Clinical research in Zimbabwe is regulated and overseen by the Medicines Control Authority of Zimbabwe (MCAZ), the Research Council of Zimbabwe (RCZ), and the National Biotechnology Authority of Zimbabwe (NBA).

Medicines Control Authority of Zimbabwe

Per the MSCAct and the MSC-Regs, the MCAZ is a statutory body that has authority for regulating and authorizing clinical trials in Zimbabwe. Further, the MSCAct authorizes MCAZ’s functions related to registering medicines, providing a national laboratory, and appointing a Director-General. The Minister of Zimbabwe’s Ministry of Health and Child Care (MOHCC) appoints MCAZ members. ZWE-3 indicates that the MCAZ is responsible for protecting public health by ensuring that medicines, allied substances, and medical devices are safe, effective, and of good quality by manufacturers and distributors.

Per the CT-AppAuth and the ZWE-GCP, all clinical trials of medicines in Zimbabwe involving human participants must not be initiated until the MCAZ has authorized the conduct of the trial, with the approval of the Secretary for Health and Child Care at the MOHCC, in accordance with the MSCAct, the MSC-Regs, and the MSC-ImportExport. ZWE-4 indicates that the Clinical Trial Unit of MCAZ’s Pharmacovigilance and Clinical Trials (PVCT) Division has regulatory oversight function for clinical trials conducted in Zimbabwe. The Clinical Trial Unit receives, processes, and evaluates applications for approval to conduct studies within Zimbabwe, as well as amendments during the conduct of a study. The CT-AppAuth further indicates that the MCAZ is responsible for authorizing the importation, exportation, and destruction of investigational products (IPs). Per ZWE-68 and the ZWE-GCP, MCAZ’s Licensing and Enforcement Division (LED) issues licenses to pharmacies, manufacturers, and dispensaries involved with IPs. See ZWE-68 for more details on LED operations and additional responsibilities of the LED’s three (3) units: the Licensing Unit, the Enforcement Unit, and the Import/Export Unit. Also see ZWE-2 for an overview of MCAZ’s licensing functions.

Research Council of Zimbabwe

As set forth in the ResearchAct, the RCZ was established as a corporate body to promote, direct, supervise, and coordinate research in the country. In addition, the RCZ is charged with registering foreign researchers and handling matters connected with or incidental to foreign researchers. According to CTEthics, the RCZ is under Zimbabwe’s Ministry of Higher and Tertiary Education, Science and Technology Development (MOST). Per ZWE-13, the RCZ provides a forum for interaction and discussion among government, academia, and industry. It is also a conduit for financial and infrastructure support for collaborative research among research institutes and councils. To achieve its mission and vision, the RCZ:

• Directs relevant quality research and creates knowledge-sharing platforms aimed at addressing national development priorities
• Develops and nurtures a research culture for evidence-based decision making
• Ensures ethical, safe, and valid research practices

National Biotechnology Authority of Zimbabwe

Established through the BioTechAct, ZWE-67 indicates that the NBA is an autonomous research and development institution with a mandate to develop Zimbabwe through the application of both conventional and new biotechnologies. It is involved in the research, development, and application of biotechnology in agriculture, medicine, energy, and the environment. According to CTEthics, the NBA is under Zimbabwe’s MOST. Per the BioTechAct, the NBA has the following functions that are relevant to clinical trials:

• Develop long-term policy for safety in biotechnology in Zimbabwe
• Promote biotechnology research, development, and application in Zimbabwe
• Review biotechnology/vaccine clinical trials and decide whether to approve, prohibit, or restrict such trials
• Review reports and monitor all ongoing approved clinical trials involving high-risk category organisms
• Approve the safety aspects of the import, export, manufacture, processing, and selling of any biotechnology products
• Advise the customs authorities on the import and export of biologically active material and biotechnology products
• Establish contact and maintain a liaison with other countries and international organizations concerned with monitoring or researching biotechnology

The CTEthics reaffirms that the NBA is empowered to approve vaccine clinical trials, as well as oversee biosafety committees and inspect laboratories that store biological agents.

Note that per the BioTechAct, in the NBA’s relation to the RCZ, the RCZ maintains the overall responsibility for the promotion, direction, supervision, and coordination of research in Zimbabwe. The NBA reports to RCZ, as requested, in relation to biotechnology research, development, and application.

Please note: Zimbabwe is party to the Nagoya Protocol on Access and Benefit-sharing (ZWE-91) 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 ZWE-92.

Contact Information

Medicines Control Authority of Zimbabwe

ZWE-66 provides the following MCAZ contact information:

Medicines Control Authority of Zimbabwe
106 Baines Avenue
Harare, Zimbabwe
Phone: +263-4-736981/5; 708255; 792165; 0772 145 191/2/3
Main Email: mcaz@mcaz.co.zw

PVCT Email: pvct@mcaz.co.zw
Imports and Exports Email: imports@mcaz.co.zw
Licensing Email: licensingunit@mcaz.co.zw

Research Council of Zimbabwe

ZWE-13 provides the following RCZ contact information for the main office:

Research Council of Zimbabwe
11 Stafford Road
Mount Pleasant
Harare, Zimbabwe
Phone: +(263) 242 304787/733/861

ProcForeignReg provides the following contact information for registration of foreign researchers:

The Executive Director
Research Council of Zimbabwe
Box CY 294
Causeway, Zimbabwe
Phone: +(263) 242-304733, 304787, and 304861
Mobile: +(263) 712954332, +263712954330
Email: technical@rcz.ac.zw

National Biotechnology Authority of Zimbabwe

ZWE-67 provides the following NBA contact information:

National Biotechnology Authority of Zimbabwe
21 Princess Drive Newlands
Harare, Zimbabwe
Phone: +(263) 242-782155, 782167, 782856
Email: nba@nba.ac.zw

Overview

As set forth in the MSCAct, the MSC-Regs, the CT-AppAuth, and ZWE-4, the Medicines Control Authority of Zimbabwe (MCAZ) is responsible for regulating and authorizing clinical trials of registered and unregistered investigational products (IPs) in human participants in Zimbabwe. The National Biotechnology Authority of Zimbabwe (NBA) and the Research Council of Zimbabwe (RCZ) also have important regulatory roles, as explained in detail below. Per ZWE-GCP and the CT-AppAuth, parallel submissions are encouraged to the regulatory authorities and to the national ethics committee (EC)—the Medical Research Council of Zimbabwe (MRCZ). However as indicated in ProcForeignReg, approval by the MRCZ is a prerequisite for RCZ’s consideration of a research permit application by a foreign researcher.

Clinical Trial Review Process

Medicines Control Authority of Zimbabwe

ZWE-4 indicates that the Clinical Trial Unit of MCAZ’s Pharmacovigilance and Clinical Trials Division (PVCT) provides regulatory oversight for clinical trials conducted in Zimbabwe. The Clinical Trial Unit receives, processes, and evaluates applications for approval to conduct studies within Zimbabwe, as well as amendments during the conduct of a study. The Clinical Trials Registry (ZWE-1) will allocate an in-house reference number and send a letter of acknowledgement of receipt of clinical trial application (CTA) to the principal investigator (PI). As set forth in the CT-AppAuth, the CTA will be reviewed by external and internal experts appointed by the MCAZ. The initial review may produce questions that need to be addressed by the applicant. Communication with the applicant should be directed through the MCAZ Director General and not through the reviewers. The reviewers will generate an evaluation or assessment report that will be considered by the MCAZ. Next, the MCAZ will make a recommendation for approval or rejection of the application to the Secretary for Health and Child Care at the Ministry of Health and Child Care (MOHCC), in accordance with the MSCAct. As set forth in the CT-AppAuth, the MCAZ may recommend approval or rejection of the application with written reasons for rejection. In the case of rejection, the applicant may appeal and provide additional information to satisfy the MCAZ’s expectations. If an application is approved, the MCAZ will issue a clinical trial authorization for the trial with conditions of authorization, including the validity period of the trial. The clinical trial authorization will be valid up to the proposed duration of the study as indicated in the CTA. The validity period may be extended upon submission of an amendment application. If MCAZ raises additional questions, the applicant will have 30 days to respond and then the MCAZ will make its decision. See CT-AppAuth, ZWE-65, and ZWE-4 for flow charts of the CTA submittal and review processes at MCAZ.

As delineated in the CT-AppAuth, amendments to an authorized clinical trial protocol must be submitted for review and approval by the MCAZ. Applications for an amendment to an authorized clinical trial must be submitted on the appropriate form (ZWE-84) with the fee. (See the Regulatory Fees section.) If the amendment is considered urgent and crucial to protect the life or well-being of trial participants or the community, the change may be implemented immediately, and the investigator must inform the EC and the MCAZ as soon as possible—by telephone followed by a written full explanation and submission of the protocol amendment application. If the amendment affects the safety of the trial participants (e.g., changes to dose, regimen, concomitant medication, or monitoring), the amendment must be submitted in full, and approval in writing from the MCAZ must be obtained prior to implementation. If the amendment is unlikely to impact participant safety (e.g., change of investigator (except PI), endpoint assay, laboratory, or statistical analysis), the full detail of the change must be submitted to the MCAZ in writing. The amendment must be implemented after receipt of approval by the MCAZ. See the CT-AppAuth for additional submission requirements, such as format and cover letter. The MCAZ will consider the clinical trial amendment application for approval/rejection and communicate its decision to the applicant in writing.

Per CT-AppAuth, the MCAZ implements an expedited review pathway for certain clinical trial applications. This pathway can be used in the case of public health emergencies or at the request of a PI. If Zimbabwe has been declared to be in a public health emergency disaster by the President or Minister of Health, the World Health Organization (WHO), or any other designated person, an expedited regulatory review pathway for clinical trials will be implemented in line with ZWE-75. Without unnecessarily compromising patient safety, the shortest realistic timelines will be made a priority. The emergency procedure will involve joint review/inspections, data sharing, and MCAZ communication with the MRCZ to speed up approval of the clinical trial.

Research Council of Zimbabwe

Per the ResearchAct, the RCZ promotes, directs, supervises, and coordinates research in the country; registers foreign researchers, and handles matters connected with or incidental to foreign researchers, including, as specified in the CTEthics, issuing permits for shipment of specimens. Per the CT-AppAuth and ProcForeignReg, foreign researchers must apply for a research permit with RCZ; they must also obtain RCZ approval to export biospecimens and/or materials. (See the Specimen Import & Export section for more information on export of specimens.) Approval by the MRCZ is a prerequisite for RCZ consideration of a research permit application by a foreign researcher. If approved, a Registration Certificate is issued to the institute of affiliation for onward transmission to the foreign researcher. Research permits are issued for a continuous period of one (1) year. After the expiration date, the research may continue upon renewal of the research permit. See ProcForeignReg and ZWE-17 for details on the renewal submission process and ZWE-60 for the renewal application form. In addition, see G-RegForeignStud for guidelines for foreign students to conduct research in Zimbabwe. The RCZ has designated days and times to answer any applicant questions as per ZWE-21.

National Biotechnology Authority of Zimbabwe

Per the BioTechAct, the NBA’s responsibilities include reviewing, approving, and monitoring biotechnology/vaccine clinical trials, as well as approving and monitoring the safety aspects of the import, export, manufacture, processing, and selling of any biotechnology products. As set forth in the ZWE-GCP and the CT-AppAuth, the NBA is responsible for clearance of recombinant DNA products and issues Trial Release Permits and Facility Registration for clinical trials involving biological products. For clinical trials involving biological products, the MCAZ requires NBA approval or proof of application to the NBA.

See the Clinical Trial Lifecycle topic for more details on the clinical trial submission and review process for these three (3) regulatory agencies.

Other Considerations

Per the CT-AppAuth, the MCAZ employs a “reliance model” for clinical trial IPs, which means it may take into account and gives significant weight to—either totally or partially rely upon—evaluations performed by another country’s regulatory authority or a trusted institution in reaching its own decision. The MCAZ implements the reliance model especially for where the safety and efficacy of the IP have already been confirmed through the WHO prequalification or when the IP has been approved in WHO-listed countries and countries considered to be trustworthy by the MCAZ. The approach facilitates conducting regulatory reviews and evaluations in a timely manner and at the same time, accelerates the evaluation process without compromising the quality, safety, and efficacy of IPs, as well as the design of clinical trials. The MCAZ, however, remains responsible and accountable for decisions taken, even when it relies on the decisions and information of others.

Medicines Control Authority of Zimbabwe

Per the MSCAct, the Medicines Control Authority of Zimbabwe (MCAZ) is authorized to make regulations to collect fees for its various medicine regulatory functions. As delineated in the MSC-Regs and the CT-AppAuth, applicants are responsible for paying various fees to submit a clinical trial application. The CT-Fees prescribes the following fees for a clinical trial application for the authorization of the use of registered and unregistered medicines with a local sponsor:

• Human medicine: $2,000 USD
• Sub-study: $1,000 USD
• Operational research study: $1,000 USD
• Observational study: $200 USD
• Any other case: $100 USD
• Initial or subsequent amendments to original application funded by a local sponsor: $50 USD
• Expedited review: the regular fees outlined above plus 50% of the process-specific fee

For an application to conduct a clinical trial by a foreign sponsor, the CT-Fees prescribes the following fees:

• Human medicine in a phase I study: $5,000 USD
• Human medicine in a phase II study: $4,000 USD
• Human medicine in a phase III or IV study: $3,000 USD
• Any other case: $500 USD
• Operational: $1,000 USD
• Bioavailability/bioequivalence: $500
• Observational: $200 USD
• Initial or subsequent amendments to original application funded by a local sponsor: $100 USD
• Expedited review: the regular fees outlined above plus 50% of the process-specific fee

For licenses, per ZWE-GCP, a MCAZ license is required for a pharmacy involved with a clinical trial. Per CT-Fees, following are the fees for a pharmacy license:

• Pharmacy in the Central Business District of a city: $1,900 USD
• Pharmacy in any other urban location: $1,000 USD
• Pharmacy under a rural district council: $600 USD
• Dispensing medical practitioner: $500 USD
• Industrial clinic: $250 USD
• Dispensary at a local authority clinic: $50 USD
• Dispensary at a public health institution: $50 USD
• Any other clinic: $150 USD

Per CT-Fees, the license application fees for a pharmaceutical manufacturer’s premises are as follows:

• Sterile pharmaceutical manufacturing unit: $6,000 USD
• Pharmaceutical manufacturer’s premises with more than three (3) dosage forms and not including sterile product manufacturing facilities: $5,000 USD
• Pharmaceutical manufacturer’s premises with up to three (3) dosage forms: $4,500 USD
• Restricted pharmaceutical manufacturing premise: $3,500 USD

Per CT-Fees, the application fees to export or import an unregistered medicine is as follows:

• Locally sponsored clinical trial: $10 USD (per medicine)
• Foreign sponsored clinical trial: $10 USD (per medicine)

Per CT-Fees, the inspection of premises fees are as follows:

• Pharmaceutical manufacturer’s premises: $1,000 USD
• Other premises: $200 USD
• Expedited inspections for other premises: $400 USD plus the cost of the re-inspection

All of the above fees are subject to a 15% value added tax (VAT) pursuant to the VATTax. See CT-Fees for additional information on MCAZ’s fee schedule, including various renewal fees.

Payment Instructions

Per ZWE-6, payments from within Zimbabwe can be made by cash deposits or direct transfer via the bank details obtained from the MCAZ accounts office. All payments from external sources should be transferred per the bank details indicated on the proforma invoice issued by the MCAZ. Applicants should cover any shortfalls caused by a commission charged by banks during a transfer. Customers are encouraged to always send scanned or physical copies after every deposit into the MCAZ account with full details of payment (e.g., registration fees). For questions, contact the MCAZ at mcaz@mcaz.co.zw or licensingunit@mcaz.co.zw.

As per ZWE-6, Zimbabwe also uses EcoCash—a mobile payment tool that enables customers to complete financial transactions directly from their mobile phone. Following are the steps for paying fees via EcoCash:

• Dial *151#
• Enter the pin number
• Select “Make Payment”
• Select “Pay Bill”
• Enter MCAZ Biller Code “03769”
• Enter amount to be paid to MCAZ
• Enter account number “0775 648 276”
• Provide EcoCash confirmation code and the reason for payment through the following platforms: Email – mcaz@mcaz.co.zw; application forms (visibly indicate the code on the forms); and mobile number 0772 609 540

Research Council of Zimbabwe

Per the ResearchAct and ProcForeignReg, foreign sponsors and researchers are required to register with the Research Council of Zimbabwe (RCZ). RegFeesForeign prescribes the following fees:

• Normal registration fee: $500 USD
• Penalty for late renewal of registration: $500 per month USD and part thereof
• Application for extension of the study: $500 USD
• Amendment fee: $500 USD
• Shipment of biospecimens (Zimbabwean students): $150 USD
• Expedited review: $1,000 USD (plus the normal registration fee of $500)

Payment Instructions

Per RegFeesForeign, the RCZ registration fee for foreign researchers must be by either international money transfer or U.S. dollar cash deposit into the RCZ Foreign Currency Bank Account:

Bank: Commercial Bank of Zimbabwe
Account Name: Research Council of Zimbabwe
Branch: Kwame Nkrumah
Currency Account: USD
Account Number: 011 200 1674 0067
Swift Code: COBZZWHAXXX
Branch Sort Code: 6119

National Biotechnology Authority of Zimbabwe

No information is currently available regarding NBA fees.

Overview

Per the ZWE-GCP, the CTEthics, and ZWE-41, all research involving human participants in Zimbabwe must be reviewed by an institutional ethics committee (EC). Further, according to ZWE-9, all health research conducted in Zimbabwe by any individual or institution is also required to receive approval from the national EC, the Medical Research Council of Zimbabwe (MRCZ) through its technical National Health Research Development Committee (NHRDC). NHRDC, a technical subcommittee of the MRCZ, was established to provide oversight on all health research conducted in Zimbabwe. NHRDC members are expected to have interest, knowledge, and experience related to the conduct of health research. Per ZWE-41, MRCZ will only accept for review and approval those research proposals that have been previously approved by an institutional EC.

Per the ResearchAct, CTEthics, ZWE-7, and ZWE-8, MRCZ’s responsibilities include serving as the national EC to provide health researchers and institutions with independent ethical advice and clearance on research. The MRCZ is established and supported by the Ministry of Health and Child Care (MOHCC). ZWE-7 also indicates that the MRCZ is a specialized council of the Research Council of Zimbabwe (RCZ) established under the ResearchAct.

Ethics Committee Composition

Institutional Ethics Committees

As delineated in the CTEthics, institutional ECs should consist of members who, collectively, have the qualifications and experience to review and evaluate the science, health aspects, and ethics of the proposed research. In addition, they should be independent, multi-disciplinary, multi-sectoral, and pluralistic. Specifically, the EC must:

• Be representative of the communities it serves and, increasingly, reflect the demographic profile of the population of Zimbabwe
• Include members of both genders, although not more than 70% should be either male or female
• Have at least nine (9) members, with 60% constituting a quorum
• Have a chairperson
• Include at least two (2) lay persons who have no affiliation to the institution, are not currently involved in medical or scientific research, and are preferably from the community in which the research is to take place
• Include at least one (1) member with knowledge of, and current experience in, areas of research that are likely to be regularly considered by the EC
• Include at least one (1) member with knowledge of, and current experience in, the professional care, counseling, or treatment of people (e.g., medical practitioner, psychologist, social worker, or nurse)
• Include at least one (1) member who has professional training in both qualitative and quantitative research methodologies
• Include at least one (1) member who is legally trained
• The institution or organization must ensure that the membership is equipped to address all relevant considerations arising from the likely categories of research. The EC must ensure that it is adequately informed on all aspects of a research protocol, including its scientific and statistical validity, which are relevant to deciding whether the protocol is acceptable on ethical grounds and conforms to the principles of the CTEthics.

ZWE-GCP also sets out guidance on EC composition and states that an EC should consist of at least three (3) professionals in the medical and scientific field with sufficient qualifications and experience; a legal professional; and a religious or consumer representative who is independent of the institution/trial site.

Medical Research Council of Zimbabwe

As described in the CTEthics, the MRCZ is composed of scientists, medical experts, ethicists, patient representatives, and community representatives. It is independent in its reflection, advice, and decisions. Per ZWE-9, the NHRDC is required to approve/disapprove and oversee all health research conducted in Zimbabwe. Members are expected to have interest, knowledge, and experience related to the conduct of health research. As described in the CTEthics, MRCZ’s NHRDC provides health researchers and institutions with independent ethical advice and clearance. The MRCZ’s responsibilities include:

• Providing guidance, advice, and approval/disapproval decisions of research protocols intended to be conducted in Zimbabwe by all researchers and health institutions
• Providing ethical guidance and advice on research programs undertaken within Zimbabwe
• Providing ethical guidance and advice on specific ethical issues presented to it by the institutional ECs and any other interested parties
• Developing and/or reviewing, as requested, ethical guidelines for Zimbabwe

Terms of Reference, Review Procedures, and Meeting Schedule

Institutional Ethics Committees

As indicated in the CTEthics, when establishing an EC, terms of reference must be set out by the institution and include the scope of its responsibilities, relationship to non-affiliated researchers, accountability, mechanisms for reporting, and remuneration, if any, for members. The institution must determine procedures for recruitment and appointment to the EC. ECs must establish and document operating procedures on the following:

• EC meetings, including frequency, preparation of agenda and minutes, distribution of papers prior to meetings, and presentation of research protocols; note the regulations delineate that 60% constitutes a quorum for EC meetings
• Presentation of all documents and other materials used to inform potential research participants
• Quorum and methods of decision-making
• Requirements for submission of research projects for ethical approval
• Registration of applications
• Timely review and written notification of decisions to researchers
• Documentation of decisions and associated reasons, including a meaningful engagement on the ethical issues
• Confidentiality of the content of the protocols and of a committee’s proceedings
• Reporting of adverse events
• Reporting of amendments to protocols
• Access to documents and regular monitoring
• Complaints procedures
• Procedures for easy and adequate access to EC members
• Fees charged
• End-of-trials review

Per ZWE-GCP, the EC should give its opinion and advice in writing clearly identifying the trial, the documents reviewed, and the dates of review.

ZWE-GCP states that only those members who are independent of the investigator/sponsor of the trial should make decisions.

Medical Research Council of Zimbabwe

ZWE-11 indicates that MRCZ has monthly meetings to review research proposals. When five (5) copies of a new research proposal are submitted for review to the MRCZ, one (1) copy becomes the MRCZ copy and the other four (4) copies are sent to external reviewers depending on their area of specialty and the title of the proposal. The external reviewers will send comments back to the MRCZ for consideration at its monthly review meetings.

Overview

Per the CTEthics and the ZWE-GCP, the primary scope of information assessed by institutional ethics committees (ECs) and the national EC—Medical Research Council of Zimbabwe (MRCZ)—relates to maintaining and protecting the rights and dignity of research participants and ensuring their safety and wellbeing throughout their participation in a clinical trial. ECs should be especially vigilant when considering research proposals involving vulnerable populations and for invasive research that has no direct benefit for its participants. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations.) The ZWE-GCP states that the MRCZ must ensure that participants are protected in accordance with international standards and guidelines, including those delineated in Appendix B of CTEthics.

Role in Clinical Trial Approval Process

Per the ZWE-GCP, the CTEthics, and ZWE-41, all research involving human participants in Zimbabwe must be reviewed by an institutional EC. Further, according to ZWE-9, all health research conducted in Zimbabwe by any individual or institution is also required to receive approval of the national EC, the MRCZ, through its technical National Health Research Development Committee (NHRDC). Per ZWE-41, MRCZ will only accept for review and approval those research proposals that have been previously approved by an institutional EC. Per ZWE-GCP and the CT-AppAuth, parallel submissions are encouraged to the regulatory authorities (the Medicines Control Authority of Zimbabwe (MCAZ), the National Biotechnology Authority of Zimbabwe (NBA), and the Research Council of Zimbabwe (RCZ)) and to the MRCZ. However as indicated in ProcForeignReg, approval by the MRCZ is a prerequisite for the RCZ’s consideration of a research permit application by a foreign researcher.

As indicated in the CTEthics, if an EC finds reason to believe that continuance of a research project will compromise participants’ welfare, it should immediately seek to establish whether ethical approval for the project should be withdrawn. This process should ensure that researchers and others involved in the project are treated fairly and with respect. Where ethical approval for a research project is withdrawn, the researcher, the institution(s), and, where possible, the participants, should be informed of the withdrawal. The institution must ensure that the researcher promptly suspends the research and arranges to meet the needs of participants. The research may not be resumed unless either the EC establishes that continuance will not compromise participants’ welfare, or the research is modified and approved by the EC.

Institutional Ethics Committees

As laid out in the CTEthics, the institutional EC’s functions are as follows:

• Review research proposals and protocols to ensure that research will be conducted to promote health, and to prevent or cure disability and disease
• Ensure that humans involved in research are treated with dignity and that their wellbeing is not compromised
• Ensure that informed consent is obtained in the case of human participants
• Grant institutional approval in instances where research proposals and protocols meet ethical standards
• Monitor all research that it approved

The ZWE-GCP states that the EC should obtain all the information relating to the trial including the protocol, investigators brochure, patient consent forms, insurance for participants, current curriculum vitaes (CVs) for investigators, and literature detailing the rationale for the study. In its review, the EC should consider the following:

• The suitability of the investigator for the proposed trial based on qualifications, experience, supporting staff, and available facilities; the suitability of the protocol in relation to the objectives of the study—its scientific efficiency and risk/benefit, including after the study, particularly in relation to chronic life-threatening conditions
• The adequacy and completeness of the written information to be given to the participants, their relatives, guardians, and if necessary, legal representatives
• Methods of initial recruitment, delivery of full information, and obtaining informed consent
• Provision for compensation/treatment in the case of injury or death of a participant if attributed to a clinical trial, and any insurance or indemnity to cover the liability of the investigator and sponsor
• The extent to which investigators and participants may be rewarded/compensated for participation
• The suitability of the study population, whether they constitute a vulnerable group, if so whether the study is justified and whether sufficient measures to protect their interest are in place
• Whether the number of participants to be recruited is adequate to demonstrate the predicted effect
• The risk-benefit analysis takes full awareness of benefits and harms beyond the life of the study itself, particularly in relation to chronic life-threatening conditions
• Whether placebos can be justified
• That by their participation in a clinical study the participants are not denied timely access to medical personnel investigations, equipment, or procedures
• That the application allows the participants and/or their representatives’ adequate time to consider the patient information package before informed consent is sought

Per CTEthics, the EC may approve, require amendment to, or reject a research proposal, and it must record its decisions in writing and should include its reasons for rejection. In considering a research protocol, the EC may seek assistance from experts, provided such experts have no conflicts of interest in relation to the research project under consideration. The EC must be satisfied that the research protocol considers participants’ welfare, rights, beliefs, perceptions, customs, and cultural heritage. For research to be conducted in community settings, the proposal must include a clear plan on how the communities will be consulted or involved in the research process, and how, they are to be kept informed. Communication between sponsors and ECs should be directed through the principal investigator (PI). All documents and other material used to inform potential research participants should be approved by the EC, including plain-language information sheets, consent forms, questionnaires, advertisements, and letters. An EC may establish procedures for expedited review of research when this is in the public interest. Expedited review and approval may be considered for research where participants have a disease that may be rapidly fatal. In general, research with potential to cause physical or psychological harm should not be considered for expedited review. This includes drug trials, research involving invasive procedures and research involving sensitive personal or cultural issues. Per ZWE-GCP, the EC should give its opinion and advice in writing clearly identifying the trial, the documents reviewed, and the dates of review.

Medical Research Council of Zimbabwe

As described in the CTEthics, the MRCZ’s NHRDC provides health researchers and institutions with independent ethical advice and clearance of research protocols intended to be conducted in Zimbabwe. According to ZWE-9, all health research conducted in Zimbabwe by any individual or institution is required to receive NHRDC approval before initiation. The MRCZ’s Board/Council may further review, approve, or disapprove health research that has been approved or not approved by the NHRDC, as appropriate. (See the Ethics Committee section for details on the MRCZ, and its Board/Council and technical committees.) Further per ZWE-49, the MRCZ’s ethical approval should be submitted to the MCAZ, or proof of submission of an application for MRCZ approval in case of parallel submission.

Per ZWE-GCP, the study’s institutional EC must apply for ethical clearance by the MRCZ. However, the CTEthics states that the PI submits the application to the MRCZ. The clinical trial application is sent to one (1) primary reviewer and two (2) external reviewers who document their comments at the NHRDC/MRCZ meetings. After 3-6 weeks, the reviewers’ and NHRDC/MRCZ’s comments are sent to the researcher for feedback. Per ZWE-9, all health research conducted in Zimbabwe by any individual or institution is required to receive approval of the NHRDC before initiation. The MRCZ may further review, approve, or disapprove health research that has been approved or not approved by the NHRDC, as appropriate. The CTEthics states that if conditional approval is granted, the sponsor should register with the RCZ if it has foreign researchers. The MRCZ’s approval is issued upon payment of a 1% levy and production of a RCZ registration permit, if applicable.

Institutional Ethics Committees

The CTEthics indicates that an institutional ethics committee (EC) should establish and record working procedures concerning review fees charged.

Medical Research Council of Zimbabwe

Pursuant to CTEthics, ZWE-41, and ZWE-11, the prescribed fees (posted in US dollars) for ethical review by the national EC, the Medical Research Council of Zimbabwe (MRCZ), are as follows (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each):

• Normal registration for new study: $500 USD
• Expedited review for new study: $1,000 USD
• Undergraduate students: $10 USD
• Masters level dissertation: $50 USD
• PhD students: $200 USD
• Penalty for late submission of annual continuing review application: $200 USD after 30 days
• Application for study extension: $100 USD per study
• Levies: 1% of total study budget
• Inspection fee: $300 USD and only applicable if inspection is requested
• Amendment application: $50 USD per amendment
• Expedited amendment: $100 USD per expedited amendment
• Penalty for late submission of serious adverse events: $20 USD per day

Payment Instructions

Per ZWE-41, payments should be submitted to the following bank:

MRCZ NOSTRO
NMB Bank
Account Name: Medical Research Council of Zimbabwe
NOSTRO Account number: 0000350046119
Branch Code: 11112
Branch: EXCELLENCE
Bank: NMB Bank Limited

Overview

In addition to its research ethics review function, the CTEthics indicates that the role of the Medical Research Council of Zimbabwe (MRCZ) is to promote, accredit, and monitor compliance of institutional ethics committees (ECs) within relevant legislation and regulations, ethical guidelines, and standards.

Registration Auditing, and Accreditation

No information is currently available.

Overview

In accordance with the MSCAct, the MSC-Regs, the CT-AppAuth, the ZWE-GCP, and ZWE-4, Zimbabwe requires the sponsor to obtain clinical trial authorization from the Medicines Control Authority of Zimbabwe (MCAZ). MCAZ is responsible for regulating and authorizing clinical trials of investigational products (IPs) in human participants in Zimbabwe, with the National Biotechnology Authority of Zimbabwe (NBA) and the Research Council of Zimbabwe (RCZ) also playing important regulatory roles. Per the ZWE-GCP and the CT-AppAuth, parallel submissions are encouraged among the regulatory authorities and to the national ethics committee (EC), the Medical Research Council of Zimbabwe (MRCZ). However, as indicated in ProcForeignReg, approval by the MRCZ is a prerequisite for RCZ consideration of a research permit application by a foreign researcher.

Regulatory Submission

Medicines Control Authority of Zimbabwe

Per the CT-AppAuth, to obtain MCAZ review and authorization, the sponsor must file a clinical trial application (CTA) on form MC 10 (ZWE-28) via the Clinical Trials Registry (ZWE-1) and include the appropriate fee and all the relevant documents. For guidance on how to navigate ZWE-1, refer to the user manual at ZWE-85. While there is no language requirement indicated, the application form at ZWE-28 is in English. Note that per the ZWE-GCP and ZWE-49, both the English and vernacular versions (e.g., Shona/Ndebele) must be used in consent materials.

CT-AppAuth indicates that a letter of acknowledgement of receipt of the CTA will be sent to the principal investigator (PI) by ZWE-1. Note the CT-AppAuth indicates that researchers may request a pre-submission meeting or submit pre-submission questions prior to submission of CTAs. Requests for pre-submission meetings should be submitted in writing to the MCAZ Director General with a summary of the proposed study, a list of preliminary questions, a summary of significant quality aspects of the IP, and any other pertinent documents. Researchers may use the MCAZ meeting request form (ZWE-37). Per ZWE-37, meeting request forms should be submitted to the receptionist at the MCAZ. (See the Regulatory Authority section for contact information.) According to ZWE-65, during a pre-submission meeting, participants may discuss document screening, fee quotations, and/or the applicable regulations.

Per CT-AppAuth, the MCAZ implements an expedited review pathway for certain clinical trial applications. This pathway can be used in the case of public health emergencies or at the request of a PI. The documentation to be submitted will be the same as outlined above but could be revised on a case-by-case basis. Researchers are encouraged to have pre-submission meetings with the MCAZ to discuss their protocol and any anticipated problems so that the approval process will be shortened. The MCAZ will also coordinate with relevant stakeholders such as the World Health Organization (WHO), the African Vaccine Regulatory Forum (AVAREF), the MRCZ, and others when necessary to achieve the desired result. To initiate the submission process, the applicant should send an email of intention to the MRCZ and the MCAZ, with a copy to the AVAREF Secretariat at afrgoavaref@who.int. The MRCZ and the MCAZ will then set up a pre-submission meeting with the applicant and communicate the meeting outcome to the AVAREF Secretariat. Also see the ZWE-GCP for additional guidance on this emergency process.

Research Council of Zimbabwe

Per the CT-AppAuth and ProcForeignReg, to obtain a research permit from the RCZ, foreign researchers should seek an affiliated institution in the area of the intended research in Zimbabwe. If accepted by that institution, then the institution of affiliation in Zimbabwe forwards the application to the RCZ. Recognized institutions of affiliation are universities, government ministries, and government departments who run their own budgets and whose head is an accounting officer, and any other publicly funded institutions as determined by the RCZ. Private and foreign institutions can have special collaborative arrangements with Zimbabwean public institutions. All foreign researchers must submit the application form (ZWE-59) and pay a non-refundable application fee of US $500.00, or as determined by the RCZ. (See the Regulatory Fees section for more information on paying this fee.) The RCZ provides a checklist to track the stages of the application process prior to RCZ submittal (ZWE-72).

National Biotechnology Authority of Zimbabwe

Per the NBA-Proc, vaccine clinical trial protocols must be submitted by the investigator to the institutional biosafety committee (IBC), followed by submission to the NBA. The applicant must answer all questions set forth in the NBA-Proc. The IBC will forward the proposal to the NBA after its approval. Where a proposal includes commercially sensitive information, the applicant may mark relevant portions as “Commercial-in-confidence” with reasons. Where material is clearly so marked, the NBA will treat it as confidential unless it decides that some disclosure is necessary. In that event, the NBA will notify the applicant in writing and subsequently negotiate a mutually agreed resolution. If agreement is not reached, then the proposal may be withdrawn, without disclosure or prejudice, at any time prior to the necessary disclosure in pursuit of approval. For clinical trials involving biological products, the MCAZ requires NBA approval or proof of application to the NBA.

Ethics Review Submission

Institutional Ethics Committee

According to the ZWE-GCP, the CTEthics, and ZWE-41, all research involving human participants in Zimbabwe must be reviewed by an institutional EC, followed by the national EC, the MRCZ. The submission process at institutional ECs will vary. For an example of an institutional EC submission process, see ZWE-25.

Medical Research Council of Zimbabwe

CTEthics states that the PI must submit an application to the MRCZ and bears full responsibility for the scientific and ethical aspects of the study. To submit an application for MRCZ ethical review, ZWE-41 specifies that four (4) copies of the application (ZWE-41) must be submitted to the MRCZ offices at 20 Cambridge Road, Avondale, Harare, Zimbabwe. However, ZWE-11 calls for five (5) copies. Online submission is also available at ZWE-71. Per ZWE-44, applicants should respond to comments using the MRCZ form (ZWE-44) within two (2) weeks of receipt of comments from the MRCZ.

Per ZWE-55, to withdraw an MRCZ application, all research activities must not have been implemented. The form (ZWE-55) and a cover letter must be submitted to MRCZ. The PI must also notify all relevant authorities that the protocol has been withdrawn from consideration by the MRCZ.

As indicated in ProcForeignReg, MRCZ approval is a prerequisite for RCZ consideration of a research permit application by a foreign researcher or for shipment of biospecimens. Per ZWE-89, the MRCZ will forward the application for registration of a foreign researcher to the RCZ. The applicant must prepare 10 flat files, with each document in all of the 10 files clearly labeled. Of the 10 copies, eight (8) are for the RCZ, one (1) is for the MRCZ, and one (1) is for the applicant. Both the MRCZ and the RCZ must sign ZWE-89 and receive a copy of it.

Regulatory Authority Requirements

Medicines Control Authority of Zimbabwe

As specified in the CT-AppAuth, a clinical trial submission package to the Medicines Control Authority of Zimbabwe (MCAZ) should contain the following documents:

• Cover letter
• Study protocol
• Investigator’s brochure
• Clinical trial pharmacy protocol/plan and MCAZ pharmacy license, where applicable
• Documentation of participant insurance for trial-related injuries
• Letter endorsing generic insurance certificate, if necessary
• Ethics approval or copy of letter applying for ethics committee (EC) approval and other relevant Zimbabwean regulatory approvals
• Proof of approval of study by the national regulatory authority in country of origin
• Proof of provision of Data Safety Monitoring Board (DSMB), Data Monitoring Committee, or Safety Monitoring Committee
• Monitoring plan
• Signed declarations: the declarations for good clinical practice (GCP) compliance by the principal investigator (PI) (ZWE-34) and the co- and sub-investigators (ZWE-33); joint declaration by the sponsor and PI regarding sufficient funds to complete the study (ZWE-35); and the applicant’s declaration (ZWE-90) that the package is complete and truthful and the study will be conducted in accordance with applicable legal, ethical, and regulatory requirements
• Recruitment advertisements (if applicable)
• Patient information leaflet(s) and informed consent forms (ICF), including vernacular versions and English translations; the MSC-Regs requires the participant’s consent documented in the ICF at ZWE-30
• Pharmaceutical dossier for new investigational medicinal products, including stability data
• Any other relevant attachments such as GCP certificates and curriculum vitaes (CVs) for the investigator(s), coordinator(s), or monitor(s); see ZWE-36 for the recommended CV format

In addition, according to ZWE-83, proof of application to the local Bio Safety Board for biological products (e.g., vaccines) must also be submitted.

National Biotechnology Authority of Zimbabwe

Per the NBA-Proc, an application for approval of a vaccine or biological product must provide answers to all the questions in NBA-Proc pertaining to:

• Aims and objectives
• The nature of the vaccine
• Population size and location of release
• Habitat and ecology
• The route of administration and associated safety concerns and treatment regimes
• Post-trial vaccine uses and risks to general population
• Existing evidence regarding level and duration of immunity
• Guidelines regarding waste disposal of the vaccine and its residue
• Information on use of the host vaccine organism in other human or animal vaccines

See NBA-Proc for additional considerations and the detailed questions.

Research Council of Zimbabwe

Per ProcForeignReg, foreign researchers must submit the following application materials to obtain a research permit from the RCZ:

• Clear statement of the purpose of their intended research on the application forms
• 10 copies of the completed application form (ZWE-59), and one (1) research proposal per project must be submitted to The Executive Director, Research Council of Zimbabwe (See the Regulatory Authority section for contact details); for joint projects, one (1) comprehensive research proposal is required and each applicant must submit 13 copies of the completed application form (ZWE-59)
• 10 copies of completed Specimens Transfer Agreement (STA) form (ZWE-63) if the application involves shipment of specimens
• 13 copies of the Materials Transfer Agreement (MTA) form (ZWE-62) for shipment of non-biological specimens
• 13 copies of each letter of support from a Zimbabwean institution of affiliation and other institutions that may be consulted during the research
• Evidence of adequate funds for the period of research

Ethics Committee Requirements

Institutional Ethics Committees

The submission process at institutional ECs will vary. For an example of institutional EC submission content requirements, see ZWE-25.

Medical Research Council of Zimbabwe

As specified in the ZWE-11, a clinical trial submission to the MRCZ should contain the following documents:

• Five (5) copies of the completed application form (ZWE-41)
• Five (5) copies of the protocol summary, to be less than three (3) pages in length
• Five (5) copies of the completed research protocol
• Five (5) copies of the consent forms in English and local language of the study population, including parental consent and assent forms where relevant
• Five (5) copies of the questionnaire being administered during the study in English and local language of participant
• Five (5) copies of drug brochure and application package to be submitted to the MCAZ
• Five (5) copies of CVs for PI and Co-PI

For applications for continuing review of research and for amendments/modifications, investigators should use ZWE-42 and ZWE-43, respectively. An application for extension of the research duration must be submitted to the MRCZ using the form at ZWE-51.

Per ZWE-89, an application for registration of a foreign researcher must contain the following documents (to be forwarded by MRCZ to RCZ):

• 10 copies of application letter from institution of affiliation
• 10 copies of MRCZ cover letter
• 10 copies of valid MRCZ approval letter
• 10 copies of the RCZ application form (ZWE-59) or renewal form (ZWE-60)
• 10 copies of proof of funding
• 10 copies of PI’s and co-investigators’ CVs
• 10 copies of study summary
• 10 copies of study protocol
• 10 copies of ICFs in English and Shona
• 10 copies of questionnaire
• 10 copies of research report if application is for renewal
• 10 copies of current registration certificate if application is for renewal
• 10 copies of GCP certificate
• 10 copies of temporary employment permit, where applicable
• 10 copies of identification documents if applicant is a permanent resident
• 10 copies of proof of payment of RCZ registration fee

See Specimen Import & Export section for the submission content for shipment of biospecimens.

Clinical Protocol

According to the CT-AppAuth, the clinical protocol should contain the follow elements:

• General information, including the protocol title, version number, and date
• Contact information for the sponsor, monitor, person(s) authorized to sign the protocol and protocol amendment for the sponsor, the sponsor’s medical expert for the trial, the investigator(s), the qualified physician who is responsible for medical decisions, and the clinical laboratory(ies) and other entities involved in the trial
• Justification for the study
• Name and description of the investigational product(s)
• The risk-benefit assessment
• Description of the route of administration, dosage, dosage regimen, and treatment period
• A statement that the trial will comply with the protocol and all other regulatory requirements
• Description of the population to be studied with adequate justification for vulnerable participants
• Trial objectives and purpose
• Trial design
• Treatment of study participants
• Assessment of efficacy
• Safety information, including safety parameters, adverse event reporting procedures, specimens collection procedures, the named composition of the Drug Safety Monitoring Board
• Statistics
• Agreement that the investigator will permit inspections and direct access to source data/documents from the MCAZ and the MRCZ
• Quality control and quality assurance in line with ZWE-73

Overview

Per ZWE-GCP, parallel submissions are encouraged among the regulatory authorities, which comprise the Medicines Control Authority of Zimbabwe (MCAZ), the National Biotechnology Authority of Zimbabwe (NBA), and the Research Council of Zimbabwe (RCZ), and to the national ethics committee (EC)—the Medical Research Council of Zimbabwe (MRCZ). However as indicated in ProcForeignReg, approval by the MRCZ is a prerequisite for the RCZ’s consideration of a research permit application by a foreign researcher.

Regulatory Authority Approval

Medicines Control Authority of Zimbabwe

As described in the CT-AppAuth, the review and approval process in Zimbabwe should take 60 working days from the time the completed application is received by the MCAZ’s Pharmacovigilance and Clinical Trials (PVCT) Division up until approval. This timeline excludes the time when the applicant is addressing any follow-up questions from the PVCT. In addition, MCAZ implements an expedited review pathway for certain clinical trial applications. The expedited review timeline is 15-30 working days subject to submission of a complete application.

Per CT-AppAuth, if Zimbabwe has been declared to be in a public health emergency, a timeline of 10 working days is recommended for processing of clinical trial applications where the product is already registered for other indication(s), or for old products which are known and 15 working days for novel products. These timelines are for the entire process from receipt application to the final decision, with exception of clock stops in line with ZWE-75. The MCAZ will also coordinate with relevant stakeholders such as the World Health Organization (WHO), the African Vaccine Regulatory Forum (AVAREF), the MRCZ, and others when necessary.

National Biotechnology Authority of Zimbabwe

While the NBA does not have review timelines available, ZWE-72 and ZWE-74 indicate that applications to review vaccine clinical trials take four (4) to six (6) weeks.

Research Council of Zimbabwe

Per ZWE-83, the RCZ review period is usually between four (4) to six (6) weeks, with their meeting dates scheduled on the last Thursday of every month for review of submissions.

Ethics Committee Approval

Institutional Ethics Committees

The timeline of review at institutional ECs will vary. For an example of institutional EC review procedures, see ZWE-25.

Medical Research Council of Zimbabwe

Per ZWE-11, it takes four (4) to six (6) weeks for MRCZ to review a clinical trial application. According to ZWE-74, clinical trials conducted in response to a public health emergency qualify for expedited review and will be reviewed within 10 business days.

Overview

Per the CT-AppAuth and the ZWE-GCP, all clinical trials of medicines in Zimbabwe involving human participants must not be initiated until the Medicines Control Authority of Zimbabwe (MCAZ) has authorized the conduct of the trial, with the approval of the Secretary for Health and Child Care at the Ministry of Health and Child Care (MOHCC), in accordance with the MSCAct, the MSC-Regs, and the MSC-ImportExport. Per the MSCAct and the CT-AppAuth, once a clinical trial is approved, the principal investigator (PI) is required to complete and sign the indemnity form (ZWE-40) appended to the authorization certificate and return it to the MCAZ prior to commencement of the clinical trial. The MSCAct mandates that before commencing an authorized clinical trial, the investigator must inform all participants about the aims and objectives of the clinical trial and how it will be conducted; the possible risks, discomforts, and other adverse effects that may result; and provide insurance to each participant to cover trial-related injuries.

The ZWE-GCP and the CT-AppAuth require that clinical trials in Zimbabwe are conducted in accordance with the good clinical practices (GCPs) in ZWE-GCP, which is derived from the International Council for Harmonisation’s (ICH) Guideline for Good Clinical Practice E6(R2) (ZWE-73) and other international guidance material. Further, regarding the conduct of clinical trials, the ZWE-GCP states that it should be read in conjunction with other ICH guidelines (ZWE-80) such as E2A (clinical safety data management), E3 (clinical study reporting), E7 (geriatric populations), E8 (general considerations for clinical trials), E9 (statistical principles), and E11 (pediatric populations).

Clinical Trial Agreement

Prior to initiating the trial, ZWE-GCP requires a written agreement between the sponsor and investigators as part of the protocol or in a separate agreement. The sponsor must obtain the investigators’/institutions’ agreement on the following items:

• The trial will be conducted in compliance with GCPs with the protocol agreed to by the sponsor
• The trial will comply with procedures for data recording/reporting and permits monitoring, auditing, and inspection/access according to the protocol; regarding access, all parties must agree to ensure direct access to all trial-related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities
• The definition, establishment, and assignment of responsibilities specified in the protocol, including data management, unblinding of treatment codes, statistical considerations, and preparation of the final clinical report

The sponsor and all investigators must sign and date the protocol to confirm agreement. In addition, the financial aspects of the trial should be documented in an agreement between the sponsor and the investigator/institution. Upon signing the application, all parties accept the responsibility that all applicable regulations and requirements will be adhered to. Furthermore, all parties are responsible for ensuring that the trial is based on and implemented according to well-founded ethical and scientific principles, as expressed in the Declaration of Helsinki (ZWE-70) and local and international guidelines for GCP.

See the Site/Investigator Selection section for details on selection requirements for investigators and clinical trial sites.

Clinical Trial Registration

As per the CT-AppAuth, the Clinical Trials Registry (ZWE-1) is the platform for both submitting clinical trial applications and registering approved clinical trials. In addition, the PI must submit the approved clinical trial to a publicly accessible registry platform, such as the Pan African Clinical Trials Registry (PACTR) platform (ZWE-27).

As explained in ZWE-23, RCZ maintains the National Research Database of Zimbabwe (NRDZ) (ZWE-22), which is an online integrated and comprehensive “one stop shop” covering all public domain research in Zimbabwe. To submit a new research entry into NRDZ, follow the steps outlined in ZWE-24.

Safety Reporting Definitions

According to the ZWE-GCP, the following definitions provide a basis for a common understanding of Zimbabwe’s safety reporting requirements:

• Adverse Event (AE) – Any undesirable experience occurring to a participant during a clinical trial, whether or not considered related to the investigational product(s) (IP). An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the IP.
• Adverse Event Following Immunization (AEFI) – Any untoward medical occurrence that follows immunization and does not necessarily have a causal relationship with the usage of the vaccine. The AE may be any unfavorable or unintended sign, abnormal laboratory finding, symptom, or disease.
• Adverse Drug Reaction (ADR) – A response to a medicinal product that is noxious and unintended, and which occurs at doses normally used for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. In the pre-approval clinical experience with a new medicinal product or its new intended usages, particularly as the therapeutic dose(s) may not be established, this includes all unintended responses to any dose. The phrase “responses to a medicinal product” means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility.
• Serious Adverse Event (SAE) – 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.
• Unexpected Adverse Drug Reaction – An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved IP or package insert/summary of product characteristics for an approved product).

See the CTEthics for additional guidance on safety definitions.

Safety Reporting Requirements

Investigator Responsibilities

Per the CT-AppAuth and the ZWE-GCP, all AE safety reports must be submitted to the Medicines Control Authority of Zimbabwe (MCAZ)’s Pharmacovigilance Electronic Reporting System (ZWE-76). The CT-AppAuth delineates that all safety reports must be submitted within seven (7) days of the principal investigator (PI) becoming aware of them. Reports of SAEs during the trial must be reported promptly to the MCAZ within 48 hours of knowledge by the PI or other investigators. However, ZWE-39 states that SAEs should be reported within three (3) days of a site becoming aware of the issue, and that AEs should be reported within seven (7) days of a site being aware. Similarly, the PharmVigHdbk states that for fatal or life-threatening, unexpected events during clinical development, the PI is required to alert the MCAZ as soon as possible but no later than seven (7) calendar days after first knowledge by the investigator that a case qualifies, followed by as complete a report as possible within eight (8) additional calendar days. Serious, unexpected reactions that are not fatal or life-threatening must be filed as soon as possible, but no later than 15 calendar days after first knowledge by the PI that the case meets the minimum criteria for expedited reporting. For additional guidance on using ZWE-76, see ZWE-87.

According to CTEthics, all AE reports and management issues should be transmitted to the ethics committee (EC), ideally through the PI, who should be fully informed of these issues. The investigator must sign the adverse event table (ZWE-48) and submit it to the EC.

Per ZWE-11, investigators must submit prompt reports to the Medical Research Council of Zimbabwe (MRCZ) of any unanticipated problems involving risks to the participants or others, and reports of serious or continuing noncompliance with the regulations or the EC’s requirements. If a death occurs during the research, ZWE-46 requires that the death report form (ZWE-46) be submitted to the MRCZ within three (3) days of the site being aware. The entire death report form must be completed by a certified medical practitioner. With regard to protocol deviations, each incident of deviation or violation must be reported to the MRCZ within seven (7) days of site awareness using the form at ZWE-53. If an institutional EC terminates a study, the investigators must report it to the MRCZ using the form at ZWE-47. The form at ZWE-56 must be used to apply to MRCZ for re-opening a study that had been previously terminated.

According to the CTEthics, the PI bears full responsibility for the scientific and ethical aspects of their study, and are the means of communication with the EC. The PharmVigHdbk affirms that the investigator is responsible for proper reporting of SAEs to the MCAZ. The ZWE-GCP requires the investigator to ensure that all SAEs are reported promptly to the MCAZ, the sponsor, and the EC. Proper protection procedures or treatments should be administered to trial participants experiencing SAEs. When significant noncompliance with the trial protocol is discovered, the PI should perform a root cause analysis and implement appropriate corrective and preventive actions. The PI is required to inform the MCAZ and the EC when the noncompliance is a serious breach of the trial protocol or good clinical practice (GCP), including deviations from, or changes to, the protocol to eliminate immediate hazards to the trial participants; changes that increase the risk to subjects and/or affect significantly the conduct of the trial; all ADRs that are both serious and unexpected; and new information that may affect adversely the safety of participants or the conduct of the trial. Per ZWE-11, in addition to the requirements of a particular research study, investigators are responsible for ongoing safety requirements in the conduct of approved research that include providing to the MRCZ prompt reports of any unanticipated problems involving risks to participants or others, and reports of serious or continuing noncompliance with the regulations or the requirements or determinations of the committee.

Sponsor Responsibilities

The ZWE-GCP requires the sponsor to report all AEs occurring during the course of the trial to the MCAZ. The sponsor should expedite reporting all SAEs to the EC and the MCAZ, and immediately undertake appropriate and necessary measures and treatment to protect trial participants in coordination with the investigator(s). In addition, per the CT-AppAuth and the ZWE-GCP, safety summaries, such as AE/ADR/SAE/AEFI logs, and IP defects must also be submitted to the MCAZ, as well as any Data Safety Monitoring Board (DSMB) safety reports in relation to the risk/benefit assessment of the study safety and subsequent protocol amendments and reports on protocol deviation(s) and violation(s) including the corrective action(s) taken. The ZWE-GCP clarifies that the SAE form should include laboratory results to enable causality assessment of the report. Follow-up information should also be submitted as soon as it becomes available. Additional information may include copies of diagnostic test results, laboratory reports, or medical record progress notes. All additional information should be clearly marked as updated information and include the Protocol Number and Volunteer ID Number. The MCAZ’s advisory Pharmacovigilance and Clinical Trials Committee meets monthly and does a causality assessment of the reports. Written feedback will be sent to the PI. The MCAZ may need to contact the site for additional information regarding the SAE. The MCAZ will maintain all SAE reports confidential on file and in a regulatory anonymized database.

Form Completion & Delivery Requirements

Medicines Control Authority of Zimbabwe

Per the CT-AppAuth and ZWE-GCP, the sponsor must submit all AE safety reports to ZWE-76. To view the ADR form, see ZWE-38; to view the SAE form, see ZWE-39. Separate forms must be used for separate reportable adverse events. The ZWE-GCP states that if there are any challenges accessing ZWE-76, hard copies of the safety report should be submitted to the MCAZ, including causality outcome by the sponsor and participant management. ZWE-66 provides the following MCAZ address for delivery of hard copies:

Medicines Control Authority of Zimbabwe
106 Baines Avenue
Harare, Zimbabwe

Institutional Ethics Committees

Because each EC has its own form completion and delivery requirements, investigators and sponsors should review their EC procedures.

Medical Research Council of Zimbabwe

To submit forms and for more information, contact the MRCZ. Per ZWE-78, MRCZ’s contact information is:

Medical Research Council of Zimbabwe
20 Cambridge Road
Avondale
Harare, Zimbabwe
Phone: +263 86 44073 772

Interim and Annual Progress Reports

Medical Control Authority of Zimbabwe

Per the CT-AppAuth and the ZWE-GCP, principal investigators (PIs) are required to submit annual progress reports (ZWE-77) for all ongoing clinical trials to the Medicines Control Authority of Zimbabwe (MCAZ). ZWE-77 specifies that all sections of the form must be completed electronically. The form and accompanying documents must be submitted by January 31^st annually to the MCAZ office or via email at mcaz@mcaz.co.zw. The progress report should contain the following:

• MCAZ reference number
• Actual date of commencement and the study duration; indicate if an extension is requested
• Protocol version number
• Study title
• Study sites
• Reporting period
• Institution
• PI name, address, phone number, and email
• Other contact information, if applicable
• Regulatory compliance information, including the number of good clinical practice (GCP) monitoring visits, GCP audits, the insurance certificate, the clinical trial indemnity form, the MCAZ premises license for the research pharmacy, and the investigational product (IP) approval
• Study status, including information on enrollment and data analysis
• Total number of people consented and screened and, of those, total number eligible for the study
• Total number of participants to which the IP has been administered
• Number of participants left to be enrolled in the coming months (years)
• Number of participants in the following categories: currently active in study; follow-up data collection only; completed intervention and any follow-up; and lost to follow-up
• Information on adverse events, protocol deviations/violations, complications, and withdrawals
• Status of the IP, including how many were imported, records of destruction, and any quality issues

Research Council of Zimbabwe

ProcForeignReg requires that all foreign researcher applications for extensions of research permits be accompanied by a brief progress report of the completed research to the Research Council of Zimbabwe (RCZ). The renewal registration form (ZWE-60) should be submitted together with a progress report, institution of affiliation letter, Medical Research Council of Zimbabwe (MRCZ) conditional approval letter, summary protocol, proof of funding, and the proof of payment of RCZ registration. This must be submitted not later than one (1) month before the expiration date.

Institutional Ethics Committees

Per the CTEthics, the ethics committee (EC) must ensure that the conduct of all research is monitored. At least annually, the EC must request reports from the PI on matters including:

• Progress to date, or outcome in the case of completed research
• Information concerning maintenance and security of records
• Evidence of compliance with the approved protocol
• Evidence of compliance with any conditions of approval

ECs should inform the PI, in writing, of decisions made after the review of progress reports. An EC may recommend and adopt any additional appropriate mechanism for monitoring, including the random inspection of research sites, data, signed consent forms, and records of interviews, with the prior consent of research participants. Because each EC has its own reporting requirements, investigators and sponsors should review their EC procedures.

Medical Research Council of Zimbabwe

Per ZWE-11, investigators are responsible for ensuring that progress reports and requests for continuing review are submitted to the MRCZ.

Final Report

Medical Control Authority of Zimbabwe

Per the MSCAct and the ZWE-GCP, not later than 30 days after the completion of a clinical trial, the PI is required to submit to the MCAZ a preliminary report on the ethical evaluation of the clinical trial. Then, not later than 90 days after the completion of the trial, a comprehensive report and a report on any serious or adverse events found during the trial must be submitted to the MCAZ.

In contrast, CT-AppAuth requires the PI and sponsor to submit a preliminary final report three (3) months after completion of the study and a final report six (6) months after completion of the study including any publications. The final report should follow international expectations for clinical trial reporting, including the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (ZWE-73). There must be a complete and comprehensive description of the study and its outcomes. The protocol, statistical, and clinical aspects should be included in the final study report to be able to verify that the final report is consistent with the study data generated. A final report is also required for a study that may be prematurely stopped due to safety reasons or other reasons. The MCAZ prohibits dissemination or publication of clinical trial results without prior submission of the same results to the MCAZ.

Research Council of Zimbabwe

ProcForeignReg requires that foreign researchers submit a detailed report and end of study form (ZWE-61) to the RCZ and the National Archives within one (1) year of completing the research.

Institutional Ethics Committees

Because each EC has its own requirements, investigators and sponsors should review their EC’s final report procedures.

Medical Research Council of Zimbabwe

Per ZWE-11, the investigator submits a final report to the MRCZ when the clinical trial is complete, i.e., all interventions or interactions with participants have been completed, and all data collection and analysis have been finished. The investigator notifies the MRCZ through a completely filled in termination form (ZWE-47) with the final report attached. In compliance with confidentiality requirements, the investigator may keep the data collected, including identifiable private data, consistent with the MRCZ-approved research plan. In addition, the investigator should meet other commitments that were agreed to as part of the approved research, for example, providing information about the study results to research participants, or honoring commitments for compensation to participants.

Per the ZWE-GCP and the CT-AppAuth, a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a trial. The CT-AppAuth adds that this excludes an individual company, institution, or organization that has been requested to provide money for a trial and does not benefit in any way from the results of the trial. A sponsor can be foreign, however, per CT-AppAuth and ProcForeignReg, their researchers must apply for a research permit with the Research Council of Zimbabwe (RCZ).

According to the ZWE-GCP, a sponsor may transfer any or all of the sponsor's trial-related duties and functions to a contract research organization (CRO), but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing and submitted for regulatory approval by the Medicines Control Authority of Zimbabwe (MCAZ) and the Medical Research Council of Zimbabwe (MRCZ) as protocol amendments. The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor's CRO(s). Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.

Overview

Per the ZWE-GCP, the sponsor is responsible for selecting investigators according to the availability of adequate clinical trial environment facilities and resources. CTEthics indicates that the investigator’s competence is assessed mainly by technical competence, including research competence, which is evaluated in terms of education, knowledge, certification, and experience. Compassion and empathy are among the characteristics required of a technically competent researcher. In all cases, the principal investigator (PI) must be a Zimbabwean-based researcher that is a permanent resident in Zimbabwe. To add or change sites, the PI must apply to the Medicines Control Authority of Zimbabwe (MCAZ) for authorization by submitting the form at ZWE-32.

The ZWE-GCP and the CT-AppAuth state that the sponsor should ensure all the selected investigators have sufficient training, qualifications, and capability, including (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each):

• Qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, provide evidence of such qualifications, and be licensed under the HProfAct
• The PI should provide evidence of qualifications and experience through an up-to-date curriculum vitae (CV), and must have had previous experience as a co-investigator in at least two (2) trials in the relevant professional area
• The PI should ensure that sufficient time has been allocated to conduct and complete the trial within the agreed time period
• Be thoroughly familiar with the characteristics and appropriate use of the investigational product (IP) as described in the protocol, current investigator’s brochure, product information, and other information sources
• Have a clear understanding and willingness to obey the ethical and legal requirements of the trial
• Will permit monitoring and auditing of the trial and inspection by the MCAZ or appointed representatives
• Will keep a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties
• Have no history of misconduct
• Have practical experience within the relevant professional area, is a resident of Zimbabwe, and will be responsible for the conduct of the clinical trial at a clinical site
• Had formal training in Good Clinical Practice (GCP) within the last three (3) years

HProfAct and CT-AppAuth state with regard to the capacity of the clinical trial site, all clinical trials must be carried out under conditions that ensure adequate safety for the participants. The site selected should be appropriate to the stage of IP development and any potential risks involved. The trial site must have adequate facilities, including laboratories, equipment, and sufficient medical, paramedical, and clerical staff to support the trial and to deal with all reasonably foreseeable emergencies. All laboratory assays must be validated, and principles of good laboratory practice (GLP) should be observed.

Foreign Sponsor Responsibilities

Per CT-AppAuth, foreign researchers must apply for a research permit with the Research Council of Zimbabwe (RCZ); they must also obtain RCZ approval to export biospecimens and/or materials. A foreign researcher is a non-Zimbabwean national and any person wishing to conduct research in Zimbabwe on behalf of a foreign institution, foreign organization, or other foreign person. As indicated in ProcForeignReg, foreign researchers should seek an institution of affiliation in the area of the intended research in Zimbabwe. If accepted by that institution, then the institution of affiliation in Zimbabwe forwards the application to the RCZ. Recognized institutions of affiliation are universities, government ministries, and government departments who run their own budgets and whose head is an accounting officer and any other publicly funded institutions as determined by the RCZ. Private and foreign institutions can have special collaborative arrangements with Zimbabwean public institutions. See the ZWE-88 for a directory of institutions of affiliation.

ZWE-GCP states that a foreign sponsor (also called an external sponsor) has certain obligations when it conducts a clinical trial in Zimbabwe. The foreign sponsor should strengthen local capacity for ethical, scientific review, biomedical research, and provide healthcare services as described in the (ZWE-79). The foreign sponsor also has an ethical obligation to provide healthcare services that are essential to the safe conduct of the research and treatment of participants who suffer injury because of research intervention. In addition, the foreign sponsor should make the beneficial intervention or product developed as a result of the clinical trial reasonably available to the population or community concerned.

Data and Safety Monitoring Board

CT-AppAuth requires that clinical trials set up a data and safety monitoring board (DSMB) or data monitoring committee. The sponsor must appoint members of a DSMB by considering a selection of individuals with relevant expertise (such as statisticians and clinicians), experience in clinical trials and in serving on other DSMBs, and absence of serious conflicts of interest. The PI must submit a DSMB charter with information on the aims and objectives, the composition, the names of the chairperson and members, and how meetings will be organized. DSMB and other types of safety reports in relation to the benefit/risk assessment of the study safety and subsequent protocol amendments or clarification memorandums should also be submitted to MCAZ via the Clinical Trials Registry (ZWE-1).

Multicenter Studies

According to CTEthics, multicenter studies should be appropriate to the local setting and modifications should be made when required to suit the local conditions. It is unacceptable for developed-country participants to be offered better standards of care than are offered to Zimbabwean participants in a similar study. When Zimbabwe is chosen for a trial or study that has not been undertaken in the country of origin, the sponsor must explain the reasons why. In terms of study design, special attention should be paid to the sampling strategy. Other issues in international studies include financing of the study, the appropriateness of incentive packages to research participants, and remuneration packages for investigators. With multi-national clinical trials, the sponsor must ensure the following:

• Benefits accrue to participants in the host country
• The potential benefits of research considerably outweigh potential risks or harms to vulnerable individuals and communities
• Research is non-exploitative and in the best interests of the research participants and their community
• Groups already vulnerable are provided with improved access to research
• Research participants are encouraged to participate in planning and conducting studies
• Research in developing countries is linked to capacity-building in healthcare, and to economic and educational empowerment to promote the delivery of healthcare and progress generally in the host country
• Honest efforts are made to translate research findings into components of accessible care in the community being researched
• Conflicts of interest are avoided
• Research protocols are modified to suit the situation in local communities
• Publication of articles should be inclusive of investigators as authors from both host and sponsoring countries where appropriate contributions have been made

Insurance

Per the MSCAct, the MSC-Regs, and the ZWE-GCP, the sponsor must provide insurance cover for all trial participants. The coverage must include the costs of any trial-related injury and be adequate to cover those costs to resolution. The sponsor must provide insurance or should indemnify the investigator/institution against claims arising from the trial except for claims that arise from malpractice and/or negligence.

The ZWE-GCP further indicates that the sponsor must submit a certificate of insurance or a letter confirming such insurance cover and the amounts set aside or limits with the clinical trial application. The level of risk that participants will be exposed to will be different across phase I-IV trials and the type of clinical trial. The sponsor and principal investigator must provide insurance cover that will be adequate to match the risk involved in the clinical trial, but not less than $1,000 US dollars for each participant.

Compensation

In the case of external (foreign) sponsors, the ZWE-GCP imposes an ethical obligation to provide healthcare services that are essential to the safe conduct of the research, and the beneficial intervention or product developed as a result of the research reasonably available to the population or community concerned.

Injury or Death

Per the ZWE-GCP, all sponsors should establish policies and procedures that address the costs of treatment of trial participants in the event of trial-related injuries and provide insurance cover for all trial participants. There should be provisions for compensation/treatment in the case of injury or death of a participant and the extent to which participants may be rewarded/compensated for participation. Additionally, foreign sponsors have an ethical obligation to provide healthcare services that are essential to the treatment of participants who suffer injury because of research intervention.

Trial Participation

As specified in the ZWE-GCP, the participant should be informed of any prorated payment, if any, for participating in the trial. In the clinical trial application, all sponsors should explain the anticipated prorated payment, if any, to the participant and the anticipated expenses, if any, for participating in the trial. Per ZWE-49, the participant should be informed of any benefits that may reasonably be expected from the research, including if the benefit is expected to be primarily for others. Benefits may include money, free treatment, free medications, or free transportation. Money may be offered to reimburse expenses, time, inconvenience, and transportation. Money may not be used as an inducement to assume risks.

Quality Assurance/Quality Control

Per the CT-AppAuth and the ZWE-GCP, the sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, good clinical practice (GCP), and the applicable regulatory requirement(s). The sponsor must secure agreement from all involved parties to ensure direct access to all trial-related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities. Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly. The quality management system should use a risk-based approach that incorporates critical process and data identification, risk identification, risk evaluation, risk control, risk communication, risk review, risk reporting, risk minimization measures, and risk management. See the ZWE-GCP for additional details on each of these risk elements.

CT-AppAuth states that the protocol should contain a description on how to maintain quality control and quality assurance of the study—such as criteria for selection of investigators, monitors, and the monitoring plan—which are in line with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (ZWE-73).

Per the ZWE-GCP, the sponsor must take prompt action to correct any noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor's staff. If noncompliance that significantly affects or has the potential to significantly affect human participant protection or reliability of trial results is discovered, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.

Monitoring Requirements

Per ZWE-GCP, when performing an audit, the sponsor should consider the purpose of an audit, which is independent of and separate from routine monitoring or quality control functions. The audit is meant to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and the applicable regulatory requirements. The sponsor should appoint individuals who are independent of the clinical trials/systems to conduct audits. The sponsor should ensure that the auditors are qualified by training and experience to conduct audits properly. The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The sponsor's audit plan and procedures for a trial audit should be guided by the importance of the trial submissions to regulatory authorities, the number of participants in the trial, the type and complexity of the trial, the level of risks to the trial subjects, and any identified problem(s). The observations and findings of the auditor(s) should be documented. Regulatory authority(ies) may seek access to an audit report on a case-by-case basis when evidence of serious GCP non-compliance exists or in the course of legal proceedings. When required by applicable law or regulation, the sponsor should provide an audit certificate.

CT-AppAuth and ZWE-GCP state that the Medicines Control Authority of Zimbabwe (MCAZ) will conduct pre-trial, trial, and post-trial GCP inspections to monitor clinical trials from start to finish. Using a risk-based approach, inspections may be routine or may be triggered by issues arising during the assessment of the protocol, annual reports, amendments, or protocol deviations or by other information such as previous inspection experience. The MCAZ’s inspections are meant to ensure compliance with GCP and may be done with or without notification. Combined inspections may be conducted with the MCAZ or the Medical Research Council of Zimbabwe (MRCZ). Aspects of the study that will be inspected may include, but are not limited to, the facilities and staff where the studies will be conducted, as approved by the MCAZ; compliance with the approved protocol and any amendment(s) to the protocol; accurate, complete, and current records according to the protocol; and serious adverse event(s) and adverse event(s) reporting according to MCAZ requirements. See the GCP-Inspections for additional guidance on how MCAZ inspections are conducted. Also see ZWE-GCP for additional details on MCAZ inspections and ZWE-86 for an inspection checklist.

Premature Study Termination/Suspension

Per the ZWE-GCP, if the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigator's/institution's participation in the trial. When an investigator's/institution's participation is terminated because of noncompliance, the sponsor should notify promptly the regulatory authority(ies). If a clinical trial is prematurely terminated or suspended, the sponsor should promptly inform the investigators/institutions, the MCAZ, and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s).

The CTEthics states that researchers should inform the relevant institution(s), the review body(ies) that approved the research and, wherever possible, the research participants, if the research project is to be discontinued before the expected date of completion. For research at more than one (1) site, or research where there have been multiple ethical reviews, it must be clearly established, before the research begins, how this information will be communicated.

Electronic Data Processing System

As indicated in the ZWE-GCP, the clinical trial should use error-free data processing programs with adequate user documentation. Adequate security and protection should be provided in the computer system for the accuracy of the data entered into the database. Any printout of the data, as well as duplicates, must be signed and dated. Procedures for corrections made at data entry, as well as documentation of corrections in the audit records, should be provided for the electronic data processing and management system or for the network system for remote data entry. Standard operating procedures (SOPs) should be maintained for using electronic systems and cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties on the use of computerized systems should be clear, and the users should be provided with training in the use of the systems. The SOPs should also clearly state those who have access to the electronic systems and timed maintenance of the electronic system.

Records Management

Per the ZWE-GCP, the investigator should maintain adequate and accurate source documents and trial records that include information on the use of a drug and all pertinent observations on each of the site’s trial participants. Source data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be traceable, not obscure the original entry, and explained, if necessary (e.g., via an audit trail). The data storage and processing systems should record, store, and transfer the information obtained from the trial participants during the conduct of the trial, and enable retrospective validation and evaluation of the progress and conduct of the trial. With respect to blinded clinical trials, the blindness should be completely maintained from the generation of random codes for allocation of treatments to the time of decision for revelation of random codes.

Regarding record retention periods, the protocol, documents, case report forms, informed consent forms, and other trial-related documents should be retained for at least 10 years by the sponsor; the trial participants’ documents should be retained for at least 10 years by the institution. The participant identification codes should be retained by the investigator and the sponsor for at least 10 years.

Per the ZWE-GCP, all required records and their duplicates should be kept at the trial-related sites for the duration of the above-mentioned retention period and should always be available for inspection by the Medicines Control Authority of Zimbabwe (MCAZ). The inspector should be allowed to photocopy or duplicate the records by other electronic and/or optical means. Upon request of the monitor, auditor, ethics committee (EC), or the MCAZ, the investigator/institution should make available for direct access all requested trial-related documents. The sponsor must keep all records related to the conduct of a clinical trial in a format that facilitates verification for the purpose of an inspection. If safety concerns arise, the sponsor must submit requested records within 48 hours. Additionally, the MCAZ can request the submission of additional information within seven (7) days to facilitate the inspection of a site.

Responsible Parties

As per the DPAct, the data controller (e.g., the sponsor) is any natural person or legal person licensed by the data protection authority—the Postal and Telecommunications Regulatory Authority of Zimbabwe (POTRAZ)—who determines the purpose and means of processing data. The data processor refers to a natural person or legal person, who processes data for and on behalf of the data controller.

Data Protection

As per the DPAct, any entity or person operating in Zimbabwe (and outside) must adhere to data protection and privacy principles when collecting data such as personal information of clinical trial participants. Per the DPAct, data includes any representation of facts, concepts, information, whether in text, audio, video, images, machine-readable code or instructions, in a form suitable for communications, interpretation, or processing in a computer device, computer system, database, electronic communications network or related devices and includes a computer program and traffic data. Genetic data is any personal information stemming from a deoxyribonucleic acid (DNA) analysis.

The DPAct states that the data controller must ensure that the processing of data is necessary and that the data is processed fairly and lawfully. The data should be collected for specified, explicit, and legitimate purposes, considering all relevant factors, especially the reasonable expectations of the data subject and the applicable legal and regulatory provisions. Personal data may only be processed if the data subject or a parent or legal guardian(s) provides consent to the processing of such data or without consent as specified in the DPAct. This consent must be in writing when it concerns genetic, biometric, health, and other sensitive personal information. The data subject must be informed of their right to withdraw consent any time and without any explanation and free of charge. Health data may only be processed under the responsibility of a healthcare professional, except if the data subject has given written consent, or if the processing is necessary for the prevention of imminent danger, or for the mitigation of a specific criminal offence. For the purposes of processing personal information under this section, the health professional and the health professional’s agents are held to principles of confidentiality. Every data controller or data processor must ensure that personal information is handled in the following manner:

• Processed in accordance with the right to privacy of the data subject
• Processed lawfully, fairly, and in a transparent manner in relation to any data subject
• Collected for explicit, specified, and legitimate purposes and not further processed in a manner incompatible with those purposes, as well as adequate, relevant, and limited to what is necessary in relation to the purposes for which it is processed
• Collected only where a valid explanation is provided whenever information relating to family or private affairs is required
• Is accurate and, where necessary, kept up to date, with every reasonable step being taken to ensure that any inaccurate personal data is erased or rectified without delay
• Kept in a form that identifies the data subjects for no longer than is necessary for the purposes for which it was collected

Regarding trans-border flow of data, the DPAct states that the transfer of personal information by a data controller to a third party in a foreign country is prohibited unless an adequate level of protection is ensured in the recipient country or international organization. If an adequate level of protection is not assured, the transfer of such information is permissible where one (1) of the following instances takes place:

• The data subject has unambiguously given their consent to the proposed transfer
• The transfer is necessary for the performance of a contract between the data subject and the controller or the implementation of pre-contractual measures taken in response to the data subject's request
• The transfer is necessary for the conclusion or performance of a contract concluded or to be concluded between the controller and a third party in the interest of the data subject
• The transfer is necessary or legally required on important public interest grounds, or for the establishment, exercise, or defense of legal claims
• The transfer is necessary to protect the vital interests of the data subject
• The transfer is made from a legal register which, is intended to provide information to the public and is open to consultation either by the public in general or by any person who can demonstrate a legitimate interest

See the DPAct for additional details, including on submittal and authorization from the data protection authority, consent requirements, and controller and processor responsibilities.

Consent for Processing Personal Data

The DPAct states that personal data may only be processed if the data subject or a parent or legal guardian(s) provides consent to the processing of such data or without consent as specified in the DPAct. This consent must be in writing when it concerns genetic, biometric, health, and other sensitive personal information. The data subject must be informed of their right to withdraw consent any time and without any explanation and free of charge. Health data may only be processed under the responsibility of a healthcare professional, except if the data subject has given written consent, or if the processing is necessary for the prevention of imminent danger, or for the mitigation of a specific criminal offence.

Obtaining Consent

In all Zimbabwean clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the MSCAct, the ZWE-GCP, the CTEthics, and the Declaration of Helsinki (ZWE-70). As per the ZWE-GCP, the CTEthics, the informed consent form (ICF) is viewed as an essential document that must be reviewed by the institutional ethics committee (EC) and national EC, the Medical Research Council of Zimbabwe (MRCZ), for approval with the clinical trial application. The MSC-Regs requires that the applicant document the participant’s consent in the ICF (ZWE-30) when submitting the application to the Medicines Control Authority of Zimbabwe (MCAZ).

To obtain consent, the ZWE-GCP and the CTEthics require that information is given in both oral and written form whenever possible. The language used in the oral and written consent information about the clinical trial should be as non-technical as practical and should be understandable to the participant or their legal representative(s) and/or guardian(s). No participant should be coerced or unduly influenced to participate or continue to participate in a trial. The participant, legal representative(s), and/or guardian(s) should be given ample opportunity to enquire about the details of the trial and be allowed sufficient time to decide whether they wish to participate. The information should make clear that refusal to participate or withdrawal from the trial at any stage is without any disadvantages for the person’s subsequent care. ZWE-49 and ZWE-50 state that the language used in the ICF should be non-coercive and written at a 6^th grade reading level, medical jargon or technical terms should be avoided (or be followed by a description in lay terms), initials and/or abbreviations should be explained, and sentences should be short and concise. The ZWE-GCP indicates that none of the information concerning the trial should contain any language that causes the participant/legal representative or guardian to waive or appear to waive any legal rights or that releases or appears to release the investigator and/or sponsor from liability for negligence. See ZWE-49 and ZWE-50 for additional instruction and templates for researchers and institutional ECs on preparing ICFs for adult participants and legal representative(s) and/or guardian(s). ZWE-57 provides a sample ICF for the long-term storage and future use of specimens. (See the Consent for Specimen section for more information.)

The CTEthics additionally indicates that informed consent means a participant has been informed about the risks and benefits of the research, understands such risks and benefits, and is able to give consent to participate without coercion, undue influence, or inappropriate incentives. Researchers must be particularly aware of the vulnerability of prospective participants in terms of access to health services and education levels.

Re-Consent

Per the ZWE-GCP, the written ICF and any other written information for participants should be revised whenever important new information becomes available that may be relevant to consent. Any revised written ICF and written information must be submitted to the MRCZ and the MCAZ for approval in advance of use. The participant and/or the legal representative(s) and/or guardian(s) must be informed in a timely manner if new information becomes available that might be relevant to their willingness to continue participation in the trial. The communication of this information should be documented.

Language Requirements

Per the ZWE-GCP and ZWE-49, both the English and vernacular versions (e.g., Shona/Ndebele) must be used in consent materials. Evidence of back translation and who performed the translation is required.

Documenting Consent

Per the ZWE-GCP and the CT-AppAuth, prior to participation in a clinical trial, the written ICF should be signed and personally dated by the participant. Informed consent is documented using a written consent form approved by the EC and signed and dated by the participant or the participant’s legally authorized representative at the time of consent. According to the ZWE-GCP, if the potential participant is not able to read (not literate), an impartial witness must observe the entire informed consent process for each ICF administered. A copy of the signed and dated consent form must be given to the person signing for the participant and another copy retained in study files. CT-AppAuth states that the investigator should ensure the signature(s) and date(s) occur as required. Version-controlled and dated English and vernacular ICFs should be provided with the clinical trial application and be in line with MRCZ guidelines and templates, as provided in ZWE-49, ZWE-50, and ZWE-57.

Waiver of Consent

CTEthics requires that informed consent must be obtained from research participants before the research can begin, unless there are good reasons to the contrary, such as a coma, emergency, or mental incapacity. Prior approval of the EC must be obtained in all situations in which it is justifiable to initiate research without the informed consent of the participant.

Per the ZWE-GCP and the CTEthics, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each.):

• The clinical trial involves research and its purpose
• The trial treatment(s) and the probability for random assignment to each treatment
• The trial procedures to be followed, including all invasive procedures
• The participant’s responsibilities
• Those aspects of the trial that are experimental
• The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
• The reasonably expected benefits; when there is no intended clinical benefit to the participant, the participant should be made aware of this
• The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks
• The compensation and/or treatment available to the participant in the event of trial-related injury
• The anticipated prorated payment, if any, to the participant for participating in the trial
• The anticipated expenses, if any, to the participant for participating in the trial
• The participant’s participation in the trial is voluntary and that the participant may refuse to participate or withdraw from the trial, at any time
• The participants’ identity will remain confidential whether results of the trial are published or not published
• The Medicines Control Authority of Zimbabwe (MCAZ) and other authorized persons will be granted direct access to the participants’ original medical records for verification of trial procedures and data
• Should any new information that is relevant to the participant’s willingness to continue participating in the trial become available, it will be conveyed to them in a timely manner
• The contact persons for further information about the trial or whom to contact in the event of trial-related injury
• The participant may be requested to terminate participation in the trial
• The expected duration of the trial
• The approximate number of participants involved in the trial
• The investigators’ qualifications
• Statement that the research has been approved by an ethics committee
• Contact details of research ethics committee representatives

In addition, see ZWE-30, ZWE-49, and ZWE-50 for additional MCAZ and Medical Research Council of Zimbabwe (MRCZ) instruction and templates on preparing ICFs for adult participants and legal representative(s) and/or guardian(s). ZWE-57 provides a sample ICF for the long-term storage and future use of specimens. (See the Consent for Specimen section for more information.)

Overview

In accordance with the ZWE-GCP, Zimbabwe’s ethical standards promote assurance that the rights, safety, and well-being of participants are protected, are consistent with the principles in the Declaration of Helsinki (ZWE-70), and that clinical trial data are credible. The CTEthics further states that the ethical principles for health research in Zimbabwe promote good, desirable, and acceptable conduct to protect the welfare and rights of research participants, and to reflect the basic ethical values of beneficence, justice, and respect for persons.

The Right to Participate, Abstain, or Withdraw

As stated in the CTEthics, potential participants must be assured that participation is voluntary, and that refusal to participate, or a decision to discontinue participation, will not involve any form of penalty. Further, the selection, recruitment, exclusion, and inclusion of research participants must be just and fair, based on sound scientific and ethical principles. No person may be inappropriately or unjustly excluded based on race, age, sex, sexual orientation, disability, education, religious beliefs, pregnancy, marital status, ethnic or social origin, conscience, belief, or language.

Per the ZWE-GCP, the informed consent discussion and written consent material should include an explanation that the participant’s participation in the trial is voluntary and that the participant may refuse to participate or withdraw from the trial, at any time.

The Right to Information

Per the CTEthics and the ZWE-GCP, potential research participants and/or their legal representative(s) or guardian(s) have the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

CTEthics states that privacy is concerned with access to personal records, and confidentiality refers to the use of personal information once it has been disclosed. A participant’s right to both privacy and confidentiality must be protected. The researcher must ensure that where personal information about research participants or a community is collected, stored, used, or destroyed, this is done in ways that respect the privacy or confidentiality of the participants or the community and any agreements made with the participants or community.

Per the ZWE-GCP, the informed consent discussion and written consent material should include an explanation that the participants’ identity will remain confidential whether results of the trial are published or not. They should also be informed that the Medicines Control Authority of Zimbabwe (MCAZ) and other authorized persons will be granted direct access to the participants’ original medical records for verification of trial procedures and data.

The Right of Inquiry/Appeal

Per the CTEthics and the ZWE-GCP, the informed consent discussion and written consent material should include an explanation that the research participant and/or the legal representative(s) or guardian(s) will be provided with contact information for the investigator(s) and the ethics committee (EC) to address trial-related inquiries and/or address any questions.

The Right to Safety and Welfare

Per the CTEthics and the ZWE-GCP, the rights, safety, and well-being of the trial participants are the most important considerations and should prevail over the interests of science and society.

As indicated in the CTEthics, written and verbal informed consent must be obtained, unless there are good reasons to the contrary, such as an emergency.

Per CT-AppAuth, if Zimbabwe has been declared to be in a public health emergency disaster by the President or Minister of Health, the World Health Organization (WHO), or any other designated person, an expedited regulatory review pathway for clinical trials will be implemented in line with ZWE-75. The emergency procedures implemented by the Medicines Control Authority of Zimbabwe (MCAZ) and the national ethics committee (EC), the Medical Research Council of Zimbabwe (MRCZ), in coordination with the African Vaccine Regulatory Forum (AVAREF) involves accelerated procedures, including EC review of consent. (See the Submission Process and Timeline of Review sections for additional details.)

Overview

The CTEthics states that in Zimbabwe, researchers must be particularly aware of the vulnerability of prospective participants in terms of access to health services and education levels. Ethics committees (ECs) should be especially vigilant when considering research proposals involving vulnerable populations, including children, pregnant and nursing women, persons with mental illnesses or handicaps, members of communities unfamiliar with medical concepts, and persons with restricted freedom, such as prisoners. If a participant lacks capacity to exercise an informed choice to participate, an appropriate person to make the choice for them must be identified by the investigator.

In addition, the ZWE-GCP identifies individuals as vulnerable who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. For example, 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 subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

ZWE-49 indicates that the age of majority in Zimbabwe is 18. Children under 18 years of age have not attained the legal age for consent to treatments or to participate in a clinical trial. Children who are seven (7) to 17 years of age can give assent through a written affirmative agreement to participate in a clinical trial. As per ZWE-50, when the research participant is a child under seven (7) years of age, the informed consent form (ICF) must be signed by the child’s legal representative(s) and/or guardian(s). For children who are seven (7) to 17 years of age, the consent and assent requirements vary and are provided below. In addition, the ICF must include signatures in the appropriate sections if the study involves specimen collection and/or recording the child with photographs, video, or audio.

Assent Requirements

Per ZWE-11, assent means a child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent. This means the child must actively show a willingness to participate in the research, rather than just complying with directions to participate and not resisting. The Medical Research Council of Zimbabwe (MRCZ) has the discretion to judge children’s capacity to assent to be involved in a proposed research activity, or on an individual basis. The MRCZ considers the nature of the proposed research activity and the ages, maturity, and psychological state of the children involved when judging whether children are capable of assent, and reviewing the proposed assent procedure and the form and content of the information conveyed to the prospective subjects. For research activities involving adolescents whose capacity to understand resembles that of adults, the assent procedure should likewise include information like what would be provided for informed consent by adults or for parental permission. For children whose age and maturity level limits their ability to fully comprehend the nature of the research activity, but who are still capable of being consulted about participation in research, it may be appropriate to focus on conveying an accurate picture of what the actual experience of participation in research is likely to be (for example, what the experience will be, how long it will take, whether it might involve any pain or discomfort). The assent procedure should reflect a reasonable effort to enable the child to understand, to the degree they are capable, what their participation in research would involve.

Per ZWE-11, A child’s assent is required, except in the following three (3) circumstances:

• The capability of some or all the children is so limited that they cannot reasonably be consulted
• The intervention or procedure involved in the research holds out the prospect of direct benefit to the health or well-being of the children and is available only in the context of the research
• The research meets the same conditions as those for waiver or alteration of informed consent in research involving adults

Per ZWE-11, the MRCZ determines the appropriate manner of documenting child assent. Based on such considerations as the child’s age, maturity, and degree of literacy, the committee decides what form of documentation, if any, is most appropriate. If adolescents are involved in research where a consent form would have been used if the participants were adults, it would generally be appropriate to use a similar form to document an adolescent’s assent. If young children are involved who cannot read, documentation should take a form that is appropriate for the purpose of recording that assent took place. The MRCZ may also decide that documentation of assent is not warranted. Finally, the MRCZ views informed consent as an ongoing process throughout the duration of a research study. When a child who was enrolled in research with parental or guardian permission subsequently reaches the legal age of consent, the participant is no longer regulated by the requirements regarding parental or guardian permission and child assent. Unless the MRCZ determines that the requirements for obtaining informed consent can be waived, the investigator should seek and obtain the legally effective informed consent, for the now-adult participant for any ongoing interactions or interventions with the participant.

As per ZWE-50, for children who are seven (7) to 17 years of age, a distinction is made between therapeutic and non-therapeutic research. For non-therapeutic research, the child’s legal representative(s) and/or guardian(s) must sign the ICF and a separate assent form must be signed by the child. For therapeutic research, the child’s legal representative(s) and/or guardian(s) must sign the ICF, and the child’s assent should be obtained with the child signing a separate assent form or with a single paragraph in the ICF that states, “I have discussed this clinical research study with the child using language which is understandable and appropriate. I believe I have fully informed this participant of the nature of the study and its possible risks and benefits. I believe the participant understood this explanation and assented to participate in this study.” This statement should be signed by the physician/investigator and by a witness. In circumstances when a specific child is not capable of providing assent and the prospect of therapeutic benefit is great, a request may be made to the ethics committee to waive consent. For children who are 13 to 17 years of age, a separate assent should be signed and dated by the child participant.

Per the ZWE-GCP, the informed consent form and other written material given to the participant must include an explanation of the reasonably foreseeable risks or inconveniences to an embryo, fetus, or nursing infant, as applicable.

The CTEthics points to the involvement of prisoners as a situation that calls for careful scrutiny. The principle of respect for persons requires that prisoners not be deprived of the opportunity to volunteer for research. However, under prison conditions they may be subtly coerced or unduly influenced to engage in research activities for which they would not otherwise volunteer. Respect for persons would then dictate that prisoners be protected. Those involved in clinical research need to balance the competing considerations.

Per ZWE-11, if a participant involved in ongoing research that was approved by the Medical Research Council of Zimbabwe (MRCZ) becomes a prisoner during the study, the researcher must promptly notify the MRCZ for re-review of the protocol. All research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated participant must be suspended. In special circumstances in which the investigator asserts that it is in the best interests of the participant to remain in the research study while incarcerated, the participant may continue to participate in the research.

The CTEthics states that in Zimbabwe, ethics committees (ECs) should be especially vigilant when considering research proposals involving vulnerable populations, including persons with mental illnesses or handicaps.

According to the ZWE-GCP, an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial including a product with a marketing authorization when used or assembled in a way different from the approved form, or when used for an unapproved indication or when used to gain further information about an approved use.

Note: The ZWE-GCP states it should be read in conjunction with other ICH guidelines (ZWE-80) that are relevant to the pharmaceutical development of investigational products, such as Q8 (R2) (pharmaceutical development).

Manufacturing

As specified in the MSCAct, ZWE-68, and ZWE-3, the Medicines Control Authority of Zimbabwe (MCAZ) authorizes the manufacture of investigational products (IPs) in Zimbabwe. Per MSCAct and MSC-Regs, to manufacture medicines and IPs, a license must be obtained from the MCAZ. To apply for a license, the application form (ZWE-29), fees, and accompanying materials should be submitted to the Director General of MCAZ. To renew a license for a manufacturing premises, ZWE-2 indicates that requests to renew can also be made via the MCAZ Online Services Login (ZWE-82). See the Regulatory Fees section for details on license fees for a manufacturer’s premises.

Per the ZWE-GCP, IPs should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP), and they should be used in accordance with the approved protocol. The sponsor should ensure that the IPs (including active comparator(s) and placebo) are manufactured in accordance with GMPs. The manufacturing of IPs is subject to control and inspection by the MCAZ, and certificates of analysis (COAs) must be provided for all IPs and comparator products. Chemistry and manufacturing information provided in the clinical trial application should be presented in a concise manner. If the pharmaceutical or chemical properties of the IP have been altered compared to those in use during animal testing or previous clinical trials, such alterations must be described and justified. Pharmaceutical and/or chemical alterations in an IP that is used in an ongoing clinical trial, and that may affect the quality, safety, and/or efficacy of the IP must immediately be reported to the MCAZ. If the composition of the medicinal product is altered, additional bioavailability or bioequivalence studies may be required.

As stated in the CT-AppAuth, the investigator’s brochure (IB) must contain proof of current GMP compliance at the manufacturing site(s). The IB should also contain documentation on quality and manufacturing of the IP (i.e., the IP dossier); stability data for initial batches, COAs for three (3) batches or batch analysis data for three (3) batches; and the name and address of the manufacturer(s) or manufacturing licenses. More details are provided in the International Council for Harmonisation’s (ICH) Guideline for Good Clinical Practice E6(R2) (ZWE-73) and may be used when compiling information on this part. For MCAZ-registered medicinal products included in the clinical trial, the following documentation should be provided: generic and brand name (if any) of the product; registration number of the product and a current Package Insert or summary of product characteristics (SmPC) of the product; COA; and current GMP certificate from a national regulatory authority. For products that are approved by other regulatory authorities, such as the US Food and Drug Administration, European Medicines Agency, and the Australian Therapeutic Goods Administration, etc., and products that are prequalified by the World Health Organization (WHO), proof of such approval should be submitted to the MCAZ, including current GMP certificates. In addition, certification of GMP compliance of manufacturing sites of the IPs, adjuvants, comparators, and placebos must be provided to the MCAZ. The amount and depth of information that would be submitted to the MCAZ depends on the clinical trial phase, novelty of the medicine, dosage form/route of administration and the known or suspected risks. See the CT-AppAuth for the specific requirements on the chemistry and manufacturing requirements to be included in the IP dossier with the clinical trial application.

Import

The Sec75-Imports and ZWE-81 indicate that institutions that may apply for importation of IPs (referred to as “unregistered medicines” in the import requirements) under the exemption provisions of Section 75 of the MSCAct. Per the CT-AppAuth, the Pharm-IMPs, and ZWE-68, the MCAZ must approve import permits for all IPs and other trial-related medical products. As delineated in the CT-AppAuth and the Pharm-IMPs, to import IPs, applicants are required to apply for authorization to the MCAZ by submitting the following:

• A cover letter stating the full name and address of the innovator and/or manufacturer, the study sponsor, the recognized clinical research entity, the name/description of the IP, placebo, and quantity to be imported
• The quantity and source of each IP and trial-related products to be imported
• Shipment documents and invoices of the IP purchased/to be purchased indicating quantities
• A COA of IPs for all batches of each product to be imported
• Lot release certificate(s) (where applicable) for all batches to be imported

Per ZWE-83, applications for importation of IPs should be emailed to mcaz@mcaz.co.zw and pvct@mcaz.co.zw using the Section 75 application tab on the Clinical Trials Registry (ZWE-1) for the relevant clinical trial, or submitted as a hard copy to MCAZ. Note that to import registered medicines for a clinical trial, the requirements in the MSC-ImportExport must be followed.

Per the CT-AppAuth and the Pharm-IMPs, the MCAZ will process an application for an import permit within five (5) working days. The CT-AppAuth states that the principal investigator must notify the MCAZ within 48 hours of each batch of IPs received. The notification must include the product name(s) and quantities/batches received. Imported IPs may be inspected by MCAZ officials at the port of entry before they are released to the recognized clinical research entity. In cases where the country has been declared to be in a public health emergency disaster by the President or Minister of Health, the WHO or any other designated person, expedited procedures for IPs will be employed in line with ZWE-75. Per ZWE-75, during emergencies, applications for the importation of study medicinal products will be expedited and be processed within three (3) working days of receipt of the application. Any post-authorization amendments will be processed within five (5) working days of receipt of the application.

Please note: Zimbabwe is party to the Nagoya Protocol on Access and Benefit-sharing (ZWE-91) 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 ZWE-92.

Investigator’s Brochure

As specified in the ZWE-GCP, the sponsor must maintain a copy of all versions of the investigator’s brochure (IB) for the investigational product (IP), as well as records regarding each change made to the IB and the rationale and supporting documentation for each change. Per the ZWE-GCP and the CT-AppAuth, the IB must provide coverage of the following areas, each with literature references where appropriate (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each.):

• Table of Contents
• A brief summary (preferably not exceeding two pages), highlighting the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information available that is relevant to the stage of clinical development of the IP
• A brief introductory statement containing the chemical name of the IP(s); all active ingredients; the IP(s) pharmacological class and its expected position within this class (e.g., advantages); the rationale for performing research with the IP(s); the anticipated prophylactic, therapeutic, or diagnostic indication(s); and the general approach to be followed in evaluating the IP
• Physical, chemical, and pharmaceutical properties and formulation
• Nonclinical studies information
• The pharmacological aspects including its metabolism in all animal species tested, and the toxicological effects in any animal species tested under a single dose study, a repeated dose study or a special study, etc.
• Results of clinical pharmacokinetic studies
• Effects in humans, including information regarding safety, pharmacodynamics, efficacy, and dose responses
• Summary of data and guidance for the investigator
• Proof of current good manufacturing practices (GMP) showing compliance of the IP manufacturing site(s) and documentation on quality and manufacturing of the IP (IP dossier)
• Stability data for initial batches, certificates of analysis (COAs) for three (3) batches or batch analysis data for three (3) batches
• Name and address of the manufacturer(s) or manufacturing licenses

Quality Management

Per the ZWE-GCP, COAs must be provided for all investigational and comparator products that are used in clinical trials. Further, IPs should be manufactured, handled, and stored in accordance with applicable GMP. As per CT-AppAuth, for products that are approved by other regulatory authorities, such as the US Food and Drug Administration, European Medicines Agency, and the Australian Therapeutic Goods Administration, etc., and products that are prequalified by the World Health Organization, proof of such approval should be submitted to the Medicines Control Authority of Zimbabwe (MCAZ). In addition, the CT-AppAuth indicates that certification of GMP compliance of manufacturing sites of the IPs, adjuvants, comparators, and placebos must be provided to the MCAZ.

Investigational product (IP) labeling in Zimbabwe must comply with the requirements set forth in the ZWE-GCP and the CT-AppAuth. Per ZWE-GCP, the sponsor should ensure that the IPs (including active comparator(s) and placebo) are adequately packed and labelled in a manner that protects the blinding (if applicable) and for clinical trial use only. In addition, the labelling should comply with the protocol. Per the Pharm-IMPs, study products must be labelled properly to ensure their safe administration and use by the research staff and participants and in a format that complies with all applicable requirements and maintains participant confidentiality. It is the site pharmacists’ responsibility to know the requirements for their jurisdiction. Prescription labels for study products should be distinguishable from other labels by an appropriate legend. According to the ZWE-GCP, the CT-AppAuth, and the Pharm-IMPs, study labels should include the following information (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each):

• A statement indicating that the drug is an IP and should only be used by a qualified investigator
• The name, number, or identifying mark of the drug
• Participant name or coded identification
• The dispensing date and expiration date of the drug
• Directions for dispensing the product, including the dosage if applicable
• Instructions should be provided to the participant and/or the appropriate nursing service personnel if they advise the participant on the correct use of the study product
• Number of dosing units dispensed
• The recommended storage conditions for the drug
• The batch/lot number of the drug
• The name and address of the sponsor and prescribing investigator’s name
• The protocol code or IP identification number
• The trial name or study identification number
• Name, address, and phone number of the dispensing site

According to the Pharm-IMPs, if a study product is mailed to a participant, it must be labelled properly, and receipt by the participant must be documented.

Supply, Storage, and Handling Requirements

Per the ZWE-GCP, the sponsor should provide an up-to-date investigator’s brochure (IB) to the investigator. The sponsor is also responsible for determining the acceptable storage temperatures and conditions, storage times, reconstitution fluids, and procedures for product infusion for the investigational products (IPs), if applicable. The investigator should be thoroughly familiar with the characteristics and appropriate use of the IP as described in the protocol, the current IB, the product information, and other information sources. Investigators in the trial should provide information on restrictions on the uses of the IP in any country. In addition, the Pharm-IMPs states that the principal investigator (PI) and/or investigator has the overall responsibility for all the medical products and IPs for the study. The pharmacist at each site participating in a clinical trial, who is designated as the pharmacist of record, is the primary individual who is expected to develop and maintain a study product management system, which includes the technical procedures for study product ordering, control, dispensing, and accountability. Their specific responsibilities are delineated in the Pharm-IMPs. The ZWE-GCP indicates that generally IPs used in clinical trials should be handled in the same way as registered medicines. The CT-AppAuth stipulates that leftover, expired, used, or broken IPs may be destroyed upon authorization by the Medicines Control Authority of Zimbabwe (MCAZ) and the study sponsor. An official request to dispose of the IPs, indicating the type, quantity of each product to be destroyed, and the method of destruction must be made to the MCAZ. The destruction certificate/letter confirming destruction must be submitted to the MCAZ. For more information on the destruction of IPs, see the Pharm-IMPs.

Record Requirements

As indicated in the ZWE-GCP, the records on IPs should document quantities, delivery, receipt, disposition, return, and destruction. The investigator should not provide the IPs to any individuals who are not trial participants. The sponsor should retain the batch samples of the IPs until at least two (2) years after the approval of a marketing application or after the conclusion of the clinical trial for an unapproved marketing application.

Per Pharm-IMPs, the pharmacist of record is responsible for ordering and maintaining records related to the receipt of protocol-provided study products, dispensing to participants, and disposition of study products. The pharmacist of record also maintains records of any trial-related products (including records for study medicines that are not provided as part of the protocol) received directly from other sources including adequate records showing the receipt, dispensing, dates, and quantities of the medicines. A copy of all records for study products should be retained, including records such as order forms, receipts for transfers and returns, packing slips, inventory, and accountability records. Trial-related records and any other unique pharmacy records should be retained until two (2) years after the investigation of the study product is discontinued. Accountability records and any other unique pharmacy information may be archived with case report forms after the protocol database is closed and the study is unblinded, if applicable. Pharmacy records and case report forms should be archived together. When archiving, pharmacy records should be placed in a folder or envelope and clearly marked as pharmacy records. The records should be available for inspection and copying by an authorized employee or representative/inspector of the regulatory authorities, upon request.

Also see the Medical Research Council of Zimbabwe (MRCZ)’s form (ZWE-52) for documenting trial-related materials.

The CTEthics defines human tissue as the substance, structure, and texture of which the human body or any part or organ of it is composed, which is removed or separated from a living human being and includes blood, blood components, and waste products. Genetic material is any source of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) that can be tested to obtain genetic information. It includes cells, whether as single cells or as part of tissues, and extracted DNA and RNA.

Import

No information is currently available related to the import of specimens.

Export

According to the CT-AppAuth, researchers must obtain approval from the Research Council of Zimbabwe (RCZ) to export biospecimens and/or materials. Per ProcForeignReg, foreign researchers’ application to the RCZ for a research permit must include the completed Specimens Transfer Agreement (STA) form (ZWE-63) for the shipment of specimens and the Materials Transfer Agreement (MTA) form (ZWE-62) for shipment of non-biological specimens. As indicated in ProcForeignReg, Medical Research Council of Zimbabwe (MRCZ) approval is a prerequisite for RCZ consideration of a research permit application for shipment of biospecimens. Per ZWE-89, the MRCZ will forward the application for registration of a foreign researcher to the RCZ. The applicant must prepare 10 flat files, with each document in all 10 files clearly labeled. Of the 10 copies, eight (8) are for the RCZ, one (1) is for the MRCZ, and one (1) is for the applicant. Both the MRCZ and the RCZ must sign ZWE-89 and receive a copy of it. Per ZWE-89, the following documents must be included:

• 10 copies of the principal investigator (PI) application letter
• 10 copies of the MRCZ cover letter
• 10 copies of the valid MRCZ approval letter
• 10 copies of the valid RCZ registration certificate if the study is registered
• 10 copies of the STA form (ZWE-63)
• 10 copies of the study summary
• 10 copies of the study protocol
• 10 copies of the informed consent forms in English and Shona
• 10 copies of the applicant’s good clinical practice (GCP) certificate
• Stated finite date of destruction of leftover biospecimens, with a commitment to avail a copy of the record of destruction within two (2) months of this date

Per G-RegForeignStud, any experimental tests, analyses, and investigational procedures on biospecimens and/or materials should be undertaken within Zimbabwe. However, where it is proven that no capacity for a particular test, analysis, and investigation of a biospecimen and/or material exists in Zimbabwe, or where exchange is needed for quality assurance purposes, the researcher must obtain approval from the RCZ to export the biospecimens and/or materials for research. The applicant must complete an STA form signed by the researcher and the recipient institution abroad. In addition, ZWE-64 indicates that a biospecimen shipment log sheet should always be filled out and attached to the RCZ biospecimen shipment certificate. Any changes to the log sheet must be signed. The log sheet allows for four (4) shipments. When submitting a new log sheet, all previous log sheets should be attached. All log sheets should be numbered with the first log sheet numbered 1.

Per ProcForeignReg and G-RegForeignStud, to export a biospecimen and/or material for research purposes, the researcher must complete an STA (ZWE-63) signed by the researcher and the recipient institution abroad. Type and quantities of specimens to be shipped, tests to be conducted, and justification for shipping to a foreign lab must be indicated on the STA annex form before submission to the RCZ. As indicated in ZWE-20, researchers exporting biospecimens out of Zimbabwe must provide the RCZ with a record of destruction of leftover biospecimens within two (2) months from the proposed date of destruction. The STA (ZWE-63) must state a destruction date and commit to completing the destruction when applying to export biospecimens.

In accordance with ZWE-57, investigators must obtain informed consent from clinical trial participants for the long-term storage and future use of specimens. The informed consent form (ICF) (ZWE-57) indicates participants must be informed that specimens will be collected for the laboratory tests described in the ICF that was signed to join the clinical trial. The following elements should be included in the specimens ICF:

• Information about the collection, storage, and future use of leftover samples
• Written permission to have leftover samples stored after the study has ended and used for future studies
• Participation is voluntary and participants may choose to not have any samples stored other than what is needed to complete the study and still be in this research study or any future study
• How the samples will be used in future research (e.g., DNA analysis or developing new diagnostic tests)
• Study researchers will not contact the participant or the participant’s regular doctor with any results from tests done on the participant’s stored samples; if, in the very rare case that a specific test result gives important health information, the researchers will tell the study staff and the study staff will try to contact the participant
• Samples will not be sold or used directly to produce commercial products
• Research studies that want to use leftover samples must be reviewed and approved by the sponsors’ ethics committee (EC) and the Medical Research Council of Zimbabwe (MRCZ)
• Each sample will be tested immediately for the tests mentioned in the study’s consent form, and the amount left over will be stored for future use
• The name of the storage facility and laboratory where the specimens will be stored safely and securely in Zimbabwe
• Only the people who work at the facility and approved researchers will have access to the samples, and they will not have any information that identifies the participant
• There is no limit on duration of the long-term storage
• In the future, any researcher who wants to use the samples for a new study must get approval from the MRCZ and the principal investigator
• If the samples are used for future studies outside of Zimbabwe, only enough of the sample will be shipped to complete the tests required
• Risks and benefits
• The donor’s information will be kept private with coded and traceable labels and study staff are required to keep personal information confidential

Per ZWE-57, for more information about storage of specimens, inquiries should be sent to the MRCZ:

Medical Research Council of Zimbabwe
Cnr Mazoe Street/ Josiah Tongogara Avenue
Harare, Zimbabwe
Phone: +263 4 791792, 791193
Mobile: 0784 956 128