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

In Uganda, the National Drug Authority (NDA) and the Uganda National Council for Science and Technology (UNCST), in collaboration with the Uganda National Health Research Organisation (UNHRO), are involved in clinical trial oversight.

National Drug Authority

As per the NDPA-CTReg, the G-CTConduct, and the G-TrialsGCP, the NDA is the regulatory authority responsible for clinical trial approval and inspections in Uganda. The NDA grants permission for clinical trials to be conducted in Uganda in accordance with the provisions of the NDPA-Act.

As stated in the NGHRP, the NDA regulates safety, quality, efficacy, handling, and use of drugs or drug related products and devices in research. According to UGA-29, the Clinical Trials Unit in the NDA’s Directorate of Product Safety is responsible for reviewing and approving clinical trial applications, conducting clinical trial site inspections for compliance with good clinical practices, and developing guidance documents.

Uganda National Council for Science and Technology

As delineated in the NDPA-CTReg, the NGHRP, and the G-CTConduct, in addition to obtaining the NDA’s permission to conduct research in Uganda, an applicant must obtain approval in the form of a research permit from the UNCST, or from an institution authorized by the UNCST.

As per UGA-30, the UNCST was established by the UNCST-Act as a semi-autonomous government agency under the Ministry of Science, Technology, and Innovation. The mandate of the UNCST is to develop and implement policies and strategies for integrating science and technology into national development policies; to advise the government of Uganda on policy matters necessary for promoting science and technology; and coordinate and guide national research and development in Uganda.

As per the NGHRP, the UNCST registers and, in liaison with the Research Secretariat in the Office of the President of Uganda, clears all research intended to be carried out in the country.

The G-CTConduct and the G-UNCSTreg also state that applicants must register their research proposals, obtain approval, and be issued a research permit from the UNCST prior to initiating a study.

Uganda National Health Research Organisation

The UNHRO-Act authorizes the UNHRO to register and renew research protocols, and to implement and enforce an ethical code of conduct for health research in Uganda. The UNHRO, in collaboration with the UNCST, conducts a scientific and ethical review of all health research protocols for approval. According to the NGHRP, the UNHRO also collaborates with the UNCST to register all health research protocols centrally at the UNCST. No additional information regarding UNHRO’s role is available.

Other Considerations

Please note: Uganda is party to the Nagoya Protocol on Access and Benefit-sharing (UGA-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 UGA-21.

Contact Information

National Drug Authority

According to UGA-23 and UGA-10, the NDA’s contact information is as follows:

National Drug Authority
Head Office
Plot 93, Buganda Road, after St. Catherine Hospital
P.O. Box 23096
Kampala, Uganda

Reception Phone: +256 [0]417 788 100
Directorate of Product Safety Phone: +256 [0]417 788 124
Directorate of Inspectorate Services Phone: +256 [0]417 788 129
WhatsApp: +256 74002080
Innovation & Research Desk: [0]800 101 999 (Toll Free Line), 0791 415555 (WhatsApp)
Email: ndaug@nda.or.ug

Uganda National Council for Science and Technology

As per the G-UNCSTreg and UGA-25, the UNCST’s contact information is as follows:

Uganda National Council for Science and Technology
Plot 6, Kimera Road, Ntinda
P.O. Box 6884
Kampala, Uganda
Phone: +256 414 705500
Fax: +256 414 234579
Email: info@uncst.go.ug

Uganda National Health Research Organisation

Per UGA-42, the UNHRO’s contact information is as follows:

Uganda National Health Research Organisation
Plot 2, Berkeley Lane, Entebbe
P.O. Box 465
Entebbe, Uganda

Tel/Fax: +256 414 321766
Email: unhrodesk4@gmail.com

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

In accordance with the NDPA-CTReg, the G-CTConduct, and the G-TrialsGCP, the National Drug Authority (NDA) is responsible for reviewing, evaluating, and approving clinical trial applications for registered or unregistered medicines in Uganda. The scope of the NDA’s assessment includes all clinical trials (Phases I-IV).

Per the NDPA-CTReg, the NDA’s review and approval of a clinical trial application are dependent upon the applicant submitting proof in the application of institutional level ethics committee (EC) (research ethics committee (REC) in Uganda) approval and a research permit from the Uganda National Council for Science and Technology (UNCST). However, the G-TrialsGCP indicates that parallel submissions may be made to the NDA and the UNCST. In that instance, the NDA would not make a final decision until after the trial receives ethical clearance. NDA approval will be dependent on receipt of the protocol’s approval by the institutional EC in consultations with the UNCST.

Clinical Trial Review Process

National Drug Authority

The NDPA-CTReg, the G-TrialsGCP, and the G-CTConduct indicate that upon receipt of a clinical trial application, the NDA initially screens the application for completeness. If the NDA is not satisfied with the information provided, the applicant will be advised in writing to provide further information or clarification. According to the G-CTConduct, the applicant must submit their responses in writing or in any other format as advised by the NDA, and in the timeframe determined by the NDA. NDA reviews are performed following a first-in first-out principle, except for clinical trials that are to be conducted in public health emergencies such as disease outbreaks, which may be exempted.

The NDPA-CTReg indicates that in considering an application for a clinical trial, the NDA must take into account the following:

• Relevance of the clinical trial
• Suitability of the principal investigator (PI)
• Quality of the facilities to be used for the clinical trial
• Adequacy and completeness of the information and procedures to obtain consent of the clinical trial participants
• Provision for indemnity for the PI and insurance for the clinical trial participants
• Terms of the agreement between the sponsor and the PI

Per the G-CTConduct, complete applications are given a Clinical Trial Application code. Applications verified as complete will undergo one (1) of three (3) types of reviews:

• Internal review, which is further subdivided into expedited or routine review
• Expert review, which involves external reviewers co-opted by the NDA following internal procedures
• Joint reviews, which are carried out jointly with other regulatory bodies including the UNCST, Uganda National Health Research Organisation (UNHRO), and the primary EC. These reviews will be coordinated by the UNCST

As stated in the G-CTConduct and the NDPA-CTReg, fast track review/authorization of an application is applicable for the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Clinical trial applications for investigational drugs to provide treatment where no therapy exists (decision will be given to the applicant within 30 working days)
• Clinical trials conducted in an emergency, such as during a disease outbreak (eligible for fast track review with a timeline of 15 working days)
• Clinical trial applications that do not explicitly meet either above criterion, but are led by the Ministry of Health in the interest of a public health intervention
• Any other circumstance that the NDA may determine

According to the G-CTConduct, the NDA may decide to a) authorize the clinical trial and issue a clinical trial certificate; b) request additional information to support the application; or c) reject the clinical trial application, providing reasoning. The NDA’s decision is communicated to the applicant in writing. The clinical trial certificate is valid for one (1) year from the date it is awarded. Per the NDPA-CTReg, the NDA may also issue a clinical trial certificate with conditions. See Appendix XI of the G-CTConduct for the NDA clinical trial process flowchart and Form 34 in Schedule 1 of the NDPA-CTReg for the format of the clinical trial certificate.

See the Submission Content section for detailed information on the contents of the clinical trial application.

The G-CTConduct states that any new information that becomes available regarding the product, such as new adverse effects or changes in formulation or the manufacturer, must be submitted to the NDA as soon as possible. Unless otherwise stated, additional information that is submitted prior to issuance of a clinical trial certificate will be considered as part of the submission and reviewed accordingly. The NDA may request supplementary information or documentation when appropriate, which should be submitted within the stated timeline, usually four (4) weeks. The NDA secretariat may grant additional time to provide information upon request by the applicant on a case-by-case basis. If the requested information is not submitted, the application will be archived within 50 working days. The application will need to be resubmitted for review.

Per the G-CTConduct, annual renewal of authorization to conduct the clinical trial is required for the trial prior to expiration of the validity. For studies that have completed follow-up for the last participant where there is no product or human participant, oversight will be deferred to the primary EC and the UNCST.

The NDPA-CTReg and the G-CTConduct indicate that the NDA may, on its own initiative, make amendments to the conditions for conducting a clinical trial where it is necessary for the safety or scientific validity of the clinical trial. The NDA will give 15 days’ notice of the intended amendment to the sponsor and the PI with reasons for the amendment and request a written response to the proposed amendments prior to effecting the amendments. As stated in the NDPA-CTReg, the NDA will, in making amendments to the conditions of conducting a clinical trial, take into consideration the response of the sponsor or PI.

The NDPA-CTReg indicates that a sponsor who intends to amend any condition of the clinical trial specified in the clinical trial certificate, or who intends to add investigators, add clinical trial sites, or change investigators, must make an application to the NDA for authorization of the amendment. The amendment applications will be considered using the procedure and requirements for an application for authorization to conduct a clinical trial.

The G-CTConduct specifies that the application to amend the conditions of a clinical trial will be screened for completeness and will essentially be complete in the first instance if it includes all the required documents, appendices, and finished checklist. Applications which are incomplete will not be evaluated, and a letter documenting the deficiencies in the application will be issued to the applicant. The NDA may request supplementary data or documentation where applicable. The NDA will consider the favorable opinion of the EC(s), the UNCST, and other relevant information, and may request that the applicant to submit an interim clinical trial study report to support the decision. Additionally, the NDA may take other regulatory action such as an inspection of the clinical trial site or investigational product (IP) manufacturing facility for regulatory and protocol compliance prior to making a decision. The NDA may approve or reject the application and specify the reasons for rejection. The decision will be communicated to the applicant in writing. Changes made to the informed consent forms will be acknowledged electronically unless they are directly related to the safety of the IP. Additionally, the NDA must be notified within 90 days about delays in trial initiation once a clinical trial has been approved and a clinical trial certificate issued.

See the G-CTConduct for detailed NDA amendment review procedures and Appendix IV of the G-CTConduct for the Categorization of Amendments.

As per the G-CTConduct, the NDA may at any reasonable time conduct inspections of the trial site prior to or after issuance of a clinical trial certificate. The purpose of the inspections is to assess the staff and facilities to be used or that are being used for the conduct of the clinical trial, and to verify the availability of the necessary resources and feasibility of conducting the study at the proposed site(s). These inspections will assess the compliance of the trial conduct with the conditions of the certificate. The NDA secretariat may contact the PI or sponsor notifying them of the date(s) of inspection. The secretariat will conduct inspections routinely, or as a result of a trigger. In addition, the inspections may be done jointly with the UNCST and/or the EC.

As indicated in the G-TrialsGCP, an inspection by the NDA may involve a comparison of the practices and procedures of the clinical trial with the commitments made in the application to conduct the trial; a comparison of the data submitted to the sponsor and the NDA with the source data; and a system inspection of the sponsor, clinical laboratory, or contract research organization generating data for submission to regulatory authorities. For more information on NDA inspections, see the G-TrialsGCP.

The NDPA-CTReg states that the NDA may, by notice, suspend or terminate a clinical trial where the conditions of a clinical trial certificate are not complied with or the NDA has information regarding the safety or scientific validity of the clinical trial or the conduct of the clinical trial. The NDA notice, which must be delivered to the sponsor or PI, will apply to the clinical trial generally or to one (1) or more of the clinical trial sites. Where a notice is for the suspension of the clinical trial, the suspension must be for the period specified in the notice. The notice must indicate, where applicable, the conditions to be fulfilled before the clinical trial or, as applicable, the conduct of the clinical trial at a particular site, may resume. Before issuing a notice, the NDA must inform the sponsor or PI of the notice and the reasons for the notice, and then advise the sponsor or PI to make a written representation on the intended suspension or termination within five (5) days. The NDA must consider the written representation and inform the sponsor or PI of its decision within seven (7) working days. However, the NDA is not required to inform the sponsor or PI of the notice if it appears that there is an imminent risk to the health or safety of any person participating in or involved in a clinical trial.

Uganda National Council for Science and Technology

According to the NDPA-CTReg, the NGHRP, and the G-CTConduct, an applicant must also submit a research proposal for review and approval to the UNCST. Per the G-UNCSTreg, the UNCST receives and reviews research protocols for their scientific merit, safety, and ethical appropriateness, and when satisfied, issues permits to conduct the research in Uganda. The research permit is granted at a national level to facilitate access to research resources within the country. The G-UNCSTreg states that as a part of its review, the UNCST liaises with the Research Secretariat in the Office of the President of Uganda to obtain security verification and clearance for the investigator. The investigator must pay a Research Administration and Clearance fee for the entire period of the research project, but such a period must not exceed five (5) years. Investigators interested in continuing a study using an approved protocol beyond the UNCST research permit expiration date should make a written request for an extension or renewal of the permit to the UNCST Executive Secretary. The request should be accompanied by a progress report, the EC approval, and any other institutional approvals, where applicable. See the G-UNCSTreg for detailed extension/renewal request submission information.

The G-UNCSTreg indicates that any changes, amendments, and addenda to the research protocol, research instruments, or the consent form must be submitted to the designated local EC or the lead agency (NDA) for review and approval prior to implementing the changes. The UNCST should be notified of the EC- or lead agency-approved changes within 10 working days.

The UNCST also reserves the right to revoke, suspend, or terminate a research permit, and, if necessary, without giving notice to the investigator, in the event of gross misconduct or violation of the G-UNCSTreg guidelines.

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

National Drug Authority

In accordance with the NDPA-CTReg, the G-CTConduct, and the NDPA-FeesReg, applicants are responsible for paying a non-refundable processing fee to submit a clinical trial application for human drugs and vaccines (except for locally manufactured herbal drugs) to the National Drug Authority (NDA). As set forth in the NDPA-FeesReg, the following fees apply:

• Application to undertake a clinical trial for a registered drug – $2,500 USD
• Application to undertake a clinical trial for an unregistered drug – $4,000 USD
• Application to amend a clinical trial application – $200 USD

Payment Instructions

According to the G-CTConduct, the application fee payment details are as follows:

National Drug Authority: TIN 1000054563
Bank: Stanbic Bank Uganda
Account numbers: 9030008068851 (US Dollars) and 9030005759829 (Ugandan shillings)
Swift code: SBICUGKXXXX

Sort Code: 040147
Acceptable forms of payment: cash in the bank, real time gross settlement (RTGS), electronic funds transfer (EFT), telegraphic transfer (TT), or check

Uganda National Council for Science and Technology

As delineated in the G-UNCSTreg, the Uganda National Council for Science and Technology (UNCST) charges a non-refundable Research Administration and Clearance fee of $300 USD, or its equivalent in Ugandan shillings, to register a research proposal. The UNCST will not register the protocol or issue a research permit until this fee has been paid. Permits are valid for the entire duration specified for a project. However, the fee covers a research period not to exceed five (5) years. Projects that extend beyond the initial five (5) year period are required to pay $300 USD for the extension. All applicants, excluding East African students, are responsible for paying this fee. East African students are only required to pay a fee of $50 USD. However, UGA-20 further indicates that this excludes those pursuing post doctorate studies.

Payment Instructions

The G-UNCSTreg delineates that applicants should make their payments to the UNCST bank accounts and are encouraged to make cash payments to avoid additional bank fees. An official receipt is issued once the UNCST receives a stamped copy of the bank deposit. See Section 6.0 of the G-UNCSTreg for detailed payment information.

According to UGA-20, the payment information is as follows:

Bank: Any Standard Chartered Bank
Account title: Uganda National Council for Science and Technology (UNCST)
Account numbers: 8705611811400 (US Dollars) and 0105610632101 (Ugandan shillings)
Swift code: SCBLUGKA

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 per the G-UNCSTreg and the NGHRP, research involving human participants must be reviewed and approved by an institutional ethics committee (EC) (referred to as a research ethics committee (REC) in Uganda), which must be accredited by the Uganda National Council for Science and Technology (UNCST).

Ethics Committee Composition

The NGHRP states that an EC must have at least five (5) members who collectively encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. Specifically, the composition should include:

• Individuals of varying backgrounds, including consideration of gender, cultural backgrounds, and sensitivity to social issues in the community from which research participants are drawn
• At least one (1) individual whose primary concern is scientific, and at least one (1) whose primary concern is non-scientific
• At least one (1) individual who is unaffiliated with the institution
• At least one (1) lay person from the community, whose primary background is not in scientific research involving human participants, and who is capable of sharing insights about the community from which participants are likely to be drawn

Additional criteria for EC membership are available in Sections 4.3 and 4.4 of the NGHRP.

Terms of Reference, Review Procedures, and Meeting Schedule

According to the NGHRP, each EC member must take at least one (1) course in human research protection within one (1) year of appointment to an EC, and thereafter, should undergo continued research ethics education at least once every two (2) years. Membership terms in any EC have a maximum three (3) year duration, after which a member is eligible for reappointment. A person may not serve as a member in more than two (2) ECs concurrently.

As set forth in the NGHRP, each EC must have written procedures, including a process to be followed for conducting reviews. The following minimum requirements must be met:

• Meet at least once every three (3) months
• At least 50% of members, including one (1) member representing community interests, must be present to conduct reviews
• Project approval requires a simple majority of those members present at the meeting
• Respond to any allegations of ethical violations in approved or rejected research projects
• Liaise with other ECs within and outside the country to better carry out its functions
• Submit annual performance reports to the UNCST

The NGHRP further indicates that no EC member may participate in the EC’s initial or continuing review of any project in which the member has a conflict of interest, except to provide information as may be requested by the EC. An EC may also, at its discretion, invite individuals with competence in special areas to assist in the review of protocols which require expertise beyond, or in addition to, that available in the EC. These individuals do not vote at EC meetings. See Sections 4.5.1 and 4.9 of the NGHRP for additional EC review requirements.

As per the NGHRP, an EC must also prepare and maintain the following:

• Detailed written procedures
• Copies of reviewed proposals and corresponding documentation (e.g., scientific evaluations, progress reports, correspondence with investigators)
• Meeting minutes
• Records of continuing review activities

Documents relating to research projects must be retained for at least five (5) years after the research project has been completed. All documents must be accessible for inspection and use by authorized UNCST representatives. See Section 4.6 of the NGHRP for additional EC recordkeeping requirements.

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

In accordance with the NGHRP, the central scope assessed by institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda) relates to safeguarding the rights, safety, and well-being of all trial participants. An EC’s primary functions include:

• Maintaining ethical standards of practice in research
• Protecting participants and investigators from harm or exploitation
• Preserving the participants’ rights and welfare
• Providing assurance to society of the protection of participants’ rights and well-being
• Ensuring adherence to an ethical conduct of research protocol

An EC 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, and Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

Role in Clinical Trial Approval Process

Per the NDPA-CTReg, proof of institutional EC approval must be submitted in a clinical trial application to the National Drug Authority (NDA). However, the G-TrialsGCP indicates that parallel submissions may be made to the NDA and the Uganda National Council for Science and Technology (UNCST). In that instance, the NDA would not make a final decision until after the trial receives ethical clearance. NDA approval will be dependent on receipt of the protocol’s approval by the institutional EC in consultations with the UNCST.

As stated in the NGHRP, the EC will notify investigators in writing about the outcome of its review. If the EC does not approve a research activity, it will include reasons for its disapproval in the written notification.

As per the NGHRP, ECs may use an expedited review process for research involving no more than minimal risk or for minor changes in previously approved research protocols during a period of one (1) year or less from which approval was given. Minor changes include an addition of a collaborator, a small change in the number of research participants, or spelling corrections. Expedited review processes may also be applied to annual renewal of studies, in which the only outstanding activity is data analysis and report writing. Major changes include, but are not limited to, significant changes in the research methodology or a change in procedures for research participants. Each EC must develop standard operating procedures to define eligibility for expedited review. See the NGHRP for more details on expedited review procedures.

According to the NGHRP, if a multicenter or collaborative trial is being conducted and the same clinical protocol is being used for all the sites, the participating institutions may enter into a joint EC review arrangement. The joint EC review must comply with the requisite ethical standards outlined in the NGHRP.

The NGHRP indicates that ECs must conduct continuing/periodic review of approved trials to ensure compliance with scientific and ethical requirements in accordance with the NGHRP. The EC must conduct the continuing review at intervals appropriate to the degree of risk, but not less than once a year, and have a plan for onsite monitoring of approved studies.

The NGHRP further delineates that changes/amendments in the research protocol cannot be implemented without prior approval from the EC, except when necessary to eliminate an apparent immediate hazard or danger to research participants. Per the NDPA-CTReg, evidence of ethical approval of the amendment to the protocol is a required element of an application to the NDA for amendment of conditions of a clinical trial.

Additionally, the NGHRP states that ECs have the authority to halt, suspend, or terminate approval of research that is not being conducted in accordance with the EC’s requirements, has been associated with unexpected serious harm to research participants, or contravenes the NGHRP. If an EC suspends or terminates its approval, it must provide a written statement for its reasons for doing so, and immediately communicate this decision to the investigator, as well as to the Uganda National Council for Science and Technology (UNCST).

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.

No applicable requirements.

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

The Uganda National Council for Science and Technology (UNCST) is the central statutory body responsible for the registration and accreditation of institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda). The UNCST’s NGHRP establishes a national framework for research involving humans to ensure that the rights, interests, values, and welfare of research participants are not compromised.

Registration, Auditing, and Accreditation

As per the NGHRP, the UNCST’s Accreditation Committee for RECs in Uganda (ACREC) must accredit all ECs. An organization that wishes to establish an EC must apply for accreditation of the EC at the UNCST, with assurance that the organization will comply with the requirements set forth in the NGHRP. The assurance must at the minimum include:

• A statement of principles for protecting the rights and welfare of human research participants of research conducted at or sponsored by the organization. This may include an appropriate existing code, declaration, or statement of ethical principles, or a statement formulated by the organization itself
• Assurance of availability of staff; office and meeting space for the EC; and sufficient resources to support the EC’s operations
• A list of EC members appointed by the head of the organization or the head’s designee. The members should be identified by name, qualifications, profession, specialty, organization of affiliation, and representative capacity in the EC
• Written standard operating procedures for the EC

The NGHRP indicates that the ACREC will review the organization’s application, and if satisfied, will accredit the EC. An EC is not permitted to commence its activities until ACREC authorization is received.

Per UGA-33, the National Research Information Management System (NRIMS) (UGA-33) supports users in applying for accreditation as an institutional EC. See UGA-9 for the accreditation application form and the NGHRP for details on EC establishment requirements. A list of UNCST-accredited ECs is also available at UGA-37.

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 NDPA-CTReg, the G-CTConduct, the NGHRP, the G-UNCSTreg, and the G-TrialsGCP, institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approval, National Drug Authority (NDA) approval, and Uganda National Council for Science and Technology (UNCST) registration are mandatory before a study may commence.

Per the NDPA-CTReg, the NDA’s review and approval of a clinical trial application are dependent upon the applicant submitting proof in the application of institutional EC approval and a research permit from the UNCST. However, the G-TrialsGCP indicates that parallel submissions may be made to the NDA and the UNCST. In that instance, the NDA would not make a final decision until after the trial receives ethical clearance. NDA approval will be dependent on receipt of the protocol’s approval by the institutional EC in consultations with the UNCST.

Regulatory Submission

National Drug Authority

According to the NDPA-CTReg, an application to the NDA for authorization to conduct a clinical trial is submitted by a sponsor, who must be one (1) of the following:

• The drug patent holder
• A licensed person
• The drug manufacturer
• An agent of the drug patent holder or the drug manufacturer

The NDPA-CTReg states that where an agent submits the clinical trial application, the agent must also submit a power of attorney verifying their appointment as an agent or a letter of authorization (See Form 30 in Schedule 1 of the NDPA-CTReg or UGA-18). Where an application for authorization to conduct a clinical trial is for a drug under patent, the principal investigator (PI) must submit a letter of authorization from the manufacturer of the drug. Furthermore, the G-CTConduct indicates that based on the clinical trial agreement between the sponsor and the PI, the NDA will liaise with the in-country PI representing the sponsor regarding the application.

As per the G-CTConduct, the sponsor or authorized person should submit one (1) copy of the completed clinical trial application form for each application. The application must be bound in a single volume (or series of volumes), and the pages numbered sequentially. Appended documents should be bound together with the application, with tabbed sections clearly identifying each appended document. The text and diagrams must be clear and legible in 12 pt Times New Roman font. Incomplete submissions will not be received at the NDA registry. See Form 29 in Schedule 1 of the NDPA-CTReg, Appendix I of the G-CTConduct, or UGA-39 for the clinical trial application form.

According to the G-CTConduct, the application package should be submitted physically to the NDA or electronically. Electronic submissions should be sent by email to clinicaltrials@nda.or.ug or through the NDA’s integrated Regulatory Information Management System (iRIMS) (UGA-40). Physical applications must be submitted to:

The Secretary to the Authority
National Drug Authority
NDA Tower
Plot 93, Buganda Road
P.O. Box 23096
Kampala, Uganda
Phone: +256-417788100; Toll Free: 0800101999

As per the G-CTConduct, all applications and supporting data submitted to the NDA should be presented in English. Supporting documents that are not in English must be accompanied by an authenticated English translation.

The NDPA-CTReg and G-CTConduct further indicate that an application to amend the conditions of a clinical trial must use Form 35, in Schedule 1 of the NDPA-CTReg and Appendix III of the G-CTConduct. The G-CTConduct also notes that that the form is on the NDA website (see UGA-19). Per the G-CTConduct, the proposed changes must be listed in a cover letter signed by the applicant. In the cover letter, a clear step-by-step justification for each proposed change(s) must be provided, and the possible consequences with regard to the benefit/risk balance for participants already enrolled in the trial must be summarized. The subject of the cover letter must be “Application to amend CTA XXX” where XXX is the Clinical Trial Application code assigned by the NDA upon authorization of the clinical trial and indicated on the clinical trial certificate. Only one (1) copy of the completed form must be sent to the NDA. As stated in the NDPA-CTReg, an application for additional investigators, additional clinical trial sites, or change of the investigators must use Form 36 in Schedule 1 of the NDPA-CTReg or UGA-13. The application forms must, where applicable, be accompanied by evidence of ethics approval of the amendment to the clinical trial protocol and the prescribed fees. Applicants may apply for renewal of a clinical trial approval using the form found in Appendix VIII of the G-CTConduct or on the NDA website at UGA-32. See Appendix VI of the G-CTConduct for the Checklist for Application for Authorization of Renewal of Conduct of a Clinical Trial, and UGA-2 for a related clinical trial application screening renewal form.

Uganda National Council for Science and Technology

Per the G-UNCSTreg, research protocols submitted to the UNCST for registration and approval must be well written and fully developed. Draft research protocols will not be accepted for registration. In order to register a research protocol, the PI should complete the necessary research application forms. Where a research protocol requires ethical approval by a foreign-based EC, it is advisable that such approval be obtained prior to submitting the protocol to the UNCST.

Applications for UNCST permission to conduct research in Uganda should be made through the National Research Information Management System (NRIMS) (UGA-33).

UGA-20 also provides the following contact information for further information on the UNCST research clearance process:

Beth Mutumba
Phone: 0414 557 025/0755 423 321
Email: b.mutumba@uncst.go.ug

Samuel Barasa
Phone: 0414 557 021/0779 452 441
Email: s.barasa@uncst.go.ug

Ethics Review Submission

UGA-20 indicates that for EC submissions, the applicant should contact the accredited committee at their institution of affiliation or obtain contacts via the UNCST website. After identifying the appropriate EC, the applicant must create an account and fill out the application on NRIMS (UGA-33).

Per UGA-33, NRIMS is an integrated online platform for accessing digital services provided by the UNCST. The platform supports users in applying for institutional EC permits and applying for UNCST approval to conduct research in Uganda. See UGA-33 for more information.

Each EC has its own required submission procedures, which can differ regarding the application format and number of copies.

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

National Drug Authority

As per the NDPA-CTReg, the G-CTConduct, UGA-39, and UGA-1, the following documentation must be submitted to the National Drug Authority (NDA) in a clinical trial application (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Proof of payment of the prescribed fees
• Applications for import and/or export of biological materials (if required)
• Application Form for Clinical Trial (See Form 29 in Schedule 1 of the NDPA-CTReg, Appendix I of the G-CTConduct, or UGA-39)
• Trial protocol (See Schedule 2 of the NDPA-CTReg)
• Investigator’s Brochure (See UGA-4 or Schedule 2 of the NDPA-CTReg)
• If the investigational product (IP) is unregistered, a dossier following the Format for Investigational Medicinal Product Dossier (See Schedule 2 of the NDPA-CTReg)
• Phytochemical analysis report and microbiological contamination report, where the clinical trial is for an herbal medicinal product
• Participant Information Leaflet and informed consent form, which must be approved by the ethics committee (EC) (research ethics committee (REC) in Uganda)
• Certificate of Good Manufacturing Practice (GMP) of the IP or other evidence of manufacturing quality, safety, and consistency
• Package insert(s)/product information leaflet for the comparator and concomitant medications
• Certificate of GMP of the placebo, if appropriate
• Evidence of accreditation of the designated laboratories or other evidence of Good Laboratory Practice (GLP) and assay validation
• Insurance certificate specific for the trial sourced from a local provider or in consultation with the NDA (valid evidence of insurance for the participants by a local insurance company and of professional indemnity for the principal investigator (PI))
• Signed and completed declarations by all investigators (See UGA-16 or Form 31 in Schedule 1 of the NDPA-CTReg)
• Approval of ECs for the protocol
• Uganda National Council for Science and Technology (UNCST) approval
• Full, legible copies of key, peer-reviewed published articles supporting the application
• Sample of the label for the IP
• Letter of authorization from the manufacturer/product owner (See UGA-18 or Form 30 in Schedule 1 of the NDPA-CTReg)
• Pharmaceutical data on dosage form (See UGA-14)
• Duly signed declaration of the monitor (See UGA-17 or Form 32 in Schedule 1 of the NDPA-CTReg)
• Clinical trial agreement between the sponsor and the PI
• Duly signed declaration by the sponsor and PI of funds of the clinical trial (See UGA-15 or Form 33 in Schedule 1 of the NDPA-CTReg)
• Other supporting documents and any other requirement as may be determined by the NDA

See Appendix II of the G-CTConduct and UGA-1 for the clinical trial application checklist.

The C-InstitutionCert further indicates that clinical trial certificates will not be issued without submission of a valid certificate of suitability of the premises supplying drugs within the respective institutions.

Applicants may apply for renewal of a clinical trial approval using the form found in Appendix VIII of the G-CTConduct or on the NDA website at UGA-32. See Appendix VI of the G-CTConduct for the Checklist for Application for Authorization of Renewal of Conduct of a Clinical Trial, and UGA-2 for a related clinical trial application screening renewal form.

As per the NDPA-CTReg, an application to amend the conditions of a clinical trial must use Form 35, and an application for additional investigators, additional clinical trial sites, or for change of the investigators must use Form 36 in Schedule 1 of the NDPA-CTReg or UGA-13.

According to the G-CTConduct, an application for amendment of the conditions of a clinical trial can also be found in Appendix III of the G-CTConduct and on the NDA website at UGA-19. The amendment application must be accompanied by a cover letter signed by the applicant together with required supporting documentation, including a submission of the protocol amendment in tracked changes, a clean copy clearly indicating the protocol version number, valid evidence of payment of amendment fees, and ethical approval of the proposed amendment. See the NDPA-CTReg, G-CTConduct, and UGA-19 for more detailed amendment application content requirements. See Appendix V of the G-CTConduct or UGA-22 for the amendments screening form.

Uganda National Council for Science and Technology

As per UGA-20, the PI should have soft copies of the following documents ready before making an online submission through the National Research Information Management System (NRIMS) (UGA-33) to the UNCST:

• A letter of introduction or recommendation from the affiliated institution in Uganda (for foreign investigators only). The letter should mention the names of the foreign investigators and it should be addressed to the UNCST Executive Secretary
• An administrative clearance letter from the head of the institution where the research is going to be conducted, addressed to the PI and/or the UNCST Executive Secretary
• Admission letter for academic research (applies to only East African students)
• Curriculum vitaes (CVs) for each investigator, dated and signed or initialed on each page
• Proof of payment of research administration and clearance fees for the study

Additionally, a permit must be obtained from the UNCST to export and import plant or animal specimens for further investigations.

See UGA-20 for detailed application requirements.

Ethics Committee Requirements

According to UGA-20, EC approval is obtained through NRIMS (UGA-33).

The NGHRP further indicates that all ECs must develop detailed standard operating procedures for submission of protocols and other requirements. However, at a minimum, the requirements should include:

• Research protocol with version and date
• Informed consent documents
• Study instruments such as questionnaires, case report forms, videos, flip charts, and any other data collection tools or forms
• Samples of trial drugs
• Evidence that the investigator(s) is appropriately qualified, experienced and, where applicable, licensed, and has adequate facilities for the safe and efficient conduct of research
• A plan for disseminating research findings to the community in which the research was carried out, and other authorized agencies in Uganda

Clinical Protocol

As delineated in Schedule 2 of the NDPA-CTReg and UGA-12, the clinical protocol should contain the following information (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• General information (trial identification; contact information of sponsor, monitor, sponsor’s medical expert, and qualified physician; name and title of investigator(s); name(s) and address(es) of clinical trial laboratory(ies) and other medical and/or technical department(s)/institutions involved in the trial; etc.)
• Background information (product name, dosage form, description of population to be studied, etc.)
• Trial objectives and purpose
• Trial design
• Selection and withdrawal of participants
• Treatment profile
• Trial parameters
• Assessment of efficacy
• Assessment of safety
• Operational aspects
• Adverse event reporting methods
• Evaluation of results, including statistics
• Direct access to source data/documents
• Quality control and quality assurance
• Description of ethical considerations relating to the trial
• Data handling and recordkeeping
• Financing and insurance, if not addressed in a separate agreement
• Publication policy, if not addressed in a separate agreement
• Supplements/appendices

For detailed information on these elements, please refer to the NDPA-CTReg and UGA-12.

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

Per the NDPA-CTReg, the National Drug Authority (NDA)’s review and approval of a clinical trial application are dependent upon the applicant submitting proof in the application of institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approval and a research permit from the Uganda National Council for Science and Technology (UNCST). However, the G-TrialsGCP indicates that parallel submissions may be made to the NDA and the UNCST. In that instance, the NDA would not make a final decision until after the trial receives ethical clearance. NDA approval will be dependent on receipt of the protocol’s approval by the institutional EC in consultations with the UNCST.

Regulatory Authority Approval

National Drug Authority

Per the G-CTConduct, NDA reviews for clinical trials are performed following a first-in first-out principle, except for clinical trials conducted in public health emergencies such as disease outbreaks, which may be exempted.

According to UGA-24, the NDA will screen and acknowledge receipt of a clinical trial application within 10 working days and reach a decision on the application within 50 working days. The G-CTConduct further specifies that the total processing time for a new clinical trial application routine review is 60 working days. Fast track reviews, under which a regulatory decision is given to the applicant within 15 or 30 working days, are applicable for certain clinical trial applications. See the Scope of Assessment section for more information.

The G-CTConduct states that the NDA may request supplementary information or documentation when appropriate, which should be submitted within the stated timeline, usually four (4) weeks. The NDA secretariat may grant additional time to provide information upon request by the applicant on a case-by-case basis. If the requested information is not submitted, the application will be archived within 50 working days. The application will need to be resubmitted for review. If the NDA, on its own initiative, makes amendments to the conditions for conducting a clinical trial for safety reasons or the scientific validity of the clinical trial, the NDA will give 15 calendar days’ notice to the sponsor or the principal investigator (PI) and request submittal of a written response to the proposed amendments.

Additionally, according to UGA-24, the NDA conducts annual reviews of ongoing trials within 20 working days and reviews amendments of clinical trial authorization within 20 working days. Per the G-CTConduct, the NDA review timelines published on UGA-24 do not include the time taken by the applicant to respond to any NDA requests for additional information. A stop-clock mechanism is applied each time the NDA requests additional information.

See Appendices X and XI of the G-CTConduct for the Service Delivery Timelines for Submitted Documents by the Authority and for the Clinical Trial Process Flow, respectively.

Uganda National Council for Science and Technology

The G-UNCSTreg states that the UNCST provides feedback on the registration status of a protocol within 10 working days from the submission date. According to the NGHRP, the UNCST registration process is normally completed within 14 working days.

Ethics Committee Approval

Per the G-TrialsGCP, an applicant must also submit the clinical trial protocol for review and approval by a UNCST-accredited institutional EC. As indicated in the NGHRP, the EC is required to review a clinical protocol within 60 days from the date of its receipt. In the case of an annual continuing review, the EC should maintain the same anniversary date of approval for any given protocol. Review outcomes must be communicated to the applicant within 14 days of the EC’s 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

According to the NDPA-CTReg, the G-CTConduct, the NGHRP, the G-UNCSTreg, and the G-TrialsGCP, institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approval, National Drug Authority (NDA) approval, and Uganda National Council for Science and Technology (UNCST) registration are mandatory before a study may commence.

As per the NGHRP and the UNHRO-Act, the UNCST also works in collaboration with the Uganda National Health Research Organisation (UNHRO) to register all health research protocols. However, the registration is conducted centrally at the UNCST.

The G-CTConduct and the NDPA-CTReg indicate that following the NDA’s approval of the clinical trial application, the applicant is also required to obtain a permit from the NDA to import investigational products (IPs) approved for the clinical trial. See the Manufacturing & Import section for more information on IP import permit requirements.

As stated in the G-TrialsGCP, research intended to be carried out at the community level (e.g. vaccine trials) should ideally ensure adequate consultation with civil society organizations that may exist within affected communities at all phases of the trial. Sponsors are encouraged to establish Community Advisory Groups/Community Advisory Boards (CAGs/CABs), which act as liaisons between the investigator and the community. Additionally, per the NGCER, community engagement is an opportunity for communities to participate in the design and conduct of research, and enhances the relevance, ownership, and applicability of research findings. See the G-TrialsGCP for more information on CAGs/CABs, and see the NGCER for UNCST guidance on how to ensure community engagement as a way to improve responsiveness to community needs and accountability in research.

Clinical Trial Agreement

As delineated in the NDPA-CTReg and the G-CTConduct, before the trial begins, the sponsor must sign a clinical trial agreement with the principal investigator (PI).

According to the G-TrialsGCP, if the sponsor decides to use a contract research organization (CRO) to conduct the trial, the transferred duties should be specified in writing and evidence of a mutual agreement must be provided. The sponsor is responsible for securing agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities. A signed agreement between involved parties (such as the PI/institution and sponsor; the PI/institution and CRO; and the sponsor and CRO), is considered an essential document before a clinical trial can commence.

Per the G-TrialsGCP, the sponsor should obtain the investigator's agreement to:

• Conduct the trial in compliance with the G-TrialsGCP, the principles of good clinical practice (GCP), the requirements of the NDA, and the protocol agreed upon by the sponsor and given approval by the relevant EC
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection
• Retain the trial-related essential documents until the sponsor informs the investigator/institution that these documents are no longer needed

According to the NGHRP, collaborating research partners must agree on appropriate data access and use rights before commencement of the study.

Clinical Trial Registration

The G-CTConduct states that clinical trial registration with a publicly accessible clinical trial registry is a requirement for all industry-funded trials in Uganda. Details of registration should be provided with the clinical trial application. It also states that clinical trials conducted in Uganda must be registered with the Pan African Clinical Trials Registry (UGA-35) and any other publicly accessible clinical trials registry recognized by the World Health Organization (WHO). The respective number should be submitted upon application. Additionally, the NDA maintains a clinical trials register (see UGA-36) that details all clinical trials that have received a regulatory decision. This includes information on clinical trial applications that are authorized, suspended, rejected, terminated, and completed.

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 NDPA-CTReg, the NDPA-PVReg, the NDPA-PVRegAmdt, the G-CTConduct, the NGHRP, and the G-TrialsGCP, the following definitions provide a basis for a common understanding of Uganda’s safety reporting requirements:

• Adverse Event (AE) – Any untoward medical occurrence in a research participant who is administered an investigational product (IP), and which does not necessarily have a causal relationship with this treatment
• Adverse Drug Reaction (ADR) – All noxious and unintended responses to a medicinal product related to any dose
• Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in a congenital anomaly/birth defect
• Unexpected Adverse Drug Reaction – An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved IP)

Safety Reporting Requirements

Investigator Responsibilities

As per the NDPA-CTReg and the G-TrialsGCP, the principal investigator (PI) must report all SAEs to the sponsor within 48 hours of first knowledge. The report must identify each participant by an assigned number. When the SAE results in a participant’s death, the PI must supply the sponsor, the National Drug Authority (NDA), and the institutional ethics committee (EC) (research ethics committee (REC) in Uganda) with any additional information requested.

The NGHRP states that the PI is required to report to the EC no later than seven (7) calendar days upon receiving notice of an SAE. A detailed report of the SAE should be submitted within seven (7) calendar days from the date it is reported to the EC. All other AEs should be reported by the PI to the EC as soon as possible, but no later than 14 calendar days. As set forth in the NDPA-CTReg, the PI must record and report to the sponsor any suspected unexpected serious adverse reaction (SUSAR) that occurs during the course of the trial.

Sponsor Responsibilities

According to the G-TrialsGCP, the sponsor is responsible for the ongoing safety evaluation of the IP(s). The sponsor should promptly notify all concerned investigator(s), the NDA, and the EC in writing of findings that could adversely affect the safety of participants, impact the conduct of the trial, or alter the EC's approval to continue the trial. Study participants should also be informed of any new information that could adversely affect their safety.

The NDPA-CTReg and the G-TrialsGCP state that the sponsor should keep detailed records of the trial-related AEs/ADRs reported by the PI.

The G-CTConduct delineates that the sponsor (or the PI, when delegated) must report all SAEs to the NDA as soon as possible, but no later than seven (7) calendar days upon receiving notice of the event. Additional follow up information must be made available to NDA as soon as possible, but in any case, no later than 15 calendar days. However, the G-TrialsGCP indicates that the PI is responsible for the aforementioned reporting of SAEs to the NDA.

In addition, according to the G-TrialsGCP, the sponsor should expedite the reporting of all AEs/ADRs that are both serious and unexpected to all concerned investigator(s)/institutions(s), EC(s), and to the NDA. The expedited reporting should occur within the timeframe and format specified by the NDA. Serious and unexpected AEs/ADRs suspected to be related to the IP(s) should be reported to the relevant EC as soon as possible. If the study is multicenter, the sponsor should ensure that all serious and unexpected AEs/ADRs that occur in other study sites are also reported within 15 calendar days of becoming aware of them.

As set forth in the NDPA-CTReg, the sponsor and the PI must also take appropriate safety measures to protect participants against any immediate hazards to their health and safety. When safety measures are taken, the sponsor must, within three (3) working days, provide written notice to the NDA of this action and the reasons why this action was taken.

As set forth in the NDPA-CTReg, the sponsor or their appointed representative must report any SUSARs within seven (7) days of first knowledge to the NDA and the Uganda National Council for Science and Technology (UNCST), or a UNCST-accredited EC.

The G-CTConduct further specifies that the sponsor (or the PI, when delegated) must report all SUSARs to the NDA as soon as possible, but no later than seven (7) calendar days of becoming aware of the event. If the initial report is not complete within the seven (7) days, a completed report should be submitted within 15 calendar days of the initial report. SUSAR reports originating from other studies using the same IP internationally must be submitted as soon as possible, but no later than 15 calendar days following notification of the PI by the sponsor.

However, the G-TrialsGCP indicates that the sponsor should report any SUSARs to the NDA within 15 calendar days of becoming aware of the event. The initial reports should be followed promptly by detailed, written follow-up reports after investigations have been completed, no later than 15 calendar days of becoming aware of the event.

According to the NDPA-CTReg and the G-TrialsGCP, the sponsor should also inform the PI of any SUSARs which occur during the course of another trial for which the sponsor is responsible, where the reaction relates to the IP used in the trial. The NDA should maintain a record of all IP-related SUSARs reported to the authority.

Form Completion & Delivery Requirements

Per UGA-31, the NDA has stated that it does not have a template for reporting AEs for clinical trials. The NDA recommends the use of internationally acceptable forms, such as the one provided by the Council for International Organizations of Medical Sciences (CIOMS) (UGA-8).

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 per the G-TrialsGCP, the principal investigator (PI) is obliged to submit progress reports as required by the sponsor, the institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda), the Uganda National Council for Science and Technology (UNCST), and the National Drug Authority (NDA). These reports should contain information on:

• How the study is progressing
• The number of participants included in relation to the number screened and the target sample size
• The number of dropouts and withdrawals
• Adverse events
• If the planned time schedule is still appropriate

The format and frequency of reporting is as prescribed by the relevant authorities.

The NDPA-CTReg and the G-CTConduct also state that the NDA may request the sponsor to submit an interim report. See Schedule 2 of the NDPA-CTReg or UGA-6 for the format of the clinical trial report.

Additionally, per the G-UNCSTreg, although annual renewal of a study is not required, investigators should electronically submit annual progress reports to the UNCST within four (4) weeks following every 12 months of the study for informational purposes only. Failure to do so may result in termination of the research.

Final Report

The NGHRP states that the sponsor is responsible for approving a final study report, regardless of whether the trial has been completed. In addition, the NDPA-CTReg and the G-TrialsGCP require the sponsor to inform the NDA in writing of the conclusion of the trial within 90 days, using the format of the clinical trial report in Schedule 2 of the NDPA-CTReg.

However, according to the G-CTConduct, either the sponsor or PI must notify the NDA upon conclusion of a trial within 90 calendar days using the format conforming to the International Council for Harmonisation (ICH)’s Harmonised Tripartite Guideline: Structure and Content of Clinical Study Reports (E3) (UGA-38). This notification must be accompanied by:

• The final soft and hard copies of the clinical trial report as specified
• A comprehensive summary of the essential findings of the trial
• Evidence of destruction or shipment of remaining investigational products or any other course of action approved by the sponsor

As stated in the G-CTConduct, the definition of the end of the study will be as defined by the specific study protocol. The NDA requires that the PI submit an end of study notification according to the end as defined in the study protocol. End of trial reports will be submitted once the trial data can answer the study endpoints. The NDA defines the end of the trial as a time when the trial ends and end points are available.

The G-TrialsGCP further indicates that upon completion of the trial, the investigator, where applicable, should inform the institution. The investigator/institution should provide the EC with a summary of the trial’s outcome and furnish the regulatory authorities with any reports required. All aspects (statistical and clinical) of the protocol should be integrated in order to obtain a final study report that is entirely consistent with the study data generated. Essential elements in the presentation of the results include:

• Baseline comparisons between the treatment groups
• The number of participants actually randomized into the study by treatment group and the number of participants excluded from any of the analyses, by reason and by treatment group
• Major efficacy and safety results by treatment group in the form of tables, graphs, test variables, and statistical parameters, as appropriate
• An assessment of between-group differences with confidence intervals

An account must be made of missing, unused, or spurious data during statistical analyses. All omissions of this type must be documented to enable review.

In accordance with the G-UNCSTreg, it is the investigator’s obligation to submit final reports of the research projects to the UNCST. Investigators are free to adopt any format for writing a final report, but the report should have an abstract, a results section, a discussion of the results, and recommendations. Investigators who are foreign nationals are required to submit a study completion report before returning to their countries.

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.

As defined in the NDPA-CTReg, the G-CTConduct, the G-GMPAnnexes, and the G-TrialsGCP, a sponsor is the person, company, institution, or organization that takes responsibility for the initiation, management, or financing of a clinical trial. The NGHRP specifically assigns responsibility to the sponsor for providing all the necessary financial support to initiate and complete a research study.

The NDPA-CTReg also specifies that in order to submit a clinical trial application, the sponsor must be one (1) of the following:

• The drug patent holder
• A licensed person (a pharmacist)
• The drug manufacturer
• An agent of the drug patent holder or the drug manufacturer

As stated in the G-TrialsGCP, a sponsor may transfer any or all of the sponsor's trial-related duties and functions to a contract research organization (CRO), but the ultimate responsibility for the quality and integrity of the trial data always rests with the sponsor. The CRO must have the required skills, experience, and competencies to safely conduct clinical trials. Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing and evidence of a mutual agreement provided. The sponsor should ensure oversight of any trial-related duties and functions carried out on the sponsor’s behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor's contracted CRO(s). Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.

Per the NDPA-CTReg, a local company in Uganda may act as an agent in the clinical trial for a foreign sponsor.

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

As per the NDPA-CTReg and the G-TrialsGCP, the sponsor oversees the selection of the investigator(s) and the institution(s) for the clinical trial. The G-CTConduct indicates that based on the clinical trial agreement between the sponsor and the principal investigator (PI), the National Drug Authority (NDA) will liaise with the in-country PI representing the sponsor regarding the application. The PI should be a Ugandan resident (local) and licensed by the relevant body in Uganda.

The G-TrialsGCP states that before entering an agreement with an investigator to conduct a trial, the sponsor should provide the investigator with the protocol and an up-to-date Investigator's Brochure (IB). The investigator should also be given sufficient time to review the protocol and the information provided. The PI/investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, meet all the qualifications specified by the applicable regulatory requirement(s), and provide evidence of such qualifications through an up-to-date curriculum vitae and/or other relevant documentation requested by the sponsor, the accredited institutional ethics committee (EC) (research ethics committee (REC) in Uganda), and/or the NDA. The PI/investigator(s) should also be thoroughly familiar with the appropriate use of the investigational product(s) (IP(s)), as described in the protocol, current IB, product information, and other information sources provided by the sponsor. Furthermore, the PI/investigator(s) should be aware of, and comply with, good clinical practice (GCP) and the applicable regulatory requirements.

According to the NDPA-CTReg, an application for additional investigators, change of investigator, or additional clinical trial sites must be made using Form 36 in Schedule 1 of the NDPA-CTReg or using UGA-13. The application must be accompanied by evidence of ethical approval of the clinical trial protocol amendment, where applicable, and the prescribed fees.

In accordance with the G-UNCSTreg, all investigators who are foreign nationals are required to identify and become affiliated with a local organization appropriate for their type of research in Uganda. Investigators arrange the affiliation themselves with the local organization. The investigator should obtain a letter of recommendation from the local organization and submit it to the Uganda National Council for Science and Technology (UNCST).

Foreign Sponsor Responsibilities

The NDPA-CTReg states that in the case of foreign sponsors, a local company in Uganda must submit a letter of authorization from the holder of the patent of the drug, licensed person, or manufacturer of the drug to be the agent in the clinical trial that is responsible for all matters pertaining to the NDA clinical trial certificate. See Form 30 in Schedule 1 of the NDPA-CTReg or UGA-18 for the letter of authorization, and Form 34 in Schedule 1 of the NDPA-CTReg for the clinical trial certificate.

Data and Safety Monitoring Board

According to the NGHRP, the G-TrialsGCP, and the NDPA-CTReg, the sponsor is responsible for establishing a Data and Safety Monitoring Board (DSMB) (also referred to as an Independent Data-Monitoring Committee (IDMC)) prior to the trial’s commencement. Per the NGHRP, the DSMB ensures that the study and the data are handled in accordance with the protocol provisions, monitors adverse events/adverse drug reactions and safety data, and preserves the integrity and credibility of the trial. The composition of the DSMB must be provided to the EC. All Phase I, Phase II, and Phase III trials must have a safety monitoring plan and a DSMB. For additional details on DSMB requirements, see 3.6.2 of the NGHRP.

The G-TrialsGCP further indicates that a DSMB should have written operating procedures and maintain written records of all its meetings. A duly signed DSMB charter must be submitted to the NDA prior to recruitment of participants, and any decision not to create a DSMB should be clearly documented and justified in the protocol.

Multicenter Studies

The G-TrialsGCP indicates that multicenter trials must adhere to all national regulatory requirements, ensuring consideration and adaptation of the local context into the general study design. The following should be considered regarding multicenter trials:

• Inclusion and exclusion criteria must be appropriate to consider local realities, as well as trial site-specific differences
• The informed consent procedure must be tailored to local conditions and informed consent forms translated into the local language submitted to the EC for approval
• Study design differences between the Ugandan site(s) and other sites must be fully explained, as well as differences between sites within Uganda Study extrapolations and conclusions should be relevant to the Ugandan context
• Where necessary, site investigators should develop site-specific standard operating procedures and/or a site implementation plan to guide the respective sites on protocol implementation

Per the G-TrialsGCP, for multicenter trials, the PI is responsible for appointing co-investigators that will be responsible for the various trial sites in Uganda. However, it is the responsibility of the sponsor to ensure all investigators conduct the trial in strict compliance with the approved protocol. In addition, the sponsor should ensure that:

• 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 at the various sites is facilitated

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 NDPA-CTReg and the G-TrialsGCP, the sponsor is responsible for providing insurance coverage for any unforeseen injury to research participants. The sponsor should provide indemnity for the investigator(s) against claims arising from the clinical trial, except for claims that arise from malpractice or negligence.

According to the NDPA-CTReg, the G-CTConduct, and the G-InsuranceCover, an insurance certificate must be provided to the National Drug Authority (NDA) that is specific to the trial for which the clinical trial application is being submitted. The G-CTConduct and the NDPA-CTReg also indicate that the clinical trial application must provide evidence that each member of the clinical trial team is covered by relevant malpractice insurance for the trial.

The G-InsuranceCover further states that the required insurance coverage for research participants in a specific trial at a given site must be obtained from a local insurance company that is registered and operating under law in Uganda. For additional details on the required elements of the insurance policy, see Section 7.0 of the G-InsuranceCover.

According to the G-TrialsGCP, the principal investigator (PI) is responsible for ensuring participants obtain their claim from the local insurance company in the event of any trial-related injury and/or resultant disability.

Compensation

Per the G-TrialsGCP, the sponsor must ensure that information on incentives offered to participants is included in the protocol and informed consent documents. If the study is multicenter, information on the incentives given at all the different trial sites must be provided. If the participating sites are multinational, then the differences in the incentives across the sites must also be explained.

According to the NGHRP, a care package for research participants should be prepared before initiation of a research project. Care and treatment for research participants should be provided with the ideal aim of providing the best proven intervention.

Injury or Death

In accordance with the NGHRP, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries, disability, or death. The sponsor must ensure that participants who suffer any trial-related injuries receive free medical treatment for such injuries, and financial or other assistance that would compensate them equitably for any resulting impairment, disability, or handicap. The sponsor should provide care until complete cure or stabilization of a trial-related injury. The investigator and/or study sponsor must pay the cost of referral and management of the condition when a referral has been made for a trial-related injury or a serious adverse event related to the study. Furthermore, the sponsor is required to ensure that research participants are not asked to waive their legal rights to seek compensation.

Per the NGHRP, a trial-related injury may be physical, social, economic, or psychological, and may be classified as follows:

• Definitely: When injury is directly caused by participation in a research project

• Probably: When injury is most likely explained by participation in a research project but when no definite proof of causality is evident

• Possibly: When explanation for injury is equally due to participation in a research project or other cause

• Unlikely: When injury is more likely explained by another cause other than participation in a research project

Subject to applicable laws in Uganda, research participants will be entitled to compensation when injury related to their participation in a research project is classified as “Probably” or “Definitely.”

According to the NGHRP, the sponsor and investigator must put in place a mechanism for compensating trial-related injury at the commencement of a study. The mechanism, which may include, inter alia, insurance, and medical care, should be acceptable to the institutional ethics committee (EC) (research ethics committee (REC) in Uganda). The EC, research participant, and/or investigator may initiate the compensation process. The EC, sponsor, and investigator must agree on an appropriate mechanism for arbitration.

Trial Participation

In the clinical trial application made to the NDA, the applicant must explain how the participant(s) will be compensated for their time and other inconveniences, in accordance with the G-CTConduct and the NDPA-CTReg.

In addition, per the NGHRP, participants must be fairly compensated for inconveniences, time spent, and expenses incurred while taking part in a study such as travel costs, refreshments, meals, and any other compensation deemed appropriate by the EC. Research participants may also receive free medical services. The compensation or medical services must not be so out of proportion as to induce prospective research participants to consent to participate in the trial against their better judgment.

According to the G-TrialsGCP, the sponsor must ensure that participants are reimbursed for all reasonable costs incurred by their participation in the trial.

Post-Trial Access

In accordance with the NGHRP, the duration and sustainability of care and treatment for the participant after the study should be negotiated before initiation of the study. Sponsors are encouraged, but not obliged, to provide care for concurrent illnesses not associated with the research project. However, investigators and sponsors are obliged to manage serious adverse events related to the study (including paying for associated costs thereof) until they are fully resolved or stabilized. Investigators should provide relevant follow up procedures for participants for an appropriate period of time after the trial.

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

The NDPA-CTReg states that the sponsor should maintain quality assurance and quality control systems for the conduct of clinical trials and for the generation of documentation, recording, and reporting of data. The G-TrialsGCP indicates that the sponsor is also responsible for implementing the systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, good clinical practice (GCP), and the applicable regulatory requirement(s). Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly.

According to the G-TrialsGCP, the sponsor should implement a quality management system throughout all stages of the trial process, and should focus on the trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach including critical process and data identification, risk identification, risk evaluation, risk control, risk communication, risk review, and risk reporting. For additional details, see the G-TrialsGCP.

Monitoring Requirements

As per the G-TrialsGCP, the sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The observations and findings of the auditor(s) should be documented and accessible to the institutional ethics committee (EC) (research ethics committees (RECs) in Uganda) and the National Drug Authority (NDA). The audit report should be submitted to the NDA if evidence of GCP or protocol non-compliance is found.

The G-TrialsGCP further states that in accordance with the NDPA-CTReg, the sponsor should appoint a monitor tasked with trial oversight and reporting on the progress of a study. The monitor should ideally have adequate medical, pharmaceutical, and scientific qualifications. The investigator(s) should accept the possibility of an audit or monitoring visit by an independent auditor appointed by the sponsor, and/or an inspection by the NDA, EC, or relevant local and international regulatory authorities.

Premature Study Termination/Suspension

Per the NDPA-CTReg, in the case of a sponsor-initiated clinical trial termination, the sponsor must notify the NDA within 15 days using the format specified in Schedule 2 of the NDPA-CTReg or UGA-5. The notification must give reasons for the termination, indicate the disposal process for the unused investigational product, and give the effective date of the termination. The G-CTConduct further requires that the sponsor provide evidence of notification to the EC of record and the Uganda National Council for Science and Technology (UNCST).

In addition, the G-TrialsGCP requires that if a trial is prematurely terminated or suspended for any reason, the investigator should inform the participants, assure appropriate therapy and follow-up for the participants, and inform the NDA. Furthermore, if the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should inform the sponsor and the EC. The investigator should provide the sponsor and the EC with a detailed written explanation of the termination or suspension.

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

According to the G-TrialsGCP, the sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, handle the data, verify the data, conduct the statistical analyses, and prepare the trial reports. When using electronic trial data handling or remote electronic trial data systems, the sponsor should:

• Ensure and document that the electronic data processing system(s) conform(s) to the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance
• Maintain standard operating procedures (SOPs) for using these systems
• Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data
• Maintain a security system that prevents unauthorized access to the data, and a list of the individuals who are authorized to make data changes
• Maintain adequate backup of the data
• Safeguard the blinding, if any
• Ensure the integrity of the data, including any data that describes the context, content, and structure

For additional details, see Section 4.8 of the G-TrialsGCP.

The G-TrialsGCP states that quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly. The sponsor should base their approach to validation of electronic data processing systems on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human participant protection and reliability of trial results. The sponsor should maintain a documented record of SOPs that guide a step-by-step retrospective assessment of data quality and study performance. These SOPs should cover system setup, installation, and use. The SOPs should also describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use.

According to the G-TrialsGCP, satisfactory maintenance and back-up procedures for computer databases must be provided. Case report forms (CRFs) should be designed to meet the specific data requirements set out in the study protocol. The effects of missing and inaccurate data should be minimized to maintain data quality. The system for routinely checking the data collection and entry throughout the course of the trial should be documented. Checks for validity and consistency of the database should be on separate items as well as on predetermined combinations of items in the CRFs. The SOP for data editing should ensure that any queries about data validation are brought to the attention of the investigators. Database lock should be done after completion of the validation and editing processes are documented.

Records Management

The G-TrialsGCP and the G-CTConduct state that the sponsor and the PI are responsible for archiving and ensuring the safety of all trial-related documentation. Per the NDPA-CTReg, the sponsor must keep the records, documents, and information provided to the National Drug Authority (NDA) in the clinical trial application for unregistered investigational products (IPs) at the clinical trial site for 20 years following the trial's completion. Documentation for trials involving IPs to be registered should be kept for two (2) years after the registration of the IP. For an IP used in a clinical trial, the sponsor must, at the clinical trial site, maintain:

• The Investigator's Brochure (IB) for the IP and a record of the changes made to the IB, if any, including the rationale for each change
• A record of the adverse events (AEs) of the IP that occurred inside or outside Uganda, showing the indication for use and the dosage form of the IP at the time of the AE
• A record of the participants with their identifications and contacts
• A record of the shipment and receipt of the IP and where applicable, a record of the return of the IP or a record of the destruction of the IP, which must be in accordance with the prescribed process
• A copy of the protocol and consent forms

The G-CTConduct further states that the holder of the clinical trial certificate should inform the NDA in writing prior to destroying the documents. Documents may be stored in electronic (soft and scanned) or hard copies.

In addition, the G-TrialsGCP requires that if the sponsor discontinues the clinical development of an IP, the sponsor should maintain all sponsor-specific essential documents for at least two (2) years after formal discontinuation. The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial-related records are no longer needed.

According to the NGHRP, collaborating research partners must agree on appropriate data access and use rights before commencement of the study. Investigators must have in place mechanisms for maintaining the confidentiality of research participants and their communities. Furthermore, a collaborating research partner must not transfer data to a third party without the written consent of the other partner. Local investigators must have unrestricted access rights to data sets collected through a collaborative research project. Lastly, investigators must ensure that research records from which the data has been obtained are available at the research site for at least five (5) years after completion of the research project. Electronic records are acceptable.

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

As per the NITA-U-PrivAct, the data controller determines the purposes for and the manner in which personal data is processed or is to be processed. The “data processor” processes personal data on behalf of the data controller. Data controllers and processors must be registered with the Personal Data Protection Office (PDPO) of the National Information Technology Authority - Uganda (NITA-U). See the NITA-U-PrivAct, the NITA-U-PrivReg, and the PDPO-Note for detailed registration requirements.

Data Protection

As per the NITA-U-PrivAct, a data controller or processor must:

• Be accountable to the data subject for data collected, processed, held, or used
• Collect and process data fairly and lawfully
• Collect, process, use, or hold adequate, relevant, and not excessive or unnecessary personal data
• Retain personal data for the period authorized by law or for which the data is required
• Ensure quality of information collected, processed, used, or held
• Ensure transparency and participation of the data subject in the collection, processing, use, and holding of the personal data
• Observe security safeguards in respect of the data

The NITA-U-PrivReg indicates that every data collector, data processor, and data controller registered under the NITA-U-PrivReg must submit an annual report to the PDPO within 90 days after the end of every financial year. The report must contain a summary of all complaints received and the status of such complaints (including whether the complaint was resolved or is still pending), as well as all data breaches and the action taken to address such data breaches. See UGA-41 for a template of the annual report. See Part III of the NITA-U-PrivAct and NITA-U-PrivReg for detailed requirements on data processing, record retention, and processing of personal data outside Uganda.

Additionally, as per UGA-43, the PDPO launched a Data Protection and Privacy Compliance Toolkit to help organizations comply with NITA-U-PrivAct. The Toolkit is a comprehensive resource that includes practical tools, templates, and step-by-step guidance that organizations can use to assess their data protection practices, identify gaps, and take corrective actions. For more details and to access the toolkit, individuals should contact compliance@pdpo.go.ug.

Consent for Processing Personal Data

As delineated in the NITA-U-PrivAct, for the purposes of processing personal data, consent means any freely given, specific, informed, and unambiguous indication of the data subject’s wish which, by a statement or by a clear affirmative action, signifies agreement to the collection or processing of the data subject’s personal data.

According to the NITA-U-PrivAct, a data controller or data processor must obtain the consent of the data subject before collecting or processing personal data, and the data must be collected for a lawful, specific purpose. Unless otherwise provided under the NITA-U-PrivAct, a data subject has the right to object to the collection or processing of personal data at any time. See the NITA-U-PrivAct and NITA-U-PrivReg for detailed requirements on consent to data collection or processing, record retention, and processing of personal data outside Uganda.

The NITA-U-PrivAct and NITA-U-PrivReg further state that data subjects have a right to (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Request a data controller to give a description of the personal data held by the controller
• Prevent processing of personal data
• Appeal a decision to continue processing personal data
• Request a data controller to correct or delete personal data about the data subject that is inaccurate, irrelevant, excessive, out of date, incomplete, misleading, or obtained unlawfully

See the NITA-U-PrivAct and NITA-U-PrivReg for more information on data subject rights.

Children

According to the NITA-U-PrivAct, personal data relating to children must not be collected or processed unless it is carried out with the prior consent of the parent/legal guardian; is necessary to comply with the law; or is for research or statistical purposes. The NITA-U-PrivReg further requires that every data collector, data processor, and data controller establish a system to determine the age of participants whose personal data is to be collected, processed, or stored, and where the data relates to a child, describe the manner of obtaining consent of a parent/legal guardian, where necessary.

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 Ugandan clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the NGHRP and the G-TrialsGCP.

As per the NGHRP, the NDPA-CTReg, the G-CTConduct, and the G-TrialsGCP, the informed consent form (ICF) and the participant information leaflet are viewed as essential documents that must be reviewed and approved by an accredited institutional ethics committee (EC) (research ethics committee (REC) in Uganda) and provided to the National Drug Authority (NDA) with the clinical trial application. (See the Required Elements section for details on what should be included in the ICF.)

The G-TrialsGCP states that before informed consent may be obtained, the principal investigator (PI), or a person designated by the PI, should provide the participant or legal representative/guardian ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the participant or legal representative/guardian.

As stated in the NGHRP, an investigator must seek informed consent only after ascertaining that the prospective research participant has adequate understanding of the relevant facts and of the consequences of participation. For certain types of research, the EC may require the investigator to administer a comprehension test (or test of understanding) to ensure that prospective research participants have acquired adequate understanding of the relevant facts and of the consequences of participation.

Per the G-TrialsGCP, if a participant is unable to read or if the legal representative/guardian is unable to read, an impartial witness should be present during the entire informed consent discussion. The written ICF and any other written information to be provided to participants should be read and explained to the participant or legal representative/guardian. According to the NGHRP, verbal consent may be obtained in studies that present no more than minimal risk or in studies where for justifiable reasons written consent may not be feasible. ECs reserve the right to determine when verbal informed consent may be appropriate and acceptable.

Additionally, as stated in the G-TrialsGCP, the language used in the oral and written information about the trial, including the written ICF, should be as non-technical as practical and should be understandable to the participant or legal representative/guardian and the impartial witness, where applicable. Neither the PI, nor the trial staff, should coerce or unduly influence a participant to participate or to continue to participate in a trial. None of the oral and written information concerning the trial, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence and/or malpractice.

See the NGHRP and the G-TrialsGCP for detailed requirements for obtaining consent.

Re-Consent

According to the G-TrialsGCP, the written ICF and any other written information to be provided to participants should be revised whenever important new information becomes available that may be relevant to the participant’s consent. Any revised written ICF and written information should receive the EC's approval/favorable opinion in advance of use. The participant or legal representative/guardian should 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.

The NGHRP specifies that re-consent from participants must be obtained if there are changes in the conditions or procedures of the research or if new information becomes available that could affect the participant’s willingness to continue in the research.

Language Requirements

As per the NGHRP and the G-CTConduct, the ICF should be written in English and in a vernacular language that the participant is able to understand. The G-TrialsGCP further indicates that for multicenter trials, the informed consent procedure must be tailored to local conditions, and ICFs must be translated into the local language and submitted to the EC for approval.

Documenting Consent

The G-TrialsGCP and the NGHRP state that prior to participation in the trial, the written ICF should be signed and personally dated by the participant or legal representative/guardian, and by the person who conducted the informed consent discussion.

The G-TrialsGCP delineates that the impartial witness for participants unable to read should sign and personally date the ICF, after the participant or legal representative/guardian has orally consented to the participation in the trial. If capable of doing so, the participant or legal representative/guardian should sign and personally date the ICF. By signing the ICF, the impartial witness attests that the information in the ICF and any other written information was accurately explained to, and apparently understood by, the participant or legal representative/guardian, and that informed consent was freely given.

According to the NGHRP, a thumbprint on the ICF is also acceptable in lieu of a signature. Where the use of signed consent forms is not feasible, alternative viable methods should be employed.

The G-TrialsGCP and the NGHRP indicate that a copy of the signed ICF must be offered to the participant or legal representative/guardian prior to participation in the trial. The G-TrialsGCP further specifies that during the course of the trial, the participant or legal representative/guardian should receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to the participant.

Waiver of Consent

According to the NGHRP, an EC may waive some or all of the requirements for the investigator to obtain informed consent and/or a signed/thumb-printed consent form for some or all of the research participants of a particular study if the EC determines that:

• The research project carries no more than minimal risk (risk that is no more than the risks encountered in normal daily life in a stable society)
• The research project could not practicably be carried out without the waiver or alteration (whenever appropriate the research participants will be provided with additional pertinent information after participation)
• Deception needs to be applied to achieve the objectives of the study
• The only record linking the research participant and the research project would be the ICF and the risk to the research participant would be potential harm resulting from a breach of confidentiality
• The research participant is involved in an emergency situation and informed consent cannot be reasonably obtained from the individual or the representative

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 NGHRP and the G-TrialsGCP, 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 involves research and an explanation of its nature and purpose
• The procedures to be followed, including all invasive procedures
• The expected duration of the trial
• The trial treatment(s) and the probability for random assignment to each treatment (where appropriate)
• The participant's responsibilities
• Those aspects of the trial that are experimental
• Any reasonably foreseeable risks or discomforts to the participant (when applicable, to an embryo, fetus, or nursing infant), and whether the project involves more than minimal risk
• Any benefits to the participant or to others that may be reasonably expected from the research; if no benefit is expected, the participant should also be made aware of this
• The disclosure of specific appropriate alternative procedures or therapies available to the participant
• The requirement to preserve the confidentiality of the participant
• Allowed access by the sponsor, National Drug Authority (NDA), Uganda National Council for Science and Technology (UNCST), relevant institutional ethics committee (EC) (research ethics committee (REC) in Uganda), and/or other regulatory authority including international regulatory authorities (pending that they have received permission to do so from UNCST) to participant records
• The policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury within the framework of clinical trials insurance and where further information may be obtained
• Where applicable, a statement of how the researcher will provide medical services to the participant
• The nature, form, and extent of compensation for participation (e.g., reimbursement for transport, time, and meals)
• The identity of a sponsor and any potential conflict of interests
• A brief description of sponsors of the research project and the organizational affiliation of the researchers
• A contact name and number of the principal investigator and/or site investigator
• Names and contact details of individual(s) who should be contacted at any time in case of questions about the research project, as well as the participants’ rights and welfare. The individual(s) should be able to communicate in a language understandable by the participant or should be able to promptly secure the services of an interpreter to assist in responding to the participant’s questions
• Participation is voluntary, the participant can withdraw from the study at any time, and withdrawal or refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled
• A statement that participants will get feedback on findings and progress of the study, and that any new information that affects the study or data that has clinical relevance to participants (including incidental findings) will be made available to research participants and/or their health care providers
• 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
• A witness may represent vulnerable populations during the informed consent process, if applicable
• The study has been approved by an accredited Ugandan-based EC
• A statement that a particular treatment or procedure may involve risks to the participant (or to the embryo or fetus, if the participant is or may become pregnant), which are currently unforeseeable
• The foreseeable circumstances and/or reasons under which participation in the trial may be terminated, whether or not the participant consents to such termination
• Additional costs/expenses to the participant that may result from participation in the study
• The consequences of a participant’s decision to withdraw from the research and procedures for orderly withdrawal by the participant
• The approximate number of participants in the research study
• If the research involves collecting biological or genetic materials, participants must be provided with an explanation on how specimens will be managed at the end of the study. If samples will be stored for future use, separate consent should be obtained
• Whether, when, and how any of the products or interventions proven by the study to be safe and effective will be made available to participants at the end of the study, and if the participants will be expected to pay for them

Compensation Disclosure

According to the G-TrialsGCP, the sponsor must ensure that information on incentives offered to participants is included in the informed consent documents. If the study is multicenter, information on the incentives given at all the different trial sites must be provided. If the participating sites are multinational, then the differences in the incentives across the sites must also be explained.

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

The G-TrialsGCP states that in obtaining and documenting informed consent, the principal investigator (PI) or delegate should comply with the ethical principles that have their origin in the Declaration of Helsinki (UGA-27), the NGHRP, and the G-TrialsGCP. Additionally, in accordance with the NGHRP and the G-TrialsGCP, a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process.

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

The Right to Participate, Abstain, or Withdraw

As set forth in the NGHRP and the G-TrialsGCP, the 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

According to the NGHRP and the G-TrialsGCP, 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 Right to Privacy and Confidentiality

The NGHRP and the G-TrialsGCP indicate that all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. It is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

As per the NGHRP and the G-TrialsGCP, the research participant or legal representative/guardian should be provided with contact information for the investigator(s) and the institutional ethics committee (EC) (research ethics committee (REC) in Uganda) to address trial-related inquiries in the event of any injury and/or to appeal against a violation of the participants’ rights.

The Right to Safety and Welfare

The NGHRP states that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the objectives of the research.

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.

The NGHRP allows the institutional ethics committee (EC) (research ethics committee (REC) in Uganda) to waive some or all of the informed consent requirements in instances of emergency situations where consent cannot be reasonably obtained from the participant or legal representative/guardian.

The G-TrialsGCP further states that in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative/guardian, if present, should be requested. When prior consent of the participant is not possible and the legal representative/guardian is not available, enrollment of the participant should require measures that are described in the protocol and/or elsewhere, with documented approval by the EC, to protect the rights, safety, and well-being of the participant and to ensure compliance with applicable regulatory requirements. The participant or legal representative/guardian should be informed about the trial as soon as possible and provide consent to continue or other consent as appropriate, should this be requested.

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

According to the NGHRP, additional safeguards must be included in a study to protect vulnerable populations. Vulnerable populations are characterized as research participants who are incapable of protecting their own interests due to insufficient power, intelligence, education, resources, strength, or other requisite attributes. These participants are also considered to be vulnerable due to their limited capacity or freedom to provide or decline consent. Vulnerable populations include children/minors, prisoners, the homeless, substance abusers, mentally and physically handicapped, armed forces, terminally ill, and pregnant women. Characteristics that constitute vulnerability in such populations include one (1) or more of the following:

• Limited economic empowerment
• Conflict and post-conflict situations
• Inadequate protection of human rights
• Discrimination on the basis of health status
• Limited availability of health care and treatment options
• Communities in acute disaster and disease epidemics

As per the G-TrialsGCP, vulnerable participants also include individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are 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.

The NGHRP states that where appropriate, there should be a provision for involvement of a community in the research process right from inception to post research period. Additionally, the institutional ethics committee (EC) (research ethics committee (REC) in Uganda) must carefully consider and approve the mode of consent for participants from vulnerable populations. In order to protect vulnerable communities, ECs must ensure that selection of the particular community is justified by the research goals, and the research is relevant to the needs and priorities of the community in which it is to be conducted.

Per the NGHRP, for all vulnerable populations and individuals:

• Research can only be conducted in the population and with individuals if the objectives of the research cannot be addressed using non-vulnerable populations and individuals
• Risk of participating in research is justified by anticipated benefits
• 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 population or individual’s disorder or condition that is of vital importance for the understanding or amelioration of that disorder or condition
• ECs may co-opt a person knowledgeable about and has experience working with the vulnerable group and individuals

The G-TrialsGCP further indicates that special protections for vulnerable populations can include:

• Allowing no more than minimal risks for procedures that offer no potential individual/direct benefits for participants
• Supplementing the participant’s agreement by the permission of family members, legal guardians, or other appropriate representatives
• Requiring that the research be carried out only when it is targeting conditions that affect these populations
• Safeguards can be designed to promote voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the interests of those at increased risk of harm
• Appointment of advocates to the EC when such proposals for clinical trials on institutionalized individuals are under review

See the Children/Minors and Pregnant Women, Fetuses & Neonates sections for additional information about these vulnerable populations. See the NGHRP and the G-TrialsGCP for more examples of and details on vulnerable populations.

Persons in Hierarchical Relationships

As per the G-TrialsGCP, there is a possibility of diminished voluntariness of consent from potential participants who are in a subordinate relationship. Their agreement to volunteer may be unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate in the study or by fear of disapproval or retaliation if they refuse. Examples include medical and nursing students; subordinate hospital and laboratory personnel; workers in settings where research studies are conducted; and members of the armed forces or police.

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 NGHRP and the G-CTChldrnWmn define a child as a person below the age of 18.

According to the G-CTChldrnWmn, data supporting the conduct of a clinical trial involving children should demonstrate that the benefit to the population outweighs the risk. For interventions or procedures that have no potential individual benefits for children:

• The risks must be minimized and no more than minimal;
• The purpose of the research must be to obtain knowledge relevant to the particular health needs of the population;
• The social value of the research for the children is compelling, and the research cannot be conducted in any other population; and
• Any research-related risk is the least possible for achieving the objectives of the research

While consent from the child’s parent or guardian is required in most cases, the NGHRP does allow for mature and emancipated minors, as described below, to provide consent. As per the NGHRP, mature minors are defined as individuals 14-17 years of age who have drug or alcohol dependency or a sexually transmitted infection. Emancipated minors are defined as individuals below the age of majority (18 years) who are pregnant, married, have a child, or are self-sufficient. Mature and emancipated minors are permitted to independently provide informed consent to participate in research if the following conditions exist:

• The institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approves the research study as acceptable to the parents/legal guardians based on evidence from the community
• The protocol provides clear justification for targeting mature and emancipated minors as participants, and for not involving parents/legal guardians in the consent process

Assent Requirements

The NGHRP requires a child’s affirmative agreement to participate in research when the child is eight (8) years of age and older. A child's assent is obtained after the parent’s/legal guardian’s consent is obtained. The child’s assent or dissent takes precedence over the parent’s/legal guardian’s consent.

The G-CTChldrnWmn further indicates that for pediatric studies, adequate provisions should be made for soliciting the assent of the children and permission of their parents/legal guardians. Investigators should provide an understandable age-specific informed assent and information sheet for children.

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-CTChldrnWmn states that data supporting the conduct of a clinical trial involving pregnant/lactating women should demonstrate that the benefit to the population outweighs the risk. For interventions or procedures that have no potential individual benefits for pregnant/lactating women:

• The risks must be minimized and no more than minimal;
• The purpose of the research must be to obtain knowledge relevant to the particular health needs of the population;
• The social value of the research for the pregnant/lactating women is compelling, and the research cannot be conducted in any other population; and
• Any research-related risk is the least possible for achieving the objectives of the research

According to the G-CTChldrnWmn, legally valid consent should be obtained from the participant or spouse as appropriate and in line with the NGHRP. As per the NGHRP, any Ugandan clinical studies involving pregnant women and fetuses require additional safeguards to ensure that the research conforms to appropriate ethical standards and upholds societal values. Informed consent should be obtained from both the mother and father of the embryos and fetuses. However, the father's consent is not required if: (i) the purpose of the study is primarily to meet the mother's health needs; (ii) the father's identity and/or whereabouts are unknown; (iii) the father is not reasonably available; or (iv) the pregnancy resulted from rape or incest and (v) the father is incompetent to give consent.

The G-CTChldrnWmn further indicates that for clinical trials involving pregnant women that have the potential for harm to the fetus, the participant should be informed about the potential risks, and research should be conducted only after assessing that the benefits (to the mother or fetus, as appropriate) outweigh the risk involved, and with informed consent of the participants.

(See the Required Elements section for general informed consent form requirements.)

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.

The G-TrialsGCP states that residents of prisons are often considered vulnerable because in a confined setting, they have few options and are denied certain freedoms that non-institutionalized persons enjoy. Some individuals with this characteristic may also have diminished capacity to consent, and therefore require the additional protections for participants who lack decisional capacity.

Institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda) must review the need for special protection of the rights and welfare of these vulnerable populations and include protections when necessary.

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

The G-TrialsGCP states that residents of mental institutions are often considered vulnerable because in a confined setting, they have few options and are denied certain freedoms that non-institutionalized persons enjoy. Some individuals with this characteristic may also have diminished capacity to consent, and therefore require the additional protections for participants who lack decisional capacity.

Institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda) must review the need for special protection of the rights and welfare of these vulnerable populations and include protections when necessary.

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 NGHRP, the NDPA-CTReg, the G-CTConduct, the G-GMPAnnexes, and the G-TrialsGCP, an investigational product (IP) (also referred to as an investigational medicinal product (IMP) in Uganda) is defined as a pharmaceutical form of an active ingredient or a placebo being tested or used as a reference in a clinical trial. Per the NDPA-CTReg, the G-CTConduct, the G-GMPAnnexes, and the G-TrialsGCP, an IP includes a product with registration when used or assembled (formulated or packaged) in a way different from the approved form; when used for an unapproved indication; or 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 NDPA-CTReg, the G-CTConduct, and the G-TrialsGCP, the National Drug Authority (NDA) is responsible for authorizing the manufacture of investigational products (IPs) in Uganda. The NDA will only approve the manufacture of an IP after approval of the clinical trial application. The NDPA-CTReg indicates that if the IP is to be manufactured in Uganda, the holder of the clinical trial certificate must apply to the NDA for a manufacturing license.

Uganda follows the G-GMPMedicinal, the G-GMP-APIs, and the G-GMPAnnexes for good manufacturing practice (GMP), which were adopted from Pharmaceutical Inspection Co-operation Scheme (PIC/S) guidance. Per the G-GMPMedicinal, the holder of the NDA’s manufacturing authorization must manufacture IPs to ensure that they are fit for their intended use; comply with the requirements of the clinical trial authorization; and do not place participants at risk due to inadequate safety, quality, or efficacy. The G-GMPAnnexes further states that for manufacturers to be able to apply and comply with GMP for IPs, cooperation between manufacturers and sponsors of clinical trials is required. This cooperation should be described in a technical agreement between the sponsor and manufacturer.

The G-GMP-APIs indicates that when manufacturing active pharmaceutical ingredients (APIs) for use in clinical trials, process and test procedures should be flexible to provide for changes as knowledge of the process increases and clinical testing of a drug product progresses from pre-clinical stages through clinical stages. Once drug development reaches the stage where the API is produced for use in IPs, manufacturers should ensure that APIs are manufactured in suitable facilities using appropriate production and control procedures to ensure the quality of the API. Additionally, the manufacture of APIs for use in clinical trials should be documented in laboratory notebooks, batch records, or by other appropriate means.

See the G-GMPMedicinal, the G-GMP-APIs, and the G-GMPAnnexes for more detailed manufacturing requirements.

Import

The NDA is responsible for authorizing the import of IPs. The NDPA-CTReg and the G-CTConduct state that prior to IP import or manufacture, the sponsor or principal investigator (PI) must be granted a clinical trial certificate by the NDA. According to the NDPA-CTReg, the holder of the clinical trial certificate must then apply for a permit to import the IP approved for the trial.

According to the G-VerImprtExprt, an application for an import verification certificate under extraordinary circumstances (which include clinical trials approved by the NDA) must be submitted electronically through the National Drug Authority Management Information System (NDAMIS) (UGA-34) by a person duly authorized to import drugs into Uganda (an import license holder). The G-VerImprtExprt includes clinical trials approved by the NDA in its definition of “extraordinary circumstances.” The application should be accompanied by:

• A clinical trial certificate for drugs for use in clinical trials
• A copy of the proforma invoice from the supplier
• A donation certificate, if applicable
• Authorization for drugs to be used in a medical camp, if applicable
• Evidence of current GMP compliance of the manufacturer. The manufacturer should have GMP certification issued by the NDA, or the national medicines regulatory authorities of the following countries/regions: the United States of America (USA), the European Union (EU), the United Kingdom (UK), Switzerland, Canada, Australia, Iceland, Liechtenstein, Norway, or prequalified by the World Health Organization
• Documented evidence/justification describing the emergency or extraordinary circumstance
• A filled application form for the authorization for importation of narcotic drugs and psychotropic substances and precursors, if applicable
• Evidence of registration of the drug(s) in the country of origin or emergency use approval of the drug by the competent authority in the country of origin, by a supranational body and any other regulatory authority if not registered

As stated in the G-VerImprtExprt, the application is screened for completion and correctness, then the applicant is billed the prescribed fees (see the NDPA-FeesReg for more information). The NDA will issue a verification certificate upon receipt of a successful application. The verification certificate is valid for 12 months from the date of issue.

See the G-VerImprtExprt for detailed import permit application submission requirements and review procedures. Additionally, see the Submission Process, Submission Content, and Regulatory Fees sections for detailed clinical trial application requirements.

Please note: Uganda is party to the Nagoya Protocol on Access and Benefit-sharing (UGA-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 UGA-21.

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 NDPA-CTReg, the sponsor is responsible for updating the Investigator’s Brochure (IB), which is a compilation of the clinical and non-clinical data on the investigational product(s) (IPs). The G-TrialsGCP further indicates that the IB should be reviewed at least annually and revised as necessary in compliance with a sponsor's written procedures. Relevant new information may be so important that it should be communicated to the investigator(s), and possibly to the institutional ethics committee(s) (ECs) (research ethics committees (RECs) in Uganda) and/or regulatory authorities, before it is included in a revised IB.

According to the G-TrialsGCP, the sponsor is generally responsible for ensuring that an up-to-date IB is made available to the investigator(s), and the investigators are responsible for providing the up-to-date IB to the responsible ECs and the National Drug Authority (NDA). In the case of an investigator sponsored trial, the sponsor-investigator should determine whether a brochure is available from the commercial manufacturer. If the IP is provided by the sponsor-investigator, then the sponsor-investigator should provide the necessary information to the trial personnel. In cases where preparation of a formal IB is impractical, the sponsor-investigator should provide, as a substitute, an expanded background information section in the trial protocol that contains the minimum current information described in this guideline.

The G-TrialsGCP, the NDPA-CTReg, and UGA-4 require the IB to provide coverage for 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 (pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post-marketing experiences)
• Summary of data and guidance for the investigator(s)

See Section 7.3 of the G-TrialsGCP for detailed content descriptions, and UGA-4 or Schedule 2 of the NDPA-CTReg for the format of the IB.

Quality Management

Uganda follows the G-GMPMedicinal, the G-GMP-APIs, and the G-GMPAnnexes for good manufacturing practice (GMP), which were adopted from Pharmaceutical Inspection Co-operation Scheme (PIC/S) guidance. Per the G-GMPMedicinal, GMP ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the clinical trial authorization. The forementioned documents must be used for periodic GMP inspection of all manufacturers of medicinal products within and outside Uganda whose products are registered or subjected to registration in the country. Manufacturers that are GMP compliant will be issued GMP compliance certificates.

According to the G-CTConduct and the G-TrialsGCP, the sponsor must ensure that the IP(s) is manufactured in accordance with GMP. The G-CTConduct further indicates that evidence of manufacture under GMP standards must be submitted with the clinical trial application to the NDA. In cases where the principal investigator (PI) is not the manufacturer and where confidentiality considerations prevent disclosure of certain information to the PI, any relevant IP/application information may be submitted to the NDA through the PI in a sealed envelope marked “CONFIDENTIAL.” Alternatively, the information may be sent to the Clinical Trials Unit with the necessary password protection at clinicaltrials@nda.or.ug.

The G-TrialsGCP states that if significant formulation changes are made in the investigational or comparator product(s) during the course of clinical development, the results of any additional studies of the formulated product(s) (e.g., stability, dissolution rate, bioavailability) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical trials and submitted to the NDA for review and authorization.

According to the G-GMPAnnexes, the manufacturer should establish and maintain a quality control system placed under the authority of a person who has the requisite qualifications and is independent of production. Quality control of the IP, including that of the comparator product, should be performed in accordance with the information submitted in the application for the clinical trial. See the G-GMPMedicinal and the G-GMPAnnexes for more information on quality control requirements.

Additionally, the G-GMPAnnexes indicates that a pharmaceutical quality system which is designed, set up, and verified by the manufacturer should be described in written procedures, taking into account the guidance in the G-GMPMedicinal that is applicable to IPs. The product specifications and manufacturing instructions may be changed during development, but full control and traceability of the changes should be documented and maintained. The selection, qualification, approval, and maintenance of suppliers of starting materials, together with their purchase and acceptance, should be documented as part of the pharmaceutical quality system to ensure the integrity of the supply chain and protect against falsified products. The product specification file should be continually updated as development of the product proceeds, ensuring appropriate traceability to the previous versions. It should include, or refer to, at least the following documents:

• Specifications and analytical methods for starting materials, packaging materials, intermediate product, bulk product, and finished product
• Manufacturing methods
• In-process testing and methods
• Approved label copy
• Relevant clinical trial authorizations and amendments thereof, clinical trial protocol, and randomisation codes, as appropriate
• Relevant technical agreements with contract givers and acceptors, as appropriate
• Stability plan and reports
• Details of plans and arrangements for reference and retention samples
• Storage and transport conditions
• Details of the supply chain including manufacturing, packaging, labeling, and testing sites for the IPs

For more information on pharmaceutical quality system requirements, see the G-GMPMedicinal and the G-GMPAnnexes.

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.

Labeling for investigational products (IPs) (known as investigational medicinal products (IMPs) in Uganda) must comply with the requirements set forth in the G-GMPAnnexes, the NDPA-CTReg, the G-CTConduct, the NGHRP, and the G-TrialsGCP. As specified in the G-GMPAnnexes, the labeling operation should be performed at an authorized manufacturing site.

As per the NGHRP and the G-TrialsGCP, the sponsor is responsible for ensuring the proper labeling of the IPs. The IPs and comparator products must be labeled in conformity with the clinical protocol.

According to the NDPA-CTReg and the G-CTConduct, the IP must be labelled as specified in UGA-7 or Form 37 of the NDPA-CTReg. The NDPA-CTReg, the G-GMPAnnexes, and UGA-7 require the following labeling information to be included on both the outer packaging and the immediate container (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• The name, address, and telephone number of the sponsor or manufacturer; the G-GMPAnnexes specifies the investigator or contract research organization could also be the main contact for IP information, clinical trial, and emergency unblinding
• The name/identifier and strength/potency, and in the case of blinded trials, all product labeling should indicate “placebo/comparator or [name/identifier] + [strength/potency]”
• The pharmaceutical dosage form, route of administration, and quantity of dosage units
• 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 or treatment number and, where relevant, the visit number
• The investigator’s name (if not already provided on the label)
• The storage conditions
• Pack sizes (unit or volume)
• The instructions for use
• The period of use (use-by date, expiration date, manufacturing date, or re-test date), in month/year format
• “For clinical trial use only” or similar wording
• “Keep out of reach of children” except when the IP is for use in trials where it is not taken home by participants

The G-GMPAnnexes further states that where products are blinded, systems should be in place to ensure that the blind is achieved and maintained while allowing for identification of “blinded” products, when necessary, including batch numbers of the products before the blinding operation. Rapid identification of the product should also be possible in an emergency. Where the manufacturer has been delegated the responsibility for generation of randomization codes, the manufacturer should ensure that unblinding information is available to the appropriate responsible investigator site personnel before the IPs are supplied. The expiry date assigned to all products for use in the trial should be the expiry of the shortest dated product so that the blinding is maintained.

For additional detailed labeling information and exceptions, see the G-GMPAnnexes.

The G-TrialsGCP requires that in blinded trials, the coding system for IPs should include a mechanism that permits rapid identification of the products in case of a medical emergency, but does not permit undetectable breaks of the blinding. The G-CTConduct further indicates that a sample of the label for imported products must be included with the clinical trial application to the National Drug Authority (NDA).

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

The G-KenyaCT also states that the sponsor must submit to the PPB a copy of the endorsed Clinical Trial Import License and/or evidence of delivery to the approved investigator(s)/institution(s) upon importing and supplying each product consignment. In addition, the IP must only be supplied to the investigator(s)/institution(s) named in the application for the Clinical Trial Import License/Clinical Trial Exemption for the purpose and use specified. The sponsor must inform the PPB in the event of any information changes including:

• Information the sponsor receives that casts doubt on the continued validity of the submitted data
• Information associated with the Clinical Trial Import License

See the G-KenyaCT for additional information on principal investigator requirements relating to the Clinical Trial Import License.

Record Requirements

As per the G-KenyaCT, the sponsor is required to maintain records that document IP(s) shipment, receipt, disposition, return, and destruction. The sponsor must also maintain a system for retrieving IPs and documenting this retrieval, and maintain a system for the disposition of unused IPs.

According to the G-KenyaCT, IP manufacturers or importers must also retain samples for each batch of bulk product, and the packaging components used for each finished batch, for at least two (2) years following the trial. The sponsor should maintain sufficient samples from each batch and keep a record of their analyses and characteristics for reference so that, if necessary, an independent laboratory could reconfirm the same data.

Supply, Storage, and Handling Requirements

As delineated in the G-TrialsGCP and the G-CTConduct, the sponsor must ensure timely delivery of the investigational product(s) (IP(s)) to the principal investigator (PI)/investigator(s). Additionally, the sponsor must maintain sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary. The G-TrialsGCP further states that the sponsor should not supply the investigator(s)/institution(s) with the IP(s) until the sponsor obtains National Drug Authority (NDA) and institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approvals. However, according to the NDPA-CTReg, the PI is responsible and accountable for the IP.

Furthermore, per the G-TrialsGCP, the sponsor should ensure that written procedures include instructions that the investigator/institution should follow for the handling and storage of IP(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from participants, and return of unused IP(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the NDA approved protocol and/or where available, applicable regulatory requirement(s)).

As delineated in the G-GMPAnnexes, IPs are normally packed individually for each participant included in the clinical trial. The number of units to be packaged should be specified prior to the start of the packaging operations, including units necessary for carrying out quality control and for any retention samples to be kept. Sufficient reconciliations should take place to ensure that the correct quantity of each product required has been accounted for at each stage of processing. Procedures should describe the specification, generation, testing, security, distribution, handling, and retention of any randomization code used for packaging IPs, as well as code-break mechanism. Appropriate records should be maintained.

Per the G-GMPAnnexes, packaging must ensure that the IP remains in good condition during transport and storage at intermediate destinations. Any opening or tampering of the outer packaging during transport should be readily discernible. Where the manufacturer is delegated by the sponsor to perform the regulatory release of the IP, the arrangements should be defined in an agreement between the sponsor and the manufacturer. Relevant clinical trial authorization and amendment information should be available for reference in the product specification file, and the manufacturer should ensure the necessary clinical trial authorizations are in place prior to shipping the product for use in the trial.

Per the G-TrialsGCP and the G-CTConduct, the sponsor must also maintain a system for retrieving IP(s), as well as for the disposal of unused IP(s). The G-GMPAnnexes further delineates that returned IPs should be clearly identified and stored in an appropriately controlled, dedicated area. The manufacturer or sponsor’s representative should destroy IPs only with prior written authorization by the sponsor. The arrangements for destruction of IPs must be described in the protocol. Any arrangement between sponsor and manufacturer regarding IP destruction should be defined in their technical agreement. Destruction of unused IPs should be carried out only after reconciliation of delivered, used, and recovered products and after investigation and satisfactory explanation of any discrepancies upon which the reconciliation has been accepted.

See the G-GMPAnnexes, the G-TrialsGCP, and the G-CTConduct for detailed sponsor-related IP requirements.

Record Requirements

As per the G-CTConduct and the G-TrialsGCP, the sponsor must maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s). The sponsor must also maintain a system for documenting the retrieval of IP(s) and the disposal of unused IP(s), as well as records of batch sample analyses and characteristics.

Per the G-GMPAnnexes, there must be sufficient documentation to demonstrate that appropriate segregation has been maintained during any IP packaging operations. To facilitate a recall of the IP, a detailed inventory of the shipments made by the manufacturer should be maintained. Inventory records of returned IPs should be kept. Additionally, records of destruction operations should be retained, including a dated certificate of destruction or a receipt for destruction to the sponsor. These documents should clearly identify or allow traceability to the batches and/or participant numbers involved, and the actual quantities destroyed.

The G-CTConduct indicates that the pharmacist of record must maintain instructions for the handling of IP(s) and trial related materials, if not indicated in the protocol or Investigator’s Brochure (IB). The pharmacist must also maintain shipping records for the IP(s) and trial related material, as well as for receipt date(s) of product delivery and quantity.

According to the G-GMPAnnexes, product specification file documents must be retained for at least five (5) years, and the sponsor should retain the clinical trial master file for at least 25 years after the end of the trial, unless otherwise specified in relevant national laws. If the sponsor and the manufacturer are not the same entity, the sponsor must make appropriate arrangements with the manufacturer to fulfil the clinical trial master file retention requirement. Arrangement for retention of such documents and the type of documents to be retained should be defined in an agreement between the sponsor and manufacturer. Per the G-GMPMedicinal and the G-GMPAnnexes, batch documentation/manufacturing records must be retained by the manufacturer for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the batch was used.

Specimens are not defined in the Kenyan regulations. However, per KEN-26, the Kenya Medical Research Institute (KEMRI) identifies biological samples and specimens as including, but not limited to, blood samples, saliva, breast milk samples, mosquito parts samples, biological cultures, tissue and tissue samples, hair samples, human stool, and environmental samples used in human health research.

In Uganda, a specimen is also referred to as human material. As delineated in the NGHRP, human biological materials consist of any substance obtained from a human research participant. This material includes, but is not limited to: blood, urine, stool, saliva, hair, nail clippings, skin, microorganisms, and other associated bio-products.

Import/Export

Per the G-ECBiomedRes, biological material must not be imported nor exported without proper justification and authorization, which includes a signed material transfer agreement (MTA) approved by the relevant institutions and deposited with the National Commission for Science, Technology and Innovation (NACOSTI). For exports, a Kenyan investigator must be included in the team that is conducting the research in the recipient country. All biological samples and data collected during research belong to the local participating institutions and country.

In addition, KEN-37 has indicated that Kenya’s Pharmacy and Poisons Board (PPB) will approve of an export for overseas research if the following requirements are met:

• PPB initial approval letter or annual approval letter
• Ethics committee (EC) approval letter
• MTA
• Study protocol with a summary justification for the participants' sample exportation
• Informed consent form that highlights the areas where study participants are informed about the exportation of their samples

The G-KenyaCT states that in the case of transfer of materials during research involving children, the sponsor or the representative or the principal investigator should provide to the EC an MTA including, but not limited to, the following information:

• Identification of the provider and recipient
• Definition of the trial and how the material will and will not be used
• Maintenance of confidentiality of background of supporting data or information, if any
• Indemnification and insurance

In addition, KEN-26 provides an example of the Kenya Medical Research Institute (KEMRI)'s procedures for handling requests to ship biological samples or specimens. KEN-17 also provides an example of an MTA form from the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee.

Import/Export

The G-CTConduct states that applications for import and/or export of biological materials, if applicable, must be included in the clinical trial application to the National Drug Authority (NDA).

Additionally, the NGHRP delineates that all exchanges and transfers, including importation and exportation of human materials for research purposes, require Uganda National Council for Science and Technology (UNCST) clearance, except for the exchange of human materials between organizations within Uganda. In order to justify transfer of human materials abroad, investigators, sponsors, and collaborators should demonstrate that in-country capacity to perform certain types of investigations/testing does not exist or is inadequate. Per the G-UNCSTreg, where it is proven that no capacity for a given investigation exists in Uganda, or where exchange of research material is needed for quality assurance purposes or other justifiable reasons, research materials may be transferred to, exported to, or exchanged with more advanced facilities abroad.

Per the NGHRP and the G-UNCSTreg, the following are the necessary steps for the exchange or transfer of human materials for research purposes abroad or from abroad:

• The research project that involves the exchange or transfer of human material must first be registered by the UNCST
• The applicant must be a legal resident of Uganda and be affiliated with a locally registered and recognized organization in Uganda
• A request for exchange or transfer of human material must be made in writing to the Executive Secretary of the UNCST
• A Material Transfer Agreement (MTA) and any other document related to the exchange or transfer of human material must accompany the request for the exchange or transfer of the material

According to the NGHRP, the UNCST is required to provide feedback within 14 calendar days from the submission date. However, the G-UNCSTreg states that the UNCST must provide feedback within 10 working days from the submission date. The feedback may be an approval or clearance, a rejection or disapproval, or comments to improve the quality of the application. Once the UNCST approval is obtained, the investigator can proceed to facilitate the transfer, export, or exchange of the research specimen.

Material Transfer Agreement

As set forth in the NGHRP and the G-UNCSTreg, the UNCST application for permission to transfer, export, or exchange samples for research purposes from one (1) organization to another, within the country and abroad, must be accompanied by an MTA between the provider organization and the recipient organization. Per the NGHRP, the MTA should include the following details:

• A list of the parties and their addresses; the MTA is signed only by authorized party representatives and the effective date of the MTA must be indicated
• A detailed description of the materials to be exchanged
• The purpose for transfer or export of the human biological substance
• A list of authorized users of the materials
• The location where the material is to be transferred
• Period of use and disposal plans for the material
• Clear arrangements for benefit sharing of any accruing or anticipated future benefit at the point of termination
• The provider organization should state whether the recipient organization is permitted to own any of the derivatives or products discovered through the use of the material
• Directions for handling product commercial rights
• Publication requirements/restrictions, including citation requirements if information about the material is published
• The governing law(s) of the provider’s and recipient’s countries
• Recipient organization’s responsibilities for the proper handling and use of the material
• Recipient and provider agreement on liability for any misuse of the material
• Description of specific restrictions for the recipient organization
• A statement indicating what technologies would be transferred to the provider organization or country, if applicable
• A warranty stating that the material is being provided “as is”
• A clause stating that the MTA may be amended at any time by written mutual consent of the parties

See Section 10.4 of the NGHRP for detailed MTA requirements. Per the UNCST-RevTemp, data ownership and associated intellectual property rights in both the Data Sharing Agreements and MTAs must be discussed and agreed upon by collaborating partners at the inception of a research study within the context of the investigator's institutional regulations/provisions. Templates of Data Sharing Agreements and MTAs, as applicable, must be presented as part of the research protocol to be reviewed by the institutional ethics committee (EC) (research ethics committee (REC) in Uganda).

See the G-Biobank for more information on the collection, receipt, storage, processing, and dissemination of biological specimens by biobanks in Uganda.

Detailed information is currently unavailable regarding Kenya’s Pharmacy and Poisons Board (PPB)’s requirements for obtaining informed consent from participants prior to collecting, storing, or using their biological sample(s). However, the G-KenyaCT states that for research involving children, the sponsor or the representative or the principal investigator should provide examples of patient information leaflets and informed consent forms (ICF) to the ethics committee (EC) for any proposed archiving of biological specimens for later research, or for genetics research.

The G-ECBiomedRes requires that participants are made aware of the use of personal data through informed consent, including secondary data and biological material in biobanks. The secondary use of data requires approval by an accredited EC. The investigator must obtain consent from the participants for the new study. For situations where this is not practicable, the relevant accredited EC can approve a waiver of individual consent following confirmation that the participants had previously consented to storage of the biological samples/data, and that this data is delinked from personal identifiers. In cases where the sample is stored in a foreign institution, the collaborating EC should also conduct its own deliberation. Researchers sending samples abroad must ensure that consent for transfer of materials was obtained during collection of the samples and that the collaborating EC gave approval.

See KEN-4 for Kenya Medical Research Institute (KEMRI)'s sample ICF that includes guidance on specimens. As another example, see KEN-17 for the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee’s form and guidance on genetic research and biobanking.

See the Required Elements and Participant Rights sections for additional information on informed consent.

In accordance with the NGHRP, investigators must comply with several informed consent requirements for the acquisition, storage, and future use of human biological samples from research participants in Uganda.

For any research involving the collection of human biological or genetic materials, the investigator must provide an explanation to the research participant in the informed consent form (ICF) regarding how the specimens will be managed at the end of the study.

For samples to be stored for future use, the investigator is also required to obtain a separate informed consent from the participant. This process includes the use of a separate ICF that states the following:

• The purpose of the sample storage
• The quantities of samples to be stored
• The location of the stored samples
• Measures the investigator will take to protect participant confidentiality
• The policies that will govern the use of the samples in future research
• The potential risks and benefits of storing samples for future research
• Any other information deemed necessary by the investigators, the institutional ethics committee (EC) (research ethics committee (REC) in Uganda), and the Uganda National Council for Science and Technology (UNCST)

As per the NGHRP, the investigator must also give the research participant the right to choose whether the samples should or should not be stored for future studies. A Ugandan scientist must be included as co-investigator in all future studies using the human materials collected from Uganda. Participants must not be penalized for their refusal to store the samples and reserve the right to withdraw their samples from storage if the samples are linked. Any future research study on such samples is subject to review by an EC. Where identifiable samples have been collected, for example, as part of routine surveillance, emergency procedures, laboratory quality control, notifiable diseases, routine counseling and testing, etc., without the prior intention of conducting research on the samples, the samples’ sources must be traced to provide consent for use of the samples in research.