Clinical research in Kenya is regulated and overseen by the Pharmacy and Poisons Board (PPB) and the National Commission for Science, Technology and Innovation (NACOSTI).

Pharmacy and Poisons Board

As per the PPA, the CTRules, and the G-KenyaCT, Kenya’s PPB is the regulatory authority responsible for clinical trial approvals, oversight, and inspections. As described in KEN-21, the PPB and its Expert Committee on Clinical Trials (ECCT) evaluate all matters relating to clinical trials and grant permission for clinical trials to be conducted in Kenya. See KEN-20, KEN-21, and KEN-16 for more information about PPB.

Per the PPA and the CTRules, the PPB is authorized to undertake various mandated duties regarding regulation of medicines including (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Advise the government in all matters relating to the safety, packaging, labelling, distribution, and disposal of medicines
• Ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy
• Ensure that the personnel, premises, and practices employed in the manufacture, storage, marketing, distribution, and sale of medicinal substances comply with the defined codes of practice and other prescribed requirements
• Grant or revoke licenses for the manufacture, importation, exportation, distribution, and sale of medicinal substances
• Maintain a register of all authorized medicinal substances
• Publish, at least once every three (3) months, lists of authorized or registered medicinal substances and lists of products with marketing authorizations
• Regulate narcotic, psychotropic substances, and precursor chemical substances
• Consider applications for approval and alterations of dossiers intended for use in marketing authorization of medical products and health technologies
• Inspect and license all manufacturing premises, importing and exporting agents, wholesalers, distributors, pharmacies (including those in hospitals and clinics), and other retail outlets
• Prescribe a system for sampling, analysis, and other testing procedures of finished medicinal products released into the market to ensure compliance with the labeled specifications
• Conduct post-marketing surveillance of safety and quality of medical products
• Monitor the market for the presence of illegal or counterfeit medicinal substances
• Regulate the promotion, advertising, and marketing of medicinal substances in accordance with approved product information
• Approve the use of any unregistered medicinal substance for purposes of clinical trials, compassionate use, and emergency use authorization during public health emergencies
• Approve and regulate clinical trials on health products
• Disseminate information on medical products to health professionals and to the public to promote their rational use
• Collaborate with other national, regional, and international institutions on medicinal substances regulation
• Advise the Cabinet Secretary on matters relating to control, authorization, and registration of medicinal substances
• Implement any other function relating to the regulation of medicinal substances

Please note: Kenya is party to the Nagoya Protocol on Access and Benefit-sharing (KEN-3), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see KEN-15.

National Commission for Science, Technology and Innovation

As delineated in the STI-Act and G-ECBiomedRes, in addition to obtaining the PPB’s permission to conduct research in Kenya, the principal investigator or the head of a research institution must obtain a favorable opinion from an ethics committee accredited by NACOSTI and a NACOSTI research license prior to initiating a study. NACOSTI’s role is to regulate and ensure quality in the science, technology, and innovation sector, and to advise the Kenyan government on related matters. According to Part II of the STI-Act, NACOSTI has specific research coordination and oversight functions, and it liaises with the National Innovation Agency and the National Research Fund to ensure funding and implementation of prioritized research programs. In addition per the STI-Act and KEN-39, NACOSTI is mandated to register and accredit research institutions in Kenya. The objective of registration and accreditation is to uphold the standard of research in the country and secure public confidence in the national research system. See KEN-32 for more information about NACOSTI’s mandate and functions.

Contact Information

Pharmacy and Poisons Board

According to the G-KenyaCT and KEN-22, the PPB contact information is as follows:

Pharmacy and Poisons Board
P.O. Box 27663 - 00506
Lenana Road Opp. DOD
Nairobi, Kenya

Telephone: (+254) 709 770 100 or (+254) 709 770 xxx (where xxx represents the extension of the officer or office)
Email: info@ppb.go.ke or info@pharmacyboardkenya.org
For Clinical Trials Inquiries: cta@pharmacyboardkenya.org

National Commission for Science, Technology and Innovation

According to KEN-29, the NACOSTI contact information is as follows:

National Commission for Science, Technology and Innovation
off Waiyaki, Upper Kabete
P. O. Box 30623
00100 Nairobi, Kenya

Phone (landline): (+254) 020 4007000, (+254) 020 8001077
Phone (mobile): 0713 788 787 / 0735 404 245

Email: customercare@nacosti.go.ke or info@nacosti.go.ke

Clinical research in Tanzania is regulated and overseen by the Tanzania Medicines and Medical Devices Authority (TMDA) and the Tanzania Commission for Science and Technology (COSTECH).

Tanzania Medicines and Medical Devices Authority

As per the TMMDAct and TZA-4, the TMDA is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in Tanzania. (Note: while the TMMDAct is formatted as a “Revised Draft,” it incorporates the final changes from 2019 that are codified in the FinanceAct.) The TMDA grants permission for clinical trials to be conducted in the country in accordance with the TMMDAct and the CT-Regs.

Per TZA-29, the TMDA is an executive agency under the Ministry of Health (MoH). The TMDA is responsible for regulating the safety, quality, and effectiveness of medicines, medical devices, and diagnostics.

Per the TMMDAct, the agency has a Ministerial Advisory Board (MAB), which consists of:

• The MoH Permanent Secretary who serves as Chairman
• Up to 12 Minister-appointed members
• The Director General who serves as Secretary to the board

In accordance with TZA-29, TMDA is responsible for the following regulatory processes:

• Regulating the manufacture, importation, distribution, and sale of medicines, medical devices, and diagnostics
• Prescribing standards of quality, safety, and effectiveness for medicines, medical devices, and diagnostics
• Inspecting manufacturing industries and business premises dealing with regulated products and ensuring the standards required are attained
• Evaluating and registering medicines, medical devices, and diagnostics so as to reach the required standards before marketing authorization
• Issuing business permits for premises dealing with regulated products
• Assessing the quality, safety, and efficacy of controlled drugs
• Conducting laboratory investigations for regulated products to ascertain their quality specifications
• Conducting pharmacovigilance of medical products and vigilance of medical devices and diagnostics circulating on the market
• Promoting rational use of medicines, medical devices, and diagnostics
• Educating and sharing accurate and reliable information to stakeholders and the general public on regulatory matters

As described in TZA-2, TMDA’s Clinical Trials Control and Pharmacovigilance (CTPV) section is under the Directorate of Human and Veterinary Medicines, and is responsible for the regulation of clinical trials, pharmacovigilance, and post-marketing surveillance. The regulation of clinical trials mainly includes authorization of clinical trials and good clinical practice (GCP) inspection of investigator sites. See the Scope of Assessment section for additional details.

The PV-Regs established the Pharmacovigilance Technical Committee, under the National Pharmacovigilance Centre of TMDA, to provide recommendations to the Director General on pharmacovigilance-related safety issues, including causality assessment of adverse drug reactions and adverse events. In addition, as stated in TZA-37, there is a TMDA Clinical Trials Technical Committee (CTTC), pursuant to the TMMDAct, that provides independent technical advice to the Director General. Members of the CTTC provide technical advice to assure that clinical trials are designed, conducted, analyzed, and reported in accordance with TMDA and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13) guidelines. Members of the CTTC are required to be prudent, transparent, independent, and committed to their professional ethics while discussing all matters pertaining to clinical trials. The CTTC, which meets at least once quarterly, is composed of experts with knowledge and experience in at least the following fields:

• Clinical Trials
• Medical Research
• Clinical Pharmacology
• Clinical Epidemiology
• Medicine
• Dental Surgery
• Pharmacy
• Medical Statistics
• Public Health
• Toxicology
• Microbiology
• Pathology
• Regulatory Affairs

Tanzania Commission for Science and Technology

According to TZA-45 and TZA-16, COSTECH is under the Ministry of Education, Science and Technology and is responsible for coordinating and promoting research and technology as the chief advisor to the government. Its principal roles and responsibilities include (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Preparing and reviewing national science, technology, and innovation programs, including dissemination and transfer of technology
• Monitoring and coordinating the activities relating to scientific research, technology development, and innovation of all persons or body concerned with such activities
• Acquiring, storing, and disseminating scientific and technical information
• Registering scientific research institutions operating in Tanzania
• Advising the government on matters such as priority areas for scientific research; the allocation and use of research and innovation funds; regional and international cooperation in scientific research, innovation, and technology development and transfer; and matters relating to the training and recruitment of research personnel
• Defining national resource priorities and research guidelines
• Communicating research results
• Providing technical support to institutions related to ethics and monitoring implementation of research and innovative activities

Per the G-ResearchClearance and TZA-47, the COSTECH must review, approve, and issue permits for all research in Tanzania. The G-ResearchClearance specifies that COSTECH, through its National Research Clearance Committee (NRCC), receives and reviews research proposals for their scientific merit, safety, and ethics. Upon approval, NRCC issues research permits. (Note that TZA-47 refers to the NRCC as the National Research Registration Committee.)

Other Considerations

Per TZA-9, Tanzania has adopted several clinical trial related guidelines of the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use including the ICH Guideline for Good Clinical Practice E6(R2) (TZA-13). See TZA-9 for a listing of the adopted guidelines.

Contact Information

Tanzania Medicines and Medical Devices Authority

Tanzania Commission for Science and Technology

According to TZA-46 and TZA-47, COSTECH’s contact information is as follows (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Tanzania Commission for Science and Technology
Ali Hassan Mwinyi Road, Kijitonyama (Sayansi) COSTECH Building
Dar es Salaam, Tanzania

Telephone: +255 22 2700749

Email: info@costech.or.tz or dg@costech.or.tz
Research Clearance Email: rclearance@costech.or.tz

Overview

In accordance with the PPA, the CTRules, the G-KenyaCT, and KEN-21, Kenya’s Pharmacy and Poisons Board (PPB), together with its Expert Committee on Clinical Trials (ECCT), is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). The G-KenyaCT specifies that the scope of the PPB’s assessment includes all clinical trials (Phases I-IV). As delineated in the CTRules, the G-KenyaCT, and KEN-21, the PPB review and approval process may not be conducted in parallel with the ethics committee (EC) review. Rather, EC approval must be obtained prior to applying for PPB approval. As delineated in the STI-Act and G-ECBiomedRes, the principal investigator or the head of a research institution must obtain a favorable opinion from an EC accredited by the National Commission for Science, Technology and Innovation (NACOSTI) and a NACOSTI research license prior to initiating a study.

Clinical Trial Review Process

Pharmacy and Poisons Board

Per the CTRules and the G-KenyaCT, the PPB, through the ECCT, communicates the decision to approve, request additional information, or reject the application to the sponsor or the representative in writing within 30 working days of receiving a valid application. The G-KenyaCT indicates that in the case of rejection, the applicant may appeal and provide additional information to satisfy PPB requirements. In specific cases, the PPB may decide to refer the matter to external experts for recommendation.

As specified in the G-KenyaCT, each ECCT member, prior to reviewing the application, will declare any conflict of interest in the study and should have no financial or personal interests, which could affect their impartiality. During the protocol review, the reviewers must use the standard criteria (including available clinical and non-clinical data etc.) defined by the PPB. Confidentiality must be maintained during the review. Per the CTRules and the G-KenyaCT, the PPB/ECCT’s review must consider:

• The reliability and robustness of the data generated in the clinical trial, taking into account statistical approaches, design of the clinical trial, and methodology, including sample size and randomization, comparator, and endpoints
• Compliance with the requirements concerning the manufacturing and import of IPs and auxiliary medicinal products
• Compliance with the labelling requirements
• The completeness and adequateness of the investigator's brochure

Regarding protocol amendments, the CTRules and the G-KenyaCT stipulate that any new information affecting the conduct/management of the trial, safety of the participants, and manufacture of the IP necessitating changes to the protocol, consent form, and trial sites require immediate submission of the amended documents to PPB for review and approval. Arrangements must be in place to take appropriate urgent safety measures to protect participants against any immediate hazard where new events relating to the conduct of the trial, or the development of the IP are likely to affect the safety of the participants. A copy of a favorable opinion letter from the EC on record must be submitted with the request for approval of a proposed amendment to the PPB. PPB approval must be obtained for all substantial amendments. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB. See Submission Process and Submission Content sections for additional details on amendment submissions. Also, see the G-KenyaCT for examples of substantial amendments.

In addition, per the G-KenyaCT, the sponsor or the representative is required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval.

Per the CTRules and the G-KenyaCT, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants in the trial is compromised or that the scientific reasons for conducting the trial have changed. Additionally, per the CTRules, the PPB may revoke the approval if it determines that the IP has expired or is not usable.

As delineated in the G-KenyaCT, the PPB may inspect clinical trial sites to ensure that the generally accepted principles of good clinical practice (GCP) are met. The objectives of the inspection are to:

• Ensure that participants are not subjected to undue risks and that their rights, safety, and wellbeing are protected
• Validate the quality of the data generated
• Investigate complaints
• Verify the accuracy and reliability of clinical trial data submitted to the PPB in support of research or marketing applications
• Assess compliance with PPB guidelines and regulations governing the conduct of clinical trials
• Provide real-time assessment of ongoing trials

Per CRO-Inspect, the PPB is responsible for inspecting clinical trial and bioequivalence study sites that generate data for registration of medicines. The PPB requires that these sponsor and contract research organization sites comply with applicable good practices, including GCP, good laboratory practice (GLP), and good documentation practices. Based on risk assessments, the PPB will determine compliance with generally accepted good practice through inspections and, where appropriate, document reviews. In addition, see Cert-Emrgcy for information about GCP and good manufacturing practice certifications during emergencies.

Special Circumstances and Public Health Emergencies

The CTRules delineates that the PPB may, in special circumstances, authorize the conduct of a clinical trial under fast-track procedures or non-routine procedures. PPB may recognize and use clinical trial decisions, reports, or information from other competent authorities authorizing fast-track clinical trials. The special circumstances may include:

• A public health emergency
• The rapid spread of an epidemic disease
• Any other circumstance as may be determined by the PPB

The G-KenyaCT outlines PPB’s scope of assessment of a clinical trial application during a public health emergency. The PPB will conduct an expedited review and liaise with relevant stakeholders (including relevant ECs and other oversight bodies) to facilitate a holistic review of an application in a fast-track manner. The following prioritization criteria must be applied in the selection of applications for expedited review:

• Epidemiology of the emergency
• Morbidity and mortality associated with the emergency and/or condition under study
• Supporting scientific data/information available for the IP at the time of submission
• Feasibility of the implementation of the trial design within the context of the emergency
• Benefit impact of the intervention and/or trial design

In addition, PPB’s assessment will consider the following:

• The research does not compromise the response to an outbreak or appropriate care
• Studies are designed to yield scientifically valid results under the challenging and often rapidly evolving conditions of disasters and disease outbreak
• The research is responsive to the health needs or priorities of the disaster victims and affected communities and cannot be conducted outside a disaster situation
• The participants are selected fairly and adequate justification is given when particular populations are targeted or excluded, for example, health workers
• The potential burdens and benefits of research participation and the possible benefits of the research are equitably distributed
• The risks and potential individual benefits of experimental interventions are assessed realistically, especially when they are in the early phases of development
• Communities are actively engaged in study planning to ensure cultural sensitivity, while recognizing and addressing the associated practical challenges
• The individual informed consent of participants is obtained from individuals capable of giving informed consent
• Research results are disseminated, data are shared, and any effective interventions developed or knowledge generated are made available to the affected communities

National Commission for Science, Technology and Innovation

STI-Act stipulates that NACOSTI issues research licenses if it finds that the conduct of the research is beneficial to the country and will not adversely affect any aspect of the nature, environment, or security of the country. The license issued will have NACOSTI’s seal and will indicate the commencement and expiration of the research. In addition, NACOSTI maintains a register of all persons granted a license, which is available for public inspection during normal working hours free of charge.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision. For approved research, NACOSTI may conduct an evaluation to assess compliance with the conditions of the license. If the research project has not been completed within the stipulated period, the researcher may apply for renewal of the license and pay the requisite fee. The researcher is expected to apply for renewal by attaching a progress report instead of a proposal. KEN-31 indicates that the duration of the research license is one (1) year.

Overview

As indicated in the TMMDAct and the CT-Regs, the Tanzania Medicines and Medical Devices Authority (TMDA) is responsible for reviewing, evaluating, and approving clinical trial applications in Tanzania. The scope of the TMDA’s assessment includes all clinical trials (Phases I-IV). As delineated in the TMMDAct, the CT-Regs, and the G-AppConductCT, the TMDA’s approval of a clinical trial application is dependent upon obtaining proof of national ethics committee (EC) approval from the National Health Research Ethics Committee (NatHREC). According to the G-AppConductCT and TZA-4, the TMDA and national EC reviews may be conducted in parallel. However, the TMDA application must include a copy of the national EC's acknowledgement of receipt for the study protocol. In addition, the TMDA's approval will only be finalized once national EC approval is obtained.

As described in TZA-2, TMDA’s Clinical Trials Control and Pharmacovigilance (CTPV) section is responsible for the regulation of clinical trials, pharmacovigilance, and post-marketing surveillance. Its functions include the following:

• Review and assess applications to conduct clinical trials in Tanzania, including evaluating clinical trial protocols, including preclinical studies, clinical data, and quality of investigational products (IPs)
• Approve clinical trial applications with minimum requirements
• Inspect clinical trial sites to ensure compliance with good clinical practices (GCPs), good clinical laboratory practices (GCLPs), clinical trials regulations, guidelines, standard operating procedures (SOPs), and internationally accepted standards
• Update and maintain the Tanzania Clinical Trials Registry, which is accessed via the Regulatory Information Management System (RIMS) Customer Self Service Portal (TZA-34)
• Review and evaluate all safety information (adverse events) from clinical trials
• Review and evaluate progress reports of all approved clinical trials
• Serve as Secretariat to Tanzania’s Clinical Trials Technical Committee
• Monitor and respond to all inquiries regarding conduct of clinical trials in Tanzania

Per the G-ResearchClearance, the Tanzania Commission for Science and Technology (COSTECH) must review and approve all research in Tanzania to:

• Ensure research conduct complies with national laws and regulations
• Document and register research
• Secure research results and promote its use in policy and practice
• Safeguard the dignity, rights, safety, and well-being of research participants
• Reduce systemic risks imposed through the research
• Provide research permits

Clinical Trial Review Process

Tanzania Medicines and Medical Devices Authority

As set forth in the TMMDAct, the CT-Regs, and G-AppConductCT, the TMDA coordinates the clinical trial application process. Upon receipt of a clinical trial application, the TMDA initially screens the application for completeness. If complete, the TMDA officer acknowledges receipt of the application by returning a signed copy of the cover sheet to the applicant (see Annex 1 of the G-AppConductCT). The TMMDAct states that the TMDA Director General must issue a Clinical Trial Certificate to authorize the trial to be conducted. (See the Submission Content section for submission requirements.) TZA-4 indicates that the TMDA may request a clarification or additional documents through the online submission system (TZA-34). The assessment will resume once the applicant has provided clarification and responded to the queries.

Per the G-AppConductCT, the TMDA reviews clinical trial applications and amendments to assess the quality of the products and determine that the use of the IP for the purposes of the clinical trial does not endanger the health of participants or other persons, the clinical trial is not contrary to the best interests of a participant, and the objectives of the clinical trial may be achieved. Evaluation of applications is conducted on a first-in, first-out basis unless the IP meets the fast-track criteria. The application assessment must involve the TMDA and external evaluators. If the TMDA requests additional information from the applicant, the evaluation process will stop until the TMDA receives a written response to the query. The response should be submitted within six (6) months after being issued with a query letter. All queries issued in the same letter must be submitted together in one (1) transaction. Non-compliance to these requirements in content and format will lead to rejection of the clinical trial. Evaluation of applications will be completed within 60 working days of receiving the application. A new clinical trial application may be fast tracked and assessed within 30 working days of its submission if the applicant has requested this and paid twice the prescribed clinical trials application fees. If authorization is not granted, an appeal may be submitted to the TMDA within 60 days of the TMDA’s decision. If no appeal is submitted by the applicant within this period or, if after consideration of any comments submitted, the TMDA is still not satisfied, it must reject the application. In an appeal, the applicant must give grounds for review for each reason given for the rejection of a clinical trial. The grounds for the appeal request must be based on the information that was submitted in the application. Any additional or new information that was not earlier submitted will only be considered upon submission of a new application. The TMDA may review, reject, or vary its own decision.

Per the G-AppConductCT, the clinical trials certification will be valid up to the proposed duration of the study indicated in the application. However, the validity will not extend beyond five (5) years. If the trial will last more than five (5) years, the applicant must request an extension. Further, the TMDA must approve amendments to a previously authorized protocol for changes that affect participant selection and monitoring; changes that affect clinical efficacy and safety requirements; changes that affect participant discontinuation; addition/deletion of an investigational site(s); changes that result in the extension of trial duration; and/or changes that relate to the chemistry and manufacturing information that may affect drug safety and quality. An application for amendment(s) must be accompanied by clearance or authorization from NatHREC.

The G-AppConductCT indicates that the TMDA must not authorize a clinical trial where it finds that:

• The information and documents as set out in the guidelines have not been provided
• The application contains false or misleading information
• The information provided is insufficient to enable the TMDA to assess the safety and risks of the IP or clinical trial
• Queries raised by the TMDA in relation to the application were not adequately responded to
• The applicant has not submitted an ethical clearance from any approved medical research institute
• The use of the IP for the purposes of the clinical trial endangers the health of a clinical trial participant or any other person
• The objectives of the clinical trial will not be achieved
• It is not in the public interest to authorize the clinical trial
• Any other reasonable grounds as may be determined by the TMDA

Next, the G-AppConductCT states that following the TMDA’s authorization of a new clinical trial or amendment, information regarding refusals by other regulatory authorities or ECs should be submitted as a notification. Further, the TMDA may suspend, terminate, or withdraw authorization of a clinical trial if it finds that the conditions of authorization of a trial have been violated; or there is information raising doubts about the safety or scientific validity of the trial or the conduct of the trial at a particular trial site. For additional information, see TZA-4.

(See the Submission Process section for additional details on the clinical trial application and amendments submissions.)

Tanzania Commission for Science and Technology

As for COSTECH review, the G-ResearchClearance indicates that once COSTECH receives a new application, the Secretariat screens the application for completeness; registers the application; sends an acknowledgement to the applicant; submits the application for the appropriate expert, local, and National Research Clearance Committee (NRCC) review; records NRCC’s final decision; and informs the applicant of the decision. COSTECH’s NRCC must reach a decision through a consensus of members forming a quorum at their meeting. The decision may be approval without amendments, approval subject to minor or major amendments, a denial, or a postponement pending further information. If approved, researchers should collect their permit within 90 days after the decision is communicated, and failure to do so requires a new application.

Per the G-ResearchClearance, permits are valid for one (1) year, and can be renewed, provided that COSTECH receives satisfactory progress reports for the previous periods. COSTECH must review the research to ensure compliance with the approved permit and see if any material changes have occurred in the research or if there are findings that may cause termination. The principal investigator (PI) must write to COSTECH two (2) months before the expiration date to request a renewal of the permit. For renewals, COSTECH will submit the registered application to an internal reviewer for evaluation, and otherwise, follow the same review and notification procedures as outlined above for a new permit. Regarding applications for amendments, if there is a change in PI, the affiliate institution must notify COSTECH within one (1) month of the departure of the outgoing PI in writing with an accompanying progress report. If a new researcher joins an ongoing project, the PI must submit a request for a research permit for the new member to COSTECH at least two (2) months prior to joining the team, accompanied with a detailed CV and rationale. Changes to the study site, objectives, and methodologies for an ongoing research project must be submitted in writing to COSTECH at least two (2) months prior to implementing the change.

See TZA-47 for additional information about national research registration.

Pharmacy and Poisons Board

Per the PPA and the G-KenyaCT, the sponsor or the representative is responsible for paying a fee to the Pharmacy and Poisons Board (PPB) to submit a clinical trial application for authorization. The PPB currently requires a non-refundable application fee of $1,000 USD, or the equivalent in Kenya Shillings at the prevailing bank rates.

Payment Instructions

As stated in Annex 2 of the G-KenyaCT, payment is to be made by a bank check payable to the “Pharmacy and Poisons Board” and presented to the PPB’s accounts office upon submitting the application.

Payment can also be made by electronic fund transfer (EFT) to the PPB Bank account, if required. The sponsor or the representative is responsible for all bank charges associated with the EFT. Details of the EFT payment should be obtained from the PPB prior to initiating such a transaction.

National Commission for Science, Technology and Innovation

As delineated in KEN-31, the National Commission for Science, Technology and Innovation (NACOSTI) charges a fee that varies depending on the applicant’s status as Kenyan or non-Kenyan, and standing as a researcher (i.e., student, public/private institution, private company). The fees are non-refundable and also apply to research license renewals. Details on additional requirements are provided in the Submission Content section.

• Student, Undergraduate/Diploma: East African Community (EAC) Countries – 100 Kenya Shillings; Kenyan Citizens – 100 Kenya Shillings; Rest of Africa – 200 Kenya Shillings; Non-Africans - $150 USD
• Research (Masters): EAC Countries – 1,000 Kenya Shillings; Kenyan Citizens – 1,000 Kenya Shillings; Rest of Africa – 2,000 Kenya Shillings; Non-Africans - $350 USD
• Research (PhD): EAC Countries – 2,000 Kenya Shillings; Kenyan Citizens – 2,000 Kenya Shillings; Rest of Africa – 4,000 Kenya Shillings; Non-Africans - $400 USD
• Post-Doctoral: EAC Countries – 5,000 Kenya Shillings; Kenyan Citizens – 5,000 Kenya Shillings; Rest of Africa – 10,000 Kenya Shillings; Non-Africans - $500 USD
• Public Institutions: Kenyan Citizens – 10,000 Kenya Shillings
• Private Institutions, Commercial/Market Research, Companies: Kenyan Citizens – 20,000 Kenya Shillings

See KEN-31 for information on service charges.

Payment Instructions

Per KEN-31, NACOSTI has migrated payment services for research licensing to the eCitizen platform (KEN-12). East African citizens have the following payment options on KEN-12 with a Kenya Shillings account: mobile money via Mpesa Express or Paybill Number 222222; or these other available payments via KEN-12:

• Airtel Money
• Kenya Commercial Bank
• Co-operative Bank
• Pesaflow Direct
• National Bank
• RTGS

KEN-31 indicates that non-Kenyans should use the US Dollar account on KEN-12 with these payment options:

• Kenya Commercial Bank (USD)
• Co-operative Bank (USD)
• NBK (USD)
• Equity Cash
• Debit/credit/prepaid card

Tanzania Medicines and Medical Devices Authority

As per the G-AppConductCT and the TMMDAFees, applicants are responsible for paying a processing fee to submit a clinical trial application. The TMMDAFees indicates that the Tanzania Medicines and Medical Devices Authority (TMDA) levies the following processing fees:

• $3,000 USD for submitting a clinical trial application
• Double the cost of registration and analysis fee for fast-track clinical trial applications
• $500 USD for amendments for major changes in clinical trials
• $300 USD for amendments for minor changes in clinical trials

See the TMMDAFees for a complete list of TMDA fees and charges.

Payment Instructions

The G-AppConductCT states that the fee must be paid to the order of the TMDA directly to the bank by draft electronic transfer through the following accounts:

Foreign applicants: Account Numbers 100380013 Citibank (T) and 02J1021399100 CRDB
Local applicants: Account Number 2041100069 NMB

Applicants are responsible for all bank charges when payment is made by bank transfer. In addition, applicants must include a note with payment details, including the applicant’s name, the product(s) paid for, and the amount of fees paid.

TZA-4 indicates that the banks accounts are linked to Government Electronic Payment Gateway (GEPG) payments as follows:

• Name: GEPG TMDA Collection Account (USD), Bank: NMB Revenue Bank, Account No: 20810015291, Branch University
• Name: GEPG TMDA Collection Account (USD), Bank: NBC USD, Account No: 040105002468, Branch: UDSM
• Name: GEPG TMDA Collection Account (USD), Bank: CRDB Bank US, Account No: 0250021399100, Branch: Holland House

The Pay-Overseas reiterates that overseas customers must make all payments via GEPG. Before making any payment, TMDA customers should receive the special payment identification number (Control Number) indicated on a Proforma Invoice issued by the TMDA as per the TMMDAFees. The TMDA’s external customers who pay for services from abroad must fill the relevant payment form (swift form), especially item/section No. 70 by ensuring that no other information is entered in this section except the payment identification number (Control Number). However, the payer should select “OUR” in the charge mode section 71A. Any payment made without a Control Number will not be reflected in any invoice. Further, payments of more than one (1) Control Number(s) cannot be combined. Note that deposited money in the TMDA’s account cannot be refunded.

Tanzania Commission for Science and Technology

As delineated in the G-ResearchClearance, the Tanzania Commission for Science and Technology (COSTECH) charges an application fee of $50 USD to review and register a research proposal. The principal investigator (PI) should pay the nonrefundable research application fee, which is paid per project. Before the permit is issued, COSTECH requires foreign researchers to pay a research permit fee of $300 USD.

Payment Instructions

Per the G-ResearchClearance and TZA-47, foreign researchers can pay the research permit fee via the following bank account:

Account name or beneficiary: Tanzania Commission for Science and Technology
Bank Name: National Bank of Commerce Ltd
Branch: Samora Avenue, P.O. Box 9002, Dar es Salaam, Tanzania
Account Number: 012105018998
Account Currency: US Dollars
Swift Number/Code: NLCBTZTX

According TZA-47, in-country applicants can pay the fee with a control number (payment bill), which will be used for a deposit. A control number for payment can be obtained through an email request to COSTECH at rclearance@costech.or.tz.

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. KEN-25 provides a list of the accredited institutional ECs.

Ethics Committee Composition

As delineated in the G-ECAccred, institutional ECs should consist of at least seven (7) members, or an odd number above seven (7). The G-ECBiomedRes states that these members should be multidisciplinary and multisectoral in composition, collectively encompass relevant scientific expertise, balanced age and gender distribution, and include laypersons representing community interests and concerns. Per the G-ECAccred, the composition should meet the following requirements:

• At least one (1) member with knowledge and understanding of Kenyan law
• At least one-third of the members must be female, and one-third must be male
• At least one (1) member who is unaffiliated with the institution
• At least two (2) members must have research expertise and experience, one (1) of whom must be in the health field
• At least one (1) member must be a lay member
• For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research
• Reflect the regional and ethnic diversity of the people of Kenya

The chairperson must also have some basic training and/or experience in bioethics and leadership. All EC appointments are the responsibility of the institution’s administrative head. See the G-ECAccred and the G-ECBiomedRes for detailed institutional EC requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

Per G-ECBiomedRes, ECs need to have independence from political, institutional, professional, and market influences. As delineated in the G-ECAccred, the G-ECBiomedRes, and the STI-Regs, institutional ECs must operate within written standard operating procedures (SOPs) which delineate the EC’s process for conducting reviews. Per the G-ECAccred, SOPs should include but are not limited to information on EC scope, responsibility, and objectives, institutions served, committee functions, terms and conditions of member appointment, business procedures including meeting schedules and types of reviews, documentation, recordkeeping, and archiving procedures, quorum requirements, communication procedures, and complaint process and dispute resolution procedures. Per the G-ECAccred and the STI-Regs, these documents must be provided to NACOSTI.

Per the G-ECAccred, the quorum for NACOSTI-accredited EC meetings must be:

• At least 50 percent of the membership must form the quorum
• A lay person must be present in all meetings
• For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research.

The G-ECBiomedRes also defines quorum requirements:

• The minimum number of members required to compose a quorum (e.g., more than half the members)
• The professional qualifications requirements (e.g., physician, lawyer, statistician, paramedical, or layperson) and the distribution of those requirements over the quorum; no quorum should consist entirely of members of one (1) profession or one (1) gender; a quorum should include at least one (1) member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the institution/research site

Per G-ECBiomedRes, EC member terms of appointment should be established that include the duration of an appointment, the policy for the renewal of an appointment, the disqualification procedure, the resignation procedure, and the replacement procedure. A statement of the conditions of appointment should be drawn up that includes the following:

• A member should be willing to publicize their full name, profession, and affiliation
• All reimbursement for work and expenses, if any, within or related to an EC should be recorded and made available to the public upon request
• A member should sign a confidentiality agreement regarding meeting deliberations, applications, information on research participants, and related matters

Regarding training, EC members should have initial and continued education regarding the ethics and science of biomedical research. The conditions of appointment should indicate the availability and requirements of introductory training, as well as on-going continuing education. This education may be linked to cooperative arrangements with other ECs in the area, country, and region.

For detailed institutional EC requirements and information on other administrative processes, see the G-ECAccred and the G-ECBiomedRes. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

Overview

As indicated in the G-AppConductCT, all clinical trials require national ethics committee (EC) approval for each trial site. Per the G-TMRCC and TZA-50, the national EC in Tanzania is the National Health Research Ethics Committee (NatHREC), which focuses on the ethical issues surrounding submitted research proposals. As delineated in the G-TMRCC, NatHREC-Charter, TZA-5, and TZA-18, NatHREC is a subcommittee of the Medical Research Coordination Committee (MRCC), which serves as the national health research coordinating body, and is responsible for supervising, controlling, coordinating, evaluating, and promoting health research in Tanzania or elsewhere on behalf of or for the benefit of Tanzania. The MRCC, which is part of the National Institute for Medical Research (NIMR), delegates the registration, review, approval, and monitoring of clinical research to the NatHREC.

As delineated in NatHREC-Charter, NatHREC provides ethical review and clearance of health research protocols and monitors and evaluates research studies. In addition, NatHREC conducts the following activities:

• Receiving and registering all health research carried out in Tanzania
• Ensuring that all health research protocols are thoroughly reviewed to safeguard the dignity, rights, safety, and well-being of research participants
• Advising researchers on the risks and responsibilities of conducting research
• Recommending to the MRCC for ethics clearance approval, all health research protocols that have complied with the country’s ethics regulations and guidelines
• Monitoring and coordinating all approved health research conducted in Tanzania
• Advocating for and overseeing all issues pertaining to health research data and material sharing and/or transfer
• Supporting health research institutions in Tanzania to establish institutional ECs or Institutional Review Boards (IRBs)
• Accrediting health research institutions’ ECs

Per the G-AppConductCT, G-EthicsHR-TZA, the G-ResearchIntegrity, the G-RevPrtcl, TZA-18, TZA-5, and TZA-1, all health research involving foreign collaborators must get ethics approval from both the institutional EC and NatHREC. In addition, TZA-5 specifies that the following also require review by both NatHREC and the zonal or institutional EC: all clinical trials; research dealing with vulnerable, special, or marginalized groups; and sensitive topics or indigenous communities. Protocols that do not involve foreign collaborators and non-clinical trials of investigational products (IP) can be reviewed and given ethics clearance at the zonal or institutional level. NatHREC may request zonal or institutional EC reviewers to assist in review or joint review of protocols when needed. The NatHREC-Charter indicates that institutional and zonal ECs complement NatHREC’s function of issuing institutional ethics clearance certificates and monitoring the approved research at their institutions. TZA-18 states that if there is no institutional EC available, the approval must be obtained from NatHREC.

The G-EthicsHR-TZA further states that institutional ECs should monitor their hosted research activities to ensure compliance. Institutional ECs may function at the institutional, zonal, or national levels. ECs act as independent reviewers of any proposed study on human research participants, to ensure ethical conduct of research, and that participant’s rights and welfare are not violated. The major responsibility of ECs is to safeguard the rights, safety, and well-being of research participants. See the Oversight of Ethics Committees section for information on the registration and accreditation of ECs by NatHREC.

Ethics Committee Composition

National Health Research Ethics Committee

Per the G-EthicsHR-TZA and TZA-5, the Director General of NIMR is responsible for appointing NatHREC members. Members are selected based on their capacity, interest, ethical and scientific knowledge, and expertise, as well as their commitment and willingness to volunteer the necessary time and effort for the NatHREC’s work. NatHREC must consist of not less than nine (9) and up to 15 members with the relevant qualifications and experience to review and evaluate the science, medical, and ethical aspects of health research protocols. In addition, NatHREC must be composed of members with varying backgrounds to promote a complete and adequate review of health research protocols commonly received by the NatHREC. Per TZA-5, committee members must include medical scientists, biomedical scientists, social scientists, legal representatives, unaffiliated community representatives, representatives of religious or faith-based organizations, a representative from the President’s Office-Regional Administration and Local Government (PO-RALG), and a representative from the Tanzania Ministry of Health. The Director General may appoint additional members depending on the need for expertise and/or representation and not exceeding the maximum number of members. Regarding leadership, the NatHREC Chairperson must be elected from among appointed members but must not be an employee of NIMR. The NatHREC Secretary, however, must always be an employee of NIMR. See TZA-5 for additional information on NatHREC’s standard operating procedures (SOPs).

Per the G-TMRCC, the NatHREC is represented by the following organizations:

• NIMR
• Tanzania Commission for Science and Technology (COSTECH)
• Muhimbili University of Health and Allied Sciences (MUHAS)) (formerly known as Muhimbili University College of Health Science (MUCHS))
• Christian Social Services Commission (CSSC)
• The National Muslim Council of Tanzania (BAKWATA)
• Economic and Social Research Foundation (ESRF)
• Tanzania Gender Networking Programme (TGNP)
• Legal and Human Rights Centre (LHRC)
• University of Dar es Salaam (UDSM)
• Ministry of Health (MoH)
• Ministry of Education (MoE)

Institutional Ethics Committees

As per the G-EthicsHR-TZA, institutional ECs must have members capable of providing a competent and thorough review of research protocols. Membership typically includes physicians, scientists, laboratory experts, nurses, lawyers, ethicists, and other professionals. In addition, the above membership also includes community members or representatives of patients’ groups who can represent the cultural and moral values of study participants. When a proposed study involves vulnerable individuals or groups, as may be the case in research involving prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such protocols will be reviewed. Regular rotation of members is desirable for balancing the advantage of experience with that of fresh perspectives. In addition, each institutional EC must include at least one (1) member who is not affiliated with the institution and is not part of the immediate family of a person who is affiliated with the institution. Further, an EC may invite individuals with competence in particular areas to assist in the review of issues, which require expertise beyond, or in addition to that available in the EC; these individuals do not vote with the EC.

Per IERC-Accredit, following are the membership requirements for ECs accredited with NIMR:

• The Chairperson must have adequate experience in health research, leadership, and have basic knowledge of bioethics
• An EC must comprise at least five (5) members or more, and the total must be an odd number
• At least one-third of the members of the EC must be of either gender
• At least one (1) member should come from outside the institution
• At least two (2) members should have research expertise and experience, and one (1) of these should be in the health field
• At least one (1) member should represent a lay group
• For ECs reviewing clinical research, the committee should have representation from medicine, laboratory, pharmacy, and nursing as needed; a clinician who is active in clinical practice (with a valid practicing license) or in clinical research is mandatory
• At least one (1) member of the EC should possess knowledge and understanding of Tanzanian law
• Where an EC has been formed to serve more than one (1) institution, the institution hosting the Secretariat is responsible for the functioning of the EC in all aspects
• Where multiple institutions are involved in one (1) EC, the appointing authority must make appointments in consultation with the relevant heads of the respective institutions

The G-ResearchIntegrity recommends that composition should not only be multi-disciplinary and multi-sector but should also balance scientific expertise, age, and gender distribution, and should have a non-technical member representing community interests. The institution should determine the type of members needed and establish procedures for selecting/appointing members and number of persons. It is recommended that ECs have seven (7) to 15 members. See the G-ResearchIntegrity and TZA-23 for additional recommendations.

Terms of Reference, Review Procedures, and Meeting Schedule

National Health Research Ethics Committee

The G-TMRCC and TZA-5 state that the NatHREC must operate within written SOPs, including a process to be followed for conducting reviews. The G-TMRCC states that the SOPs should include information on NatHREC composition, meeting schedules, frequency of reviews, requirements for initial and ongoing evaluation of the research study, and requirements for notifying the investigator and the institution of results related to the study’s initial and ongoing evaluation. Committee members should agree to disclose their names, occupations, and affiliations, and to sign the confidentiality and conflict of interest agreements. Per TZA-5, the SOPs facilitate and support ethical review by improving the standard and uniformity of decision-making and assuring and gaining the confidence of the public in the NatHREC. Membership must be for three (3) years, renewable once, under the discretion of the MRCC Chairperson. A member of the NatHREC may resign by submitting an official letter of resignation to the MRCC Chairperson. A member of the NatHREC may also be disqualified from membership should the appointing authority provide adequate written reasons to the NatHREC and there is unanimous agreement. The NatHREC must request a replacement of any member when there is protracted illness that prevents the member from participating; persistent absenteeism or missing three (3) consecutive committee meetings; voluntary withdrawal or resignation; and/or ethical misconduct.

According to TZA-5, the NatHREC Secretary oversees the daily operations of the Secretariat and arranges training and educational programs to new and continuing committee members and the scientific community on health research ethics. The training must include programs about the basic principles of human participant protection, current literature, and regulations and guidelines affecting the committee and NIMR. Further, the Secretary assists in recruiting new committee members, as well as preparing and submitting an annual committee operational budget and plan to NIMR in consultation with the Chair. See TZA-5 for details on the functions of the NatHREC Secretariat.

Per TZA-5, NatHREC members must fulfill the following responsibilities:

• Review, discuss, and consider health research protocols submitted for ethical clearance evaluation
• Review research study progress reports and monitor on-going studies as appropriate
• Review reports on adverse events, serious adverse events, and/or suspected unexpected serious adverse reactions, as well as any other safety reports and recommend appropriate actions
• Maintain professional confidentiality of documents and deliberations of the committee review proceedings and meetings
• Declare conflicts of interest when they exist
• Participate in continuing education activities in biomedical ethics and research
• Undertake committee duties assigned to them by the NatHREC Chairperson
• Attend NatHREC meetings regularly and participate actively during deliberations
• Participate in the review of NatHREC SOPs
• Conduct research site monitoring visits as deemed necessary

According to TZA-5, the NatHREC must convene at least once a month with a quorum of at least half the number of committee members. The NatHREC Secretary, with support from the Secretariat, must prepare an annual almanac of meetings. The meeting package must include the agenda; all research protocols; and all related materials including, but not limited to, copies of the protocols, informed consent materials, continuing and final reviews, and safety reports. The Secretariat must keep a record of attendance as well as meeting deliberations, indicating which members were present and the discussions of review applications. If members have reviewed a protocol and identified issues that require the principal investigator (PI) to be present during the meeting for further deliberations, then the PI of that research protocol may be invited to answer questions or clarify issues. The meeting members must reach decisions by a consensus; however, if a consensus cannot be achieved, a formal vote must be taken. All members have the right to vote. The committee must provide formal recommendations to the MRCC on the approval of applications, along with minutes that include protocol title and date of review, a checklist of documents reviewed, and a decision reached by the committee, whether approved, approved with stipulation, recommended for resubmission after revision, or not recommended with reasons. For detailed NatHREC procedures and information, see TZA-5.

Institutional Ethics Committees

Per the G-EthicsHR-TZA, the EC members are appointed by institutional appointing authorities. The EC must be constituted according to a document that specifies the manner in which members and the Chair will be appointed, reappointed, and replaced. EC members must regularly update their knowledge about the ethical conduct of health-related research. If committees do not have the relevant expertise to adequately review a specific protocol, they must consult external persons with the required skills or certification. Each EC member must undergo at least one (1) basic training in research ethics within one (1) year of appointment and, thereafter, should undergo continued ethics training at least once every two (2) years. Members of an EC must serve for a term of three (3) years. EC members must guard against any tendencies of unethical conduct on their part. For example, they must protect the confidentiality of research projects, documents, and discussions; an EC member must not appropriate the submitted protocol for their own use; and they must not compel investigators to submit to an unnecessary repetition of review.

In addition, as delineated in the G-EthicsHR-TZA, ECs are responsible for determining whether the research objectives are responsive to the health needs and priorities of the proposed study population, particularly in Tanzania. The ability to judge the ethical acceptability of various aspects of a research protocol requires a thorough understanding of a community’s customs and traditions. For example, the EC should include members that are able to indicate suitable community members to serve as intermediaries between investigators and research participants and to advise on whether material benefits or inducements may be regarded as appropriate considering a community’s gift exchange and other customs and traditions. ECs must have mechanisms to ensure the independence of their operations. They must avoid undue influence and minimize and manage conflicts of interest. ECs must require that their members disclose to the committee any interests that could constitute a conflict of interest or otherwise bias their evaluation of a research protocol. ECs must evaluate each study considering any disclosed interests and ensure appropriate steps are taken to mitigate possible conflicts of interest. ECs may receive a fee for reviewing protocols, and this need not constitute a conflict of interest.

As required in the G-EthicsHR-TZA, ECs should hold meetings as frequently as possible to facilitate timely ethical clearance. ECs must review proposed research at convened meetings where at least 50 percent of the members are present, including at least one (1) member who represents the interests of the community. The Chairperson may be given powers to approve minor matters on behalf of the EC but ensure that the papers are made available to the rest of the EC members at the next meeting. ECs should have the power to co-opt professional or lay members where necessary. For a research protocol to be approved, it must receive the approval of a simple majority of those members present at the meeting; the only exception to the simple majority requirement is in the case of expedited review.

Regarding documentation, per the G-EthicsHR-TZA, the institution must ensure that the EC prepares and maintains adequate documentation and retain the records for at least five (5) years after the completion of the study. All records must be accessible for inspection and copying by authorized representatives, including the following:

• Detailed written procedures for the EC
• Copies of all research protocols reviewed, scientific evaluations that accompany the protocols, approved sample consent documents, progress reports submitted by the investigator(s), reports of injuries to research participants, etc.
• Minutes of EC meetings that must be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions, including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controversial issues and their resolution
• Records of continuing review activities
• Copies of all correspondence between the EC and investigator(s)
• Statements of significant new findings that were provided to research participants

Per the G-ResearchIntegrity, institutions should have clear documentation of candidacy requirements and procedures for identifying or recruiting EC members. The recruitment methods, duration of membership, terms of service, qualifications, disqualifications, resignation procedures, re-appointment/renewal, and other duties and responsibilities should be documented in EC SOPs. Appointment of EC members must be done at the institutional managerial level in consultation with experts, relevant boards, and peer institutions. Institutions should minimize conflicts of interest and establish mechanisms for maximizing transparency and confidentiality of review processes. These qualities may be enhanced by rotation and turnaround of members to allow inflow of new ideas and accountability. The conditions of appointment must clearly indicate the decision on whether to release professional profiles to the public, level of accessibility, members’ cost recovery ceilings for EC-related activities, confidentiality, and any other mechanisms geared to enhancing confidence over the EC’s operations. The pros and cons of each option must be carefully considered and communicated to candidates. Both scientific and support staff must sign a confidentiality agreement and declare any conflicts of interest from the outset.

Overview

According to G-ECBiomedRes, the primary scope of information assessed by the institutional ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. The G-ECAccred further states that the National Commission for Science, Technology and Innovation (NACOSTI) accredits ECs in order to uphold the standard of ethics review in the country; develop public confidence and trust in the national research system; facilitate equitable access to research and human health records in health facilities; and facilitate coordination and collaboration among ECs. See the G-ECAccred and the G-ECBiomedRes for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the G-KenyaCT and KEN-21, the Pharmacy and Poisons Board (PPB)’s review and approval of a clinical trial application is dependent upon obtaining approval by an accredited institutional EC. Consequently, the PPB and EC reviews may not be conducted in parallel.

As set forth in the G-ECBiomedRes, ECs must be constituted to ensure an independent and competent review and evaluation of all ethical aspects of clinical trials. ECs must review research involving human participants to ensure they meet these ethical principles:

• Respect for persons, including respect of autonomy, protection of vulnerable groups, and protection of privacy and confidentiality
• Beneficence
• Justice, which in research means equitable distribution of the benefits and the burdens

For additional details on the principles and benchmarks for ethical review, see G-ECBiomedRes.

Per the G-ECBiomedRes, expedited review may be permitted for protocols involving no more than minimal risk to research participants.

The G-ECBiomedRes indicates that all ECs should carry out regular monitoring of approved protocols involving human participants. In case of any adverse events, the EC should report this immediately to Kenya’s National Bioethics Committee (NBC).

Per the G-ECBiomedRes, with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

Overview

According to the G-TMRCC and the G-EthicsHR-TZA, the primary scope of information assessed by the National Health Research Ethics Committee (NatHREC) and the institutional ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in health research studies. The NatHREC and the institutional ECs must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations). The NatHREC is responsible for ensuring an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. TZA-5 states that the NatHREC must function in accordance with national and international standards and guidelines on health research, and guided specifically by the ethical principles expressed in the Declaration of Helsinki (TZA-30), international ethical guidelines such as the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13), and the G-EthicsHR-TZA.

As indicated in the G-ResearchIntegrity, institutional ECs review, approve, and recommend for approval, research proposals that have met scientific merit, ethical, and professional standards. The institutional ECs are expected to provide recommendations on proposals that would need approval from a nationally overseeing ethics body where available. Per the G-EthicsHR-TZA, institutional ECs act as independent reviewers of any proposed study on human research participants to ensure ethical conduct of research and that participant’s rights and welfare are not violated. The major responsibility of institutional ECs is to safeguard the rights, safety, and well-being of research participants. In addition, it is essential that they review the scientific soundness of the research protocols, which involves a proper scientific review to verify that a competent expert body has determined the research to be scientifically sound, or consult with qualified experts to ensure that the research design and methods are appropriate. If the EC does not have expertise to judge science or feasibility, they must draw on relevant expertise. See G-EthicsHR-TZA for more information on the scientific review.

Role in Clinical Trial Approval Process

National Health Research Ethics Committee

As per the TMMDAct, the CT-Regs, and the G-AppConductCT, the Tanzania Medicines and Medical Devices Authority (TMDA) and the NatHREC must approve a clinical trial application prior to the sponsor, the contract research organization (CRO), or the principal investigator (PI) initiating the clinical trial. According to the G-AppConductCT and TZA-4, the TMDA and NatHREC reviews may be conducted in parallel. However, the TMDA application must include a copy of the national EC's acknowledgement of receipt for the study protocol. In addition, the TMDA's approval will only be finalized once national EC approval is obtained.

As described in TZA-31, the NatHREC’s ethics review is managed through its Research Ethics Information Management System (REIMS) (TZA-32) (also referred to as the National Health Research Management Information System (NHRMIS)), an online web application for the submission of research protocols for NatHREC’s review, validation of protocols per NatHREC checklist (TZA-1), online review of proposals, and application status tracking. The G-RevPrtcl indicates that the NatHREC Secretariat will validate submissions for completeness upon receipt in REIMS. The G-RevPrtcl recommends the following review sequence after the materials are checked for completeness: write comments in an MS Word document; read the PI’s cover letter, the institution’s commitment letter, and other supporting letters; review the abstract/summary; review the application form, protocol, and appendices; and synthesize and submit comments online through REIMS (TZA-32). Per TZA-5, following successful validation of an application to the REIMS, the system generates a unique protocol number/identifier; this unique identifier must be used in reference to all communications to the PI or applicant regarding the application. Depending on the research area of the submitted protocols, at least two (2) primary reviewers must be assigned to review a new protocol by the NatHREC Secretariat. Comments from reviewers will reach the PI within two (2) days, depending on the type of study protocol. If the applicant fails to respond to the comments within 30 days, the NatHREC Secretariat must notify the PI of its intent to remove the protocol from the REIMS. Once the research protocol is removed from the REIMS, the PI must re-apply for ethical clearance and pay the application fee. For clinical trial applications, reviewers’ comments and the outcome of the NatHREC meeting must be forwarded to the PI within 30 days from the date of acceptance by the NatHREC. If the research protocol is cleared and the ethical clearance certificate is issued, the PI must receive it via mail at the institution’s postal address. Additionally, the PI may be able to download the soft copy of the ethical clearance certificate from the REIMS account. A PI may appeal a decision in writing to the Medical Research Coordination Committee (MRCC) Chairperson within 30 days of receipt of the decision, stating the precise issues upon which the appeal is based. The MRCC will respond to PIs in writing within 30 days or upon scrutiny of the appeal. The MRCC Chairperson may invite the PI to appear in person to the MRCC within 30 days of receiving the written appeal.

Expedited Review

TZA-5 delineates the categories of research that qualify for NatHREC expedited review:

• Research activities that present no more than minimal risk to human participants
• Minor changes (modification or amendment) to a previously approved research proposal
• Studies that involve interviews of a non-confidential nature and not likely to harm the status or interest of study participants
• Studies that involve collection of small amounts of biological specimens by non-invasive means (e.g., body fluids, excreta, hair or nail in non-disfiguring or threatening manner) for local analysis and no transfer of specimens outside of Tanzania
• Collection of data for research purposes through non-invasive procedures (not involving general anesthesia or sedation), routinely employed in clinical practices and using medical devices which have been already approved for use
• Research involving data, documents, or specimens that have been already collected or will be collected for on-going medical treatment or diagnosis
• Continuing review of certain research previously approved by the NatHREC
• Research that aligns with disease outbreaks or public health emergencies

TZA-5 states that expedited review must be conducted by two (2) or more experienced reviewers designated by the Secretariat. The expedited review must include a review of the complete study protocol with all required attachments. Results of the review process may be communicated to the PI even before being reported to the NatHREC. Expedited reviewers may exercise all the authorities of the committee except that the NatHREC reviewers may not disapprove of the research. Any research activity may be disapproved only after reviewing the protocol in accordance with the non-expedited procedure. Approval for expedited protocols is given by the MRCC through the Chairperson upon recommendation for approval from the reviewers. Once expedited approval has been granted, the protocol may be implemented as approved. Clinical trials with investigational products (IP) are not eligible for expedited review but may be considered for accelerated review. The final decision for a protocol to undergo an expedited review is determined by the NatHREC Chairperson, the NatHREC Secretariat, and/or the MRCC Chairperson, as needed. The Secretariat must notify the NatHREC of all expedited reviews at the next scheduled meeting through a listing in the meeting agenda.

Reviews During Public Health Events

Per TZA-5, rapid review of public health research and clinical trials may be implemented during public health events of national and/or international concern. During public health emergencies, the declaration will come from the public health authority of the country or an internationally recognized organization responsible for international public health. To expedite commencement of the research, many of the preliminary research processes (drafting of documents, translations, approvals) will be allowed to happen in parallel. Protocols should be sent to reviewers within 24 hours of submission by the Secretariat, and reviewers should complete their reviews within three (3) days. The consolidated review and suggested revisions (or approval) should be communicated to the PI(s) within five (5) days. The PI should respond to the review notification within 48 hours. See TZA-5 for additional details on the emergency review requirements.

Approval Duration

Regarding duration of the NatHREC approval, per TZA-5, the NatHREC Secretariat determines how often the committee must re-evaluate the research study, appropriate to the degree of risk, but not less than once per year. Studies whose approval has expired must be suspended until an extension through a renewal process is approved. The PI must submit an electronic continuing review report through REIMS with a frequency as indicated in the terms and conditions of the ethics clearance certificate. The NatHREC Secretary must place the continuing review report on the next meeting’s agenda for review. The NatHREC may provide directives or guidance to the study following review that will be communicated to the PI. In addition, the committee may recommend that the research study is halted.

Protocol Amendments

Per TZA-5, the NatHREC recognizes certain protocol amendments as minor/insubstantial or major/substantial; see TZA-5 for examples of each type. Amendments made to protocols may not be implemented until approved by the NatHREC. Upon receipt of the amendment package, the Secretariat must follow the receiving and validation procedures of submitted protocols. After review of the amendment submission, the Secretariat must determine whether the protocol requires expedited or full review. The amended protocol will be sent to the reviewers of the original submission; in absence of the original reviewers, the Secretariat must appoint and send the amendment application to another reviewer with the same or similar expertise. The number of reviewers will range from one (1) to three (3), depending on the number of the amendments. Minor amendments may be reviewed by members of the Secretariat. If the committee requires modifications to any of the documents, specific changes required must be communicated to the PI with instructions to make the necessary changes and resubmit the documents to the Secretariat. If the committee does not recommend approval of the protocol amendment, this information will be communicated to the MRCC who will review the decision and make the final decision on the approval. If an application is not approved, the PI must be informed of the reasons for not approving the amendment.

Institutional Ethics Committees

Per the G-EthicsHR-TZA, ordinary review is the institution’s normal process for reviewing minimal or more than minimal risk studies. For research that is externally sponsored, the ethical standards should not be less stringent than they would be for research carried out in the country of the sponsoring organization. Local ECs must be fully empowered to disapprove a study they believe is unethical. An EC must require that information given to research participants as part of informed consent complies with the general requirements for informed consent. However, the EC may require that more information be given to the research participants, provided such additional information would meaningfully add to the protection of the rights and the welfare of the research participants. An EC must generally require documentation of the informed consent process. For certain types of research, however, the EC may need the investigator to administer a comprehension test (or test of understanding) to ensure that prospective research participants have acquired adequate knowledge of the relevant facts and consequences of participation in the study. Within 14 days of its review, the EC must notify investigators in writing of the outcome of the research protocol review. If an EC does not approve a research activity, it must include in its written notification a statement of the reasons for its decision.

The G-ResearchIntegrity states that ECs must review protocols in accordance with their standard operating procedures (SOPs) and in a timely and professional manner. Names, titles, and institutional affiliation of reviewers for each proposal will be kept confidential. The decision should be communicated to the investigators in a written letter that is signed or stamped by the EC chair. The letter should include the research/study title as written in the application, the name of the applicant, research site, draft number, date submitted, name and date of EC sitting for that proposal, suggested changes, and a clear statement of final decision by EC. The investigators must notify the EC of protocol amendments, unforeseen circumstances affecting the study, termination of the study, progress reporting, and study termination before or at completion. ECs should also establish monitoring and/or inspection mechanisms for ongoing research projects to ensure compliance with approved criteria.

Expedited Review

As delineated in the G-EthicsHR-TZA, expedited review is a process by which studies that involve no more than minimal risk may be reviewed and approved in a timely manner by an individual EC member or a designated subset of the full EC. Relevant authorities or ECs must establish a list of criteria for protocols that qualify for an expedited review process. Further, relevant authorities or ECs may establish procedures for the expedited review of research protocols, which should specify the following:

• The nature of the applications, amendments, and other considerations that will be eligible for expedited review
• The minimum number of committee members required for expedited review
• The status of decisions (for example, subject to confirmation by a full EC or not)

Accelerated Review

Per the G-EthicsHR-TZA, an accelerated review process may be used for a clinical trial protocol submitted for ethical approval. In reviewing a clinical trial, reviewers may exercise all the authorities of the committee to recommend approval of the submitted protocol. Final approval for protocol is granted in accordance with the standard procedures outlined above. However, applications for accelerated review of clinical trial protocols will be reviewed on a case-by-case basis by the EC, and the applicant may be required to undergo an ordinary review process due to the nature of the trial or else, as determined by the EC.

Continuing Review

As required in the G-EthicsHR-TZA, the EC must conduct additional reviews on approved studies as necessary, particularly if there are significant changes in the protocol that require re-consent by participants or affect the safety of participants, or if other ethical matters emerge during the study. These further reviews include amendments, progress reports submitted by researchers, and possible monitoring of researchers’ compliance with approved protocols. For approved studies, ECs must conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once a year, and must have authority to observe or have a third party observe the informed consent process. The EC must investigate research fraud and take appropriate action where scientific fraud has been suspected or proven.

Suspension or Termination

Per the G-EthicsHR-TZA, the EC has the authority to halt, suspend, or terminate approval of research that is not being conducted in accordance with the EC’s requirements, or research that has been associated with unexpected serious harm to research participants. For example, the EC may suspend research when:

• It finds that the investigator has implemented significant changes in the research protocol without the prior approval of the EC
• The investigator has failed to follow specific procedures or requirements articulated by the EC in its initial review of the research protocol
• When there is severe unexpected harm to the research participants, including, but not limited to, serious physical injury or death

Per the G-EthicsHR-TZA, any suspension or termination of ethics approval must include a written statement of the reasons for the EC’s action. It must be reported promptly to the investigator(s), appropriate institutional officials, and the National Institute for Medical Research (NIMR) Director General.

Multicenter Research

For multicenter research, the G-EthicsHR-TZA states that the study must be conducted in a methodologically identical way at each center, and ECs at individual centers have the authority to adapt the informed consent document provided by the lead institution to make it culturally appropriate. To avoid lengthy procedures, multicenter research within Tanzania should be reviewed by only one (1) EC and other applicable ECs should accept that review. To be informed of the necessary approach, the study team should be consulted. In cases of multicenter research, if a local review committee proposes changes to the original protocol that it believes are necessary to protect the research participants, these changes must be reported to the research institution or sponsor responsible for the whole research program for consideration and possible action. This should ensure that all persons are protected and that the research will be valid across sites. Ideally, review procedures should be harmonized, which may decrease the time needed for review and, accordingly, speed up the research process. Joint reviews may be organized and requested by the study team or sponsor across country borders or institutions in compliance with guidelines. Joint reviews are based on voluntary cooperation between the relevant national regulatory authorities and ECs. In the case of multi-country joint reviews, each country is solely responsible for granting regulatory or ethics approval to the sites within its borders. To harmonize review processes and to maintain sufficient quality of these processes, ECs should develop quality indicators for ethical review.

Exemption

Per the G-EthicsHR-TZA, some studies may be exempt from EC review. If an investigator considers that their research project satisfies the requirements for exemption from ethics review, the EC must ensure that the proposed research satisfies the requirements for exemption from EC review and grant exemption through procedures set by the EC. The following studies may be exempt from EC review:

• Research with negligible risk that involves using existing collections of data or records that contain only non-identifiable data about human beings
• Use of publicly available unlinked data that does not identify individuals or communities
• Use of existing collections of data or records that contain only non-identifiable data about human beings
• Quality assurance/evaluation activities undertaken in the normal course of conducting the business of the institution, i.e., educational assessments, student feedback surveys, audits of organizational activities and systems, and quality assurance reviews
• Emergency use of a test article provided that such emergency use is reported to the EC within five (5) working days; any subsequent use of the test article at the institution is subject to EC approval
• Health systems research if public officials are interviewed in their official capacity on issues that are in the public domain

As per the G-KenyaCT, G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. The EC fee to review a clinical trial application will vary depending on the institution. See KEN-25 and KEN-38 for lists of NACOSTI-accredited institutional ECs. For an example of institutional fee requirements charged by the Scientific and Ethics Review Unit (SERU) at the Kenya Medical Research Institute (KEMRI), see KEN-27.

National Health Research Ethics Committee

According to the G-TMRCC, the National Health Research Ethics Committee (NatHREC) requires the sponsor, the contract research organization, or the principal investigator (PI) to pay a nonrefundable fee to submit a clinical trial research protocol for ethical review and approval.

As per TZA-17, the fees are as follows:

• Tanzanian researchers, expedited review – 3,875,000 Tanzanian Shillings
• Tanzanian researchers, ordinary review – 2,625,000 Tanzanian Shillings
• Tanzanian researchers, amendment – 750,000 Tanzanian Shillings
• Tanzanian researchers, extension – 300,000 Tanzanian Shillings
• Tanzanian students, expedited review – 390,625 Tanzanian Shillings
• Tanzanian students, ordinary review – 390,625 Tanzanian Shillings
• Tanzanian students, amendment – 250,000 Tanzanian Shillings
• Tanzanian students, extension – 125,000 Tanzanian Shillings
• International researchers, expedited review – $5,125 USD
• International researchers, ordinary review – $2,625 USD
• International researchers, amendment – $750 USD
• International researchers, extension – $300 USD
• International students, expedited review – $548 USD
• International students, ordinary review – $548 USD
• International students, amendment – $375 USD
• International students, extension – $125 USD

See TZA-17 for appeal fees and late renewal penalties.

Payment Instructions

No information is current available regarding payment instructions for the NatHREC.

Institutional Ethics Committees

Institutionally based ethics committees (ECs) may independently decide whether to charge fees for a protocol review. Per the G-ResearchIntegrity, ECs should delineate procedures for the fee structure, mode of payment, and proof of payment in their standard operating procedures (SOPs). Applicants should contact ECs individually for specific fees and payment instructions.

Overview

As set forth in the STI-Act and KEN-32, the National Commission for Science, Technology and Innovation (NACOSTI) is the central body responsible for the oversight, promotion, and coordination of research. NACOSTI’s role is to regulate and ensure quality in the science, technology, and innovation sector, and to advise the Kenyan government on related matters. As per the G-ECAccred, NACOSTI has delegated the task of reviewing research proposals for ethical clearance to accredited institutional ethics committees (ECs) to ensure that research conducted in the country observes high research ethics standards.

Per the G-ECBiomedRes, Kenya's National Bioethics Committee (NBC) advises NACOSTI on research ethics. In addition, NBC offers dispute resolution if an applicant is dissatisfied with the decision of an EC. Finally, the NBC must terminate research at any stage if it is found to be harmful to the participants.

Registration, Auditing, and Accreditation

As per the STI-Regs and the G-ECAccred, NACOSTI is responsible for accrediting institutional ECs. Per the G-ECAccred, the application requirements for accreditation are:

• A completed application form (KEN-10 or Annex III of the G-ECAccred)
• Copy of the standard operating procedures (SOPs)
• Copies of abridged curriculum vitaes (CVs) (no more than four (4) pages) for each member of the proposed EC (including the training attended)
• Profile of the organization/institution detailing the areas of competence (no more than four (4) pages)

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), users can perform the following functions:

• Researchers: Apply for researcher registration, register and track applications, and maintain research profile
• Research Institutions: Apply for new research institution registration, maintain/update data, and submit annual reports
• Institutional ECs: Apply for accreditation, preview and track accreditation proposals, submit annual reports, and maintain/update data

Per the G-ECAccred, NACOSTI issues a certificate of accreditation to accredited institutional ECs, which is valid for three (3) years from the date of NACOSTI’s notification. All accredited ECs must submit annual reports to NACOSTI by July 31st for review and monitoring. Applications for renewal of accreditation should be made six (6) months before expiry of the accreditation period. Failure to renew accreditation or failure to maintain the appropriate standards for continuity of accreditation will mean that the accredited status of the EC will lapse at the end of the current accreditation period. Accreditation must be terminated if the accredited committee fails to maintain the required standards. For re-accreditation review purposes, ECs must provide the SOPs under which they will operate. The SOPs are not required as part of the annual reporting process, unless they have been amended, but are required to be stated/included for the re-accreditation review process (every three (3) years). See the G-ECAccred for additional details on the accreditation process.

See the Site/Investigator Selection section for more information on the sponsor and site’s registration and application requirements.

Overview

As mandated by the MedRsrchAct, the National Institute for Medical Research (NIMR) is the central body responsible for oversight, and for the promotion and coordination of research in Tanzania. The NIMR is a semi-autonomous organization under the Ministry of Health (MoH). The IERC-Accredit, the G-EthicsHR-TZA, the G-TMRCC, and TZA-5 state that the NIMR’s Medical Research Coordination Committee (MRCC) serves as the national health research coordinating body, and is responsible for supervising health research in Tanzania. The MRCC, as the NIMR’s clearance body, delegates the registration, review, approval, and monitoring of research to the National Health Research Ethics Committee (NatHREC), which is a subcommittee of the MRCC. The NatHREC focuses on the ethical issues surrounding submitted research proposals. All clinical trial protocols to be conducted in Tanzania are also reviewed by a specialized nine (9)-member Clinical Trials Sub-Committee, which meets monthly and reports to the NatHREC. For detailed information on NatHREC responsibilities, see the G-TMRCC, the G-EthicsHR-TZA, and TZA-5.

TZA-5 acknowledges that not all human subjects research requires review and approval at the national level—i.e., research that does not involve investigational products or collaboration with foreign institutions. For studies that may not need national review, the local ethics committee (EC) must submit quarterly reports listing studies that were approved by the local EC. The NatHREC may request any information related to approved research studies at the institutional level, and ECs are subject to audit.

Registration, Auditing, and Accreditation

Per the G-EthicsHR-TZA, institutions that intend to establish an institutional EC must make a written request to the Director General of NIMR and, upon approval, submit quarterly and annual progress reports to NIMR. In the initial request, the institution must indicate that it will comply with the following minimum requirements:

• A statement of principles governing the institution's discharge of its responsibilities for protecting the rights and welfare of human research participants of research conducted at or sponsored by the institution; this may include an appropriate existing code, declaration, or statement of ethical principles or a statement formulated by the institution itself
• Details on ensuring meeting space availability and sufficient staff and resources to support the EC’s review and record-keeping duties
• A list of members identified by name, qualifications, profession, representative capacity, indicators, or experience such as board certification, and licenses
• Written procedures for monitoring the conduct of studies approved by the EC

As delineated in the IERC-Accredit, institutional ECs may apply for accreditation. Registered and accredited ECs support the NatHREC function of facilitating institutional ethical clearance and monitoring the approved research studies at the level of the institutions to which they belong or are affiliated. ECs are not mandated to approve research protocols for clinical trials and those involving foreign collaborators. These types of research are cleared at the national level only. Following are the EC accreditation assessment criteria:

• Suitability of infrastructure and office space for EC activities
• Adequacy of equipment to support ethics review management
• Adequacy of qualified EC Secretariat staff (technical and support staff) to manage the ethics review procedures
• Appropriateness of the EC governance and structure
• Plan for capacity building/training program for the EC Secretariat, members, and reviewers
• Plan for monitoring of research activities by the EC
• Adequacy of institutional support services
• Appropriateness of EC standard operating procedures (SOPs)

The IERC-Accredit indicates that ECs approved for full accreditation will be published on the NIMR website. The duration of accreditation is three (3) years from the date of notification (certification) by NIMR. Applications for renewal must be made six (6) months before the expiry of the accreditation period. Failure to renew accreditation or failure to maintain the appropriate standards for continuity of accreditation will mean that the accreditation status of the EC will lapse at the end of the current accreditation period and the committee must cease to function. Accreditation must be terminated if NIMR, in consultation with NatHREC, finds that the accredited EC has failed to maintain the required standards. See IERC-Accredit for additional accreditation information, including application procedures and reporting.

See the Tanzania Commission for Science and Technology’s (COSTECH) and the G-ResearchIntegrity for institutional guidance on the introduction and strengthening of research integrity mechanisms. When such mechanisms are well established, institutional ECs can advance to a stage of accreditation.

Overview

In accordance with the PPA, the STI-Act, the CTRules, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, Kenya requires the sponsor or the representative to obtain clinical trial authorization from the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) and an independent ethics review through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in a local institution. In addition, the STI-Act and KEN-31 specify that applicants must obtain a research license from NACOSTI prior to initiating a study. The G-KenyaCT also states that the PPB review and approval process may not be conducted in parallel with the EC review. EC approval must be obtained prior to applying for PPB approval.

Regulatory Submission

Pharmacy and Poisons Board

As described in the G-KenyaCT and KEN-16, the sponsor or the representative is expected to submit the clinical trial application electronically via the PPB online system (KEN-16). The clinical trial application form is available in KEN-16. Per the G-KenyaCT, in the event of a multicenter clinical trial, the sponsor should only file one (1) application to the PPB. According to KEN-34, all application documents should be signed, dated, and version referenced, if applicable, and should be in English. See Annex 7 of the G-KenyaCT to view a flowchart of the submission and approval process.

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness. When an application for a clinical trial is accepted, an acknowledgement of receipt will be issued with a reference number for each application. This PPB/ECCT reference number must be quoted in all correspondence concerning the application in the future. This will be communicated through email to the applicant or through KEN-16.

Per the G-KenyaCT, sponsors (applicants) can request pre-submission meetings with the PPB to discuss pertinent issues prior to making a formal submissions. The request must be made via KEN-16 or in an official letter and include the following information:

• Background information on the disease to be treated
• Background information on the product
• Quality development
• Non-clinical development
• Clinical development
• Regulatory status
• Rationale for seeking advice
• Proposed questions and applicant’s positions

In addition, per the G-KenyaCT, the letter must be addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting at least three (3) weeks away.

Per G-KenyaCT, any new information that affects the conduct/management of the trial; safety of the participants; and manufacture of the product necessitating changes to the protocol, consent form, and trial sites, etc. will require immediate submission of the amended documents to the PPB for review and approval. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB.

National Commission for Science, Technology and Innovation

Per KEN-31, an application for a NACOSTI research license should be submitted online via the Research Information Management System (RIMS) (KEN-24).

Ethics Review Submission

Each institutional EC has its own required submission procedures, which can differ significantly regarding the application format and number of copies. See KEN-17 for an example of a NACOSTI-accredited EC’s guidelines.

Overview

According to the TMMDAct, the CT-Regs, and the G-AppConductCT, the Tanzania Medicines and Medical Devices Authority (TMDA) requires the sponsor, the designated contract research organization (CRO), or the investigator to obtain TMDA approval. Per TZA-5, the principal investigator (PI) is required to submit an application for ethical review of a research study to the national ethics committee (EC), the National Health Research Ethics Committee (NatHREC). All clinical trials must get ethics approval from both the institutional EC and the NatHREC. TZA-18 states that if there is no institutional EC available, the approval must be obtained from NatHREC. According to the G-AppConductCT and TZA-4, TMDA and NatHREC reviews may be conducted in parallel. However, the TMDA application must include a copy of the NatHREC's acknowledgement of receipt for the study protocol. In addition, the TMDA's approval will only be finalized once NatHREC approval is obtained.

Per the G-ResearchClearance, the Tanzania Commission for Science and Technology (COSTECH) must review and approve all research in Tanzania.

Regulatory Submission

Tanzania Medicines and Medical Devices Authority

Per the G-AppConductCT, applicants must submit both paper and electronic copies of the clinical trial application (CTA). Per TZA-4 and TZA-36, electronic CTAs must be completed online via the Regulatory Information Management System (RIMS) Customer Self Service Portal (TZA-34). Applicants must fill out CTAs as per the Modules and the Common Technical Document (CTD) highlighted in the G-AppConductCT. Applications for amendment(s) to a previously authorized clinical trial must be submitted on the applicable form in RIMS. The clinical trial application form is available at TZA-38, and the application forms for protocol amendments are at TZA-43 and TZA-44. Note that a list of clinical trial forms is posted to TZA-35.

Per the G-AppConductCT, the hard copy of the application may be delivered in person or by courier to the TMDA at the following address:

Mabibo External along Mandela Express way
P.O. Box 77150
Dar es Salaam, Tanzania

In addition, TZA-34 provides applicants with various online regulatory services.

As per the G-AppConductCT and the TZA-36, applicants must submit paper (A4) and electronic copies. The paper documents should be arranged in spring file folders. The G-AppConductCT specifies that the electronic documents should be in MS Word format, Bookman Old Style font size 11 and submitted on CD-ROM. TZA-36 requires electronic format on CDs. The number of copies to be submitted is not specified in the G-AppConductCT. Annex 1 of the G-AppConductCT provides the Clinical Trial Application Form template. Applicants should submit their applications as per the Modules in the G-AppConductCT and the CTD highlighted in the G-AppConductCT. The overall organization of the CTD format should not be modified.

Per the G-AppConductCT and TZA-4, all applications and supporting documents must be in English. The informed consent documents must be in both Kiswahili and English.

Tanzania Commission for Science and Technology

Per the G-ResearchClearance, the PI should submit an application for a research permit. It must be submitted to the Director General of COSTECH through the online system (TZA-48) at least three (3) months before the intended commencement of research in Tanzania. According to TZA-47, when the online COSTECH system is not working, applicants should email COSTECH at either rclearance@costech.or.tz or dg@costech.or.tz. After a foreign researcher obtains a research permit, the researcher is required to apply for a class C residence permit from the Tanzanian Immigration Services Department. See the G-ResearchClearance and TZA-47 for additional information about applying for a research permit through the National Research Clearance Committee (NRCC).

Ethics Review Submission

National Health Research Ethics Committee

The TZA-5 specifies that the NatHREC requires all applicants to complete the Application Form for Ethics Approval (see Form 03 in TZA-5) with the research protocol to obtain ethics approval. PIs or applicants must submit all required documents at least two (2) months prior to the commencement of the research study, and they must select either an expedited or ordinary review (for the case of clinical trials, an accelerated review) and pay the relevant fee. An application for ethical review of a research study should be made by the PI for that study. Applications may not be submitted by the sponsor(s) on behalf of the PI. Applications must be accompanied by a completed checklist (TZA-1). As described in the G-RevPrtcl, TZA-5, and TZA-31, applicants should submit the form to the online Research Ethics Information Management System (REIMS) (TZA-32) (also referred to as the National Health Research Management Information System (NHRMIS)).

The G-TMRCC indicates that four (4) copies of the research proposal with a cover letter should be submitted to the NatHREC.

Institutional Ethics Committees

While the submission requirements will vary by institution, the G-ResearchIntegrity indicates that the lead researcher or PI is responsible for submitting a research proposal to the EC. The institutional EC’s procedures for receiving an application should be clearly stated, and could include some of the following submission elements:

• The name and/or title of the EC member who will receive applications
• Application template or standard forms for submitting applications
• Recommended channel for submissions (e.g., email) and format (e.g., MS word)
• Proper submission of supporting documents with the application
• Use of appropriate language (as recommended) and number of copies
• Name and addresses of contact person for follow up with comments
• Fee structure, mode of payment, and process for submitting proof of payment
• Applicable procedures for proposal amendments, submissions, and supporting tools

Regulatory Authority Requirements

Pharmacy and Poisons Board

As per the CTRules, the G-KenyaCT, and KEN-34, the following documentation must be submitted (signed, dated, and version referenced) to the Pharmacy and Poisons Board (PPB) (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Cover letter
• Study protocol
• Proof of study registration in the Pan African Clinical Trials Registry (KEN-19)
• Patient information leaflet and informed consent form (ICF)
• Investigators brochure (IB) and package inserts
• Investigational Medicinal Product Dossier (IMPD), including stability data for the investigational product (IP)
• Adequate data and information on previous studies and phases to support the current study
• Good manufacturing practice (GMP) certificate of the IP from the site of manufacture issued by a competent health authority in the manufacturer’s jurisdiction of origin
• Certificate of analysis of the IP
• Pictorial sample of the IPs, including the labeling text
• Signed investigator(s) curriculum vitae(s) (CV(s)), including that of the study pharmacist (the CV should include the current workload of the principal investigator (PI))
• Evidence of contractual agreement between the relevant parties
• Evidence of recent good clinical practice (GCP) training of the core study staff
• Data and Safety Monitoring Board (DSMB) information, including the charter, composition, and meeting schedule
• Detailed study budget
• Financial declaration by the sponsor and PI (KEN-2 and Annex 5 of the G-KenyaCT)
• No conflict of interest declaration by the sponsor and PI
• Signed declarations by the sponsor, PI, and the monitor that the study will be carried out according to the protocol and applicable laws, regulations, and GCP requirements (KEN-1 and Annex 4 of the G-KenyaCT)
• Indemnity cover for PI, investigators, and study pharmacist
• Clinical trials insurance cover for the study participants
• Copy of favorable opinion letter from local ethics committee (EC)
• Copy of current practice licenses for the investigators and study pharmacist
• Copy of approval letter(s) from collaborating institutions or other regulatory authorities, if applicable
• For multicenter/multi-site studies, an addendum for each of the proposed sites including, among other things, the sites’ capacity to carry out the study (e.g., personnel, equipment, laboratory)
• A signed statement by the applicant indicating that all information contained in, or referenced by, the application is complete and accurate, and is not false or misleading (Annex 4 of the G-KenyaCT)
• Payment of fees
• Statistical analysis plan
• A signed checklist (KEN-34 and Annex 2 of the G-KenyaCT)

Per the G-KenyaCT, a request for approval of an amendment must include a summary of the proposed amendments; the reason for the amendment; the impact of the amendment on the original study objectives; the impact of the amendments on the study endpoints and data generated; and the impact of the proposed amendments on the safety and wellbeing of study participants.

KEN-35 describes the submission content for requesting annual approval from the PPB.

National Commission for Science, Technology and Innovation

Per the STI-Regs and KEN-31, non-Kenyan applicants must be affiliated with a Kenyan institution. Per KEN-31, applicants must apply online through National Commission for Science, Technology and Innovation (NACOSTI)’s Research Information Management System (RIMS) website (KEN-24) and upload the following:

• Passport size color photo in JPG or PNG format
• Scanned ID/passport in PDF format
• Introductory letter from relevant institution signed by an authorized officer
• Affiliation letter from relevant local institution for foreigners signed by an authorized officer and valid for one (1) year
• Grant letter from the funding agency to support the amount indicated to fund the research
• PPB clinical trial approval
• Prior Informed Consent (PIC), Mutually Agreed Terms (MAT), or Material Transfer Agreement (MTA) where applicable, for applications to conduct research on genetic resources and derivatives
• Approved research proposal in PDF format
• Certificate of ethical clearance of the research (see list of accredited ECs in KEN-25)
• Evidence of payment as the last page of the uploaded proposal

Per KEN-31, the following conditions apply to the research license:

• The research license is valid for the proposed research, site, and specified period
• Both the research license and any rights thereunder are non-transferable
• NACOSTI may monitor and evaluate the research
• The licensee must inform the relevant County Director of Education, County Commissioner, and County Governor before research commencement
• Excavation, filming, and collection of specimens are subject to further permissions from relevant government agencies
• The research license does not give authority to transfer research materials
• The licensee shall submit one (1) hard copy and upload a soft copy of their final report within one (1) year of completion of the research
• NACOSTI reserves the right to modify the conditions of the research license including its cancellation without prior notice

KEN-31 states that if the research is not completed within the stipulated period, the applicant may apply for renewal of the research license and pay the requisite fee. A progress report should be submitted with the request for renewal instead of a proposal. The progress report must indicate the objectives and activities that have been accomplished, as well as the research work that has yet to be undertaken. KEN-31 further indicates that submissions requesting renewal should be made at least 30 days prior to the expiration of the approval period.

Ethics Committee Requirements

EC requirements vary depending on the specific EC. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

As set forth in the G-ECBiomedRes, a foreign sponsoring agency must also submit its research protocol for ethics review according to its own country’s standards. This research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted.

Clinical Protocol

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). The CTRules the G-KenyaCT, the G-ECBiomedRes, and KEN-14 outline the key elements of a research protocol in Kenya (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• A project title that adequately captures the essence of the study
• The names, addresses, signatures, and updated abridged curriculum vitae of the investigators
• Evidence that the PI has prior training in GCP
• Contact information for the EC and collaborating institutions
• A summary of the project
• Introduction, background, and literature review, including nonclinical data
• Study objectives, rationale, questions, and hypothesis/es
• Study site, design, and methodology
• Ethical considerations
• Role of investigators
• Schedule
• References
• Budget
• Publication policy
• Consent explanation - elements of consent explanations
• ICF with signature provisions for participants and the PIs
• Risks and benefits
• Mode of assessment of the safety and efficacy of the IP
• Mode of collecting, analyzing, and reporting the statistics of the clinical trial
• Source data documents of the clinical trial
• Quality control and quality assurance
• Confidentiality
• Recruitment, selection, treatment, and withdrawal of participants
• Compensation and post-trial access program
• Undue inducement and coercion
• Voluntariness
• Alternative treatment(s) if available
• Storage of specimens
• MTA, where applicable
• Data management and statistical analysis

In addition, per the G-KenyaCT, the protocol should have a clear description of study stoppage rules indicating reasons, who makes the decision, and how the decision will be communicated to the PPB and the EC.

Regulatory Authority Requirements

Tanzania Medicines and Medical Devices Authority

As per the CT-Regs and the G-AppConductCT, the following documentation must be submitted to the Tanzania Medicines and Medical Devices Authority (TMDA):

• Comprehensive table of contents
• Cover letter
• Application form (See the Regulatory Information Management System (RIMS) Customer Self Service Portal (TZA-34) or Annex 1 of the G-AppConductCT and First Schedule of the CT-Regs)
• General investigational plan
• Capacity building plans (including plans for staff training and updates)
• Overall summary of the protocol (See Annex 2 of the G-AppConductCT)
• Protocol, signed and approved with data compiled as prescribed in Annex 3 of G-AppConductCT and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13), including case report form (CRF) copies or descriptions; See TZA-42 for a clinical trial protocol template
• Participant Information Leaflet, informed consent forms (ICFs), and any other information to be given to participants
• Declarations by the principal investigator (PI) (TZA-39), co/sub investigators (TZA-41), and monitors (TZA-40) (Also see Annexes 5-7 of the G-AppConductCT)
• Joint declaration by sponsor and national PI in format prescribed in Annex 8 of the G-AppConductCT
• Investigator’s Brochure (IB), nonclinical overall summary (See Annex 10 of the G-AppConductCT), and prescribing information data sheet, if applicable
• Certified copy of insurance of research participants
• Ethics clearance certificate or a copy of protocol submission acknowledgement from the National Institute for Medical Research (NIMR)’s National Health Research Ethics Committee (NatHREC) or any approved medical research institute
• Investigator(s) Curriculum Vitae(s) (CVs) (See Annex 9 of the G-AppConductCT)
• Blank CRFs and serious adverse events reporting form to be used in the study
• Certificate of good manufacturing practice (GMP) for manufacture of the trial medicine or other evidence of manufacturing quality, safety, and consistency
• GMP certificate for manufacture of the placebo, if applicable
• Investigational product (IP) labels and packages insert(s)
• Mock-up labels for IPs
• Evidence of accreditation/certifications of the designated laboratories or other evidence of good laboratory practice
• Letters of access (if applicable) authorizing the TMDA to access related files
• Copies of key, peer-reviewed published articles supporting the application
• Completed, quality overall summary – Chemical Entities Template (See Annex 11 of the G-AppConductCT)
• Investigational medicinal product dossier
• Application fees
• Summaries of nonclinical, clinical, and quality data (See Module 2 of the G-AppConductCT)
• Quality of the IP (See Module 3 of the G-AppConductCT)
• Nonclinical study reports (See Module 4 of the G-AppConductCT)
• Clinical study reports (See Module 5 of the G-AppConductCT)

As delineated in G-AppConductCT, an application must not cross reference the details or documentation between different clinical trials. The applicant must include a statement indicating that all the information in the application is complete and accurate. In the case of multi-center trials, a coordinating investigator must also sign the application form. If the trial is part of an international study, information must be provided regarding the other participating countries and the part of the trial that will be conducted locally.

In addition, per the G-AppConductCT, applicants can submit an application for amendment to a previously authorized clinical trial, using the required forms (Annexes 12 and 13). The sponsor or sponsor’s agent must submit the following to the TMDA:

• Amendment fees
• Description and reasons for the proposed amendment
• Original wording, revised wording, and the rationale for the change, including a complete protocol incorporating all amendments
• Supporting data for the amendment: updated overall risk-benefit assessment, possible consequences for participants already in the trial and for assessment of trial results, and summaries of data

For details on when TMDA approval must be obtained for amendments, see G-AppConductCT.

Tanzania Commission for Science and Technology

According to the G-ResearchClearance and TZA-47, to obtain a research permit for a clinical trial, the following must be submitted to the Tanzania Commission for Science and Technology (COSTECH) (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• A full research proposal, including a summary, abstract, introduction, research objectives, problem statement, hypotheses or questions framework, methodologies, and timeframe
• Literature review
• Beneficiaries of the research
• Bibliography
• Detailed CV(s) of all researchers
• Sponsor’s cover letter
• For foreign applicants, scientific and ethics committee approval from an institution in the PI’s country of residence
• Clearance from the TMDA
• A supporting letter from a Tanzanian affiliate institution
• A Tanzanian applicant should submit either a copy of their national ID, passport details, driving license, or voters ID
• A foreign applicant should submit a copy of their passport details page and a current passport size photo with a blue background
• A scanned copy of a receipt as proof of payment of the non-refundable research application fee to COSTECH (See Regulatory Fees section for details)

The G-ResearchClearance indicates that an application to renew a permit must contain a renewal application form, an annual progress report, a supporting letter of recommendation from the affiliate institution, passport information, updated CVs, and an extension table form.

Ethics Committee Requirements

National Health Research Ethics Committee

As per the G-TMRCC, the G-RevPrtcl, and the NatHREC’s Checklist for Ethical Clearance Application Submission (see TZA-1), the NatHREC requires applicants to submit the following documentation for ethics approval (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Application Form for Ethics Approval (see Form 3 in TZA-5 and the Research Ethics Information Management System (REIMS) (TZA-32))
• Full protocol, including benefits sharing, placebo rationale, information on randomization/blinding, and a commitment to register the trial in a public registry
• Cover letter signed by PI or co-PI
• Summary, introduction, and literature review
• Statement of the problem, the rationale, and study objectives
• Budget and budget justification
• Ethical consideration (e.g., written information to be provided to participants in English and Kiswahili, obtaining verbal/written informed consent, obligations of investigators and sponsors, benefits and risks of study participation, recruitment, cultural values, and confidentiality measures)
• Limitations of the study
• Information on the study site(s)
• Review of the known risks and if they are acceptable for the expected benefit
• Interim analysis and stopping rules
• Dissemination of research results
• Commitment letter from affiliated institution and/or local government officials
• Letter from student supervisors
• ICFs/Assent Forms in English and Kiswahili
• EC approval certificate from affiliating institution(s), where applicable
• Methodology, including data collection tools in English and Kiswahili
• Elaborated recruitment procedure
• Research team CVs
• Evidence of payment of application and registration fees (Bank slip)
• Completed Data Transfer Agreement (see TZA-8) and/or Material Transfer Agreement (see TZA-10), where applicable
• IBs and CRFs
• Proof of insurance coverage
• List of Data and Safety Monitoring Board members (with at least one (1) Tanzanian)

Per TZA-5, a request for amendment of a previously approved protocol must describe the requested amendment, provide the rationale for the amendment, and describe the impact, if any, of the amendment on the protocol’s risk-benefit profile.

Institutional Ethics Committees

While the submission requirements vary by institution, the G-ResearchIntegrity indicates that the following are typically required:

• Completed application, signed by the lead investigator/researcher(s)
• Full proposal completed in all sections with supporting documents
• A lay summary of the application and/or a flow chart representing key milestones
• Description of ethical issues pertaining to the research, and how they will be managed
• Tools for operationalizing the research and how they will be applied
• Safety issues related to the use of instruments, materials, and research data
• Investigators’ CVs, up to date and signed
• Research context, including criteria for identifying research participants, research environment, and relevant protection measures
• Information to be provided to participants, which may include tools and use of local translators, if needed
• Procedures for informed consent by participants
• Compensation plans for research participants, if any
• Description of indemnity and/or insurance coverage for participants, if applicable
• A history of rejection of the same research protocol, reasons for rejection, and measures taken to address the concerns; withholding such information should be regarded as misconduct and managed in accordance with misconduct guidelines

Clinical Protocol

The G-AppConductCT indicates that the protocol should state the background, rationale, and objectives of the trial, and describe its design, methodology and organization, including statistical considerations, and the conditions under which it is to be performed and managed. In addition, Tanzania requires the following protocol contents in the format prescribed in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13):

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

The G-EthicsHR-TZA states that research protocols submitted for ethics review and approval must, at the least, include the following information:

• A clear statement of the objectives of the research, the present state of knowledge, and a justification for undertaking the research
• A precise description of all proposed procedures and interventions, including the duration of the study
• A statistical analysis plan
• Description of the study population, including the number of study participants to be recruited
• The inclusion and exclusion criteria for study participants and procedures for the withdrawal of individual participants
• Complete details of the informed consent process, including the proposed means of obtaining informed consent (or assent in case of minors)
• Evidence that the investigators are appropriately qualified and experienced, and have adequate facilities for the safe and efficient conduct of the research
• Provisions that will be made to protect the confidentiality of information/data obtained from research participants
• The study tool(s) (e.g., questionnaires, CRFs, videos, flip charts, and other data collection tools)

Also see the G-RevPrtcl for additional guidance on the NatHREC’s review of the protocol.

Overview

Based on the CTRules and the G-KenyaCT, the Pharmacy and Poisons Board (PPB)'s review and approval of an application to conduct a clinical trial is dependent upon obtaining ethics approval from a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC). Therefore, the PPB and EC reviews may not be conducted in parallel. In addition, the STI-Act and KEN-31 specify that all applicants must obtain a research license from NACOSTI prior to initiating a study.

Regulatory Authority Approval

Pharmacy and Poisons Board

Per the G-KenyaCT, sponsors (or applicants) can request pre-submission meetings to discuss pertinent issues prior to making a formal submission. The request must be made via the PPB online system (KEN-16) or in an official letter addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting with the proposed dates being at least three (3) weeks away. (See Submission Process section for details on the content of request.)

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness, which takes five (5) days. If accepted, an automatic system-generated reference number will be issued for each application. If additional information is needed, the sponsor will have 10 days to respond. The PPB aims to respond to applications within 30 working days. The sponsor or the representative must reference the PPB/Expert Committee on Clinical Trials (ECCT) number in all future application-related correspondence. The application is then evaluated by the ECCT and PPB staff according to their respective standard operating procedures. The PPB/ECCT’s decision to approve, request additional information, or reject the application is communicated to the sponsor or the representative in writing within 30 days of receiving a valid application. If additional information is requested, the sponsor has 90 days to respond after which the PPB has 15 days to issue a final decision. In certain cases, the PPB may refer the application to external experts for their recommendation.

Per the G-KenyaCT, the sponsor or the representative is also required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval. Refer to the Checklist for Submitting a Request for Annual Approval (KEN-35) for relevant documentation requirements.

National Commission for Science, Technology and Innovation

Per KEN-5 and KEN-31, the timeline for NACOSTI’s license application process is 30 days.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision.

Ethics Committee Approval

The EC review and approval process timeline will vary by institution.

Overview

Based on the TMMDAct, the CT-Regs, and the G-AppConductCT, the Tanzania Medicines and Medical Devices Authority (TMDA)'s approval of a clinical trial application is dependent upon obtaining proof of ethical approval from the national ethics committee (EC), the National Health Research Ethics Committee (NatHREC). According to the G-AppConductCT, TMDA and NatHREC reviews may be conducted in parallel. However, the TMDA application must include a copy of the NatHREC's acknowledgement of receipt for the study protocol. In addition, the TMDA's approval will only be finalized once NatHREC approval is obtained. As per the G-ResearchClearance, after receiving TMDA and NatHREC approvals, the researcher must submit an application for research clearance to the Tanzania Commission for Science and Technology (COSTECH).

Regulatory Authority Approval

Tanzania Medicines and Medical Devices Authority

According to the G-AppConductCT, the TMDA review process is conducted on a first-in, first out basis. The TMDA will evaluate complete applications within 60 working days of receiving the application. The fast-track evaluation provides that a new clinical trial application may be fast tracked and assessed within 30 working days of its submission if the applicant has requested and paid twice the prescribed clinical trial application fee. The CTC-Time validates the timelines in the G-AppConductCT.

As set forth in the TMMDAct, the CT-Regs, and the G-AppConductCT, the TMDA coordinates the clinical trial application process. Upon receipt of a clinical trial application, the TMDA initially screens the application for completeness. If complete, the TMDA officer acknowledges receipt of the application by returning a signed copy of the cover sheet to the applicant (see Annex 1 of the G-AppConductCT or First Schedule of the CT-Regs). Per the G-AppConductCT, the TMDA may request clarification, certificates, and/or samples through a query letter. Once a query has been raised and sent to the applicant, the evaluation process stops until the TMDA receives a written response to the query. The response should be submitted within six (6) months after the query letter was issued. In addition, TMDA reserves the right to request information or set conditions not specifically described in the G-AppConductCT to allow it to adequately assess the safety, efficacy, or quality of an investigational product (IP). If authorization is not granted, an appeal may be submitted to the TMDA within 60 days of the TMDA’s decision. If no appeal is submitted by the applicant within this period or, if after consideration of any comments submitted, the TMDA is still not satisfied, it must reject the application.

The TMMDAct states that the TMDA Director General must issue a Clinical Trial Certificate to authorize the trial to be conducted. Per the G-AppConductCT, the TMDA’s clinical trial authorization will be valid up to the proposed duration of the study indicated in the application. However, the validity will not extend beyond five (5) years. If the trial needs more than five (5) years, the applicant must request an extension. If granted, the TMDA will issue an updated certificate.

Tanzania Commission for Science and Technology

The G-ResearchClearance indicates that once COSTECH receives a new application, the Secretariat screens the application for completeness; registers the application; and sends an acknowledgement to the applicant within five (5) business days. If approved after COSTECH’s review, the principal investigator (PI) is then required to collect the research permit certificate from COSTECH. Per TZA-47, COSTECH’s review committee meets every two (2) months, and applicants are advised to apply two (2) months before the research commencement date.

Ethics Committee Approval

National Health Research Ethics Committee

As set forth in the G-TMRCC and TZA-5, the NatHREC meets once a month to evaluate application submissions. TZA-5 indicates an e-mail notification acknowledging receipt and successful validation of the clinical trial application must be sent to the PI or applicant by NatHREC within two (2) working days from the date of receipt. Comments from reviewers will reach the PI within two (2) days through the Research Ethics Information Management System (REIMS) (TZA-32) (also referred to as the National Health Research Management Information System (NHRMIS)), depending on the type of study protocol. If the PI or applicant fails to respond to the committee’s and reviewers’ comments within 30 days, the NatHREC Secretariat must notify the PI of intent to remove the protocol from the REIMS. For clinical trials applications, reviewers’ comments and the outcome of the NatHREC meeting must be forwarded to the PI within 30 days from the date of acceptance by the NatHREC. A PI may appeal that decision in writing to the Medical Research Coordination Committee (MRCC) Chairperson within 30 days of receipt of the decision. The MRCC will respond to PIs in writing within 30 days or upon scrutiny of the appeal. The MRCC Chairperson may invite the PI to appear in person to the MRCC within 30 days of receiving the written appeal. For protocol reviews during public health events of national and/or international concern, protocols should be sent to reviewers within 24 hours of submission by the Secretariat. Reviewers should complete their reviews within three (3) days. The consolidated review and suggested revisions (or approval) should be communicated to the PI(s) within five (5) days. The PI should respond to the review notification within 48 hours.

Per TZA-18, the whole process of receiving, reviewing, and approving the protocols takes a maximum of six (6) weeks.

Institutional Ethics Committees

According to TZA-5, the institutional EC review may occur prior to the proposal review by the NatHREC as the application to the NatHREC requires an EC approval certificate from an affiliated institution(s), where applicable (i.e., for foreign sponsors and when an institution has an EC). As required in the G-EthicsHR-TZA, the EC must notify investigators in writing of the review decision within 14 days of its review.

Overview

In accordance with the PPA, the STI-Act, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, a clinical trial can only commence after the sponsor or the representative receives authorization from Kenya’s Pharmacy and Poisons Board (PPB), and ethics committee (EC) approval from an institutional EC that has been accredited by the National Commission for Science, Technology and Innovation (NACOSTI) prior to initiating a study. ECs are accredited pursuant to the requirements delineated in the G-ECAccred. The G-KenyaCT specifies that the PPB review and approval process may not be conducted in parallel with the EC review. In addition, the STI-Act and KEN-31 state that all applicants must obtain a research license from NACOSTI prior to initiating a study. No waiting period is required following the applicant’s receipt of these approvals. Regarding notifications, KEN-31 requires the licensee to inform the relevant County Director of Education, County Commissioner, and County Governor before commencement of the research. Further, the licensee must disclose to NACOSTI, the institutional ECs, and the relevant national agencies any findings that are of national strategic importance.

As per the PPA and the G-KenyaCT, the sponsor or the representative is required to obtain an import license for the shipment of an investigational product to be used in the trial. (See the Manufacturing & Import section for additional information).

As stated in the G-KenyaCT, Kenyan clinical trials should be conducted in compliance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14).

Clinical Trial Agreement

Prior to initiating the trial, the G-KenyaCT requires that the sponsor agree with investigator(s) on the definition, establishment, and assignment of responsibilities specified in the protocol. These responsibilities include conduct of the trial in compliance with KEN-14 and the approved protocol; data management; unblinding of treatment codes; statistical considerations; and preparation of the final clinical report. The sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. Prior to the initiation of the clinical trial, the agreement between the sponsor and investigators should be in writing as part of the protocol submitted for PPB approval or in a separate agreement. The sponsor and investigators must sign and date the protocol of the trial to confirm the agreement.

Clinical Trial Registration

As per the G-KenyaCT, all clinical trials taking place in Kenya must be registered in the PPB’s Online Clinical Trials Registry System (KEN-16). The principal investigator is required to log in and set up an account to register a study.

In addition, as required by KEN-34, all clinical trials taking place in Kenya must be registered in the Pan African Clinical Trials Registry (KEN-19).

Overview

In accordance with the TMMDAct, the CT-Regs, and the G-AppConductCT, a clinical trial can only commence after an applicant receives permission from the Tanzania Medicines and Medical Devices Authority (TMDA) and approval from the national ethics committee (EC), the National Institute for Medical Research (NIMR)’s National Health Research Ethics Committee (NatHREC). Per the G-ResearchClearance, following TMDA and NatHREC approvals, the applicant must also apply to the Tanzania Commission for Science and Technology (COSTECH) for review, registration, and to obtain a research permit prior to initiating a study. No waiting period is required following the applicant’s receipt of these approvals.

In addition, as per the TMMDAct, the CT-Regs, the TFDCA-ImptExpt, and the G-AppConductCT, the sponsor or the principal investigator (PI) is required to obtain an import license for the shipment of an investigational product to be used in the trial. (See the Manufacturing & Import section for additional information).

Clinical Trial Agreement

Prior to the trial’s commencement, the G-AppConductCT specifies that the protocol must be dated and signed by the investigator, the host institution, and the sponsor, and can function as a contract. In addition, as per the G-CTInsurance-TZA, a clinical trial agreement must be signed by the chief executive of the host institution, the sponsor, and the PI. G-EthicsHR-TZA also states that the PI must sign the protocol and holds primary responsibility for managing and ensuring the integrity of the research study from initiation to finalization.

Per the G-AppConductCT, the sponsor and researchers are required to conduct the clinical trial in compliance with applicable Tanzanian laws and regulations and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13). TZA-13 states that the sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. A written agreement must be signed by both the sponsor and the investigator, or any other parties involved with the clinical trial, verifying that both parties agree to the trial protocol, the monitoring and auditing practices, the standard operating procedures (SOPs), and their respective duties. The sponsor must also obtain the investigator(s)’ and the institution(s)’ agreement to:

• Conduct the trial in compliance with TZA-13, applicable regulatory requirement(s), and the protocol agreed to by the sponsor and approved by the EC
• Comply with data recording and reporting procedures
• Permit monitoring, auditing, and inspection
• Retain essential documents until the sponsor indicates that they are no longer needed

Also, per the CT-Regs, the sponsor must ensure that all agreements made with the PI and any other parties involved in a clinical trial are in writing, as part of the protocol or in a separate agreement.

Clinical Trial Registration

As per the CT-Regs and the G-AppConductCT, all clinical trials taking place in Tanzania must be registered with the Tanzania Clinical Trials Registry (TzCTR) which is accessed via the Regulatory Information Management System (RIMS) Customer Self Service Portal (TZA-34). An applicant must submit detailed clinical trial information to the TzCTR not later than 21 days after the first participant is enrolled in the trial. See the CT-Regs for complete registry submission requirements. The G-AppConductCT further stipulates that applicants have the option to register in any other publicly accessible registries accepting international clinical trial information and recognized by the World Health Organization (WHO). The registration number should be made available to the TMDA.

Safety Reporting Definitions

According to the CTRules and the G-KenyaCT, the following definitions provide a basis for a common understanding of Kenya’s safety reporting requirements:

• Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant in a clinical investigation study or intervention product, and which does not necessarily have a causal relationship with the treatment
• Adverse Drug Reaction (ADR) – All noxious and unintended responses to a clinical trial study or interventional product related to any dose or all unintended noxious responses to a registered medicinal product which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function
• Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
• Suspected Unexpected Serious Adverse Reaction (SUSAR) – A serious adverse reaction that is not identified in practice, severity, or frequency by the referenced safety information

Safety Reporting Requirements

Investigator Responsibilities

Per G-KenyaCT, the investigator must ensure that all SAEs are reported promptly to Kenya’s Pharmacy and Poisons Board (PPB) within the mandated timelines, as described below. Proper protection procedures or treatments should be administered to trial participants with SAEs.

Sponsor Responsibilities

As indicated in the CTRules and the G-KenyaCT, the sponsor should report to the PPB and all relevant institutions, all SAEs and SUSARs occurring during the course of the trial. The G-KenyaCT specifies that the sponsor should expedite reporting all SAEs to the PPB and the ethics committee (EC), and the sponsor and investigators should immediately undertake appropriate and necessary measures and treatment to protect the trial participants. The CTRules delineates that where a sponsor conducts a clinical trial on the same health product or active pharmaceutical substance in another country, the sponsor must submit a report of any SUSAR or SAE that occurs in the other clinical trial to the PPB. Per the CTRules and the G-KenyaCT, a sponsor must submit an initial report of an fatal or life-threatening SUSAR or SAE as soon as it occurs but, in any case, not later than seven (7) days after the occurrence of the event. The G-KenyaCT indicates that if the initial report is incomplete, the sponsor must submit a completed report based on the initial information within an additional eight (8) days. As required in the CTRules and the G-KenyaCT, a report of the occurrence of a SUSAR or SAE must specify whether the SUSAR or SAE is related to the clinical trial.

As indicated in the CTRules and the G-KenyaCT, other important considerations and timelines include the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• The sponsor must notify all the investigators involved in ongoing clinical trials of the investigational product (IP) of all SAEs and SUSARs within 15 calendar days
• Any IP-related SAE must receive immediate medical attention and be reported to the PPB
• The SAE report form must be completed (including lab results) and submitted to enable causality assessment
• All fatal cases must be accompanied by a formal autopsy report, and a verbal autopsy report should be submitted in those exceptional cases where a formal autopsy is not possible
• Any frequent IP related AE/ADR must receive immediate medical attention and be reported to the PPB within seven (7) days
• The sponsor must submit a report on a SUSAR that is not fatal or life-threatening within 15 days after the occurrence of the event
• The principal investigator (PI) is required to submit follow-up information as soon as it becomes available
• All additional information should be clearly marked as updated and must include the Protocol Number and Participant Number
• Foreign regulatory decisions that affect the safety or use of the product under study must be reported to the PPB within seven (7) days through a detailed report
• Literature reports that have implications for the safety of the IP must be submitted within 15 days with a detailed report and a copy of the publication
• New information or notification of change in nature, severity, or frequency of risk factors for the product under study or conduct of trial must be submitted within 15 days

Other Safety Reports

The G-ECBiomedRes indicate that ECs should monitor research, and will report to the National Bioethics Committee upon notification of an AE.

The CTRules and the G-KenyaCT state that the sponsor must also submit a safety report to the PPB once a year throughout the clinical trial, or upon request. The purpose of the annual safety report is to briefly describe all new safety information relevant to one (1) or more clinical trial(s), and to assess the safety conditions of the participants enrolled in these trial(s). The safety report must include a log of SAE and SUSAR events. The SAE and SUSAR log should include the following:

• Patient Identification
• Age
• Date of recruitment into the study
• Type of SAE or SUSAR
• SAE or SUSAR start and end dates
• Reason for reporting the event as an SAE or SUSAR
• Relation to IP
• SAE or SUSAR outcome

Note that the PPB may require more frequent reporting of the safety reports depending on the nature of the clinical trial being implemented. When this is the case, the PPB must communicate the required frequency to the PI and sponsor in writing.

Form Completion & Delivery Requirements

As per the G-KenyaCT and KEN-16, all SAEs and SUSARs must be reported to the PPB via the Pharmacovigilance Electronic Reporting System (PvERS) (KEN-6).

Safety Reporting Definitions

In accordance with the CT-Regs, the G-ReptSafetyData, and the G-AppConductCT, the following definitions provide a basis for a common understanding of Tanzania’s safety reporting requirements:

• Adverse Event (AE) – Any adverse medical occurrence in a research participant to whom a drug product was administered, and which does not necessarily bear a causal relationship to the treatment
• Adverse Drug Reaction (ADR) – All noxious and unintended responses to a medicinal product related to any dose
• Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
• Suspected Unexpected Serious Adverse Reaction (SUSAR) (also referred to as Unexpected ADR) – A serious adverse reaction where the nature and severity of the event is not consistent with the medicinal product

The PV-Regs reaffirms that the reporting of SAEs and SUSARs occurring during clinical trials should comply with the requirements in the CT-Regs.

Per the G-EthicsHR-TZA, the severity of an AE must be graded as follows:

• Mild: Includes events that do not interfere with activities of daily living and do not require treatment
• Moderate: Includes events that have minimal effect on activities of daily living and usually require out-patient treatment
• Severe: Includes activities that significantly affect activities of daily living and may require inpatient hospitalization
• Life-threatening: Includes all events that are life threatening and usually require emergency procedures
• Death

The G-EthicsHR-TZA states that an AE must be deemed unexpected if:

• It is previously unobserved or undocumented in humans under the health research intervention (or one substantially similar)
• The nature or severity is not consistent with information in the investigator’s brochure or other safety information known at the time
• The event is observed with higher frequency or severity than previously documented

See the G-EthicsHR-TZA for additional details on grading AEs.

Safety Reporting Requirements

Investigator Responsibilities

As stated in the G-ReptSafetyData and the G-AppConductCT, the investigator is responsible for documenting and reporting all AEs/ADRs, SAEs/SADRs, and SUSARs to the sponsor using the case report form (CRF)/reporting form and the SAE/SADR Reporting Form approved in the protocol, or CIOMS Form I (TZA-7). See section 3.0 of the G-ReptSafetyData for key data elements to include on the form. TZA-5 requires the principal investigator (PI) to ensure that the protocol includes all required elements for safety monitoring, including assessment and reporting of any anticipated or unanticipated AEs and SAEs. Ethics committees (ECs) (both the National Health Research Ethics Committee (NatHREC) and institutional ECs) must review and address AEs, SAEs, and/or SUSARs. Investigators must be familiar with the regulations, policies, and procedures concerning reporting and continuing review requirements, as well as timelines for submission of notifications and reports.

The CT-Regs states that the PI must immediately report to the Tanzania Medicines and Medical Devices Authority (TMDA) any SAE/SADR that occurs to a participant at a trial site where the PI is responsible for the conduct of the trial. The report may be made orally or in writing and must be followed up with a written report in 14 days. Also, the PI must report AEs that the protocol identifies as critical to safety evaluations. The reports must identify each participant by a number assigned to that participant in accordance with the protocol.

The CT-Regs further states the PI or sponsor must record and report SUSARs that are fatal or life-threatening to the TMDA within seven (7) days and other SUSARs within 15 days.

The G-EthicsHR-TZA requires the investigator to promptly investigate all SAEs, take appropriate measures to ensure the safety of all research participants, and report these and any other information that is likely to affect the safety of the research participants or the conduct of the research events, to the regulatory authority, institutions, and sponsor within the timelines stated in standard operating procedures. Specifically, the investigator must report the following to the EC and TMDA:

• All SAEs irrespective of relationship to the health-related intervention
• All unexpected events of greater than moderate severity irrespective of relationship to health-related intervention
• All events associated with protocol violations irrespective of severity and relationship to health-related intervention
• When criteria for stopping or pausing a study as stipulated in the protocol are met
• Any event mandated by regulatory authorities
• Any event stipulated in the protocol as reportable to the regulatory bodies

Per the G-EthicsHR-TZA, all SAEs must be reported to the local EC as soon as possible and in any case no later than seven (7) days of becoming aware of the event. Thereafter, a detailed report of the SAE should be submitted within eight (8) days. All other reportable AEs should be reported to the EC as soon as possible and in any case not later than 15 days. TZA-5 requires the investigator to submit an initial report on an SAE to NatHREC within 24 hours of its occurrence and a final or followup report on the SAE within 14 days of its occurrence.

Further the G-EthicsHR-TZA requires the investigator to clearly outline in the protocol how management of both foreseeable and unforeseeable AEs will be done. Certain categories of interventions whose long-term effects are not known or cannot be extrapolated will require extended monitoring for AEs, such as genetically modified substances, gene therapy, and DNA-based therapies.

Sponsor Responsibilities

The G-ReptSafetyData states that the sponsor is responsible for the assessment and timely reporting of SAEs/SADRs and SUSARs to the TMDA. The sponsor must retain detailed records of safety information reported by the investigator(s) and ensure that all reports required by the TMDA are submitted on time. In addition, the sponsor must report all SAEs and SUSARs occurring from trial sites outside the country to the TMDA.

The G-ReptSafetyData requires that fatal or life-threatening SAEs/SADRs or SUSARs must be immediately reported to the TMDA by telephone, fax, or email followed by a complete report within seven (7) additional calendar days. The G-AppConductCT specifies that the immediate reporting period is within 24 hours. Further, the report should include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar products. All deaths during the study, including the post-treatment, follow-up period, and deaths that resulted from a process that began during the study, should be reported.

Per the G-ReptSafetyData and the G-AppConductCT, all other SAEs and SUSARs that are not fatal or life-threatening must be filed as soon as possible but no later than 14 calendar days after first knowledge by the sponsor. Please note that the CT-Regs states that non-life-threatening SUSARs should be reported in 15 days.

See the CT-Regs and the G-ReptSafetyData for detailed reporting requirements.

Form Completion & Delivery Requirements

As per the G-ReptSafetyData and the G-AppConductCT, all SAEs/SADRs and SUSARs must be reported on the protocol-approved CRF/reporting form, or CIOMS Form I (TZA-7), and should include trial specific details such as participants’ ID numbers and/or protocol number. The form must be submitted to the TMDA office by courier, mail, email (as an attachment), or by fax.

According to TZA-26, the TMDA address and contact information is as follows:

See Annex 15 of the G-AppConductCT and Appendix 1 of the G-ReptSafetyData for the reporting forms.

Interim and Annual Progress Reports

As stated in the G-KenyaCT, the sponsor and/or the principal investigator (PI) is required to send progress reports to the Pharmacy and Poisons Board (PPB) on an annual basis, or as may be required, from the date of the trial’s initiation. The progress report should contain the following:

• Current status of the study
• Summary of the participants screened (e.g., failed screenings, participants enrolled, withdrawn, or lost to follow-up, and other challenges)
• Summary of protocol deviations and violations
• Updated investigational product Investigator’s Brochure
• Drug Safety Update Report
• Copy of the latest Data Safety Management Board report
• Copy of favorable opinion from the ethics committee (EC) on record
• Copy of annual practice license for the investigators and pharmacists
• Suspected, Unexpected, Serious Adverse Event (SUSAR) and Serious Adverse Event (SAE) Log

For multisite trials, per the G-KenyaCT, the sponsor or the representative must submit a summarized report for all of the sites and include the information listed above.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-KenyaCT, for annual renewal of the study, the sponsor or the representative must submit a copy of the progress report including the documents listed above. The request must also be accompanied by copies of annual practice licenses for the investigators and pharmacists, and a copy of valid insurance coverage for the participants. All documents must be submitted using the PPB’s Online Clinical Trials Registry System (KEN-16). The sponsor or the representative must receive an acknowledgement of this submission before proceeding with the study. These documents must be submitted to the PPB at least six (6) weeks prior to the expiration of the previous approval.

Pursuant to KEN-14, the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested.

Final Report

Per the G-KenyaCT, the sponsor must notify the PPB of the end of a clinical trial taking place at a Kenyan site within 15 days. After the trial has been conducted and closed, the applicant must submit an executive summary report of the study within 30 days. This should be followed by a clinical study report within 180 days of the study closure unless otherwise justified. The report must comply with the International Council for Harmonisation's ICH E3 format (KEN-13). The report must include a short but comprehensive summary of the trial’s essential findings and methodology and should also contain a layman’s summary. Additionally, the sponsor must inform the PPB of any results that will be publicly released at least 14 days before release. In addition, upon completion of the trial, as delineated in KEN-14, the investigator is required to submit a final report to the institutional EC summarizing the trial’s outcome.

For multi-site research, the G-ECBiomedRes requires all parties to decide on procedures for drafting a common final report and publication at the onset of the research. Individual sites or institutions must not publish any data until the appropriate authorities accept the combined report.

KEN-31 further indicates that the research license applicant must submit one (1) hard copy and upload a soft copy of the final research report to the National Commission for Science, Technology and Innovation (NACOSTI) within one (1) year of the research’s completion.

Interim and Annual Progress Reports

As delineated in the G-AppConductCT, the sponsor or the principal investigator (PI) must submit progress reports to the Tanzania Medicines and Medical Devices Authority (TMDA) on a six (6)-month basis from the date of the clinical trial’s commencement. The content should be as prescribed in TZA-11. In addition, the TMDA provides a six (6)-month progress report form for clinical trials of investigational products (TZA-3). The CT-Regs states that progress reports should be submitted annually, or more frequently, as required by the TMDA.

Per the G-EthicsHR-TZA, researchers must submit progress reports to the ethics committee (EC). The investigator must ensure appropriate and timely feedback on the research process including progress reports at regular intervals as stipulated by the EC. Periodic progress reports enable the EC to determine whether the research study is progressing according to the approved protocol.

According to TZA-5, the investigator must submit written progress reports every six (6) months to the National Health Research Ethics Committee (NatHREC) for all ongoing approved health research activities in Tanzania.

In addition, per the G-ResearchClearance, the PI is required to submit annual progress reports (as part of the annual permit-renewal process) to the Tanzania Commission for Science and Technology (COSTECH) that include the title of the study, COSTECH registration reference number, study site, brief background and objective of the study, progress in the reporting period, any problems encountered, and implementation plan for the next period.

Final Report

The G-AppConductCT requires the sponsor or the PI to submit a closing report to the TMDA within 60 days of the trial’s completion. This report should be followed by a final study report within six (6) months after trial closure unless otherwise justified. The structure and content of the final report should comply with TZA-11.

In addition, per TZA-5, the PI is required to submit a final report to the NatHREC once the last participant has completed all visits and all adverse experiences have been brought to appropriate resolution. Final reports must be submitted to the NatHREC on a Close-out Form (Form 08 in TZA-5) and processed as an expedited review. The Secretariat will review the Close-out Form. The expedited reviewer will request additional information from the researcher, as needed. Written documentation acknowledging the closeout will be provided to the investigator and a copy retained in the proposal file. Further, the G-EthicsHR-TZA requires researchers to submit a final report to the institutional EC containing a summary of the study's key findings, recommendations, and conclusions.

The G-ResearchClearance requires the researcher to submit a soft and hardcopy of the final report to COSTECH. The report should be accompanied with any relevant publications, electronic raw data, and proof of dissemination if applicable. The final report should include:

• COSTECH registration reference number
• Title of study
• Summary of report in English and Swahili
• Brief background and objective of the study
• Methodology, including study sites
• Key findings
• Constraints or problems encountered
• Conclusions and recommendations

As per the G-KenyaCT, a sponsor is defined as an individual, a company, an institution, or an organization who takes legal responsibility for the initiation, management, and financing of a trial. According to the G-KenyaCT, a sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. The G-ECBiomedRes indicates that sponsors may be foreign, but must comply with certain conditions including affiliating themselves to institutions recognized in Kenya.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, Kenya permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.

Per the CT-Regs and the G-AppConductCT, a sponsor is defined as an individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial. The Tanzanian government also permits a sponsor to authorize a contract research organization (CRO) to perform one (1) or more of a sponsor’s trial-related duties and functions.

As required in the G-EthicsHR-TZA, the sponsor is responsible for providing all the necessary financial support for the initiation and completion of the research study. Additional sponsor responsibilities include developing the final study report; providing forms for safety monitoring and reporting; securing compensation or indemnity in the event of research-related injuries, disability, or death; and managing matters related to the investigational new drug.

The G-EthicsHR-TZA states that research may be externally sponsored, meaning that it is sponsored, financed, and sometimes wholly or partly carried out by an external organization with the collaboration or agreement of the appropriate authorities of the host community.

Overview

The G-KenyaCT, which requires sponsors to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by education, training, and experience.

Per the CTRules and the G-KenyaCT, investigators must also meet the following requirements (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Provide evidence of their qualifications and experience through an up-to-date curriculum vitae (CV)
• Have a current practice license from the relevant regulatory authority
• Be familiar with the characteristics and appropriate use of the investigational product (IP) as described in the protocol, current investigator’s brochure (IB), in the product information, and in other information sources
• Have a clear understanding and willingness to obey the ethical, good clinical practice (GCP) and legal requirements in the conduct of the trial
• Permit monitoring and auditing of the trial and inspection by the Pharmacy and Poisons Board (PPB) or appointed representatives
• Keep a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties
• The principal investigator (PI) must be an appropriately qualified and competent person having practical experience within the relevant professional area and who is responsible for the conduct of the clinical trial at a clinical site
• The PI must have a degree in medicine, pharmacy, pharmacology, toxicology, biochemistry, dentistry, or a related discipline from a university recognized in Kenya
• The PI must have a valid practice license from the relevant regulatory authority
• The PI must have a valid professional indemnity cover
• The PI must be a citizen of Kenya or a permanent resident in Kenya
• A PI must have had previous experience as a co-investigator in at least two (2) trials in the relevant professional area
• Have adequate time and resources to carry out the study (See Annex 6 of the G-KenyaCT for the PPB’s recommended format to document the investigator’s workload)

Further, the G-KenyaCT states that sponsors must ensure that investigators have had formal training in GCPs with proof that a GCP course was attended within the last two (2) years. If training has not been completed, it is the responsibility of the sponsor to organize this training prior to initiating the study. The investigators will need to provide evidence of having obtained this training. As delineated in KEN-14, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an IB. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. (See the Submission Content section for additional information on clinical trial application requirements.)

Institutional Registration

The STI-Act and the STI-Regs require research institutions to register with the National Commission for Science, Technology and Innovation (NACOSTI) and obtain a Certificate of Registration. For detailed guidance on the vetting and approval process, see the STI-Regs and the G-InstitutionRegistration.

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), research institutions can apply for new research institution registration, maintain/update data, and submit annual reports. The application for registration of research institutions is also provided in KEN-11, and the reporting tool for registered research institutions is provided in KEN-36.

Foreign Sponsor Responsibilities

The G-ECBiomedRes requires that with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

Data and Safety Monitoring Board

The G-KenyaCT indicates that the PPB recommends establishing a Data and Safety Monitoring Board (DSMB) to monitor trials in the following types of studies:

• Where the endpoint is such that a highly favorable or unfavorable result, or even a finding of futility at an interim analysis, might ethically require the trial to be terminated early
• When there are safety concerns due to the use of a particularly invasive treatment
• Where there is prior information suggesting the possibility of serious toxicity with the study treatment
• Where the participants involved represent a vulnerable population (e.g., children, pregnant women, elderly, terminally ill, or mentally incapacitated)
• When the participants represent a population at higher risk of death or other serious outcomes
• When the study is large, of long duration, and multi-center

KEN-14 states that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Per the G-KenyaCT, the DSMB must provide the following documentation to the PPB:

• DSMB composition
• Copy of DSMB charter
• DSMB reports to be submitted to the PPB within two (2) weeks of its deliberations and in the request for annual approval

For multicenter trials, the G-ECBiomedRes requires that centralized data management and analysis should be planned as per G-WHO-DSMB.

Multicenter Studies

Per the G-KenyaCT, for multicenter studies in Kenya, the coordinating investigator should be a Kenyan resident and should assume full responsibility for the trial.

The G-ECBiomedRes requires that multicenter trials conducted simultaneously by several investigators at different sites follow the same protocol. Ideally, these trials should be initiated at the same time at all sites. The sponsor must provide the protocol to the investigators, who will accept the protocol in writing. If approved by the EC of the local host institution, the protocol may be modified to suit the local conditions. Meetings should be organized at the initial and intermediate stages of the trial to ensure uniform procedures at all sites. All sites and parties should also agree on procedures for publication of a final report. Research staff should receive training at every trial site on the uniform procedures. In addition, research staff at all sites should implement standard methods for recruitment and evaluation/monitoring of laboratory procedures and conduct of trial. There must be monitoring to ensure the sites are following the protocol, which must include measures to terminate the participation of some sites, if necessary. Finally, centralized data management and analysis should be planned as per G-WHO-DSMB.

Additional multicenter guidance is delineated in KEN-14:

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

Overview

The Tanzanian government complies with the requirements delineated in the G-AppConductCT and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13) for conducting clinical trials. As set forth in TZA-13, the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial, and for ensuring that the investigator(s) are qualified by training and experience. Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. As delineated in TZA-13 and the G-AppConductCT, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s).

The G-AppConductCT delineates that the principal investigator (PI) must have the following minimum qualifications and experience:

• University degree in medicine, pharmacy, pharmacology, toxicology, or biochemistry and related fields
• Practical experience within the relevant professional area
• Previous experience as a co-investigator in at least two (2) trials in the relevant professional area
• Must be responsible for the conduct of the clinical trial at a clinical trial site
• Tanzanian resident
• In good standing with a professional organization
• For multicenter studies where the PI is not a resident of Tanzania, the appointed national PI must be a resident and should assume full responsibilities for all local clinical trial sites
• Ensure that sufficient time is available to conduct and complete the trial, and that other commitments or trials do not divert essential subjects, resources, or facilities away from the trial in hand
• The maximum number of clinical trials that a PI is allowed to supervise at the same time is five (5)

All investigators in a clinical trial, as well as the trial monitor, must have had formal training in Good Clinical Practices (GCPs) within the last three (3) years. Evidence of attending the GCP course should be submitted.

Per the G-AppConductCT, 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 development of the product and the 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.

Per G-EthicsHR-TZA, institutions hosting research are overall accountable for research projects within their institutions. The institution must work closely with the investigators and monitor implementation of the research activities. Specifically, the host institution must ensure that they have qualified and competent investigators to carry out the research studies at the institution; facilitate the smooth implementation of research studies conducted at the institution; and take appropriate disciplinary action against investigators for non-compliance.

Foreign Sponsor Responsibilities

The G-EthicsHR-TZA states that research may be externally sponsored. The ethical standards should not be less stringent than they would be for research carried out in the country of the sponsoring organization. Local ethics committees (ECs) are fully empowered to disapprove a study they believe is unethical.

The G-ResearchClearance requires all foreign researchers to identify and affiliate to a local institution that has the appropriate capacity in the relevant type of research and obtain a local collaborator. Minimum qualifications of the local collaborator should be a person with a master’s degree and an expert in the relevant field of study. There should be a memorandum of agreement between the local institution/collaborator and the foreign researcher that includes methods for sharing data, material transfer agreements, access benefit sharing agreements, managing intellectual property, and dissemination of research results.

Data and Safety Monitoring Board

Per the G-EthicsHR-TZA, all Phase I, II, and III clinical trials, including drug efficacy trials, conducted in Tanzania must have a safety monitoring plan and Data and Safety Monitoring Board (DSMB) or a Data Monitoring Committee (DMC). Other interventional studies, such as community trials, may be required to set up DSMBs on a case-by-case basis. The National Health Research Ethics Committee (NatHREC) must ensure the establishment of a DSMB in all clinical trials to periodically assess the progress of implementation of safety data and the efficacy endpoints and to recommend to the sponsor whether to continue, modify, or terminate a trial. See the G-EthicsHR-TZA for details on the DSMB composition, qualifications, affiliation, terms of reference, and reporting.

As delineated in TZA-5, NatHREC considers DSMBs to be relevant in the following kind of studies:

• Controlled studies with mortality and/or severe morbidity as a primary or secondary endpoint
• Randomized controlled studies focused on evaluating the clinical efficacy and safety of a new intervention
• Early studies of a high-risk intervention
• Studies in the early phases of a novel intervention with very limited information on clinical safety
• Studies where the design or expected data accrual is complex, particularly studies with a long duration
• Studies carried out in emergency situations

The CT-Regs states that the DSMB requirement may depend on trial design and scientific background, risk and benefit assessment, or any other reasons determined by the NatHREC.

TZA-5 states that for clinical trials conducted only in Tanzania, the DSMB must include representation from Tanzania. For multi-country clinical trials, the DSMB must include regional representation, and a Tanzanian must be among the members. Where necessary, NatHREC may request that the sponsor submit the most recent report from the DSMB. In contrast, per TZA-1, for clinical trials that require a DSMB, the PI must submit a list of DSMB members, including at least one (1) Tanzanian, to the National Institute for Medical Research (NIMR). Additionally, the CT-Regs requires the following information:

• Trial objectives and terms of reference
• Member composition, qualifications, specific roles, and relationship to the investigators and study
• How meetings will be organized

The G-AppConductCT also specifies that a DSMB/DMC is required in situations where safety concerns may be unusually high. A DMC is recommended for any controlled trial of any size that will compare rates of mortality or major morbidity. It also indicates that a DSMB or DMC must be considered in the following situations:

• The study endpoint is such that a highly favorable or unfavorable result, or even a finding of futility, at an interim analysis might ethically require termination of the study before its planned completion
• There are a priori reasons for a particular safety concern (e.g., if the procedure for administering the treatment is particularly invasive)
• There is prior information suggesting the possibility of serious toxicity with the study treatment
• The study is being performed in a potentially fragile population such as children, pregnant women, the very elderly, other vulnerable populations, or those who are terminally ill or of diminished mental capacity
• The study is being performed in a population at elevated risk of death or other serious outcomes, even when the study objective addresses a lesser endpoint
• The study is large, of long duration, and multi-center

Additional details on the procedures and composition of the DSMB or DMC are provided in the G-AppConductCT and Part VIII of the CT-Regs. In addition, per the G-ReptSafetyData, the sponsor must also ensure that the DSMB’s interim safety data analyses are submitted to the Tanzania Medicines and Medical Devices Authority (TMDA).

Multicenter Studies

Per the G-EthicsHR-TZA, for multicenter studies, the study must be conducted in a methodologically identical way at each center. See the Scope of Review section for more details on multicenter studies.

As delineated in TZA-13, in the event of a multicenter clinical trial, the sponsor must ensure that:

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

The CT-Regs and the G-AppConductCT also state that in the case of multicenter studies where the PI is foreign, the appointed national PI must be a resident and assume full responsibilities for all local clinical trial sites.

Insurance

As set forth in the G-KenyaCT and the G-ECBiomedRes, the sponsor must provide insurance cover for the study participants and ensure that the clinical trial institution, contract research organization (CRO), and researchers have sufficient insurance cover for the clinical trial. Per the G-KenyaCT, the sponsor’s policies and procedures should address the treatment costs for trial participants in the event of trial-related injuries, and the sponsor should submit this information as part of the clinical trial application (see KEN-34). In addition, a no-fault insurance cover must be obtained for all controlled human infection studies. The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) guides sponsors on providing insurance. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

For all sponsor-initiated studies, insurance coverage must be provided by an insurer registered by Kenya’s Insurance Regulatory Authority (IRA), and a valid insurance certificate must be issued by the IRA prior to the trial’s initiation and cover the duration of the study. The insurance certificate must be submitted as evidence to the Pharmacy and Poisons Board (PPB). The certificate must be properly executed by an insurance company under a valid insurance policy which makes explicit reference to the proposed study. In addition, the policy must grant coverage for any participant injury that is causally linked to trial activities. The policy must also cover the investigator(s)’ and the sponsor(s)’ liability in the trial, without excluding any damage which may be attributed to negligence. Moreover, self-insurance of the participants by other entities, such as the National Health Insurance Fund, will not be sufficient.

Further, per the G-KenyaCT, the sponsor must ensure that the investigators and CROs have professional indemnity insurance coverage for the period of the trial. The host institution must also have in place sufficient insurance to meet the potential liability of its investigators, those acting on behalf of the investigators, and its research members.

Compensation

Injury or Death

As specified in the G-KenyaCT and the G-ECBiomedRes, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. Per the G-ECBiomedRes, participants are entitled to such financial or other assistance as would compensate them equitably for any temporary or permanent impairment or disability. In the case of adverse events, there should be proper assessment, evaluation, and compensation. The G-ECBiomedRes also indicates that when investigational vaccines contain active or live-attenuated micro-organisms, should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.

In addition, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

The G-ECBiomedRes defines compensation to include offers to participants, monetary or otherwise, to offset the time and inconvenience for participating in research.

Post-Trial Access

Per the G-KenyaCT, the sponsor must put in place measures to ensure that the study participants have access to successful investigational products for their disease condition before the products have received a marketing authorization in Kenya, especially for the Phase III clinical trials. The G-ECBiomedRes indicates that when investigational vaccines contain active or live-attenuated micro-organisms, post-trial access to the vaccine should be available to the control group.

Insurance

As set forth in the CT-Regs, the G-AppConductCT, the G-CTInsurance-TZA, and TZA-5, the sponsor or the designated contract research organization (CRO) is responsible for providing insurance coverage for any unforeseen injury to research participants. Before a clinical trial begins, the sponsor should also provide insurance and indemnify the investigator and the institution against claims arising from malpractice or negligence, and provide a copy of a valid insurance certificate from a recognized insurer in the clinical trial application submission. Additionally, per the CT-Regs, the insurance policy should be obtained from an insurance company registered in Tanzania. The G-CTInsurance-TZA and the G-AppConductCT state that details and proof of insurance must be provided in the ethics review submission. Furthermore, per the CT-Regs, for investigator-initiated trials, proof of current malpractice insurance that covers clinical trials must be provided to the Tanzania Medicines and Medical Devices Authority (TMDA). (See the Submission Content section for additional submission requirements.) The G-EthicsHR-TZA requires that insurance issues are clearly described in all clinical trial protocols, and that sponsors and investigators comply with the G-CTInsurance-TZA.

As per the CT-Regs and the G-CTInsurance-TZA, the sponsor or the designated CRO must sign an indemnity agreement with the host institution and the investigator(s) to cover any risks related to a research participant being injured by an investigational product, or from any procedure deemed necessary by the protocol. The sponsor and the institution’s chief executive officer must sign the indemnity. See Appendix 1 of the G-CTInsurance-TZA for a sample agreement. Per the CT-Regs, the sponsor must also indemnify the investigator against claims arising from the trial, except for claims that arise from malpractice or negligence.

The G-CTInsurance-TZA states that the insurance policy must meet the following requirements:

• Cover the conduct of the relevant clinical trial in Tanzania

• Provide a policy registered by the Tanzania Insurance Regulatory Authority (TIRA)

• Contain insurance coverage for an amount sufficient to meet the indemnification requirements applicable to the ethics committee (EC)-specified level of risk

• Cover claims made by research participants during the trial as well as those made after the trial is completed

Compensation

Injury or Death

As specified in the G-CTInsurance-TZA and the G-EthicsHR-TZA, the sponsor or the designated CRO is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. The sponsor must also ensure that participants who suffer any trial-related injuries are provided with free medical treatment for such injuries. The G-EthicsHR-TZA states that research study participants must not be asked to waive the right to compensation and must retain the legal rights to seek monetary compensation for research-related injuries including settlements out of court, in accordance with applicable laws in Tanzania.

Per TZA-5, investigator(s) must ensure participants (or their dependents in case of participant death) are equitably compensated should they sustain unexpected serious injuries (physical, psychological, or social harm) that are judged to be related to the investigational product (IP) or study procedure. Participants must not be compensated if they sustain expected adverse events or those related to other licensed medicines appropriately prescribed during the trial.

As per the G-CTInsurance-TZA, the amount of compensation paid should be appropriate to the nature, severity, and persistence of the injury. Compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):

• The seriousness of the disease being treated

• The degree of probability that adverse reactions will occur and any warning given
• The risks and benefits of the established treatments relative to those known or suspected of the trial medicines

Trial Participation

As per the CT-Regs and the G-AppConductCT, participants may also be compensated for travel and incidental expenses incurred while participating in the trial. Per the G-AppConductCT, the clinical trial application must indicate the compensation to be received by participants, including a breakdown of costs.

The G-EthicsHR-TZA indicates that research study participants may be reimbursed for lost earnings, travel costs, lunch, and other expenses incurred in taking part in a study; they may also receive free medical services. Research participants, particularly those who receive no direct benefit from the research, will be compensated for inconvenience and time spent. Compensation must not be so large as to induce potential participants to consent to participate in the research study against their better judgement (undue inducement). A local EC must approve reimbursement and compensation for research study participants. Incentives to research study participants for their participation in research studies must not be considered a research benefit, but a recruitment incentive, and should not present undue influence on potential research participants.

Post-Trial Access

Per the study protocol template in the G-AppConductCT and TZA-42, details on post-trial access to products must be provided in the study protocol.

Per the G-EthicsHR-TZA, where appropriate, the clinical trial protocol should include a provision for the involvement of the community in the research process including the post-research period. The community in this context may be geographical or the study population. Further, there should be optimization of collateral benefits to the research communities including access to the products of the research. If the investigational product is found to be beneficial, the investigator should assist to secure its provision, without charge, to participants in the research study following the conclusion of the study.

Quality Assurance/Quality Control

As stated in the CTRules and the G-KenyaCT, the sponsor is responsible for maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), the STI-Regs, and other applicable regulatory requirements. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. In addition, per the STI-Regs, all persons and research institutions (i.e., sponsors) undertaking research in Kenya must ensure the highest standards and quality of research for the realization of institutional mandates and national priorities.

In addition to complying with KEN-14, the G-KenyaCT indicates QA processes should be developed to ensure:

• Regular and continuous monitoring of the study and the implementation of monitoring reports’ recommendations
• Submission of the study monitoring plan to the Pharmacy and Poisons Board (PPB) during the initial submission of the application
• The clinical trials research site must have valid registrations and approvals
• Patient safety and confidentiality are not compromised
• Analysis or evaluation of samples is performed in accordance with the protocol and good clinical practice (GCP) principles and, where applicable, the contract/agreement, the work instruction, and associated methods
• Adherence to the laboratories’ policies and SOPs
• Trial data is recorded and reported accurately, legibly, completely, and in a timely manner
• Trial data is archived
• Preparation of a work instruction detailing the procedures that will be used to conduct the analysis or evaluation prior to the initiation of sample analysis or evaluation, as necessary
• Be built or adapted for the purpose
• Have automated equipment for routine hematology, biochemistry, and serology tests
• Have procedures for analyzer calibration and quality control
• Regular maintenance of all the equipment, including point-of-care equipment
• Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
• Have written procedures for all assays, and to validate the assays
• Reagents and consumables are used within their expiry dates based on a stock control procedure
• Records are kept, including source documents and final reports
• Have a procedure for authorizing and releasing results
• Have a procedure for ‘flagging’ and notifying medical staff of abnormal results
• Have a laboratory information management system, and validate and back up the system
• Protective clothing and safety equipment are provided for staff
• Have a central alarm system for all fridges and freezers
• Have an internal audit program

Per KEN-14, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

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

Per the G-KenyaCT protocol violations and protocol deviations must be reported to the PPB within seven (7) days of the principal investigator (PI) becoming aware of them. The details to be reported must include:

• Date of the deviation/violation
• Study participant(s) affected
• Name of the treating physician
• Detailed description of the deviation/violation
• Indication whether the study participants were adversely affected by the deviation/violation
• Explanation of why the deviation/violation occurred
• Measures taken to address the deviation/violation
• Measures taken to preclude future recurrence of the deviation/violation

In addition, see G-KenyaCT for information about medical care of trial participants during and following the clinical trial. Also see the Bft-Risk for a standardized approach for evaluating and reporting the balance between the benefits and risks of health products, which includes investigational products (IPs) undergoing clinical trial application.

The CT-Emrgcy provides guidance to sponsors, PIs, and institutions on the conduct of clinical trials during public health emergencies to maximize the safety of research participants, minimize risks to participants and the community, and ensure the integrity of the clinical trials. See CT-Emrgcy for details on a range of issues, including contingency planning, communications with participants, changes to studies, protocol deviations, reporting, and supply of IPs during a public health emergency.

Controlled Human Infection Studies

The G-KenyaCT also provides detailed information on controlled human infection studies (CHIS) requirements to ensure investigator/study personnel compliance with GCP and other QA/QC requirements, including the following:

• The well characterized strain of an infectious agent should be administered at a controlled dose and by a specific route to carefully selected adult volunteers
• The studies require safe and accurate microbiology, good clinical facilities, careful recruitment, and monitoring
• Participants must be monitored for evidence of carriage or infection under medical supervision to anticipate or manage symptoms of disease and adverse events
• The value of the information to be gained should clearly justify the risks and the study must have a risk mitigation plan
• The investigators should be adequately qualified, trained, and experienced in the conduct of CHIS as well as treating patients with the infectious disease being investigated

For the complete list of requirements, see the G-KenyaCT.

The G-ECBiomedRes provides additional considerations when investigational vaccines contain active or live-attenuated micro-organisms:

• The participant to be vaccinated should be given adequate information about the adverse effects.
• Should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.
• Because the risks associated with vaccines produced by recombinant DNA techniques are not completely known, PPB guidelines must be strictly followed.
• Post-trial access to the vaccine should be available to the control group

Monitoring Requirements

As part of its QA system, the G-KenyaCT requires the sponsor to develop an internal audit program. The G-KenyaCT defines an audit as a systematic examination, carried out independently of those directly involved in the trial, to determine whether the conduct of a trial complies with the agreed study protocol and whether data reported are consistent with those on record at the site. Further, the sponsor is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities An investigator must, upon request from any properly authorized officer or employee of PPB, at reasonable times, permit such officer or employee to have access to, and copy and verify any records or reports made by the investigator.

Per KEN-14, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose onsite monitoring, a combination of onsite and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

KEN-31 indicate that the National Commission for Science, Technology and Innovation (NACOSTI) may conduct an evaluation, or cause an evaluation to be conducted, of a research study to assess and evaluate compliance with the conditions of the applicable research license.

Premature Study Termination/Suspension

The G-KenyaCT states that if a trial is terminated by the PI or the sponsor, the PI or the sponsor must inform the PPB not later than 15 days following the termination date. The co-investigators must also be informed as soon as possible and should be advised in writing of potential risks to the research participants, and they must ensure that patients continue to receive medical care. The PPB must be provided with reason(s) for the termination and its impact on the proposed or ongoing trials with respect to the IP, including issues relating to IP accountability and disposal as well as record(s) maintenance. In addition, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants is compromised or that the scientific reasons for conducting the trial have changed.

According to KEN-14, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

Quality Assurance/Quality Control

As stated in the CT-Regs and the G-AppConductCT, the Tanzanian government complies with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13) requirement that the sponsor implement and maintain quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol. Per the G-EthicsHR-TZA, the investigator is responsible for documenting all steps in data management to allow a step-by-step retrospective assessment of the quality of the data and the performance of the research study.

Per G-EthicsHR-TZA, during the conduct of clinical trials, deviations from the original study might occur, such as changes in the sample size or analysis of the data as described in the protocol. Deviations must be reported to ethics committees (ECs). In the case of permanent deviations, researchers may write an amendment. The EC must decide whether a deviation is accidental or purposeful. Protocol violations are deviations from the original protocol that significantly affect the rights or interests of research participants and the scientific validity of the data. In the case of protocol violations, study participants must be informed and provisions made to protect their safety and welfare. ECs may halt the continuation of a previously approved protocol if they find protocol violations or other misconduct. Any serious or continuing non-compliance with ethical standards in the conduct of previously approved research projects must be reported to the sponsor and institutional or governmental authorities by the study’s principal investigator (PI) and the Data and Safety Monitoring Board (DSMB).

Per TZA-13, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

• Identifying processes and data that are critical to ensure participant protection and the reliability of trial results during protocol development
• Identifying risks to critical trial processes and data
• Evaluating the identified risks, against existing risk controls
• Deciding which risks to reduce and/or which risks to accept
• Documenting quality management activities and communicating to those involved in or affected by these activities
• Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
• Describing the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report

The G-AppConductCT states that the sponsor should ensure that the protocol or other written agreement specifies that the investigator(s)/institution(s) will permit Tanzania Medicines and Medical Devices Authority (TMDA) inspection(s) and provide direct access to source data/documents. Further, TZA-13 indicates that the sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

As described in the G-AppConductCT, study design, statistical considerations, choice of control groups, reporting of data, and conduct of the trial should also comply with the International Council for Harmonisation’s Efficacy Guidelines (E3-E16), provided in TZA-24.

Monitoring Requirements

As part of its QA system, the G-AppConductCT and TZA-13 note that the sponsor should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, TZA-13, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial, ensure that the auditors are qualified by training and experience, and document their qualifications. The sponsor must also ensure that the audit is conducted in accordance with any custom SOPs, the auditor observations are documented, and data are available as needed for the TMDA. No specific timeframe is provided for the audit process. The sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

The G-GCPInspections provides guidance on clinical trial inspections to ensure the trial is conducted in accordance with the study protocol, procedures, TZA-13, and regulatory requirements, and that the data are accurate and valid. Inspectees (i.e., sponsor, investigator site, and contract research organization) should follow the G-GCPInspections requirements to ensure consistent conduct of trial inspections, including uniform reporting.

Per Pub-Rpts, to promote transparency of clinical trial oversight in the country, the TMDA will publish to its website clinical trial public assessment reports (CTPAR) and clinical trial public inspection reports (CTPIR) of all approved and ongoing clinical trials on an annual basis. The publication will only be undertaken after obtaining the consent of the respective PIs and sponsors. The PIs and sponsors are required to provide their consent within 14 days from the TMDA’s notification letter. Failure to respond is assumed to mean that the PIs and sponsors have consented to the publication of the CTPAR and CTPIR. For further clarification on this notice, contact TMDA at clinicaltrials@tmda.go.tz or info@tmda.go.tz.

Premature Study Termination/Suspension

The CT-Regs and the G-AppConductCT state that if a trial is prematurely terminated or suspended, the PI or the sponsor must inform the TMDA no later than 15 days after the date of the termination, and explain the reason(s) for the termination and its impact on the proposed or ongoing clinical trials. The sponsor or PI must also inform all co-investigators of the termination, the reasons for the termination, and advise them in writing of potential health risks to research participants. For each discontinued clinical trial site, the sponsor must stop the use or importation of the investigational product (IP) from the date of the trial’s discontinuation and take all reasonable measures to ensure the recovery of all unused quantities of the IP.

The G-EthicsHR-TZA also indicates that in the event of early termination of the research study, the investigator must inform, in writing, the appropriate EC, the National Institute for Medical Research (NIMR), the TMDA, and the research sponsor of the early termination and the underlying reason for such termination. Per TZA-5, the National Health Research Ethics Committee (NatHREC) should be notified if the investigator chooses to suspend the study. To resume a suspended study regardless of who initiated the suspension, the PI must submit a request to the Medical Research Coordination Committee (MRCC) with a report on the progress of addressing corrective actions. Research studies may be terminated based on the recommendation of the NatHREC, zonal or institutional ECs, DSMB, study sponsor, PI, or regulatory authority. In addition, a research study can be terminated due to an arising conflict of interest among investigators or financial misuse, which negatively affects implementation of the research project.

According to TZA-13, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

Electronic Data Processing System

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Per KEN-14, the sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to KEN-14 for additional information.

Records Management

According to the G-KenyaCT, it is the responsibility of the investigator and the sponsor to archive safely all trial-related documentation. All Kenyan trial site-related documentation must be archived within the country and not exported. Additionally, the sponsor/applicant must inform the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) in writing prior to destroying any trial documents. The notification must include the protocol number, start and end date, and the license number.

The G-KenyaCT states that study documents must be archived for a minimum of 10 years from the end of the study. Also, records must be made available to the PPB within three (3) days if there is a concern regarding the use of a clinical trial drug and/or a risk to the health of the clinical trial participant. In any other case, records must be provided within seven (7) days of request.

Per the STI-Regs, sponsors should store research findings and information regarding research systems in a designated location with clear labels of the subject area. Research findings must be documented in bound books or documents with the research title, author, year, and other relevant information clearly printed on the cover page. A report of research work by staff and the research institution must be submitted to the National Commission for Science, Technology and Innovation (NACOSTI) within two (2) months after publication or compilation of the research report.

In addition, KEN-14 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Electronic Data Processing System

As stated in the CT-Regs and the G-AppConductCT, the Tanzanian government complies with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (TZA-13). As per TZA-13, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Per TZA-13, the sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to TZA-13 for additional information.

Records Management

The CT-Regs states that the investigator and the sponsor must retain all trial-related records, documents, and information at the trial site for a period not less than 20 years following the trial’s completion. Further, documentation should be retained for at least two (2) years after the last approval of a marketing application. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed. See the CT-Regs for detailed record retention requirements. As set forth in TZA-13, all sponsor-specific essential documents used in the trial should be retained for at least two (2) years after formal discontinuation of the trial.

In addition, TZA-13 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Responsible Parties

For the purposes of data protection requirements, DPA delineates that the sponsor acts as the “data controller” in relation to research data. This is because the sponsor determines the purpose and means of processing personal data. The "data processor" processes personal data on behalf of the data controller. Data controllers and processors must be registered with the Kenya Data Commissioner. Per the DataProtect, an application for registration of a data controller or data processor must be on Form DPR1 (found in the First Schedule of DataProtect) with supporting materials and the required registration fees as specified in the Second Schedule. See the DataProtect for additional details on registration requirements.

Data Protection

Per the DPA, the data controller (sponsor) must ensure that personal data is:

• 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
• 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
• 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
• Not transferred outside Kenya, unless there is proof of adequate data protection safeguards or consent from the data subject

The DataProtect, which implements the DPA, requires data controllers and data processors to develop, publish, and regularly update a policy on their personal data handling practices. The policy should include the nature of personal data collected and held, how a data subject may access their personal data, complaints handling mechanisms, the lawful purpose for processing personal data, and requirements for when personal data is to be transferred outside Kenya. Regarding cross-border transfers of data, a data controller or data processor who is a transferring entity must (before transferring personal data out of Kenya) ascertain that the transfer is necessary. This necessity decision should be based on considerations such as data protection safeguards, an adequacy decision made by the Data Commissioner, and if there is consent of the data subject.

Per the DataProtect, data controllers and/or data processors must retain personal data processed for a lawful purpose and only as long as may be reasonably necessary for the purpose for which the personal data is processed. A data controller or data processor must establish a personal data retention schedule with appropriate time limits and periodic reviews. When the retention period has ended, the personal data must be erased, anonymized, or pseudonymized.

See DataProtect for additional details on data protection, including data subject rights, data protection design and principles, notification of breaches, impact assessments, and exemptions.

See Parts IV-VII of the DPA for detailed requirements on data processing, sensitive personal data, exemptions, and transfer of personal data outside of Kenya. The G-ECBiomedRes requires compliance with the DPA.

Consent for Processing Personal Data

Per the DPA, the data controller (sponsor) or data processor must bear the burden of proof for establishing a data subject’s consent to the processing of their personal data for a specified purpose. For the purposes of processing personal data, consent means any manifestation of express, unequivocal, free, specific, and informed indication of the data subject’s wishes by a statement or by a clear affirmative action, signifying agreement to the processing of personal data relating to the data subject. Unless otherwise provided under the DPA, a data subject has the right to withdraw consent at any time. The withdrawal of consent must not affect the lawfulness of processing based on prior consent before its withdrawal.

The DataProtect requires data controllers and data processors to ensure that a data subject has the capacity to consent and voluntarily gives consent. In seeking consent (prior to the processing), the data subject should be informed of:

• The identity of the data controller or data processor
• The purpose of each of the processing operations for which consent is sought
• The type of personal data that is collected and used
• Information about the use of the personal data for automated decision-making, where relevant
• The possible risks of data transfers due to absence of an adequacy decision or appropriate safeguards
• Whether the personal data processed will be shared with third parties
• The right to withdraw consent
• The implications of providing, withholding, or withdrawing consent

Per the DataProtect, this information may be presented to the data subject through a written notice, oral statement, audio or video message. The data controller or a data processor must ensure that the data subject has the capacity to voluntarily give consent that is specific to the purpose of processing.

Children

The DPA indicates that in cases where the data subject is a minor, a person who has parental authority or a guardian may exercise personal data protection rights conferred on the subject. With regard to data processing, the DPA requires that every data controller (sponsor) or data processor must not process personal data relating to a child unless consent is given by the child's parent or guardian and the processing is in a manner that protects and advances the rights and best interests of the child. A data controller or data processor must incorporate appropriate mechanisms for age verification and consent to process personal data of a child, including available technology, volume of personal data processed, proportion of such personal data likely to be that of a child, possibility of harm to a child arising out of processing of personal data, and other factors as may be specified by the Kenya Data Commissioner.

Mentally Impaired

The DPA indicates that in cases where the data subject has a mental or other disability, a person duly authorized to act as the participant’s guardian or administrator may exercise personal data protection rights conferred on the subject.

Responsible Parties

For the purposes of data protection requirements, PDP-Act delineates that the “data controller” (i.e., the natural/legal person or public body designated by law) is responsible for determining the purpose and means of processing personal data. The "data processor" processes personal data on behalf of the data controller. The “data protection officer” is an individual appointed by the data controller or data processor to ensure compliance with the PDP-Act and its regulations. Data controllers and processors must be registered with the Personal Data Protection Commission (PDPC). See the PDP-Reg-TZA for detailed procedures on registering with PDPC.

Data Protection

Per the PDP-Act, the data controller or data processor must protect personal data by ensuring that it is:

• Processed lawfully, fairly, and transparently
• Collected for explicit, specified, and legitimate purposes and not further processed in a manner incompatible with those purposes
• Adequate, relevant, and limited to what is necessary in relation to the purposes for which it is processed
• Accurate and where necessary, kept up to date, with every reasonable step taken to ensure that any inaccurate personal data is erased or rectified without delay
• Stored in a form which permits identification of data subjects for no longer than is necessary for the purposes for which the personal data is processed
• Processed in accordance with the rights of a data subject
• Processed in a manner that ensures appropriate security of the personal data, including protection against unauthorized or unlawful processing and against any loss, destruction, or damage
• Not transferred abroad contrary to the provisions of the PDP-Act

Regarding transborder data flow, the PDP-Act prohibits the transfer of personal data outside of Tanzania except under the following circumstances:

• If the data is transferred to a country that also has a data protection law enacted
• If the country does not have a data protection law, data may only be transferred outside of Tanzania based on several factors, including the recipient state's federal legal frameworks, security and privacy principles, the type of information being shared, the data transfer mechanisms in place, the specific reason for the transfer, and the proposed length of data processing (See the PDP-Act for more details)

See the PDP-Reg-TZA for detailed implementation requirements.

Consent for Processing Personal Data

Per the PDP-Act, before collecting data, a data controller must ensure that the data subject is aware of the purposes for which the personal data is collected; the fact that collection of the personal data is for authorized purposes; and any intended recipients of the personal data. However, the data controller is not required to inform the data subject if the personal data is publicly available, the data subject concerned authorizes the collection of the personal data from a third party, compliance is not reasonably practicable in the circumstances of the particular case, non-compliance is necessary per other written laws, or compliance would prejudice the lawful purpose of the collection.

As required in the PDP-Act, sensitive personal data must not be processed without obtaining prior written consent of the data subject, which may be withdrawn by the data subject at any time and without any explanation or charges. If the data subject is a minor, a person of unsound mind, or any other person unable to consent, such person’s consent must be obtained or sought from the legal representative(s)/guardian(s). Exceptions to this rule apply where the processing is necessary in these circumstances:

• Compliance with other written laws
• To protect the vital interests of the data subject or of another person, where the data subject is incapable of giving consent or is not represented by a legal representative
• Necessary for the institution, trial, or defense of legal claims
• Relates to personal data that has been made public by the data subject
• The purposes of scientific research and the PDPC has, by special guidelines, specified the circumstances under which such processing may be carried out
• For the purposes of medical reasons in the interest of the data subject and the sensitive personal data concerned is processed under the supervision of a health professional in accordance with the law

Further, the PDP-Act delineates that data collected may only be disclosed if the data subject has consented to such disclosure and if the disclosure is authorized or required by law, directly related to the purpose for which such data was collected, and/or would preserve health or reduce harm to another person or the society. Disclosure of information may also be permitted where the data subject is not identified for statistical or research purposes and where it is guaranteed that such data will not be published in a manner that will identify the data subject. Additionally, data collectors must establish a code of ethics for personal data protection during collection or processing of personal data, and they must maintain a proper security system.

Per the PDP-Reg-TZA, the rights of participants regarding their personal data are the autonomous right to control their personal data, the right to communicate and exercise their data rights, and the right to human intervention to minimize biases that automated processes may create. In addition, per the G-EthicsHR-TZA, researchers using online and digital tools must protect the individual’s right to privacy and confidentiality including whether they knew or were expected to know that records and data were being kept. If individuals have reasonable expectations of privacy and impermanence of their online activities, then researchers may need to take specific measures to inform the respondents and obtain their consent to use their data for research. Further, if studies use artificial intelligence, the participant’s “right to be forgotten” must be protected by enabling their ability to request that a search engine remove information about them.

Obtaining Consent

In all Kenyan clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14). (Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in KEN-14.) The informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a National Commission for Science, Technology and Innovation (NACOSTI)-accredited institutional ethics committee (EC). The ICF must be provided to the Pharmacy and Poisons Board (PPB) with the clinical trial application. (See the Required Elements section for details on what should be included in the form.)

The CTRules, the G-KenyaCT, and the G-ECBiomedRes state that the investigator, or the designated representative, must provide detailed research study information to the participant or legal representative/guardian. Per G-ECBiomedRes, all individual consent must be written and, in no case, should collective community agreement or the consent of a community leader or other authority substitute for an individual informed consent. The G-KenyaCT and the G-ECBiomedRes also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive the legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or the representatives from their liabilities for any negligence. The participant or legal representative/guardian should also be given adequate time to consider whether to participate.

Re-Consent

According to the CTRules, the G-KenyaCT, and KEN-14, any change in the ICF due to a protocol modification should be approved by the EC before such changes are implemented. The participant or legal representative/guardian will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

Language Requirements

As stated in the CTRules and the G-KenyaCT, the ICF content should be presented in either English or Kiswahili, and the local spoken language of the area, where applicable. Copies of the English ICF should be submitted to the PPB and to the EC.

Documenting Consent

The CTRules and the G-KenyaCT state that the participant or legal representative/guardian, and the person who conducted the informed consent discussion should sign and personally date the ICF. Where the participant is illiterate, and/or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. Before participating in the study, the participant should receive a copy of the signed and dated ICF, and any other written information provided during the informed consent process. The participant or legal representative/guardian should also receive a copy of any updates to the signed and dated ICF.

According to KEN-14, where the participant is illiterate and/or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

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

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

Waiver of Consent

No information is available.

Obtaining Consent

In all Tanzanian clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the CT-Regs, the G-AppConductCT, and the G-EthicsHR-TZA. As per the G-AppConductCT and the G-EthicsHR-TZA, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by the national ethics committee (EC), the National Health Research Ethics Committee (NatHREC), and provided to the Tanzania Medicines and Medical Devices Authority (TMDA) for approval with the clinical trial application. (See the Required Elements section for details on what should be included in the form.)

The G-AppConductCT and the G-EthicsHR-TZA state that the investigator, or the designated representative, must provide detailed research study information to the participant or the legal representative/guardian. The G-AppConductCT, the G-EthicsHR-TZA, and TZA-5 also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant and the legal representative/guardian, should also be given adequate time to consider whether to participate. The G-EthicsHR-TZA indicates that informed consent protects the individual’s freedom of choice and respects the individual’s autonomy. The consent process should be a flow of information exchange between the researcher and research participants during the whole research process. The information provided should be adequate, and clearly understood by the research participants. Seeking consent must be carried out under circumstances that provide the prospective research participant or the representative sufficient opportunity to consider whether to participate and minimize the possibility of coercion or undue influence. The information given to the research participant or the representative, whether it is conveyed orally, in writing, or another delivery mechanism, must be in a language and form understandable to the participant or the legal representative/guardian.

As per the G-AppConductCT and the G-EthicsHR-TZA, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or to appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Per the G-EthicsHR-TZA, for verbal consent, the procedures used to obtain consent must be described within the ethics application, and the verbal consent must still contain all of the elements required for informed consent.

Re-Consent

According to G-AppConductCT, any change in the ICF due to a protocol modification or an alteration in treatment modality, procedures, or site visits, should be approved by the NatHREC and the TMDA prior to implementing any changes. The participant or the legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented.

Per the G-EthicsHR-TZA, the investigator must ensure that there is continued adequacy of the informed consent process and renewal of informed consent if there are significant changes in the conditions or procedures of the research project or if new information becomes available that could affect the research participant’s willingness to continue in the research project.

Regarding secondary use of materials or data in databases, registries, and repositories, the G-EthicsHR-TZA states that in the absence of broad consent to future use of material or data, including images, for research purposes, the following is recommended:

• The nature of the previously obtained consent should be determined to ascertain whether subsequent usage was envisaged and whether it falls within the scope of the current protocol. If so, new consent is not required
• If the scope of the current protocol is different, then new consent may be required
• If samples are anonymous and the results of research would not place any individual, family, or community at social, psychological, legal, or economic risk of harm, then new consent is not required
• If the link to identifiers exists but is not provided to the research team and the results of research will not place any individual, family, or community at social, psychological, legal, or economic risk of harm, then new consent is not required. The person who holds the code or link should sign an explicit written agreement not to release the identifiers to the research team. This agreement should be submitted to the EC
• If the samples can be linked to identifiers, the EC must decide on a case-by-case basis whether expedited or full review is necessary

Language Requirements

As stated in the G-AppConductCT, the ICF content should be presented in both English and Kiswahili, and all information given to participants, both oral and written, must be in both English and Kiswahili.

Documenting Consent

The G-AppConductCT and the G-EthicsHR-TZA state that the participant or the legal representative/guardian, and the person who conducted the informed consent discussion must sign and date the ICF. Where the participant is illiterate and/or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. Before participating in the study, the participant should receive a copy of the signed and dated ICF, and any other written information provided during the informed consent process. The G-AppConductCT states that the participant or the legal representative/guardian should also receive a copy of any updates to the signed and dated ICF, and copies of any amendments to the written information originally provided.

Per the G-EthicsHR-TZA, the study participant may imply consent by voluntary actions (e.g., express consent verbally or sign (written consent form)). A verbal or oral consent process is where the researcher and participant have a conversation to give information and obtain consent. Usually, oral consent is used when it is not possible to get written consent. The verbal consent may be deemed appropriate and applied under the following situations where:

• The study is deemed to be of minimal risk
• There are cultural or political concerns with signing contract-like documents
• The researcher and or participants could be put at risk by the existence of a paper record
• The study is conducted remotely via video conferencing software, telephone, etc.
• It may not be feasible in large information-taking settings (e.g., some focus group discussions (FGDs)); however, documentation of verbal consent for participants in FGDs must be written down to include the names of participants who consented verbally and those that did not

Waiver of Consent

Per the G-EthicsHR-TZA, for research that is no more than minimal risk, the EC may approve a request to waive some or all of the required elements of informed consent under specific circumstances. Waivers of informed consent are primarily requested for projects involving the secondary analysis of existing data. To waive or alter informed consent elements, the following conditions must be met:

• The study could not practicably be carried out without the waiver or alteration (whenever appropriate the study participants will be provided with additional pertinent information after participation)
• In situations where deception needs to be applied to achieve the objectives of the study
• The only record linking the study participant and the study would be the consent document and the principal risk to the research participant would be potential harm resulting from a breach of confidentiality
• The study participant presents in an emergency situation and informed consent cannot be reasonably obtained (See the Emergencies section for more information)

The G-EthicsHR-TZA states that if a waiver of written informed consent is granted by the EC, then each study participant should be asked whether they wish to have documentation that links them with the study; and the participant’s wishes must govern.

Based on the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Title of the project and that the study involves research and an explanation of its nature and purpose
• The expected duration of the participant’s participation
• The participant’s responsibilities in participating in the trial
• Experimental aspects of the study
• Approximate number of participants involved in the trial
• Trial treatment schedule and the probability for random assignment to each treatment
• Principal investigator(s), institution, and ethics committee (EC) contact information, the person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
• Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
• Any expected benefits or prorated payment to the participant; if no benefit is expected, the participant should also be made aware of this
• Alternative procedures or treatment that may be available to the participant, including a statement on disclosure of appropriate alternative procedures or courses of treatment that might be advantageous to participants when the research involves non-validated procedures, devices, or therapies
• Compensation and/or medical treatment available to the participant or the family or dependents in the event of a trial-related injury
• Any additional costs to the participant that may result from participation in the research
• The extent to which confidentiality records identifying the participant will be maintained, and if the results of the trial are published, the participant’s identity will remain confidential
• That the Pharmacy and Poisons Board (PPB) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
• The details on storage and exportation of biological samples, if applicable
• The details on storage and ownership of personal data
• Information about unblinding, if applicable
• The extent of the investigator’s responsibility, if any, to provide medical services to the participant
• That therapy will be provided free of charge for specified types of research-related injury, including the investigators’ responsibilities in this regard
• That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
• That the participant will be informed about the dissemination of findings and about any publication of the participant’s medical information, including photographs and pedigree charts
• Foreseeable circumstances under which the investigator(s) may remove the participant without consent
• That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant’s willingness to continue
• Consent to incomplete disclosure, for example, if it is necessary to inform participants that some information is being withheld deliberately and the reasons for that decision; an offer to disclose the purpose at the conclusion of the study can be made

Note that per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, the CTRules delineates that if the potential participant is a child, the ICF must also contain these elements:

• The pathophysiology of the disease or subject of the clinical trial
• The methods of diagnosis
• The currently available treatment or prevention strategy in the pediatric population
• The incidence and prevalence of the disease or subject of the clinical trial in the overall population and in the pediatric population
• The evidence and assumptions on key differences between the disease or subject of the clinical trial in the overall population and the pediatric population

Based on the G-AppConductCT and the G-EthicsHR-TZA, the informed consent form (ICF) should include the following statements or descriptions, as applicable. (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• The study purpose, procedures, and duration
• Approximate number of participants involved in the trial
• Experimental aspects of the study
• The participant’s responsibilities in participating in the trial
• Expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
• Disclosure of alternate procedures or treatments available to participants
• Clinical trial treatment schedule(s) and the probability for random assignment to each treatment
• Benefits or prorated payment to the participant or others reasonably expected from the research; if no benefit is expected, the participant should be made aware of this
• Compensation and/or treatment available for the participant in the case of trial-related injury, with a description of such compensation/treatment and where further information may be obtained
• Participation is voluntary, and that the participant can withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
• A statement of the extent of the investigator’s responsibility, where applicable, to provide medical services to the study participant
• A statement of the nature, form, and extent of compensation for study participation (e.g., reimbursement for transport, time, and meals)
• A brief description of the research project sponsors and the investigators’ institutional affiliation
• Extent to which confidentiality of records identifying the participant will be maintained, and the possibility of record access by the Tanzania Medicines and Medical Devices Authority (TMDA)
• The participant or the legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant’s willingness to continue
• Individuals to contact for further information regarding the trial, the rights of trial participants, and whom to contact in the event of trial-related injury; these contacts must speak the participant’s language
• Foreseeable circumstances under which the investigator(s) may remove the participant without consent
• Consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
• A statement that study participants will get feedback on findings and the progress of the study and that any new information that affects the study or data that has clinical relevance to the participants will be made available to the participants or their health care providers
• Where necessary (e.g., illiterate, mentally incapacitated, or physically disabled study participants), the provision for a witness at appropriate stages of the informed consent process should be ensured
• A statement that the study has been approved by a recognized Tanzanian-based ethics committee (EC)
• Whether, when, and how any of the products or interventions proven by the study to be safe and effective will be made available to the study participants at the end of the study and whether they will be expected to pay for them
• With regard to research involving the collection of biological/genetic materials, an explanation should be provided on how specimens will be managed at the end of the study; if the samples are stored for future use, separate consent should be obtained
• Additional costs to the participant that may result from participation in the research

Per the G-EthicsHR-TZA, for protocols involving verbal consent, the following minimum information must be communicated to the participant:

• Introduction - who is the caller/interviewer, affiliation, organization
• A statement that the study involves research
• Study purpose
• What the participant will be asked to do and the time commitment
• Any compensation and any information to be collected to make that payment (mailing address, email address, etc.)
• The voluntary nature of participation in the study
• Any risks or benefits associated with participating (leave this out if there are none)
• That notes are being taken or data is being recorded, if applicable
• Whether the information collected will remain confidential or if it is planned to keep identifiers with the research data
• Contact information for the researcher and/or the EC
• Ask if the participant has any questions
• Ask explicitly, “Do you agree to participate in this study?”
• Depending on the nature of the study and the participant pool, the researcher may offer other pertinent information to ensure that participants are fully informed about the study and any risks or benefits from participating in it

Compensation Disclosure

Regarding compensation, TZA-5 states that investigator(s) must ensure participants are aware of the compensation guidelines and that their rights regarding compensation are protected. Participants must not be asked to waive their rights to free treatment or compensation for research-related harms, nor must they be required to show negligence or lack of a reasonable degree of skill on the part of the researcher to claim free treatment or compensation. The informed consent process or form must not contain statements that would absolve a researcher from responsibility in the case of harm, or that would imply that participants waive their right to seek compensation.

See the Vulnerable Populations and Consent for Specimen sections for further information.

Overview

In accordance with the Declaration of Helsinki (KEN-33) principles upheld in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), Kenya’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

The Right to Participate, Abstain, or Withdraw

As set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The DPA further indicates that data subjects have a right to:

• Be informed of how their personal data is to be used
• Access their personal data in custody of the data controller (sponsor) or data processor
• Object to the processing of all or part of their personal data
• Correct false or misleading data
• Delete false or misleading data about them

The Right to Privacy and Confidentiality

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-14, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-KenyaCT, KEN-14, and the G-ECBiomedRes state that the participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries. Further, the G-ECBiomedRes requires that the ethics committee contact information also be provided.

The Right to Safety and Welfare

The G-ECBiomedRes and KEN-14 state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society. KEN-14 upholds the Declaration of Helsinki (KEN-33). (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

Overview

As stated in the G-AppConductCT, the Tanzanian government complies with the ethical principles set forth in the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (TZA-13) and the Declaration of Helsinki (TZA-30), which promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

As set forth in the G-AppConductCT and the G-EthicsHR-TZA, the participant or the legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the G-AppConductCT and the G-EthicsHR-TZA, a potential research participant or the legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Required Elements section for more detailed information regarding participant rights.) The G-EthicsHR-TZA states that information about the research study must be communicated in understandable and legally accepted language and format, and in a conducive environment, at all stages of the research.

The Right to Privacy and Confidentiality

As per the G-AppConductCT and the G-EthicsHR-TZA, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-AppConductCT and the G-EthicsHR-TZA state that the research participant or the legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

As specified in the CT-Regs, the G-EthicsHR-TZA, and the G-AppConductCT, the Tanzanian government complies with the principles in TZA-13 that state a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society.

The G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergencies. Per the G-KenyaCT, research must be conducted in accordance with KEN-14. As delineated in the G-KenyaCT and the G-ECBiomedRes, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If the prior consent of the participant or legal representative/guardian cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, to ensure compliance with ethics committee (EC) and the Pharmacy and Poisons Board (PPB) requirements. The G-ECBiomedRes requires that the principle of clinical equipoise be applied, which essentially means the participant is not any worse off by enrolling.

During a public health emergency, the G-KenyaCT stipulates that the informed consent of participants must be obtained in individuals capable of giving informed consent. The CT-Emrgcy includes safeguards to protect clinical trial participants during a public health emergency, including the recommendation to reconsent if there are amendments as a result of the emergency.

Per KEN-14, in an emergency, if the signed ICF has not been obtained from the participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the EC must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

As per the G-AppConductCT, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If prior consent from the participant or the legal representative/guardian cannot be obtained, participant enrollment should require measures described in the protocol and/or elsewhere. Tanzania Medicines and Medical Devices Authority (TMDA) approval should also be obtained in order to protect the participant’s rights, safety, and well-being and to ensure compliance with National Health Research Ethics Committee (NatHREC) and TMDA requirements. The participant or the legal representative/guardian should provide consent as soon as possible.

In addition, per the G-EthicsHR-TZA, an EC may approve a waiver of consent if the study participant presents in an emergency situation and informed consent cannot be reasonably obtained from the participant or the legal representative/guardian. During a public health emergency of national and international concern, some of the activities focusing on diseases or events threatening national and international health security are considered non-research and need immediate attention. Informed consent may not be required in non-research activities.

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), in all Kenyan clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include those participants with diminished autonomy whose decision to participate in a clinical trial may be unduly influenced by the expectation of benefits associated with participation or by coercion. This may include, but is not limited to, children/minors, pregnant women, neonates, fetuses, medical students, members of the uniformed forces, prisoners, orphans, homeless populations, unemployed, internally displaced persons, economically or educationally disadvantaged persons, marginalized social groups, individuals with terminal illnesses, and the mentally challenged. KEN-14 also includes 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 persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

Elderly Persons

The G-ECBiomedRes defines an elderly/senior citizen as a person who has attained the age of 65 years. Their physical or mental state may affect their ability to make voluntary decisions regarding their participation in research projects. Such research involving elderly/senior citizens must comply with the following requirements:

• Strict adherence to ethical principles
• The risk-benefit ratio must be favorable to the research participant
• The participants must be protected from gross violation of human rights

Persons in Dependent Groups

Per the G-ECBiomedRes, research involving data collection by superiors on their subordinates involves relationships such as employer-employee, teacher-students, supervisor-staff, sponsor-dependent, and parent-children. This relationship impairs independent consent by the participants leading to complacency. Therefore, research involving the superior/subordinate relationships must fulfill the following requirements:

• The superior must strictly follow ethical principles to avoid undue pressure
• Subordinates must be protected from gross violation of human rights
• The trial design must be based on a need-to-know principle and improve the conditions of the participants

Persons in Low-Resource Communities

The G-ECBiomedRes provides the following requirements related to conducting research on participants in low-resource settings:

• Persons in such settings should not be involved in research that could be carried out reasonably well in developed communities
• The research should be responsive to the health needs and priorities of the community in which it is to be implemented
• Undue inducement to participate in the research must be avoided at all costs

Armed Forces

The G-ECBiomedRes stipulates that research involving the members of the armed forces may be vulnerable because of the conditions of their service, which may affect their ability to make voluntary decisions regarding their participation in research. Such research must be conducted to ensure that:

• Participants are protected from gross violations of human rights
• There is strict adherence to ethical principles
• There is at least one (1) member of the ethics committee approving such research who is an enlisted and authoritative member of the armed forces

Terminally Ill

Per the G-ECBiomedRes, research involving participants who are terminally ill with an incurable medical condition are vulnerable. Their state may affect their ability to make voluntary decisions regarding their participation in research. Such research can only be conducted when:

• The objectives of the project(s) cannot be achieved using another non-vulnerable group
• There is strict adherence to ethical principles
• The risk-benefit ratio should be favorable to the research participant

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

Overview

As per the G-AppConductCT and the G-EthicsHR-TZA, in all Tanzanian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include those who are incapable of protecting their own interests due to a lack of autonomy, intelligence, education, resources, strength, or other necessary attributes, and have an increased likelihood of being wronged or of incurring additional harm during clinical trials. For example, the G-AppConductCT includes persons who are illiterate, marginalized by their social status or behavior, or living in an authoritarian environment. Vulnerable groups include individuals in hierarchical relationships, institutionalized persons, nomads, refugees or displaced persons, people living with disabilities, people with incurable or stigmatized conditions or diseases, and people faced with physical frailty. The G-EthicsHR-TZA additionally identifies children, mature and emancipated minors, street children, prisoners, the homeless, substance abusers, handicapped (mentally and physically), armed forces, and pregnant women. In some cases, willingness to volunteer to participate in research is unduly influenced by the expectation of benefits associated with their participation, or fear of retaliation from interested senior members of the hierarchy in case of refusal to participate. Characteristics that constitute vulnerability with reference to communities include one (1) or more of the following:

• Limited economic empowerment
• Inadequate protection of human rights
• Discrimination on the basis of health status
• Inadequate understanding of scientific research
• Limited availability of health care and treatment options
• Limited ability in the community to provide informed consent

As per the G-EthicsHR-TZA, clinical trials involving vulnerable persons require additional attention to ensure their protection. Where factors relating to vulnerability are an aspect of the research study, ethics committees (ECs) must ensure that researchers specify how that vulnerability would be addressed, particularly:

• Selection of the particular communities is justified by the research goals
• Research study is relevant to the needs and priorities of the community in which it is to be conducted
• Research study is beneficial to that community
• The community can access products of the research
• Where appropriate, feedback of results should be provided to the community
• Study participants must be fully aware that they are participating in the research and should provide informed consent
• Special attention should be paid to the content, language of the consent document, procedures for obtaining informed consent, monitoring of the process, and testing comprehension

TZA-5 requires the investigator to specify in the clinical trial application if a research protocol involves a vulnerable population or special group, provide adequate justification for their involvement, and provide information on how the participants’ rights and welfare will be safeguarded. Further, the investigator should include information about how they will assess the participants’ capacity to consent for themselves. If the participant is not able to consent, the researcher should include information about how consent will be obtained from the participant’s legal representative/guardian and how assent will be obtained from the participant (where appropriate).

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

Information on the specific vulnerable populations specified in the G-EthicsHR-TZA is provided below.

Persons Highly Dependent on Medical Care

Per the G-EthicsHR-TZA, persons highly dependent on medical care, such as those living with disabilities (physical or mental) or terminally ill patients, require special attention because they are prone to being socially marginalized. Therefore, their dignity, rights, and well-being in research must be respected. For persons living with disabilities, careful consideration should be made where proxy consent is used, and where the use of signed consent forms is not feasible, alternative viable methods should be employed. Persons living with disabilities should not be unfairly excluded from participating in research. Researchers should make efforts to address communication, disability, and comprehension constraints. (See Mentally Impaired section for requirements on persons with mental disabilities). For terminally ill patients, their dire state may affect their ability to make voluntary decisions regarding participation in research studies. A research protocol involving terminally ill patients as study participants must meet the following additional requirements: the research can only be conducted with terminally ill patients; if the research objectives of the study cannot be addressed using another non-vulnerable group; and the risk-benefit ratio should be favorable to the patients.

Elderly Persons

As per the G-EthicsHR-TZA, it is important to exercise special care when involving the elderly who have been in the hospital or in a residential home for a long time because they may be more dependent on others for their care. Independent, but caring observer(s) for the elderly must be fully informed about the study and be satisfied that the elderly participant understands the intended research activities prior to consent.

As per the G-AppConductCT, TZA-14 should be followed for clinical trials that involve:

• New investigational products that are likely to have significant use in the elderly
• New formulations and new combinations of established medicinal products when there is specific reason to expect that conditions common in the elderly are likely to be encountered and are not already dealt with in current labeling
• New formulation or new combination is likely to alter the geriatric patient’s response in a way different from previous formulations
• New uses that have significant potential applicability to the elderly

Students

The G-EthicsHR-TZA states that research studies involving students can be conducted as long as the following conditions are met:

• The tutor involved in the tuition of the student should not be involved in the recruitment and other negotiations on the terms and research conditions
• The informed consent should clearly state that the student may wish at any stage of the research study to withdraw without any undue consequences
• An impression should not be created that acceptance to participate in the study will benefit the student in the passing of their examinations
• An impression should not be created that non-acceptance will result in discrimination and consequences on the student’s studies
• There should not be any form of coercion, pressure, or financial inducement other than that proposed as reimbursements for participants

Homeless Persons

Per the G-EthicsHR-TZA, the category of homeless persons includes street children, adults staying on the street, refugees, and internally displaced persons. In conducting research with people who are homeless, researchers should be guided by the following principles:

• Research must be conducted with respect to the human rights, welfare, and dignity of study participants
• The research study must be conducted in a non-judgmental way regarding the person’s appearance, strategies for making money, or personal habits
• The right to privacy and security must be respected at all times for people who are homeless

Armed Forces

For research involving participants in the armed forces, the G-EthicsHR-TZA requires the following consent conditions:

• Any possible advantages accruing to participants through their participation in the research study (when compared to the general living conditions, medical care, quality of food, amenities, and opportunity for earnings) are not of such magnitude so that it might impair participants’ ability to weigh the risks of the study against the value of these advantages in the military environment
• The risks involved in the research study are commensurate with the risks that would be accepted by non-armed force volunteer participants
• Procedures for the selection of study participants from within the military are fair to all military personnel and insulated from arbitrary intervention by military authorities or by other members of the armed forces
• The information conveyed to the participants is presented in a language that is understandable to them
• There is adequate assurance that a participant’s participation or refusal to participate in the study will not be considered in decisions regarding their promotion, pay, or any other career opportunities

According to the G-KenyaCT, a minor is someone under 18 years of age. As set forth in the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), when the research participant is a minor, informed consent should be obtained from the parent/guardian. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. The informed consent forms, assent forms, and the patient information sheets should be in a language that the parent/guardian clearly understand. All pediatric participants should be fully informed about the trial and its risks and benefits in a language and terms that they are easily able to understand.

Per the G-KenyaCT, a minor should take part in the informed consent procedure in a way tailored to their age and mental maturity. If capable, the participant should sign and personally date the written informed consent. In addition, consent given by pediatric participants should not be considered valid without prior approval by the ethics committee (EC).

The CTRules, the G-ECBiomedRes, and the G-KenyaCT state that a study may only be conducted on minors if several conditions are fulfilled including (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Pediatric participants will not be involved in research that might be equally carried out in adults
• The purpose of the research is to generate knowledge relevant to the health needs of children
• The parent/guardian must provide proxy consent and ensure assent has been obtained to the extent of the child’s capabilities. However, if the minor refuses to participate after proxy consent is given, the minor’s refusal must be respected unless there is no other medical alternative from which the minor could benefit
• The risk presented by interventions not intended to benefit the minor is low and commensurate with the importance of the knowledge to be gained
• Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual child as any available alternative
• No incentives or financial inducements are given to the participant or parent/guardian except to provide compensation for expenses and loss of earnings directly related to the participation in the trial

Additionally, per the G-KenyaCT, the trial should also address the following considerations:

• Provide useful answers to the study population
• The medicine satisfies a need for the population being studied
• Children are adequately monitored and protected
• If there is no direct benefit to the child, or there is no more than minimal risk to the participant(s)
• Trial results will be published
• End-of-trial treatment provisions will be made

Assent Requirements

As delineated in the G-KenyaCT, before undertaking research involving children, the investigator must ensure that the agreement (assent) of each child has been obtained to the extent of the child’s capabilities, and a child’s refusal to participate or continue in the research must be respected. Assent is defined as a child’s affirmative agreement to participate in research, where the child is below the age of the majority but old enough to understand the proposed research in general, its expected risks and possible benefits, and the activities expected of them as participants. The G-ECBiomedRes provides that in children above seven (7) years and below 18 years where the parent(s)/guardian(s) gives proxy consent, assent must be obtained from the child.

For an example of an accredited EC’s assent requirements, see the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee’s sample minor assent form (KEN-17).

The ChildAct states that a person less than 18 years of age should be known as a child. As per the G-AppConductCT and the G-EthicsHR-TZA, when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian.

According to the G-EthicsHR-TZA, research involving greater than minimal risk, but presenting the prospect of direct benefit to a child, may be conducted only if:

• The risk is justified by the anticipated benefit to the child
• The relation of the anticipated benefit to the risk is at least as favorable to the research study participants (children) as that presented by available alternative approaches
• Adequate provisions have been made for the solicitation of the child’s assent and the informed consent of the child’s parent/legal guardian

Further, per the G-EthicsHR-TZA, research that involves greater than minimal risk and entails no prospect of direct benefit to the individual child participant, but is likely to yield generalizable knowledge about the child’s disorder or condition may not be conducted unless:

• The risk represents a minor increase over minimal risk
• The intervention or procedure presents experiences that are commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations
• The intervention or procedure is likely to yield generalizable knowledge about the child’s disorder or condition that is of vital importance for the understanding or amelioration of that disorder or condition
• Adequate provisions have been made for the solicitation of the child’s assent and their parents’/legal guardians’ informed consent
• When the child’s participation is indispensable and participation is not contrary to the child’s best interest

As delineated in the G-EthicsHR-TZA, mature minors are individuals 14 to 17 years of age who are able to demonstrate the ability and capacity to manage their own affairs and to live wholly or partially independent of their parent/legal guardian. This is someone who has not reached adulthood (as defined by country law) but who may be treated as an adult for certain purposes (e.g., consenting to medical care). Emancipated minors refer to persons who have not reached the age of majority (18 years) and are empowered by law to make autonomous decisions. They are free from control by their parent/legal guardian, and the parent/legal guardian is free from the responsibility for the child. Mature and emancipated minors may independently provide informed consent to participate in research if:

• In the ethics committee’s (EC’s) view, the research is not objectionable to parents/legal guardians in the community (established with evidence from the community)
• The research protocol includes clear justification for targeting mature and emancipated minors as participants, and a clear justification for not involving parents/legal guardians in the consent process

The G-AppConductCT delineates that data on the appropriate use of investigational products (IPs) in the pediatric population should be generated unless its use in pediatric patients is clearly inappropriate. The pediatric development program should not delay completion of adult studies and availability of IPs for adults. The decision to proceed with a pediatric development program for an IP and the nature of that program should follow the requirements in TZA-12.

Assent Requirements

The G-EthicsHR-TZA, states that the child’s assent takes precedence over the parent’s/legal guardian’s consent. For all research involving children, there must be no financial or other inducements to participate for the parent, guardian, or child, although reimbursements and a token for the child after completion of the study may be acceptable.

Per the G-EthicsHR-TZA, children and adolescents who are minors cannot give legally-valid informed consent, but they may be able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research study discussion in accordance with their capacities. Assent must be considered as a process and is not merely the absence of dissent. Furthermore, the researcher must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is particularly important to inform the child or adolescent and obtain assent as described above, preferably in writing for children who are literate. Specific protections to safeguard children and adolescents’ rights and welfare in the study are necessary. Before undertaking research studies involving children and adolescents, the researcher and the ECs must ensure that:

• A parent/legal guardian of the child or adolescent has given permission
• Assent of the child or adolescent has been obtained, after having been provided with adequate information about the study tailored to the child’s or adolescent’s level of maturity
• If children reach the legal age of maturity during the study period, their consent to continued participation should be obtained

Per the G-EthicsHR-TZA, children or adolescents are required to assent if they are between 10 and 17 years old and can read and write, as well as understand the description of the study. In general, the refusal of a child or adolescent to participate or continue in the study must be respected unless, in exceptional circumstances, where participation is considered the best medical option. For research interventions or procedures that have the potential to benefit children or adolescents, the risks must be minimized and outweighed by the prospect of potential individual benefit. For research interventions or procedures that have no potential individual benefits for children/adolescents, the interventions should be studied in adults first, unless the necessary data cannot be obtained without participation of children/adolescents and the risks are minimized.

Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

As per the G-ECBiomedRes, research involving pregnant, lactating, and breastfeeding women may pose compromised long-term outcomes for the child. In addition, potential parent(s) can make decisions on behalf of the fetus(es), embryo(s), and zygote(s).

For fetal, embryo, and zygote(s) cases, research should be limited as follows:

• Cases that present no harm or offer assistance to the life system of the participants
• No procedures should be permitted that are likely to harm them
• A fetus ex-utero and alive, embryo, and zygote must not be involved in research unless it is intended to enhance the life of that fetus, embryo, and zygote or unless the research involves no risk to them

Additionally, the following guidelines must be followed for research involving pregnant, lactating, and breastfeeding women:

• The research carries no more than minimal risk to the fetuses or nursing infants
• Pregnant or nursing women should generally not be clinical trial participants except where such trials are designed to protect or advance the health of the pregnant/nursing women or fetuses/nursing infants, and for which women who are not pregnant or nursing would not be suitable participants
• The justification for such research should be that participants must not be arbitrarily deprived of the opportunity to benefit from investigational drugs, vaccines, or other agents that promise therapeutic or preventive benefits

The G-AppConductCT recommends that women of child-bearing potential be included at the earliest possible stages of clinical trial research so that potential sex-related differences are identified and taken into consideration when planning Phase III trials. The timing of including women of childbearing potential or pregnant women in clinical trials should comply with guidance in the International Council for Harmonisation's Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (TZA-15). Any research involving pregnant women should be individualized and based on a careful risk/benefit assessment, considering:

• The nature and severity of the disease
• The availability and results of previous nonclinical and clinical data
• The availability of alternative therapy and knowledge about their risks
• The stage of pregnancy in relation to the overall development of the fetus, especially regarding fetal brain development
• The potential for harm to the woman, the fetus, or child
• The long-term follow up of the pregnancy, fetus, and child, when possible

Additional considerations for including pregnant women in clinical trials are provided in the G-AppConductCT.

The G-AppConductCT identifies the following considerations for deciding whether to include breastfeeding women in clinical trials:

• A new indication is being sought for an approved therapeutic product and there is evidence of use or anticipated use by breastfeeding women
• After market authorization, use of a therapeutic product in breastfeeding women becomes evident
• There is concern that the consequences of uninformed dosages for use while breastfeeding are potentially serious and/or severe
• A therapeutic product is under review for market authorization and is expected to be used by women of reproductive age
• The trial involves marketed medications that are commonly used by women of reproductive age
• The risk to the infant or mother is not greater than that from established procedures routinely used during breastfeeding, is comparable to those being studied, and the purpose of the research is the development of biomedical knowledge which cannot be obtained by any other means

As per the G-EthicsHR-TZA, research studies relating to pregnant women or fetuses may be undertaken under the following conditions:

• The risk to the fetus is minimal and is the least possible risk for achieving the objectives of the research study, except where the purpose of the research study is to meet the health needs of the mother and the fetus, and the foreseeable benefits outweigh the potential risks
• No procedural changes that could cause greater than minimal risk to the fetus or to the pregnant woman may be introduced into the procedure for termination of the pregnancy
• No inducements, whether financial or any other form, may be offered to terminate the pregnancy for the purposes of the research study
• Appropriate studies on animals and non-pregnant individuals have been completed
• The purpose of the proposed research is to meet the health needs of the mother and the fetus will be placed at risk to the minimum extent necessary to meet these needs or the risk to the fetus is minimal
• The mother and the father are both legally competent and have been fully informed of the possible impact on the fetus and have given their informed consent to proceed; however, the father’s consent is not required if the purpose of the research is primarily to meet the health needs of the mother, the father’s identity and/or whereabouts are unknown, the father is not available, or the pregnancy resulted from rape or incest

Per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. A research study involving prisoners should ensure that these prospective participants are informed and given the opportunity to make their own decisions without any interference or reprisals from a higher authority. The ethics committee must also ensure that the study will be independently monitored to assure the dignity and rights of the prisoners involved in the research.

According to the G-EthicsHR-TZA, prisoners are vulnerable to abuse by research because their freedom for consent can easily be undermined, which could affect their ability to make a voluntary decision regarding their participation in research. Research involving prisoners may not be approved unless the proposed research has the intent and a reasonable probability of improving the health and well-being of the study participants, and appropriate knowledgeable persons in penology, medicine, and ethics have been consulted in the course of reviewing the research protocol. Further, research with prisoners can be conducted only if:

• The research offers a distinctly favorable benefit to risk ratio, not because the prisoners are a convenient source of participants
• The research improves the well-being of prisoners while taking great care to protect their health, well-being, and human rights
• The ethics committee (EC) reviews and verifies that the criteria for permissible research are satisfied
• EC members have no association with the prison(s) involved other than their status as members of the EC reviewing the proposed research study
• Where possible, a prisoner or an ex-prisoner should be co-opted to the EC in reviewing the proposed research study
• The risks involved in the research study are commensurate with risks that will be accepted by non-prisoner volunteers
• The procedure for selecting participants in the prison are fair to all prisoners
• There is adequate assurance that a prisoner’s participation or refusal to participate will not be considered in decisions regarding their release or further detention and each prisoner is clearly informed in advance that participation in the research study will have no effect on their release
• Any possible advantages accruing to the prisoner through participation in the research study, when compared to the general living conditions, medical care, quality of food, amenities, and opportunity for earnings in the prison, are not of such magnitude that the prisoner’s ability to weigh the risks of the research against the value of these advantages in the prison environment is impaired

As per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), an ethics committee (EC) within the relevant institution must approve the participation of adult research participants who are incapable by reason of physical and mental capacity to give consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, as delineated in the G-ECBiomedRes, a research study may involve participants with mental incapacities or behavioral disorders under the following conditions:

• Such research could not be carried out equally well with individuals who are in possession of their full mental faculties
• The knowledge gained would be relevant to the health needs of persons with mental or behavioral disorders
• The participant’s consent has been obtained to the extent of the participant’s capabilities, and a prospective participant’s refusal to participate is always respected
• In the case of incompetent individuals, informed consent shall be obtained from a legal guardian or other duly authorized person
• The degree of risk attached to the intervention not intended to benefit the individual participant is low and commensurate with the importance of knowledge to be gained
• Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual participant as any alternative

As indicated in the G-EthicsHR-TZA, persons living with mental disabilities require special attention because they are prone to being socially marginalized, and therefore, their dignity, rights, and well-being in research must be respected. Careful consideration should be made where proxy consent is used. Where the use of signed consent forms is not feasible, alternative viable methods should be employed. Persons living with disabilities should not be unfairly excluded from participating in research. Researchers should make efforts to address communication, disability, and comprehension constraints. Persons with mental health conditions including psychiatric, cognitive, or developmental conditions, and substance abuse related disorders at times may be hospitalized or institutionalized, which may further compromise their ability to make voluntary decisions to participate in a research project. Research must not be conducted if the purpose of the research is not relevant to the particular health needs of persons living with disabilities, or alternative interventions exist that are at least as advantageous to the individual participant as that under the proposed study. Further, the following should be scrutinized:

• There is sufficient justification for inclusion
• There are appropriate evaluation procedures for ascertaining study participants’ ability to give informed consent; if such study participants are deemed unable to understand and to make an informed decision, then an appropriate proxy should be identified
• An informed consent process that is free from coercion
• Be of no more than minimal risk; if minimal risk is involved, the risk is outweighed by the anticipated benefits of the research study to the participants

The G-EthicsHR-TZA outlines the requirements to safeguard the rights and welfare of adults who are incapable of giving informed consent in research studies. Before undertaking research with adults who are not capable of giving informed consent, the researcher and the EC must ensure that:

• A legal representative of the person who is incapable of giving informed consent has given permission and this permission takes account of the participant’s previously formed preferences and values (if any)
• The assent of the participant has been obtained to the extent of that person’s capacity, after having been provided with adequate information about the study at the level of the participant’s capacity for understanding this information
• If participants become capable of giving informed consent during the study, their consent to continued participation must be obtained; in general, a potential participant’s refusal to enroll in the study must be respected, unless in exceptional circumstances where study participation is considered the best available medical option for an individual who is incapable of giving informed consent

The G-KenyaCT defines an investigational product (IP) as any pharmaceutical product, including a new product or existing product for a new indication, in the 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 (formulated or packaged) 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.

As delineated in the G-AppConductCT, an investigational medicinal product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. Further, per the G-EthicsHR-TZA, an IP refers to a preventative (vaccine), therapeutic (drug or biologic), device, diagnostic, or palliative used in a clinical trial. The G-AppConductCT and the G-EthicsHR-TZA state that an IP includes:

• A product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form
• When used for an unapproved indication
• When used to gain further information about an approved use

Manufacturing

According to the PPA and the G-KenyaCT, the Pharmacy and Poisons Board (PPB) is responsible for authorizing the manufacture of all drug products, including investigational products (IPs) in Kenya. Per the CTRules and the G-KenyaCT, an IP must be manufactured in accordance with the requirements of good manufacturing practice (GMP). The CTRules requires a sponsor to immediately notify the PPB in writing when a pharmaceutical or chemical alteration may affect the quality, safety, or efficacy of the IP product during an ongoing clinical trial. The G-KenyaCT states that the sponsor must submit the IP dossier directly to the PPB or may submit it through the principal investigator. The IP dossier must be prepared as per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), which is required per G-KenyaCT. The manufacture of IPs may be subject to GMP inspection by the PPB in the same way as in the case of marketed drug products. See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB.

KEN-14 also requires IPs to be manufactured, handled, and stored in accordance with applicable GMPs and used in accordance with the approved protocol.

Per the PPA, the PPB is authorized to regulate the manufacturing of medicine, including:

• Ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy
• Ensure that the personnel, premises, and practices employed in the manufacture, storage, marketing, distribution, and sale of medicinal substances comply with the defined codes of practice and other prescribed requirements
• Grant or revoke licenses for the manufacture, importation, exportation, distribution, and sale of medicinal substances
• Inspect and license all manufacturing premises, importing and exporting agents, wholesalers, distributors, pharmacies (including those in hospitals and clinics), and other retail outlets

See the KenyaGMP, for PPB’s compilation of recommended World Health Organization GMP guidelines to help comply with GMP requirements and prepare for an inspection, including for manufacture of IPs.

Import

Per the PPA and the ImpExp, the PPB is authorized to regulate the import and export of health products and technologies, including IPs. As per the ImpExp and the G-KenyaCT, to obtain an import permit for a clinical trial, the sponsor or investigator must submit an application online to the Kenya Trade Network Agency’s Kenya TradeNet Single Window System (KEN-28). The following documents must be submitted (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• The proforma invoice or invoice
• The ethics committee favorable opinion letter
• The Expert Committee on Clinical Trials approval letter from the PPB
• Registration of the institution where the research is being undertaken

The G-KenyaCT states that the sponsor must submit to the PPB a copy of the endorsed clinical trial import permit and/or evidence of delivery to the approved investigator(s)/trial center(s) on importation and supply of each consignment of the product. The product must only be supplied to the investigator(s) at the trial site(s) named in the clinical trial import license application for the purpose and use as stated in the said application. Prior PPB notification and approval is required for changes in the investigator, trial site, or protocol. The sponsor must inform PPB of any change in information, or any information received that casts doubt on the continued validity of the data, which was submitted with, or in connection with the application for the import permit. The sponsor must also inform the PPB of any decision to discontinue the trial to which the permit relates and state the reason for the decision. See KEN-8 for additional details on the procedures for obtaining an import license.

Per the CTRules, the import of an IP must comply with the applicable regulatory requirements to ensure integrity and accountability of the products. The PPB may revoke or suspend an import permit if the IP was manufactured in conditions not consistent with GMP; if the clinical trial was discontinued; or if the sponsor provided false information.

Please note: Kenya is party to the Nagoya Protocol on Access and Benefit-sharing (KEN-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see KEN-15.

Manufacturing

According to the TMMDAct, the CT-Regs, and the G-AppConductCT, the Tanzania Medicines and Medical Devices Authority (TMDA) is responsible for authorizing the manufacture of investigational products (IPs) in Tanzania. The TMDA will approve the manufacture of an IP after the clinical trial application has been approved via the Regulatory Information Management System (RIMS) Customer Self Service Portal (TZA-34). Regarding inspection frequency, the GMP-Insp and TZA-19 state that a domestic manufacturing facility must be inspected once a year to renew its annual business permit. The GMP-Insp also states that a manufacturing facility must be inspected once every three (3) years. However, a facility may be inspected at any time when necessary. See the G-AppConductCT for details on the quality requirements for manufacturing IPs.

Per the GMP-Insp, domestic and foreign manufacturing facilities of human medicinal products must comply with the good manufacturing practice (GMP) in the latest versions of the World Health Organization (WHO)’s Technical Report Series (WHO-TRS). In addition, other guidelines—such as those by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Pharmaceutical Inspection Co-operation Scheme—may be used as supplementary guidance when establishing compliance of facilities to GMP requirements. See the GMP-Insp for additional details and information on the inspection of manufacturing facilities of human medicinal products.

Import

Per the TMMDAct, the CT-Regs, the TFDCA-ImptExpt, the G-AppConductCT, and the G-ImpExp, the TMDA is also responsible for authorizing the import of IPs. As per the TMMDAct, the TFDCA-ImptExpt, and the G-ImpExp, the sponsor or the principal investigator (PI) may apply for an import license once the clinical trial application has been approved by the TMDA. The TFDCA-ImptExpt specifies that in order to be granted an import license, the applicant must:

• Have a pharmacist registered by the Pharmacy Council who must be a Superintendent of the business
• Have premises registered by the TMDA
• Hold a valid business permit

The G-ImpExp states that importation of pharmaceutical products and raw materials must be done by importers whose premises are registered by the TMDA or the relevant government institutions. All importers should import pharmaceutical products and raw materials through authorized ports of entry. A person must not import any pharmaceutical product with a shelf life of more than 24 months whose remaining shelf life is less than 60%, or a pharmaceutical product with a shelf life of less than or equal to 24 months whose remaining shelf life is less than 80%.

The TFDCA-ImptExpt specifies that the import license application should be accompanied by the clinical trial approval letter issued by the TMDA. The applicant must fill out the Application for Importation of Pharmaceutical Products provided in the First Schedule of the TFDCA-ImptExpt and pay the fee pursuant to the TMMDAFees. In addition, the application should be accompanied by three (3) copies of the proforma invoice numbered, dated, and signed by the superintendent of the business. (A proforma invoice is an abridged or estimated invoice sent in advance of a shipment or delivery of goods.) The proforma invoice should include the following:

• Name and address of the supplier
• Name and address of the manufacturer of each product
• Trade or proprietary name of each product
• The international nonproprietary name (generic name) of the drug and its strength
• In the case of the product containing more than one (1) active ingredient, the name and strength of each product
• The pharmacopoeia specification of the ingredient of each product
• Product registration number issued by the authority for each product
• The quantity, pack size, unit value, and total value in convertible currency
• Batch or lot number where applicable for each product
• Manufacturing and expiration date, where applicable, for each product
• Mode of shipment (sea, air, or road)
• Authorized port of entry
• Signature and stamp of the supplier

Per TZA-34, the import license application can be submitted to the TMDA via TZA-34, which can be accessed by first creating a trader account. An online access registration form is available in Annex I of the G-ImpExp.

As delineated in the TFDCA-ImptExpt and the G-ImpExp, the import permit is valid for six (6) months, not transferable, and issued to cover only one (1) shipment. Per the G-ImpExp, in the case of partial shipments, two (2) shipments may be allowed based on the initial import permit. See the TFDCA-ImptExpt and the G-ImpExp for detailed import application requirements.

The TFDCA-ImptExpt and the G-ImpExp identify the authorized ports of entry for pharmaceutical products imported into Tanzania. The TFDCA-ImptExpt states that an importer must provide all necessary documents as may, from time to time, be requested by the inspector. When it is deemed necessary to collect samples or where the inspector suspects that any product may contravene any regulation or law, the inspector may take samples for further investigation.

Investigator’s Brochure

In accordance with the CTRules and the G-KenyaCT, the sponsor must provide an up-to-date investigator’s brochure (IB). An updated IB and Drug Safety Update Report (DSUR) must be submitted whenever available but at least once year as a notification to the Pharmacy and Poisons Board (PPB) or when there are substantial changes to the previous version.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As specified in the G-KenyaCT and KEN-14, the IB must provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties
• The pharmacological aspects including its metabolites in all animal species tested
• The pharmacokinetics and metabolism including its biological transformation in all animal species tested
• Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
• Results of clinical pharmacokinetic studies
• Information regarding safety, pharmacodynamics, efficacy, and dose responses that were obtained from previous clinical trials in humans

The G-KenyaCT indicates that the sponsor must also follow the guidance contained in KEN-14.

Quality Management

In accordance with the G-KenyaCT, a good manufacturing practice (GMP) certificate must be provided by a competent authority from the country of manufacture to the PPB in the clinical trial application. At a minimum, the GMP certificate should include the competent authority’s name and contact details, address of the manufacturing site, date of inspection, and validity period. Certificates of Analysis (CoAs) must also be provided to the PPB for all investigational products (IPs) and comparator products. Per KEN-14, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB. In addition, see Cert-Emrgcy for information about good clinical practice (GCP) and GMP certifications during emergencies.

(See Product Management section for additional information on sponsor requirements).

Investigator’s Brochure

In accordance with the CT-Regs and the G-AppConductCT, the Tanzanian government follows the International Council for Harmonisation's (ICH) Guideline for Good Clinical Practice E6(R2) (TZA-13), and requires the sponsor or the designated contract research organization (CRO) to provide investigators with an Investigator’s Brochure (IB). The G-AppConductCT states that the IB should be presented in a concise, simple, objective, balanced, and non-promotional form that enables a clinician, or potential investigator, to understand it and make an unbiased risk-benefit assessment of the appropriateness of the proposed trial. The contents of the IB should be approved by the disciplines that generated the described data and a medically qualified person should generally participate in the editing of an IB. If the investigational product (IP) is locally marketed and its pharmacology is well established and widely understood by medical practitioners, an extensive IB may not be necessary, and a current summary of product characteristics may be submitted as an alternative. If a marketed product is being studied for a new use (i.e., a new indication), an IB specific to that new use should be prepared. The IB should be reviewed at least annually and revised as necessary in compliance with a sponsor’s written procedures. More frequent revision may be appropriate depending on the stage of development and the generation of relevant new information.

TZA-13 specifies that the IB must contain all of the relevant information on the IP(s) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. Per the CT-Regs, the sponsor should also update the IB as significant new information becomes available and maintain records of each change.

TZA-13 requires the IB to provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties and formulation parameters
• Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
• Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post-marketing experiences)
• Summary of data and guidance for the investigator(s)
• Bibliography

See Section 7.3 of TZA-13 for detailed content guidelines.

Quality Management

Per the G-AppConductCT, the sponsor must document details regarding the chemistry, manufacturing, and control of the IP as prescribed in Module 3. This should include data to demonstrate the quality of the IP, including relevant batch analyses results. If a comparator medicinal product is used, the proprietary name of the medicinal product, non-proprietary or common name of the active pharmaceutical ingredient, company name, country from which the clinical supplies were obtained (as well as the market status in that country), dosage form(s), and strength(s) should be listed. Batch analysis results for the active pharmaceutical ingredient may be provided in either the quality summary or by providing a copy of the certificate of analysis. The certificate of good manufacturing practice should also be included in the clinical trial application.

As delineated in the GMP-Insp, domestic and foreign manufacturing facilities of human medicinal products must comply with good manufacturing practice (GMP) in the latest versions of the World Health Organization’s Technical Report Series (WHO-TRS). In addition, other guidelines—such as those by the ICH and Pharmaceutical Inspection Co-operation Scheme—may be used as supplementary guidance when establishing compliance of facilities to GMP requirements. The manufacturing facilities are subject to inspection by the Tanzania Medicines and Medical Devices Authority (TMDA). The GMP-Insp describes the types of inspections, inspection fees, and other procedures. If the TMDA finds noncompliance, the manufacturer must prepare and implement a Corrective Action and Preventive Action plan (CAPA). The CAPA plan must be prepared based on quality risk management principles and submitted to the TMDA. The CAPA report must indicate root cause analysis, corrections, corrective actions and preventive actions, timelines, and evidence of implementation for each non-compliance observation. Manufacturers must be allowed a maximum of two (2) rounds to submit CAPA responses. The first CAPA response must be submitted within 90 calendar days of the TMDA’s inspection report cover letter. If the assessment of the first CAPA response is deemed to be non-satisfactory, the manufacturer will have an opportunity to submit a second CAPA response within 60 calendar days. If the assessment of the second CAPA response is still non-satisfactory, the facility must be re-inspected. If the company fails to submit CAPA report within the prescribed period without any request for extension, the facility is deemed non-compliant.

Per the G-KenyaCT, investigational products (IPs) used in Kenyan clinical trials must be properly labelled. A final copy/version of the labelling must be submitted to the Pharmacy and Poisons Board (PPB) for approval and should contain the following minimum information:

• Statement indicating that the product is for “clinical trial purpose only”
• Recommended storage conditions
• Protocol code or identification
• Name, address, and telephone number of the sponsor, contract research organization, or investigator (the main contact for information on the product, clinical trial, and emergency unblinding)
• Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
• The batch and/or code number to identify the contents and packaging operation
• A trial reference code allowing identification of the trial, site, investigator, and sponsor, if not given elsewhere
• The trial participant identification number/treatment number and, where relevant, the visit number
• The name of the investigator (if not included above)
• Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
• Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
• The complete physical address of the manufacturing site

As indicated in the G-KenyaCT, it is recommended that an IP is not re-labeled wherever possible. It is, however, accepted that in certain cases it is necessary to re-label and the PPB will review applications for the extension of expiration dates based on sufficient evidence being provided by the applicant that an extended expiration date is warranted. A written justification and evidence should be provided to the PPB. Any re-labelling of remaining IPs from previously manufactured batches must be performed in accordance with good manufacturing practice (GMP) principles and is limited to an extension of the expiration date where sufficient evidence is available to support such extension. Any request for re-labelling should be accompanied by a certificate of analysis of the product from a PPB-recognized laboratory or World Health Organization (WHO) prequalified laboratories (KEN-18). After approval, the re-labelling must be carried out under the supervision of a pharmaceutical inspector on the ground. In case of use-date extension, an additional label should be affixed to the IP to indicate the new use date and repeat the batch number. It may be superposed on the old use date, but not on the original batch number. PPB will not approve re-labelling of a product if the proposed additional label obscures the original labelling. At all times, the original label should be visible. This operation may be performed onsite by the clinical trial monitor(s) or the clinical trial site pharmacist, in accordance with specific and standard operating procedures. The operation should be checked by a second person. Documented evidence of this additional labelling should be available in the trial documentation and in the batch records. KEN-34 indicates that all documents submitted to the PPB in a clinical trial application should be in English, including a pictorial sample of the IP with the labeling text.

The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), which the G-KenyaCT requires following, states that the IP must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Investigational product (IP) labeling in Tanzania must comply with the requirements set forth in the CT-Regs, the TFDCA-ImptExpt, and the G-ImpExp. The TFDCA-ImptExpt and the CT-Regs state that for an IP to be used in a clinical trial, it must be properly labeled in English or Kiswahili (also known as Swahili) language or both, and the information printed on the labels must be indelible, engraved, or embossed on a primary and secondary container.

As set forth in the CT-Regs, the TFDCA-ImptExpt, and the G-ImpExp, the following information must be included on the label (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Statement indicating that the product is for “clinical trial purpose only”

• Name, number, or identifying mark

• Recommended storage conditions

• Sponsor name and address

• Protocol code or identification

• Trade or brand name where appropriate

• International Non-Proprietary Name (INN, Generic name)

• Active ingredient quantities listed in the formulation

• Manufacture and expiration dates

• Batch or lot number

• Storage conditions

• Manufacturer name and address

• Product registration number issued by the Tanzania Medicines and Medical Devices Authority (TMDA) included in the outer and inner packaging, where applicable

• Immediate outer packaging and the enclosed and accompanying literature must be in English or Kiswahili

• Active pharmaceutical ingredient specification (BP, USP, etc.)

According to the CT-Regs, where applicable, investigational medicinal products must be labeled in a manner that protects the blinding. Also, re-labelling of any remaining investigational medicinal product from previously manufactured batches must be performed in accordance with established written procedures and good manufacturing practice principles.

Per the G-EthicsHR-TZA, the sponsor is responsible for proper labelling of the IP(s). The investigational and comparator products must be labelled in conformity with the research protocol and the labelling must state that the product is for investigational purposes only.

Supply, Storage, and Handling Requirements

Per the PPA, the Pharmacy and Poisons Board (PPB) is responsible for the regulation of investigational products (IPs), including all matters relating to the safety, packaging, and distribution of medicines. The PPB must ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy. Further, the PPB must ensure that the personnel, premises, and practices employed in the manufacture and storage of IPs complies with prescribed requirements.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As defined in the G-KenyaCT and KEN-14, the sponsor must ensure the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Timely delivery of IPs to the investigator(s)
• Records that document shipment, receipt, disposition, return, and destruction of the IPs are maintained
• A system for retrieving IPs and documenting that this retrieval is maintained
• A system for the disposition of unused IPs is maintained
• Steps taken to ensure that the IPs are stable over the period of use
• Sufficient quantities of the IPs used in the trials are maintained

To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.

As defined in the G-KenyaCT and KEN-14, the sponsor must also supply the investigator(s)/institution(s) with the IPs, including the comparator(s) and placebo, if applicable. The sponsor or the representative should not supply either party with the IP(s) until approval from the PPB and a favorable opinion letter from the local and national ethics committees (ECs) are obtained. In addition, the G-KenyaCT requires the following supply, storage, and handling processes:

• Analysis or evaluation of samples is performed in accordance with the protocol and, where applicable, the contract/agreement, the work instruction, and associated methods
• Adherence to the laboratories, policies, and standard operating procedures (SOPs)
• Prior to the initiation of sample analysis or evaluation, it is often necessary to prepare a work instruction detailing the procedures, which will be used to conduct the analysis or evaluation
• Have automated equipment for routine hematology, biochemistry, and serology tests
• Have procedures for analyzer calibration and quality control
• Regularly maintain all the equipment, including point-of-care equipment
• Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
• Have written procedures for all assays, and validate the assays
• Have a stock control procedure to make sure that reagents and consumables are used within their expiry dates
• Keep records, including source documents and final reports
• Have a laboratory information management system, and validate and backup the system
• Provide protective clothing and safety equipment for staff
• Have a central alarm system for all fridges and freezers
• Have an internal audit program