ capacity, understanding, and informed consent or assent
Safeguards may include NHSRC monitoring of the consent process where possible

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

5.2, 7.0, and 9.2

1.61 and 4.8

Last content review/update: March 21, 2024

Overview

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

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

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

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

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

1.61

2.2.2 and 3.4

Children/Minors

Last content review/update: August 29, 2024

The G-NHSRC states that a minor is a person less than 18 years of age. When the research participant is a minor, assent must be obtained in tandem with permission from the parent/legal guardian.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes minors, the minors should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.

Assent Requirements

As per the G-NHSRC, assent must be obtained from a minor who is deemed capable of providing assent. The National Health Sciences Research Committee (NHSRC) bases its assessment of a minor’s ability to assent on the minor’s age, maturity, and psychological state. In certain cases, the NHSRC may regard assent by minors to represent informed consent without requiring the permission of a parent/legal guardian. A typical case is when the minors are emancipated, and may include those that are legally married or are university students under the age of 18.

7.0 and 9.2

4.8

Last content review/update: March 21, 2024

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

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

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

Assent Requirements

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

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

4.8.12

2.2.2 and 3.4

Part II (Sections 19 and 20)

Pregnant Women, Fetuses & Neonates

Last content review/update: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states 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.

4.8

Last content review/update: March 21, 2024

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

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

4.8.10

2.2 and 3.4

Prisoners

Last content review/update: August 29, 2024

No information available regarding consent requirements for prisoners.

Last content review/update: March 21, 2024

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

2.2, 3.2, and 3.4

Mentally Impaired

Last content review/update: August 29, 2024

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participants should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.

The G-NHSRC states that consent for those who are not mentally able should be sought from their legal representative/guardian in the form of a signature or thumbprint.

7.0

1.61, 3.1, and 4.8

Last content review/update: March 21, 2024

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

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

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

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

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

3.4.5

Sections 3, 17, and 20-22

Definition of Investigational Product

Last content review/update: August 29, 2024

As delineated in the D-ImprtRelIMPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), an investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) is defined as a pharmaceutical form of an active substance 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 unauthorized indication, or when used to gain further information about an approved use. Per MWI-25, clinical trials in Malawi are required to follow MWI-22.

7

1.33

Last content review/update: March 21, 2024

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

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

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

1.33

7.1 and Annex 5

Manufacturing & Import

Last content review/update: August 29, 2024

Manufacturing

According to the PMRAAct, the D-ImprtRelIMPs, and the G-CTARevVacBiol, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for authorizing the manufacture of investigational products (IPs) (also referred to as an investigational medicinal products (IMPs)) in Malawi.

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 requires IPs to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol. See MWI-11 for the PMRA’s GMP inspection application form.

Import

As stated in the PMRAAct, the D-ImprtRelIMPs, and the G-ImpExpMP, the PMRA is also responsible for authorizing the import of IPs. Per the PMRAAct and the G-ImpExpMP, the PMRA’s authorization is issued as an import permit. The G-ImpExpMP designates the principal investigator of a registered clinical trial as an authorized importer. IP import permit applications should be made by the pharmacist of record for the trial.

As per the G-CTAProcsVacBiol and the G-CTARevVacBiol, the applicant may apply for an import permit at the same time that the clinical trial application is submitted to the PMRA. (Per MWI-34, the guidance in the G-CTAProcsVacBiol and the G-CTARevVacBiol also apply to clinical trials of drugs.)

The G-ImpExpMP further states that upon receipt of an import application, the PMRA will conduct an assessment to verify whether the requirements, as described in the G-ImpExpMP, have been fulfilled. If the application meets the prescribed requirements, the applicant will be required to pay applicable import permit fees (See the Regulatory Fees section) and the PMRA will issue an import permit. In the case that an application has been rejected, the applicant will be issued a rejection letter (see Annex 2 of the G-ImpExpMP) stating clearly reason(s) for rejection. The regulatory processing time for an import permit application is 10 working days. The import permit will be valid for six (6) months, not transferable to any other person, and may be extended for a period not exceeding three (3) months upon successful application to the PMRA. For additional information on general import application requirements, see the G-ImpExpMP.

Per the D-ImprtRelIMPs, shipping of IPs should be conducted according to instructions given by or on behalf of the sponsor in the shipping order. A pre-clearance inspection should be carried out at the port of entry by the PMRA. The sponsor must complete the cover sheet contained in Annex 1 of the D-ImprtRelIMPs for the importation and release of IPs. Please note: Malawi is party to the Nagoya Protocol on Access and Benefit-sharing (MWI-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see MWI-35.

1, 3, 5, and Annex 1

3, 5, and 7 (Checklist of Required Documents (Fees), and Check of Appended Documents (Fees))

2.1 and 3.2

Part II (Section 4), Part V (Section 58), and Part X (Section 96)

1, 3.1, 3.3-3.5, 3.7, and Annex 2

2.12 and 5.13

Last content review/update: March 21, 2024

Manufacturing

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

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

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

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

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

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

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

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

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

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

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

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

Import

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

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

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

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

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

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

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

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

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

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

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

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

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

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

14.2 and 16.2

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

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

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

Articles 2 and 3

Articles 2 and 3, and Letter 1

Quality Requirements

Last content review/update: August 29, 2024

Investigator's Brochure

In accordance with the G-CTAProcsVacBiol and the G-CTARevVacBiol, the Malawi government requires the sponsor to provide investigators with an Investigator’s Brochure (IB). Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 specifies that the IB must contain all of the relevant information on the investigational product(s) (IPs) (also referred to as investigational medicinal products (IMPs) in Malawi) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.

As specified in MWI-22, the IB must include the following sections:

Table of Contents
Summary
Introduction
Physical, Chemical, and Pharmaceutical Properties and Formulation
Nonclinical Studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
Effects in Humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
Summary of Data and Guidance for the Investigator(s)

See MWI-22 for detailed content guidelines.

Quality Management

MWI-60 requires that an Investigational Medicinal Product Dossier (IMPD) or alternative be submitted in the clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA). The IMPD must include information on the quality of any IP, the manufacture and control of the IP, and data from non-clinical studies and from its clinical use.

As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the D-ImprtRelIMPs, the PMRA requires the following documents to accompany the IP (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 good manufacturing practice (GMP)
A release of specifications and tests, including a Certificate of Analysis (CoA) for each batch of IPs, as well as comparator(s), if applicable
A copy of the PMRA’s letter of approval of the clinical trial
Batch release certificate
A copy of a valid Certificate of Manufacture issued by the competent authority in the country of origin
A copy of a valid World Health Organization certificate of a pharmaceutical product issued by the competent authority in the country of origin

The D-ImprtRelIMPs states that the CoA should identify the product name or code; the sponsor/company name; batch numbers; expiration dates; date of issue; signature, qualification, and title of responsible person; and the results of physical and analytical tests. Per MWI-22, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

The sponsor should complete the cover sheet in Annex 1 of the D-ImprtRelIMPs, include it with each IP shipment, and use the checklist in Annex 2 to ensure the required documentation is attached. As delineated in the D-ImprtRelIMPs, the sponsor should also prepare IP shipping instructions, including information about the shipment’s overall physical condition, for PMRA review and approval. The sponsor should provide information on the acceptable storage temperatures and storage conditions.

5, 6, Annex 1, and Annex 2

7 (Checklist of Required Documents (Appendices 2 and 10) and CTA Section 3)

3.2 and Screening Form

5.13, 5.14, 7, and 8.2

Last content review/update: March 21, 2024

Investigator's Brochure

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

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

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

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

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

Quality Management

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

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

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

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

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

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

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

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

Appendices 1, 6-7, and 12

Appendices 2, 7-8, 11, and 18

1.36, 5.14, and 7

Annex 5 (6.2, 12.2, and 13)

3, 6, 10, and 14.1

Chapter III (25 and 27)

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

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

Labeling

Last content review/update: August 29, 2024

Investigational product (IP) labeling in Malawi must comply with the requirements set forth in the D-ImprtRelIMPs. The D-ImprtRelIMPs states that for an IP to be used in a clinical trial, it must be properly labeled in the official language of the country where the trial is being conducted.

As set forth in the D-ImprtRelIMPs, the following labeling information must be included on the outer packaging or on the immediate packaging when there is no outer packaging:

Wording that clearly indicates the IP is clinical trial material
Product name or unique code
Storage temperature and conditions
Expiration date
Sponsor contact details

Additionally, the G-ImpExpMP provides the following minimum labeling requirements for all imported medicines and/or active pharmaceutical ingredient (API):

The information printed on labels must be indelible, engraved, or embossed on a primary and secondary container
The immediate outer packaging of the medicine or API should be clearly labeled in English
The trade or brand name where applicable should be stated
The International Non-Proprietary Name (INN, generic name) should be clearly stated
State quantities of each API in the given formulation or quantities of the raw material
Date of manufacture and expiry or retest date in case of active raw materials
Batch or lot number
Storage conditions
Name and address of manufacturer
Registration number of the product issued by the Pharmacy and Medicines Regulatory Authority (PMRA) in both outer and inner package of the product(s) where applicable
Enclosed and accompanying literature must be in English
The specification of the API is given according to officially recognized pharmacopoeia, where applicable

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). The D-ImprtRelIMPs and MWI-22 state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

5.13

4

3.3

Last content review/update: March 21, 2024

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

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

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

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

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

Refer to ClinImprtOrdr and ClinSampleProd for additional primary label requirements.

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

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

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

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

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

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

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

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

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

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

Appendices 1, 5, 7, and 14

Appendix 2, 6-7, 11, and 18

5.13

Annex 5 (13.1)

3 and 8

1.7 and Appendices 1, 5, 7, and 14

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

Appendix 12

Product Management

Last content review/update: August 29, 2024

Supply, Storage, and Handling Requirements

Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). As defined in the D-ImprtRelIMPs and MWI-22, the sponsor must also supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)), including the comparator(s) and placebo, if applicable. The sponsor should not supply either party with the IP(s) until after obtaining Pharmacy and Medicines Regulatory Authority (PMRA) and ethics committee approvals.

The D-ImprtRelIMPs and MWI-22 indicate that IPs must be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Additionally, the sponsor must ensure the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

IP product quality and stability over the period of use
IP is manufactured according to any applicable good manufacturing practice (GMP)
Proper coding, packaging, and labeling of the IP(s)
Records are maintained for document shipment, receipt, disposition, return, and destruction of the IP(s)
Acceptable storage temperatures, conditions, and times for the IP

Timely delivery of the IP(s)
Written procedures are established, 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
Sufficient quantities of the IP(s) are maintained to reconfirm specifications, should this become necessary

Refer to the D-ImprtRelIMPs for detailed sponsor-related IP requirements.

In addition, the PharmG-InvestDrugs states that the pharmacist at each clinical trial site, designated as the Pharmacist of Record, is the primary individual who is expected to develop and maintain an IP control system, which includes the technical procedures for product ordering, control, dispensing, and accountability. In addition, the Pharmacist of Record is responsible for the establishment of internal policies and procedures for the safe and proper use of IPs. The Pharmacist of Record will perform the day-to-day dispensing and accountability activities. A pharmacy plan must be created by the Pharmacist of Record for each clinical research site, addressing the control and use of IPs. See the PharmG-InvestDrugs for more information.

Record Requirements

In accordance with the D-ImprtRelIMPs, the sponsor is required to maintain a system for retrieving IP(s) and document this retrieval process (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim). The sponsor must also maintain a system for the disposition of unused IP(s) and for the documentation of this disposition. Finally, the sponsor should maintain sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. Moreover, to the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.

G-GMP-MWI requires that for IPs, the batch documentation must be retained for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the batch was used. Additionally, the G-ImpExpMP indicates that upon issuance of import authorization by the PMRA, the importer is expected to retain such records for five (5) years from the date of importation, either as hard or electronic copies. Stored import records should be easily accessible and availed for review to the PMRA’s inspector/officers for any post-import audit or investigations.

1, 3, 4, and 5

2.2.4

Pharmacy Plan

3.3

2.12, 5.5, 5.12-5.14, and 7

Last content review/update: March 21, 2024

Supply, Storage, and Handling Requirements

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

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

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

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

Record Requirements

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

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

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

Definition of Specimen

Last content review/update: August 29, 2024

In Malawi, as per the G-StorExptSpecimens, specimens are defined as human or animal materials, collected directly from humans or animals, including, but not limited to excreta, secreta, blood and its components; tissue and tissue fluid swabs; and body parts being transported for purposes such as research and investigational activities.

Specimens are also referred to as human materials or biological products. The G-StorExptSpecimens defines human material as all biological material of human origin, including organs, tissues, bodily fluids, teeth, hair, nails, and substances extracted from such material as DNA or RNA.

Please refer to G-StorExptSpecimens for more specific definitions for selected terms including genetically modified micro-organisms and infectious substances.

5.4-5.6

Last content review/update: March 21, 2024

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

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

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

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

1.4, 7.5-7.7, and Annex 8

Specimen Import & Export

Last content review/update: August 29, 2024

Import/Export

As delineated in the G-CTAProcsVacBiol, MWI-14, and MWI-7, the applicant must obtain approval from the Pharmacy and Medicines Regulatory Authority (PMRA) to import and export human biological specimens into and out of Malawi. The G-CTAProcsVacBiol notes that the applicant may apply to the PMRA for permission to import and/or export materials at the same time that the applicant submits the clinical trial application.

The G-StorExptSpecimens specifies that the sponsor is responsible for shipping specimens, for preparing the required documentation (e.g., nationally authorized import/export permits and dispatch/shipping documents), and for ensuring that the samples collected from research participants are sent through the appropriate carrier to their destination. The sponsor may delegate these functions to the principal investigator (PI). Refer to Annex 1 of the G-StorExptSpecimens for a checklist to be completed by the PI for the proper storage and export of clinical trial samples. As per the G-StorExptSpecimens, the transport of specimens is subject to regulation by the International Air Transport Association.

In cases where investigators are unable to complete all required research tests in Malawi, MWI-14 and MWI-7 state that justification must be provided for the importation and exportation of samples.

Per the G-GenResReqs, the National Health Sciences Research Committee (NHSRC) requires investigators who wish to export biological/genetic materials to apply for a transfer under a material transfer agreement (MTA) that must be reviewed, approved, and signed for by NHSRC. The investigator must provide a satisfactory description of how the privacy and confidentiality of the individuals and communities and the safety of such materials will be maintained. Furthermore, an investigator is not permitted to transfer biological/genetic material to another research group locally and internationally unless NHSRC has approved a collaborative study between the two (2) parties and the material and information provided protects the participants. Additionally, as stated in the SciTechOrder, an NCST-issued license is required for the collection, storage, and use of human samples for research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC requirements described above.

Material Transfer Agreement

MWI-14, MWI-16, and MWI-7 indicate that the PMRA, the NHSRC, and the College of Medicine Research and Ethics Committee (COMREC) must ensure a MTA is in place that includes the following:

Intention of the importation and exportation of samples
Duration and location of storage
Appropriate informed consent authorizing the exportation and importation
Person(s) who will have access to the samples
The controlling officer of the samples
Ownership of the samples
Capacity building (only applicable for MWI-7)

See MWI-14, MWI-16, and MWI-7 for the PMRA, NHSRC, and COMREC MTA forms, respectively.

The G-BioSampCompense also confirms that MTAs remain an instrument to be used by a researcher in requesting the approval of an ethics committee (EC) for the transfer of samples for analysis outside of Malawi.

Other Considerations

According to the G-GenResReqs and MWI-6, COMREC and NHSRC-approved samples can be stored for a maximum of five (5) years during which time all tests/analyses approved for that particular study should be concluded. MWI-6 further states that if the sample is to be used beyond five (5) years, an updated authorization must be provided, which will last another five (5) years before it can be renewed. Per G-BioSampCompense, while samples are primarily allowed to be stored as long as they are needed for the initial study, leftover samples are also permitted to be stored as long as needed for a research endeavor. See G-BioSampCompense for additional details regarding EC approval requirements.

(a)(iv) to (ix)

3, 5, and 7 (Checklist of Required Documents (Fees))

4.12

3, 6.4, and Annex 1

Last content review/update: March 21, 2024

Import/Export

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

Material Transfer Agreement

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

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

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

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

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

Supporting Documents - 22. Material Transfer Agreement

7.5 and Annex 8

Consent for Specimen