Clinical research in Malawi is regulated and overseen by the Pharmacy and Medicines Regulatory Authority (PMRA) and the National Commission for Science and Technology (NCST).

Pharmacy and Medicines Regulatory Authority

As per the PMRAAct, the PMRA is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in Malawi. MWI-47 indicates that in accordance with the PMRAAct, the PMRA has replaced the Pharmacy, Medicines and Poisons Board (PMPB) and the PMRA is currently in the process of developing regulations for the PMRAAct. (Note: While the PMRA continues to update its website and develop new regulations, ClinRegs will continue to reference PMPB documents. New PMRA regulations will be incorporated into the Malawi profile as they become available.)

According to the PMRAAct, the Ministry of Health (MOH) established and manages the PMRA, which is overseen by the Minister of Health. The MOH grants authority to PMRA to monitor the registration and quality of drugs in Malawi. Further, per MWI-45, the PMRA’s registration department registers clinical trials; issues import permits; conducts pharmacovigilance; and registers medicinal products and pharmacy personnel and businesses. The PMRAAct indicates that the PMRA is composed of part-time members appointed by the Minister. See MWI-49 for a list of the current PMRA Board of Directors.

The G-CTARevVacBiol and the G-CTAProcsVacBiol specify that the PMRA must appoint a Clinical Trial Review Committee (CTRC) to review clinical trial applications and make recommendations. The G-CTARevVacBiol delineates that the committee should include, but is not limited to, the following members:

• Medical practitioners
• A pediatrician from the National Health Sciences Research Committee (NHSRC)
• A public health specialist from the College of Medicine Research and Ethics Committee (COMREC)
• An internal medicine specialist
• A biostatistician
• Experts in clinical pharmacology, epidemiology, toxicology and drug safety, biotechnology, virology and microbiology, immunology, bioethics, and veterinary science

The CTRC chairperson should be nominated by the PMRA, and the vice-chairperson should be nominated by the CTRC.

Please note: Malawi is party to the Nagoya Protocol on Access and Benefit-sharing (MWI-3), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see MWI-35.

National Commission for Science and Technology

The SciTechAct and MWI-56 indicate that the NCST appraises, reviews, monitors, and evaluates priority research and development programs, plans, and projects of research and development institutions. The NCST also encourages the use of local expertise in science and technology matters via a set of professional standards, ethics, and guidelines.

As delineated in the SciTechAct and MWI-38, the NCST consists of 15 members:

• One (1) chairperson, appointed by the Minister of Health
• Nine (9) Minister of Health-appointed members with at least six (6) members selected from industry academic, research, and development institutions, as well as one (1) community representative and one (1) gender expert
• Five (5) permanent secretaries or their representatives who are ex-officio members, and represent ministries relevant to science and technology

The NCST Director General acts as the secretary of the commission. In addition, a vice-chairperson is elected by the commission from among its members. An ex-officio member cannot be elected as a vice-chairperson.

For detailed information on the NCST composition and responsibilities, see the SciTechAct, MWI-56, MWI-37, and MWI-38.

Contact Information

Pharmacy and Medicines Regulatory Authority

As per MWI-46, the PMRA contact information is as follows:

Postal Address:

Pharmacy and Medicines Regulatory Authority
P.O Box 30241
Lilongwe, Area 5, Malawi

Physical Address:
Off Paul Kagame Road
Next to MRA Offices
Area 5 Lilongwe

Phone: +265 212 755 165 or +265 212 750 108
Email: info@pmra.mw

National Commission for Science and Technology

Per MWI-57, the NCST contact information is as follows:

Mailing Address:
National Commission for Science and Technology
1st Floor Lingadzi House, Robert Mugabe Crescent
Private Bag B303
Lilongwe 3, Malawi

Phone: +265 1 771 550
Email: infor@ncst.mw

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). (Note: While the PMRA continues to update its website and develop new regulations, ClinRegs will continue to reference PMPB documents. New PMRA regulations will be incorporated into the Malawi profile as they become available.)

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.

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.

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 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.

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.

(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.)

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 sponsor is responsible for paying the following clinical trial fees:

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

Payment Instructions

No information is available regarding instructions for payment of the clinical trial application fee.

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 R-HlthResCoord, the G-HlthResConduct, 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 human research studies. The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of 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-56 indicates that as of July 2022, COMREC is operating under KUHeS and will be changing its name. However, 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.

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. As shown in MWI-27, the ECs’ scope of review includes whether research is in accordance with national policy requirements, procedures, and guidelines for the conduct of health and social sciences, as well as the international guidelines, the Declaration of Helsinki (MWI-42) and The Belmont Report (MWI-23).

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 his/her country prior to submitting an application to the NHSRC or COMREC for ethical review and approval. MWI-28 also indicates that COMREC prefers the investigator apply for ethics approval first from an external/overseas EC.

Per the G-NHSRC and the G-COMREC, the applicable EC will screen submitted applications for completeness, and to 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.

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. 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, he/she 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.

National Health Sciences Research Committee

According to the G-NHSRC and MWI-5, non-Malawian researchers must pay $150 USD and Malawian researchers must pay 500 Malawian Kwacha to the National Health Sciences Research Committee (NHSRC) upon submission of a research proposal. Per MWI-15, Malawian students are required to pay 5000 Malawian Kwacha.

The G-NHSRC and MWI-5 indicate that following the protocol’s approval, the 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-5 further 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

No information is currently available regarding payment instructions for the NHSRC.

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.

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

No information is available on registration, auditing, and accreditation responsibilities by the NCST.

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 attesting that he/she is 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

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.

As stated in the G-HlthResConduct, the applicant is required to 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.

Per MWI-55, applicants should submit research protocols and relevant materials to mohdoccentre@gmail.com. However, MWI-51 indicates that new protocol submissions to the NHSRC should be made through the Proposal Review System. The G-HlthResConduct, the G-NHSRC, and MWI-15 also state that applications should be submitted to the NHSRC at the following address:

The Chairperson
National Health Sciences Research Committee
Ministry of Health
P.O. Box 30377
Lilongwe 3, Malawi

Tel: +265 1 789 400/414, +265 1 726 422/418
Fax: +235 1 789 527/536

According to MWI-15 and MWI-4, 20 copies of the study proposal must be submitted to the NHSRC. Data collection tools and informed consent forms must be provided in both English and Chichewa (or the appropriate local language). MWI-15 further indicates that five (5) copies for Malawian student proposals (up to master’s level) must also be submitted to the NHSRC secretariat for expedited review. Per MWI-51, the submission must be bound as one (1) document, stamped, and signed.

See MWI-15 for the NHSRC Application to Conduct Health Research in Malawi.

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.

The G-COMREC provides the following contact information for COMREC:

College of Medicine Research and Ethics Committee
Private Bag 360, Chichiri
Blantyre 3, Malawi

Tel: +265 1 874 377
Fax: +265 1 874 740
Email: comrec@medcol.mw

MWI-1 indicates that for submissions to COMREC, all documents should be submitted in one (1) PDF file by email to comrec@medcol.mw, 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).

 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: The regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• 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 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 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
• Signed and completed declaration by investigators
• 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
• Completed PMRA Material Transfer Agreement Form on Shipping of Samples (Form CT 12) (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
• Electronic or soft copy of the clinical trial application dossier to be sent to registration@pmra.mw, info@pmra.mw
• Three (3) hard copies of the clinical trial application dossier in a lever arch file to be sent to the PMRA Director General
• Each section of the clinical trial application dossier above should be well demarcated for ease of reference by PMRA reviewers
• 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. See MWI-60 for more details.

Ethics Committee Requirements

National Health Sciences Research Committee

According to the G-NHSRC, MWI-4, MWI-15, and MWI-51, any proposals submitted to the National Health Sciences Research Committee (NHSRC) must be accompanied by the following (Note: The regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• The NHSRC checklist (MWI-4)
• Cover letter from the PI
• The NHSRC application form (MWI-15)
• Research proposal summary, maximum four (4) pages
• Full research proposal (see the G-NHSRC, MWI-4, and MWI-15 for details)
• Data collection instruments in both English and Chichewa (or other appropriate language)
• Informed consent in both English and Chichewa (or other appropriate 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
• Approval certificate from the PMRA where the research involves products such as new pharmaceutical products

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

Please note that while the NHSRC checklist (MWI-4) indicates that PMRA approval must be provided, the R-HlthResCoord states that EC approval must be obtained prior to submitting the clinical trial application to the PMRA.

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-56, 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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• 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.

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.

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.

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). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.

The requirements do not specify a required waiting period following the applicant’s receipt of these approvals.

In addition, as per the PMRAAct and the D-ImprtRelIMPs, the sponsor is required to obtain an import permit for the shipment of the investigational product (IP) to be used in 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 his/her contract research organization must sign an agreement specific to the clinical trial.

Per MWI-56, 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 practices (GCPs), 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.

Safety Reporting Definitions

In accordance with the G-SAEs, 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, the sponsor or the investigator(s) is required to report all SAEs/SADRs that meet the Pharmacy and Medicines Regulatory Authority (PMRA)’s reporting requirements within 24-48 hours of site awareness, and submit the SAE form within three (3) working days. 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 must be submitted within three (3) working days of site awareness.

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 adverse event. 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.

Additionally, per MWI-28, for studies conducted under the College of Medicine Research and Ethics Committee (COMREC)’s jurisdiction, the investigator is responsible for reporting all SAEs within 24 hours of occurrence. Electronic copies can be submitted to the secretariat at comrec@medcol.mw followed by hard copies.

Form Completion & Delivery Requirements

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

The Registrar
Pharmacy and Medicines Regulatory Authority
P.O. Box 30241
Lilongwe 3, Malawi
Tel: 265-1755166/165
Fax: 265-1755204

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)

Interim and Annual Progress Reports

Per MWI-56, 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.

Per MWI-28, the requirement for the investigator to provide research results to COMREC can be fulfilled in the form of a journal article. Additionally, an investigator should complete and submit a COMREC closeout form, which can be accessed from the COMREC secretariat.

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-56, 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, Malawi permits a sponsor to 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.

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-56, 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 to sponsors on investigator and site selection. According to MWI-22:

• 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 of 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.

Per MWI-28, the College of Medicine Research and Ethics Committee (COMREC) requires DSMBs to be instituted for all clinical studies involving humans where:

• The investigation of a research question has direct implications for clinical care or public health, including all Phase III trials
• The population is classified as highly vulnerable
• The clinical trials involve high-risk intervention
• Large multicenter clinical trials are involved

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

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 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-56, 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 he/she will agree to pay compensation to participants and/or his/her 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 his/her participation in a trial
• When a child is injured in utero through his/her mother’s participation 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 him/her 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 at his/her own cost, the opinion of a mutually acceptable independent expert. 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.

Quality Assurance/Quality Control

Per MWI-56, 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

See also MWI-61 for information on Pharmacy and Medicines Regulatory Authority (PMRA) procedures for conducting and reporting Good Clinical Practice (GCP) inspections.

Monitoring Requirements

As part of its quality assurance (QA) 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 his/her own SOPs, the auditor observations are documented, and data are available as needed for the 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).

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. 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.

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 COMREC of the reasons for suspension/termination, and a summary of the results obtained should be communicated to the committee.

Electronic Data Processing System

Per MWI-56, 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.

Responsible Parties

No information is currently available.

Data Protection

No information is currently available.

Consent for Processing Personal Data

No information is currently available.

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-56, 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 contents to be included in the form.)

The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the participant and/or his/her legal representative(s) or guardian(s) 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.

Re-Consent

No information is currently available specifying requirements for re-consent.

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 and/or the participant’s legal representative(s) or guardian(s) 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 he/she is illiterate. However, the script or information sheet to be read to the potential participant must be approved by NHSRC and be signed for by the participant’s legal representative(s) and/or guardian(s).

MWI-22 states that where the participant is illiterate and/or his/her legal representative(s) and/or guardian(s) 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 his/her legal representative(s) and/or guardian(s)
• The participant and his/her legal representative(s) and/or guardian(s), 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 his/her legal representative(s) and/or guardian(s) should receive a copy of the signed and dated ICF.

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 and/or his/her legal representative(s) and/or guardian(s) to waive or to appear to waive his/her 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.

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

Per MWI-56, 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, G-NHSRC-ICF, MWI-22, and MWI-13, the ICF should include the following statements or descriptions, as applicable (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• 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 his/her consent
• The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
• That the participant and/or his/her legal representative(s) or guardian(s) 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, including the last sentence, which should explicitly read “I voluntarily agree”

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

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-56, 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 his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she 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 and/or his/her legal representative(s) or guardian(s) 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 and/or his/her legal representative(s) or guardian(s) 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 his/her 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 his/her health and welfare must take precedence over the interests of science and society.

Per MWI-56, 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 special circumstances, including medical emergencies.

Per MWI-22, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant and/or his/her legal representative(s) or guardian(s), 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 and/or his/her legal representative(s) or guardian(s) 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.

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-56, 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(s) and/or guardian(s) 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.

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 his/her legal representative(s) and/or guardian(s).

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 his/her age, maturity, and psychological state. In certain cases, the NHSRC may regard assent by minors to represent informed consent without requiring the signature from a legal representative(s) and/or guardian(s). 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.

Per MWI-56, 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 minor should be informed about the trial to the extent compatible with his or her understanding and, if capable, he or she should sign and personally date the written informed consent.

Per MWI-56, 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.

Per MWI-56, 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 participant should be informed about the trial to the extent compatible with his or her understanding and, if capable, he or she 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(s) and/or guardian(s) in the form of a signature or thumbprint.

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-56, clinical trials in Malawi are required to follow MWI-22.

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-56, 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 practices (GMPs) and used in accordance with the approved protocol. See MWI-11 for the PMRA’s GMP inspection application form.

Import

The PMRA is also responsible for authorizing the import of IPs. As per the G-CTAProcsVacBiol and the G-CTARevVacBiol, the sponsor may apply for an import permit at the same time that he/she submits the clinical trial application to the PMRA. The G-CTAProcsVacBiol further indicates that the applicant must submit proof of payment of a fee for an application to import IPs for the study, if required.

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.

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-56, 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 Documentation

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 manufacturer to provide the following (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• Evidence of manufacture under conditions compliant with current good manufacturing practices (GMPs)
• A release of specifications and tests, including a Certificate of Analysis (CoA) for each batch of IPs, as well as comparator(s), if applicable
• 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. He/she should provide information on the acceptable storage temperatures and storage conditions.

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

Per MWI-56, 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. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Supply, Storage, and Handling Requirements

Per MWI-56, 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 he/she obtains the Pharmacy and Medicines Regulatory Authority (PMRA) and ethics committee (EC) approvals.

The D-ImprtRelIMPs and MWI-22 indicate that the sponsor must ensure the following (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• IP product quality and stability over the period of use
• IP is manufactured according to any applicable Good Manufacturing Practices (GMPs)
• 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). He/she 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.

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 he/she 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.

In addition, per MWI-28, the College of Medicine Research and Ethics Committee (COMREC) specifically requires investigators wishing to export biological samples to clearly demonstrate that no local capacity is currently available to analyze the 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 an 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.

Material Transfer Agreement

MWI-14, MWI-16, and MWI-7 indicate that the PMRA, the NHSRC, and 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.

In accordance with the G-StorExptSpecimens, the G-NHSRC, the G-HlthResConduct, and MWI-6, prior to collecting, storing, or using a research participant’s specimen(s), written consent must be obtained from the participant and/or his/her legal representative(s) and investigators should comply with internationally accepted ethics guidelines for specimen collection and handling. The G-BioSampCompense also confirms that consent must be obtained.

As per the G-GenResReqs, the G-StorExptSpecimens, and the G-NHSRC, a clear explanation and justification for the collection and import/export of specimens must be provided. The investigator(s) are responsible for clarifying to the participant and his/her legal representative(s) how the sample is to be used, and how the research results might affect their interests. MWI-60 also recommends that the clinical trial protocol submitted to the Pharmacy and Medicines Regulatory Authority (PMRA) include plans for collection, laboratory evaluation, and storage of specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable.

The G-StorExptSpecimens states that consent must also be obtained for sample storage and potential future use.

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. In addition, researchers may use secondary samples with permission of the samples’ custodial entity and if the study receives ethics committee (EC) approval. See G-BioSampCompense additional details regarding EC approval requirements.

Further, the G-GenResReqs, the G-NHSRC, and MWI-6 state that all forms of studies and testing designed to collect and store biological specimens for future unspecified genetic research/analyses, including any scientific retrospective genetic analyses, is not permitted. The G-BioSampCompense also confirms that researchers are not allowed to collect human biological samples for undefined research with the intention of storage for unspecified future use. Furthermore, it states that commercialization of human biological samples is prohibited.

Per the G-NHSRC, investigators should also avoid collecting excess specimens from participants. (See the Required Elements and Participant Rights sections for additional information on informed consent).

The G-GenResReqs states that the investigator(s) must obtain written consent for human genetic research from the participant and his/her legal representative(s). The informed consent form must include statements on what is being studied and why; details about study procedures; known risks, discomforts, and benefits; and alternatives to participation. In addition, the sponsor or the investigator(s) is required to provide the participant(s), the community(ies), or the tribe(s) with detailed information on how their privacy will be protected, and how the confidentiality of obtained information will be maintained. See the G-GenResReqs for consent requirement details.