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 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.

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-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

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).

No applicable 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

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

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

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

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

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 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 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

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 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

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

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

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 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 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

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 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

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.

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.

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.)

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.

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.

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 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 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.

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

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.

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

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.

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.