Regulatory Authority
Ethics Committee
Clinical Trial Lifecycle
Sponsorship
Informed Consent
Investigational Products
Specimens
Quick Facts
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. In accordance with the PMRAAct, the PMRA replaced the Pharmacy, Medicines and Poisons Board (PMPB) in 2019.
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. 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.
Per MWI-47, the PMRA regulates clinical trials and issues import and export permits. MWI-36 specifies that the Clinical Trial Review Committee (CTRC), a sub-committee of the Medicines Committee, advises the PMRA on matters related to authorization and monitoring of clinical trials.
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-24 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 stated in the SciTechOrder, an NCST-issued license is required for research activities involving humans; research involving clinical trials; research activities of multicentered research; the collection, storage and use of human samples for research; the accreditation of research institutions; and the establishment of an institutional research ethics committee (EC). Additionally, per MWI-26, research conducted in Malawi is approved through the NCST’s established and recognized ECs, which include the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC). The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC and COMREC approvals.
For detailed information on the NCST composition and responsibilities, see the SciTechAct, the SciTechOrder, MWI-24, MWI-26, MWI-37, and MWI-38.
Contact Information
Pharmacy and Medicines Regulatory Authority
As per MWI-46, the PMRA contact information is as follows:
Pharmacy and Medicines Regulatory Authority
Off Paul Kagame Road, Area 5
P.O. Box 30241
Lilongwe 3, Malawi
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
Pharmacy Board of Sierra Leone
As per the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in the country. SLE-22 states that the PBSL was originally established through an Act of Parliament in 1988, and re-established in 2001 by the PDA2001, to regulate pharmaceutical products, medical devices, cosmetic chemical substances, food and dietary supplement and herbal products, the practice of pharmacy, and any other related matters. The PBSL operates within the Ministry of Health and Sanitation (MoHS). Per SLE-13, the PBSL is responsible for the safety, efficacy, and quality of all locally manufactured, imported, exported, distributed, sold or used drugs, medical devices, cosmetics, and nutritional agents.
Per the G-SLAppClinTrial, the PBSL monitors a clinical trial from beginning to end in order to ensure adequate protection of the general public against the risk of adverse events from authorized clinical trials. The PBSL also conducts on-site inspections of the clinical trial site, sponsor, or manufacturing facilities to ensure the safety of clinical trial participants, the quality and reliability of data obtained in a trial, and that the facilities used continue to be acceptable throughout the clinical investigation.
The G-SLAppClinTrial requires that the PBSL establish an Expert Committee on Pharmacovigilance and Clinical Trials to provide support in reviewing and authorizing clinical trial applications, and to give medical and scientific opinions on issues related to clinical trials and medicines safety. The PBSL acts as the Secretariat for the committee. For more information, see the G-SLAppClinTrial.
SLE-15 indicates that the PBSL’s Pharmacovigilance and Clinical Trials department is responsible for ensuring that the PBSL’s legal obligations in relation to drug safety are fulfilled in accordance with PDA2001.
Other Considerations
Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), 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 SLE-18.
Contact Information
According to the PBSL website, the contact information for the PBSL is as follows:
Pharmacy Board of Sierra Leone
Central Medical Stores Compound
New England Ville, Freetown
P.M.B. 322
Sierra Leone
Phone: +232 73994830 and +232 99117117
Email: info@pharmacyboard.gov.sl; registrar@pharmacyboard.gov.sl
SLE-4 provides the following details for the Pharmacovigilance and Clinical Trials Department:
Head of Department: Pharm. Onome Abiri Thomas
Phone: +232 78534757
Overview
In accordance with the PMRAAct, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for reviewing and approving clinical trial applications for new drugs, generic drugs, and imported drugs to be registered in Malawi. The PMRA has replaced the Pharmacy, Medicines and Poisons Board (PMPB).
The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.
As per the SciTechOrder, an NCST-issued license is required for research activities involving humans; research involving clinical trials; and research activities of multicentered research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC and COMREC approvals. See the Scope of Review section for information on NHSRC and COMREC approvals of the aforementioned research activities.
Clinical Trial Review Process
According to MWI-50, the PMRA receives clinical trial applications through the office of the Director General, and the applicant must submit evidence of ethical clearance from either the NHSRC or COMREC.
Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs. The G-CTARevVacBiol and the G-CTAProcsVacBiol indicate that upon receipt of a clinical trial application, the PMRA initially screens the application for completeness and assigns a PMRA reference number to the application. According to the G-CTARevVacBiol, the result of the screening will be communicated, and the screening form will be forwarded by fax, to the applicant. The applicant will forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert, or to an evaluator for scientific review.
The G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection.
MWI-50 further specifies that the PMRA may grant full or conditional approval depending on the nature of the CTRC’s findings. Depending on the study’s risk profile, the PMRA may conduct post-authorization good clinical practice (GCP) inspections for select clinical trials. Per the G-CTARevVacBiol, if the application is neither approved nor rejected, the PMRA’s technical staff will communicate its recommendation to the applicant. The response from the applicant will be considered at the PMRA’s subsequent scheduled meeting, and the subsequent decision will be communicated to the applicant. If changes must be made to the protocol, investigator’s brochure, or any other document, the amended document should be submitted with the applicant’s response.
The G-CTAProcsVacBiol states that the applicant may appeal a rejection decision, providing additional information, or amending the application to meet the PMRA’s requirements. The appeal will be referred to the CTRC for a final recommendation to the PMRA.
Per MWI-61, the PMRA may conduct GCP inspections during ongoing clinical trials to provide real-time assessment of the investigator’s conduct of the trial and protection of participants. Clinical trial sites may be inspected before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. See MWI-61 for more information.
(See the Submission Process and Timeline of Review sections for details on the administrative and technical processing and review timelines. See also the G-CTARevVacBiol and the G-CTAProcsVacBiol for more information on the PMRA’s review procedures.)
Overview
In accordance with the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for reviewing, evaluating, and approving applications for clinical trials using registered and unregistered investigational products (IPs). The scope of the PBSL’s assessment includes all clinical trials (Phases I-IV). As delineated in the G-SLAppClinTrial, clinical trial application submissions to the PBSL and the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.
Clinical Trial Review Process
As set forth in the G-SLAppClinTrial and the SL-GCPs, the PBSL coordinates the clinical trial application process. The SL-GCPs states that the sponsor/principal investigator (PI) must apply to the PBSL for approval to conduct a trial for a non-registered drug or a registered drug for new indications. The PBSL is responsible for reviewing the study design, which involves reviewing all significant ethical questions. The PBSL does a thorough scientific review of all applications for clinical trials to be conducted in Sierra Leone. According to the G-SLAppClinTrial, the PBSL must issue a Clinical Trial Certificate to authorize the initiation and conduct of the clinical trial.
As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance, and the applicant must address formal grounds for non-acceptance. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. During evaluation, additional documents or changes may be requested through a query letter. Once a query has been raised and issued to the applicant, the process stops until the PBSL receives a written response to the query. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.
The G-SLAppClinTrial indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. If the amendments are substantial and are likely to have an impact on the safety of the trial participants, or are likely to change the interpretation of the scientific documents in support of the conduct of the trial, the sponsor must notify PBSL of the reasons for, and the content of, the amendments. For more details on amendment requirements, see the G-SLAppClinTrial.
According to the G-SLAppClinTrial, the Clinical Trial Certificate must be renewed annually with an application for renewal to the PBSL. A Clinical Trial Certificate will be revoked if conditions for which the certificate was issued are violated.
The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The applicant must give grounds for review for each reason given in the clinical trial rejection. The grounds for the request must be based on the information that was submitted in the application. Upon review of the appeal application, the PBSL must provide the appeal application decision in writing, including a statement of reasons (e.g., findings, references to evidence, and reasons for the decision). For more information on appeal contents and timelines, see the G-SLAppClinTrial.
The G-SLInspect indicates that clinical trial inspections through on-site visits form part of the PBSL’s monitoring activities. Periodic good clinical practice (GCP) inspections of trial sites are conducted to ensure that the facilities used continue to be acceptable throughout the clinical investigation. The inspections may be carried out randomly and/or for specific reasons and are either announced or unannounced. An inspection would consist of a comparison of the procedures and practices of the PI with the commitments set out in the protocol and reports submitted to the PBSL by the investigator or the sponsor. See the G-SLInspect for more information.
Expedited Review During a Public Health Emergency
According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. This will allow for a review team to be assembled and plans to be made to manage the workload as well as interactions with other oversight bodies such as the SLESRC. To ensure a rapid start of the clinical study, the PBSL will conduct simultaneous review, rather than sequential review, of the application with the SLESRC. For more information on expedited review, see the G-SLAppClinTrial.
Other Considerations
The G-SLAppClinTrial indicates that the PBSL may accept the decisions or scientific opinions of other national regulatory authorities, regional bodies, and international bodies if the IP or trial has been authorized by:
- International Council for Harmonisation (ICH) founding regulatory members
- ICH standing regulatory members
- ICH regulatory members
- ICH legislative and administrative authorities
- The African Vaccine Regulatory Forum (AVAREF) at a joint review meeting facilitated by the World Health Organization (WHO) with the provision of a favorable scientific opinion
- Any other regulatory decision deemed appropriate by the PBSL
According to the G-SLAppClinTrial, the PBSL may also consider an application for joint or assisted review by multiple national regulatory authorities and ECs for certain medical products of high public health value to countries on the African continent. For more information, see the G-SLAppClinTrial.
For information on applications involving biosimilar products, see the G-SLBiosimilar.
Pharmacy and Medicines Regulatory Authority
According to the PMRAAct, a person who intends to conduct a clinical trial must apply to the Pharmacy and Medicines Regulatory Authority (PMRA) for a clinical trial certificate upon payment of the prescribed fee.
Per the PMRAFeesRegs, the following fees apply to clinical trials:
- Application, review, and registration: 5% of total budget
- Annual renewal: $2,200 USD
- Amendments: $300 USD
As delineated in the PMRAFeesRegs, a fee equaling 6% of the total invoice value must also be paid for the importation of unregistered medicines or allied substances from authorized sources. The G-ImpExpMP further indicates that this fee is subject to change from time to time.
Payment Instructions
No information is available regarding payment instructions.
National Commission for Science and Technology
No information is available regarding fees for the National Commission for Science and Technology (NCST).
Pharmacy Board of Sierra Leone
As per the G-SLAppClinTrial, the applicant is responsible for paying a non-refundable fee to the Pharmacy Board of Sierra Leone (PBSL) to submit a clinical trial application for authorization. As delineated below, the authorization fees for foreign sponsored clinical trials of therapeutics, vaccines, and other biological products are as follows:
- Industry Funded (Phase I): $6,500 USD
- Industry Funded (Phase II): $6,500 USD
- Industry Funded (Phase III): $7,000 USD
- Research Institution Funded: $5,000 USD
- Protocol Amendment: $1,000 USD
- Expedited Protocol Review: $1,200 USD
- Renewal of Clinical Trial Certificate (yearly): $100 USD
For locally sponsored clinical trials of therapeutics, vaccines, and other biological products the fees are as follows:
- Investigator/Local Phases: $2,000 USD
- Protocol Amendment: $750 USD
- Expedited Protocol Review: $900 USD
- Renewal of Clinical Trial Certificate (yearly): $50 USD
Payment Instructions
No information is currently available regarding payment instructions for the clinical trial application fee to the PBSL.
Overview
Malawi has a centralized registration process for ethics committees (ECs) and EC review. As mandated by the SciTechAct, the National Commission for Science and Technology (NCST) is the governmental body responsible for EC oversight, and for the promotion and coordination of research in Malawi.
As per the G-NHSRC, the G-COMREC, MWI-5, and MWI-50, the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC) are the two (2) NCST-approved ECs responsible for monitoring and evaluating health research studies involving humans. The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of the NHSRC, only reviews and approves studies involving or originating from College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions. Per the R-HlthResCoord, each EC has members representing the other committee in order to facilitate the transfer of information between the ECs. The NHSRC and COMREC report to and are centrally monitored by the NCST.
MWI-25 indicates that as of August 2024, COMREC is operating under KUHeS and will be changing its name to Kamuzu University of Health Sciences Research Committee (KUREC), following approval from the NCST. The COMREC guidance and forms provided in the Malawi profile are still being used.
Ethics Committee Composition
National Health Sciences Research Committee
As per the G-NHSRC, NHSRC must consist of members with varying backgrounds, including the social sciences, to promote complete and adequate research proposal review. The committee should include one (1) lay person, as well as members from the following organizations:
- National Research Council of Malawi (one (1) member)
- Ministry of Health (MOH) headquarters (two (2) members)
- COMREC (two (2) members)
- Community Health Sciences Unit (one (1) member)
- National AIDS Commission (one (1) member)
- Center for Social Research (one (1) member)
- Queen Elizabeth Central Hospital (one (1) member)
- Zomba Central Hospital (one (1) member)
- Lilongwe Central Hospital (one (1) member)
- Christian Health Association of Malawi (one (1) member)
- Mzuzu University (one (1) member)
- Mzuzu Central Hospital (one (1) member)
- Nurses and Midwives Council of Malawi (one (1) member)
- Ministry of Justice (one (1) member)
The members elect the chairperson and the vice-chairperson.
College of Medicine Research and Ethics Committee
The G-COMREC specifies that COMREC should be multidisciplinary, and its members must have the basic qualifications, experience, and expertise to conduct fair scientific and ethical proposal reviews. The committee must have a maximum membership of 15, and include representatives from the biomedical sciences, research methods, behavioral science, and research ethics areas. Additionally, there must also be representatives from the NCST, the NHSRC, the KCN, and the lay community.
Furthermore, the committee must be diverse, have balanced gender representation, and embody community interests and concerns. Members are also required to sign a confidentiality agreement and refuse projects in which they have a conflict of interest. Members from the COM staff serving on the committee must be a minimum grade of senior lecturer, and preferably have peer reviewed publications.
See the G-NHSRC and the G-COMREC for additional EC membership criteria and qualification requirements.
Terms of Reference, Review Procedures, and Meeting Schedule
National Health Sciences Research Committee
The G-NHSRC states that the MOH’s Research Unit serves as a secretariat for NHSRC, and is responsible for preparing materials and meeting logistics. Research proposals must be distributed to NHSRC members two (2) weeks before the scheduled meetings to allow members time to adequately review the submitted proposals. Half of the NHSRC’s membership constitutes a quorum of any meeting, and the meeting is rescheduled within the following two (2) weeks if a quorum is not reached. Half of the ordinary quorum forms a quorum for the rescheduled meeting if no ordinary quorum is reached. Otherwise, the meeting must be rescheduled.
As delineated by the G-NHSRC, NHSRC decisions are reached by consensus. If there is no consensus, a decision is made by simple majority of members present through an open ballot. In the event of a tie, the chairperson casts a vote.
According to the G-NHSRC, when new NHSRC members have been appointed, they may attend the first one (1) or two (2) meetings as an observer in order to learn about the workings of the NHSRC before being assigned reviewer responsibility. Such members will undergo NHSRC orientation sessions covering guidelines and standard operating procedures (SOPs) of the committee and any practical matters with the secretariat and chairperson. Continuing education for all members in matters of health research ethics and related disciplines in human research protections is also essential, and the chairperson is responsible for fostering local and international networks, links, and partnerships for the purposes of continuing the NHSRC’s education and development.
Per the G-NHSRC, NHSRC members must serve on the committee for three (3) years and are required to renew their appointments if requested by their organizations. The G-NHSRC and the G-HlthResConduct also indicate that the NHSRC meets once every two (2) months.
College of Medicine Research and Ethics Committee
COMREC requires written SOPs to be maintained, and all relevant records (e.g., SOPs, reports, curriculum vitaes (CVs), meeting minutes, and correspondence) to be archived for three (3) years following the study’s completion, as delineated in the G-COMREC. The COMREC secretariat must compile all the relevant documents and materials required for review of a proposal and circulate them to the members at least 14 days before the date of the scheduled meeting. Quorum of any meeting is achieved when a majority of the members attend. The quorum should preferably include members of both genders, a member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the COM. If the quorum cannot be achieved, the meeting must be rescheduled within two (2) weeks of the failed meeting. If the subsequent meeting does not achieve quorum, then the chairperson must make a decision based on the expertise and number of members present.
The G-COMREC further states that COMREC’s final decision will be reached through a consensus. If there is no consensus, a decision is made through a majority vote.
Per the G-COMREC, COMREC members must receive initial and continuing training regarding the ethics and science of research. The appointment of committee members is valid for three (3) years, and a member may be reappointed to serve another three (3) year term. According to the G-COMREC and the G-HlthResConduct, COMREC meets every month.
Overview
The G-SLAppClinTrial states that in Sierra Leone, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone). Ethical clearance for all phases of clinical trials involving humans must be sought from the SLESRC. The SLESRC is responsible for ensuring the protection of the rights, safety, and well-being of trial participants, and providing assurance of that protection by reviewing, approving, and providing comments on trial protocols and the suitability of the investigator(s), facilities, and the methods and materials to be used in obtaining and documenting informed consent of the trial participants.
Ethics Committee Composition
As per the SL-GCPs, the EC (i.e., the SLESRC) should consist of members who collectively have the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. Specifically, it is recommended that the EC should include:
- At least five (5) members
- At least one (1) member whose primary area of interest is nonscientific
- At least one (1) member who is independent of the institution/trial site
Terms of Reference, Review Procedures, and Meeting Schedule
As set forth in the SL-GCPs, the EC (i.e., the SLESRC) must perform its functions according to written standard operating procedures (SOPs), maintain written records of its activities and meeting minutes, and comply with good clinical practice (GCP) and other applicable regulatory requirements. An EC must make its decisions at announced meetings where a quorum, as stipulated in the SOPs, is present. Only those EC members who are independent of the trial’s principal investigator (PI) and sponsor should vote or provide an opinion on any trial-related matters. In addition, only members who participate in the EC review process and discussion should vote and provide their opinion.
The SL-GCPs also states that the EC must retain all relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for at least three (3) years after the study’s conclusion, and make them available to the Pharmacy Board of Sierra Leone (PBSL) upon request. The EC may be asked by investigators, sponsors, or the PBSL to provide its written procedures and membership lists.
Overview
According to the G-NHSRC and the G-COMREC, the primary scope of information assessed by the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial.
The G-HlthResConduct states that scientific design; recruitment of research participants; care and protection of research participants; ethical consideration; and community consideration are essential elements that the NHSRC and COMREC must review in a clinical trial application. Per the G-NHSRC, the NHSRC must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).
The G-HlthResConduct and the R-HlthResCoord indicate that COMREC, as a subsidiary of NHSRC, only reviews and approves studies involving or originating from the College of Medicine (COM) or Kamuzu College of Nursing (KCN) (now known collectively as the Kamuzu University of Health Sciences (KUHeS), per MWI-62) faculty members and students, and their collaborators/coinvestigators/affiliates. The NHSRC has the sole jurisdiction to review studies with a national interest and multicenter studies, including those from COM and KCN, as well as studies from all other researchers and institutions.
Role in Clinical Trial Approval Process
The R-HlthResCoord indicates that before submitting a clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA), the sponsor or principal investigator (PI) must obtain full ethical approval from either the NHSRC or COMREC. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.
Moreover, as specified in the R-HlthResCoord, for all studies originating outside Malawi, the sponsor or the PI is required to obtain approval from an EC based in their country prior to submitting an application to the NHSRC or COMREC for ethical review and approval.
Per the G-NHSRC and the G-COMREC, the applicable EC will screen submitted applications for completeness, and help determine the type of review to be conducted.
The G-NHSRC states that new studies submitted to the NHSRC are generally reviewed by a fully convened NHSRC meeting. The following studies will be reviewed by the full NHSRC:
- All high-risk studies
- Studies involving vulnerable populations (including pregnant women, prisoners, mentally incompetent patients, etc.)
- Any clinical interventional study that randomly assigns human participants to alternative experimental or placebo groups
- Studies involving sensitive information connected to personal identifiers
- Studies previously reviewed that require major issues to be addressed
The G-NHSRC and the G-COMREC indicate that following the NHSRC’s or COMREC’s review, the EC will decide to approve the research, stipulate minor changes for approval, or not approve the research. A negative decision on an application must be supported by clearly stated reasons. In addition, the G-NHSRC states that if the NHSRC determines that substantive changes/clarifications must be made before approval may be granted, the study will be deferred for a full NHSRC meeting.
The G-COMREC specifies that the COMREC’s approval of a new application is valid for one (1) year. However, the R-HlthResCoord indicates that EC approval of a study is valid for the period of the study as described in the protocol, which is effective from the date of approval as indicated in the approval letter.
The R-HlthResCoord, the G-NHSRC, and the G-COMREC state that the EC must review and approve any protocol amendments prior to those changes being implemented. See MWI-52 and MWI-44 for the NHSRC and COMREC amendment request forms, respectively. Any changes cannot be implemented until approved by the EC.
The G-COMREC requires that COMREC follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. The follow-up review intervals are determined by the nature of the research project. However, each protocol should undergo a follow-up review at least once a year. As part of its monitoring process, COMREC conducts inspections of institutions and study sites.
Studies of National Interest
All studies of national interest, as defined in the G-NHSRC, the G-COMREC, and the R-HlthResCoord to include all vaccine trials and stem cell research, should be referred to the NHSRC, regardless of the origin of the protocol. The NHSRC may form a standing committee for that specific project, which will monitor the project through to its conclusion, composed of members to be drawn on the basis of their expertise.
Multicenter Studies
As delineated in the R-HlthResCoord, the NHSRC is designated and mandated to review and approve multicenter clinical trials, including those originating outside Malawi. The NHSRC will conduct a full initial review of the same protocols for a multicenter study submitted by different investigators provided that such protocols are submitted simultaneously. Protocols for the same multicenter trial to be implemented at different institutions may also be merged into one (1) protocol that the NHSRC will treat as a joint submission for review.
Continuing Review
According to the G-NHSRC and the G-COMREC, all approved studies running for more than one (1) year are subject to continuing annual review by the approving EC (the NHSRC or COMREC). If the materials for continuing EC review are not received within one (1) month following the expiration date of the previous approval, then the study will be classified as lapsed and inactive. If a study has lapsed, the EC will order that all study-related operations cease, except those necessary for the welfare of the participants. Per the G-NHSRC, if the PI wants to continue an NHSRC-reviewed study that has lapsed for two (2) months, the PI must submit a new application for NHSRC review and wait for approval before resuming research under the protocol. MWI-53 indicates that the NHSRC follows, at a minimum, the regulations set forth in the Declaration of Helsinki (MWI-42) and the Council for International Organizations of Medical Sciences (CIOMS) guidelines as the criteria for continuing review of a study. The PI is responsible for timely submission of a continuing review application to prevent any lapse in NHSRC approval. NHSRC regulations do not provide for exceptions to the requirement for continuing review. The NHSRC’s continuing review application form is available at MWI-53.
Expedited Review
Per the G-NHSRC and the G-COMREC, research studies that have previously been reviewed by a fully convened committee and require the PI to address minor issues, may be approved through the NHSRC’s or COMREC’s expedited processes. Studies by students may also be considered for expedited review. Expedited review can be considered for continuing review of research previously approved by the NHSRC or COMREC, where the research is permanently closed to the enrollment of new subjects, and all subjects have completed all research related interventions.
Per the G-COMREC, COMREC’s review period for such a resubmission must not exceed 14 days from the date of the resubmission. The G-NHSRC further indicates that the NHSRC will also consider expedited review for continuing review of research previously approved by NHSRC where no subjects have been enrolled and no additional risks have been identified, or where the remaining research activities are limited to data analysis and report writing.
For more information on each EC’s expedited review procedures, see the G-NHSRC and the G-COMREC.
Exemption from Review
As delineated in the G-NHSRC and the G-COMREC, certain types of human participants research may be exempted from NHSRC or COMREC review. Exemption may be considered for research involving the collection or study of existing data, documents, records, program evaluation, pathological specimens, or diagnostic specimens, if the sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects.
Suspension or Termination of Study/Approval
Per the G-NHSRC, the NHSRC chairperson or the convened NHSRC may suspend a study at any time if it is determined that the study requires further review or evaluation. This determination may be made in the event of an adverse event, non-compliance, or other danger to human participants. The study will be reviewed at the next convened meeting to determine if it requires changes. The NHSRC must notify the PI and the sponsor in writing specifying reasons for suspension or termination with a copy to the National Research Council of Malawi (NRCM). The NRCM must be informed of all the suspended or terminated studies with detailed reasons for the decision. In the event of documented serious adverse events and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. In the case of any officially or unofficially reported noncompliance, protocol violation, or deviation by the researcher, the NHSRC must suspend the study to ensure safety of the study participants and carry out an investigation. Upon investigation of the problem prompting the suspension of the study, the convened NHSRC must terminate the study if convinced beyond any reasonable doubt that there was noncompliance, deviation, or violation of the protocol.
The G-COMREC states that COMREC may recommend to COM management suspension or termination of approval of research that is not being conducted in accordance with the guidelines, or that has been associated with unexpected serious harm to participants. Any suspension or termination of approval must include a statement of the reasons for COMREC's action and must be reported promptly to the investigator, appropriate institutional officials, Dean of Postgraduate Studies and Research, and the Principal of the COM. The Principal of the COM must then send a report of suspended or terminated studies with the reasons contained therein to the NCST and the PMRA, or any other government agency responsible for research policy matters.
Overview
According to the G-SLAppClinTrial and the SL-GCPs, the primary scope of information assessed by the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), relates to protecting the well-being and rights of research participants and ensuring their safety throughout their participation in a clinical trial.
As per the SL-GCPs, the EC (i.e., the SLESRC) must also pay special attention to trials that may include vulnerable subjects.
Role in Clinical Trial Approval Process
As indicated in the G-SLAppClinTrial, clinical trial application submissions to the Pharmacy Board of Sierra Leone (PBSL) and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.
The G-SLEthics further specifies that the principal investigator (PI) must obtain approval for a clinical trial from the SLESRC. The PI should submit a proposal along with other required documentation to the SLESRC Chair at least two (2) calendar months prior to the anticipated commencement of the proposed study.
The SL-GCPs requires that the EC review a proposed clinical trial within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: approval/favorable opinion; modifications required prior to its approval/favorable opinion; disapproval/negative opinion; and termination/suspension of any prior approval/favorable opinion. The EC must conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human participants, but at least once per year.
There is no stated expiration date for EC approval in the G-SLAppClinTrial, the SL-GCPs, or the G-SLEthics.
(See the Submission Process and Timeline of Review sections for detailed submission process requirements.)
National Health Sciences Research Committee
According to MWI-4 and MWI-15, non-Malawian researchers must pay $150 USD or its equivalent in Malawian Kwacha to the National Health Sciences Research Committee (NHSRC) upon submission of a research proposal. Malawian students (Masters and below) are required to pay 5000 Malawian Kwacha.
The G-NHSRC and MWI-5 indicate that following the protocol’s approval, the principal investigator must also pay the Ministry of Health (MOH) a fee of 10% of the total budget indicated in the proposal to cover NHSRC institutional capacity strengthening and administrative operating expenses. MWI-15 further specifies that the fee, referred to as a 10% NHSRC Human Subject Protection (HSP) fee, must be paid by PhD students and above.
MWI-5 clarifies that the NHSRC fee and the Pharmacy and Medicines Regulatory Authority (PMRA)’s Clinical Trial Review Committee (CTRC) fees are included in the 10%. Payment of the 10% fee must be made for all NHSRC-approved research projects prior to commencement of the research study.
Payment Instructions
Per MWI-15, the application fee and the 10% HSP fee may be paid at the MOH Headquarters Cash Office or through the following bank details:
Account Name: NHSRC NCST Review Fees
Account Number: 1010759176
Bank Name: National Bank of Malawi
Bank Address: Capital City Branch, Lilongwe 3, Malawi
Swift Code: NBMAMWMW008
College of Medicine Research and Ethics Committee
As per MWI-5, non-Malawian researchers must pay $150 USD and Malawian researchers must pay 500 Malawian Kwacha to the College of Medicine Research and Ethics Committee (COMREC) upon the submission of a research proposal. COMREC is also mandated to charge a College of Medicine (COM) fee of 10% of the total budget indicated in the proposal. As delineated in MWI-1, the COM’s Dean of Postgraduate Studies and Research can grant waivers for the 10% fee.
However, the G-COMREC states that the COM’s processing fee is $100 USD for each new protocol submission and resubmission for the fourth time, and that eligible investigators may apply to management for exemption from paying the fee.
Payment Instructions
No information is currently available regarding payment instructions for COMREC.
Sierra Leone Ethics and Scientific Review Committee
The G-SLEthics indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), requires the principal investigator (PI) to pay a nonrefundable administrative fee to submit a protocol for ethical review and approval. The fees are as follows:
- For self-funded, individual Sierra Leonean researchers based in Sierra Leone: 300,000 Leones
- For graduate students studying in Sierra Leone: 200,000 Leones
- For Sierra Leonean students studying abroad: $100 United States Dollars (USD)
- For Sierra Leonean academics abroad: $150 USD
- For all foreign students studying abroad: $200 USD
- For self-funded, international researchers: $400 USD
- For national/local non-governmental organizations (NGOs)/community-based organizations (CBOs): 2,000,000 Leones
- For international NGOs based in Sierra Leone and international universities conducting non-clinical research: 4,000,000 Leones
- For multinational institutions, donor agencies, and institutions not ordinarily based in Sierra Leone: $1,500 USD
- For exclusively government funded studies: 500,000 Leones (must be submitted with a cover letter from the Permanent Secretary of the relevant Ministry or the Chief Medical Officer in the case of the Ministry of Health and Sanitation (MoHS))
- For any amendment made to a previously approved application: 25% of the current fee for the first request, 50% for the second, and 100% for subsequent ones. Sierra Leonean students are exempt from this charge.
- For an application extension: 25% of the original fee
- For exclusively electronic applications: additional $50 USD
Payment Instructions
No information is currently available regarding payment instructions for the SLESRC.
Overview
The R-HlthResCoord indicates that the National Commission for Science and Technology (NCST) is the central statutory body responsible for coordinating and regulating all research, science, and technology related activities in Malawi, as mandated by the SciTechAct.
The R-HlthResCoord further specifies that the NCST provides oversight to the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC). The NCST’s core responsibilities in this capacity include:
- Participating as an ex-officio member for the NHSRC and COMREC by having a voting representative from the NCST sit on both committees
- Reviewing and approving the ethics committees’ (EC) guidelines and standard operating procedures
- Monitoring the ECs’ performance and adherence to relevant national policies, laws, regulations, and guidelines
Registration, Auditing, and Accreditation
As stated in the SciTechOrder, an NCST-issued license is required for the accreditation of research institutions and the establishment of an institutional EC. Additional information regarding the NCST-issued license is not available at this time.
Overview
SLE-3 indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), does not have a supervisory or oversight mandate over institutional ECs for health research. Few institutions have their own institutional ECs.
Registration, Auditing, and Accreditation
No applicable requirements.
Overview
According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval of a clinical trial application.
The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC). Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.
Regulatory Submission
According to MWI-60, an electronic or soft copy of the clinical trial application dossier must be sent to registration@pmra.mw and info@pmra.mw.
As per the G-CTARevVacBiol and MWI-9, applicants must submit three (3) copies of the clinical trial application to the PMRA. MWI-60 further requires that the three (3) dossier hard copies be submitted in a lever arch file to the Director General. Each section of the dossier must be well demarcated for ease of reference by PMRA reviewers. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent.
There is no specified language requirement for the clinical trial documents to be submitted to the PMRA.
Ethics Review Submission
National Health Sciences Research Committee
As stated in the G-HlthResConduct and MWI-15, the applicant is required to bind and submit application materials (plus an electronic copy, per MWI-15) to the NHSRC at least three (3) weeks before the date of the review meeting.
MWI-15 states that applications should be submitted to the NHSRC at the following address:
The Chairperson
National Health Sciences Research Committee
Ministry of Health Research Department Area 2/124
P.O. Box 30377
Lilongwe 3, Malawi
Tel: +265 1 789 400
The electronic copy should be submitted at the same time to research@health.gov.mw and mohdoccentre@gmail.com.
MWI-15 indicates that three (3) copies of each item indicated in the NHSRC Checklist (MWI-4) must be submitted in the research proposal package to the NHSRC (See the Submission Content section for a list of these items). Three (3) copies for Malawian student proposals (up to master’s level) must also be submitted to the NHSRC secretariat for expedited review. The submission must be bound in the order indicated by MWI-4 as one (1) PDF document. (See the Submission Content section for more details on the individual elements of the NHSRC research proposal submission.)
According to MWI-15 and MWI-4, the data collection tools and informed consent forms must be provided to the NHSRC in both English and Chichewa (or the appropriate local language).
The R-HlthResCoord indicates that for multicenter trials, sponsors and PIs may plan to hold a pre-clinical trial submission and authorization meeting with the NHSRC, at their own choice and cost. The sponsor or PI must write to the NHSRC secretariat of the review committee to request the meeting’s arrangement at least four (4) weeks in advance of the suggested meeting date. For more information, see the R-HlthResCoord.
College of Medicine Research and Ethics Committee
Per the R-HlthResCoord, COMREC may at its own discretion allow a pre-clinical trial application procedure, where applicable, at the request and cost of the sponsor. As stated in the G-HlthResConduct, the applicant is required to submit application materials to COMREC at least three (3) weeks before the date of the review meeting.
According to MWI-10, protocol submissions to COMREC may be made through the Research Ethics Information Management System (REIMS) (MWI-19). Following submission, the protocol will be reviewed, and feedback will be given through the applicant’s registered email address. All file attachments should be in PDF format with clear, descriptive names. Per MWI-19, ECs in Tanzania, Rwanda, and Kenya also participate in REIMS. See MWI-10 for more information on the REIMS submission portal.
MWI-19 provides the following additional contact information for COMREC:
Tel: +265 888 118 993
Email: comrec@medcol.mw
However, MWI-1 indicates that all documents should be submitted to COMREC by email to comrec@medcol.mw in one (1) PDF file, if the file size does not exceed 5MB. If the file size is over 5MB, then the file should be sent as a compressed zipped file. The data collection tools and informed consent forms must be provided in both English and Chichewa (or the appropriate local language).
Overview
In accordance with the G-SLAppClinTrial and the SL-GCPs, Sierra Leone requires the sponsor and principal investigator (PI) to obtain clinical trial authorization from the Pharmacy Board of Sierra Leone (PBSL) before commencement of the clinical trial. Furthermore, per the G-SLEthics, the PI is required to obtain ethics approval from the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC).
As indicated in the G-SLAppClinTrial, a favorable opinion from the SLESRC is a required element of a clinical trial application to the PBSL. However, submissions to the PBSL and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.
Regulatory Submission
The G-SLAppClinTrial indicates that applicants must submit 15 hard copies of all clinical trial application documents to the PBSL, as well as one (1) soft copy in Microsoft Word format (Acrobat PDF files are also acceptable).
As per the G-SLAppClinTrial, the delivery address for a clinical trial application is as follows:
The Registrar
Pharmacy Board of Sierra Leone
Central Medical Stores
New England Ville, Freetown
P.M.B. 322
Sierra Leone
As per SLE-23, the clinical trial application and accompanying material must be provided in English.
Ethics Review Submission
The G-SLEthics states that the PI should submit to the SLESRC five (5) hard copies of the full research proposal (and all supporting documents) detailing the ethical issues in the study and how they will be addressed (only three (3) copies for extensions), each in a separate envelope. In addition, an electronic copy of the application should be emailed to efoday@health.gov.sl. The G-SLEthics also indicates that the PI may submit an exclusively electronic application for an additional fee. See the Ethics Committee Fees section for more information.
The G-SLEthics states that PIs should submit their applications with a cover letter addressed to the Chair of the SLESRC at least two (2) calendar months before the anticipated commencement of the proposed study.
Per the G-SLEthics, the delivery information for the SLESRC is as follows:
Office of the Sierra Leone Ethics and Scientific Review Committee
Ministry of Health and Sanitation
Directorate of Policy, Planning & Information (DPPI)
Youyi Building, Fifth Floor, East Wing
Freetown
Sierra Leone
Phone: +23278 366493
Regulatory Authority Requirements
As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and MWI-60, the following documentation must be submitted to the Pharmacy and Medicines Regulatory Authority (PMRA) in an application to conduct a clinical trial (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
- Comprehensive table of contents for the entire application, including a complete list of all documents provided in the application. The location of each document should be identified by tab identifiers. In general, the name for the tab identifier should be the name of the document
- Cover letter signed by the principal investigator (PI) or sponsor
- Proof of payment of the application and registration fees
- Signed and stamped Clinical Trial Application (Form CT 8) (MWI-9)
- Current version of the study protocol signed and dated by the sponsor and investigator (in the format provided in the International Council for Harmonisation’s (ICH) good clinical practice (GCP) guidelines and/or in line with Attachment 1 of MWI-60)
- Investigator’s Brochure (IB), where applicable (in the format provided in the ICH GCP guidelines)
- Certificate of Good Manufacturing Practice (GMP) of the investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) and/or placebo, or evidence of manufacture quality, safety, and consistency
- Mock-up labels for the IP
- Blank case report forms (CRFs) and serious adverse events (SAEs) reporting form to be used in the study
- Investigational Medicinal Product Dossier (IMPD) or alternative as provided in Attachment 2 of MWI-60
- Stability data of the IP and auxiliary medicine(s) for climatic zone IVa if not registered in Malawi by the PMRA
- Evidence of registration of the IP or auxiliary medicines in a country with Stringent Regulatory Authority (SRA) and/or Certificate of Pharmaceutical Product (CoPP), i.e., if IP/auxiliary medicines are not registered by the PMRA
- Summary of Product Characteristics (SmPC) for IP and auxiliary medicines
- Pharmacy plan
- Report summaries of prior clinical trials with the IP (part of IB if it is in the ICH format)
- Capacity building plans including training and updating of staff involved in the trial
- Informed consent form (ICF) (in ICH format)
- Declaration of intent by the national PI or contact person (MWI-31)
- Signed and completed declaration by investigators (MWI-32)
- Investigator(s) Curriculum Vitae(s) (CVs), including that of pharmacist(s)
- Financial declaration by sponsor and PI (MWI-59)
- Ethical clearance certificate from an independent ethics committee (EC) recognized by the laws of Malawi
- Certified copy of clinical trial insurance for study participants endorsed by the National Commission for Science and Technology (NCST)
- Malpractice insurance for investigators and associated staff endorsed by the NCST
- Evidence of accreditation or equivalent of the designated laboratories (see the World Health Organization (WHO)’s guidance on Good Clinical Laboratory Practice (MWI-30))
- Completed PMRA Material Transfer Agreement Form on Shipping of Samples (MWI-14)
- Description of the site facilities (pictorial presentations may be included)
- Evidence of registration of investigators with appropriate bodies
- Evidence of registration of pharmacists with the PMRA
- Evidence of GCP training by investigators and pharmacists in the last three (3) years
- Batch release certificate
- Authorization of the clinical trial from the country of origin, if applicable
- Full, legible copies of key, peer-reviewed published articles supporting the application
- Any other requirement as may be determined by the PMRA
If any above items are not submitted, justification for not submitting the document must be provided. The application may be made by a sponsor or the sponsor’s agent, who must submit a power of attorney (MWI-33) attesting to be a duly appointed agent. See MWI-60 for more details. According to MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.
Ethics Committee Requirements
National Health Sciences Research Committee
According to the G-NHSRC, MWI-4, and MWI-15, any proposals submitted to the National Health Sciences Research Committee (NHSRC) must be accompanied by the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
- The NHSRC checklist (MWI-4)
- Cover letter from the PI
- The NHSRC application form (MWI-15)
- Research proposal summary, maximum four (4) pages
- Full/main research proposal (see the G-NHSRC, MWI-4, and MWI-15 for details)
- Data collection instruments in both English and Chichewa (or other appropriate local language)
- Informed consent in both English and Chichewa (or other appropriate local language)
- Letter of approval from foreign EC, where applicable (for all students studying in foreign universities)
- Support letters from affiliating institutions (e.g., universities, hospitals, research institutions, or companies where the study is going to take place)
- A copy of the receipt for the paid application fee
- CVs for all the investigators
- Proof of funding from the sponsor/funder (where applicable)
MWI-4 requires that if any of the above items are not included in the submission to the NHSRC, an explanation must be provided.
College of Medicine Research and Ethics Committee
MWI-1 indicates that for submissions to the College of Medicine Research and Ethics Committee (COMREC), a single PDF file should include the following information in the following order:
- Completed copy of the COMREC checklist (MWI-1)
- Cover letter from the PI
- Protocol
- ICFs in both English and Chichewa for adult participants ages 18 and above, parental consent forms for all minors, and assent forms (in addition to the parental consent forms) for all minors between the ages of 7 and 17
- Data collection tools (those that will involve obtaining information from research participants should be translated into Chichewa)
- Material transfer agreement forms and documents
- Waiver letter for the 10% College of Medicine (COM) overhead fee, if applicable
- Information regarding whether the research proposal has been submitted to another EC
- Letter of support from COM head of the principal department hosting the research
- Letter(s) of support from heads of all other departments and institutions in which any research work will be done
- Evidence of current active registration with the Medical Council of Malawi for the PI and other investigators
- Investigator(s) CV(s)
MWI-1 further indicates that the proposal should not be submitted unless every item on the checklist is included, or unless a reason can be provided for the absence of any item. The completed checklist must be attached to the front of the submission. See the G-COMREC and MWI-1 for more information.
Clinical Protocol
As delineated in the G-CTAProcsVacBiol, the clinical protocol should comply with the format provided in the ICH's GCP guidelines. Per MWI-25, clinical trials in Malawi are required to follow the ICH's Guideline for Good Clinical Practice E6(R2) (MWI-22). In addition, MWI-60 provides recommended items to address in a clinical trial protocol and related documents, based on SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidance.
Per the G-HlthResConduct, MWI-60, MWI-1, and MWI-22, the following elements should be included in the protocol (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
- Cover page
- General information (protocol title, identifying number, and date; registry name; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study, along with role responsibilities)
- Protocol summary/abstract
- Background and justification
- Investigator(s) CV(s) and contact information
- IP description (See the Investigational Products topic for detailed coverage of this subject)
- Form, dosage, route, method, and frequency of administration and treatment period
- Summary of potential risks and known benefits to research participants
- Hypothesis
- Trial objectives and purpose
- Study setting
- Trial design, random selection method, and blinding level
- Work plan/Gantt chart
- Participant selection/withdrawal, timeline, and sample size
- Participant treatment
- Safety and efficacy assessments
- Literature review
- Adverse event reporting requirements (See the Safety Reporting section for additional information)
- Statistics and methods to track trial data
- Sponsor specifications for direct access to source data/documents
- Quality control/quality assurance procedures and practices
- Data monitoring, including composition of a data monitoring committee, and auditing
- Ethical considerations, including confidentiality, and plans for seeking EC approval
- Plans for communicating important protocol modifications to relevant parties
- Data management and recordkeeping
- Dissemination of findings
- Financing and insurance details
- Publication policy
- Consent form, and information on who will obtain consent
- Plans for collection, laboratory evaluation, and storage of biological specimens
For more detailed protocol requirements and recommendations, refer to MWI-60, MWI-22, MWI-1, and the G-HlthResConduct.
Regulatory Authority Requirements
As per the G-SLAppClinTrial and SLE-9, the following documentation must be submitted to the Pharmacy Board of Sierra Leone (PBSL) (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):
- Cover letter, including the list of documents submitted and their version number and date
- Non-refundable application fee as specified in the PBSL’s Fee Schedule (see Appendix I of the G-SLAppClinTrial)
- Protocol with all the relevant sections including site-specific addendums (see below for detailed protocol requirements)
- Two (2) copies of the completed clinical trial application forms signed by authorized persons, including cover page (see Appendix II of the G-SLAppClinTrial)
- Proof of registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19) or an internationally recognized PBSL-approved online registry
- Investigator’s Brochure (IB)
- Synopsis of previous trial(s) with the investigational product(s) (IP(s)), if applicable
- Summary of product characteristics or other professional information for all registered medicines used in the trial, or the international equivalent if the medicines are not registered in Sierra Leone
- A list of the planned clinical trial sites and the planned number of trial participants at the sites
- The name and position of the principal investigator(s) (PI(s)) who will be responsible for the sites where the trial is to be conducted, who must be registered with the relevant statutory health council, where applicable, and a resident in Sierra Leone
- Signed curriculum vitae(s) (CVs) for all key staff participating in the conduct of the clinical trial, as well as other relevant documents (see Annex 8 of SLE-6 for the recommended CV format for staff conducting clinical trials)
- Proof of current training in good clinical practice (GCP) for investigator(s), pharmacist(s), and monitor(s)
- Proof of registration of the key investigators with a professional statutory body, if applicable
- Any previous training in the principles of GCP or experience obtained from work with clinical trials and patient care
- Any conditions, such as economic interests and institutional affiliations, that might influence the impartiality of the investigator(s)
- Proof of current, relevant, and appropriate study insurance for all participants undertaken by the sponsor
- Proof of sponsor indemnification for investigator(s) and trial site(s) (see Annex 7 of SLE-6 for suggested wording of the sponsor indemnification)
- Professional indemnity insurance for investigator(s) and other trial staff
- Details of the site(s) where the trial is to be conducted and a duly justified written statement on the suitability of the clinical trial sites adapted to the nature and use of the IP. This should include a description of the suitability of facilities, equipment, and human resources, and a description of expertise, issued by the head of the clinic/institution at the clinical trial site or other responsible party
- A favorable opinion from the Sierra Leone Ethics and Scientific Review Committee (SLESRC). In the case of a parallel submission, proof of clinical trial application submission to the SLESRC and the updated versions of documents or information as requested by the SLESRC are required
- Recruitment arrangements
- Signed joint financial declaration between the sponsor and the PI (see Appendix IIIc of the G-SLAppClinTrial and Annex 4 of SLE-6)
- Data Safety Monitoring Board (DSMB) membership, CVs, and signed charter
- IP dossier and label
- Product information if the IP is registered: summary of product characteristics, patient information leaflet/package insert, and labelling
- Current good manufacturing practice (GMP) certificate issued from the national regulatory authority of the country where the IP is manufactured
- Product information and certificate of analysis for the concomitant and rescue medications
- Certificate(s) of analysis of the IP
- Certificate(s) of accreditation for the central laboratories
- Participant information sheet, informed consent form (ICF), and informed consent procedure
- Signed declaration by the applicant (see Annex 2 of SLE-6)
- Sponsor/PI contractual agreement, including the study budget
- Signed declaration by the PI and the sponsor of the trial that they are familiar with and understand the protocol, and will comply with GCP as determined by the PBSL in the conduct of the trial (see Appendix IIIa of the G-SLAppClinTrial and Annex 4 on page 12 of SLE-6)
- Workload forms for investigator(s)
- Signed declaration(s) by the local PI, as well as each investigator and key staff participating in the clinical trial (see Appendix IIIb of the G-SLAppClinTrial and Annex 5 of SLE-6)
- Signed declaration(s) by the sub-investigators and key staff participating in the clinical trial
- CVs and signed declaration by regional monitor(s) (see Annex 6 of SLE-6)
- Copies of recruitment advertisement(s) and questionnaires, if applicable
- Electronic copies of key peer reviewed publications following International Committee of Medical Journal Editors (ICMJE) recommendations to support the application, if applicable
- Labelled CD-ROM (list of files submitted on CD-ROM)
See the G-SLAppClinTrial for more details, including the application submission checklist (Appendix IIa) and the application form (Appendix IIb). The application checklist and form are also available at SLE-9 and SLE-6, respectively.
Additionally, see Appendix V of the G-SLAppClinTrial for the Clinical Trial Amendment Form. See also SLE-8 for the amendment checklist.
Ethics Committee Requirements
As per the G-SLEthics, the SLESRC requires the PI to submit the following documentation for ethics approval:
- Cover letter to the Chair of the Committee
- ICF attached to each proposal (Committee does not accept verbal consent, except where it is supported by an independent witness)
- Completed checklist for the Essential Elements in the Application for Approval (see the G-SLEthics)
- Brief CV for the PI and associates clearly stating their roles (not more than four (4) pages each)
- Study proposals submitted for award of a degree must be accompanied by a letter of confirmation from the supervisor and approval by the institution’s review board
- Requests for amendment or extension of study should include a copy of the previous approval letter
- A non-refundable administrative fee for each proposal submitted (see the Ethics Committee Fees section for detailed fee information)
Clinical Protocol
The G-SLAppClinTrial indicates that the clinical trial protocol must comply with the International Council for Harmonisation's (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24) and the SL-GCPs. Accordingly, the protocol must include:
- General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
- Background information
- Objectives and purpose
- Trial design
- Selection, withdrawal, and treatment of participants
- Assessment of efficacy
- Assessment of safety
- A description of the statistical methods to be used in the trial
- Direct access to source data and documents
- Quality control and quality assurance
- Ethical considerations
- Data handling and recordkeeping
- Financing and insurance
- Publication policy
Overview
As stated in the R-HlthResCoord, one (1) of the two (2) government approved ethics committees (ECs), the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC), must review and approve a clinical trial application prior to the Pharmacy and Medicines Regulatory Authority (PMRA) initiating its review and approval process. Parallel submissions of a clinical trial application to an EC and the PMRA are prohibited.
Regulatory Authority Approval
According to the G-CTARevVacBiol, the PMRA review process takes approximately six (6) weeks.
As per the G-CTARevVacBiol and the G-CTAProcsVacBiol, once the dossier is submitted to the PMRA, the application is screened for completeness. According to the G-CTARevVacBiol, the result of the screening will be communicated to the applicant within 10 working days after receipt of the application, and the screening form will be forwarded by fax. The applicant will have 10 working days to forward any outstanding documents to the PMRA. The PMRA’s technical staff then reviews the application or may forward it to an expert or evaluator for scientific review, with an allocated review period of three (3) weeks.
However, the G-CTAProcsVacBiol specifies that the application is evaluated by three (3) PMRA-appointed expert clinical trial reviewers who will provide a written report within 14 days to the designated registration office, also known as the “Focal Point” division. The Focal Point will then collate and present the expert reviews to the PMRA Clinical Trial Review Committee (CTRC). The CTRC then reviews all the available documentation and provides a recommendation for approval or rejection. The PMRA considers the CTRC’s recommendation and issues a written approval or rejection. (Per MWI-34, the guidance in the G-CTARevVacBiol and the G-CTAProcsVacBiol also apply to clinical trials of drugs.)
As stated in the G-ImpExpMP, the PMRA’s processing time for an import permit application is 10 working days.
Ethics Committee Approval
National Health Sciences Research Committee
The G-NHSRC indicates that in the case of an approval with no changes, the chairperson must inform the investigator in writing within seven (7) days. The NHSRC’s timeline for review of research proposals is not otherwise specified in the requirements.
College of Medicine Research and Ethics Committee
According to the G-COMREC, COMREC must ensure that submitted complete proposals are reviewed in a timely manner, i.e., within the month of submission. A written decision is provided to the applicant within two (2) weeks of the meeting at which the decision was made.
Overview
The G-SLAppClinTrial indicates that the Pharmacy Board of Sierra Leone (PBSL) and the Sierra Leone Ethics and Scientific Review Committee (SLESRC) reviews may be conducted in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.
Regulatory Authority Approval
Per the G-SLAppClinTrial, the PBSL’s processing times of clinical trial applications for different investigational products (IPs) are as follows, unless otherwise specified by the PBSL on a case-by-case basis:
- Medical devices - 40 working days
- Pharmaceuticals - 50 working days
- Biological and biotechnology medical products - 60 working days
- Genetically modified organisms - 120 working days
As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance within 10 working days from the receipt of the application. The applicant must address formal grounds for non-acceptance within 10 working days. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.
According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. The timeline for processing such applications is 10-20 working days. For more information on expedited review, see the Scope of Assessment section and the G-SLAppClinTrial.
The G-SLAppClinTrial further indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. The PBSL’s processing time for protocol amendment applications is 30 working days. For more details on amendment requirements, see the G-SLAppClinTrial.
The G-SLAppClinTrial states that the PBSL must issue a Clinical Trial Certificate to authorize the trial to be conducted, which must be renewed annually. The PBSL’s processing time for a Clinical Trial Certificate renewal application is 15 working days.
The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The PBSL’s response to the appeal application must be addressed to the affected person or institution within 90 days of the appeal’s submission. For more information on appeal contents and timelines, see the G-SLAppClinTrial.
According to the G-SLAppClinTrial, the PBSL’s processing time for IP import permits is 10 working days.
Ethics Committee Approval
No information is currently available on the SLESRC’s timeline of review.
Overview
According to the G-CTARevVacBiol, the R-HlthResCoord, and MWI-50, the Pharmacy and Medicines Regulatory Authority (PMRA) requires the applicant to obtain PMRA approval and ethics committee (EC) approval before initiating a clinical trial.
The R-HlthResCoord indicates that before submitting a clinical trial application to the PMRA, the sponsor or principal investigator (PI) must obtain full ethical approval from either of the two (2) National Commission for Science and Technology (NCST)-approved ECs—the National Health Sciences Research Committee (NHSRC) or the College of Medicine Research and Ethics Committee (COMREC).
In addition, as per the D-ImprtRelIMPs, the sponsor should not supply the investigational product (IP) to be used in the clinical trial until the sponsor obtains all required documentation. As stated in the G-ImpExpMP, IP import permit applications should be made by the pharmacist of record for the trial. (See the Manufacturing & Import section for additional information.)
Clinical Trial Agreement
The G-CTAProcsVacBiol requires the sponsor to sign a letter of agreement with the participating institution(s) before the trial begins. In addition, the investigators and the sponsor or the contract research organization must sign an agreement specific to the clinical trial.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 indicates that the sponsor should obtain the investigator’s/institution’s agreement to:
- Conduct the trial in compliance with good clinical practice (GCP), with the applicable regulatory requirement(s), and with the approved protocol
- Comply with procedures for data recording/reporting
- Permit monitoring, auditing, and inspection
- Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed
The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.
Clinical Trial Registration
No clinical trials registry exists at this time and there is no stated requirement to register in an international registry.
Overview
In accordance with the G-SLAppClinTrial, a clinical trial can only commence after the sponsor and the principal investigator (PI) receive authorization from Sierra Leone’s Pharmacy Board of Sierra Leone (PBSL) via a Clinical Trial Certificate. Additionally, per the G-SLAppClinTrial, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone) in the country. Ethics approval must be obtained from the SLESRC prior to initiating a study. The G-SLEthics indicates that the PI must obtain the SLESRC approval.
In addition, as per SLE-23, no waiting period is required following the applicant’s receipt of PBSL and SLESRC approval. According to the G-SLAppClinTrial, the PBSL must be informed of the trial’s initiation in writing on the exact date the study commences. If the trial does not begin or is delayed, then the PBSL must be informed of the new commencement date within 90 days of the Clinical Trial Certificate’s issuance. SLE-23 further indicates that investigators are required to notify their local institution prior to initiating a trial.
As per the G-SLAppClinTrial, a permit from the PBSL is required for the import of an investigational product (IP) to be used in a trial. (See the Manufacturing & Import section for additional information.)
Clinical Trial Agreement
The G-SLAppClinTrial and the SL-GCPs state that the clinical protocol submitted to the PBSL must include a signed contractual agreement between the sponsor and the PI.
As required by the G-SLAppClinTrial, the sponsor/PI contractual agreement must have sections indicating:
- Study title
- Protocol version and date
- Trial site
- IP information
- Definitions of all terms
- Effective date of agreement
- Outline of the sponsor’s responsibilities, which must include general management of the trial; provision of adequate funding, resources/logistics and IPs for the study; and insurance for the study participants
- Outline of the PI’s responsibilities, which must include retaining all trial related essential documents until the sponsor informs the PI these documents are no longer needed
- Term (period of study duration) and termination of agreement (conditions for this)
- Confidentiality
Per the SL-GCPs, the sponsor should obtain the investigator’s/institution’s agreement to:
- Conduct the trial in compliance with good clinical practice (GCP), with the applicable regulatory requirement(s), and with the PBSL-approved protocol
- Comply with procedures for data recording/reporting
- Permit monitoring, auditing, and inspection
The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.
Clinical Trial Registration
The G-SLAppClinTrial states that proof of trial registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19), or an internationally recognized PBSL-approved online registry, must be submitted as part of a clinical trial application to the PBSL.
Safety Reporting Definitions
In accordance with the G-SAEs-PMRA, the following definitions provide a basis for a common understanding of Malawi’s safety reporting requirements:
- Adverse Event (AE) – Any AE associated with the use of a medicine in humans, and which does not necessarily bear a causal relationship to the treatment. This may include an AE occurring in the following circumstances: during use in professional practice; from an overdose, whether accidental or intentional; from drug abuse; from drug withdrawal; and as a result of any failure of expected pharmacological action.
- Adverse Drug Reaction (ADR) – A reaction characterized by the suspicion of a causal relationship between the drug and the occurrence.
- Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – An adverse experience occurring at any dose that results in death, is life-threatening, requires or extends patient hospitalization, results in persistent or significant disability, is a birth defect or congenital anomaly; or is an important medical event that, based upon appropriate medical judgment, may jeopardize the participant, and may require intervention to prevent one (1) of the listed outcomes.
Safety Reporting Requirements
As stated in the G-SAEs-PMRA, the sponsor or the investigator(s) is required to report all SAEs that meet the Pharmacy and Medicines Regulatory Authority (PMRA)’s reporting requirements as soon as possible (within 24-72 hours) following site awareness using the SAE Form (MWI-12). All deaths that are assessed as definitely, probably, or possibly related must be reported to the PMRA within 24 hours of site awareness, and the SAE Form (MWI-12) must be submitted within three (3) working days of site awareness. See the G-SAEs-PMRA for additional details on reporting timelines for different reportable SAE situations.
The G-NHSRC indicates that the National Health Sciences Research Committee (NHSRC) requires the investigator to submit a written report for any occurrence of an AE. In the event of documented SAEs and any unanticipated problems as documented by the researcher, the NHSRC must terminate the study and order the investigator to follow up with study participants. Per the G-COMREC, AE and SAE reports must also be submitted to the College of Medicine Research and Ethics Committee (COMREC).
Form Completion & Delivery Requirements
As per the G-SAEs-PMRA, all SAEs that meet reporting requirements must be reported to the PMRA on an SAE Form (MWI-12). The G-SAEs-PMRA indicates that the form must be submitted to the PMRA office by email or hand delivered to the offices at the following address:
The Director General
Pharmacy and Medicines Regulatory Authority
P.O. Box 30241
Lilongwe 3, Malawi
Tel: 265-1755166/165
Email: info@pmra.mw, registration@pmra.mw
According to the G-NHSRC, AE reports submitted to the NHSRC must provide the following details:
- Title of protocol
- NHSRC assigned reference number
- Name of investigator
- Local affiliating institution for studies originating from outside Malawi
- Subject identifier
- Date and site/place of event
- Description of event (i.e., nature of injury or other adverse occurrence, assessment of severity, and assessment of relationship of the event to the study)
- Action taken by the researcher
- Signature of the principal investigator (PI)
See MWI-2 for the NHSRC SAE Reporting Form.
Safety Reporting Definitions
According to the G-SLAppClinTrial and the SL-GCPs, the following definitions provide a basis for a common understanding of Sierra Leone’s safety reporting requirements:
- Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom an investigational product (IP) has been administered, including occurrences which are not necessarily caused by or related to that product
- Adverse Drug Reaction (ADR) – Any noxious and unintended response to an IP which is related to any dose administered to that participant
- Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
- Unexpected Adverse Event/Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information
Safety Reporting Requirements
As stated in the G-SLAppClinTrial, the sponsor and the principal investigator(s) (PIs) are responsible for proper reporting of AEs and SAEs. The sponsor should expedite the reporting of all AEs that are both serious and unexpected. Any SAEs/SADRs must be reported to the Pharmacy Board of Sierra Leone (PBSL) immediately where possible. In any event, the SAEs/SADRs must be reported to the PBSL within 48 hours of site awareness, but no later than 15 calendar days.
The SL-GCPs indicates that all SAEs/SADRs should be reported immediately except for those incidents documented by the protocol or the investigator’s brochure that do not require immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The reports should identify participants by unique code numbers. AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the PBSL. Furthermore, per the G-SLAppClinTrial, any SAE/SADR related to the IP should receive immediate medical attention.
In addition, per the G-SLAppClinTrial, any frequent AEs/ADRs should be reported to the PBSL immediately where possible, and in any event, within seven (7) days of site awareness. Non-serious AEs must be reported to the PBSL on request and, where applicable, submitted as part of an application for registration.
The G-SLAppClinTrial indicates that non-serious AEs must be reported on request and where applicable, submitted as part of an application for registration.
Investigator Responsibilities
The G-SLAppClinTrial states that in the event of an SAE/SADR, the PI is required to submit follow-up information (e.g., copies of diagnostic test results, laboratory reports, medical record progress notes) as soon as it becomes available. This information should be clearly marked as updated information and include the protocol and participant numbers. Follow-up reports must be submitted immediately when there is a change in the severity of the SAE/SADR initially reported, whenever there is any new development on an initially reported SAE/SADR, and/or when the SAE/SADR is resolved. Follow-up reports must include an assessment of the importance and implication of any findings. All fatal cases must be accompanied by a formal autopsy report. In exceptional circumstances where a formal autopsy is not practicable, provision of a verbal autopsy report must be prior approved by the PBSL and be given with ample reasons. SLE-23 indicates that the investigator is responsible for submitting these follow-up reports, but the sponsor can also report through the contract research organization.
As per the SL-GCPs, the investigator should also comply with applicable regulatory requirements related to reporting unexpected SAEs/SADRs to the PBSL. For a reported death, the investigator should supply the PBSL with any additional requested information (e.g., autopsy reports and terminal medical reports).
Sponsor Responsibilities
According to the G-SLAppClinTrial and the SL-GCPs, the sponsor is required to expedite the reporting of all AEs/ADRs that are both serious and unexpected to the PBSL. The SL-GCPs further indicates that the sponsor must also expedite the reporting of all AEs/ADRs that are both serious and unexpected to all concerned investigator(s)/institutions(s) and the ethics committee(s).
Per the SL-GCPs, the sponsor is responsible for the ongoing safety evaluation of IPs, and should promptly notify the investigator(s)/institution(s) and the PBSL of findings that could adversely affect participant safety, impact the conduct of the trial, or alter the PBSL’s approval of the trial.
Other Safety Reports
The G-SLAppClinTrial indicates that notifications of changes in nature, severity, or frequency of risk factors must be submitted to the PBSL within 28 days, and new information that impacts the risk benefit profile of the product or conduct of the trial must be reported within seven (7) days.
Per the G-SLSftyMntrng and the G-SLAppClinTrial, a Development Safety Update Report (DSUR) must be submitted annually to the PBSL.
According to the G-SLSftyMntrng, the main objective of a DSUR is to present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed, by:
- Examining whether the information obtained by the sponsor during the reporting period is in accord with previous knowledge of the IP’s safety
- Describing new safety issues that could have an impact on the protection of clinical trial participants
- Summarizing the current understanding and management of identified and potential risks, and
- Providing an update on the status of the clinical investigation/development program and study results
For more information on DSURs, see Section 12 of the G-SLSftyMntrng.
For safety reporting from foreign sites and other reporting requirements, see Appendicies VIa – VIc of the G-SLAppClinTrial.
Form Completion & Delivery Requirements
According to the G-SLAppClinTrial, the SAE/SADR report form must include detailed information to enable a causality assessment report to be prepared by the PBSL’s Expert Committee on Drug Safety. The SAE/SADR form must conform to the format of the Council for International Organizations of Medical Sciences’ (CIOMS) Form I (SLE-7), or must be previously approved by the PBSL. Furthermore, all SAEs/suspected unexpected serious adverse reactions (SUSARs) and AEs/ADRs must be reported using the SLE-7 form format and also electronically through the PBSL’s online reporting platform (SLE-14). Frequent AEs/ADRs should be reported to the PBSL in a line listing and through the PBSL’s online reporting platform. Electronic submissions must be E2B compliant. See SLE-12 for the International Council for Harmonisation (ICH)’s E2B Guidelines.
For non-serious AEs, the G-SLAppClinTrial indicates that individual reporting must be formatted in accordance with the data elements specified in the ICH Harmonised Tripartite Efficacy Guideline on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (see SLE-12).
Interim and Annual Progress Reports
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 notes that the investigator should promptly provide written reports to the sponsor and the institutional ethics committee (EC) on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.
According to the G-NHSRC, the National Health Sciences Research Committee (NHSRC) requires an initial submission of a progress report within three (3) months of approval of the study, and an annual report for medium to long-term studies.
The G-COMREC requires that the College of Medicine Research and Ethics Committee (COMREC) follow the progress of studies for which a positive decision has been reached and establish a subcommittee responsible for monitoring ongoing studies. As part of the monitoring process, every approved study must submit annual reports by November 30, regardless of the date of its approval.
As required in MWI-58, the principal investigator (PI) must submit an annual progress report to the Pharmacy and Medicines Regulatory Authority (PMRA). All sections of the Clinical Trial Annual Progress Reporting Form for Investigators (MWI-58) must be completed in typescript and submitted together with accompanying documents to the PMRA Director General at info@pmra.mw. Both hard and soft (electronic) copies must be submitted.
The G-NHSRC and the G-COMREC further state that all approved studies continuing for more than one (1) year are subject to continuing review by the approving EC. As part of this review, applicant(s) are required to submit a progress report describing the number of participants enrolled, any problems that occurred during the prior approval period, any new knowledge regarding the study, and any procedural changes.
See MWI-54 and MWI-8 for the NHSRC and COMREC report forms, respectively.
Final Report
As required by the G-NHSRC and the G-COMREC, the applicant is required to submit a final report to the approving EC when a study is completed.
According to the G-NHSRC, the investigator must submit three (3) copies of the final technical report when submitting written notice of the completion of the study to NHSRC.
Other Considerations
The G-NHSRC states that all data originating from a research study conducted in Malawi are the property of the Malawi Government irrespective of the source of funds for carrying out the study. Therefore, investigators are required to submit copies of their reports to NHSRC for review prior to submitting for publication within or outside of Malawi. Investigators are expected to have plans for disseminating research findings in Malawi.
Interim and Annual Progress Reports
Per the SL-GCPs, the investigator should submit written summaries of the trial status to the Pharmacy Board of Sierra Leone (PBSL) as required in the G-SLAppClinTrial, or more frequently, if requested by the PBSL. The investigator should also promptly provide written reports to the PBSL on any changes that significantly affect the conduct of the trial and/or increase the risk to participants.
As set forth in the G-SLAppClinTrial, quarterly reports must be submitted starting from the date the Clinical Trial Certificate is issued using the Quarterly Progress Report Form provided in Appendix VIIb. The reports must be submitted to the PBSL within 21 days following the end of the previous quarter, and an interim report must be submitted within 21 days after the end of the first half of the trial period, and as stipulated in the protocol. If the trial is interrupted, the reason must be communicated in writing to the PBSL within 10 working days. See the G-SLAppClinTrial for additional details on preparing progress reports.
Final Report
According to the G-SLAppClinTrial, the principal investigator (PI) or the sponsor must notify the PBSL no later than 30 days following the trial’s completion and submit a preliminary report on the trial. This report, referred to as a close-out report in the G-SLAppClinTrial, must be submitted to PBSL after study completion in the recommended format as per Appendix VIII.
The G-SLAppClinTrial delineates that in addition to the close-out report, the PI or the sponsor must compile and submit a comprehensive formal report to the PBSL no later than 90 days following the trial’s completion. The report should conform to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline - Structure and Content of Clinical Study Reports (E3) (SLE-11). The report must include a short but comprehensive summary of the essential findings of the trial, as well as its methodology and course, and be submitted in hard and soft copies. Publication(s) of the study in a scientific journal or other medium for the purpose of disseminating the information obtained to stakeholders may be done only after notification of the PBSL.
The SL-GCPs indicates that the investigator is responsible for submitting the final report summarizing the trial’s outcome to the PBSL.
As per the D-ImprtRelIMPs and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22), a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. Per MWI-25, clinical trials in Malawi are required to follow MWI-22. MWI-22 goes on to specify that a sponsor-investigator is an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.
In accordance with MWI-22, a sponsor may transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.
A sponsor may be domestic or foreign. As specified in the R-HlthResCoord, a sponsor that is a foreign company, organization, or individual(s), must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.
As per the G-SLAppClinTrial and the SL-GCPs, a sponsor is defined as an individual, company, institution, or organization that takes ultimate responsibility for the initiation, management, and financing of a trial.
In accordance with the G-SLAppClinTrial and the SL-GCPs, the sponsor may authorize a contract research organization (CRO) to perform one (1) or more of its trial-related duties and functions. However, the ultimate responsibility for the trial’s data quality and integrity always resides with the sponsor.
The SL-GCPs further requires that any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing. The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s contracted CRO(s). Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.
Additionally, as delineated in the SL-GCPs, a sponsor-investigator is defined as 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.
Per SLE-23, a foreign individual/organization may be the sponsor of a clinical trial, but a local representative in Sierra Leone is required.
Overview
The G-CTAProcsVacBiol specifies that the investigator(s) must be qualified, experienced, and have specific good clinical practice (GCP) training. The principal investigator (PI) should have acted as a sub-investigator in at least one (1) prior clinical study. The investigator must also commit to complying with the clinical trial protocol, have no conflicts of interest, and have no history of GCP noncompliance.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides the following guidance to sponsors on investigator and site selection:
- The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicenter trials, their organization and/or selection are the sponsor’s responsibility.
- Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and should provide sufficient time for the investigator/institution to review the protocol and the information provided.
As stated in the G-CTAProcsVacBiol, all clinical trials must also be conducted in a laboratory that can provide evidence of accreditation with a recognized control authority to conduct the specified test. In the absence of an accreditation authority, proof of Good Laboratory Practice compliance and validation of assay methods should be provided.
Foreign Sponsor Responsibilities
According to the G-NHSRC, foreign researchers must be affiliated to a local institution and provide a supporting letter from the institution as evidence. Additionally, they must have a local collaborator. The R-HlthResCoord further indicates that any foreign-based institution or organization must first be affiliated with a local Malawian institution that is recognized by the National Commission for Science and Technology (NCST) prior to commencing any operations in the country.
Data and Safety Monitoring Board
Although not specified as a sponsor requirement, the G-CTAProcsVacBiol states that a Data Safety Monitoring Board (DSMB) or a similar body must be established and empowered to regularly assess the trial and to recommend a pause or termination of the trial for safety reasons. MWI-22 notes that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.
Multicenter Studies
As delineated in MWI-22, in the event of a multicenter clinical trial, the sponsor must ensure that:
- All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and given ethics committee (EC) approval
- The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
- Investigator responsibilities are documented prior to the start of the trial
- All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
- Communication among investigators is facilitated
Overview
The SL-GCPs states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by training and experience. Additionally, the sponsor must define and allocate all trial-related duties and responsibilities to the relevant parties. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure.
As stated in the G-SLAppClinTrial, the principal investigator (PI) directly in charge of a trial, and at each site in a multi-center trial, must possess appropriate qualifications, training, and experience. The PI must be a scientist and domicile in Sierra Leone.
The G-SLAppClinTrial and the SL-GCPs further indicate that the PI must be responsible for the proper conduct of the trial(s), have previous experience as a co-investigator in at least two (2) trials in the relevant professional area, and have proof of formal training in good clinical practice (GCP) for at least two (2) years. See the G-SLAppClinTrial and the SL-GCPs for additional requirements.
Foreign Sponsor Responsibilities
Per SLE-23, a foreign individual/organization may be the sponsor of a clinical trial, but a local representative in Sierra Leone is required.
Data and Safety Monitoring Board
As indicated in the G-SLAppClinTrial, the sponsor must establish an independent data-monitoring committee, such as a Data and Safety Monitoring Board (DSMB), to regularly assess the trial’s progress and analyze safety data. The applicant must provide a copy of the DSMB’s membership, curriculum vitaes, and signed charter in the clinical trial application package submitted to the Pharmacy Board of Sierra Leone (PBSL). However, the SL-GCPs indicates that establishing a DSMB is optional.
The G-SLAppClinTrial further indicates that a duly signed and authenticated DSMB report(s) and/or minutes must be forwarded to the PBSL upon request. For more information on DSMB requirements, see the G-SLAppClinTrial.
Multicenter Studies
As delineated in the SL-GCPs, 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 the approvals of the PBSL and the ethics committee
- The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
- Investigator responsibilities are documented prior to the start of the trial
- All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
- Communication between investigators is facilitated
In addition, the sponsor may organize a coordinating committee or select coordinating investigators.
Insurance
As set forth in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC, the sponsor or the investigator(s) are responsible for providing insurance coverage for any unforeseen injury to research participants. Before a clinical trial begins, the sponsor should also provide insurance or indemnify the investigator and the institution against claims arising from malpractice or negligence. See the G-CTInsurance-MWI, the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the G-COMREC for detailed information on when insurance is required.
As per the G-CTInsurance-MWI, the sponsor or the investigator(s) must provide the participants with a no-fault insurance policy and certificate for the duration of the trial, and for five (5) years following the trial’s completion. “No-fault” is defined as insurance for which proof of negligence or other wrongful conduct need not be established. However, the causal connection between the trial and harm, bodily injury, or death must be proven to trigger the obligation to make a compensation payment. The National Health Sciences Research Committee (NHSRC), the College of Medicine Research and Ethics Committee (COMREC), or the Pharmacy and Medicines Regulatory Authority (PMRA)'s Clinical Trial Review Committee are responsible for determining which clinical trials fall within the scope of this requirement.
Per the G-CTInsurance-MWI, obtaining and submitting insurance is a requirement and a prerequisite to obtaining clinical trial ethics and regulatory approval. The insurance documentation must be included as part of the application package submitted to either the NHSRC or COMREC, and the PMRA. As specified in the G-CTAProcsVacBiol, the sponsor or the investigator(s) must also comply with the insurance and compensation requirements delineated in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20).
The PMRA’s Indemnity Form for Conducting Clinical Trials (Form CT 10) is available at MWI-18.
Compensation
Injury or Death
As specified in the G-CTInsurance-MWI, the G-CTAProcsVacBiol, and the G-COMREC, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.
As per the G-CTAProcsVacBiol, the sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (MWI-21 and MWI-20) to comply with Malawi’s participant compensation and treatment requirements due to trial-related injuries. The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or the legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committees (ECs).
MWI-21 provides several basic principles to guide sponsors in fulfilling their compensation obligations. Compensation should be paid as follows:
- When it can be demonstrated that a causal relationship exists between a participant’s injury and participation in a trial
- When a child is injured in utero through participation by the child’s mother in a clinical trial
- When the injury results in permanent injury or disability to the participant
- When there is an adverse reaction to a medicinal product under trial, and injury is caused by a procedure adopted to deal with that adverse reaction
MWI-21 states that the likelihood of an adverse reaction, or the fact that the participant has freely consented (whether in writing or otherwise) to participate in the trial should not exclude the participant from being eligible for compensation. The amount of compensation paid to the participant should be appropriate to the nature, severity, and persistence of the injury. The compensation should also be generally consistent with the amount of damages commonly awarded for similar injuries.
According to MWI-21, the amount paid in compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):
- The seriousness of the disease being treated
- The degree of probability that adverse reactions will occur and any warning given
- The risks and benefits of the established treatments relative to those known or suspected of the trial medicines
Per MWI-21, in any case where the sponsor agrees to pay the participant, but the two (2) parties differ on what is the appropriate level of compensation, it is recommended that the sponsor agree to seek the opinion of a mutually acceptable independent expert at the sponsor’s own cost. This opinion should then be made available to the participant(s), and the expert’s opinion should be given substantial weight by the sponsor in reaching a decision on the payment amount.
Additionally, any participant claims pursuant to MWI-21, should be made to the sponsor, preferably via the investigator. The participant should include details on the nature and background of the claim, which the sponsor should review expeditiously. The review process may be delayed if the participant requests an authority to examine any medical records relevant to the claim.
Trial Participation
Per G-BioSampCompense, participants may also be reimbursed for trial-related expenses, if allowed by the EC. However, payments to participants that are construed to affect the voluntary participation of the subjects are not allowed. Furthermore, lump sum payments for research participation are not allowed. Participants who incur direct costs from trial participation must be reimbursed if required by the EC. Such reimbursable expenses include travel and communications costs associated with routine clinical trial evaluations. During review of the protocol, the EC will make a case-by-case determination if the study should provide any form of acceptable recompense.
Insurance
The G-SLAppClinTrial states that for all sponsor-initiated trials, a valid insurance certificate for the duration of the study must be provided before initiating the study, and a copy of this coverage must be included in the clinical trial application submission to the Pharmacy Board of Sierra Leone (PBSL). Sponsors and principal investigators (PIs) must ensure insurance cover for clinical trial participants and must submit a certificate of insurance cover for participants as evidence. The certificate must at least contain:
- Insurance company
- Policy number
- Initial date
- Expiry date
- Insured (Policy Holder/Sponsor)
- Description of activity (purpose of the policy)
The G-SLAppClinTrial and the SL-GCPs also state that the sponsor must provide insurance or indemnify the investigator(s)/institution(s) against claims arising from the trial, except for those claims arising from malpractice and/or negligence as stipulated in the G-SLAppClinTrial. See Annex 7 of SLE-6 for suggested wording of the sponsor indemnification.
Compensation
Injury or Death
The SL-GCPs indicate that the sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable requirement(s). In addition, when trial participants receive compensation, the method and manner of compensation should comply with the PBSL's requirements.
Trial Participation
According to the SL-GCPs, the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should review both the amount and method of payment to participants to assure that neither presents problems of coercion or undue influence. Payments to a participant should be prorated and not wholly contingent on the participant’s completion of the trial. The EC should also ensure that information regarding payment to participants, including the methods, amounts, and schedule of payment, is set forth in the written informed consent form and any other written information to be provided to participants. The way payment will be prorated should be specified.
Quality Assurance/Quality Control
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 guides sponsors on quality, data, and records management.
Per MWI-22, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:
- During protocol development, identification of processes and data that are critical to ensure participant protection and the reliability of trial results
- Identification of risks to critical trial processes and data
- Evaluation of the identified risks against existing risk controls
- Decisions on which risks to reduce and/or which risks to accept
- Documentation of quality management activities and communication to those involved in or affected by these activities
- Periodic review of risk control measures to ascertain whether the implemented quality management activities are effective and relevant
- In the clinical study report, a description of the quality management approach implemented in the trial and a summary of important deviations from the predefined quality tolerance limits and remedial actions taken
Monitoring Requirements
As part of its quality assurance system, the G-CTAProcsVacBiol notes that the sponsor should perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, standard operating procedures (SOPs), and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with the sponsor’s own SOPs, the auditor observations are documented, and data are available as needed for the Pharmacy and Medicines Regulatory Authority (PMRA) to review. No specific timeframe is provided for the audit process.
Per MWI-22, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).
Per MWI-61, the PMRA may conduct good clinical practice (GCP) inspections of clinical trial sites before regulatory approval, while the trial is ongoing, when participants are being enrolled in a trial, on a routine basis, when triggered by a complaint, or if there is a suspicion of serious non-compliance integrity issues and/or scientific/ethical misconduct. In general, the inspectee will be notified one (1) to four (4) weeks prior to the proposed announced inspection date and asked to confirm availability. The notification will identify the study and the proposed sites to be inspected. In relation to triggered inspections, the PMRA may provide a shorter notice period. The inspection dates will be confirmed with the inspectee, who may be required to submit information to the PMRA within 14 days of the receipt of the notice of GCP inspection. The inspection plan is finalized by the PMRA before the inspection. See MWI-61 for more information on PMRA GCP inspections.
Premature Study Termination/Suspension
According to MWI-22, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor. Refer to MWI-17 for the National Health Sciences Research Committee (NHSRC)’s protocol termination form.
The G-COMREC states that if a study is prematurely suspended/terminated, the applicant should notify the College of Medicine Research and Ethics Committee (COMREC) of the reasons for suspension/termination, and a summary of the results obtained should be communicated to the committee.
Quality Assurance/Quality Control
As stated in the SL-GCPs, the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, good clinical practice (GCP), and the Pharmacy Board of Sierra Leone (PBSL)’s regulatory requirement(s). The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.
Monitoring Requirements
As part of its QA system, the SL-GCPs notes that the sponsor may choose to perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the PBSL, and other applicable regulatory requirements. The sponsor should ensure that the auditors are qualified by training and experience, and that their qualifications are documented. The sponsor must also ensure that the audit is conducted in accordance with the sponsor’s own written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The observations and findings of the auditor(s) should be documented. No specific timeframe is provided for the audit process. See the SL-GCPs for detailed audit requirements.
Premature Study Termination/Suspension
As per the SL-GCPs, if a trial is terminated or suspended prematurely, the sponsor should promptly inform the investigator(s)/institution(s) and the PBSL of the termination or suspension, and explain the reason(s) for the termination or suspension. The ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution.
Electronic Data Processing System
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). As per MWI-22, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. The sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to MWI-22 for additional information.
Records Management
As set forth in MWI-22, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.
In addition, MWI-22 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.
According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the National Health Sciences Research Committee (NHSRC).
Electronic Data Processing System
As delineated in the SL-GCPs, when using electronic trial data handling and/or remote electronic data systems, the sponsor must ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that the sponsor maintains standard operating procedures (SOPs) for using these systems. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. Refer to the SL-GCPs for detailed information on electronic trial data systems.
Records Management
As set forth in the SL-GCPs, the sponsor, or other data owners, should retain all sponsor-specific essential documents pertaining to the trial for at least two (2) years after formal discontinuation of the trial or in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). In addition, all clinical and experimental data (electronic or paper) must be kept in a secure place for a period of five (5) years, or 20 years for a new drug application, after a trial’s completion. The data must also be readily available for review upon request by the Pharmacy Board of Sierra Leone (PBSL).
See the SL-GCPs for a list of essential documents for the conduct of a clinical trial.
Responsible Parties
For the purposes of data protection requirements, as stated in the G-DataPrtct-MWI, the data controller means a natural or legal person who, alone or jointly with another natural or legal person, determines the purpose and means of processing personal data. The data processor means a natural or legal person who processes personal data on behalf of a data controller. The Malawi Communications Regulatory Authority (MACRA) regulates the processing of personal data and is responsible for the enforcement of the G-DataPrtct-MWI.
Data Protection
A data controller and data processor must process personal data lawfully, fairly, and in a transparent manner, as described in the G-DataPrtct-MWI. Additionally, a data controller and data processor must collect personal data for a specific and legitimate purpose and must not process the data in a manner that is incompatible with the purpose for which it was collected. They also must not store personal data for a period that is longer than necessary to achieve the purpose for which the data is processed, except where the data is stored for the purpose of archiving for public interest or for research or statistical purposes. The appropriate technical or organizational security measures must be implemented to guarantee the security of personal data, including protection against unauthorized or unlawful processing and accidental loss, destruction, or damage of the data.
See the G-DataPrtct-MWI for more details on the duties of a data controller and data processor.
Consent for Processing Personal Data
The G-DataPrtct-MWI indicates that a data controller must obtain the consent of a data subject before processing the personal data of the data subject. Where a data controller seeks consent from a data subject on several matters in the form of a written declaration, each matter on which consent is sought must be presented in a clearly distinguishable manner. A data subject may, at any time, withdraw consent given to a data controller and the withdrawal of the consent shall, where practicable, be in the same manner the consent was provided. The withdrawal must not affect the legality of the data processing that occurred before the withdrawal of the consent. Where a question arises on whether consent was freely provided, consideration must be taken of whether the performance of a contract between the data controller and the data subject, or the delivery of a good or a service by the data controller to the data subject, is conditional on provision of the consent.
According to the G-DataPrtct-MWI, a data controller must, at the time of collecting personal data from a data subject, provide the following information to the data subject:
- The identity and contact details of the data controller or representative of the data controller
- The legal basis for processing the personal data
- The purpose for processing the personal data
- Where possible, the storage period for the personal data
- The existence of automated decision-making, including profiling
- The rights of the data subject provided in the G-DataPrtct-MWI (described below)
- The right to lodge a complaint with the MACRA
- Whether the data controller intends to transfer the personal data to a place outside Malawi
As per the G-DataPrtct-MWI, a data subject has the right to obtain confirmation of whether personal data concerning the data subject is being processed by the data controller or data processor. Where the data controller or data processor confirms the processing of the personal data of the data subject, the data controller or data processor must provide the data subject with a copy of the personal data being processed (i) in a commonly used electronic format; (ii) within 30 days of receipt of the request; and (iii) where practicable, at no expense to the data subject. The data subject also has a right to data portability, rectification of personal data, erasure of personal data, restriction of processing personal data, object to the processing of personal data, and not to be subject to a decision based solely on automated processing. See the G-DataPrtct-MWI for more information on these rights.
Children and Incapacitated Persons
The G-DataPrtct-MWI delineates that where a data subject is a child or any other natural person lacking the legal capacity to exercise the rights of the data subject, a parent or legal representative/guardian of the data subject must exercise the rights of the data subject on behalf of the data subject. A data controller or data processor who intends to process personal data of a data subject who is a child or any other natural person lacking legal capacity to provide consent must obtain the consent from a parent or legal representative/guardian of the data subject. Additionally, the data controller or data processor who obtains such consent must put in place appropriate mechanisms to verify the age of the child or the mental capacity of the other natural person, as well as the identity of the parent or legal representative/guardian providing the consent.
No information is currently available regarding personal data protection requirements.
Obtaining Consent
In all Malawian clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the G-NHSRC and G-COMREC-IC. The G-BioSampCompense also confirms that a participant’s voluntary informed consent is required. Also, per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22).
As per the G-NHSRC, the G-CTAProcsVacBiol, the G-CTARevVacBiol, the G-COMREC, and MWI-22, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by one (1) of the two (2) National Commission for Science and Technology (NCST)-approved ethics committees (ECs)—the National Health Sciences Research Committee (NHSRC) and the College of Medicine Research and Ethics Committee (COMREC)—and provided to the Pharmacy and Medicines Regulatory Authority (PMRA) with the clinical trial application. (See the Required Elements section for details on the contents to be included in the form.)
The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the participant or legal representative/guardian must be provided with detailed research study information. Per the G-NHSRC, the ICF content should be presented orally and in writing, in a manner that is easy to understand, commensurate with the comprehension level of the research participants, and without coercion. When drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education.
As per the G-NHSRC and MWI-22, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or appear to waive the participant’s legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence. The G-BioSampCompense also confirms that researchers must not duly induce participants to participate in any proposed research. Rather, they must design and implement their studies in a manner that calls for the participants’ informed voluntary consent to participate.
Re-Consent
According to MWI-22, the written ICF and any other written information to be provided to participants should be revised whenever important new information becomes available that may be relevant to the participant’s consent. Any revised written ICF and written information should receive the EC's approval/favorable opinion in advance of use. The participant or legal representative/guardian should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant or legal representative/guardian should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.
Language Requirements
As stated in the G-NHSRC, the G-COMREC, and the G-COMREC-IC, the ICF should be written in English and any other relevant local languages that the participant is able to understand.
Documenting Consent
The G-NHSRC and MWI-22 specify that the participant or legal representative/guardian must sign the ICF. The G-NHSRC indicates that where the participant is illiterate, the NHSRC will permit the participant to provide a thumbprint in the presence of a witness, who must also sign the ICF. NHSRC also permits the participant to provide verbal consent in cases where the participant is illiterate. However, the script or information sheet to be read to the potential participant must be approved by NHSRC and signed for by the participant’s legal representative/guardian.
MWI-22 states that where the participant is illiterate or legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:
- The written ICF and any other written information provided to the participant is read and explained to the participant and the legal representative/guardian
- The participant and the legal representative/guardian, have orally consented to the participant’s involvement in the trial, and has signed and dated the ICF, if capable of doing so
Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.
According to MWI-15, consent forms must be kept for three (3) years after the completion of the investigation, unless otherwise stipulated by the NHSRC.
Waiver of Consent
Per the G-NHSRC, the NHSRC may waive the requirement for the investigator to obtain a signed ICF in cases where circumstances warrant such a waiver. The following conditions may be considered for a waiver:
- The research presents no more than a minimal risk of harm to the participants and involves no procedures for which written consent is normally required outside of the research context
- The research could not practically be carried out without the consent waiver and obtaining informed consent is not practicable
- The consent document is the only link between the participant and the research and the principal risk of harm would come from a breach of confidentiality
- Waiver is consistent with the individual’s rights
The G-NHSRC indicates that in lieu of a signed ICF, the NHSRC may require the investigator to provide participants with a written statement regarding the research in the form of an information or fact sheet. This statement should contain, at a minimum:
- A statement verifying that the project involves research
- A description of the level of involvement and amount of time expected from participants
- A description of the study
- A description of the risks and benefits to the participants
- A statement describing the participant’s rights
- A description of the compensation to be provided to participants
- Contact information for both the investigator and NHSRC chairperson
Obtaining Consent
In all Sierra Leone clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the SL-GCPs. In obtaining and documenting informed consent, the investigator should comply with Pharmacy Board of Sierra Leone (PBSL) requirements and should adhere to good clinical practice (GCP) and to the ethical principles that have their origin in the Declaration of Helsinki (SLE-5), which is available in Appendix 3 of the SL-GCPs.
As per the SL-GCPs and the G-SLAppClinTrial, the informed consent form (ICF) is viewed as an essential document. The sponsor and principal investigator (PI) must submit the ICF to the PBSL with the clinical trial application. The G-SLEthics further indicates that the PI must also submit the ICF to the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), for review. (See the Required Elements section for details on what should be included in the form.)
The SL-GCPs states that the investigator, or the investigator’s designated representative, must provide detailed research study information to the participant or legal representative/guardian. In addition, the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant or legal representative/guardian should also be given adequate time to consider whether to participate.
As per the SL-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.
Re-Consent
According to the SL-GCPs, the participant or legal representative/guardian should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant or legal representative/guardian should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.
Language Requirements
As per SLE-23, the clinical trial application and accompanying material must be provided to the PBSL in English.
Documenting Consent
The SL-GCPs states that the participant or legal representative/guardian, as well as the investigator(s), must sign and date the ICF.
Where the participant is illiterate or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after:
- The written ICF and any other written information is read and explained to the participant or legal representative/guardian;
- The participant or legal representative/guardian has orally consented to the participant’s involvement in the trial; and
- The participant or legal representative/guardian has signed and dated the ICF, if capable of doing so.
According to the G-SLEthics, the SLESRC does not accept verbal consent, except when supported by an independent witness.
Per the SL-GCPs, before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.
Waiver of Consent
The SL-GCPs delineates that where the protocol indicates that prior consent of the participant or legal representative/guardian is not possible, the EC (i.e., the SLESRC) should determine whether the proposed protocol and/or other document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials. See the Emergencies and Mentally Impaired sections for more information.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 provides guidance on the elements to include in the informed consent form (ICF). The G-NHSRC and MWI-22 state that information about the research study should be clearly presented in both written and oral form.
Based on the G-NHSRC, the G-COMREC-IC, the G-NHSRC-ICF, MWI-22, and MWI-13, the ICF should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
- The study title, purpose, procedures, and duration
- Experimental aspects of the study
- The responsibilities and expected duration of the participant's participation
- The trial treatment(s) and the probability for random assignment to each treatment
- Any expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
- Any expected benefits to the participant, others, or to the country as a whole that may reasonably be expected from the research
- Description of procedures, including data collection, that will be followed
- Identification of any experimental procedures
- Disclosure of alternate procedures or treatments available to participants that might be advantageous to the participant
- Compensation and/or treatment available for the participant in the case of trial-related injury
- The anticipated prorated payment, if any, to the participant for participating in the trial
- The anticipated expenses, if any, to the participant for participating in the trial
- That participation is voluntary, and that the participant can refuse to participate or withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
- That the monitor(s), the auditor(s), the ethics committee (EC), and the regulatory authority(ies) will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written ICF, the participant or the participant's legally acceptable representative is authorizing such access
- The extent to which confidentiality of records identifying the participant will be maintained
- Name and contact details of institutions that have approved the study
- Contact information for the sponsor and investigator in the event of participant problems or trial-related injuries
- EC contact information
- Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
- The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
- That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
- Any additional costs to the participant that may result from participation in the research
- The site of the study
- Consent and signature or thumb print, including the last sentence, which should explicitly read “I voluntarily agree”
See the Vulnerable Populations and Consent for Specimen sections for further information.
Based on the SL-GCPs, the informed consent form (ICF) should include the following statements or descriptions, as applicable:
- The study involves research and an explanation of its nature and purpose
- Trial procedures to be followed, including all invasive procedures
- Expected duration of participation
- Participant’s responsibilities in the trial
- Experimental aspects of the study
- Approximate number of participants involved in the trial
- The trial treatment(s) and the probability for random assignment to each treatment
- Any foreseeable risks or discomforts, and when applicable, to an embryo, fetus, or nursing infant
- Any expected benefits or prorated payment; if no benefit is expected, the participant should also be made aware of this
- Alternative procedures or treatment that may be available
- Compensation and/or medical treatment available to the participant in the event of a trial-related injury
- Person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
- Any additional costs that may result from participation in the research
- That the monitor(s), the auditor(s), the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)), and the Pharmacy Board of Sierra Leone (PBSL) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
- That records identifying the participant will be kept confidential and, to the extent permitted by applicable laws and/or regulations, will not be made publicly available. If the results are published, the participant’s identity will remain confidential
- Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
- That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
- The participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
Additionally, see Annex 1 of SLE-6 for standardized wording for the ICF.
Overview
Per the G-NHSRC, Malawi’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), which addresses participant rights.
(See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)
The Right to Participate, Abstain, or Withdraw
As set forth in the G-NHSRC, the G-COMREC-IC, and MWI-22, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.
The Right to Information
As delineated in the G-NHSRC, the G-COMREC-IC, and MWI-22, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Required Elements section for more detailed information regarding participant rights.)
The Right to Privacy and Confidentiality
As per the G-NHSRC, the G-COMREC-IC, and MWI-22, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. It is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.
The Right of Inquiry/Appeal
The G-NHSRC, the G-COMREC-IC, and MWI-22 state that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights. (See the Required Elements section for more detailed information regarding participant rights.)
The Right to Safety and Welfare
The Malawi government complies with MWI-22 principles that state a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society.
Overview
In accordance with the SL-GCPs, which is guided by the International Council for Harmonsation’s Guideline for Good Clinical Practice E6(R2) (SLE-24), the Declaration of Helsinki (SLE-5), and other international guidelines, Sierra Leone’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The SL-GCPs and the G-SLAppClinTrial state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.
The Right to Participate, Abstain, or Withdraw
As stated in the SL-GCPs, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.
The Right to Information
As per the SL-GCPs, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.
The Right to Privacy and Confidentiality
According to the SL-GCPs and the G-SLAppClinTrial, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.
The Right of Inquiry/Appeal
The SL-GCPs states that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or the participant’s rights.
The Right to Safety and Welfare
As set forth in the SL-GCPs and the G-SLAppClinTrial, the research participant’s dignity, safety, and welfare must take precedence over the interests of science and society.
See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies.
Per MWI-22, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee (EC) must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.
As per the G-NHSRC, a waiver of consent may be justified if the research being conducted could not practically be carried out without the consent waiver, and obtaining informed consent is not practicable. See the Documentation Requirements section for more information on waiver of consent.
The SL-GCPs make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergency situations.
As delineated in the SL-GCPs, if the signed informed consent form (ICF) cannot be obtained from the research participant in an emergency, then the consent of the legal representative/guardian, if present, should be obtained. If prior consent of the participant or legal representative/guardian cannot be obtained, then the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, with documented approval/favorable opinion by the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) and the Pharmacy Board of Sierra Leone (PBSL) to protect the rights, safety, and well-being of the participant and ensure compliance with EC and PBSL requirements. The participant or legal representative/guardian should be informed about the trial and provide consent as soon as possible.
In addition, per the SL-GCPs, because the participants who are experiencing medical emergencies are usually extremely vulnerable, these individuals should be excluded from all but minimally invasive observational research. ECs must also take great care when assessing emergency care research. Once the researcher has presented clear reasons to justify the initiation of emergency care research without consent to the EC, the EC may approve the research provided it is satisfied that:
- Reasonable steps are being taken to ascertain the religious and cultural sensitivities of participants experiencing medical emergencies
- The condition of the participant precludes the giving of consent
- Inclusion in the trial is not contrary to the interests of the participant
- The research is intended to be therapeutic and poses no more risk than is inherent to the patient’s condition or would be caused by alternative methods of treatment
- The participant and the legal representative/guardian will be informed as soon as is reasonably possible of the patient’s inclusion in the study and of the option to withdraw from the research project at any time
- The participant will be informed, and consent obtained, once the participant who has undergone the necessary emergency procedures has regained consciousness
- The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care
Overview
As per the G-NHSRC, in all Malawian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The G-NHSRC characterizes vulnerable populations as those who are relatively or absolutely incapable of protecting their own interests due to illiteracy, a lack of education, autonomy, resources, or other necessary attributes. These participants may include children, pregnant women, prisoners, refugees, orphans, sex workers, people living with HIV and AIDS, persons with mental disabilities, and persons in dependent relationships (e.g., some women who culturally must ask their husbands before consenting to participate in a research study).
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 includes the following as vulnerable populations: members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable populations include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.
The G-NHSRC specifies that National Health Sciences Research Committee (NHSRC) members must pay special attention to protecting participants who are from vulnerable populations. Consent for those who are not legally, mentally, and physically able should be sought from their legal representative/guardian in the form of a signature or thumbprint.
As per the G-NHSRC, trials involving vulnerable persons require the research to be directly related to the specific conditions of the vulnerable population involved, and that the participants should personally benefit from the research. In addition, the following elements must be considered when studies are conducted using vulnerable populations:
- The methods of recruitment, selection, and inclusion/exclusion criteria, as well as informed consent, data confidentiality, and the participant’s willingness to volunteer
- Group characteristics such as economic, social, physical, environmental, and cultural conditions
- Applicable local laws that bear on the decision-making abilities of potentially vulnerable participants
- Research studies involving potentially vulnerable population groups should have adequate procedures in place for assessing and ensuring participants’ capacity, understanding, and informed consent or assent
- Safeguards may include NHSRC monitoring of the consent process where possible
See the Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these vulnerable populations.
Overview
As per the SL-GCPs, in all Sierra Leonean clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.
According to the SL-GCPs and the G-SLAppClinTrial, vulnerable populations include individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with the participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. The SL-GCPs states that other participants representing vulnerable populations include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Additionally, types of research that need additional attention include research involving collectivities, indigenous medical systems, innovative therapy or interventions, HIV and AIDS clinical and epidemiological research, and emergency care research.
The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors, women, persons with mental disabilities or substance abuse related disorders, persons in dependent relationships or comparable situations, prisoners, and persons highly dependent on medical care.
Persons Highly Dependent on Medical Care
According to the SL-GCPs, participants who are highly dependent on medical care must be given special attention to protect the welfare of this vulnerable study population. Researchers need to acknowledge that the participant’s medical condition may compromise the participant’s informed consent and affect the participant’s ability to form an opinion or to communicate. There may also be a perception of coercion if a participant is reluctant to refuse consent for fear that it may compromise the participant’s medical treatment.
As delineated in the SL-GCPs, the following research areas require investigators to pay special attention to these participants to safeguard their welfare and ensure proper consent:
- Intensive care research – Characteristic features are the difficulties in communicating with participants receiving ventilatory assistance and the impairment of cognition in heavily sedated participants. Whenever possible, information should be obtained from potential participants prior to their admission to intensive care. These participants should be excluded from all but minimally invasive observational research due to their extreme vulnerability.
- Neonatal intensive care research – Research involving infants should be conducted in strict accordance with the principles discussed in the Children/Minors section. These principles do not permit research that is contrary to the child’s best interests.
- Terminal care research – Research in terminal care is distinguished by the short remaining life expectancy of participants and potential vulnerability to unrealistic expectations of benefits. Researchers must ensure that the prospect of benefit from research participation is neither exaggerated nor used to justify a higher risk than that involved in the participant’s current treatment.
- Research involving persons with impaired capacity to communicate or unconscious persons – Refer to the Mentally Impaired section.
Persons in Dependent Groups
As set forth in the SL-GCPs, for participants whose proposed involvement in research arises from dependent or comparable relationships, the EC must be satisfied that the participants’ consent is both adequately informed and voluntary. The following list provides some examples of hierarchically structured groups and the junior or subordinate relationships that may exist in these groups:
- Older persons and their caregivers
- Persons with chronic conditions or disabilities and their caregivers
- Wards of the state and guardians
- Patients and healthcare professionals
- Students and teachers
- Prisoners and prison authorities
- Persons with life-threatening illnesses
- Employees and employers (e.g., farm workers and their employers, members of the uniformed services and hospital staff and their employers)
See the Children/Minors; Pregnant Women, Fetuses & Neonates; 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 the parent/legal guardian.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes minors, the minors should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.
Assent Requirements
As per the G-NHSRC, assent must be obtained from a minor who is deemed capable of providing assent. The National Health Sciences Research Committee (NHSRC) bases its assessment of a minor’s ability to assent on the minor’s age, maturity, and psychological state. In certain cases, the NHSRC may regard assent by minors to represent informed consent without requiring the permission of a parent/legal guardian. A typical case is when the minors are emancipated, and may include those that are legally married or are university students under the age of 18.
According to the SL-GCPs, a minor is someone under 18 years of age.
As set forth in the SL-GCPs, when the participant is a minor, informed consent must be obtained from the participant’s parent/legal guardian. Assent from the minor must also be obtained where the minor is capable of understanding. A minor’s refusal to participate in research must be respected.
The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors. Research involving minors should be approved only if:
- The research interventions, including those in observational research, presents the participant with no greater than minimal risk; or
- The research interventions present more than minimal risk but hold out the prospect of direct benefit for the participant; or
- The research interventions, including those in observational research, present more than minimal risk and do not hold out the prospect of direct benefit to the participant, but have a high probability of yielding generalizable knowledge.
In all cases, the protocol must provide sufficient information to justify clearly why minors should be included as participants.
Assent Requirements
The G-SLAppClinTrial also states that in trials involving minors, the parent/legal guardian of a minor is required to sign an informed consent form (ICF). In addition, an assent form similar to the ICF must also be signed and dated by a minor who is capable of understanding as a confirmation of the minor’s willingness to participate in a trial, after having been informed of all aspects of the trial that are relevant to the minor’s decision to participate.
As delineated in the SL-GCPs, assent refers to a minor’s affirmative agreement to participate in research. If a minor fails to object, this should not be construed as assent. The EC (i.e., the SLESRC) must ensure that adequate steps are specified in the protocol to obtain the minor’s assent when, in the EC’s judgment, the minor is capable of providing such assent. Additionally, when the EC determines that assent is required, it must also indicate whether and how such assent must be documented.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.
The SL-GCPs requires that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), pay special attention to protecting the welfare of certain classes of participants, including women who are or may become pregnant.
The SL-GCPs states that the following conditions must be met for research conducted with pregnant women and fetuses:
- Applicable studies on animals and non-pregnant individuals have been completed
- The purpose of the study is to meet the health needs of the mother of the particular fetus, the risk to the fetus is minimal and, in all cases, presents the least possible risk for achieving the study’s objectives
- Individuals engaged in the study will have no part in any decision as to the timing, method, and procedures used to terminate the pregnancy, and determining the viability of the fetus at the termination of the pregnancy
- No procedural changes that could cause greater than minimal risk to the fetus or the pregnant woman will be introduced into the procedure for terminating the pregnancy solely in the interest of the activity
Per the SL-GCPs, for any study to be conducted that is associated with either the fetus in utero or ex utero, the parents should be legally competent and have given their informed consent.
The SL-GCPs also specifies that the father’s informed consent does not need to be obtained if any of the following applies:
- The study purpose is to meet the mother’s health needs
- The father’s identity or whereabouts cannot be reasonably established
- The father is not reasonably available
- The pregnancy is the result of rape
Further, per the SL-GCPs, no fetus in utero may be involved as a research participant unless:
- The purpose of the study is to meet the health needs of the particular fetus, and the fetus will be placed at risk only to the minimum extent necessary to meet these needs
- The risk to the fetus in the proposed study is minimal, and the study’s objective is to obtain biomedical knowledge that cannot be achieved by other means
According to the SL-GCPs, until it has been established whether a fetus ex utero is viable, a fetus ex utero may not be involved as a participant in any research study unless one (1) of the following conditions is met:
- The fetus faces no added risk from participation in the study, and the purpose of the study is to develop biomedical knowledge that cannot be obtained by other means
- The purpose of the study is to enhance the possibility of survival of the particular fetus to the point of viability
The SL-GCPs states that nonviable fetuses may not be involved as participants in any research activity unless both of these conditions are met:
- The vital functions of the fetus will not be artificially maintained; experimental activities that would terminate the heartbeat or respiration of the fetus will not be employed
- The purpose of the study is to acquire biomedical knowledge not otherwise obtainable
Participants engaged in the study will have no part in any decision as to timing, method, and procedures used to terminate the pregnancy, and/or determining the viability of the fetus at the pregnancy’s termination.
No information available regarding consent requirements for prisoners.
The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including prisoners. Prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study may only involve prisoners as participants when the EC (i.e., the SLESRC) has ensured that the clinical trial involves:
- The study of the possible causes, effects, and processes of incarceration and of criminal behavior with no more than minimal risk and inconvenience to the participants
- The study of prisons as institutional structures or of prisoners as incarcerated persons
- Research on conditions particularly affecting prisoners as a class (e.g., vaccine trials and other research on diseases that may be more prevalent in prisons, and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) only after appropriate experts have been consulted
- Research on practices, both innovative and accepted, that have the intent and probability of improving the health or wellbeing of prisoners
In addition, per the SL-GCPs, in a study where some prisoners may be assigned to control groups that may not benefit from the research, the study may proceed only after appropriate experts have been consulted. Research that could be conducted on a population other than prisoners should not be permitted unless the EC is presented with a valid case and is convinced that the study does not represent exploitative research.
The SL-GCPs also states that when the EC reviews research involving prisoners, the following requirements must be met:
- The majority of the EC members, other than prison members, must have no association with the prison(s) involved
- At least one (1) member of the EC must be a prisoner, or a prisoners’ representative with appropriate background and experience to serve in that capacity. Where a research project is reviewed by more than one (1) EC, only one (1) EC need satisfy this requirement
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participants should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.
The G-NHSRC states that consent for those who are not mentally able should be sought from their legal representative/guardian in the form of a signature or thumbprint.
According to the SL-GCPs, the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to research participants with mental disabilities, including those with psychiatric, cognitive, or developmental disorders, or participants with substance abuse related disorders. Individuals who have been institutionalized may be further compromised in terms of their capacity to make a truly voluntary decision to participate in a study.
Per the SL-GCPs, research involving people with mental disabilities or with substance abuse related disorders must therefore:
- Be relevant to mental disabilities or substance abuse related disorders so that it is necessary to involve people who have a mental disability and/or a substance abuse related disorder(s)
- Justify the involvement, as the study population, of institutionalized people with mental disabilities
- Ensure appropriate evaluation procedures for ascertaining the participants’ ability to provide informed consent. If participants are deemed unable to understand and make a choice, then consent should be obtained from the participant’s legal representative/guardian
- Ensure that consent is free from coercion and risk to participants
- Ensure that only minimal risk is involved, and that the risk is outweighed by the anticipated benefits for the participants and by the importance of the knowledge that will be derived from the research
In addition, the SL-GCPs notes that persons with intellectual or mental impairment should not participate in research that might be conducted equally well with individuals without those impairments. Consent cannot be given that is contrary to the interests of a participant with mental or intellectual impairment, and the person's refusal to participate in research must always be respected. Accordingly, consent must be obtained from one (1) of the following:
- The participant to the extent that the participant is competent to give informed consent
- The participant’s legal representative/guardian when the participant is deemed not competent to do so
- An authority, organization, or individual legally authorized to do so
The SL-GCPs further states that research involving participants with impaired capacity to communicate also requires special attention. The distinguishing features of research involving participants with impaired capacity to communicate include acute impairment states requiring medical care, as well as non-acute states. In acute impairment states, the condition and medical care may mask the participant’s degree of cognition and require different means of expression. In non-acute impairment states, the condition may prevent the participant from expressing wishes at all.
As indicated in the SL-GCPs, research involving unconscious persons requires consent to be provided by the participant’s legal representative/guardian, including any relevant statutory authorities, on that person’s behalf. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive observational research. When neither the prospective participant nor the legal representative/guardian is able to give consent in advance, the EC (i.e., the SLESRC) may approve a research project without prior consent if it is satisfied that:
- Inclusion in the trial is not contrary to the interests of the participant
- The research is intended to be therapeutic and poses no more risk than is inherent to the participant’s condition or would be caused by alternative methods of treatment
- The participant and the legal representative/guardian will be informed as soon as is reasonably possible of the participant’s inclusion in the study and of the option to withdraw from the research project at any time
- The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care
As delineated in the D-ImprtRelIMPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22), an investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Malawi) is defined as a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unauthorized indication, or when used to gain further information about an approved use. Per MWI-25, clinical trials in Malawi are required to follow MWI-22.
As delineated in the G-SLAppClinTrial and the SL-GCPs, an investigational product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use.
Manufacturing
According to the PMRAAct, the D-ImprtRelIMPs, and the G-CTARevVacBiol, the Pharmacy and Medicines Regulatory Authority (PMRA) is responsible for authorizing the manufacture of investigational products (IPs) (also referred to as an investigational medicinal products (IMPs)) in Malawi.
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 requires IPs to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol. See MWI-11 for the PMRA’s GMP inspection application form.
Import
As stated in the PMRAAct, the D-ImprtRelIMPs, and the G-ImpExpMP, the PMRA is also responsible for authorizing the import of IPs. Per the PMRAAct and the G-ImpExpMP, the PMRA’s authorization is issued as an import permit. The G-ImpExpMP designates the principal investigator of a registered clinical trial as an authorized importer. IP import permit applications should be made by the pharmacist of record for the trial.
As per the G-CTAProcsVacBiol and the G-CTARevVacBiol, the applicant may apply for an import permit at the same time that the clinical trial application is submitted to the PMRA. (Per MWI-34, the guidance in the G-CTAProcsVacBiol and the G-CTARevVacBiol also apply to clinical trials of drugs.)
The G-ImpExpMP further states that upon receipt of an import application, the PMRA will conduct an assessment to verify whether the requirements, as described in the G-ImpExpMP, have been fulfilled. If the application meets the prescribed requirements, the applicant will be required to pay applicable import permit fees (See the Regulatory Fees section) and the PMRA will issue an import permit. In the case that an application has been rejected, the applicant will be issued a rejection letter (see Annex 2 of the G-ImpExpMP) stating clearly reason(s) for rejection. The regulatory processing time for an import permit application is 10 working days. The import permit will be valid for six (6) months, not transferable to any other person, and may be extended for a period not exceeding three (3) months upon successful application to the PMRA. For additional information on general import application requirements, see the G-ImpExpMP.
Per the D-ImprtRelIMPs, shipping of IPs should be conducted according to instructions given by or on behalf of the sponsor in the shipping order. A pre-clearance inspection should be carried out at the port of entry by the PMRA. The sponsor must complete the cover sheet contained in Annex 1 of the D-ImprtRelIMPs for the importation and release of IPs. Please note: Malawi is party to the Nagoya Protocol on Access and Benefit-sharing (MWI-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see MWI-35.
Manufacturing
As set forth in the PDA2001, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the manufacture of all drug products in Sierra Leone. According to the SL-GCPs, the sponsor must ensure that the investigational product (IP) is manufactured in accordance with applicable good manufacturing practice (GMP).
The G-SLAppClinTrial states that a GMP certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.
Import
The G-SLAppClinTrial states that the PBSL is responsible for authorizing the import of IPs. A request to import an IP may be submitted after the PBSL has approved the clinical trial application.
The G-SLAppClinTrial indicates that the import application submission must include the following documentation:
- Letter stating the name/description and quantities of each IP, placebo, and trial related product to be imported as well as the details of the location where the product is coming from and details of the recipient in Sierra Leone
- Certificate of analysis of IP and placebo for all batches to be imported
- Lot release certificate (where applicable) for all batches to be imported
- Investigator, sponsor, and recognized clinical research entity’s name and address
According to the G-SLAppClinTrial, the PBSL’s processing time for IP import permits is 10 working days. Imported IPs may be inspected by PBSL officials at the port of entry before they are released to the recognized clinical research entity. The PBSL may order for destruction or re-exportation of the IPs if it has any reason to believe that there is a protocol violation resulting in the termination of the study. See the G-SLAppClinTrial for detailed IP import requirements.
As per the G-FastReg, if a product being registered in Sierra Leone is going to be used in a clinical trial, the registration application may be expedited. If the conditions for expedited registration are fulfilled, the PBSL will process the application and communicate its decision within 21 calendar days.
Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see SLE-18.
Investigator's Brochure
In accordance with the G-CTAProcsVacBiol and the G-CTARevVacBiol, the Malawi government requires the sponsor to provide investigators with an Investigator’s Brochure (IB). Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). MWI-22 specifies that the IB must contain all of the relevant information on the investigational product(s) (IPs) (also referred to as investigational medicinal products (IMPs) in Malawi) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.
As specified in MWI-22, the IB must include the following sections:
- Table of Contents
- Summary
- Introduction
- Physical, Chemical, and Pharmaceutical Properties and Formulation
- Nonclinical Studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
- Effects in Humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
- Summary of Data and Guidance for the Investigator(s)
See MWI-22 for detailed content guidelines.
Quality Management
MWI-60 requires that an Investigational Medicinal Product Dossier (IMPD) or alternative be submitted in the clinical trial application to the Pharmacy and Medicines Regulatory Authority (PMRA). The IMPD must include information on the quality of any IP, the manufacture and control of the IP, and data from non-clinical studies and from its clinical use.
As per the G-CTAProcsVacBiol, the G-CTARevVacBiol, and the D-ImprtRelIMPs, the PMRA requires the following documents to accompany the IP (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
- Evidence of manufacture under conditions compliant with current good manufacturing practice (GMP)
- A release of specifications and tests, including a Certificate of Analysis (CoA) for each batch of IPs, as well as comparator(s), if applicable
- A copy of the PMRA’s letter of approval of the clinical trial
- Batch release certificate
- A copy of a valid Certificate of Manufacture issued by the competent authority in the country of origin
- A copy of a valid World Health Organization certificate of a pharmaceutical product issued by the competent authority in the country of origin
The D-ImprtRelIMPs states that the CoA should identify the product name or code; the sponsor/company name; batch numbers; expiration dates; date of issue; signature, qualification, and title of responsible person; and the results of physical and analytical tests. Per MWI-22, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.
The sponsor should complete the cover sheet in Annex 1 of the D-ImprtRelIMPs, include it with each IP shipment, and use the checklist in Annex 2 to ensure the required documentation is attached. As delineated in the D-ImprtRelIMPs, the sponsor should also prepare IP shipping instructions, including information about the shipment’s overall physical condition, for PMRA review and approval. The sponsor should provide information on the acceptable storage temperatures and storage conditions.
Investigator’s Brochure
In accordance with the G-SLAppClinTrial and the SL-GCPs, the Investigator’s Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational product(s) (IP(s)) which is relevant to the study of the IP(s) in human participants.
As per the SL-GCPs, the sponsor is responsible for providing the investigators with an IB, and the sponsor should update the IB as significant new information becomes available. The G-SLAppClinTrial further specifies that an updated IB should be submitted at least once a year, or whenever it is updated within this period. Additional information and any changes that have been incorporated in the updated IB should be highlighted for ease of review and evaluation.
According to the G-SLAppClinTrial, the content and structure of the IB must comply with the SL-GCPs and the International Council for Harmonisation’s (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24). Accordingly, the IB must provide coverage of the following areas:
- Physical, chemical, and pharmaceutical properties and formulation parameters
- Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
- Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
- Summary of data and guidance for the investigator(s)
- Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
See the SL-GCPs and SLE-24 for detailed content guidelines.
Quality Management
According to the G-SLAppClinTrial, a good manufacturing practice (GMP) certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.
Investigational product (IP) labeling in Malawi must comply with the requirements set forth in the D-ImprtRelIMPs. The D-ImprtRelIMPs states that for an IP to be used in a clinical trial, it must be properly labeled in the official language of the country where the trial is being conducted.
As set forth in the D-ImprtRelIMPs, the following labeling information must be included on the outer packaging or on the immediate packaging when there is no outer packaging:
- Wording that clearly indicates the IP is clinical trial material
- Product name or unique code
- Storage temperature and conditions
- Expiration date
- Sponsor contact details
Additionally, the G-ImpExpMP provides the following minimum labeling requirements for all imported medicines and/or active pharmaceutical ingredient (API):
- The information printed on labels must be indelible, engraved, or embossed on a primary and secondary container
- The immediate outer packaging of the medicine or API should be clearly labeled in English
- The trade or brand name where applicable should be stated
- The International Non-Proprietary Name (INN, generic name) should be clearly stated
- State quantities of each API in the given formulation or quantities of the raw material
- Date of manufacture and expiry or retest date in case of active raw materials
- Batch or lot number
- Storage conditions
- Name and address of manufacturer
- Registration number of the product issued by the Pharmacy and Medicines Regulatory Authority (PMRA) in both outer and inner package of the product(s) where applicable
- Enclosed and accompanying literature must be in English
- The specification of the API is given according to officially recognized pharmacopoeia, where applicable
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MWI-22). The D-ImprtRelIMPs and MWI-22 state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.
Investigational product (IP) labeling in Sierra Leone must comply with the requirements set forth in the G-SLAppClinTrial and the SL-GCPs. As stated in the G-SLAppClinTrial, all label information should be in English and the print should be clear, legible, and indelible.
As set forth in the G-SLAppClinTrial, the Pharmacy Board of Sierra Leone (PBSL) requires the following information be included on the labels:
- Sponsor details
- Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
- Batch number
- Trial reference number
- Trial subject identification number
- Name and address of the clinical trial site and the principal investigator
- Directions for use and any warnings or precautions that may be necessary
- Statement indicating “For clinical trial/research use only”
- Storage conditions
- Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity as well as date of dispensing, if applicable
- Statement indicating “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by participants
The SL-GCPs further states that in blinded trials, the coding system for the IP(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding.
Supply, Storage, and Handling Requirements
Per MWI-25, clinical trials in Malawi are required to follow the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MWI-22). As defined in the D-ImprtRelIMPs and MWI-22, the sponsor must also supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)), including the comparator(s) and placebo, if applicable. The sponsor should not supply either party with the IP(s) until after obtaining Pharmacy and Medicines Regulatory Authority (PMRA) and ethics committee approvals.
The D-ImprtRelIMPs and MWI-22 indicate that IPs must be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Additionally, the sponsor must ensure the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):
- IP product quality and stability over the period of use
- IP is manufactured according to any applicable good manufacturing practice (GMP)
- Proper coding, packaging, and labeling of the IP(s)
- Records are maintained for document shipment, receipt, disposition, return, and destruction of the IP(s)
- Acceptable storage temperatures, conditions, and times for the IP
- Timely delivery of the IP(s)
- Written procedures are established, including instructions for handling and storage of the IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
- Sufficient quantities of the IP(s) are maintained to reconfirm specifications, should this become necessary
Refer to the D-ImprtRelIMPs for detailed sponsor-related IP requirements.
In addition, the PharmG-InvestDrugs states that the pharmacist at each clinical trial site, designated as the Pharmacist of Record, is the primary individual who is expected to develop and maintain an IP control system, which includes the technical procedures for product ordering, control, dispensing, and accountability. In addition, the Pharmacist of Record is responsible for the establishment of internal policies and procedures for the safe and proper use of IPs. The Pharmacist of Record will perform the day-to-day dispensing and accountability activities. A pharmacy plan must be created by the Pharmacist of Record for each clinical research site, addressing the control and use of IPs. See the PharmG-InvestDrugs for more information.
Record Requirements
In accordance with the D-ImprtRelIMPs, the sponsor is required to maintain a system for retrieving IP(s) and document this retrieval process (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim). The sponsor must also maintain a system for the disposition of unused IP(s) and for the documentation of this disposition. Finally, the sponsor should maintain sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. Moreover, to the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.
G-GMP-MWI requires that for IPs, the batch documentation must be retained for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the batch was used. Additionally, the G-ImpExpMP indicates that upon issuance of import authorization by the PMRA, the importer is expected to retain such records for five (5) years from the date of importation, either as hard or electronic copies. Stored import records should be easily accessible and availed for review to the PMRA’s inspector/officers for any post-import audit or investigations.
Supply, Storage, and Handling Requirements
As delineated in the SL-GCPs, the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)). The sponsor should not supply either party with the IP(s) until obtaining approval from the Pharmacy Board of Sierra Leone (PBSL).
The SL-GCPs specifies that the sponsor must:
- Ensure timely delivery of the IP(s) to the investigator(s)
- Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
- Maintain a system for retrieving IPs and documenting this retrieval
- Maintain a system for the disposition of unused IP(s) and documenting this disposition
- Take steps to ensure IP stability over the period of use
- Maintain sufficient quantities of the IP(s) to reconfirm specifications, if needed, and maintain records of batch sample analyses and characteristics
- Ensure the IP is manufactured according to any applicable good manufacturing practice (GMP)
- Ensure proper coding, packaging, and labeling of the IP(s)
Refer to the SL-GCPs for detailed sponsor-related IP requirements.
Per the SL-GCPs, the IP(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage. Additionally, per the G-SLAppClinTrial, the PBSL requires the IP packaging to comply with the following requirements:
- The container in which the product is contained should be of good quality
- The container and closure should be properly sealed in order to protect the product from the impact of outside environmental factors
- Each sample should contain an insert
According to the G-SLAppClinTrial, the principal investigator (PI) must notify the PBSL of each consignment of IP batches received on site. The notification must include the product name(s), quantities received, and batches received. The PBSL must approve destruction of IPs, which should be carried out in such a manner that all operations may be accounted for. These documents should clearly identify, or allow traceability to, the batches and/or participant numbers involved, and the actual quantities destroyed. A destruction certificate will be issued by the PBSL.
Record Requirements
The G-SLAppClinTrial indicates that for IPs purchased locally, the PI must document the source, proof of purchase, quantities purchased, and the Certificate of Analysis for each batch of IPs. Copies of all documents on the IP(s), whether purchased locally or imported, must be kept on site for verification and accountability during good clinical practice (GCP) inspections.
As per the SL-GCPs, the sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). All sponsor-specific essential documents should be retained for at least two (2) years after formal discontinuation of the trial or in conformance with applicable regulatory requirements. In addition, all clinical and experimental data (electronic or paper) should be kept in a secure place for a period of five (5) years, and 20 years for a new drug application after a trial’s completion, and be readily available for review upon request by the PBSL.
In Malawi, as per the G-StorExptSpecimens, specimens are defined as human or animal materials, collected directly from humans or animals, including, but not limited to excreta, secreta, blood and its components; tissue and tissue fluid swabs; and body parts being transported for purposes such as research and investigational activities.
Specimens are also referred to as human materials or biological products. The G-StorExptSpecimens defines human material as all biological material of human origin, including organs, tissues, bodily fluids, teeth, hair, nails, and substances extracted from such material as DNA or RNA.
Please refer to G-StorExptSpecimens for more specific definitions for selected terms including genetically modified micro-organisms and infectious substances.
In Sierra Leone, a specimen is referred to as a biological specimen or a biological sample. As delineated in the G-SLAppClinTrial, a biological specimen or a biological sample is defined as material derived from various animal and human sources (e.g., blood, tissues, and cells) used to treat and prevent diseases.
SLE-1 further defines biological material as original material, progeny, and unmodified derivatives, but not new intellectual property. The terms referenced in this definition are explained as follows:
- Progeny refers to an unmodified descendant from the original material, such as a virus from a virus, a cell from a cell, or an organism from an organism
- Unmodified derivatives refer to substances and other materials created by the recipient that constitute an unmodified functional subunit or product expressed by the original material, including subclones of unmodified cell lines, purified or fractionated subsets of the original material, proteins expressed by DNA/RNA supplied by the provider, or monoclonal antibodies secreted by a hybridoma cell line
New intellectual property includes the following:
- Modifications (but not the material that is contained or incorporated therein)
- Other substances and materials created by the recipient through the use of the material or modifications, but that are not progeny, unmodified derivatives, or modifications (i.e., do not contain the original material, progeny, or unmodified derivatives)
- Any new use of the material, modifications, or the substances and materials created by the recipient, and
- Any new or improved process, method, or technique conceived or developed by the recipient through the use of the material, modifications, or the substances and materials previously described
Import/Export
As delineated in the G-CTAProcsVacBiol, MWI-14, and MWI-7, the applicant must obtain approval from the Pharmacy and Medicines Regulatory Authority (PMRA) to import and export human biological specimens into and out of Malawi. The G-CTAProcsVacBiol notes that the applicant may apply to the PMRA for permission to import and/or export materials at the same time that the applicant submits the clinical trial application.
The G-StorExptSpecimens specifies that the sponsor is responsible for shipping specimens, for preparing the required documentation (e.g., nationally authorized import/export permits and dispatch/shipping documents), and for ensuring that the samples collected from research participants are sent through the appropriate carrier to their destination. The sponsor may delegate these functions to the principal investigator (PI). Refer to Annex 1 of the G-StorExptSpecimens for a checklist to be completed by the PI for the proper storage and export of clinical trial samples. As per the G-StorExptSpecimens, the transport of specimens is subject to regulation by the International Air Transport Association.
In cases where investigators are unable to complete all required research tests in Malawi, MWI-14 and MWI-7 state that justification must be provided for the importation and exportation of samples.
Per the G-GenResReqs, the National Health Sciences Research Committee (NHSRC) requires investigators who wish to export biological/genetic materials to apply for a transfer under a material transfer agreement (MTA) that must be reviewed, approved, and signed for by NHSRC. The investigator must provide a satisfactory description of how the privacy and confidentiality of the individuals and communities and the safety of such materials will be maintained. Furthermore, an investigator is not permitted to transfer biological/genetic material to another research group locally and internationally unless NHSRC has approved a collaborative study between the two (2) parties and the material and information provided protects the participants. Additionally, as stated in the SciTechOrder, an NCST-issued license is required for the collection, storage, and use of human samples for research. The SciTechOrder does not specify whether the process of obtaining an NCST-issued license is separate from the NHSRC requirements described above.
Material Transfer Agreement
MWI-14, MWI-16, and MWI-7 indicate that the PMRA, the NHSRC, and the College of Medicine Research and Ethics Committee (COMREC) must ensure a MTA is in place that includes the following:
- Intention of the importation and exportation of samples
- Duration and location of storage
- Appropriate informed consent authorizing the exportation and importation
- Person(s) who will have access to the samples
- The controlling officer of the samples
- Ownership of the samples
- Capacity building (only applicable for MWI-7)
See MWI-14, MWI-16, and MWI-7 for the PMRA, NHSRC, and COMREC MTA forms, respectively.
The G-BioSampCompense also confirms that MTAs remain an instrument to be used by a researcher in requesting the approval of an ethics committee (EC) for the transfer of samples for analysis outside of Malawi.
Other Considerations
According to the G-GenResReqs and MWI-6, COMREC and NHSRC-approved samples can be stored for a maximum of five (5) years during which time all tests/analyses approved for that particular study should be concluded. MWI-6 further states that if the sample is to be used beyond five (5) years, an updated authorization must be provided, which will last another five (5) years before it can be renewed. Per G-BioSampCompense, while samples are primarily allowed to be stored as long as they are needed for the initial study, leftover samples are also permitted to be stored as long as needed for a research endeavor. See G-BioSampCompense for additional details regarding EC approval requirements.
According to the G-SLAppClinTrial and SLE-23, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the import and export of all biological specimens in Sierra Leone. However, the G-SLAppClinTrial does not have any additional information regarding specimens import.
Export
As set forth in the G-SLAppClinTrial, all institutions or individuals that wish to export any clinical information, medical records, and/or biological samples from Sierra Leone to an institution outside of the country must complete the PBSL’s requirements for material transfer authorization. The sponsor must provide annual updates on the use of, and results obtained from, biological samples exported out of Sierra Leone.
Per the G-SLAppClinTrial and the G-MTA, the local principal investigator or study lead must submit an application for an export permit submitted through the Ministry of Health and Sanitation (MoHS) to the PBSL. All applications must be accompanied by the following documents:
- Evidence of informed consent for use of medical records, clinical information, and biological samples from living participants
- MoHS authorization for deceased patients
- Memorandum of understanding (MOU) between MoHS and the applicant
- Signed and dated Material Transfer Agreement (MTA)
- Payment of PBSL prescribed export permit fee
Please refer to SLE-1 for the materials transfer template.
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 the 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 the 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 the 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.
In accordance with the G-SLAppClinTrial, consent forms for the research protocol should include a separate section for trial participants who are requested to provide their consent for the use of their biological specimens for research purposes. Separate consent may be appropriate in some cases (e.g., if investigators are requesting permission to conduct basic research which is not a necessary part of the trial), but not in others (e.g., the trial requires the use of participants’ biological materials).
As per the G-SLAppClinTrial, medical records and biological specimens taken in the course of clinical care may be used for research without the consent of the participants only if an ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) has determined that the research poses minimal risk, that the rights or interests of the participants will not be violated, that their privacy and confidentiality or anonymity are assured, and that the research is designed to answer an important question and would be impracticable if the requirement for informed consent were to be imposed. Participants have a right to know that their records or specimens may be used for research. Records or specimens should not be used when patients/participants refuse to give their permission unless the records are being used to aid in public health emergencies.
As set forth in the G-SLAppClinTrial, if informed consent or permission was required to authorize the original collection or use of such records or specimens for research purposes, then the secondary use of this information will generally be limited by the conditions specified in the original consent. During the initial consent process, prospective participants should be informed about the following potential uses of their records or specimens:
- Whether there will or may be secondary use of their research records or biological specimens, and whether this use will be limited to specific types of studies
- The conditions under which the investigators will be required to contact the participants for additional authorization for secondary use
- The investigators’ plans, if any, to destroy or to strip the records or specimens of personal identifiers
- The participants’ rights to request that their specimens or records be destroyed or personal identifiers removed for those parts of the records that they might consider to be particularly sensitive, such as photographs, videotapes, or audiotapes
In addition, per SLE-1, the Pharmacy Board of Sierra Leone (PBSL) requires the recipient of the transferred original materials to agree to treat the material and provider information as confidential except when the material or information falls under the following conditions:
- It is in the public domain at the time it is received by the recipient
- It enters the public domain after the recipient’s receipt other than through the recipient’s breach of the Materials Transfer Agreement (MTA)
- The recipient can show that the material or information was, prior to receipt from the provider, lawfully in the recipient’s possession and therefore the recipient is not obligated to maintain confidentiality
- The recipient can demonstrate the material or information was independently developed by employees, agents, or consultants of the recipient without any knowledge or use of the information disclosed by the provider under the MTA
- It was approved in writing by the provider for disclosure, provided that such disclosure was made by the recipient in accordance with the terms of such approval
SLE-1 further states that during the period of use and for five (5) years after, the recipient will use reasonable effort to maintain the confidentiality of the material and provider information covered by the MTA. To this end, the recipient will not, directly or indirectly, deal with, use, exploit, or disclose the material or provider information to any person or entity for any purpose other than those established in the MTA, or, unless the provider expressly authorizes the recipient to do so in writing. If the recipient is required by judicial, administrative, or any other legal process to provide or disclose the materials or provider information, the recipient will promptly notify the provider and allow the provider reasonable time to oppose the process prior to taking action.
See the Required Elements and Participant Rights sections for additional information on informed consent.