Directorate of Pharmacy and Medicine (DPM)

Per DecreeNo2011-753, the Directorate of Pharmacy and Medicine (la Direction de la Pharmacie et du Médicament (DPM)) is the competent authority 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 clinical trial’s commencement, the DPM must review the clinical trial application research data submitted by the sponsor or principal investigator, as well as the opinion(s) of the ethics committee(s) consulted.

As set forth in DecreeNo2011-753, the DPM is a regulatory body under the Ministry of Health and Social Development (Ministère de la Santé et du Développement Social (MSDS)). An MSDS-appointed director is authorized to direct, coordinate, oversee, and control the directorate’s pharmaceutical activities. LawNo01-040 and Law-MOHOrg also note that the DPM’s mission is to define pharmaceutical regulations, examine and monitor drug marketing authorization dossiers, develop and implement national programs for essential drugs, and create support tools in the rational use of medicines.

DecreeNo2011-753 and OrderNo00-3476 further specify that the DPM consists of three (3) divisions including the Regulation and Monitoring Division of the Practice of the Pharmaceutical Profession (also known as the Medicine Regulation Division), the Quality Assurance and Economics of Medicines Division (also known as the Quality Assurance Division), and the Biomedical Analysis Laboratories Division.

Per DecreeNo2011-753 and OrderNo00-3476, the Regulation and Monitoring Division of the Practice of the Pharmaceutical Profession is responsible for regulating and defining the rules governing market authorization, supervising the procedures for importing, exporting, and placing pharmaceutical products on the market, and managing pharmaceutical product storage, distribution, and destruction.

DecreeNo2011-753 also explains that the Quality Assurance and Economics of Medicines Division coordinates the DPM’s quality assurance procedures, handles the review of clinical trial authorization records, ensures the evaluation and follow up of clinical trials, and manages the development of Mali’s pharmacovigilance program.

Per DecreeNo2017-0245, the DPM must:

• Ensure strict compliance with ethical standards, and good clinical and laboratory practices by researchers
• Arbitrate between the participants and/or researchers in case of occurrence of offense(s) and/or deviation(s)
• Apply the law in force for any offense(s) and deviation(s) from the protocols by the researchers

Other Considerations

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.

Contact Information

Per MLI-10, the DPM’s contact information is as follows:

Ministry of Health and Social Development
Directorate of Pharmacy and Medicine (DPM)
Darsalam
BPE 5202
Bamako
Mali

Phone: +223 20 22 24 63 and +223 2022 65 70
Email: info@dirpharma.ml

Ministry of Health

As per the ClinDrugTrialGCP, PharmLaw-VNM, DecreeMOH, and ASTTReg, Vietnam’s Ministry of Health (MOH) is the regulatory authority responsible for clinical trial approvals, registration, oversight, and inspections. The MOH grants permission for clinical trials to be conducted in Vietnam.

As indicated in DecreeMOH, the MOH is a governmental agency whose mission is to oversee all aspects of public health care management and protection for the Vietnamese population. With regard to pharmaceuticals, the MOH’s activities include, but are not limited to, formulating and promulgating legal documents, regulations, and national standards; granting and withdrawing pharmaceutical practice certificates; and issuing certificates of eligibility, registration permits, medicine import/export permits, and certificates of good manufacturing practice (GMP).

The ClinDrugTrialGCP and ASTTReg specify that the MOH’s Administration of Science, Technology and Training (ASTT) is responsible for managing the clinical trial review process. As per the ClinTrialSup, the MOH’s ASTT is also responsible for registering contract research organizations (CROs) that support clinical studies and provide other research services. (See the ClinTrialSup for detailed information on clinical trial research support activities and the related registration forms.)

Pursuant to the DrugRgstrtn, an Advisory Council created by the MOH issues registration papers for drug and medicinal ingredient circulation. The Advisory Council consists of experts with appropriate professional qualifications and experience to ensure the ability to evaluate dossiers, critique experts' opinions and recommendations of the MOH’s Drug Administration of Vietnam (DAV), and advise the Minister of Health on issues related to pharmaceutical legislation, quality, safety, and efficacy records of drugs and medicinal ingredients. See the Scope of Assessment section for more information on the Advisory Council’s role in drug clinical trial phase exemptions.

Please note: Vietnam is party to the Nagoya Protocol on Access and Benefit-sharing (VNM-2), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see VNM-6.

Contact Information

According to VNM-11, the contact information for the ASTT is as follows:

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

Phone: 04.33846688
Fax: 04.32373236
Email: cuck2dt@moh.gov.vn

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.

Overview

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

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

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

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

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

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

Clinical Trial Review Process

Registration Dossier Review

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

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

Approval Dossier Review

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

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

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

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

Inspection

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

Clinical Trial Exemptions

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

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

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

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.

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

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.

Overview

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

Ethics Committee Composition

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

Per the ECReg, EC membership should include the following:

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

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

Council of Ethics in Biomedical Research at the Grass Root Level

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

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

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

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

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

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

National Ethics Committee in Biomedical Research

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

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

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

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

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

Terms of Reference, Review Procedures, and Meeting Schedule

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

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

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

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

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

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

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.

Overview

According to the ECReg, the CEBRGLReg, the ClinDrugTrialGCP, and the PharmLaw-VNM, the primary scope of information assessed by ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. The ECs involved in clinical trial approval in Vietnam include institutional level ECs, called Councils of Ethics in Biomedical Research at the Grass Root Level (CEBRGLs), and the Ministry of Health (MOH)’s National Ethics Committee in Biomedical Research (NECBR).

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

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

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

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

Role in Clinical Trial Approval Process

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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.

Overview

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

Registration, Auditing, and Accreditation

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

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.

Overview

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

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

Regulatory Submission

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

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

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

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

Ethics Review Submission

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

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

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

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

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).

Regulatory Authority Requirements

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

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

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

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

See the ClinDrugTrialGCP for detailed requirements.

Ethics Committee Requirements

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

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

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

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

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

Clinical Protocol

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

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

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

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.

Overview

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

Regulatory Authority Approval

Registration Dossier Review

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

Approval Dossier Review

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

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

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

Ethics Committee Approval

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

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

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

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

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

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.

Overview

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

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

Clinical Trial Agreement

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

Clinical Trial Registration

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

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.

Safety Reporting Definitions

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

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

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

Safety Reporting Requirements

Investigator Responsibilities

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

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

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

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

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

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

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

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

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

Sponsor Responsibilities

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

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

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

Form Completion & Delivery Requirements

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

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.

Interim and Annual Progress Reports

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

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

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

Final Report

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

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.

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

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

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

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

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

Overview

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

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

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

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor requirements.

Data and Safety Monitoring Board

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

Multicenter Studies

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

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.

Insurance

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

Compensation

Injury or Death

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

Trial Participation

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

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.

Quality Assurance/Quality Control

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

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

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

Monitoring Requirements

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

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

Premature Study Termination/Suspension

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

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.

Electronic Data Processing System

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

Records Management

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

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

Responsible Parties

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

Decree13 states that the personal data controller must:

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

Additionally, Decree13 indicates that the personal data processor must:

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

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

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

Data Protection

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

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

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

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

Consent for Processing Personal Data

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

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

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

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

Withdrawal of Consent

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

Children

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

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

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.

Obtaining Consent

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

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

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

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

Re-Consent

No information is currently available on re-consent.

Language Requirements

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

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

Documenting Consent

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

Waiver of Consent

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

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

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

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

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

Compensation Disclosure

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

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.

Overview

In accordance with the ClinDrugTrialGCP, Vietnam’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

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

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

The Right to Information

As per the ClinDrugTrialGCP and the PharmLaw-VNM, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, and any compensation or treatment in the case of injury.

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

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

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

The Right to Safety and Welfare

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

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

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.

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

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.

Overview

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

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

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.

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

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

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

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

Assent Requirements

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

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.

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

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.

No information is currently available.

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.

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

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.

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

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.

Manufacturing

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

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

Import

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

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

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

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

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

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

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

Please note: Vietnam is party to the Nagoya Protocol on Access and Benefit-sharing (VNM-2), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see VNM-6.

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)

Investigator's Brochure

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

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

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

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

Quality Management

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

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

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.

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

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

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

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

• Drug name
• Production batch number
• Expiry date

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

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

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

Supply, Storage, and Handling Requirements

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

Record Requirements

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

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

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

No applicable requirements

No applicable requirements

Per DecreeNo2017-0245, during the informed consent process, the participant must be informed that withdrawal is possible at any time, and that the withdrawal of the participant’s data and biological material may also be requested.

No information is currently available.