Congolese Pharmaceutical Regulatory Authority (ACOREP)

As per D-ACOREP, the Congolese Pharmaceutical Regulatory Authority (Autorité Congolaise de Réglementation Pharmaceutique (ACOREP)) of the Ministry of Public Health, Hygiene and Prevention (Ministère de la Santé Publique, Hygiène et Prévention) is the regulatory authority responsible for regulating clinical trials in the Democratic Republic of the Congo (DRC). Per DRC-4, the Clinical Trials Department is responsible for clinical trial authorization and monitoring. See DRC-4 for the Clinical Trials Department organizational chart.

As stated in DRC-6, ACOREP is responsible for proposing any legislation or regulation relating to the quality and safety of medicines, foods, medical devices, herbal products, cosmetics, psychotropic drugs, and other health products. In collaboration with the Ministry of Foreign Trade, ACOREP also authorizes and controls the import, export, manufacture, labeling, marking or identification, storage, promotion, sale, and distribution of the aforementioned products, or any material or substance used in their manufacture.

In accordance with D-ACOREP, the equipment and infrastructures of the Directorate of Pharmacy and Medicine (Direction de la Pharmacie et du Médicament (DPM)) and the National Quality Control Laboratory (Laboratoire National de Contrôle Qualité (LAPHAKI)) became the assets of ACOREP as of March 5, 2020. ACOREP is comprised of a Board of Directors, the General Management, and the College of Auditors. (Note: ClinRegs will continue to reference DPM documents when this name is still used in website and regulatory material. New ACOREP regulations will be incorporated into the DRC profile as they become available.)

Order1250-SP013 indicates that the DRC’s National System of Pharmacovigilance, implemented by ACOREP, aims to identify as early as possible all the adverse effects of health products, especially those that are serious and unexpected. It includes ACOREP’s National Pharmacovigilance Commission, which evaluates the risks incurred by participants in a clinical trial and advises ACOREP on the trial’s continuation or discontinuation. In addition, the National Pharmacovigilance Center, established within the University of Kinshasa’s Unit of Clinical Pharmacology and Pharmacovigilance, is responsible for collecting information from manufacturers, health professionals, and other individuals on the adverse effects of health products; establishing accountability; and assessing the relative risk. See DRC-16 for more information on ACOREP’s Pharmacovigilance Department.

Other Considerations

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

Contact Information

Per DRC-5 and DRC-9, ACOREP’s contact information is as follows:

Ministry of Health
Congolese Pharmaceutical Regulatory Authority (ACOREP)
66 Boulevard du 30 juin immeubles
Building 5à sec 4 eme niveau
Kinshasa, Democratic Republic of the Congo

Phone: +243 824 007 007
Email: contact@acorep.gouv.cd

Overview

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

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

Clinical Trial Review Process

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

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

Congolese Pharmaceutical Regulatory Authority (ACOREP)

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

Payment Instructions

No information is available regarding payment instructions.

Overview

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

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

Ethics Committee Composition

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

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

National Committee of Health Ethics (CNES)

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

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

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

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

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

Terms of Reference, Review Procedures, and Meeting Schedule

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

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

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

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

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

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

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

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

National Committee of Health Ethics (CNES)

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

Overview

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

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

Role in Clinical Trial Approval Process

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

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

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

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

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

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

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

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

Overview

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

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

Registration, Auditing, and Accreditation

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

Overview

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

Regulatory Submission

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

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

Ethics Review Submission

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

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

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

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

Regulatory Authority Requirements

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

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

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

Ethics Committee Requirements

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

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

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

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

Clinical Protocol

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

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

Additionally, DRC-3 requires the following protocol contents:

• General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
• Background information
• Objectives and purpose
• Trial design
• Selection, withdrawal, and treatment of participants
• Assessment of efficacy
• Assessment of safety
• A description of the statistical methods to be used in the trial
• Direct access to source data and documents
• Quality control and quality assurance
• Ethical considerations
• Data handling and recordkeeping
• Publication policy

Overview

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

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

Regulatory Authority Approval

No official timelines are specified in the available regulatory documentation.

Ethics Committee Approval

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

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

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

Overview

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

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

Clinical Trial Agreement

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

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

• Conduct the trial in compliance with GCP, with the applicable regulatory requirement(s), and with the approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection
• Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

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

Safety Reporting Definitions

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

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

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

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

Safety Reporting Requirements

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

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

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

Form Completion & Delivery Requirements

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

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

Interim and Annual Progress Reports

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

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

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

Final Report

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

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

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

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

The G-EthicalEval also indicates that the principal investigator (PI) must agree to work in accordance with the Declaration of Helsinki (DRC-11), the World Health Organization’s (WHO) Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (DRC-10), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 specifies that a sponsor-investigator is an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

DRC-3 also notes that a sponsor may transfer any or all trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.

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

Overview

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

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

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

As per DRC-3, the sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If the organization of a coordinating committee and/or the selection of coordinating investigator(s) are to be utilized in multicenter trials, their organization and/or selection are the sponsor's responsibility. Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date investigator's brochure, and the sponsor should provide sufficient time for the investigator/institution to review the protocol and the information provided.

Foreign Sponsor Responsibilities

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

Data and Safety Monitoring Board

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

DRC-3 notes that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Multicenter Studies

As delineated in DRC-3, in the event of a multicenter clinical trial, the sponsor must ensure that:

• All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and given EC approval
• The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
• Investigator responsibilities are documented prior to the start of the trial
• All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
• Communication among investigators is facilitated

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

Insurance

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

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

Compensation

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

Injury or Death

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

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

Trial Participation

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

Quality Assurance/Quality Control

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

Per DRC-3, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

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

Monitoring Requirements

Per DRC-3, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

Premature Study Termination/Suspension

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

According to DRC-3, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

Electronic Data Processing System

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

As per DRC-3, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. The sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to DRC-3 for additional information.

Records Management

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

As set forth in DRC-3, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, DRC-3 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Responsible Parties

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

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

Data Protection

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

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

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

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

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

Consent for Processing Personal Data

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

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

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

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

See the DigiCode for additional details on data subject rights.

Obtaining Consent

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

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

In addition, DRC-3 states that that the participant or legal representative/guardian must be provided with detailed research study information. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

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

Re-Consent

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

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

Language Requirements

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

Documenting Consent

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

The G-EthicalEval indicates that if the participant is illiterate, an independent witness must sign the consent. DRC-3 further specifies that where the participant is illiterate or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

• The written ICF and any other written information to be provided to the participant is read and explained to the participant and legal representative/guardian
• The participant and legal representative/guardian have orally consented to the participant’s involvement in the trial, and signed and dated the ICF, if capable of doing so

Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

Waiver of Consent

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

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

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

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

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

Overview

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

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

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

The Right to Participate, Abstain, or Withdraw

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

The Right to Information

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

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

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

DRC-3 states that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

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

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

Per DRC-3, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

Overview

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

In addition, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3). DRC-3 includes the following as vulnerable populations: members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable populations include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

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

Indigenous Peoples

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

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

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

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

Assent Requirements

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

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

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

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

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

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

However, the G-EthicalEval requires principal investigators to work in accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (DRC-3), which states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participants should be informed about the trial to the extent compatible with their understanding and, if capable, they should sign and personally date the written informed consent.

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

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

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

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

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

Please note: DRC is party to the Nagoya Protocol on Access and Benefit-sharing (DRC-1), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see DRC-7.

Investigator’s Brochure

The G-EthicalEval indicates that the principal investigator must agree to work in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (DRC-3), which provides detailed Investigator’s Brochure (IB) requirements. DRC-3 specifies that the IB must contain all of the relevant information on the investigational product(s) (IP(s)) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.

As specified in DRC-3, the IB must include the following sections:

• Table of Contents
• Summary
• Introduction
• Physical, Chemical, and Pharmaceutical Properties and Formulation
• Nonclinical Studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
• Effects in Humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
• Summary of Data and Guidance for the Investigator(s)

See DRC-3 for detailed content guidelines.

Quality Management

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

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

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

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

Supply, Storage, and Handling Requirements

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

Per DRC-3, the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)). The sponsor should not supply either party with the IP(s) until the sponsor obtains all required documentation. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

The sponsor must ensure the following:

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

Record Requirements

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

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

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

Import/Export

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