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.

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.

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.

Contact Information

National Drug Authority

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

National Drug Authority
Head Office
Plot 19 Lumumba Avenue
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
Innovation & Research Desk Toll Free Line: [0]800 101 999
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-26, 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 and UGA-20, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the institutional level ethics committee (EC) (research ethics committee (REC) in Uganda) and the Uganda National Council for Science and Technology (UNCST) approvals in the application. UGA-33 further notes that for clinical trials involving human participants, institutional EC approval must be obtained through the institutional EC portal before the NDA portal. Therefore, the NDA and institutional EC reviews may not be conducted in parallel. 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 UNCST clearance.

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, as amended by the NDPA-CTRegAmdt, 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.

Expedited review of an application is applicable for:

• Clinical trial applications for investigational drugs to provide treatment where no therapy exists
• Clinical trials conducted in an emergency, such as during a disease outbreak
• 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

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 (See Form 35 in Schedule 1 of the NDPA-CTReg, as amended by the NDPA-CTRegAmdt). Applicants may apply for renewal of this approval with the Application Form for Renewal of Authorisation of Clinical Trial (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 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.

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.

As per the NDPA-CTReg, an application for deviation from a condition of a clinical trial must use Form 36 and must be accompanied by evidence of ethical approval of the amendment to the clinical trial protocol, where applicable. Per the G-CTConduct, the 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 proposed changes must be listed in a cover letter signed by the applicant, and a clear step-by-step justification for each proposed change(s) must be provided. The possible consequences with regard to the benefit/risk balance for participants already enrolled in the trial must also be summarized in the cover letter.

See the G-CTConduct for detailed NDA amendment review procedures.

See Appendix V of the G-CTConduct or UGA-22 for the clinical trial application amendments screening form. (See the Submission Process, Submission Content, and Timeline of Review sections for detailed submission requirements and review timeline information.)

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. (See the Submission Content and Submission Process sections for submission requirements.) 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 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: 9003008068851 (US Dollars) and 903005759829 (Ugandan shillings)
Swift code: SBICUGKX
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

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

See Sections 4.5.1 and 4.9 of the NGHRP for additional 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 and UGA-20, proof of institutional EC approval must be submitted in a clinical trial application to the National Drug Authority (NDA). UGA-33 further notes that for clinical trials involving human participants, institutional EC approval must be obtained through the institutional EC portal before the NDA portal. Therefore, the NDA and institutional EC reviews may not be conducted in parallel.

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 deviation from a condition 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).

According to the G-RECs, institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda) may independently decide what fee to charge for a protocol review. The only instruction provided is that an EC must indicate its fee policy and structure in its self-assessment report submitted to the Uganda National Council for Science and Technology (UNCST) to meet its accreditation requirements.

Overview

The Uganda National Council for Science and Technology (UNCST) is the central statutory body responsible for the registration, auditing, and accreditation of institutional ethics committees (ECs) (research ethics committees (RECs) in Uganda). As per the G-RECs, the UNCST was created under the UNCST-Act to conduct research and development coordination and oversight. 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.

According to the G-RECs, the UNCST’s core responsibilities center on:

• Improving the efficiency and effectiveness of EC operations
• Ensuring that ECs provide the highest possible ethical standards and protection to research participants
• Building public trust and confidence in Uganda’s national ethical review system

Registration, Auditing, and Accreditation

As per the NGHRP and the G-RECs, the UNCST must accredit all ECs.

Per the G-RECs, UNCST accreditation involves a two (2)-stage process in which the EC conducts a self-assessment and submits a report along with an accreditation application. The Accreditation Committee for RECs in Uganda (ACRECU) then reviews the application and inspects the institution. The outcome of the ACRECU reviews is communicated to the EC and the institution within 14 working days from the site inspection date. Accreditation is granted for three (3) years. In order to apply for renewal, an EC must follow the same procedures as in its initial application. The renewal application must be submitted three (3) months prior to the accreditation expiration date. The NGHRP indicates that an EC is not permitted to commence its activities until authorization is received from the ACRECU. See the G-RECs for additional details on the UNCST accreditation process, and UGA-9 for the accreditation application form. See Section 4.2 of the NGHRP for details on EC establishment requirements. A list of UNCST-accredited ECs is also available through UGA-11.

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 a mandatory before a study may commence.

Per the NDPA-CTReg and UGA-20, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the institutional EC and UNCST approvals in the application. UGA-33 further notes that for clinical trials involving human participants, institutional EC approval must be obtained through the institutional EC portal before the NDA portal. Therefore, the NDA and institutional EC reviews may not be conducted in parallel. 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 UNCST clearance.

According to UGA-31, before a clinical trial can be conducted, approvals must be obtained in the following order:

• Administrative clearance from the institution where the trial will be conducted (institutional requirement). Foreign entities applying to the NDA or UNCST are required to obtain a letter of support or introduction from a local Ugandan institution
• Primary EC review and approval
• UNCST research clearance and approval
• NDA regulatory approval for clinical trial certificate
• NDA authorization to import the investigational product (Import Verification certificate). The Importer of Record should have an NDA Annual Import License

In addition, the applicant must seek approval(s) from any required foreign EC(s). Submission to the foreign EC can occur before, concurrently with, or after local EC review and approval.

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

In those cases 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). Furthermore, the G-CTConduct indicates that based on the clinical trial agreement between the sponsor and the principal investigator (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. See Appendix I of the G-CTConduct for the clinical trial application form.

Per C-IncompleteCTA, incomplete submissions will not be received at the NDA registry. All submissions that are deemed incomplete will be returned with a checklist indicating the missing regulatory requirements.

According to the G-CTConduct, an application to conduct a clinical trial must be submitted to:

The Secretary to the Authority
National Drug Authority
P.O. Box 23096
Rumee Towers, Plot 19 Lumumba Avenue
Kampala, Uganda
Phone: (+256) 417 788 100 / 1 0417 799 124 0417 788 129
Fax: (+256) 41 255758 / 343921
Email: ndaug@nda.or.ug; or clinicaltrials@nda.or.ug (per UGA-31)

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.

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.

The online application for UNCST permission to conduct research in Uganda is provided in UGA-28.

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 the National Research Information Management System (NRIMS) (UGA-33).

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 G-CTConduct and UGA-1, the following documentation must be submitted to the National Drug Authority (NDA) in a clinical trial application (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• Proof of payment
• Applications for import and/or export of biological materials (if required)
• Clinical Trial Application Form
• Trial Protocol
• Investigator’s Brochure (See UGA-4 or Schedule 2 of the NDPA-CTReg)
• Participant Information Leaflet and informed consent
• Certificate of Good Manufacturing Practice (GMP) of the trial medicine or other evidence of manufacture quality, safety, and consistency
• Package insert(s) for other trial medicines
• 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
• Signed and completed declarations by all investigators (See UGA-16 or Form 31 in Schedule 1 of the NDPA-CTReg)
• Approval of ethics committees (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 investigational products (IPs)
• 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 or Form 34 in Schedule 1 of the NDPA-CTReg)
• 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 principal investigator (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

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.

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 UGA-28 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 and UGA-28, EC approval is obtained through the National Research Information Management System (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:

• Product name and dosage form
• Trial identification
• Trial objective
• Trial design
• Trial participants
• Treatment profile
• Trial parameters
• Operational aspects
• Adverse event reporting methods
• Evaluation of results
• PI and co-investigator(s) names

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

Overview

Per the NDPA-CTReg and UGA-20, the National Drug Authority (NDA)’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the institutional ethics committee (EC) (research ethics committee (REC) in Uganda) and Uganda National Council for Science and Technology (UNCST) approvals in the application. UGA-33 further notes that for clinical trials involving human participants, institutional EC approval must be obtained through the institutional EC portal before the NDA portal. Therefore, the NDA and institutional EC reviews may not be conducted in parallel. 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.

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 60 working days.

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.

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.

The G-CTConduct indicates that expedited review, under which a regulatory decision is given to the applicant within 30 working days, is applicable for certain clinical trial applications. See the Scope of Assessment section for more information.

Additionally, UGA-24 indicates that the NDA conducts annual reviews of ongoing trials within 20 working days and reviews amendments of clinical trial authorization within 20 working days.

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 is 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.

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 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

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.

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)/Serious Adverse Drug Reaction (SADR) – 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/SADRs to the sponsor within 48 hours of first knowledge. The report should identify each participant by an assigned number. When the SAE/SADR results in the participant’s death, the PI should 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/SADR. A detailed report of the SAE/SADR 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.

The G-TrialsGCP and the G-CTConduct further indicate that the PI is also required to report to the NDA no later than seven (7) calendar days upon receiving notice of an SAE/SADR. The initial reports to the NDA 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.

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.

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 should provide written notice to the NDA within three (3) working days of this action and the reasons why this action was taken.

Reporting Requirements for SUSARs

As set forth in the NDPA-CTReg, the PI should record and report to the sponsor any suspected unexpected serious adverse reaction (SUSAR) that occurs during the course of trial. In turn, the sponsor should 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.

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.

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.

See Schedule 2 of the NDPA-CTReg or UGA-6 for the format of the clinical trial report.

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.

However, 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-GMPMedicinalAnnexes, 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. Further, the G-GMPMedicinalAnnexes states that sponsors are required to assume ultimate responsibility for all aspects of the clinical trial including the quality of investigational medicinal products.

The NDPA-CTReg also specifies that in order to submit a clinical trial application, the sponsor must be one 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

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

Overview

Based on 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 and licensed by a 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, additional clinical trial sites, or investigator changes must be made using Form 37 in Schedule 1 of the NDPA-CTReg or UGA-13 and 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 35 in Schedule 1 of the NDPA-CTReg, as amended by the NDPA-CTRegAmdt, for the clinical trial certificate.

Data and Safety Monitoring Board

In addition, 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 also indicates that the clinical trial application must provide evidence that each member of the investigator 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

According to 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.

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 evidence of the NDA notification be provided to the EC 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 step-by-step retrospective assessment of data quality and study performance. These SOPs should cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties 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 NDPA-CTReg and the G-CTConduct state that the sponsor should retain documents for a minimum period of 20 years and inform the National Drug Authority (NDA) in writing prior to destroying any documents.

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

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

Responsible Parties

For the purposes of data protection requirements, the sponsor may act as a “data controller” in relation to research data. 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 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

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.

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: the requirements provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• 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 legal representative(s) and/or guardian(s); 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 legal representative(s) and/or guardian(s), 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s).

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(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s). 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 participants and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s), 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 and/or the legal representative(s) or guardian(s) has orally consented to the participation in the trial. If capable of doing so, the participant and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s), 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 and/or the legal representative(s) or guardian(s) prior to participation in the trial. The G-TrialsGCP further specifies that during the course of the trial, the participant and/or the legal representative(s) or guardian(s) 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 of, 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, the NDPA-CTReg, and the G-TrialsGCP, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• The study involves research and an explanation of its nature and purpose
• The procedures to be followed
• 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, 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 extent to which confidentiality of records identifying the participant will be maintained and who will have access to the participant’s medical records
• For research involving more than minimal risk, the policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury
• The extent of the investigator’s responsibility, where applicable, to provide medical services to the participant
• The nature, form, and extent of compensation for participation
• The identity of a sponsor and any potential conflict of interests
• The sponsors’ and the investigators’ institutional affiliation(s)
• A contact name and number of the principal investigator and/or site investigator
• Participation is voluntary, the participant can withdraw from the study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled
• The participant and/or the legal representative(s) or guardian(s) 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 institutional ethics committee (EC) (research ethics committee (REC) in Uganda)
• The 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
• Foreseeable circumstances under which the investigator(s) may remove the participant without consent
• Additional costs 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, the NDPA-CTReg, 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 the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 and the NDPA-CTReg state 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 biomedical 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 individual and/or the legal representative(s) or guardian(s).

The G-TrialsGCP further states that in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative(s) or guardian(s), if present, should be requested. When prior consent of the participant is not possible and the legal representative(s) or guardian(s) 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 the legal representative(s) or guardian(s) 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 defines a child as a person below the age of 18. 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 legal representative(s) and/or guardians based on evidence from the community
• The protocol provides clear justification for targeting mature and emancipated minors as participants, and for not involving legal representative(s) and/or guardian(s) 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 legal representative(s) and/or guardian’s consent is obtained. The child’s assent or dissent takes precedence over the legal representative’s and/or guardian’s consent.

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.

(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-GMPMedicinalAnnexes, and the G-TrialsGCP, an investigational product (IP) 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 G-GMPMedicinalAnnexes, the G-CTConduct, and the G-TrialsGCP, an IP is also referred to as an investigational medicinal product (IMP) in Uganda and includes:

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

Manufacturing

According to the NDPA-CTReg, the G-CTConduct, the G-GMPMedicinal, 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-GMPMedicinalAPIs, and the G-GMPMedicinalAnnexes 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-GMPMedicinalAPIs indicates that when manufacturing active pharmaceutical ingredients (APIs), 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 intended for clinical trials, manufacturers should ensure that APIs are manufactured in suitable facilities using appropriate production and control procedures to ensure the quality of the API.

See the G-GMPMedicinal, the G-GMPMedicinalAPIs, and the G-GMPMedicinalAnnexes 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. As per UGA-31, the NDA authorizes import of the IP through an Import Verification certificate, and the Importer of Record should have an NDA Annual Import License.

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

Per the G-GMPMedicinal, the NDA conducts periodic good manufacturing practice (GMP) inspections of all manufacturers of medicinal products within and outside Uganda. The NDA will issue a GMP compliance certificate to manufacturers that are GMP compliant. 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 sponsor or the PI is not the manufacturer, and where confidentiality considerations prevent disclosure of certain information to the sponsor or the PI, any relevant IP/application information should be submitted to the NDA through the sponsor or 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-CTConduct and the G-TrialsGCP, the sponsor must ensure that the IP(s) is manufactured in accordance with GMP. According to the G-GMPMedicinalAnnexes, the sponsor must also ensure that the IP is consistent with the details in the clinical trial application and the NDA’s authorization. This can be achieved through a change control process for the product specification file and defined in a technical agreement between the sponsor and the authorized person.

As specified in the G-GMPMedicinalAnnexes, the manufacturer or importer must design, set up, and verify a quality system that is described in written procedures and available to the sponsor. This system should take into account GMP principles and guidelines that apply to IPs.

In addition, the G-GMPMedicinal and the G-GMPMedicinalAnnexes require the manufacturer to create and/or maintain the following documentation (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• A site master file describing GMP-related activities
• A written order from the sponsor that requests the processing and/or packaging of a certain number of units and/or their shipping; it should be formally authorized and refer to the product specification file and the relevant clinical trial protocol
• Product specification file (See the documentation requirements in Annex 13 of the G-GMPMedicinalAnnexes for more information on the contents of this document)
• Specifications to serve as a basis for quality evaluation
• Manufacturing formula, processing, packaging, and testing instructions
• Standard operating procedures
• Protocols for performing and recording operations
• Technical agreements
• Records to demonstrate compliance with instructions
• A Certificate of Analysis to provide a summary of testing results on product samples with the evaluation for compliance to a stated specification
• Reports that document the conduct of investigations and the results

The G-GMPMedicinalAPIs further states that the production of active pharmaceutical ingredients (APIs) for use in clinical trials should be documented in laboratory notebooks, batch records, or by other appropriate means.

(See the Product Management section for additional information on IP supply, storage, and handling requirements).

Labeling for investigational products (IPs) (known as investigational medicinal products (IMPs) in Uganda) must comply with the requirements set forth in the G-GMPMedicinal, the G-GMPMedicinalAnnexes, the NDPA-CTReg, the G-CTConduct, the NGHRP, and the G-TrialsGCP. As specified in the G-GMPMedicinalAnnexes, for an IP to be used in a clinical trial, it must be properly labeled in the official language of the country where the trial is being conducted.

As per the NGHRP, the G-TrialsGCP, and the G-GMPMedicinalAnnexes, 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 38 of the NDPA-CTReg. The NDPA-CTReg, the G-GMPMedicinalAnnexes, and UGA-7 require the following labeling information to be included on both the outer packaging and the immediate container (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• The name, address, and telephone number of the sponsor or manufacturer; the G-GMPMedicinalAnnexes specifies the investigator or contract research organization could also be the main contact for IP information, clinical trial, and emergency unblinding
• The pharmaceutical dosage form, route of administration, quantity of dosage units, and strength of active substance
• The batch number
• 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 product name or unique code (if blinded)
• The storage conditions and storage temperature
• The instructions for use
• The period of use (use-by date, expiration date, or re-test date), in month/year format
• The product is a clinical trial material (e.g., For Clinical Trial Use Only)

For additional detailed labelling information and exceptions, see the G-GMPMedicinalAnnexes.

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 specified in the G-GMPMedicinalAnnexes, the sponsor has ultimate responsibility for all aspects of the clinical trial including the quality of the investigational product(s) (IP(s)). The NDPA-CTReg, the G-TrialsGCP, and the G-CTConduct indicate that the sponsor must supply the investigator(s)/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable. However, according to the NDPA-CTReg, the principal investigator (PI) is responsible and accountable for the IP.

The G-TrialsGCP 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.

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)).

Per the G-GMPMedicinalAnnexes, the sponsor and manufacturer and/or importer must agree to written IP retrieval procedures. The sponsor should ensure that the supplier of any comparator or other trial medication has a system in place to communicate any recalls for supplied products. In addition, IPs should be returned on conditions defined by the sponsor and specified in approved written procedures. Returned IPs should be clearly identified and stored in an appropriately secure area. Inventory records of returned IPs should be kept.

The sponsor is also responsible for the destruction of unused and/or returned IPs. IPs should not be destroyed without prior written authorization by the sponsor. Quantities must be specific for each trial site and the sponsor must verify the period. A dated certificate or receipt of destruction should be provided to the sponsor.

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

Record Requirements

As per the NDPA-CTReg, the G-CTConduct, the NGHRP, the G-TrialsGCP, and the G-GMPMedicinalAnnexes, the sponsor must ensure maintenance of the following (Note: The regulatory sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• Records documenting IPs shipment, receipt, disposition, return, and destruction
• A system for retrieving IPs and documenting this retrieval
• A system to dispose of unused IPs and corresponding documentation
• Sufficient quantities of the IPs used in the trial to reconfirm specifications, should this become necessary, and maintenance of records of batch sample analyses and characteristics
• The Investigator’s Brochure (IB) and record(s) of changes made to the IB, if any, including the reasons for these changes
• A record of adverse events (AEs) of the IP
• Participant records including their identification(s) and contact(s)
• A copy of protocol and consent forms

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. The holder of the clinical trial certificate should inform the NDA in writing prior to destroying the documents. Per the NDPA-CTReg, trial records for unregistered IPs should be kept for 20 years following the study's completion. Documentation for trials involving IPs to be registered should be kept for two (2) years after the registration of the IP.

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 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.

Per the G-GMPMedicinal, IP documentation should be retained for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the IP was used. See the G-GMPMedicinalAnnexes for detailed IP shipping requirements.

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 state 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)

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.