Clinical Research Regulation For DRC and Mali

Last content review/update: November 27, 2024

Overview

According to D-ACOREP, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) is the regulatory authority responsible for regulating clinical trials, as well as authorizing and controlling drug imports and exports, in the Democratic Republic of the Congo (DRC). In addition, the G-EthicalEval indicates that an ethics committee (EC) must review the scientific validity and ethical acceptability of any research proposal involving human subjects.

As per the G-EthicalEval, the study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, ACOREP approval is contingent upon EC approval. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

Clinical Trial Review Process

DRC-12 states that upon receiving a clinical trial application, ACOREP screens it for completeness. The G-EthicalEval indicates that in the event of a favorable opinion from the EC, ACOREP decides whether to approve the trial. If the EC issues an adverse opinion, ACOREP cannot authorize the study.

Per DRC-12, ACOREP issues a decision on approving or denying complete applications within 30 days. The decision is sent to the principal investigator (PI) by email, or the PI can pick up a hard copy of the decision at the secretariat of ACOREP.

Title II (Articles 3-4)

Guidelines 4 and 5

Last content review/update: December 5, 2024

Overview

As indicated in DecreeNo2011-753 and MLI-2, the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) within the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) is responsible for regulating clinical trials, examining applications to import investigational drugs, and reviewing clinical trial authorization records for drugs to be registered in Mali. In addition, as stated in LawNo09-059, prior to a trial’s commencement, the DPM must review the clinical trial application research data submitted by the sponsor or principal investigator, as well as the opinions of the ethics committees (ECs) consulted.

According to LawNo09-059 and the DPM-ClinTrialDocs, the DPM review and approval process takes place after the EC review and approval process. Per LawNo09-059, the EC must communicate its opinion on a research project to the DPM. LawNo09-059 also indicates that the EC’s opinions of the research data must be submitted along with the application to the DPM prior to the agency commencing its review. Therefore, the DPM review and approval process may not be conducted in parallel with the EC review.

Per DecreeNo2017-0245, all clinical research conducted in Mali must benefit the country in general and its local populations.

Clinical Trial Review Process

According to MLI-1, upon receipt of the completed and signed application, the research and evaluation section of the DPM completes the reviewer section of the form (see MLI-1). This section requires the reviewer to provide the following information: date/time of application receipt; file number; reviewer name and signature; date/time, if additional information is requested; date of receipt of additional information requested; date/opinion of the Technical Committee; and any other information.

Per MLI-9, the DPM secretary provides the clinical trial application to the DPM director once it is received. The DPM director then initially assigns the application to either the Medicine Regulation Division or the Quality Assurance Division. The Quality Assurance Division conducts an evaluation once it receives the application. Additional information from the applicant may be requested. Once the division completes its evaluation, it sends the application and evaluation to the Minister of Health and Social Development for final approval and issuance of a certificate. The approval decision is then provided to the applicant as well as regional offices, health professional councils, health inspectors, and all MSDS departments.

Context

2nd Part - Admissibility and Receipt of the Application File Section 1 (Checklist)

Title 3 (Article 13)

Chapter 1 ((Section 1, Articles 2-3) and (Section 2))

Article 3

Regulatory Fees

Last content review/update: November 27, 2024

Congolese Pharmaceutical Regulatory Authority (ACOREP)

According to DRC-12, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) charges a fee for the submission of a clinical trial application, in accordance with a fee schedule. Applicants should contact ACOREP for the fee schedule.

Payment Instructions

No information is available regarding payment instructions.

Last content review/update: December 5, 2024

Directorate of Pharmacy and Medicine (DPM)

According to MLI-1, applicants are required to pay application fees to submit an application to the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)). Applicants should contact the DPM for application fee information.

Payment Instructions

No information is available regarding payment instructions.

2nd Part - Admissibility and Receipt of the Application File Section 1 (Checklist)

Ethics Committee

Last content review/update: November 27, 2024

Overview

According to the G-EthicalEval, any research proposal in the Democratic Republic of the Congo (DRC) involving human participants must be submitted for evaluation of its scientific validity and ethical acceptability to an ethics committee (EC). An EC may be established under the auspices of national or local health authorities, national (or centralized) medical research councils, or other national representative bodies. Additionally, the EC must be independent of the research team and approved by the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

Order1250-ZKM043 indicates that the purpose of the DRC’s national EC, the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), is to review proposals for research on human beings based on the ethical principles of respect for the individual, beneficence, and justice. The CNES is also responsible for promoting the creation of and accrediting institutional ECs across the country, among other duties.

Ethics Committee Composition

The G-EthicalEval indicates that an EC should be made up of physicians, scientists, and representatives of other groups, such as nurses, lawyers, ethicists, and non-professionals, who are able to represent the cultural and moral values of the community and uphold the rights of the research participants. An EC must include both men and women.

According to the G-EthicalEval, to ensure the EC is composed of members that have experience as well as new members with a fresh perspective, a certain number of EC members may be renewed periodically. In addition, to ensure the independence of ECs and to avoid any conflict of interest, any members of the committee having special interests, direct or indirect, in a research proposal must exclude themselves from the evaluation of the proposal.

National Committee of Health Ethics (CNES)

As per Order1250-ZKM043, the CNES has 40 members, including:

One (1) delegate per province from institutional ECs
Scientific individuals (at most 10)
Religious individuals (at most five (5))
A delegate from the Order of Physicians
A delegate of the Order of the Pharmacists
A delegate from other health professional associations
A delegate from the Health Administration

Additionally, Order1250-ZKM043 states that CNES members are recruited on the basis of the following criteria:

Proven moral and scientific reputation
Professional experience of at least five (5) years
Practical training in bioethics
Great availability
Community leadership

Order1250-ZKM043 further indicates that CNES’ mandate is five (5) years, which is renewable once. The CNES is governed by an office composed of a president, a vice-president, a secretary-rapporteur, a deputy secretary-general, and a treasurer, all elected by and from among the members. The government’s Public Health authority appoints members of the office.

Terms of Reference, Review Procedures, and Meeting Schedule

The G-EthicalEval states that the EC’s written procedures must define all EC operating standards.

According to the G-EthicalEval, an EC must clearly define the roles necessary for smooth ethical evaluation. The different roles within the EC (such as president and secretary), the requirements of each role, the terms and conditions of attaining a role, and the duties and responsibilities associated with the roles must be detailed in writing.

As per the G-EthicalEval, EC members should receive basic training and access to continuing education on the ethical and scientific aspects of biomedical research. The conditions of appointment should detail the arrangements for providing EC members with initial training on the EC's work, as well as opportunities to strengthen their expertise in conducting an ethics review. These provisions should also include the requirements or expectations for basic and continuing education of EC members. This training can be carried out in the context of cooperation with other ECs in the country or region, and also on other occasions favorable to the basic training and the continuous training of the EC’s members.

The G-EthicalEval indicates that the EC is responsible for establishing well-defined procedures for submitting an application for review. These procedures, as well as any standard forms, must be public and available to applicants. In order to aid researchers, it is desirable that these procedures and forms be harmonized among all the active ECs in the country.

The G-EthicalEval requires that ECs establish specific quorum requirements to review a proposal and make a decision. These requirements must include or specify at least the following:

The minimum number of members required to reach a quorum
The professional qualifications required and distribution of these requirements within the quorum
No quorum shall be composed exclusively of members of the same profession or the same sex
The quorum must include at least one (1) member whose primary area of expertise is not scientific and at least one (1) independent member of the institution or research site

The G-EthicalEval further requires that an EC meet regularly, on scheduled dates announced in advance in a publicly available calendar. The meeting requirements must include or specify at least the following:

Meetings should be scheduled according to a pre-established schedule, which can be modified according to the workload
EC members should have sufficient time, defined before the meeting, to review submitted documents
Meetings must be documented in minutes, and there must be a procedure for approval of the minutes
The applicant, the sponsor, and/or the investigator may be invited to present their proposal or to elaborate on certain specific points
Independent consultants may be invited to the meeting or provide written comments, subject to the confidentiality agreements in force
The EC must send its opinion within 15 days of the meeting

National Committee of Health Ethics (CNES)

According to Order1250-ZKM043, the CNES’ operating mode and the frequency of meetings are determined by internal regulations previously submitted to the Minister of Health for review. The CNES operates in committees and may create, as needed, ad-hoc subcommittees for specific problems. Additionally, the CNES may call upon any resource person whose expertise or experience can be used to resolve or address a problem. The CNES draws up its action plan and activity reports and is subject to the authority of the Ministry of Health, to which it reports.

Guidelines 5, 6, 9, 10, 12, 13, and 15

Title I (Articles 1 and 2), Title II (Article 4), Title III (Articles 6-10), and Title IV (Articles 11-14)

Last content review/update: December 5, 2024

Overview

As stated in LawNo09-059, Mali requires investigators to obtain approval from a scientific committee and an approved ethics committee (EC) for each clinical trial. The scientific committee evaluates the technical validity of the research protocol. The EC provides its opinion on the validity of the research methods, particularly as they relate to participant protection and consent. Per DecreeNo2017-0245, all clinical research protocols must be submitted to the National Committee of Ethics for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)) or to an accredited institutional EC. Furthermore, the EC assumes the moral responsibility of the state and is directed to follow the investigator’s implementation of the protocol at its own expense.

According to MLI-17, Mali’s EC system consists of six (6) committees:

CNESS
Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako)
National Institute of Public Health (Institut National de Santé Publique (INSP)) EC
Ethics Committee for the Center for Sickle Cell Disease Research and Control (le Comité d’Ethique de Centre de Recherche et Lutte Contre la Drépanocytose) (CRLD))
Bamako Dermatology Hospital (Hôpital de Dermatologie de Bamako (HDB)) EC
Alioune Blondin Beye Peacekeeping School (EMP-ABB) of Bamako (l’Ecole de Maintien de la Paix Alioune Blondin BEYE de Bamako) EC

The ClinRegs profile will focus on the CNESS, the CIESS/USTTB, and the INSP EC. Refer to DecreeNo2019-0246 and OrderNo2021-5895 for additional information on the HDB EC, and MLI-19 for additional information on the EMP-ABB EC.

Ethics Committee Composition

National Ethics Committee for Health and Life Sciences (CNESS)

As specified in DecreeNo02-200 and OrderNo2019-5050, the CNESS consists of 37 members, including a president, a vice-president, and a permanent secretary. The committee’s composition is specifically represented by the following:

Three (3) members nominated by the President of the Republic of Mali
Twenty-seven (27) members from the scientific community selected for their competence and interest in ethical issues
Seven (7) researchers from the research sector, including representatives from the CIESS/USTTB and CRLD

Please refer to DecreeNo02-200 for detailed information on member composition and responsibilities. See also DecreeNo2015-0864 and OrderNo2019-5050 for details on the appointment of the president and a list of CNESS board members.

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

Per D-No2021-0415 and D-No2021-0416, the CIESS/USTTB consists of 14 members appointed by the USTTB rector and chosen from the different departments within the USTTB and from civil society. As indicated in D-No2021-0416, the members specifically include: a forensic pharmacist; an anthropologist/ethicist; an evangelist; an immunologist/genomicist; a parasitologist/clinical research specialist; a pediatrician; a public health professional; an anesthesiologist; an entomologist; a pharmacist/biologist; a pulmonologist; a civil society representative; a jurist; and a chemist.

D-No2021-0415 states that the CIESS/USTTB is presided over by a scientific person appointed by the rector and selected from among the committee members for a period of three (3) years, which is renewable one (1) time. The president is seconded by a vice-president. The CIESS/USTTB may also call upon a competent person with specific expertise to assist the committee in its work.

National Institute of Public Health (INSP) Ethics Committee

OrderNo2019-011 and DecreeNo2019-0247 state that the INSP EC members are appointed by the Minister of Health and Social Development and the committee elects a president from among its members.

As delineated in D-No2020-001817 and OrderNo2019-011, the INSP EC consists of 12 members including a representative of the General Directorate of Health and Public Hygiene; a representative of the Institute of Human Sciences; four (4) representatives of the Minister in charge of Scientific Research; a representative of the High Islamic Council; a representative of the Catholic Church of Mali; a representative of the Association of Groups of Evangelical Protestant Churches and Missions of Mali; a representative of the Malian Human Rights Association; a representative of the National Order of Physicians of Mali; and a representative of communication professionals. Per OrderNo2019-011, the EC may call upon any resource person according to their skills.

Terms of Reference, Review Procedures, and Meeting Schedule

DecreeNo2017-0245 states that the institutions promoting the research and the EC must take necessary measures to minimize conflicts of interest.

National Ethics Committee for Health and Life Sciences (CNESS)

According to DecreeNo02-200, the CNESS is required to develop standard operating procedures (SOPs) specifying detailed rules for the operation of the committee, the technical committee(s), and the Permanent Secretariat. The Minister of Health and Social Development must approve the SOPs.

Per DecreeNo02-200, the CNESS must convene upon the request of the president. The committee may also meet at the request of a simple majority of its members in sessions, in special sessions, or whenever circumstances require the members to do so. CNESS meetings are not open to the public, and the committee may deliberate only if at least half of its members are present. For additional CNESS procedures and information on other administrative processes, see DecreeNo02-200.

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

As explained in D-No2021-0415, the term of office for CIESS/USTTB members is three (3) years and is renewable one (1) time. Committee membership is free. The president leads the meetings and represents the CIESS/USTTB among various organizations and institutions. When the president is absent, the vice-president performs the president’s duties.

In addition, per D-No2021-0415, the CIESS/USTTB meets whenever necessary, when convened by its president. The president is required to convene the meeting at the written request of two thirds of its members. The committee cannot review proposals without the absolute majority of its members. If a quorum is not reached, the members are reconvened within a period of eight (8) days and the committee’s deliberations are then valid regardless of the number of members present. In addition, per D-No2021-0415, the agenda and the necessary documents are made available to members at least one (1) week prior to the meeting.

D-No2021-0415 further states that consensus is the basic principle governing the functioning of the CIESS/USTTB. If consensus is not reached, the decision may be made by a relative majority vote. The president must have an additional vote if a majority does not emerge. The president may propose that the committee sessions be extended to observers in an advisory capacity.

Additionally, per MLI-17, CIESS/USTTB members are required to take the Human Subjects Research course prepared by the Collaborative Institutional Training Initiative (CITI) Program and the ICH Good Clinical Practice E6 (R2) course prepared by the Global Health Training Centre.

National Institute of Public Health (INSP) Ethics Committee

As per DecreeNo2019-0247, the INSP EC meets each time as needed, mainly for reviewing protocols submitted for its approval, upon convocation by its president, or at the request of two thirds of its members. The EC members are appointed by the Minister of Health and Social Development for a period of three (3) years and it is renewable.

Title 3 (Article 13)

Article 1

Chapter III (Articles 22-23)

Articles 4-11 and 16

Article 1

Chapter 2

Articles 5, 17, and 19

Articles 22-23

Scope of Review

Last content review/update: November 27, 2024

Overview

The G-EthicalEval indicates that the main task of an ethics committee (EC) is to review research proposals and supporting documents, with particular attention to the process of obtaining informed consent, documentation, and the relevance and feasibility of the protocol. The EC must take into account previous scientific and ethical assessments, if any, and the requirements of applicable laws and regulations. An EC may perform its function at the institutional, local, regional, or national level.

According to the G-EthicalEval, ECs are responsible for protecting the rights of research participants, their safety, and their well-being. ECs must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, methods, and scientific design of the study; assessing the participant recruitment process; and verifying the adequacy of confidentiality and privacy safeguards.

Role in Clinical Trial Approval Process

According to the G-EthicalEval, the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention)’s Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) and the EC must approve a clinical trial application for research involving human participants prior to the sponsor or the principal investigator (PI) initiating the clinical trial. The G-EthicalEval further specifies that the PI must submit the request for ethics review. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

As per the G-EthicalEval, the study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. The EC must communicate its opinion on the protocol to the PI. A copy of the EC’s opinion should be sent to ACOREP. EC approval of the protocol must be obtained before ACOREP may approve the trial. In the event of a favorable opinion from the EC, ACOREP decides whether to approve the trial. If the EC issues an adverse opinion, ACOREP cannot authorize the study. However, the PI may resubmit the protocol to the EC after modifying the elements that led to the adverse opinion.

According to the G-EthicalEval, ECs must establish procedures for expedited review of research proposals. These procedures must address certain processes, including the nature of the requests, amendments, and other considerations acceptable for expedited review, as well as the quorum requirements for expedited review.

As per the G-EthicalEval, ECs must also establish a procedure for monitoring the progress of all research that has been approved, from the date the decision was made to the end of the research. The follow-up intervals should be determined by the nature of the study and other events, although each protocol should be monitored at least once a year during the recruitment period. The EC must review and approve any protocol amendments prior to those changes being implemented.

The G-EthicalEval also indicates that the PI must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

There is no stated expiration date for an EC approval in the G-EthicalEval.

(See the Submission Process section for detailed submission requirements.)

1.25, 4, 5.5

Guidelines 4, 5, 13, 16, 17, 20, 33, and 35

Last content review/update: December 5, 2024

Overview

According to LawNo09-059, the primary mission of Mali’s ethics committees (ECs) is to ensure the scientific quality and ethical conduct of health research in the country, specifically with regard to participant protection and consent. ECs must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and by verifying the adequacy of confidentiality and privacy safeguards. ECs must also confirm that the study’s goal is to increase scientific understanding of humans and to provide approaches likely to improve the health conditions under consideration. See LawNo09-059 for detailed ethical review guidelines. Per DecreeNo2017-0245, the rights of vulnerable persons, must be particularly protected when they are participating in a study. See also MLI-4 for additional information related to the protection of personal data in biomedical research.

Per MLI-17, all six (6) ECs in Mali follow the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (MLI-7).

Per MLI-17, Mali’s ECs also require researchers to comply with MLI-7.

National Ethics Committee for Health and Life Sciences (CNESS)

According to DecreeNo02-200, the National Ethics Committee for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)) was established by the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) as an advisory committee on ethical issues raised by advances in knowledge in the fields of medicine, pharmacy, biology, health, and other life sciences, and to make recommendations in these areas.

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

As indicated in D-No2021-0415, the mission of the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) is to give opinions on the ethical problems raised by the progress of research in the field of health and life sciences and to make recommendations on these subjects. See the D-No2021-0415 for additional information on the CIESS/USTTB’s responsibilities.

Per the FMPOS-USTTB-ECProcs, in addition to complying with the MLI-7, the CIESS/USTTB complies with the World Health Organization (WHO)’s Good Clinical Research Practices (MLI-3), the Declaration of Helsinki (MLI-16), and any other requirements in force in Mali. (Note: Per MLI-17, the CIESS/USTTB is still using the FMPOS-USTTB-ECProcs.) Additionally, per MLI-17, the CIESS/USTTB also follows the MLI-7 guidelines.

Per the FMPOS-USTTB-ECProcs, the CIESS/USTTB must also establish a monitoring and evaluation procedure for all research protocols with a favorable decision. This follow-up monitoring should be in effect from the initial decision through the conclusion of the trial.

National Institute of Public Health (INSP) Ethics Committee

Per OrderNo2019-011, the National Institute of Public Health (Institut National de Santé Publique (INSP))’s mission is to set up a health watch system and epidemiological surveillance and to promote health policy and systems research. In accordance with LawNo2019-023, which ratifies OrderNo2019-011, the INSP established an EC as one (1) of its administrative and management bodies. Per OrderNo2019-011, taking into account the socio-cultural context, the INSP EC is charged with giving its opinions on response measures to health threats and crises, research projects and information programs, and education and communication. See also MLI-15 for additional information on the INSP.

Role in Clinical Trial Approval Process

As set forth in LawNo09-059 and the DPM-ClinTrialDocs, EC approval is required prior to obtaining the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM))’s approval. The EC must communicate its opinion on a research project to the DPM. Further, the sponsor or investigator must send the EC’s opinion with its application to the DPM prior to the agency commencing its review. Therefore, the DPM review and approval process may not be conducted in parallel with the EC review.

Per DecreeNo2017-0245, the EC must notify the investigator of its decision in writing. The CNESS must be informed when an institutional EC, such as the CIESS/USTTB, approves a research protocol. If the protocol is rejected, then the EC must notify other ECs in Mali and the DPM. The investigator may request a reassessment after integrating the feedback and requested changes from the EC. The EC is obliged to consider this request.

Per DecreeNo2017-0245, the EC must also review and approve any protocol amendments prior to those changes being implemented.

Additionally, per DecreeNo2017-0245, the investigator must comply with all decisions and recommendations from the EC. Investigators must also immediately inform the EC of any problems encountered during the course of the study, including deviations from the protocol and complaints from participants. DecreeNo2017-0245 mandates that clinical research must follow good clinical and laboratory practices.

There is no stated expiration date for an EC approval in LawNo09-059, DecreeNo2017-0245, or the FMPOS-USTTB-ECProcs.

National Ethics Committee for Health and Life Sciences (CNESS)

According to MLI-17, the CNESS’s EC only participates in the EC review process with the CIESS/USTTB when the research pertains to an emerging infectious disease, such as during the Ebola virus disease outbreak. MLI-17 also notes that the CNESS is responsible for reviewing and approving protocols submitted by the Mali government or protocols of public health importance to the country.

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

MLI-17 indicates that the CIESS/USTTB is the primary EC responsible for reviewing and approving clinical research protocols. Per D-No2021-0415, the CIESS/USTTB is specifically responsible for analyzing and evaluating health research projects in compliance with scientific and ethical principles; deciding on the ethical validity of research protocols submitted for its assessment; and carrying out the mid-term review of approved research protocols and regularly monitoring them in the field to ensure the research is carried out in accordance with the ethical principles.

National Institute of Public Health (INSP) Ethics Committee

According to MLI-17, the INSP's EC only participates in the EC review process with the CIESS/USTTB when the research pertains to an emerging infectious disease, such as during the Ebola virus disease outbreak.

1.25, 4, and 5.5

Title 2 (Article 3) and Title 3 (Articles 10 and 12-15)

Articles 1 and 21

Articles 2-3

Chapter 1

Articles 3, 5-6, 14, 18-19, and 21

Chapters I and II, Annex, and Guide to Ethics Committee Protocol Review

Ethics Committee Fees

Last content review/update: November 27, 2024

According to the G-EthicalEval, an ethics committee (EC) may charge a fee for the ethical and scientific evaluation of research protocols, to be directed toward its operating costs. The fee must be a predetermined public rate and should not exceed 2% of research costs, excluding the cost of investment. Applicants should contact ECs individually for specific fees and payment instructions.

Guideline 5

Last content review/update: December 5, 2024

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

Per the FMPOS-USTTB-ECProcs, the cost to submit a protocol for review by the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) is 20,000 West African CFA francs.

However, according to MLI-17, CIESS/USTTB investigators are required to pay a fee of 300,000 West African CFA francs to submit a protocol for EC review and approval.

Payment Instructions

No information is available regarding payment instructions for the CIESS/USTTB.

National Ethics Committee for Health and Life Sciences (CNESS)

No information is available regarding fees or payment instructions for the National Ethics Committee for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)).

National Institute of Public Health (INSP) Ethics Committee

No information is available regarding fees or payment instructions for the National Institute of Public Health (Institut National de Santé Publique (INSP)) EC.

Chapter I (Section I, Article 8)

Oversight of Ethics Committees

Last content review/update: November 27, 2024

Overview

Order1250-ZKM043 indicates that the Democratic Republic of the Congo’s (DRC) national ethics committee (EC), the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), is responsible for promoting the creation of and accrediting institutional ECs across the country.

According to Order1250-ZKM043, the CNES coordinates the national network of institutional ECs, both public and private, throughout the country, and mobilizes funds for the functioning of the network of ECs.

Registration, Auditing, and Accreditation

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

Title II (Article 4)

Last content review/update: December 5, 2024

Overview

No information is available regarding ethics committee (EC) authorization in Mali. However, per DecreeNo2017-0245, the state, the local authorities, the development partners, and the clinical research promoters provide financing and capacity building for ECs.

Registration, Auditing, and Accreditation

No information is available on registration, auditing, and accreditation.

Article 22

Submission Process

Last content review/update: November 27, 2024

Overview

Per D-ACOREP and the G-EthicalEval, the Democratic Republic of the Congo (DRC) requires clinical trial authorization from the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention). According to DRC-12, the sponsor, through the principal investigator (PI), obtains this authorization from ACOREP. In addition, the G-EthicalEval indicates that the PI is required to obtain approval from an ethics committee (EC) for any research proposal involving human subjects. The study protocol must be submitted to the EC for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, ACOREP approval is contingent upon EC approval.

Regulatory Submission

Per DRC-12, ACOREP’s delivery address is:

Ministère de la Santé Publique, Hygiène et Prévention
Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)
4ème niveau, immeubles 5 à sec, boulevard du 30 juin
Kinshasa I, B.P. 11998, République Démocratique du Congo

Ethics Review Submission

The G-EthicalEval indicates that the EC is responsible for establishing well-defined procedures for submitting an application for review, including requirements for language and assembly. These procedures, as well as any standard forms, must be public and available to applicants. In order to aid researchers, it is desirable that these procedures and forms be harmonized between all the active ECs in the country. Applicants should contact ECs individually for specific submission instructions.

According to a subject matter expert as of March 2019, research protocols and relevant materials to be submitted to the national EC, the National Committee of Health Ethics (Comité National d'Éthique de la Santé (CNES)), should be sent to:

National Committee of Health Ethics
Local 5, Immeuble PNMLS, 1er Niveau, Commune of Kasa-Vubu
Kinshasa, Democratic Republic of the Congo

Per a subject matter expert as of March 2019, CNES requires one (1) copy of the dossier, in addition to seven (7) copies of the protocol. Documents submitted to CNES must be in French.

Title II (Articles 3-4)

Guidelines 4, 5, and 13

Last content review/update: December 5, 2024

Overview

In accordance with LawNo09-059 and DPM-ClinTrialDocs, Mali requires the sponsor (also referred to as the promoter in Mali) or the principal investigator (PI) to obtain clinical trial authorization from the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) within the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)). As delineated in LawNo09-059, the investigator is required to obtain approval from a scientific committee and ethics committee (EC) prior to obtaining the DPM’s approval. According to MLI-17, the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d’Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) is the primary EC for reviewing clinical research protocols in Mali. As per LawNo09-059 and the DPM-ClinTrialDocs, the sponsor or the PI must send the EC’s opinion with its application to the DPM prior to the agency commencing its review. Therefore, the DPM review and approval process may not be conducted in parallel with the EC review. (See the Submission Content section for detailed submission requirements).

Regulatory Submission

As per DPM-ClinTrialDocs and MLI-1, applicants must submit an application for clinical trial authorization. DPM-ClinTrialDocs states that one (1) hard copy of the application should be submitted with a commitment signed by the sponsor along with one (1) hard copy of each of the clinical trial application documents. However, MLI-1 indicates that two (2) copies of the application file should be submitted in paper format along with one (1) copy in electronic format (specifying CD or USB drive). MLI-1 further explains that the application file consists of three (3) parts:

Letter of request addressed to the Minister of Health (template provided)
Admissibility and receipt of the application file (consisting of a Checklist to be completed by the applicant and the DPM, and a Receipt box to be completed by the DPM’s research and evaluation section)
Application form (to be completed by the applicant)

Per MLI-9, there are no guidelines on the format of the clinical trial application or proposed protocol amendments.

There is no specified language requirement for all the documents to be submitted to the DPM. However, per DPM-ClinTrialDocs, the investigator’s brochure must be provided in French. MLI-1, by comparison, only indicates that the protocol must be written in French. DecreeNo2017-0245 also states that the protocol must be written in French.

Ethics Review Submission

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

According to the FMPOS-USTTB-ECProcs, investigators are required to submit 15 hard copies of the application packet to the CIESS/USTTB. The protocol must be submitted in paper and electronic form and the documents must be in French.

National Ethics Committee for Health and Life Sciences (CNESS)

No information is available regarding submission procedures for the National Ethics Committee for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)).

National Institute of Public Health (INSP) Ethics Committee

No information is available regarding submission procedures for the National Institute of Public Health (Institut National de Santé Publique (INSP)) EC.

Title 1 (Chapter 2, Article 2), Title 3 (Article 13), and Title 4 (Articles 22-23)

Article 3

Annex

Submission Content

Last content review/update: November 27, 2024

Regulatory Authority Requirements

Per DRC-12, the following documents are required in a clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention):

Cover letter
Non-refundable application fee in accordance with ACOREP’s prescribed fee schedule
Application forms completed by ACOREP for the conduct of clinical trials and signed by authorized persons (principal investigator (PI) and authorized representative of the sponsor)
Clinical trial protocol
Proof of enrollment in a clinical trial registry
Investigator's brochure (IB)
Investigational product (IP) dossier
Certificate of good manufacturing practice (GMP)
Certificate of good clinical practice (GCP) and PI curriculum vitae (CV) for each site
Ethics committee (EC) approval
Insurance cover
Financial statement
Data and Safety Monitoring Board (DSMB) information and signed charter
Sponsor/PI contractual agreement
Informed consent and assent forms (if applicable)
Statistical analysis plan (SAP)
Material transfer agreement (if applicable)
Labeling materials

According to DRC-12, applications submitted to ACOREP should also comply with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

Ethics Committee Requirements

As specified in the G-EthicalEval, the PI must file the request for ethics review. The requirements for the submission must be clearly described in the EC’s application procedures. These requirements must include or specify at least the following:

Name(s) and address(es) of the secretary of the EC or the member(s) to whom the application is to be filed
Application form(s), made available by the EC, with a list of the documentation requested by the EC
Format of the application, clearly referring to the title, date, and version of the protocol
Documentation, the study protocol, the informed consent form (ICF), the IB, the PI's CV, and the certificate of insurance obtained
Language(s) in which the (essential) documents are to be filed
Number of copies to be filed
Application deadlines, based on review dates (15 days prior to the meeting)
Means by which the receipt of applications will be acknowledged, including communication regarding incomplete applications
Deadline for notification of the decision after examination (within 15 days)
Time limit in case the EC requests additional information or changes to the documents from the PI
Application examination fee, if applicable
Standard procedure for requesting amendments to the protocol

As per the G-EthicalEval, the following documentation must be submitted to the EC for the proposed research:

Application form dated and signed by the PI
Proposed research protocol (clearly identified and dated), describing objectives, data collection procedures, ethical considerations, and details of the research process
Supporting documents for information not detailed in the protocol
When the research involves a product under study (such as a drug or medical device), an adequate summary of all available safety, pharmacological, pharmaceutical, and toxicological data available on the product being evaluated, as well as a summary of the clinical experience gained to date on this product
Current CVs of the investigator(s), dated and signed
Planned means (including classified advertising) for the recruitment of potential research participants, if not described in the protocol
Description of the procedure to obtain the informed consent of the subjects according to the degree of instruction, if not sufficiently described in the protocol
Information pamphlet (clearly identified and dated) and other forms of information for potential participants, in the language(s) understood by them and, if necessary, in other languages
ICF (clearly identified and dated) in the language(s) understood by potential participants and, if necessary, in other languages
Statement regarding possible compensation for research subjects, for their participation (including reimbursement of expenses and access to medical care), if not sufficiently described in the protocol
Description of arrangements made, if any, for compensation for injury, if not sufficiently described in the protocol or certificate of insurance
A copy of the sponsor’s insurance policy, for the insurance coverage of the participants (if in a language other than French, a translation into French must also be provided)
Statement by the investigator committing to respect the ethical principles set out in the applicable guidelines, if not sufficiently described in the protocol
Any significant prior decisions made by other ECs or regulatory authorities regarding the research in question (whether in the same research site or another) and an indication of the change(s) made to the protocol in this regard (reasons for previous adverse decisions must be provided)
Any other information, such as the establishment of a Tolerance Data Monitoring Committee, also known as DSMB or Independent Committee

Clinical Protocol

According to the G-EthicalEval, the protocol should be prepared by the researcher(s) and contain a summary of the project, general information, a brief justification of the project, bibliographical references, and a documentary review. The protocol should describe the goals and objectives of the study, as well as its design and the methodology used. In addition, the protocol should address safety or tolerability considerations, monitoring, statistical data management and analysis, quality assurance, expected results and dissemination, and publication policy.

The G-EthicalEval further requires that the protocol provide guidance on the duration of the project and anticipated problems, project management and ethical considerations, the documents used to gather informed consent from subjects, the budget and funding agencies, and collaborators. Finally, the protocol should attach the CV of each researcher, listing all the projects in which the researcher is currently participating, and the percentage of time to be devoted to the project. Possible financing or insurance arrangements should also be specified in documents presented to the EC.

Additionally, DRC-3 requires the following protocol contents:

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
Publication policy

6

Guidelines 4, 5, 13, and Glossary

Last content review/update: December 5, 2024

Regulatory Authority Requirements

As specified in DPM-ClinTrialDocs and MLI-1, the following documentation must be submitted by the sponsor (also known as the promoter in Mali) to the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Completed clinical trial authorization application signed by the sponsor
Copy of the ethics committee (EC) approval of clinical trial protocol
Copy of the clinical trial protocol signed by the sponsor in French
Copy of investigator’s brochure (IB) in French
Copy of insurance contract covering entire trial period
Updated and valid certificate of clinical trial insurance
Declaration forms completed and signed by the investigator(s)
Copy of informed consent form (ICF)
Participant information note/flyer
Statement of commitment signed by the sponsor
Copy of investigators’ curriculum vitaes (CVs)
Certificate(s) of Good Manufacturing Practices for Products issued by the pharmaceutical regulatory authority in the country of manufacture (clinical trial IP, placebo, comparator product, other products used in the clinical trial)
Copy of product stability certificate
Establishment opening certificates and/or authorization certificates of manufacturing laboratories issued by the pharmaceutical regulatory authority of the country of manufacture
Copies of import and/or export requests for investigational products (IPs)
Supporting documents for payment of application fees
Other documents provided (specify)

Per MLI-9, there are no guidelines on the format and content of the clinical trial application or proposed protocol amendments.

Ethics Committee Requirements

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

As per the FMPOS-USTTB-ECProcs, investigators must submit the following documentation to the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) in the clinical trial application packet:

Application letter
Application form (dated and signed)
Protocol (dated and in print and electronic form) with supporting documents/annexes
Protocol synopsis (non-technical language, if possible)
Description of research related ethical considerations
Summary of IP (e.g., tolerance, pharmacological, pharmaceutical, and toxicological data) (See Investigational Products topic for detailed coverage of this subject)
Summary of clinical experience acquired to date (e.g., IB, publication(s), and product characteristic summaries)
ICF and other related information for potential participants (See Informed Consent topic for additional information)
Participant compensation information (see Insurance & Compensation section for additional information)
Participant information (e.g., booklet of observations, patient diaries, and questionnaires)
Study insurance policy
Opinion of the Scientific Committee from the applicant institution, if available
Investigators’ CVs (dated and signed) and their percentage of time on the project
Recruitment procedures
Investigator declaration to comply with ethical principles
Decision of previous review by other ECs or regulatory authorities (if applicable)
Budget

See the FMPOS-USTTB-ECProcs for detailed CIESS/USTTB submission requirements.

National Ethics Committee for Health and Life Sciences (CNESS)

No information is available regarding submission content for the National Ethics Committee for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)).

National Institute of Public Health (INSP) Ethics Committee

No information is available regarding submission content for the National Institute of Public Health (Institut National de Santé Publique (INSP)) EC.

Clinical Protocol

Per MLI-17, the clinical study protocol should include the following elements:

Protocol summary
Sponsor information
CVs of key personnel and their level of effort within the project
Budget
Trial schedule rationale
Recruitment and enrollment process
Informed consent process
Procedures
Compensation
Risks and benefits
Event grading and reporting

According to DecreeNo2017-0245, the protocol must be written in an easy-to-understand language and comply with international standards. It must also describe the conditions for obtaining the free and informed consent of research participants. Per MLI-17, Mali’s ECs require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7).

2nd Part - Admissibility and Receipt of the Application File Section 1 (Checklist)

6

Articles 3-5

Chapter I, Section II, Annex, and Guide to Ethics Committee Protocol Review

Timeline of Review

Last content review/update: November 27, 2024

Overview

As per D-ACOREP, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) is the regulatory authority responsible for regulating clinical trials in the Democratic Republic of the Congo (DRC).

The G-EthicalEval indicates that for research involving human subjects, the study protocol must be submitted to an ethics committee (EC) for review concurrently with a request to ACOREP for study authorization and registration. Therefore, regulatory and ethics reviews are conducted in parallel. However, the principal investigator (PI) must obtain the EC’s approval of the protocol before ACOREP may approve the trial.

Regulatory Authority Approval

No official timelines are specified in the available regulatory documentation.

Ethics Committee Approval

As per the G-EthicalEval, the EC must communicate its opinion on the protocol to the PI within 15 days of making a decision, and send a copy to ACOREP.

The G-EthicalEval further requires that ECs establish procedures for expedited review of research proposals. These procedures must address certain processes, including the nature of the requests, amendments, and other considerations acceptable for expedited review, as well as the quorum requirements for expedited review.

There is no stated expiration date for an EC approval in the regulatory resources referenced for the DRC.

Title II (Articles 3-4)

Guidelines 4, 5, 13, and 17

Last content review/update: December 5, 2024

Overview

Per LawNo09-059 and the DPM-ClinTrialDocs, the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM))’s review and approval of a clinical trial application is dependent upon obtaining written proof of the ethics committee (EC) approvals. Therefore, the DPM review and approval process may not be conducted in parallel with the EC review.

Regulatory Authority Approval

Per MLI-9, the DPM Quality Assurance Division has set the timeline for evaluating applications at 15 days, but there are no guidelines stipulating specific timelines for review. The DPM secretary provides the clinical trial application to the DPM director once it is received. The approval decision is provided to the applicant as well as regional offices, health professional councils, health inspectors, and all Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) departments.

Ethics Committee Approval

Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB)

As specified in the FMPOS-USTTB-ECProcs, the investigator must submit a request to the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d’Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) President at least 15 days before the date of the EC’s meeting to review the protocol. The CIESS/USTTB will then acknowledge receipt of the application and will inform the investigator if the application is complete. The CIESS/USTTB will complete its review of the protocol within a minimum period of 15 days. Only those members who attended the meeting or communicated their opinion at the meeting are permitted to be involved in the decision-making process. The decision will be one (1) of the following: approved, conditional approval (modifications/response to stipulations), or rejected.

The FMPOS-USTTB-ECProcs further states that in the event the president is requested to provide an urgent protocol review (referred to as a restricted review), then the evaluation is conducted according to the same review process used by the EC, but involves only six (6) committee members specifically selected for their expertise in a particular research area. In this case, the decision made by the restricted review committee is communicated to the rest of the EC during the next session. The investigator is notified in writing about the committee’s decision within seven (7) business days.

National Ethics Committee for Health and Life Sciences (CNESS)

No information is available regarding timeline of review for the National Ethics Committee for Health and Life Sciences (Comité National d’Éthique pour la Santé et les Sciences de la Vie (CNESS)).

National Institute of Public Health (INSP) Ethics Committee

No information is available regarding timeline of review for the National Institute of Public Health (Institut National de Santé Publique (INSP)) EC.

Title 3 (Article 13)

Section II and Annex

Initiation, Agreements & Registration

Last content review/update: November 27, 2024

Overview

As per D-ACOREP and the G-EthicalEval, the Democratic Republic of the Congo (DRC) requires clinical trial authorization from the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention). According to DRC-12, the sponsor, through the principal investigator (PI), obtains this authorization from ACOREP. As stated in the G-EthicalEval, for research proposals involving human participants, the PI must also obtain approval from an ethics committee (EC) before ACOREP can approve the trial. Per DRC-12, ACOREP accepts ethics review from any approved local EC.

According to DRC-12, an import license is required for the shipment of the investigational product (IP) to be used in the trial. The sponsor may apply for IP import approval through ACOREP’s Digital Platform (DRC-13). (See the Manufacturing & Import section for additional information).

Clinical Trial Agreement

The G-EthicalEval states that before submitting a clinical trial application, a memorandum of understanding must be developed between the sponsor or PI and the partner research institutions. The PI must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

As per DRC-3, the sponsor should obtain the investigator's/institution's agreement to:

Conduct the trial in compliance with 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

As per DRC-12, proof of enrollment in a clinical trial registry is a required element of a clinical trial application to ACOREP.

5.6

Title II (Articles 3-4)

Guidelines 4 and 5

Last content review/update: December 5, 2024

Overview

According to LawNo09-059 and DPM-ClinTrialDocs, a clinical trial can only commence after the sponsor (also known as the promoter in Mali) or the principal investigator (PI) receives authorization from the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) within the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)). According to LawNo09-059, the investigator is also required to obtain approval from a scientific committee and ethics committee (EC) prior to obtaining the DPM’s approval.

Per DecreeNo2017-0245, the research must also meet the following conditions:

Benefit the country in general and the people concerned
Be conducted by a person and/or team qualified with reference to their scientific skills proven in the field
Meet the criteria of good clinical practice and internationally recognized laboratories
Respect the habits and customs recognized locally
Respect national and international standards

In addition, per MLI-17, the applicant is required to obtain an import license from the DPM which approves the protocol and forwards the EC letter to the MSDS, also noting that all of the protocol requirements have been met and approved. The MSDS, in turn, signs the clinical trial approval letter and approves the import license for the shipment of an investigational product to be used in the trial (See the Manufacturing & Import section for additional information).

Clinical Trial Agreement

Per DecreeNo2017-0245, national sponsors are required to have a written undertaking of acceptance and collaboration of the team leader of each institution where the research activities take place.

The DPM-ClinTrialDocs also states that before the trial begins, the sponsor(s) should sign the protocol and a statement of commitment to comply with ethical principles. Per MLI-1, prior to initiating the trial, the sponsor should also sign the statement of commitment in the application form for clinical trial authorization (see MLI-1) certifying the accuracy of the information provided in the application; that the trial will comply with the protocol, Malian regulations, and good clinical practice (GCP) principles; and that unexpected serious adverse effects will be declared along with submitting safety reports and a final clinical trial report to the DPM.

In addition, according to the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), the sponsor should obtain the investigator's/institution's agreement to:

Conduct the trial in compliance with GCP guidelines, the applicable regulatory requirement(s), and 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.

3rd Part - Application (Section 8 - Promoter Commitment)

5.6

Title 1 (Chapter 2, Article 2), Title 3 (Article 13), and Title 4 (Articles 22-23)

Articles 3 and 15

Safety Reporting

Last content review/update: November 27, 2024

Safety Reporting Definitions

As delineated in the G-PV, the following definitions provide a basis for a common understanding of the Democratic Republic of the Congo’s (DRC) safety reporting requirements:

Adverse Event (AE) – Any medical event occurring after the administration of a drug to a patient or subject of a clinical trial, without necessarily being caused by that drug. This includes any harmful and unwanted reaction such as a clinical or paraclinical sign or symptom, or a disease associated with taking a drug
Adverse Drug Reaction (ADR) – Any response to the administration of a drug that is harmful and undesirable. An ADR may result from the use of a drug at therapeutic doses, overdose, misuse, or medication error
Serious Adverse Event (SAE) – Any adverse reaction that causes death, is life-threatening, requires hospitalization or prolongation of hospitalization, leads to significant or persistent disability, or causes congenital malformation
Unexpected Adverse Event (UAE) – Any adverse event that does not match the known information on the drug in nature, severity, or outcome

According to the G-PV, the requirements in the G-PV are based on the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). The G-EthicalEval further indicates that before the start of the trial, the principal investigator (PI) must ensure adequate safety reporting procedures in accordance with DRC-3 and the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10).

Order1250-SP013 states that the DRC’s National System of Pharmacovigilance, implemented by the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention), aims to identify as early as possible all of the adverse effects of health products, especially those that are serious and unexpected. The National System of Pharmacovigilance includes the National Pharmacovigilance Center, which is responsible for collecting information from manufacturers, health professionals, and other individuals on the adverse effects of health products; establishing accountability; and assessing the relative risk.

Safety Reporting Requirements

The G-PV indicates that it is mandatory to report any AE, even when it is the result of abuse or misuse. All providers are required to systematically report AEs.

According to G-PV, all AEs that are both serious and unexpected must be reported through the expedited notification process. Any serious and unexpected AE that is fatal or life-threatening, including those occurring during a clinical trial, should be notified to the National Pharmacovigilance Center as soon as the notifier becomes aware of it, within seven (7) calendar days. Updated information may be provided within an additional period not exceeding 15 calendar days. All other serious and unexpected AEs should be reported immediately, but no later than 15 calendar days after becoming aware of them. All other AEs must be reported within 90 calendar days.

In addition, according to DRC-12, SAEs must be reported to the national ethics committee (EC), the National Committee of Health Ethics (Comité National d’Éthique de la Santé (CNES)), or to the EC that approved the study.

Form Completion & Delivery Requirements

As per the G-PV, all AEs must be reported on a form (See Annex I of G-PV) and submitted in a sealed envelope or via internet to the National Pharmacovigilance Center:

Clinical Pharmacology Unit
Faculty of Medicine and Pharmaceutical Sciences
University of Kinshasa
Tel: 0998110172 / 0813261360 / 0993547926 / 0815171991 / 0815171766
Email: cnpvrdc@yahoo.fr and pharmacoclinique@unikin.ac.cd

5.16-5.17

Guideline 35

Introduction, I (I.1), III (III.2 and III.5), and Annex I

Chapter I (Article 2), Chapter III (Article 6), and Chapter VII (Article 18)

Last content review/update: December 5, 2024

Safety Reporting Definitions

According to OrderNo2011-4201 and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), the following safety reporting definitions provide a basis for a common understanding of Mali’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Adverse Drug Reaction (ADR) or Adverse Reaction (AR): All harmful and unintended responses to a medicinal product related to any dose
Adverse Event (AE): Any untoward medical occurrence in a patient or clinical investigation participant who was administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment
Serious Adverse Event (SAE)/Serious Adverse Effect or Serious Adverse Drug Reaction (SADR): Any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Severe Adverse Effect: Effect requiring, in addition to discontinuation of the drug, additional care
Moderate Adverse Effect: Effect that is neither serious nor severe
Unexpected Adverse Drug Reaction or Unexpected Adverse Reaction: An adverse reaction, the nature or severity of which is not consistent with the applicable product information or summary of product characteristics concerned

Per MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with MLI-7.

OrderNo2011-4201 established the procedures for implementing pharmacovigilance via Mali’s National Pharmacovigilance System. The system includes the National Pharmaceutical Regulatory Authority (ANRP), the National Pharmacovigilance Reference Center (CNRP), and several advisory bodies. The ANRP is represented by the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)), which is responsible for ensuring compliance with pharmacovigilance operating standards and procedures; transmitting to the manufacturing laboratory the information concerning the undesirable effects of health products, and more. The CNRP is responsible for carrying out technical pharmacovigilance activities and is concerned with the safety of using medicinal products in order to verify facts reported by the notifications received. (See OrderNo2011-4201 for additional details).

Safety Reporting Requirements

As specified in the FMPOS-USTTB-ECProcs, all SAEs/SADRs that occur during the study must be reported to the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d’Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) within 72 hours of the event. All AEs/ADRs and non-serious AEs/ADRs should be identified in the continuing review report.

OrderNo2011-4201 further delineates the following reporting obligations:

Any doctor, dental surgeon, midwife, or health agent with prescribing responsibility who has observed an AE likely to be due to a health product, whether or not the responsible party is the prescriber, must report it immediately to the CNRP
Any pharmacist who becomes aware of an undesirable effect likely to be due to a health product that has been delivered must declare it immediately to the Pharmacovigilance Committee of the district to which the pharmacist belongs
Any member of a healthcare profession having made the same observation must also inform the nearest Pharmacovigilance Committee
The pharmaceutical industry and any producer or distributor of a health product are required to declare any undesirable effect relating to the products they market
Anyone who has had an AE can report to the health worker and/or the nearest health structure

Sponsor Responsibilities

Per the DPM’s application form for clinical trial authorization in Mali (MLI-1), the sponsor (also known as the promoter in Mali) is required to declare unexpected serious adverse effects and to submit safety reports in accordance with the regulations in force in Mali.

Form Completion & Delivery Requirements

No information is available regarding form completion and delivery requirements.

3rd Part - Application (Section 8 - Promoter Commitment)

1, 4.11, and 5.16

Chapter 1 (Articles 1-2), Chapter 2 (Articles 4-8), and Chapter 3

Article 21

Progress Reporting

Last content review/update: November 27, 2024

Interim and Annual Progress Reports

The G-EthicalEval also indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

DRC-3 notes that the investigator should submit written summaries of the trial status to the institutional ethics committee (EC) annually, or more frequently, if requested by the EC. The investigator should also promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

As per the G-EthicalEval, the EC must establish a procedure for monitoring the progress of all research that has been approved, from the date the decision was made to the end of the research. The follow-up intervals should be determined by the nature of the study and other events, although each protocol should be monitored at least once a year during the recruitment period.

Final Report

According to the G-EthicalEval, the PI must notify the EC of the closure of a study, and the EC should receive a copy of the final summary or final report of the research.

The G-EthicalEval further requires that community leaders receive an adapted report specifically for their understanding, with the relevant information. The results of the clinical trial should be shared with the participants based on the context and budgetary constraints.

4.10 and 4.13

Guidelines 20, 35, and 36

Last content review/update: December 5, 2024

Interim and Annual Progress Reports

No information is available regarding progress reporting requirements for the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)).

However, DecreeNo2017-0245 notes that if the study lasts longer than one (1) year, an annual report must be provided to the ethics committee (EC).

According to MLI-17, Mali’s ECs follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which also explains that the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial and/or increasing the risk to participants.

In addition, as delineated in the FMPOS-USTTB-ECProcs, the principal investigator (PI) must submit an annual progress report to the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d’Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako).

Final Report

Per MLI-1, the sponsor (promoter) is required to submit a final clinical trial report to the DPM no later than one (1) year after the end of the trial.

Per the FMPOS-USTTB-ECProcs, the PI must submit a final report to the CIESS/USTTB following the trial’s conclusion.

In addition, per DecreeNo2017-0245, researchers must provide the results of the research in the form of a workshop, final report, and/or a publication. In addition, a copy of the final report must be provided to the EC, which the committee must keep for at least 10 years. DecreeNo2017-0245 also states that Malian sponsors must inform the national authorities of the research results.

3rd Part - Application (Section 8 - Promoter Commitment)

4.10 and 4.13

Article 20

Section III (Articles 19 and 22)

Definition of Sponsor

Last content review/update: November 27, 2024

As per the G-EthicalEval, the sponsor is defined as the person, company, institute, or organization responsible for launching, managing, and/or financing a clinical trial, as well as legally responsible for the trial. In non-commercial research, it is often the case that the sponsor and the funding agency are different entities. In this case, the legal responsibility rests with the sponsor.

The G-EthicalEval indicates that for biomedical research on humans, the sponsor is the person who initiates, manages, and verifies the funding of the research.

The G-EthicalEval also indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 specifies 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.

DRC-3 also notes that a sponsor may transfer any or all 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.

According to the G-EthicalEval, a sponsor may be domestic or foreign.

1.53, 1.54, 5.1, and 5.2

Guideline 35 and Glossary

Last content review/update: December 5, 2024

As per LawNo09-059, a sponsor (also referred to as a promoter in Mali) is defined as a natural or legal person, an institution, or an organization that supports research through the initiation or financing of a clinical trial.

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which also specifies 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.

MLI-7 also notes that 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.

Per DecreeNo2017-0245, a sponsor may be domestic or foreign. Per MLI-17, an in-country representative is not required.

1.53-1.54 and 5.1-5.2

Title 1 (Chapter 2, Article 2)

Articles 15-16

Site/Investigator Selection

Last content review/update: November 27, 2024

Overview

According to the G-EthicalEval, the principal investigator (PI) must be a qualified and experienced person in the relevant field of research, with an understanding of the concepts and research activities, the drug, its toxicity, and its safety. The PI reports to the sponsor, as well as to the regulatory authorities and the ethics committees (ECs).

Per the G-EthicalEval, before a trial begins, the PI must:

Be based in the Democratic Republic of the Congo (DRC), with some exceptions
Ensure that the approval of a recognized EC and regulatory authority are obtained, and that the information package developed by the sponsor regarding clinical trials has been read and accepted
Have a good knowledge of the protocol, related documents, and regulatory requirements of the regulatory authority or other regulatory body
Have read, understood, and agreed to work in accordance with the protocol, the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), or other applicable legal and regulatory documents
Use the investigational product (IP) only for the purpose of the study as described in the protocol
Take responsibility for the IP
Document the sequence of events to be followed in the conduct of the clinical trial, including the timeline, roles, and responsibilities
Ensure the availability of all necessary infrastructure, equipment, and finances for the conduct of the test or study
Develop any appropriate mechanism to obtain informed consent from the participant
Accept the involvement of the instructors to review and verify the quality control procedures and the conduct of the data
Accept the possibility of an audit and/or inspection by an independent auditor engaged by the sponsor, the regulator, or the EC
Obtain the right to publish (it is unethical for the sponsor to reserve the right to publish the research data)
Ensure adequate safety reporting procedures, etc. (see DRC-3 and DRC-10)

As per DRC-3, 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 the organization of a coordinating committee and/or the 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 the sponsor should provide sufficient time for the investigator/institution to review the protocol and the information provided.

Foreign Sponsor Responsibilities

The G-EthicalEval requires that if a sponsor is a foreign person or entity, the sponsor must work closely with the PI(s) from the partner institution(s) with which the sponsor has signed a memorandum of understanding. Each PI, who must be based in the DRC, in turn works with one (1) or more local investigators at their site.

Data and Safety Monitoring Board

The G-EthicalEval indicates that, as appropriate, the EC should evaluate the adequacy of the arrangements made for monitoring and auditing research, including setting up a Data and Safety Monitoring Board (DSMB). Any information regarding the establishment of a DSMB should also be included in the documentation submitted to the EC in the clinical trial application packet. Per DRC-12, any DSMB information must also be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

DRC-3 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 DRC-3, 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 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

The G-EthicalEval also states that a coordinating investigator should be appointed to coordinate activities of PIs at each site of a multicenter trial.

1.25, 4, 5.5, 5.6, and 5.23

Guidelines 13, 16, and 35

Last content review/update: December 5, 2024

Overview

As set forth in LawNo09-059, the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical research study, taking into account the appropriateness and availability of the study site and facilities. When the research is to be conducted in one (1) or more public or private institutions, the sponsor or the principal investigator (PI) is required to inform the director(s) of these institutions prior to initiating the study.

Per DecreeNo2017-0245, all members of the research team must be properly trained on the needs of the research as well as in research ethics. The sponsoring institution must do the following:

Ensure the training of staff who participate in the conduct of biomedical research
Require researchers to disclose their conflicts of interest in advance
Have the conflict-of-interest declarations reviewed by an ethics committee (EC) and, where appropriate, make adjustments

In addition, DecreeNo2017-0245 mandates that clinical research must follow good clinical practices. According to MLI-17, Mali’s ECs follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which provides guidance to sponsors on investigator and site selection. According to MLI-7:

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 the organization of a coordinating committee and/or the 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.

Foreign Sponsor Responsibilities

DecreeNo2017-0245 further states that international sponsors are required to:

Take charge of the scientific and ethical evaluation of biomedical research protocols
Ensure that the proposed biomedical research is compatible with the ethical, regulatory, and national legal systems
Provide financial, documentary, and other assistance with a view to promoting the strengthening of ethical evaluation capacity
Develop reasonable and appropriate activities so that the results can be made available to participants
Help to define specific policies and procedures to encourage the integrity of biomedical research and to serve as a guide in case of allegations or evidence of scientific misconduct

In addition, per MLI-17, a foreign sponsor is not required to use a local representative or contract research organization.

Data and Safety Monitoring Board

MLI-7 notes that a Data Safety Monitoring Board 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

LawNo09-059 notes that a research coordinator should also be appointed to coordinate activities of investigators working on the same project in different centers.

As delineated in MLI-7, 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 EC approval provided
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

1.25, 5.5-5.6, and 5.23

Title 3 (Articles 2 and 13) and Title 4 (Article 20)

Articles 3, 14, and 16-18

Insurance & Compensation

Last content review/update: November 27, 2024

Insurance

As per the G-EthicalEval, the sponsor is required to carry a valid insurance policy to cover research participants. A copy of the sponsor’s insurance policy must be submitted to the ethics committee (EC) as part of the application for ethics review of the proposed research. If the insurance policy is in a language other than French, a French translation must also be provided.

Per DRC-12, insurance cover documentation must also be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

Compensation

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on providing compensation to research participants.

Injury or Death

The G-EthicalEval indicates that the clinical trial application packet submitted to the ethics committee (EC) must include a description of arrangements made, if any, for compensation for injury, if not sufficiently described in the protocol or certificate of insurance.

DRC-3 states that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

As per the G-EthicalEval, the application packet submitted to the EC must also include a statement regarding possible compensation for research subjects for their participation (including reimbursement of expenses and access to medical care), if not sufficiently described in the protocol.

4.8 and 5.8

Guidelines 13 and 35

Last content review/update: December 5, 2024

Insurance

According to LawNo09-059, DecreeNo2017-0245, and DPM-ClinTrialDocs, the sponsor is required to carry a valid insurance policy for the expected duration of the study for any unforeseen injury to research participants. The LawNo09-059 specifically states that in the case of biomedical research on human beings, the sponsor (also referred to as a promoter in Mali) must take out an insurance policy guaranteeing the civil liability of the sponsor and all involved parties, regardless of the nature of the relationship between the parties and the sponsor. Furthermore, a sponsor whose civil liability is not guaranteed by an insurance policy is at risk of being imprisoned for one (1) to six (6) months and/or fined 300,000 to 1,000,000 West African CFA francs.

In addition, MLI-1 indicates that an updated and valid certificate of clinical trial insurance should be included in the application submission package (see MLI-1 for the application form).

Compensation

Injury or Death

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which provides guidance for sponsors on how to compensate 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 specified in LawNo09-059 and the FMPOS-USTTB-ECProcs, the sponsor is responsible for providing compensation to participants in the event of trial-related injuries or death.

Per LawNo09-059, in the case of biomedical research without direct benefit to the participant, the sponsor must provide compensation to the injured participant and indemnify liable parties for any harmful consequences as a result of the research, regardless of whether the sponsor is at fault. In the case of biomedical research with direct benefit to the participant, the sponsor must provide compensation to the injured participant and indemnify liable parties, unless proof is provided verifying that the trial-related injuries are not attributable to the sponsor or that of any intervening party. In either scenario, the sponsor is not permitted to oppose the legal claims of a third party (including the trial participant) or the voluntary withdrawal of the participant who had initially consented to the research.

Trial Participation

Per LawNo09-059 and the FMPOS-USTTB-ECProcs, the participant may also be reimbursed for expenses incurred in connection with participating in the study. However, per LawNo09-059, in the case of commercial benefit of a research study, the sponsor must negotiate patronage dividends for the community being studied.

Post-Trial Access

DecreeNo2017-0245 requires the researcher to ensure that the local community has access to post-study benefits after the trial’s conclusion.

2nd Part - Admissibility and Receipt of the Application File Section 1 (Checklist)

4.8 and 5.8

Title 2 (Articles 8-9), Title 3 (Article 16), and Title 4 (Article 23)

Articles 7 and 14-15

Annex

Risk & Quality Management

Last content review/update: November 27, 2024

Quality Assurance/Quality Control

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on clinical trial quality management.

Per DRC-3, 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, identify processes and data that are critical to ensure participant protection and the reliability of trial results
Identify risks to critical trial processes and data
Evaluate the identified risks against existing risk controls
Decide which risks to reduce and/or which risks to accept
Document quality management activities and communicate to those involved in or affected by these activities
Periodically review risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

Per DRC-3, 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).

Premature Study Termination/Suspension

The G-EthicalEval indicates that in the event of suspension or premature termination of a trial, the PI must inform the ethics committee (EC) of the reasons for the decision. A summary of the results up to that point must then be submitted to the EC.

According to DRC-3, 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 EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

5.0, 5.1, 5.2, 5.5, 5.18, 5.19, 5.21, and 6.10

Guidelines 20 and Glossary

Last content review/update: December 5, 2024

Quality Assurance/Quality Control

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which provides details on quality, data, and records management. Per MLI-7, 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, identifying processes and data that are critical to ensure participant protection and the reliability of trial results
Identifying risks to critical trial processes and data
Evaluating the identified risks against existing risk controls
Deciding which risks to reduce and/or which risks to accept
Documenting quality management activities and communicating to those involved in or affected by these activities
Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, describing the quality management approach implemented in the trial and summarizing important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

Per MLI-7, 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).

Premature Study Termination/Suspension

LawNo09-059 states the sponsor must inform the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) of any premature termination of the investigation and explain the reason for this decision. The FMPOS-USTTB-ECProcs also specifies that in the case of suspension or termination of the study, the investigator must inform the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) within 72 hours and provide reasons for this decision.

5.1, 5.15, 5.19, 5.21, and 6.10

Title 3 (Article 13)

Data & Records Management

Last content review/update: November 27, 2024

Electronic Data Processing System

The G-EthicalEval indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance for sponsors on clinical trial data and records management.

As per DRC-3, 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 DRC-3 for additional information.

Records Management

According to the G-EthicalEval, the research protocol should address monitoring, statistical data management and analysis, quality assurance, expected results and dissemination, and publication policy.

As set forth in DRC-3, 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, DRC-3 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.

1.65, 5.5, and 8

Guidelines 20 and Glossary

Last content review/update: December 5, 2024

Electronic Data Processing System

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7). Per MLI-7, 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's approach to validating such systems should be based on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. 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 MLI-7 for additional information.

Records Management

As set forth in LawNo09-059, the sponsor and the investigator must record, process, and maintain research information in such a manner as to permit the presentation of complete and accurate research reports and to facilitate their interpretation and verification.

Per MLI-7, 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, MLI-7 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.

1.65, 5.5, and 8

Title 3 (Article 18)

Personal Data Protection

Last content review/update: November 27, 2024

Responsible Parties

As per the DigiCode, the data controller is a natural or legal person, public authority, agency, or other body which, alone or jointly with others, determines the purposes and means of the processing of personal data. The representative of the data controller is a natural or legal person permanently established in the territory of the country, who replaces the data controller in fulfilling the obligations provided for in the DigiCode. Additionally, the data controller must appoint a data protection officer to ensure that any processing of personal data is not likely to infringe on the rights and freedoms of the data subjects. The data protection officer is responsible for ensuring, in an independent manner, the internal application of the provisions of the DigiCode, and for keeping a register of the processing carried out by the data controller.

Additionally, the DigiCode provides for the establishment of the Data Protection Authority (APD), which will be responsible for monitoring compliance with the DigiCode provisions related to the processing of public and personal data hosted in the Democratic Republic of Congo (DRC). As of November 2024, there is no information available on the establishment of the APD. See the DigiCode for more information on the APD.

Data Protection

As stated in the DigiCode, personal data must be treated confidentially and protected, in particular when the processing involves transmissions of data over a network. The personal data must be kept in a form that permits identification of the persons concerned for a period not exceeding that necessary to achieve the purposes for which they are collected or for which they are processed. Personal data may be kept for longer periods to the extent that they will be processed exclusively for archival purposes in the public interest, for scientific or historical research purposes, or for statistical purposes, provided that the appropriate technical and organizational measures are implemented to guarantee the rights and freedoms of the person concerned. The personal data collected must be reliable, adequate, relevant, accurate, complete, and not excessive. All appropriate measures must be taken to ensure that data that is inaccurate or incomplete, in relation to the purposes for which it was collected or for which it is subsequently processed, is erased or rectified.

According to the DigiCode, the processing of personal data is subject to a prior declaration to the APD. The declaration, which includes an undertaking that the processing meets the requirements of the DigiCode, is made by the data controller or their representative. Additionally, the processing of personal data relating to genetic and medical data, as well as scientific research in these areas, requires prior authorization from the APD before any implementation. The intended transfer of personal data to a third country also requires prior authorization. The request for authorization is submitted by the data controller or their representative. See the DigiCode for more information on declarations and authorizations.

The DigiCode indicates that the request for declaration or authorization may be sent to the APD electronically, by post, or by any other means where the receipt is acknowledged by the APD. The APD will make a decision within 30 days of receipt of the request for declaration or authorization. This period may be extended once by 30 days upon reasoned decision of the APD. If the declaration or authorization requested from the APD is not made within the prescribed period, the silence of the APD will be deemed to be acceptance. In the event of refusal by the APD, the data controller may appeal within 15 days of notification of the refusal decision.

The DigiCode states that the processing of personal data is carried out within the framework of respect for human dignity, privacy, and public freedoms. The processing of personal data, whatever its origin or form, must not infringe the rights of persons protected by the laws and regulations in force and it is, in all cases, prohibited to use this data to harm persons or their reputation. Additionally, the personal data must be processed in a manner that ensures appropriate security, including protection against unauthorized or unlawful processing and against accidental loss, destruction or damage, using appropriate technical or organizational measures.

See the DigiCode for more information on the responsibilities of the data controller and the data protection officer.

Consent for Processing Personal Data

The DigiCode indicates that the processing of personal data will be lawful only to the extent that the data subject has consented to the processing of their personal data or if the processing is necessary for the performance of a legal obligation to which the controller is subject. If the data subject is incapable of giving consent, consent is governed by the principle of common law.

Per the DigiCode, where processing is based on consent, the controller must be able to demonstrate that the data subject has given consent for the processing of their personal data. Where the data subject's consent is given in the context of a written statement which also concerns other matters, the request for consent must be completed in a form which clearly distinguishes it from these other matters, in a comprehensible and easily accessible manner, and formulated in clear and simple terms. The data subject has the right to withdraw consent at any time, by the same means used to give it. Withdrawal of consent will not affect the lawfulness of processing based on consent prior to its withdrawal. The data subject must be informed of this before giving consent. Withdrawal should be as simple as giving consent. When determining whether consent is freely given, the utmost regard should be given, among other things, to whether the performance of a contract (including the provision of a service) is subject to consent for personal data processing, but such processing is not necessary for the performance of that contract.

According to the DigiCode, the data subject may request from the controller:

Information allowing them to know and contest the processing of their personal data
Confirmation as to whether or not personal data concerning them are being processed, as well as information on the purposes of the processing; the categories of data to which it relates and the categories of recipients to whom the data is communicated; the recipients or categories of recipients to whom the personal data have been or will be communicated, where possible; and the existence of automated decision-making, including profiling, and, at least in those cases, meaningful information about the logic involved, as well as the significance and envisaged consequences of such processing for the data subject
The communication in intelligible form of personal data concerning them, as well as any available information as to the origin of such data
Where applicable, information relating to the transfers of personal data envisaged to a third party, after consultation with APD
Where possible, the envisaged period for which the personal data will be retained or, where this is not possible, the criteria used to determine that period
The existence of the right to request from the controller rectification or erasure of personal data, or restriction of processing of personal data concerning the data subject, or to object to such processing
The right to lodge a complaint with the competent authority
Any available information as to their source, where the personal data are not collected from the data subject

See the DigiCode for additional details on data subject rights.

Preliminary Book (Article 2), Book I (Articles 15-18), and Book III – Digital Content (Articles 187, 189-194, 196, 209-216, 222, and 262-270)

Last content review/update: December 5, 2024

Responsible Parties

For the purposes of data protection regulation in Mali, the Mali-DPL delineates responsibilities for the “data controller.” The data controller is defined as any person who, alone or jointly with others, makes the decision to collect and process data of a personal character and determines its purposes. A “subcontractor,” in turn, is defined as any natural or legal person, public or private, or any other body or association that processes data on behalf of the data controller.

Data Protection

Per the Mali-DPL, the law provides conditions under which personal information may be gathered and processed. The data controller must ensure that all of the necessary precautions are taken to preserve the security of the personal data being collected. In particular, the data controller must prevent the data from being distorted, damaged, or accessed by unauthorized third parties. The authorities who are legally empowered within the framework of a particular investigative mission, such as the judicial authority, the judicial or control police, may ask the controller to communicate personal data to them. The data controller’s subcontractor must also present sufficient guarantees to ensure the implementation of security and confidentiality measures. This requirement does not exempt the data controller from the obligation to ensure compliance with these measures.

The Mali-DPL further explains that the collection and processing of personal data must comply with the following principles:

Be collected and processed in a fair, lawful, and non-fraudulent manner for specific, explicit, and legitimate purposes
Not be used for other purposes
Be adequate, proportionate, and relevant to the purposes for which they are collected or used
Be accurate, complete, and, if necessary, updated
Be kept in a form identifying the persons concerned only for the period needed to serve the purposes for which they are collected or used

These provisions do not preclude the conservation and use of data processed for archival management purposes or for historical, statistical, or scientific purposes in accordance with the procedures defined by law.

See also MLI-4 for additional information related to the processing of personal data in biomedical research.

For additional information about consent, see the Documentation Requirements and Required Elements sections.

Consent for Processing Personal Data

As delineated in the Mali-DPL, a data participant’s consent is defined as any expression of explicit, unequivocal, free, specific, and informed will by which the person concerned or the person’s legal, judicial, or contractual representative, accepts that their personal data be processed.

Mali-DPL also provides a definition for sensitive personal data that encompasses health-related considerations. Sensitive data is defined as any personal data relating to religious, philosophical, political, union, sexual, or racial opinions or activities, as well as health, social measures, prosecutions, criminal, or administrative sanctions. Processing related to sensitive data is prohibited because of the risk of discrimination and infringement of individual rights and freedoms.

However, per Mali-DPL, sensitive data may be processed with the appropriate guarantees as defined by the authority in charge of personal data protection, if the processing is necessary or is implemented to safeguard the life of the data participant or of a third party, when the data participant cannot give consent, due to legal incapacity or material impossibility.

Mali-DPL further explains that when personal data is collected directly from a data participant, during the collection and regardless of the means and media used, the data controller must provide the data participant with the following information:

The data controller’s identity, and where applicable, the representative’s identity
The determined purpose(s) of the processing for which the data is intended
The categories of data concerned
The recipient(s) or categories of recipient(s) to whom the data is likely to be communicated
Whether the answer is compulsory or optional as well as the possible consequences of a lack of response
Whether the data participant can ask to no longer be included in the file
The existence of a right of access to the data concerning the data participant and the rectification of this data
The data retention period
The planned transfers of personal data to foreign countries, where applicable

Chapter 2 (Article 3), Chapter 4 (Article 9), and Chapter 5 (Article 15)

Documentation Requirements

Last content review/update: November 27, 2024

Obtaining Consent

For any biomedical research involving humans in the Democratic Republic of the Congo (DRC), the investigator must obtain the free and informed consent of the prospective participant in accordance with the requirements set forth in the G-EthicalEval, the Declaration of Helsinki (DRC-11), the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), and the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10).

As per the G-EthicalEval and DRC-3, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC). The G-EthicalEval further states that when reviewing the informed consent process, the EC should review the arrangements for receiving and responding to requests and complaints from research participants or their representatives during the course of a study. (See the Required Elements section for details on what should be included in the form.)

In addition, DRC-3 states that that the participant or legal representative/guardian must be provided with detailed research study information. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive 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.

The G-EthicalEval indicates that in the process of obtaining informed consent, sponsors and investigators must refrain from unjustified deception, attempts to exert undue influence, or intimidation. The sponsor and investigator may solicit consent only after making sure that the potential participant understands the details of participation and has been given time to consider it.

Re-Consent

The G-EthicalEval indicates that when material changes occur in the modalities or procedures of a study, or periodically for long-term studies, the investigator must again seek the informed consent of the participants. Sponsors and investigators have a duty to obtain the informed consent of each participant in the event of a significant change in the terms and conditions of the research, or if new information emerges that may affect the willingness of the participants to continue. For example, new pieces of information may have emerged from the study or from other sources (other studies or pharmacovigilance) about the risks or benefits of the products being investigated or about products to replace them. If it changes the risk, then this information must be promptly communicated to the participants. However, the results of the study will be disclosed at the end of the research after analysis of the data.

The sponsor and investigator must also seek renewed informed consent for each participant in long-term studies at predetermined intervals, even if there is no change in the design or objectives of the research.

Language Requirements

The G-EthicalEval requires that the ICF be provided in the language(s) understood by potential participants and, if necessary, in other languages. The investigator must convey the information in the informed consent process, orally and in writing, in a language that corresponds with the level of understanding of the participant. The investigator should also consider that the participant’s ability to understand the information required to express informed consent depends on the maturity, comprehension ability, level of education, and belief system of the participant.

Documenting Consent

According to the G-EthicalEval and DRC-3, the participant or legal representative/guardian must sign the ICF. The G-EthicalEval states that it is advisable to give participants information sheets to keep that may be similar to ICFs, but do not require a signature. The EC must approve the content of the informed consent material. When consent has been obtained orally, investigators are required to provide documentation or evidence of consent.

The G-EthicalEval indicates that if the participant is illiterate, an independent witness must sign the consent. DRC-3 further specifies that 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 following steps have occurred:

The written ICF and any other written information to be provided to the participant is read and explained to the participant and legal representative/guardian
The participant and legal representative/guardian have orally consented to the participant’s involvement in the trial, and 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.

Waiver of Consent

The G-EthicalEval states that the EC may authorize, in extraordinary cases, the waiver of a signed consent form, such as in a case where the existence of a signed consent form would constitute an unreasonable threat to the privacy of the participant.

2, 4.4, 4.8, 8.2, and 8.3

Guidelines 13, 16, 24-26, and 35

Last content review/update: December 5, 2024

Obtaining Consent

In all Malian clinical trials, a freely given, written informed consent is required to be obtained from each participant in accordance with the principles set forth in LawNo09-059 and DecreeNo2017-0245. In addition, DecreeNo2017-0245 mandates that clinical research must follow good clinical practices. According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7).

As per the FMPOS-USTTB-ECProcs, DecreeNo2017-0245, and MLI-7, the informed consent form (ICF) and patient information sheet(s) are essential documents that must be reviewed and approved by the EC and provided to the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) for approval with the clinical trial application. (See the Required Elements section for details on what should be included in the form.)

LawNo09-059, DecreeNo2017-0245, and MLI-7 state that the investigator or the physician who represents the participant must provide detailed research study information to the participant or the legal representative/guardian. Per DecreeNo2017-0245, in order to provide consent, the participant must have previously received and understood all necessary information on the proposed research and have reached a decision without coercion, influence, undue inducement, or intimidation.

In addition, per DecreeNo2017-0245, the participant's involvement in clinical research must be strictly voluntary. The refusal to participate in clinical research, or the desire to withdraw from the study at any time, must not cause any harm to the participant or the loss of expected benefits.

Per MLI-7, 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 to 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.

Re-Consent

No information is available regarding re-consent requirements.

Language Requirements

The FMPOS-USTTB-ECProcs requires the ICF to be presented in written form in the language that the potential participant is able to understand. Per DecreeNo2017-0245, the ICF must also be translated into the language of the person whose consent is required, under the responsibility of the investigator or the legal representative/guardian.

Documenting Consent

LawNo09-059, DecreeNo2017-0245, and MLI-7 state that the participant must sign the ICF. However, per LawNo09-059, if it is not possible for the participant to do so, the participant’s consent may be recorded or filmed. A participant’s consent must be obtained in the presence of a third party who is completely independent of both the investigator(s) and the sponsor. In addition, where biomedical research is carried out on minors or prohibited adults with either direct individual benefit or without direct individual benefit, and the research does not present a serious foreseeable risk, consent must be provided by the legal representative/guardian of these participants.

MLI-7 states that 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 following steps have occurred:

The written ICF and any other written information to be provided to the participant is read and explained to the participant and the legal representative/guardian
The participant and 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 the legal representative/guardian should receive a copy of the signed and dated ICF.

Waiver of Consent

No information is available regarding waiver of consent requirements.

2, 4.4, 4.8, and 8.2-8.3

Title 3 (Articles 10 and 12)

Articles 8-10 and 13-14

Annex and Guide to Ethics Committee Protocol Review

Required Elements

Last content review/update: November 27, 2024

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance on the elements to include in the informed consent form (ICF) and states that information about the research study should be clearly presented in both written and oral form.

The G-EthicalEval and DRC-3 state that before seeking the consent of a person to participate in research, the investigator must indicate the following to the person using language or any other form of intelligible communication (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each):

That the person is invited to participate in the research as a subject, the reasons for which the person is eligible, and that participation is voluntary
That the person is free to refuse to participate and may at any time terminate participation without being penalized or losing any advantage to which the person would normally have been entitled
The purpose of the research and the procedures to be used by the investigator and the participant, and how the research departs from the usual medical care
For controlled trials, the modalities of the research (randomization, double-blind, etc.) and that the participant will only be informed of the assigned treatment once the study has been completed and the double-blind procedure has ended
The expected duration of participation (including the number and duration of visits to the research center and the resulting total duration) and the possibility of early termination of the trial or participation in the trial
Whether money or other types of material gratuity will be given in return for participation and, if so, their nature and amount
The anticipated expenses, if any, to the participant for participating in the trial
That, after completion of the study, the participant will be informed of the findings of the research in general terms and will be individually informed of any findings regarding the participant’s personal health status
That the participant will be able to access, upon request, data concerning the participant even if these data have no immediate clinical utility
That the participant or legal representative/guardian will be informed in a timely manner if information becomes available that may be relevant to the participant's willingness to continue participation in the trial
All risks, pain, or discomfort foreseeable for the participant (or other persons) arising from participation in the research, including risks to the health or well-being of the spouse or partner of the participant
The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
Where appropriate, the direct benefits that the participant can expect from participation in the research
The expected benefits of research for the community or society, or the contributions of this research to scientific knowledge
If, when, and how any of the products or interventions that research has shown to be safe and effective will most likely be made available to the participant after ending participation in the research
Any intervention or alternative treatment currently available
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 legal representative/guardian is authorizing such access
The arrangements that will be made to ensure the participant’s privacy and the confidentiality of the files where the participant is identified
The legal or other limitations of the investigators' ability to maintain confidentiality and the potential consequences of breaches of confidentiality
The rules applicable to the use of genetic test results and family genetic information, and the precautions taken to prevent the disclosure of genetic test results of a participant to the close family or to third parties without the participant’s consent
The proponents of the research, the institution to which the investigators report, and the nature and sources of funding for the research
Possible uses, direct or secondary, of the participant’s medical record and biological samples collected as part of clinical care
If it is anticipated that the biological samples taken from the research will be destroyed when the research is completed, and if not, a detailed description of how they will be preserved (where, how, for how long, and how it will be disposed of) and the future uses envisaged, and whether the participant has the right to decide on these future uses, to refuse the conservation, and to demand the destruction of the material in question
Whether commercial products can be derived from biological samples, and whether the participant will receive pecuniary or other benefits from the development of such products
If the investigator's sole function is to be an investigator, or both an investigator and the treating physician of the participant
The extent of the investigator's responsibility for providing medical benefits to the participant
That treatment will be provided free of charge for specified types of physical injury related to research or for research-related complications, the nature and duration of such treatment, the name of the organization or individual treatment, and if there are uncertainties about the funding of the treatment
How and by which organization the participant or family, or dependents of the participant, will be compensated for any disability or death resulting from such bodily injury (or, if applicable, that nothing is provided for this purpose)
That an EC has approved or authorized the research protocol (name and date)
Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
Approximate number of participants involved in the study
The 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

The G-EthicalEval further indicates that this list is not exhaustive, and it is recommended to follow the latest edition of DRC-11, DRC-10, and DRC-3.

4.4 and 4.8

Guidelines 25 and 35

Last content review/update: December 5, 2024

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7). Based on LawNo09-059, DecreeNo2017-0245, and MLI-7, the informed consent form (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 purpose, the procedures, the duration of the trial, and the enrollment conditions
The trial treatment(s) and the probability for random assignment to each treatment
The participant’s responsibilities and the expected duration of participation
Experimental aspects of the study
Any expected risks to the participant, including if the study is prematurely concluded. Risks should not be minimized. If applicable, risks to the embryo, fetus, or nursing infant should be described.
Explanation of the compensation and/or medical treatment available in case of adverse events that occurred during the study
Any expected benefits to the participant; benefits should not be exaggerated; it should be made clear when there is no intended clinical benefit
A description of other possible benefits for the participant and/or community, whether or not related to participation
That participation is voluntary, and that the participant can withdraw from the study at any time without liability and without detriment to the overall scientific quality of the results
In the case of withdrawal, the participant may request the withdrawal
Any compensation provided for time spent participating in the study
Any anticipated expenses for participating in the study
The contact information for the EC, the principal investigator, and any organization or person to be contacted regarding the clinical research and the participant's rights
That the monitor(s), the auditor(s), the 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
That the participant or the legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study that may affect the participant's willingness to continue
Foreseeable circumstances under which the investigator(s) may remove the participant without their consent
Approximate number of participants involved in the study

4.4 and 4.8

Title 3 (Article 10)

Article 12

Participant Rights

Last content review/update: November 27, 2024

Overview

As delineated in the G-EthicalEval, a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process.

In addition, the G-EthicalEval states that the principal investigator (PI) should closely follow the guidelines provided by the Declaration of Helsinki (DRC-11), the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the Council for International Organizations of Medical Sciences’ (CIOMS) International Ethical Guidelines for Biomedical Research Involving Human Subjects (DRC-2).

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

The Right to Participate, Abstain, or Withdraw

As set forth in the G-EthicalEval and DRC-3, the participant should be informed that participation is voluntary, and that the participant may withdraw from the research study at any time without being penalized or losing any advantage to which the participant would normally have been entitled.

The Right to Information

As delineated in the G-EthicalEval and DRC-3, a potential research participant has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, and any potential benefits, risks, or constraints. (See the Required Elements section for more detailed information regarding participant rights.)

The G-EthicalEval further states that information collected during the study should be shared with the indigenous community in the research community. Researchers must consider community input and allow dissenting voices to speak in public if differences of opinion were not resolved earlier.

The Right to Privacy and Confidentiality

According to the G-EthicalEval and DRC-3, the participant should be informed of arrangements that will be made to ensure the participant’s privacy and the confidentiality of the files where the participant is identified.

The Right of Inquiry/Appeal

DRC-3 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 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 G-EthicalEval states that the PI is responsible for the well-being and integrity of the participants. In addition, the principles in DRC-3 state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society.

2, 3.1, and 4.8

Guidelines 25, 35, and 36

Last content review/update: December 5, 2024

Overview

As delineated in LawNo09-059 and DecreeNo2017-0245, a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which addresses participant rights.

(See the Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Prisoners sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

As set forth in LawNo09-059, DecreeNo2017-0245, and MLI-7, the participant should be informed that participation is voluntary, that the participant may withdraw from the research study at any time without liability and without detriment to the overall scientific quality of the results.

The Right to Information

As delineated in LawNo09-059, DecreeNo2017-0245, and MLI-7, a potential research participant has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, and any potential compensation, benefits, risks, or constraints. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

Per DecreeNo2017-0245 and MLI-7, 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.

See also MLI-4 for additional information related to the protection of personal data in biomedical research.

The Right of Inquiry/Appeal

Per DecreeNo2017-0245 and MLI-7, the research participant or the legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries 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

DecreeNo2017-0245 and MLI-7 principles state that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

2, 3.1, and 4.8

Title 3 (Article 10)

Articles 9 and 11-14

Emergencies

Last content review/update: November 27, 2024

According to the G-EthicalEval, the principal investigator must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergencies.

Per DRC-3, 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 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.

4.8

Guideline 35

Last content review/update: December 5, 2024

LawNo09-059 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies. According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which addresses consent in the case of medical emergencies.

As per LawNo09-059 and MLI-7, the EC may approve emergency medical research when informed consent cannot be obtained from the participant. The investigator must submit a protocol for the EC’s approval that requires only the consent of the participant’s legal representative/guardian, if they are present. The participant should be informed about the research as soon as possible, at which time consent will be requested.

4.8

Title 3 (Article 11)

Vulnerable Populations

Last content review/update: November 27, 2024

Overview

In all clinical trials in the Democratic Republic of the Congo (DRC), research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process in accordance with the G-EthicalEval. Vulnerable populations, which have a limited ability to give informed consent, include children and adolescents, adults with serious mental or behavioral disorders, people with reduced levels of consciousness, pregnant women, prisoners, and socio-economically disadvantaged individuals. Research on these populations must be justified in detail, and efforts must be made to obtain the consent of the legal guardian(s) of these participants.

In addition, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 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.

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

Indigenous Peoples

According to the G-EthicalEval, special provisions must also be made for research related to the traditional or sacred knowledge of an indigenous community, or its members as indigenous people. The researcher should consult with community leaders and obtain their consent before approaching members individually. After obtaining the consent of the community, the researcher must still make sure to have the prior free and informed consent of each participant.

The G-EthicalEval further states that it is advisable to establish an informed consent process for communities and individual participants early in the research process or authorization, which should take into account the legitimate decision-making processes of communities at all stages of the process.

1.61 and 4.8

Guidelines 24, 28, and 35, and Glossary

Last content review/update: December 5, 2024

Overview

In all Malian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. LawNo09-059 states that biomedical research may only be carried out on persons incapable of giving consent or those who are unable to give consent due to restricted freedom, if consent is provided by their legal representative/guardian, and they will benefit individually or collectively from participating in the study.

According to LawNo09-059, these participants may include minors and adults incapable of giving their consent and under guardianship, pregnant women or women of childbearing age, persons deprived of their freedom, persons staying in a health or social institution, and patients in emergency situations.

DecreeNo2017-0245 mentions the following as vulnerable persons: pregnant or breastfeeding women, persons deprived of liberty, persons unable to express themselves with full cognizance, and minors.

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which 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.

Per LawNo09-059, if a study is to be conducted without direct benefit to the participant(s), the research must comply with the following conditions:

Present no serious and foreseeable health risks
Be useful to people with the same age, illness, or disability characteristics
Provide results that cannot be achieved otherwise

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

1.61 and 4.8

Title 2 (Articles 4-7) and Title 3 (Article 12)

Article 6

Children/Minors

Last content review/update: November 27, 2024

According to the FamilyCodeMemo, the age of majority is 18 years old in the Democratic Republic of the Congo (DRC).

The G-EthicalEval recommends that children be included in the decision to participate in research based on their physical, psychological, and social developmental abilities. In addition, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which 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, should sign and personally date the written informed consent.

Assent Requirements

As per the G-EthicalEval, a child's ability to give informed assent to participate in research is globally established at the minimum age of 13. The research team should consider the complexity of the research and other aspects to raise this age, but never go below it. A minor’s parent/legal guardian must provide consent for the minor to participate in the research. Once the minor reaches the minimum age of 13, the minor must also give assent. It is therefore necessary to first obtain the consent of the parent/legal guardian, and then the assent of the child.

The G-EthicalEval further indicates that the refusal of the parent/legal guardian or child constitutes dissent and precludes the child's participation in the research.

4.8

Guidelines 27 and 35

Book II (Section 3)

Last content review/update: December 5, 2024

DecreeNo2017-0245 states that the rights of participants who are minors must be particularly protected. According to MLI-17, Mali’s definition of a child/minor and the age of consent refers to individuals up to 17 years of age.

Per LawNo09-059, minors may be solicited for biomedical research only if they can benefit individually or collectively.

In accordance with LawNo09-059, when the research participant is a minor with either direct individual benefit or without direct individual benefit, their parent/legal guardian most provide consent. In addition, the research must not present a serious foreseeable risk to participants who are minors.

In addition, per LawNo09-059, if a study is to be conducted without direct benefit to participant(s) who are minors, the research must comply with the following conditions:

Present no serious and foreseeable health risks
Be useful to people with the same age, illness, or disability characteristics
Provide results that cannot be achieved otherwise

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which states that when a clinical trial includes minors, the minor should be informed about the trial to the extent compatible with their understanding and, if capable, the minor should sign and personally date the written informed consent.

Assent Requirements

No information is available regarding assent requirements.

4.8

Title 2 (Article 7) and Title 3 (Article 12)

Article 6

Pregnant Women, Fetuses & Neonates

Last content review/update: November 27, 2024

While G-EthicalEval lists pregnant women as a vulnerable population, there are no relevant provisions regarding any special consent procedures for pregnant women, fetuses, or neonates.

However, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which states that the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

4.8

Guidelines 24 and 35, and Glossary

Last content review/update: December 5, 2024

DecreeNo2017-0245 states that the rights of participants who are pregnant or breastfeeding must be particularly protected.

As per LawNo09-059, any Malian clinical studies involving a woman of childbearing age or one who is pregnant may only be conducted if the benefits of the research outweigh the risks to the woman and her embryo, her fetus, or her child.

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which states that the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

4.8

Title 2 (Article 5)

Article 6

Prisoners

Last content review/update: November 27, 2024

While G-EthicalEval lists prisoners as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them.

Guideline 24 and Glossary

Last content review/update: December 5, 2024

While there is no information available specifically regarding prisoner consent requirements, DecreeNo2017-0245 states that the rights of participants deprived of liberty must be particularly protected.

According to LawNo09-059, persons deprived of liberty may only be solicited for biomedical research if they are expected to receive a direct and major benefit for their health.

Title 2 (Article 6)

Article 6

Mentally Impaired

Last content review/update: November 27, 2024

While G-EthicalEval lists adults with serious mental or behavioral disorders as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them.

However, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which 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.

1.61, 3.1, and 4.8

Guidelines 24 and 35, and Glossary

Last content review/update: December 5, 2024

DecreeNo2017-0245 states that the rights of participants unable to express themselves with full cognizance must be particularly protected.

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participant should be informed about the trial to the extent compatible with their understanding and, if capable, the participant should sign and personally date the written informed consent.

1.61, 3.1, and 4.8

Article 6

Definition of Investigational Product

Last content review/update: November 27, 2024

As delineated in the G-PV and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), an investigational product (IP) is defined as a pharmaceutical form of an active ingredient being studied or used as a reference in a clinical trial. This includes products already authorized but used or formulated and packaged in a different way from the authorized version, when used for an unauthorized indication, or when used to gain further information about an approved use.

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with DRC-3.

1.33

Guideline 35

I (I.1)

Last content review/update: December 5, 2024

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which defines an investigational product 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.

1.33

Manufacturing & Import

Last content review/update: November 27, 2024

As per D-ACOREP and DRC-15, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention), in collaboration with the relevant foreign trade ministry, is responsible for authorizing and controlling drug manufacture and imports in the Democratic Republic of the Congo (DRC).

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 requires investigational products (IPs) to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol.

According to DRC-12, an import license is required for the shipment of the IP to be used in the trial. The sponsor may apply for IP import approval through ACOREP’s Digital Platform (DRC-13).

Please note: DRC is party to the Nagoya Protocol on Access and Benefit-sharing (DRC-1), 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 DRC-7.

2.12 and 5.13

Title II (Article 4)

Guidelines 2 and 35

Last content review/update: December 5, 2024

Manufacturing

According to DPM-ClinTrialDocs, the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) is responsible for authorizing the manufacture of investigational products (IPs) in Mali. The DPM reviews the manufacture of an IP as part of its review and approval of the clinical trial application. (See the Submission Process section for detailed application requirements).

According to MLI-17, Mali’s ethics committees (ECs) also follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which requires IPs to be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP) and used in accordance with the approved protocol.

DecreeNo2017-0245 further mandates that clinical research must follow good clinical practices. In addition, as specified in MLI-1, the sponsor (also known as the promoter in Mali) must provide the following documentation to the DPM in the clinical trial application submission package:

Certificate(s) of GMPs for products issued by the pharmaceutical regulatory authority in the country of manufacture (Clinical trial IP, placebo, comparator product, other products used in the clinical trial)
Establishment opening certificates and/or authorization certificates of manufacturing laboratories issued by the pharmaceutical regulatory authority of the country of manufacture (see MLI-1 for application)

Import

According to MLI-17, the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) is responsible for authorizing the import of IPs in Mali. Once the DPM receives the EC approval letter, it reviews and forwards the letter to the MSDS, noting that the protocol has met all of the requirements and is approved. The MSDS, in turn, signs the clinical trial approval letter and approves the import license prior to product shipment. Per DPM-ClinTrialDocs, the import license is valid for six (6) months. (See the Scope of Assessment section for more details on the clinical trial application review process). Per MLI-1, the sponsor must also provide copies of import and/or export requests for IPs to the DPM in the clinical trial application submission package (see MLI-1 for application).

Please note: Mali is party to the Nagoya Protocol on Access and Benefit-sharing (MLI-6), 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 MLI-14.

2nd Part - Admissibility and Receipt of the Application File Section 1 (Checklist)

2.12 and 5.13

Articles 3 and 18

Quality Requirements

Last content review/update: November 27, 2024

Investigator’s Brochure

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3), which provides detailed Investigator’s Brochure (IB) requirements. DRC-3 specifies that the IB must contain all of the relevant information on the investigational product(s) (IP(s)) 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 DRC-3, 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 DRC-3 for detailed content guidelines.

Quality Management

In accordance with the G-EthicalEval, an applicant must provide the ethics committee (EC) with the following IP information in the clinical trial application submission:

An adequate summary of all safety, pharmacological, pharmaceutical, and toxicological data available on the IP to be evaluated
A summary of the clinical experience to date with this IP (e.g., recent IB, publication(s), and summarized product characteristics)

Per DRC-3, the sponsor must maintain a Certificate of Analysis (CoA) to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

5.13, 5.14, 7, and 8.2

Guidelines 13 and 35

Last content review/update: December 5, 2024

Investigator’s Brochure

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which provides detailed Investigator’s Brochure (IB) requirements. MLI-7 specifies that the IB must contain all of the relevant information on the investigational products (IPs) 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 MLI-7, 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 MLI-7 for detailed content guidelines.

Quality Management

MLI-7 requires IPs to be manufactured, handled, and stored in accordance with applicable Good Manufacturing Practice (GMP).

Per MLI-7, the sponsor must also maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

In accordance with the FMPOS-USTTB-ECProcs, an applicant must also provide the Institutional Ethics Committee for Health and Life Sciences Research (CIESS)/University of Sciences, Techniques and Technologies of Bamako (USTTB) (Comité Institutionnel d'Éthique de la Recherche en Santé et en Sciences de la Vie/Université des Sciences, des Techniques et des Technologies de Bamako) with the following IP information in the clinical trial application submission:

An adequate summary of all tolerance, pharmacological, toxicological, and pharmaceutical data available on the IP to be evaluated
A summary of the clinical experience to date with this IP (e.g., recent IB, publication(s), and summarized product characteristics)

5.13, 5.14, 7, and 8.2

Annex

Labeling

Last content review/update: November 27, 2024

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 provides guidance on labeling of investigational products, stating that they should be coded and labeled in a manner that protects the blinding, if applicable. Per DRC-12, labeling materials must be included in the clinical trial application to the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention).

5.13

Guidelines 2 and 35

Last content review/update: December 5, 2024

According to MLI-17, Mali’s ethics committees follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which states that the investigational product be coded and labeled in a manner that protects the blinding, if applicable.

5.13

Product Management

Last content review/update: November 27, 2024

Supply, Storage, and Handling Requirements

The G-EthicalEval requires that the principal investigator agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3).

Per DRC-3, 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 the sponsor obtains all required documentation. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

The sponsor must ensure the following:

IP product quality and stability over the period of use
IP manufactured according to any applicable Good Manufacturing Practice (GMP)
Proper coding, packaging, and labeling of the IP(s)
Records maintained for document shipment, receipt, disposition, return, and destruction of the IP(s)
Acceptable storage temperatures, conditions, and times for the IP(s)
Timely delivery of the IP(s)
Written procedures including instructions for handling and storage of the IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
Maintain sufficient quantities of the IP(s) to reconfirm specifications, should this become necessary

Record Requirements

Per DRC-3, the sponsor should comply with the following records requirements:

Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
Maintain a system for retrieving IPs and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, and expired product recovery)
Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

2.12, 5.5, and 5.12-5.14

Guidelines 2 and 35

Last content review/update: December 5, 2024

Supply, Storage, and Handling Requirements

According to MLI-17, Mali’s ethics committees (ECs) follow and require researchers to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (MLI-7), which provides guidance on investigational product (IP) management. Per MLI-7, the sponsor must supply the investigator(s)/institution(s) with the IP(s), but not until approval is obtained from the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)) and an EC.

The sponsor must ensure the following:

IP product quality and stability over the period of use
IP manufactured according to any applicable Good Manufacturing Practice (GMP)
Proper coding, packaging and labeling of the IP(s)
Records 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 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
Maintain sufficient quantities of the IP(s) to reconfirm specifications, should this become necessary

Additionally, per MLI-7, the IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Record Requirements

Per MLI-7, the sponsor should comply with the following records requirements:

Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
Maintain a system for retrieving IPs and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, and expired product recovery)
Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

2.12, 5.5, 5.12-5.14, and 7

Definition of Specimen

Last content review/update: November 27, 2024

In the G-EthicalEval, a specimen is referred to as a “biological sample.” The G-EthicalEval does not define biological samples, but indicates that they should be considered a loan made to the investigator, unless otherwise specified in the research agreement. This requirement is inspired by the philosophies of the Bantu community on “bodily integrity,” according to which every product and part of the human body is an essential and sacred component of the person. The investigator should therefore be considered the guardian of the samples, rather than the owner.

Guideline 34

Last content review/update: December 5, 2024

No applicable requirements

Specimen Import & Export

Last content review/update: November 27, 2024

Import/Export

In accordance with the G-EthicalEval, the transfer of data or biological samples to a third party requires the consent of the researcher, the participant concerned, and the community. If the data or biological samples are transferred abroad, the applicable authorities often need to be given the Materials Transfer Agreement.

Guideline 33

Last content review/update: December 5, 2024

No applicable requirements

Consent for Specimen