Clinical Research Regulation For Malawi and Vietnam

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: May 22, 2024

Overview

In accordance with the ClinDrugTrialGCP, PharmLaw-VNM, and ASTTReg, Vietnam’s Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) manages the clinical trial review process for registered and unregistered investigational products (IPs). The ASTT is responsible for reviewing all clinical study documents, and per the ClinDrugTrialGCP, PharmLaw-VNM, the ECReg, and the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), the MOH’s national level ethics committee (EC), the National Ethics Committee in Biomedical Research (NECBR), is responsible for approving the research protocol. The ECReg further indicates that for research involving humans, institutions with ECs are responsible for overseeing an initial ethical and scientific appraisal of the research before it is reviewed by the NECBR. (Note: institutional level ECs are known as Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs) in Vietnam.) For institutions conducting research that do not have a CEBRGL, the review and evaluation of the research is performed by the NECBR or the CEBRGL of another institution with appropriate expertise.

According to the ClinDrugTrialGCP, the ASTT reviews a clinical trial registration dossier submitted by the sponsor, as well as a study approval dossier submitted by the institution. Evidence of institutional EC approval from a CEBRGL is a required element of the study approval dossier, so CEBRGL and ASTT approval cannot be conducted in parallel. Additionally, the NECBR’s review of the protocol is initiated by the MOH as part of the ASTT’s study approval dossier review procedures. Per the ClinDrugTrialGCP and PharmLaw-VNM, ASTT review is finalized once NECBR approval is obtained and the entire study approval dossier is sent to the Minister of Health for final approval. (Note: The ClinDrugTrialGCP and BioequivTrial also refer to the sponsor as “organizations and individuals with clinical reagents” or “donor”.)

As per the ClinDrugTrial and PharmLaw-VNM, the scope of the MOH’s assessment includes all clinical trials (Phases I-IV) for the following:

Drugs that contain a new active ingredient, or products with a new combination of marketed ingredients
Newly developed biologics or biologics with a new combination of marketed ingredients
Newly developed vaccines that are manufactured and used for the first time in Vietnam
Drugs, biologics, and vaccines which have been legally marketed for a period of less than five (5) years in the country of origin (or a country of reference if provided for under international treaties to which Vietnam is a signatory)
Drugs, biologics, and vaccines for which a clinical trial has been conducted, but have not met the MOH’s or internationally recognized good clinical practice (GCP) requirements

In addition, per the TradMedicine, the MOH also reviews and approves traditional medicines to be used in clinical trials (Phases I-IV) unless deemed exempt by the agency. The category of traditional medicine includes drugs developed from a provincial-level scientific research project or higher, drugs that were granted a certificate, or drugs used for treatment at health establishments at a provincial level or higher for 10 years or more and for 200 or more patients. The drugs must also have been approved by a Science and Technology Council or an EC specialized in traditional medicine as effective and safe to treat traditional medical diseases. Traditional medicines also include ancient methods.

For information on bioequivalence trials and testing, see the BioequivTrial and the BioTestReq.

Clinical Trial Review Process

Registration Dossier Review

According to the ClinDrugTrialGCP, the ASTT requires the sponsor to submit a clinical trial registration dossier. Upon receipt of the appropriate files, the ASTT will check the validity of the dossier. If the dossier is incomplete, the ASTT will provide a written notice and specific instructions for the sponsor to supplement the dossier. The sponsor is responsible for coordinating with the ASTT to complete the dossier within a maximum of 60 days from the date of receipt of the written notice. Past this time limit, the submitted application is no longer valid. Following the review of a complete and valid dossier, the ASTT Director will either issue a written approval (see Form 13 in Appendix III of the ClinDrugTrialGCP) or clearly state the reason for disapproval in writing.

See the Submission Process, Submission Content, and Timeline of Review sections for more information on registration dossiers.

Approval Dossier Review

Per the ClinDrugTrialGCP, research institutions must submit dossiers requesting clinical drug trial approval to the ASTT. The ASTT checks the validity of the dossier, and if it is incomplete, the ASTT will provide a written notice and specific instructions for the institution to supplement the dossier. The institution is responsible for coordinating with the ASTT to complete the dossier within a maximum of 60 days from the date of receipt of the written notice. Past this time limit, the research approval procedure must be repeated from the beginning.

The ClinDrugTrialGCP states that following receipt of a complete and valid dossier, the MOH will organize a meeting of the NECBR. After receiving the NECBR’s evaluation report of the research protocol, the ASTT will synthesize and complete the dossier, then submit it to the Minister of Health for approval if the protocol meets the requirements. If the protocol is not approved or needs correction, the ASTT will notify the institution in writing and clearly state the reason. If the protocol needs to be modified, the institution is responsible for coordinating with the ASTT to complete the dossier in up to 90 days from the date of receipt of the written notice. Past this time limit, the protocol approval procedure must be repeated from the beginning.

Procedures for the approval of research protocol amendments follow the same procedure described above for clinical drug trial approval. For more information, see the ClinDrugTrialGCP.

See Submission Process, Submission Content, and Timeline of Review sections for more information on the approval dossier.

Inspection

The BioequivTrial indicates that the ASTT may conduct inspections to ensure the rights and health of participants in the trial, ensure the quality and integrity of the research data, ensure that the responsibilities of stakeholders in the research are implemented in accordance with applicable regulations, and promptly detect violations of the research protocol. The MOH will determine the inspection scale and frequency based on the objective, purpose, design, complexity, blinding technique, scale, and end date of the research. The MOH must send an inspection notice to the sponsor and institution at least five (5) days before the inspection, and the inspection report must be completed and sent to the sponsor and institution within 20 days of the inspection.

Clinical Trial Exemptions

The DrugRgstrtn indicates that based on the opinion of the MOH’s Advisory Council, the Minister of Health may exempt certain new drugs, vaccines, and biological products from one (1) or more phases of a clinical trial (including clinical data exemption or reduction). Registration certificates may be issued with the clinical trial phase exemption in the following cases:

Medicines that meet urgent needs for national defense and security, epidemic prevention and control, and overcoming the consequences of natural calamities and catastrophes in which other drugs are not yet available on the market
The drug has been licensed for circulation by at least one (1) of the reference regulatory agencies specified in Article 2 of the DrugRgstrtn
Medicines used to treat rare and fatal diseases
Vaccines and biological products manufactured in Vietnam in the form of technology transfer in one (1), several, or all phases of the finished product manufacturing process, which have clinical data on the products prior to the technology transfer in compliance with the DrugRgstrtn

See the DrugRgstrtn and the PharmLaw-VNM for more information on drugs that are exempted from a trial or certain phases of a trial.

Article 5

Articles 89 and 94

Articles 2, 13, and 17

Appendix (Articles 1, 8, and 18 and Form 1)

Articles 1 and 7

Articles 19, 21-23, and 29 and Appendix III (Form 13)

Articles 3 and 15

Articles 1-3

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: May 22, 2024

No information is currently available regarding fees required to submit a clinical trial application for authorization to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT).

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: May 22, 2024

New Info (Not Yet in Profile)

Effective February 1, 2025, the Ministry of Health’s Circular No. 43/2024/TT-BYT provides for the establishment, organization, and operation of the National Biomedical Research Ethics Council and the Grassroots Biomedical Research Ethics Council and repeals the ECReg.

Overview

As per the ECReg, the ClinDrugTrialGCP, the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), and PharmLaw-VNM, Vietnam requires institutional and national level ethics committee (EC) approval for clinical trials. According to the ECReg and VNM-12, institutional level EC approval is provided by a Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL). PharmLaw-VNM states that national level EC approval is conducted by the Ministry of Health (MOH)’s National Ethics Committee in Biomedical Research (NECBR).

Ethics Committee Composition

The ECReg details general EC requirements applicable to both the CEBRGLs and the NECBR, as well as specific requirements for each type of EC.

Per the ECReg, EC membership should include the following:

Members with a professional degree in the health sector related to the common research areas assessed by the EC, including at least one (1) person independent from the organization that establishes the EC
Clinical doctors
Members with legal expertise or knowledge of ethical principles in biomedical research, with a university degree or higher
Members with no expertise in the health sector
Members under 40 years of age, members from 40 years old to under 50 years old, and members aged 50 or older
Male and female members (neither gender may be less than 20% of the total membership)

The ECReg further indicates that EC members must have the necessary experience, knowledge, skills, and ability to perform their duties in order to validate the science and protect the interests of research participants. Members with expertise in the health sector must have at least five (5) years of experience working in the field of research assessed by the EC. All members must also have time to participate in and perform the duties of the EC, and keep confidential any information related to the research, opinions discussed during the meeting, commercial secrets of individuals and organizations participating in the study, and personal information about the research participant. Members must also receive training and certification from the MOH or MOH-accredited organizations in Good Clinical Practice (GCP) and the EC’s standard operating procedures (SOPs).

Council of Ethics in Biomedical Research at the Grass Root Level

As explained in the ECReg and the CEBRGLReg, institutional ECs, known as CEBRGLs, should consist of at least five (5) members. The ECReg states that a CEBRGL consists of one (1) chair, one (1) to two (2) vice-chairs, a standing division, and specialized subcommittees (if necessary).

The CEBRGLReg further indicates that CEBRGLs may have at most 11 members. All members must be honest, objective, and have biomedical research ethics knowledge and expertise. The chair and vice-chair should be prestigious scientists.

The ECReg requires that the chair and vice-chairs have at least 15 years of experience working in the field of research evaluated by the EC, a good reputation, and the capacity to independently manage and run the EC. The chair and vice-chairs must also be fair and impartial, and not be pressured by the research institution, investigators, and other agencies, organizations, and individuals. An individual cannot be appointed as the chair of the EC for more than two (2) consecutive terms.

According to the ECReg, a CEBRGL should have no more than two (2) professional secretaries and no more than two (2) administrative secretaries. Professional and administrative secretaries must be honest, objective, and university educated. Furthermore, professional secretaries must have knowledge about scientific and technological management, scientific research, and ethics in biomedical research, while administrative secretaries must have administrative, clerical, and archival skills.

According to the CEBRGLReg, a secretariat based in the host institution’s Science Research Management Office should assist the CEBRGL with application processing and other administrative tasks.

See the ECReg and the CEBRGLReg for additional CEBRGL membership criteria.

National Ethics Committee in Biomedical Research

The ECReg requires the NECBR to have at least nine (9) official members, including one (1) chair, three (3) vice-chairs, and other official members, including professional and administrative secretaries. The NECBR also includes data monitoring and other subcommittees as needed. The Administration of Science, Technology and Training (ASTT) and the MOH act as standing members of the office of the NECBR.

The ECReg requires that the chair and vice-chairs have at least 15 years of experience working in the field of research evaluated by the EC, a good reputation, and the capacity to independently manage and run the EC. The chair and vice-chairs must also be fair and impartial, and not be pressured by the research institution, investigators, and other agencies, organizations, and individuals. An individual cannot be appointed as the chair of the EC for more than two (2) consecutive terms.

According to the ECReg, the NECBR should have no more than three (3) professional secretaries, and two (2) administrative secretaries at most.

The ECReg states that professional and administrative secretaries must be honest, objective, and university-educated. Professional secretaries must have knowledge about scientific and technological management, scientific research, and ethics in biomedical research, while administrative secretaries must have administrative, clerical, and archival skills.

See the ECReg for additional NECBR membership criteria and VNM-1 for the list of 2023-2028 NECBR term members.

Terms of Reference, Review Procedures, and Meeting Schedule

According to the ECReg, both CEBRGLs and the NECBR have five (5) year terms. However, the CEBRGLReg indicates that CEBRGLs have three (3) to five (5) year terms, as specified in the EC’s establishment decision. The ECReg also stipulates that the EC must be established or reorganized at the end of the term. The EC for the next consecutive term must include at least 25% new members.

As stated in the ECReg, EC activities are non-profit. The EC must fully apply the ethical principles prescribed in the ECReg and relevant legal documents, and comply with ethical guidelines of international organizations. The ethical guidelines used by the EC should be clearly stated and disseminated to investigators. In addition, ECs function on the principles of collectivity, democracy, and independence when evaluating research proposals and making decisions. If necessary, ECs may invite an independent consultant to provide a professional opinion to the EC. ECs should also facilitate the coordination of and/or reference the evaluation results of other domestic or foreign ECs.

According to the ECReg, the EC’s decision for a research proposal should be based on the consensus of the EC members and must be recorded in the EC’s meeting minutes. In case it is difficult to reach a consensus, the EC’s chair has the right to decide to immediately commence voting, or request that the principal investigator supplement the research dossier for the EC to consider and vote on during the next EC meeting. Research is approved only when there is no more than one (1) disapproval vote out of the total number of valid votes.

In addition, the ECReg states that ECs must conduct periodic assessments of ongoing studies within a time period that is consistent with the level of risk for study participants, but at least once a year on or before the date the EC approved the research protocol. The conclusion of the periodic assessment results should state that the EC’s previous decisions are still valid, or have been changed, suspended, or revoked.

The ECReg requires that EC members be trained prior to appointment and provided with updated and supplementary training in the ethical and scientific aspects of biomedical research. The head of the organization that establishes the EC is responsible for assigning a unit to manage scientific research activities to develop and deploy training plans for EC members. The updated and supplementary training must be conducted at least once every two (2) years. For more information on training requirements for EC members, see the ECReg.

As set forth in CEBRGLReg, the CEBRGLs should operate within written SOPs to conduct their reviews. The chair oversees the meetings, makes conclusions, and reports this information to the institutional head. Voting members must have no conflict of interest with the research. The CEBRGL members must review research documentation and prepare comments for the secretary prior to the meeting. Most CEBRGLs do not meet regularly but instead meet upon request for review and on the availability of the majority of its members. The CEBRGLs should also refer to the NECBR’s SOPs to develop their own SOPs. See CEBRGLReg for detailed CEBRGL review procedures.

Article 94

Articles 3-4 and Chapters II-III

Appendix (Article 8)

Articles 19 and 22

Articles 3, 5-9, 13, 15, 18, and 21

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: May 22, 2024

Overview

According to the ECReg, the CEBRGLReg, the ClinDrugTrialGCP, and the PharmLaw-VNM, the primary scope of information assessed by 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. The ECs involved in clinical trial approval in Vietnam include institutional level ECs, called Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs), and the Ministry of Health (MOH)’s National Ethics Committee in Biomedical Research (NECBR).

As per the ECReg, the CEBRGLReg, and the PharmLaw-VNM, ECs must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable or those with limited or no legal capacity. The ECReg further indicates that when considering research related to vulnerable groups, representatives of the research participants or experts with knowledge and experience working with the groups must participate in the EC meeting. (See the Vulnerable Populations; Children/Minors; and Pregnant Women, Fetuses & Neonates sections for additional information about these populations.)

The ECReg and the CEBRGLReg also state that CEBRGLs and the NECBR are responsible for ensuring independent, timely, and competent reviews of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, and methods; and verifying the adequacy of confidentiality and privacy safeguards. See the ECReg and the CEBRGLReg for detailed ethical review guidelines.

The ECReg indicates that when ECs conduct research record evaluations, ongoing research supervision, and research results evaluations, they should evaluate the following:

Research design and conduct
Potential risks and benefits
Selection of research populations and participant selection and protection
Financial benefits and financial costs related to research participants
Protecting the research participants’ privacy and confidentiality
The process of providing information and obtaining participants’ written consent to participate in research
Impact of research on the participants’ community
Researcher capacity and research goal

Role in Clinical Trial Approval Process

As delineated in the ClinDrugTrialGCP, the MOH’s Administration of Science, Technology and Training (ASTT) is responsible for reviewing the clinical trial registration and study approval dossiers for completeness. Evidence of institutional EC approval from a CEBRGL is a required element of the study approval dossier, so CEBRGL and ASTT approval cannot be conducted in parallel. Additionally, the NECBR’s review of the protocol is initiated by the MOH as part of the ASTT’s study approval dossier review procedures. Per the ClinDrugTrialGCP and the PharmLaw-VNM, the ASTT’s review is finalized once NECBR approval is obtained and the entire study approval dossier is sent to the Minister of Health for final approval.

The ECReg indicates that for research involving humans, institutions with ECs are responsible for overseeing an initial ethical and scientific appraisal of the research before it is reviewed by the NECBR. For institutions conducting research that do not have a CEBRGL, the review and evaluation of the research is performed by the NECBR or the CEBRGL of another institution with appropriate expertise.

The ECReg indicates that ECs may assess a research dossier or application under an expedited process if:

The research involves minimal risk
The research documents have been previously reviewed by an EC
The research documents have been reviewed and approved by an EC of the same level
It is a periodic report on implementation of research that has already been approved
It is an application for amendment and supplementation of a research protocol that has already been approved
It is reporting adverse events occurring in research that has already been approved
It is reporting violations of an approved research protocol

According to the ECReg, research dossiers are reviewed under the EC’s full process if they do not qualify for expedited review as stipulated above, or if the evaluator requests that the dossier be examined according to the full process. The EC’s decision under the full review process is legally valid when at least five (5) members (including at least one (1) member with appropriate expertise in the health sector, one (1) member with no expertise in the health sector, and one (1) independent member), including members of both sexes, are present at the EC’s meeting and vote in the decision. The meeting must also have been convened by the EC’s chair or vice-chair (if authorized), and record meeting minutes. The EC's expedited review process decision is legally valid when at least two (2) members of the EC have reviewed and evaluated the dossier. See the Timeline of Review section for more information on the expedited and full review processes.

According to the ECReg, the EC must send a written notification of its evaluation to the leading research institution and principal investigator (PI), and publish the evaluation results on a bulletin board or on the website of the EC or the organization that established the EC. The EC may approve, conditionally approve, or decide not to approve a research dossier, and the written notifications must be issued accordingly.

Per the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), for administrative changes to the clinical trial protocol, the research institution must report in writing to the ECs at all levels and the ASTT. Changes that do not affect the health and interests of trial participants, or the research designs, processes, and procedures, must be approved by the CEBRGL and the NECBR. The application and evaluation process are carried out in accordance with the provisions of the ECReg. Changes affecting the health and interests of trial participants, or the research designs, processes, and procedures, must be approved by competent regulatory agencies. The application for approval of changes and procedures must comply with the ClinDrugTrialGCP. See the ECReg and the ClinDrugTrialGCP for more information.

For internal NECBR forms and documents, see VNM-3.

According to the BioequivTrial, ECs may also conduct periodic or unscheduled inspections. The sponsor and EC should determine the scale and frequency of the inspections based on the objectives and design of the research. The purpose of the inspection should be to evaluate trial conduct and PI/study team compliance with the protocol, standard operating procedures (SOPs), good clinical practices (GCPs), and other applicable regulatory requirements. The sponsor or the EC must send an inspection notice to the institution and PI at least five (5) days before the inspection, and the inspection report must be completed and sent to the institution and PI within 20 days of the inspection.

The ECReg indicates that ECs must conduct periodic reviews of ongoing studies within a time period that is consistent with the level of risk for study participants, but at least once a year on or before the date the EC approved the research protocol. The conclusion of the periodic review results should state that the EC’s previous decisions are still valid, or have been changed, suspended, or revoked. Circumstances for unscheduled reviews include:

Modification of the protocol that has the potential to affect the rights, safety, and/or interests of the research participants or investigators
A serious adverse event related to the research or the research product
Discovery of new facts or information that could affect a potential benefit or risk of harm related to the study
A request to suspend all or a portion of the study by the sponsor or regulatory agency

Articles 90 and 94

Articles 5 and 8-9

Appendix (Articles 8 and 18)

Articles 2, 19, and 22-23

Articles 3, 15-21, and 24

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: May 22, 2024

As stated in the ECReg, ethics committees (ECs) should indicate the fee structure (if any) required to assess a proposed study. Fee requirements should be included in the written instructions provided to investigators for submitting research dossiers for evaluation. The head of the organization that establishes the EC is responsible for allocating sufficient resources for the EC to perform its duties effectively.

According to VNM-12, the Ministry of Health (MOH)’s National Ethics Committee in Biomedical Research (NECBR) and institutional level ECs (known as Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs)) charge a fee to review clinical trial documentation. The current NECBR and CEBRGL fees are $1,000-$2,000 USD.

Articles 12 and 22

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: May 22, 2024

Overview

According to the ECReg, the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) is responsible for registering the institutional level ethics committees (ECs), known as Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs) in Vietnam.

Registration, Auditing, and Accreditation

The ECReg indicates that the ASTT is responsible for maintaining a list of ECs on the ASTT website. The ASTT must update the list within 15 days from the date of receiving a notice of establishment from the EC. ECs are periodically inspected by the ASTT to ensure that they comply with the requirements specified in the ECReg. If the EC is found to be noncompliant, the ASTT will withdraw the EC’s name from the updated list on the website. The ASTT may suspend, or propose suspension to a competent authority, of an EC’s operation in case it is found that the EC violates the provisions of the ECReg, affecting the protection of rights, safety, and health of research participants.

Article 27

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: May 22, 2024

New Info (Not Yet in Profile)

Effective February 1, 2025, the Ministry of Health’s Circular No. 43/2024/TT-BYT provides for the establishment, organization, and operation of the National Biomedical Research Ethics Council and the Grassroots Biomedical Research Ethics Council and repeals the ECReg.

Overview

In accordance with the ClinDrugTrialGCP, PharmLaw-VNM, and ASTTReg, Vietnam requires the applicant to obtain clinical trial authorization from the Ministry of Health (MOH). The Administration of Science, Technology and Training (ASTT) is the department within the MOH that manages the clinical trial review process. As delineated in the ClinDrugTrialGCP, the MOH’s national level ethics committee (EC), the National Ethics Committee in Biomedical Research (NECBR), must also approve the research protocol.

As per the ClinDrugTrialGCP, evidence of institutional EC approval from a Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL) is a required element of the study approval dossier submitted to the ASTT, so CEBRGL and ASTT approval cannot be conducted in parallel. Additionally, the NECBR’s review of the protocol is initiated by the MOH as part of the ASTT’s study approval dossier review procedures. Per the ClinDrugTrialGCP and the PharmLaw-VNM, ASTT review is finalized once NECBR approval is obtained and the entire study approval dossier is sent to the Minister of Health for final approval.

Regulatory Submission

According to VNM-12, the registration dossier and the study approval dossier should be submitted to the MOH’s ASTT at the address found in VNM-11:

Ministry of Health
Administration of Science, Technology and Training
No. 138B Giang Vo
Ba Dinh District
Hanoi City, Vietnam

As per the ClinDrugTrialGCP, the sponsor must submit, directly or via post, one (1) copy of the clinical trial registration dossier signed by the sponsor’s representative(s) to the ASTT. Separately, research institution(s) must submit one (1) copy of the study approval dossier, signed by the principal investigator (PI) and the head of the testing facility, directly or via post to the ASTT. See Appendix III of the ClinDrugTrialGCP for the registration form and the forms that comprise the study approval dossier. (Note: The ClinDrugTrialGCP also refers to the sponsor as “organizations and individuals with clinical reagents” or “donor” throughout the document.)

As delineated in the ClinDrugTrialGCP, the clinical trial application and accompanying material must be provided in Vietnamese or English. If the document is not available in Vietnamese or English, a notarized translation of the document must be provided in Vietnamese or English. The ClinDrugTrialGCP also indicates that the Investigator’s Brochure (IB) summary (also referred to as the research product profile in Vietnam) submitted to the MOH with the registration application should be in Vietnamese or in English with a supplementary summary in Vietnamese. See the Submission Content section for detailed information on documentation to be submitted.

Ethics Review Submission

As per VNM-12, the application for NECBR approval should also be submitted at the address found in VNM-11:

Ministry of Health
Administration of Science, Technology and Training
No. 138B Giang Vo
Ba Dinh District
Hanoi City, Vietnam

VNM-12 indicates that for NECBR review, the applicant must submit four (4) copies of the relevant documents directly or via post to the ASTT. Except for the IB, the Certificate of Analysis, and the good manufacturing practices (GMP) certificate, which may be in English, all relevant documents must be submitted in Vietnamese.

According to the ECReg, ECs issue their own guidelines for research evaluation submissions, providing information and regulatory forms for investigators. See the Submission Content section for the minimum requirements of the EC evaluation guidelines.

Article 94

Articles 19-22 and Appendix III (Forms No. 6 and 7)

Articles 15 and 22

Articles 1-3

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: May 22, 2024

Regulatory Authority Requirements

As per the ClinDrugTrialGCP, the following documentation must be submitted to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) for clinical trial registration dossiers:

Clinical trial registration application form signed by a representative of the sponsor (See Form No. 6 in Appendix III of the ClinDrugTrialGCP)
Summary of the Investigator’s Brochure (IB) (also referred to as the research product profile in Vietnam) including general information about the clinical reagent (name, ingredients, indications, physical properties, chemistry, preparation, and other relevant information), pre-clinical research materials, and clinical trial study documents from previous phases

For clinical trial study approval dossiers, the ClinDrugTrialGCP indicates that the following documentation must be submitted to the MOH’s ASTT:

Clinical trial approval application form signed by the principal investigator (PI) and the head of the research institution (See Form No. 7 in Appendix III of the ClinDrugTrialGCP)
Full IB, including proof of compliance with Good Laboratory Practices (GLPs) for research institutions or proof of compliance with Good Manufacturing Practices (GMPs) (also referred to as good medicine production standards in Vietnam) for drug manufacturers, and proof of compliance with quality testing requirements from national inspection agencies or ex-warehousing certificates for vaccine or biological batches (Refer to the Quality Requirements section for detailed IB requirements)
A copy of the written approval for clinical trial registration from the MOH’s ASTT
For phase IV clinical trials, a certified or notarized copy of the written request for phase IV clinical drug testing from the respective regulatory authorities
A certified or notarized copy of the research institution’s certificate of eligibility for pharmaceutical business
Certification of participation by all study sites for multicenter research studies in Vietnam
A certified or notarized copy of the approval from the People’s Provincial Committee (for community-based studies)
Contract/agreement between the sponsor and the host institution; and contract/agreement between sponsor and the contract research organization (CRO), if applicable
Explanation of study protocol (See Form No. 8 in Appendix III of the ClinDrugTrialGCP)
Case report form (CRF)
PI’s Curriculum Vitae (CV) and a copy of the Good Clinical Practice (GCP) certificate issued by the MOH or an institution recognized by the MOH
Informed Consent Form (ICF) (See Form No. 9 in Appendix III of the ClinDrugTrialGCP) (See also the Required Elements section for additional information)
Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL) evaluation report
Investigational product (IP) labeling

See the ClinDrugTrialGCP for detailed requirements.

Ethics Committee Requirements

The ECReg indicates that both the institutional level ethics committees (ECs) (CEBRGLs) and the national EC (National Ethics Committee in Biomedical Research (NECBR)) issue guidelines for research evaluation submissions, providing information and regulatory forms for investigators. The guidelines include information on the following:

Name and address of the secretary, employee, or member of the EC receiving the application file, or address of the website (if any)
List of all written material in record
Specifications of the documents
Language of the document in the record
Number of copies to be submitted
Application deadline compared to evaluation date
Recording and notification processes for invalid documents
Estimated time for post-assessment decision announcement
The timeframe that should be followed if the EC requires the applicant to provide additional information or documents
Evaluation fee of research records (if any)
Procedures for requesting EC approval of an amendment of the outline or related documents
Specification of materials for selection, information, and consent to participate in the study

According to ECReg, the documents that ECs must review when evaluating a research proposal include:

Signed and dated application, including signatures of co-applicant and representative of the relevant organization
Research protocol (with version number and date), with documents and appendices (if any)
A summary of the study in simple and understandable language
Description of ethical considerations relevant to the study (may be included in the protocol); measures that will be taken to protect participant privacy and data confidentiality; protective care for participants; compensation to be provided to participants; and insurance package for participants (if applicable) (See the Required Elements and Participant Rights sections for detailed information)
IB
Study data collection forms (with version numbers and dates)
Forms, documents, and advertisements used in the participant selection process
ICF (with version number and date) for participants that are 18 years or older and have full civil capacity to give consent
ICF (with version number and date) for participants and their parents and/or legal guardian(s), if the participant is 16 years old to under 18 years old
ICF (with version number and date) for parents and/or legal guardian(s), if the participant is under 16 years old
Assent form (with version number and date) for participants who do not have the capacity to give legal consent, including children from 12 years old to under 16 years old, a person with inadequate civil act capacity, or a patient in a limited cognitive condition
Description of participant selection and ICF collection processes
Procedures for monitoring, evaluating, and managing adverse events (AEs) (See the Safety Reporting section for additional AE/serious adverse event information)
All previous decisions of other ECs or regulatory authorities regarding the proposed study (including decisions and reasons for objecting or proposing amendments to the previous protocol)
Documents demonstrating that the research institution has agreed to allow the study after the regulatory authority’s approval (if the study is conducted outside the organization that established the EC)
Investigators' commitment to agree to comply with the ethical guidelines
The PI’s current scientific background and qualifications related to the relevant research

See the ECReg for additional information on documentation requirements for research protocol re-evaluation or amendments, as well as for evaluation applications for periodic reports, AE reports, protocol violation reports, and research result reports.

Clinical Protocol

As per the ClinDrugTrialGCP, the MOH requires the following elements to be included in a protocol submission:

Title
Protocol code
Duration
Management level (state/ministry/institution/province)
PI/co-investigator(s) names and contact information
Funding
Phase requested
Institution to conduct research
Sponsor and contact information
Situation of domestic and foreign research
Objectives
Methodology (including trial design, random selection method, and standard operating procedures (SOPs) for each research technique)
Participant selection/withdrawal
Participant treatment
AE reporting requirements (See the Safety Reporting section for additional information)
Laboratory test methods
Ethical considerations
Inspection and monitoring
Post study medical care
Study team training
International cooperation
Implementation progress
Format of the expected results
Activities of coordinating organizations

See Appendix III in the ClinDrugTrialGCP for a copy of the full form.

Article 19 and Appendix III (Forms No. 6, 7, 8, and 9)

Articles 22-23

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: May 22, 2024

Overview

As per the ClinDrugTrialGCP, evidence of institutional ethics committee (EC) approval from a Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL) is a required element of the study approval dossier submitted to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT), so CEBRGL and ASTT approval cannot be conducted in parallel. Additionally, the National Ethics Committee in Biomedical Research (NECBR)’s review of the protocol is initiated by the MOH as part of the ASTT’s study approval dossier review procedures. Per the ClinDrugTrialGCP and the PharmLaw-VNM, ASTT review is finalized once NECBR approval is obtained and the entire study approval dossier is sent to the Minister of Health for final approval.

Regulatory Authority Approval

Registration Dossier Review

As delineated in the ClinDrugTrialGCP, the ASTT initially checks the validity of the sponsor-submitted registration dossier (which includes the registration application form and Investigator’s Brochure (IB) summary) within five (5) working days from the date of receipt of the application. If any issues are identified, the ASTT will issue a written notice to the sponsor, who must coordinate with the ASTT to complete the dossier within 60 days of receipt. Past this time limit, the submitted application is no longer valid. The ASTT Director will issue a written decision within five (5) working days of receiving a complete and valid dossier.

Approval Dossier Review

The ClinDrugTrialGCP indicates that research institutions must submit dossiers requesting clinical drug trial approval to the ASTT. The ASTT checks the validity of the study approval dossier within five (5) working days from the date of receipt of the application. If any issues are identified, the ASTT will issue a written notice to the institution, which must coordinate with the ASTT to complete the dossier within 60 days of receipt. Past this time limit, the research approval procedure must be repeated from the beginning.

The ClinDrugTrialGCP states that within 25 days of receiving a complete and valid study approval dossier, the MOH will organize a meeting of the NECBR. Within five (5) working days after receiving the NECBR’s evaluation report, the ASTT gathers all materials related to the dossier and submits it to the Minister of Health for approval.

If the research protocol is not approved or needs to be corrected, the ASTT must notify the institution and state the reason, as per the ClinDrugTrialGCP. The institution must coordinate with the ASTT to complete the dossier within 90 days from the date of the notice. Past this time limit, the protocol approval procedure must be repeated from the beginning. Within five (5) working days after receiving the completed research protocol in accordance with the written notice, the ASTT gathers all materials related to the dossier and submits it to the Minister of Health for approval.

Ethics Committee Approval

The ECReg indicates that ECs issue their own guidelines for research evaluation submissions, providing information and regulatory forms for investigators. The guidelines include information regarding the application deadline in relation to the evaluation date, the expected timeframe for notification of a decision, and the timeframe to follow if the EC requires applicants to submit additional information or documents. See the Submission Content section for detailed information on minimum requirements for the EC guidelines.

According to VNM-12, the review and approval process for CEBRGLs takes 30 days. Meetings are scheduled upon request and are based on the availability of the majority of its members.

The ECReg indicates that under both the expedited and full review processes, within 30 days from the date of receipt of a complete and valid dossier, the EC must organize an examination of the dossier and notify the applicant of the EC’s decision. While both processes may take up to 30 days, the expedited review is streamlined with fewer reviewers.

According to the ECReg, within five (5) working days from the date that the research dossier evaluation results are available, the EC must send a written notification to the leading research institution and principal investigator, and publish the evaluation results on a bulletin board or on the website of the EC or the organization that established the EC.

See Scope of Review section for details on the EC’s role in the clinical trial approval process.

Article 94

Articles 19 and 21-22

Articles 15, 20, 22, and 24

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: May 22, 2024

Overview

As delineated in the ClinDrugTrialGCP, the PharmLaw-VNM, and the ASTTReg, a clinical trial can only commence in Vietnam after authorization from the Ministry of Health (MOH) has been received. The MOH’s Administration of Science, Technology and Training (ASTT) manages the clinical trial review process. The ClinDrugTrialGCP indicates that the ASTT is responsible for reviewing the clinical trial registration and study approval dossiers. The MOH’s national level ethics committee (EC), the National Ethics Committee in Biomedical Research (NECBR), is responsible for approving the research protocol. Once the ASTT has completed its review and the NECBR has reviewed and approved the research protocol, the Minister of Health must give final approval to the entire study approval dossier. The ECReg further indicates that for research involving humans, institutions with ECs are responsible for overseeing an initial ethical and scientific appraisal of the research before it is reviewed by the NECBR. (Note: institutional level ECs are known as Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs) in Vietnam.) For institutions conducting research that do not have a CEBRGL, the review and evaluation of the research is performed by the NECBR or the CEBRGL of another institution with appropriate expertise.

As per the ExprtImprtMeds, an import license must be obtained for the shipment of an investigational product (IP) to be used in the trial from the MOH’s Drug Administration of Vietnam (DAV). See the Manufacturing & Import section for additional information.

Clinical Trial Agreement

As per the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), the sponsor is required to enter an agreement with the participating principal investigator (PI)/host institution(s) before the trial begins to demonstrate the financial agreement between the parties. The PharmLaw-VNM also states that the sponsor is required to sign a clinical trial contract with the investigator(s).

Clinical Trial Registration

According to VNM-12, the ASTT encourages the sponsor and the PI to register their study with the United States National Institutes of Health’s ClinicalTrials.gov (VNM-13).

Articles 92 and 94

Appendix (Article 8 and Form 1)

Articles 19 and 21-22

Articles 3 and 15

Article 3

Articles 1-3

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: May 22, 2024

Safety Reporting Definitions

As delineated in the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP) and the AERprtingD62, the following definitions provide a basis for a common understanding of Vietnam’s safety reporting requirements:

Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence (including any signs, symptoms, illnesses, or test results) in a participant to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product
Serious Adverse Event (SAE) – Any untoward medical occurrence that may lead to death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or permanent incapacity, creates a congenital anomaly/birth defect, or requires appropriate medical intervention to prevent the aforementioned situations or medically important event
Unexpected AE – AEs in which the essence, severity, specificity, or consequences are different or have not been recorded or considered in the study protocol or relevant study documents

Also, according to VNM-12, the Ministry of Health (MOH) uses the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (VNM-5) to define its safety reporting terminology.

Safety Reporting Requirements

Investigator Responsibilities

As per the BioequivTrial and the AERprtingD62, the principal investigator (PI) is responsible for detecting and settling SAEs and updating AE/SAE information to ensure the timeliness of reporting and the safety of the research participants. The PI is required to report to the sponsor, the institutional ethics committee (EC), also known as a Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL), the MOH’s National Ethics Committee in Biomedical Research (NECBR), the MOH’s Administration of Science, Technology and Training (ASTT), and the National Centre for Drug Information and Adverse Drug Reaction Monitoring (National DI and ADR Centre).

The ECReg further states that the NECBR is responsible for assessing the PI's recording, reporting, and handling of AEs occurring during the study.

The BioequivTrial indicates that depending on the type of AE/SAE, the PI must comply with the following reporting requirements:

Fatal or life-threatening SAEs in Vietnam: A report, in accordance with Form 4 in the Appendix of the BioequivTrial, must be submitted to the NECBR, the ASTT, and the National DI and ADR Centre within seven (7) working days from the date of receiving information about the SAE. Updates on the SAE must be provided in additional reports until the participant recovers or stabilizes.
SAEs that are not fatal or life-threatening in Vietnam: A report, in accordance with Form 4 in the Appendix of the BioequivTrial, must be submitted to the NECBR, the ASTT, and the National DI and ADR Centre within 15 working days from the date of receiving information about the SAE.
Non-serious AEs occurring in Vietnam: The AEs must be recorded and summarized in a periodical report, and reported in the full results of the trial research results to the NECBR and the ASTT.

The BioequivTrial indicates that in the event of fatal or life-threatening AEs/SAEs, the PI and the host institution are required to suspend the trial immediately, provide care and treatment to the participant(s), overcome and resolve the consequences, and document the events. According to the AERprtingD62, the PI must also document any deaths. The BioequivTrial and the AERprtingD62 further indicate that the PI and the host institution must report these events to the CEBRGL, the NECBR, the ASTT, and the National Center of DI and ADR.

For AEs that cause harm to the participant’s health, the BioequivTrial and the AERprtingD62 indicate that the PI is responsible for treating and following up on the participant’s health until the person is stable.

According to the BioequivTrial, the PI should provide periodic updates regarding AEs/SAEs to the sponsor, the CEBRGL, the NECBR, the ASTT, and the National Center of DI and ADR. If the extent and frequency of AEs/SAEs exceeds the allowable limit, investigators may propose to the sponsor, EC, and competent regulatory authority that the clinical trial be suspended.

The BioequivTrial and the AERprtingD62 indicate that all the following must be reported:

SAEs occurring at study sites in Vietnam
SAEs occurring at study sites outside of Vietnam in a multicenter Vietnamese study that lead to cessation/suspension of the study or a change in the protocol
All other AEs occurring in clinical drug trials at study sites in Vietnam

Sponsor Responsibilities

Per the BioequivTrial and the AERprtingD62, the sponsor must coordinate with the PI to report AEs/SAEs occurring at study sites in Vietnam to the CEBRGL, the NECBR, the ASTT, and the National Center of DI and ADR. The sponsor must collect AE/SAE data.

For SAEs occurring at study sites outside of Vietnam in a multicenter Vietnamese study, the BioequivTrial states that the sponsor must report to the NECBR, the ASTT, and the National Center of DI and ADR within 10 working days from the date of a decision to stop/suspend the study, withdraw participants from the study, or change the research protocol.

In addition, the AERprtingD62 requires that the sponsor report findings from clinical studies, epidemiology studies, in vitro studies, and other information that may lead to an important risk of the investigational product.

Form Completion & Delivery Requirements

Per the BioequivTrial, SAEs in Vietnam should be reported using a Reporting Form for SAEs in Clinical Trials (Appendix, Form 4).

1, 5.16-5.17, and 7

1-3

Appendix (Articles 1 and 19-20, and Form 4)

Article 15

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: May 22, 2024

Interim and Annual Progress Reports

The BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP) indicates that investigators are responsible for providing periodic and unscheduled reports.

According to the ECReg, progress reports submitted to ethics committees (EC) for evaluation must contain the following:

Summary of research protocol
Complete research protocol, including previously approved revisions, if applicable
Reports on research progress
Reports on the number of participants who were selected for the study, completed the study, and withdrew from the study
Detailed report on adverse events (AEs) and issues causing risks to participants, if applicable
Summary of relevant information, especially safety information
Current informed consent form (ICF)
Independent inspection report of investigator and sponsor
Notice of principal investigator (PI) or sponsor regarding early suspension/termination or completion of the study, if applicable

Final Report

The BioequivTrial and the ClinDrugTrialGCP indicate that the PI, the sponsor, and the host institution are responsible for submitting a final report to the Ministry of Health (MOH) when a study is completed. The final report, which must include an analysis of the data and information on AEs/serious adverse events (SAEs), must be submitted in accordance with Form No. 12 in Appendix III of the ClinDrugTrialGCP. The BioequivTrial further states that the clinical trial results must be made public within three (3) years from the date of issuance of the competent authorities' decision approving the results, and should comply with applicable copyright regulations.

Appendix (Articles 5, 20, and 23 and Form 3)

Appendix III (Form No. 12)

Article 23

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: May 22, 2024

New Info (Not Yet in Profile)

Effective February 1, 2025, the Ministry of Health’s Circular No. 43/2024/TT-BYT provides for the establishment, organization, and operation of the National Biomedical Research Ethics Council and the Grassroots Biomedical Research Ethics Council and repeals the ECReg.

As per the ECReg and the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), the sponsor is defined as an individual, entity, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. (Note: The ClinDrugTrialGCP and the BioequivTrial also refer to the sponsor as “organizations and individuals with clinical reagents” or “donor”.)

In addition, per the PharmLaw-VNM, the sponsor may select a qualified contract research organization (CRO) (also known as a research support organization in Vietnam) to run the clinical trial. The ClinTrialSup defines a CRO as an organization with the legal status to operate in the field of clinical trial research support and that is staffed with appropriately qualified personnel.

According to the ClinTrialSup, CROs may perform clinical research support activities such as implementing sponsors’ clinical research responsibilities, carrying out administrative support activities, and conducting clinical research monitoring. The ClinDrugTrialGCP indicates that a cooperative contract should exist between the sponsor and a CRO, if applicable. According to the PharmLaw-VNM, a sponsor and the CRO may be domestic or foreign.

In addition, as per the ClinTrialSup, CROs are also responsible for registering their organizations with the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT). Before implementing any activities in support of a clinical trial, a CRO must submit a registration dossier and the applicable forms for approval. The CRO is also required to report annually on its clinical research activities to the MOH’s ASTT. (See the ClinTrialSup for detailed information on clinical trial research support activities and the related registration forms.)

Articles 1 and 92

Articles 3, 9-11, 15, and 17, and Appendix I (Forms No. 1-2)

Appendix (Article 1)

Article 19

Article 2

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: May 22, 2024

Overview

As set forth in the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP) and PharmLaw-VNM, the sponsor is responsible for selecting the investigator(s), the principal investigator (PI), the consultant experts, and the research institutions, taking into account the appropriateness and availability of the study site and facilities.

As stated in the BioequivTrial, all investigators must possess appropriate qualifications, training, and experience. All investigators involved in the trial must obtain completion certificates for a good clinical practice (GCP) course and a safety reporting course, each to be updated every three (3) years, from the Ministry of Health (MOH) or an authorized training facility.

See the BioequivTrial for information on PI and investigator rights and responsibilities.

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor requirements.

Data and Safety Monitoring Board

According to VNM-12, there are no requirements for establishing a Data and Safety Monitoring Board (DSMB). However, the MOH’s National Ethics Committee in Biomedical Research (NECBR) may recommend the establishment of a DSMB.

Multicenter Studies

The BioequivTrial states that for multicenter studies, in addition to analyzing general research results, it is necessary to conduct a separate analysis of key safety and efficacy variables on Asian or Vietnamese research populations using drugs for which racial factors are considered to have an effect on efficiency and safety. Furthermore, per the ClinDrugTrialGCP, the clinical trial study approval dossier must include documentation certifying the participation of research institutions in multicenter studies in Vietnam.

Article 92

Appendix (Articles 3, 5-6, 16, and 23)

Article 19

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: May 22, 2024

Insurance

According to VNM-12, there is no specific Vietnamese guidance that addresses indemnity agreements between the sponsor and the contract research organization (CRO), investigator(s), or institution(s). However, the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP) lists an insurance contract as an essential document to be obtained by the principal investigator (PI), institution, and sponsor before conducting a clinical trial. The purpose of the insurance contract is to ensure that research participants will be compensated in the event of a trial-related injury.

Compensation

Injury or Death

As specified in the PharmLaw-VNM, the sponsor is responsible for providing compensation to research participants in the event of trial-related injuries. The BioequivTrial also states investigators are responsible for compensating participants when an adverse event that seriously impacts the participant’s health was caused by the investigator’s violation of the research protocol.

Trial Participation

According to the BioequivTrial, payment and compensation, if any, to clinical trial participants must be clearly indicated in the research protocol. Per the ECReg, ethics committees (ECs) must consider the amount and method of payment to ensure that there is no coercion or influence on the voluntariness of participants. Payments should be made according to each visit.

Article 92

Appendix (Articles 5-6 and 21, and Form 1)

Article 17

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: May 22, 2024

Quality Assurance/Quality Control

As stated in the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), the sponsor is responsible for assigning a monitor to assist in maintaining a quality assurance (QA) system with written standard operating procedures (SOPs) that ensure trials are conducted and data are generated, recorded, and reported in compliance with the protocol. In addition, the quality management system applied in clinical trials must meet International Organization for Standardization (ISO) 9001-equivalent standards or higher.

Per the BioequivTrial, the principal investigator (PI) is responsible for ensuring the accuracy, truthfulness, confidentiality, integrity, and verifiability of the research data. Correction of data must be in accordance with applicable regulations: without deleting the original data, the assigned researcher must name, sign for confirmation, and specify the date of correction. The lead investigator must submit an encrypted list of trial participants to the regulatory agency after the clinical trial ends. The retention and submission of the list of participants after decryption must be kept secret.

The trials should be conducted in compliance with good clinical practice (GCP) principles and standards outlined in the ClinDrugTrialGCP and the BioequivTrial Appendix, which are based on the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (VNM-5) and the World Health Organization’s (WHO) Guidelines for Good Clinical Practice for Trials on Pharmaceutical Products (Please refer to Annex 3 of The Use of Essential Drugs: Sixth Report of the WHO Expert Committee for these guidelines (VNM-10)).

Monitoring Requirements

As part of its QA system, the BioequivTrial states that the sponsor should assign a monitor to inspect the trial. The sponsor should appoint individuals who are independent from the trial and are qualified by training and experience to conduct inspections, in accordance with the ClinTrialSup. The ClinDrugTrialGCP further indicates that SOPs, the monitoring/inspection plan, and procedures must also be submitted to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT).

For information on ASTT and ethics committee (EC) monitoring responsibilities, see the Scope of Assessment and Scope of Review sections.

Premature Study Termination/Suspension

According to the BioequivTrial, the sponsor may terminate a trial early if the sponsor learns of any serious protocol violations that seriously affect the health of trial participants, or, the accuracy and truthfulness of the data during an inspection. The sponsor should send notices to the Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGL), the MOH’s National Ethics Committee in Biomedical Research (NECBR), and the relevant authority, in addition to notifying the institution and PI.

Annex 3 (Guidelines for Good Clinical Practice for Trials on Pharmaceutical Products)

Article 3

Appendix (Articles 15, 17, and 18 and Forms 1-2)

Article 4 and Appendix III (Form No. 8)

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: May 22, 2024

Electronic Data Processing System

According to the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), when using electronic trial data processing systems, the sponsor should use appropriate data handling programs and have adequate standard operating procedures (SOPs) for these systems. In addition, per the ClinDrugTrialGCP, the research institution’s general documentation must include a brief description of any electronic document system in its technical and professional standards, if applicable.

Records Management

As per the BioequivTrial, all information on clinical trials must be recorded, handled, managed, and kept in accordance with applicable regulations in order to accurately report, interpret, monitor, and check the accuracy and reliability of clinical trial information and data. Research institution facilities for storing clinical trial records and documents must ensure confidentiality; restricted access; fire and explosion prevention and control; and avoidance of adverse effects of light, temperature, humidity, and penetration of insects and other animals. In addition, research dossiers and documents should be archived and preserved according to the contract between the sponsor and the institution. For research and development of new products, documentation needs to be kept for at least 10 years.

Appendix (Articles 2, 14, 15, and 22)

Appendix II

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: May 22, 2024

Responsible Parties

Per Decree13, the personal data controller is an organization or individual that decides the purposes and means of processing personal data. The personal data processor is an organization or individual that performs data processing on behalf of the data controller, through a contract or agreement with the data controller. An organization or individual that both decides the purposes and means for, and directly processes, personal data is referred to as a personal data controller and processor.

Decree13 states that the personal data controller must:

Implement organizational and technical measures, as well as appropriate safety and security measures, to prove that data processing activities have been carried out in accordance with Decree13, reviewing and updating these measures as necessary
Record and store a system log of personal data processing
Notify the Ministry of Public Security (MPS) of violations of regulations on protection of personal data as prescribed in Decree13
Select a personal data processor in accordance with a clear mandate and work only with a personal data processor that has appropriate safeguards in place
Ensure the rights of data subjects as prescribed in Decree13

Additionally, Decree13 indicates that the personal data processor must:

Only receive personal data after having a contract or agreement on data processing with the personal data controller, and process personal data in accordance with the contract or agreement
Fully implement measures to protect personal data specified in Decree13 and other relevant legal documents
Delete and/or return all personal data to the personal data controller after finishing data processing

According to Decree13, both the personal data controller and processor are also responsible to the data subject for damages caused by the processing of personal data. In addition, they must cooperate with the MPS and competent state agencies in protecting personal data by providing information for investigation and handling of violations of Decree13.

Per VNM-8, the MPS is responsible for protecting the rights of data subjects against violations of Decree13, and for maintaining the National Information Portal on Personal Data Protection (VNM-7). See VNM-7 for additional personal data protection resources.

Data Protection

Per Decree13, organizations and individuals involved in personal data processing must apply personal data protection measures to prevent unauthorized collection of personal data from translation systems and equipment. It is illegal to set up software systems, enact technical measures, or organize activities of collecting, transferring, buying, and selling personal data without the consent of data subjects.

According to Decree13, personal data protection measures must be applied from the beginning and throughout the processing of personal data, including management, technical, investigational, and procedural measures. Network security for the data processing system, as well as the means and equipment, must be checked before processing data, irrecoverably deleting data, or destroying devices containing personal data.

Decree13 states that in the case of sensitive personal data, a department with the function of protecting personal data must be designated, personnel in charge of personal data protection must be appointed, and information about the department and individual in charge of personal data protection must be exchanged with the agency specializing in personal data protection (e.g., MPS). Additionally, data subjects must be notified that their sensitive personal data is being processed.

Decree13 states that if a violation of Decree13 has been detected, the personal data controller/personal data controller and processor must notify the MPS’s Department of Cybersecurity and Prevention within 72 hours after the violation occurs using Form No. 03 (see Appendix of Decree13 or VNM-9). If the notification is submitted after 72 hours, the reason for the late notice must be attached. Additionally, the personal data processor must notify the personal data controller of the violation as quickly as possible. See Decree13 and VNM-9 for more information on notification requirements for violations of personal data protection regulations.

Consent for Processing Personal Data

Decree13 delineates that a data subject’s consent is only valid when the data subject voluntarily and clearly knows the type of personal data to be processed; the purpose of processing personal data; that organizations and individuals are allowed to process the personal data; and the rights and obligations of data subjects. The data subject’s consent must be expressed clearly, specifically in writing, by voice, by ticking the consent box, in the syntax of consent via text message, by selecting consent technical settings, or through another action that demonstrates consent. When there are multiple purposes for the data collection, the personal data controller/personal data controller and processor must list the purposes for the data subject to agree to one (1) or more of the stated purposes, and consent must be given for each purpose. The data subject’s consent must be expressed in a format that can be printed or reproduced in writing, including in electronic or verifiable formats. Silence or non-response of the data subject is not considered as consent, and the data subject may give partial or conditional consent. The data subject’s consent is valid until the data subject decides otherwise or when the competent state agency requests in writing.

Per Decree13, data subjects also have a right to: be aware of data processing activities; access their data; delete data; restrict data processing; provision of data; object to data processing; complain, denounce, and initiate lawsuits; claim damages; and self-defense. For the processing of sensitive personal data, the data subject must be informed that the data to be processed is sensitive personal data.

Decree13 states that in certain cases, the data subject’s consent is not required for the processing of personal data. This includes urgent cases where it is necessary to immediately process relevant personal data to protect the life and health of the data subject or others, and in the event of a state of emergency on national defense, security, social order and safety, major disasters, or dangerous epidemics.

See Decree13 for more details on obtaining consent from data subjects; the rights of data subjects; and situations where consent is not required for the processing of personal data.

Withdrawal of Consent

According to Decree13, withdrawal of consent must be in a format that can be printed or reproduced in writing, including in electronic or verifiable format. Upon receiving a request from a data subject to withdraw consent, the personal data controller/personal data controller and processor must notify the data subject of possible consequences and damages that may occur when consent is withdrawn. The personal data controller, personal data processor, personal data controller and processor, and any third parties must stop, and request any relevant organizations and individuals to stop, processing the data of the data subject that has withdrawn consent. Withdrawal of consent does not affect the legality of the data processing that was agreed to prior to the withdrawal.

Children

Per Decree13, children’s personal data must be processed in accordance with the principle of protecting the rights and ensuring the best interests of the children. The processing of children’s personal data must have the consent of the child if the child is seven (7) years of age or older, as well as the consent of the parent(s) or legal guardian(s). The personal data controller, personal data processor, personal data controller and processor, and any third parties must verify the age of the children before processing the children's personal data. The relevant parties must stop processing the children’s personal data and/or irreversibly delete or destroy the children’s personal data in the following cases:

The data was processed for improper purposes, or the purpose of processing personal data with the consent of the data subject has been fulfilled, unless otherwise provided for by law
The child’s parent(s) or legal guardian(s) withdraws consent for the processing of the child’s personal data, unless otherwise provided for by law
At the request of a competent authority when there are sufficient grounds to prove that the processing of personal data affects the children’s legitimate rights and interests, unless otherwise provided for by law

Articles 2, 9, 11-12, 17, 20, 22-23, 26-28, and 38-39 and Appendix (Form No. 03)

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: May 22, 2024

New Info (Not Yet in Profile)

Effective February 1, 2025, the Ministry of Health’s Circular No. 43/2024/TT-BYT provides for the establishment, organization, and operation of the National Biomedical Research Ethics Council and the Grassroots Biomedical Research Ethics Council and repeals the ECReg.

Obtaining Consent

In all Vietnamese clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the ClinDrugTrialGCP, the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), and the PharmLaw-VNM. As per the ClinDrugTrialGCP, the BioequivTrial, and the ECReg, the informed consent form (ICF) is viewed as an essential document that must be sent to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) as part of the clinical trial study approval dossier, for which the Minister must issue final approval.

The ECReg indicates that a research proposal involving humans, including the ICF, must undergo ethical and scientific review by the MOH’s National Ethics Committee in Biomedical Research (NECBR) and an institutional level ethics committee (EC) (known as a Council of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs)).

The BioequivTrial states that the principal investigator (PI) or the clinical testing facility is responsible for obtaining written consent from trial participants before carrying out any study procedures.

As per the ECReg, the ICF should be provided in easy-to-understand language, suitable for potential research participants to support their ability to give fully informed consent. For participants with limited education, the ICF should be provided and explained verbally. According to the BioequivTrial and the ECReg, the information should also be presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The ClinDrugTrialGCP further states that the participant or legal representative/guardian should also be given the opportunity to ask questions about the research, and given adequate time to consider whether to participate.

Re-Consent

No information is currently available on re-consent.

Language Requirements

As delineated in the ClinDrugTrialGCP, the clinical trial application and accompanying material must be provided in Vietnamese or English. If the document is not available in Vietnamese or English, a notarized translation of the document must be provided in Vietnamese or English.

VNM-12 indicates that the ICF content should be presented in Vietnamese and English for global clinical studies, but for studies with domestic sponsors, only Vietnamese is required. The English copy serves as a reference to the NECBR. The study information sheet should be in Vietnamese.

Documenting Consent

As per the ClinDrugTrialGCP, the BioequivTrial, the ECReg, and the PharmLaw-VNM, the participant or the legal representative/guardian must sign and date the ICF. No information is provided in these sources concerning copies to be issued to the participant or legal representative/guardian.

Waiver of Consent

The ECReg indicates an EC may waive the requirement for written voluntary consent from research participants if the study requires absolute confidentiality. The EC’s decision to waive the voluntary written consent requirement must consider the benefits and risks of the study to the participants, as well as measures to protect the rights and safety of the participants.

Articles 90 and 91

Appendix (Forms 1-2)

Articles 19-20 and 22 and Appendix III (Form No. 9)

Articles 2, 15-17, and 23

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: May 22, 2024

Based on the ClinDrugTrialGCP, the informed consent form (ICF) should include the following statements or descriptions, as applicable:

Description of research with an explanation of its purpose and objectives
Expected duration of study
Research methods to be followed
Inclusion and exclusion criteria for research participants
Identification of investigator(s) who will be responsible for assessing confidential medical information to select study participants
Number of participants involved in the study
Description of any foreseeable risks to the participant
Any expected benefits to the participant and/or the community, and any study-related payment to the participant
Alternative procedures or treatment that may be available to the participant
The extent to which confidentiality of records identifying the participant will be maintained
Selection of those parties who will be able to access, inspect, supervise and monitor the participant’s records
Compensation and/or medical treatment available in the event of a trial-related injury
Person(s) to contact for further information regarding the trial and the rights of trial participants and whom to contact in the event of trial-related injury
Statement that participation is voluntary and the participant may withdraw at any time for any reason

See Form No. 9 in Appendix III of the ClinDrugTrialGCP for a copy of the ICF.

Compensation Disclosure

Per the ECReg, ethics committees (ECs) must ensure that information relating to payment for study participants, including the method, amount, and payment schedule, is included in the ICF and other documents given to participants.

Articles 19 and 22 and Appendix III (Form No. 9)

Article 17

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: May 22, 2024

Overview

In accordance with the ClinDrugTrialGCP, Vietnam’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.

The Right to Participate, Abstain, or Withdraw

As stated in the ClinDrugTrialGCP and the PharmLaw-VNM, the participant or the legal representative/guardian should be informed that participation is voluntary and that the participant may withdraw from the research study at any time for any reason without being held liable.

Additionally, the PharmLaw-VNM states that participants have the responsibility to comply with investigators’ instructions according to approved clinical trial documents.

The Right to Information

As per the ClinDrugTrialGCP and the PharmLaw-VNM, 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, and any compensation or treatment in the case of injury.

The Right to Privacy and Confidentiality

According to the ClinDrugTrialGCP and the PharmLaw-VNM, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The ClinDrugTrialGCP states that the research participant or legal representative/guardian should be provided with contact information for a person to contact regarding trial-related inquiries.

Furthermore, the PharmLaw-VNM states that the participant has the right to file a complaint or lawsuit against any illegal acts committed by the sponsor or investigator.

The Right to Safety and Welfare

As set forth in the ECReg, the risks to the research participant must take precedence over any anticipated benefits to the participant and the interests of society.

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

Articles 90 and 91

Appendix III (Form No. 9)

Article 17

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: May 22, 2024

The ECReg indicates an ethics committee (EC) may waive the requirement for written voluntary consent from research participants for research in emergency situations where the participant or the legal representative/guardian cannot voluntarily agree to participate in the study. The EC’s decision to waive the voluntary written consent requirement must consider the benefits and risks of the study to the participants, as well as measures to protect the rights and safety of the participants.

Article 16

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: May 22, 2024

Overview

As per the ECReg and VNM-4, in all Vietnamese clinical trials, research participants selected from vulnerable populations must be provided additional protections by the ethics committee and the investigator(s) to safeguard their health and welfare during the informed consent process. VNM-4 characterizes vulnerable populations as those incapable of giving consent, which may include children, pregnant women, people with mental disabilities, people living with HIV/AIDS, people who are illiterate, prisoners, detainees, sex workers, and other special populations.

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

Approval of Protocol, Monitoring and Evaluation, Final Review, and Dissemination of Research and Ethical Aspects of Biomedical Research

Article 17

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: May 22, 2024

According to ChildLaw, a child is someone under 16 years of age.

As set forth in the PharmLaw-VNM, when the participant is a minor, informed consent must be obtained from the legal representative/guardian.

Per the ECReg, signed informed consent forms (ICFs) are required for:

The parent/legal guardian, if the participant is under 16 years old
The participant and the parent/legal guardian, if the participant is 16 years old to under 18 years old
Participants that are 18 years or older and have full civil capacity to give consent

Assent Requirements

The ECReg further specifies that a signed assent form is required for participants who do not have the capacity to give legal consent, including children from 12 years old to under 16 years old. The assent form should contain information similar to an ICF, but be simpler, shorter, and easier to understand. For participants from seven (7) years old to under 12 years old, the assent form content should be provided and explained verbally.

Article 90

Chapter I (Article 1)

Articles 2 and 23

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: May 22, 2024

The PharmLaw-VNM states that for studies involving women who are pregnant or breastfeeding, the rationale for participant selection and appropriate protection measures for these participants must be clearly stated in the study approval dossier.

Article 90

Prisoners

Last content review/update: August 29, 2024

No information available regarding consent requirements for prisoners.

Last content review/update: May 22, 2024

No information is currently available.

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: May 22, 2024

The ECReg states that a signed assent form is required for participants who do not have the capacity to give legal consent, including people with inadequate civil act capacity or in a limited cognitive condition. The assent form should contain information similar to an informed consent form (ICF), but be simpler, shorter, and easier to understand.

Article 2

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: May 22, 2024

The ClinDrugTrial defines an investigational product (IP) as a pharmaceutical product, biomedical product, vaccine, traditional medicine, or herbal medicine that contains a new active ingredient or substance, or a product with a new combination of already marketed pharmaceutical substances.

Chapter II (Article 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: May 22, 2024

Manufacturing

As set forth in the PharmLaw-VNM, Decree54, and the ClinDrugTrialGCP, the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) has overall responsibility for authorizing the manufacture of all drug products. According to VNM-4, once the ASTT reviews and the Minister of Health approves the study approval dossier, the Drug Administration of Vietnam (DAV) coordinates with the ASTT to review and approve the investigational product (IP) for manufacture or import.

In addition, the ClinDrugTrialGCP states that IPs which are under review for phase IV clinical trials require a certified or notarized copy of the written request for phase IV clinical drug testing from the respective regulatory authorities.

Import

As delineated in the ExprtImprtMeds, the MOH’s DAV is responsible for authorizing the import and export of drugs in Vietnam. According to ExprtImprtMeds, IPs for use in clinical trials are categorized as finished drugs without registration numbers. Once the MOH approves the study approval dossier, an import permit application must be submitted to the MOH’s DAV for approval of the IP. The import permit is valid for one (1) year.

The PharmLaw-VNM further indicates that a drug/medicinal ingredient that does not have a certificate of free sale must be licensed for import with a quantity not exceeding that which is written on the import license when it is to be used in a clinical trial, a bioequivalence study, a bioavailability assessment, or as a sample for registration, testing, scientific research, or display at a fair or exhibition.

The ExprtImprtMeds and Decree54 require the following documents to be included in an import permit dossier (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Import order form (three (3) copies)
Copy of study protocol approved by the MOH
A Certificate of Pharmaceutical Product (CPP) (may be substituted with a Free Sale Certificate (FSC) or Good Manufacturing Practice (GMP) certificate)
The importer’s document bearing the importer’s seal, specifying the purposes and quantity of imported drugs and commitment to use the drugs for its intended purposes
Quality standards and testing methods
Drug label(s) and instruction manual(s) with importer seal (See the Labeling section for detailed labeling requirements)
Preclinical and clinical records for drug(s) containing new pharmaceutical substances, or drug(s) with new combinations of circulating pharmaceutical substances, and an information sheet on placebo’s composition, if applicable

According to the ExprtImprtMeds, dossiers and documents attached to the order form must be prepared on size A4 paper and bound into a solid set. The records must be arranged in the order of the table of contents, with separation between the sections. The separators must be numbered for easy reference and must be affixed for certification by the importing enterprise on the first page of each section of the entire dossier and must have a cover page clearly stating: the name of the importer, order number, date of order, and type of order. The application for foreign drug import must be written in Vietnamese or English. If the application is written in English, the information in the package insert must be written in Vietnamese, except for the following information that may be written in other languages with Latin origin:

Brand name, generic name, or international generic name of the drug
International generic or scientific name of ingredient or ingredient quantity of the drug in case it cannot be translated into Vietnamese
Name and address of the foreign enterprise that manufactures or franchises the drug

The MOH’s DAV will review and approve the import permit application within 15 working days from the date of receipt. According to VNM-12, however, the DAV review and approval process may take two (2) to eight (8) weeks if the DAV requires further clarification on the application. See the ExprtImprtMeds for applicable forms.

Please note: Vietnam is party to the Nagoya Protocol on Access and Benefit-sharing (VNM-2), 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 VNM-6.

Approval of Protocol, Monitoring and Evaluation, Final Review; Procedures for Manufacture and Import of Medicinal Drugs for Clinical Research

Chapter II (Article 10) and Chapter V Section 2 (Article 60)

Article 19

Chapter I (Articles 4-5), Chapter III (Articles 11 and 17), and Annex I (Form 11a)

Articles 1 and 73

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: May 22, 2024

Investigator's Brochure

According to the BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP), the Investigator’s Brochure (IB) is considered an essential document to submit before a clinical trial may be conducted. Vietnam requires the sponsor to submit a summary of the IB to the Ministry of Health (MOH)’s Administration of Science, Technology and Training (ASTT) in the clinical trial registration dossier. Research institutions are required to submit the full IB to the ASTT in the study approval dossier. (Note: The ClinDrugTrialGCP and the BioequivTrial also refer to the sponsor as “organizations and individuals with clinical reagents” or “donor”.)

As per the ClinDrugTrialGCP and the BioequivTrial, the IB contains information and data about preclinical research and clinical trials on the investigational product(s) (IPs). The IB also demonstrates that clinical information related to the IP has been provided to the principal investigator (PI).

As specified in the ClinDrugTrialGCP, the IB must provide coverage of the following areas:

Information about the IP, including the ingredients, production processes, and quality standards
For pharmaco-chemical drugs, pharmaceutical drugs, traditional medicines: proof of compliance with Good Laboratory Practices (GLPs) for research institutions or proof of compliance with Good Manufacturing Practices (GMPs) (also referred to as good medicine production standards in Vietnam) for drug manufacturers
For vaccines: proof of compliance with quality testing requirements from national inspection agencies or ex-warehousing certificates for vaccine or biological batches
Preclinical research documents for the IP: research reports on pharmacological effects, toxicity, safety, recommendations on dosage, route of administration, and usage
Clinical research papers from the previous phases (if clinical trials are recommended in the next phase and the IP is not subject to exemption from previous phases)

Quality Management

The ClinDrugTrialGCP specifies that the IPs must be manufactured in a GMP-certified facility. The research institutions must also include a copy of the GMP certificate in the study approval dossier that is submitted to the ASTT.

(See the Product Management section for additional information on IP supply, storage, and handling requirements).

Appendix (Form 1)

Articles 3, 19, and 22

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: May 22, 2024

Investigational product (IP) labeling in Vietnam must comply with the requirements set forth in PharmLaw-VNM. Per VNM-12, the requirements in Articles 7 and 8 of the MedLabel should also be applied to IP labeling.

According to the MedLabel, the outer packaging label of the drug must show the following:

Drug name
Dosage form
Ingredients, content, and volume or concentration of pharmaceutical ingredients and medicinal materials in the drug formula
Packaging specifications
Indications, usage, and contraindications of the drug
Circulation registration number or import license number (if any)
Production batch number, date of manufacture, expiry date of the drug, quality standards, and drug storage conditions
Signs to note and recommendations when using the drug
Name and address of the drug manufacturing facility
Name and address of the import facility (for imported drugs)
Origin of the drug

Additionally, as stated in the MedLabel, the intermediate packaging label of the drug must contain at least the following information:

Drug name
Production batch number
Expiry date

As set forth in PharmLaw-VNM, the IP must also be clearly labeled with the wording: “Products used for clinical trials. Use for other purposes is prohibited.” While there is no specified language requirement for IP labeling in the regulatory resources, according to VNM-12, this wording should be in Vietnamese. A sample IP with the label in the smallest packed unit must also be included in the study approval dossier.

(See the Product Management section for additional information on IP supply, storage, and handling requirements).

Article 88

Articles 7-8

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: May 22, 2024

Supply, Storage, and Handling Requirements

The BioequivTrial (which amends Appendix I of the ClinDrugTrialGCP) indicates that at the end of a clinical trial, the principal investigator (PI) must inventory the investigational product (IP). The sponsor is responsible for storing the IP and for working with the host institution to withdraw and destroy the unused or remaining products, in accordance with applicable regulations.

Record Requirements

As stated in the BioequivTrial, the sponsor and the PI are responsible for filing the following essential documents before the trial begins and during the conduct of the trial:

Sample(s) labels attached to IP container(s) (only the sponsor is required to file this information)
Instructions for handling IPs and trial-related materials (if not included in protocol or Investigator’s Brochure (IB))
Shipping records for IP- and trial-related materials

In addition, the sponsor and the PI are responsible for maintaining records of handling instructions and shipping records for IPs and trial-related materials.

Appendix (Article 22 and Forms 1-2)

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: May 22, 2024

In Vietnam, as per Decree89 and the MgmtInfctSpcmn, specimens are defined as human blood, serum, plasma, urine, feces, human body fluids, and other specimens that contain infectious substances and microorganisms pathogenic to humans. In addition, as per the MgmtInfctSpcmn, infectious substances are those that are known or expected to contain pathogens affecting humans, and are classified as Category A and B. Category A specimens are those capable of causing life-threatening diseases, death, or permanent disability to humans when they are exposed (see Appendix I of the MgmtInfctSpcmn). Category B specimens are those not listed in Category A. Specimens are also referred to as “medical microbiological samples” in Decree89.

Chapter I (Article 2) and Appendix I

Article 2

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: May 22, 2024

Import

As set forth in the MgmtInfctSpcmn, the Ministry of Health (MOH)’s General Department of Preventive Medicine (DPM) is responsible for regulating the transportation of infectious specimens.

According to Decree89, samples of medical microorganisms, biological products, tissues, and organs transported across the Vietnamese border must be medically declared (See Form No. 13 in the Decree89).

VNM-12 further states that an import license from the DPM is required only if the specimens are infectious. Decree155Amend requires that application dossiers for the import of infectious specimens include:

A written request for the grant of an import license
A copy of the competent agency’s approval permitting the implementation of a valid research project, a copy of the approved project proposal or project document, or a copy of the valid written agreement between domestic and foreign establishments regarding the import of specimens
A declaration regarding compliance with applicable biosafety standards

As delineated in Decree155Amend, establishments applying for import permits must submit their dossiers directly or by post to the MOH. If there is no request to amend or supplement the dossier, the MOH must grant the import license within 15 days from the date of receipt of the application. See Decree155Amend for additional information on import licensing procedures.

Export

Per VNM-12, no license is required for the export of specimens.

Chapter III (Article 11) and Appendix II

Article 15

Article 34 and Appendix (Form No. 13)

Consent for Specimen