Country Selection

South Africa
Uganda

Regulatory Authority

Regulatory Authority

Regulatory authority(ies), relevant office/departments, oversight roles, contact information

Scope of Assessment

Regulatory review and approval processes, renewal, monitoring, appeals, termination

Regulatory Fees

Regulatory fees (e.g., applications, amendments, notifications, import) and payment instructions

Ethics Committee

Ethics Committee

Ethics review landscape, ethics committee composition, terms of reference, review procedures, meeting schedule

Scope of Review

Ethics committee review and approval processes, renewal, monitoring, termination

Ethics Committee Fees

Ethics review fees and payment instructions

Oversight of Ethics Committees

Authorization of ethics committees, registration, auditing, accreditation

Clinical Trial Lifecycle

Submission Process

Submission procedures for regulatory and ethics reviews

Submission Content

Essential elements of regulatory and ethics submissions and protocols

Timeline of Review

Regulatory and ethics review and approval timelines

Initiation, Agreements & Registration

Pre-trial approvals, agreements, clinical trial registration

Safety Reporting

Safety reporting definitions, responsibilities, timelines, reporting format, delivery

Progress Reporting

Interim/annual and final reporting requirements

Sponsorship

Definition of Sponsor

Sponsor role and responsibilities, contract research organizations, representatives

Site/Investigator Selection

Site and investigator criteria, foreign sponsor responsibilities, data and safety monitoring boards, multicenter studies

Insurance & Compensation

Insurance requirements, compensation (injury, participation), post-trial access

Risk & Quality Management

Protocol and regulatory compliance, auditing, monitoring, inspections, study termination/suspension

Data & Records Management

Electronic data processing systems and records storage/retention

Personal Data Protection

Responsible parties, data protection, obtaining consent

Informed Consent

Documentation Requirements

Obtaining and documenting informed consent/reconsent and consent waivers

Required Elements

Essential elements for informed consent form and other related materials

Participant Rights

Rights regarding participation, information, privacy, appeal, safety, welfare

Emergencies

Obtaining or waiving consent in emergencies

Vulnerable Populations

Definition of vulnerable populations and consent/protection requirements

Children/Minors

Definition of minors, consent/assent requirements, conditions for research

Pregnant Women, Fetuses & Neonates

Consent requirements and conditions for research on pregnant women, fetuses, and neonates

Prisoners

Consent requirements and conditions for research on prisoners

Mentally Impaired

Consent requirements and conditions for research on persons who are mentally impaired

Investigational Products

Definition of Investigational Product

Description of what constitutes an investigational product and related terms

Manufacturing & Import

Investigational product manufacturing and import approvals, licenses, and certificates

Quality Requirements

Investigator's Brochure and quality documentation

Labeling

Investigational product labeling, blinding, re-labeling, and package labeling

Product Management

Investigational product supply, storage, handling, disposal, return, record keeping

Specimens

Definition of Specimen

Description of what constitutes a specimen and related terms

Specimen Import & Export

Specimen import, export, material transfer agreements

Consent for Specimen

Consent for obtaining, storing, and using specimens, including genetic testing
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South Africa
Uganda

Quick Facts

Clinical trial application language
Regulatory authority & ethics committee review may be conducted at the same time
Clinical trial registration required
In-country sponsor presence/representation required
Age of minors
Specimens export allowed

Regulatory Authority

Last content review/update: December 18, 2023

South African Health Products Regulatory Authority

As stated in the MRSA and ZAF-9, the South African Health Products Regulatory Authority (SAHPRA) is the regulatory authority overseeing medicines and clinical research, as well as medical devices and radiation safety. As stated in the MRSA and GRMRSA, SAHPRA is responsible for clinical trial oversight, approval, and inspections in South Africa. The agency grants permission for clinical trials to be conducted in South Africa in accordance with the provisions of the GRMRSA.

Per the MRSA and ZAF-39, the SAHPRA is an independent, state-owned entity established to oversee the regulation of medicines in South Africa. According to ZAF-39, this agency is responsible for:

  • The regulation of health products intended for human and animal use
  • The licensing of manufacturers, wholesalers, and distributors of medicines and medical devices; radiation emitting devices; and radioactive nuclides
  • The conduct of clinical trials in a manner that is compatible with national medicines policy

Per the MRSA, SAHPRA is a state-owned entity within the public administration but outside the public service. It acts through a Board appointed by South Africa’s Minister of the National Department of Health (NDOH). For details on the Board appointments, see ZAF-39 and ZAF-38.

As described in ZAF-39 and the SA-GCPs, SAHPRA is tasked with regulating (monitoring, evaluating, investigating, inspecting, and registering) all health products. This includes clinical trials, complementary medicines, medical devices, and in vitro diagnostics (IVDs). Its mission is to promote access to health products and protect human and animal health in South Africa through science-based regulatory decisions. Per ZAF-36, SAHPRA’s Clinical Trial Committee (CTC), within the Clinical Trial Unit, reviews clinical trial applications and bioequivalence studies for human participants and recommends approval of the conduct of clinical trials. SAHPRA also authorizes the importation of unregistered medicine for the purpose of conducting clinical trials. The SA-GCPs also states that SAHPRA is responsible for the following: ensuring efficient, effective, and ethical evaluation or assessment of health products that meet defined standards of quality, safety, efficacy, and performance; ensuring that the process of evaluating or assessing and registering health products is transparent, fair, objective, and concluded in a timely fashion; ensuring periodic re-evaluation and monitoring of health products; and conducting announced and unannounced inspections.

Please note: South Africa is party to the Nagoya Protocol on Access and Benefit-sharing (ZAF-8), 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 ZAF-34.

Contact Information

Per ZAF-35, SAHPRA’s postal address is:

South African Health Products Regulatory Authority
Private Bag X828
Pretoria
0001
South Africa

SAHPRA’s physical address is:

Building A
Loftus Park
402 Kirkness Street
Arcadia, Pretoria
South Africa

As provided in the G-CTA-Electronic and ZAF-36, the following are the SAHPRA Clinical Trial Unit emails:

New clinical trials application alert, responses to new clinical trial applications and related queries: ctcresponses@sahpra.org.za
Protocol amendments, responses to amendments and related queries: ctcamendments@sahpra.org.za
Additional investigators and sites, responses to additional and related queries: ctcinvestigators@sahpra.org.za
Bioequivalence (BE) studies, BE amendments, responses to BE studies and related queries: ctcbeprotocols@sahpra.org.za
Notifications and related queries: ctcnotifications@sahpra.org.za
Individual patient serious adverse events and related queries: ctcsaes@sahpra.org.za
Guidelines, forms, and related queries: ctcguidelines@sahpra.org.za

See ZAF-47 for clinical evaluation and management contacts.

2.1
Clinical Evaluation and Management
4.2
1, 2, 3, and 35
30
Last content review/update: February 9, 2024

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

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

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

Uganda National Council for Science and Technology

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

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

Uganda National Health Research Organisation

Per UGA-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

Introduction and 6.0
3.1-3.4
6.0-7.0
1.6-1.7
Part I (3) and Part IV (40)
4-5 and 15
Part II
Part II (3-6) and Schedule 1 (Form 29)

Scope of Assessment

Last content review/update: December 18, 2023

Overview

In accordance with the GRMRSA, the South African Health Products Regulatory Authority (SAHPRA) is responsible for reviewing and approving all clinical trial applications for an unregistered medicine, and for any new indication or dosage regimen of a registered medicine. The scope of the SAHPRA’s assessment includes all clinical trials (Phases I-IV) and bioequivalence/bioavailability studies. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and an accredited ethics committee (EC) may be conducted in parallel.

ZAF-36 states that the SAHPRA’s Clinical Trial Unit (CTU) provides the legal framework for the review of clinical trials and bioequivalence studies for human participants and recommends approval of the conduct of clinical trials. The unit also authorizes the importation of unregistered medicines for the purpose of conducting clinical trials. As per G-GenInfo, the CTU is responsible for the evaluation of clinical trial applications, clinical trial amendments, and adverse event reports arising from a clinical trial.

Clinical Trial Review Process

Per ZAF-36, the CTU of SAHPRA receives, processes, and evaluates clinical trial applications and any subsequent amendments for approval to conduct a study within South Africa. Researchers must submit a completed application and the prescribed fee on predetermined dates (ZAF-11). The proof of delivery, proof of payments, and cover page must be sent to SAHPRA via email.

As stated in ZAF-36, the CTU completes a preliminary screening of the application and sends an official letter to the applicant with the outcome and follow-up questions on a screening checklist. As indicated in ZAF-23, incomplete documentation or sub-standard submissions will be rejected. Additionally, applications submitted without clinical trial insurance will be rejected. Applicants will be allowed a maximum of two (2) rounds of queries to respond to, and if the responses are not satisfactory the application will be rejected. Per ZAF-36, if an application is rejected, no response is required; the screening checklist should be used as guidance for resubmission during the next review cycle. Next, the CTU’s Clinical Trial Committee (CTC) (which includes an expert committee of specialists, as needed) reviews the proposed clinical trials pursuant to the schedule on SAHPRA’s website. (See ZAF-11 for 2024 dates). Clinical trial reviews will result in one (1) of the following outcomes:

  • Category 1A: Approved; no items pending
  • Category 1B: Approved; ethics approval pending
  • Category 2A: Not approved; for approval by in-house evaluators, 1-2 or more items outstanding as deemed by the committee
  • Category 2B: Not approved; for approval by the original evaluator and in-house if a need arises
  • Category 3: Not approved; items outstanding to be discussed at the next CTC meeting
  • Category 4: Not approved; for referral for specialist opinion
  • Category 5: Not approved – technical/scientific deficiencies; applicant to resubmit for the next cycle
  • Category 6: Rejected due to administrative and technical items outstanding; applicant to resubmit for the next cycle

If an applicant would like to request a meeting with the CTC, the request should be submitted through the SAHPRA Chief Executive Office pursuant to the procedures in the G-ConsultMtg.

Other Considerations

Per the G-Capacity, SAHPRA will also review clinical trial applications for evidence of plans to build capacity at each study site as well as enhancing research activities and skills of professionals from historically disadvantaged groups. See G-Capacity for detailed information on actions that will comply with this requirement.

In addition, see G-Clin for South Africa's use of a “reliance model” to register medicines based on clinical trial data from other regulatory authorities.

Checklist (Note for all applications), 3.1, Annex 3, Annex 5, and Appendix
9.3.2
Part 30 (1)
Last content review/update: February 9, 2024

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 are dependent upon the applicant submitting proof in the application of institutional level ethics committee (EC) (research ethics committee (REC) in Uganda) approval and a research permit from the Uganda National Council for Science and Technology (UNCST). UGA-33 further notes that for clinical trials involving human participants, approval must be obtained through the institutional EC portal (the National Research Information Management System (NRIMS) (UGA-33)) before NDA approval. 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.

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.

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

Per the G-CTConduct, applicants may also submit a form to amend the conditions of a clinical trial. The amendment application will be screened for completeness and will essentially be complete in the first instance if it includes all the required documents, appendices, and finished checklist. Applications which are incomplete will not be evaluated, and a letter documenting the deficiencies in the application will be issued to the applicant. The NDA may request supplementary data or documentation where applicable. The NDA will consider the favorable opinion of the EC(s), the UNCST, and other relevant information, and may request that the applicant to submit an interim clinical trial study report to support the decision. Additionally, the NDA may take other regulatory action such as an inspection of the clinical trial site or investigational product manufacturing facility for regulatory and protocol compliance prior to making a decision. The NDA may approve or reject the application and specify the reasons for rejection. The decision will be communicated to the applicant in writing.

See the G-CTConduct for detailed NDA amendment review procedures, and Appendix V of the G-CTConduct or UGA-22 for the clinical trial application amendments screening 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.

Uganda National Council for Science and Technology

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

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

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

Introduction, 5.0-5.5, 5.7, 6.0, 7.0, 7.3, 8.0, and Appendices V and VI
1.6-1.7
Introduction, 6.0-7.0, 12.0-13.0, and 14.2
3.1-3.2
Part II (3-8 and 11) and Schedule 1 (Forms 29 and 35)

Regulatory Fees

Last content review/update: December 18, 2023

South African Health Products Regulatory Authority

Per the MRSA, the South African Health Products Regulatory Authority (SAHPRA) is authorized to make regulations to collect fees for its various medicine regulatory functions. As delineated in the MRSA-Fees and ZAF-37, applicants are responsible for paying several non-refundable fees to submit a clinical trial application. MRSA-Fees delineates the following fees:

For a clinical trial application for the authorization of the use of unregistered medicines:

  • Clinical trial application (safety and efficacy): South African Rand (R)32 400
  • Clinical trial application (bioequivalence study): R30 400
  • Clinical trial application (postgraduate study): R10 800
  • Any other clinical trial application: R5 000

For amendments to clinical trials:

  • Technical amendment applications: R7 000
  • Administrative amendment applications: R4 100
  • Any other application except for the purpose of performing a clinical trial: R350

For licenses:

  • New manufacturing license: R25 200
  • New import/export license to the holder of certificate of registration: R15 000
  • Renewal of manufacturing license: R22 000
  • Renewal of import license to the holder of the certificate of registration: R9 200
  • Renewal of export license to the holder of the certificate of registration: R9 200
  • Annual retention of all licenses: R4 200

For inspections to assess the quality, safety, and efficacy of medicines:

  • Local and international manufacturing sites: R1 600 per hour
  • Local and international clinical trial sites: R1 600 per hour

Payment Instructions

Per the G-SAHPRAFees, when making payments, applicants should follow these guidelines:

  • Applicants should submit a cover page that identifies the services requested using the template provided in ZAF-37
  • Payments should be referenced in accordance with the SAHPRA Fee Categorization Guideline (Annexure A of G-SAHPRAFees)
  • If the applicable bank limits reference spacing, follow the sequence listed in Annexure A as far as the limitation allows; spacing and dashes (/) may be omitted
  • Fee payments may be transferred directly into the bank account of SAHPRA via an electronic or manual deposit process
  • No check payments will be accepted
  • For administrative control purposes, applicants should make one (1) payment per service
  • Payment should only be made once the application and required dossiers are ready for submission
  • Payments do not have to be made upon request of an application number; however, the applications and required dossiers should be submitted within a reasonable time upon receipt of an application number or as specified in the relevant application guidelines
  • As soon as the fee payment has been made, the proof of payment and cover page should be attached and sent via email to SAHPRA Finance at pop@sahpra.org.za, and the relevant unit(s) processing the application should be copied on the email.
  • If the proof of payment has not been submitted, or no details to identify the payment reference as per the G-SAHPRAFees have been provided, and any further attempts to clear these payments fail after 12 months, any liability for SAHPRA to refund these payments will be forfeited
  • If a payment has been received without an application, the applicant will be notified to submit the required application within 14 working days, failing which, the amount will be forfeited
  • Requests for refunds should be submitted in line with Annex B in the G-SAHPRAFees
  • Payment and pro forma invoice queries and requests can be directed to finance@sahpra.org.za or 012 501 0323
  • See the G-SAHPRAFees for details on special requests for extensions to the deadline

Per the G-SAHPRAFees, the bank and account details are as follows:

Account name: South African Health Products Regulatory Authority
Special Name: The Medicines Control Council
Account type: Cheque/Current Account
Account number: 40-5939-2080
Bank: ABSA
Bank Branch Code: 632005
Bank physical address: 240 Vermeulen Street, Pretoria, 0001, South Africa
Swift Code: ABSAZAJJ

Fee payment questions can be directed to finance@sahpra.org.za or 012 501 0323.

Sections 1-3 and Annexure A
35
Fees for Clinical Trials, Fees for New Licenses, and Fees for Inspections
Last content review/update: February 9, 2024

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

4.4
6.0
Part II (4)
2 and Schedule (Part 9)

Ethics Committee

Last content review/update: December 18, 2023

Overview

Per ZAF-51, ethics committees (ECs) in South Africa are governed by the National Health Research Ethics Council (NHREC), which is a statutory body established under the NHA. According to ZAF-52, NHREC gives direction on ethical issues relating to health and develops guidelines for the conduct of research involving humans and animals. As delineated in the NHA, the G-EthicsHR-ZAF, and the SA-GCPs, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study.

The NHA requires that every institution, health agency, and health establishment at which research is conducted establish an EC or have access to an independent EC. The EC must be registered with the NHREC. The SA-GCPs note that the NHREC accredits and audits the ECs.

Ethics Committee Composition

As delineated in the SA-GCPs and the G-EthicsHR-ZAF, an EC must consist of members who collectively encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of all proposed research studies.

The G-EthicsHR-ZAF indicates that an EC should comprise:

  • Members who have documented proof of research ethics training, refreshed at least once within the period of appointment
  • At least nine (9) members
  • At least one (1) layperson
  • At least one (1) member with knowledge of, and current experience in the professional care, counselling, or health-related treatment of people; such a medical practitioner, psychologist, social worker, or nurse
  • At least one (1) member with professional training and experience in qualitative research methodologies
  • Members with professional training and experience in quantitative research methodologies
  • A member with expertise in bio-statistics
  • A member with expertise in research ethics
  • At least one (1) member who is legally qualified

Terms of Reference, Review Procedures, and Meeting Schedule

Per the G-EthicsHR-ZAF, an institution or organization must select EC members according to prescribed recruitment and appointment procedures. Members must receive a formal notice of appointment and assurance that they will be legally protected with respect to any liabilities that may arise during their term. EC quorum should be a simple majority, and where the number of members is more than 15, the quorum may be 33%. An EC must also establish and record written procedures to address several administrative issues including meetings, agenda/minutes preparation, research protocol presentations, application registration, protocol submission requirements, review and decision notification process, adverse event reporting, protocol amendment reporting, and end-of-trials review. A reasonable term of office is between two (2) and four (4) years, renewable twice, after which the person should stand down for at least one (1) term. Further, EC members and researchers are expected to familiarize themselves with the institutional documentation as well as national and international research ethics guidelines and should have documented proof of such familiarity. Training of all EC members is critical, especially for ECs that review high-risk research. Training and refresher courses should be available, and EC members should produce, at least once during a term of appointment, evidence of recent training. This ensures that both expertise and responsibility are distributed and encouraged in a range of members, and that institutional memory is accumulated. The SA-GCPs stipulate that EC members who review clinical trial proposals should have research ethics training and good clinical practice training, evidenced by certificates issued in the last three (3) years.

Per the SA-GCPs, the EC should retain all relevant records for a period of at least three (3) years or as per institutional requirement, whichever period is longer, after completion of the trial and make them available upon request from the applicable regulatory authority. The G-EthicsHR-ZAF indicates that ECs should keep written records of all research protocols received for review in the form in which they were approved. Electronic records are acceptable if the signatures are properly documented and included in the record. EC records must provide a reliable and authoritative record of the EC’s business that will stand up to scrutiny in the event of queries, conflicts, and audits.

4.2-4.5, 5.1, and 5.2-5.4
4.3 and 12
Chapter 9 (72 and 73)
Last content review/update: February 9, 2024

Overview

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

Ethics Committee Composition

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

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

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

Terms of Reference, Review Procedures, and Meeting Schedule

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

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

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

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

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

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

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

7.0
1.0, 3.1, 3.4-3.6, 4.1-4.6, and 4.8-4.9

Scope of Review

Last content review/update: December 18, 2023

Overview

Per the SA-GCPs, clinical trials should be conducted in accordance with all ethical principles outlined in the Declaration of Helsinki (ZAF-44) and consistent with good clinical practice and other applicable regulatory requirements. In accordance with the NHA, the SA-GCPs, and the G-EthicsHR-ZAF, ethics committees (ECs) must evaluate the ethical and scientific rigor of all research studies to be conducted in the country. An EC’s primary responsibilities are to (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • Review protocols to ensure that research involving human participants has scientific merit and will promote health, and prevent or cure disability and disease; in addition, ensure the research has social merit in light of South Africa’s research priorities or is otherwise justified
  • Ensure clinical trials are governed by the ethical principles of beneficence and non-maleficence, distributive justice (equity), and respect for persons (dignity and autonomy)
  • Grant approval for research where the protocols meet the ethical standards of the institution, agency, or establishment
  • Determine whether and why randomization is relevant, and how this is addressed
  • Evaluate the appropriateness of the inclusion/exclusion criteria and the recruitment process in the South African context
  • Ensure the feasibility of obtaining meaningful results with the lowest possible risk of harm for participants and whether the risk of harm is appropriately weighed against anticipated benefits for participants or the class of persons from which they are drawn; high risk of harm may be justifiable where the anticipated benefit is of high importance to increase relevant knowledge and appropriate mitigating measures are in place to minimize harm to participants; and attention must be given to harms and benefits beyond the life of the trial itself, especially in respect to early phase studies and (pharmacovigilance) surveillance for chronic and life-threatening conditions

An EC must also pay special attention to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Informed Consent topic for additional information about these populations).

Role in Clinical Trial Approval Process

Per the G-EthicsHR-ZAF, the SA-GCPs, and the NHAParticipants, the principal investigator (PI) or the sponsor must submit a clinical trial application to both the South African Health Products Regulatory Authority (SAHPRA) and a registered EC for review and approval before a study may commence. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and an accredited EC may be conducted in parallel.

The G-EthicsHR-ZAF indicates that after the deliberative review process, the EC should approve, require amendment to, or reject a research protocol. In considering a research protocol, the EC may seek assistance from experts. EC decisions should be recorded in writing. A decision to approve should include the conditions (e.g., the duration of the approval, the reporting requirements, etc.). Reasons for a decision to require an amendment or to reject a research protocol should be recorded. Outright rejection should be avoided if a researcher can be advised to improve the protocol. Researchers should be encouraged to address the concerns and improve their protocols. ECs should require researchers to report immediately if a project is terminated or suspended before the anticipated date of completion. ECs should require researchers to report immediately anything that might warrant reconsideration of ethical approval of the protocol, including but not limited to:

  • Serious or unexpected adverse effects on participants
  • Proposed changes in the protocol
  • Unforeseen events that might affect continued ethical acceptability of the project

Per the G-EthicsHR-ZAF, ECs may, at their own discretion, recognize prior review and approval of a research protocol by another registered EC to avoid duplication of effort. Reciprocal recognition means that two (2) or more registered ECs decide to recognize each other’s prior review. ECs that recognize prior review in this manner must determine the nature of the documents to be filed locally, which must, at minimum, include a copy of the approval letter from the other ECs. In addition, ECs may establish procedures for expedited review for research that poses no more than minimal risk of harm to participants.

The SA-GCPs requires the EC’s approval of the following before the clinical trial may begin: protocol and any amendments; case report form, if applicable; informed consent form(s); any other written information to be provided to the participants; advertisement for participant recruitment (if used); participant compensation; and any other documents given approval/favorable opinion.

The SA-GCPs mandate that the sponsor receive confirmation of EC review from the investigator(s) or institution(s). The sponsor must receive the following information prior to the trial’s commencement:

  • The name and address of the relevant EC registered with National Health Research Ethics Council (NHREC), with its documented approval
  • If EC approval is conditional on required modifications, a copy of the modification(s) made and the date the final approval was granted by the EC
  • Documentation and dates of any EC re-approvals/re-evaluations

As delineated in the G-EthicsHR-ZAF, ECs have the right to monitor the research it approves, and researchers should provide appropriate information to the EC to facilitate monitoring, including alerts and investigator brochures. The frequency and type of monitoring should reflect the degree and extent of risk of harm to participants or animals. ECs may recommend and adopt any additional appropriate mechanism for monitoring.

Per ZAF-20, if there is an amendment to the protocol, the sponsor must notify the EC and get its approval. This approval should be sent to the SAHPRA using the Application for Protocol Amendment to an Approved Trial (ZAF-20).

3 (Part 4)
3.1 and Appendix
2, 4, 5, and Appendix 1
2.1, 2.6, 4.3, and 9.2
3
Chapter 9, Sections 72 and 73
Last content review/update: February 9, 2024

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, approval must be obtained through the institutional EC portal (the National Research Information Management System (NRIMS) (UGA-33)) before NDA approval. 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).

3.0-5.0 and 7.1
Part II (3-8 and 10) and Schedule 1 (Forms 29 and 36)

Ethics Committee Fees

Last content review/update: December 18, 2023

Based on the G-EthicsHR-ZAF, ethics committees (ECs) may independently decide whether to charge fees for a protocol review. The G-EthicsHR-ZAF states that an EC should establish and record working procedures concerning fees charged, if any. Researchers without affiliation to an institution or organization with an EC should approach a registered EC to request it to review their health research protocols. If the EC is willing to review external applications, a fee for service may be levied.

4.2 and 4.3.1
Last content review/update: February 9, 2024

No information is currently available.

Oversight of Ethics Committees

Last content review/update: December 18, 2023

Overview

Per ZAF-51, ethics committees (ECs) in South Africa are governed by the National Health Research Ethics Council (NHREC), which is a statutory body established under the NHA. As delineated in the NHA, the NHREC was created by the Minister of Health to provide ethical oversight of clinical research and to safeguard the rights and welfare of human participants involved in clinical studies. According to ZAF-52, NHREC gives direction on ethical issues relating to health and develops guidelines for the conduct of research involving humans and animals. Further, NHREC upholds the principle that research involving human participants is based on a moral commitment to advancing human welfare, knowledge, and understanding, and to exploring cultural dynamics, especially in large-scale trials conducted in developing countries. Of fundamental importance is the duty to conduct scientifically sound research while acting in the participant’s best interests and respecting and protecting the participant’s autonomy.

As delineated in the NHA, the SA-GCPs, and the G-EthicsHR-ZAF, the NHREC’s core responsibilities center on promoting, ensuring, and monitoring compliance by ECs. According to ZAF-52, the functions of the NHREC include:

  • Determine guidelines for the functioning of ECs
  • Register and audit ECs
  • Set norms and standards for conducting research on humans and animals including clinical trials
  • Adjudicate complaints about the functioning of ECs
  • Refer to the relevant statutory health professional council matters involving the violation or potential violation of an ethical or professional rule by a health care provider
  • Institute such disciplinary action as prescribed
  • Advise the national department and provincial departments on any ethical issues concerning research

Registration, Auditing, and Accreditation

As delineated in the NHA, the G-EthicsHR-ZAF, and the SA-GCPs, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study. The application to register an EC is available at ZAF-53. ZAF-54 states that the EC registration is recorded and publicly listed by the NHREC. The annual report form that ECs must submit to NHREC is available at ZAF-54. Per the SA-GCPs, the NHREC accredits and audits the ECs.

4.6, 5.2, and 5.4
4.1 and 12.0 (National Health Research Ethics Council)
Chapter 9, Sections 72 and 73
Last content review/update: February 9, 2024

Overview

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

Registration, Auditing, and Accreditation

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

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

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

See UGA-9 for the accreditation application form and the NGHRP for details on EC establishment requirements. A list of UNCST-accredited ECs is also available through UGA-11.

3.2, 3.4-3.5, and 4.1-4.2

Submission Process

Last content review/update: December 18, 2023

Overview

As delineated in the SA-GCPs, the sponsor and the investigator must obtain approval from the South African Health Products Regulatory Authority (SAHPRA) and a registered ethics committee (EC) to begin a clinical trial in South Africa. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and an accredited EC may be conducted in parallel. Per ZAF-20, the same process applies to the review and approval of an amendment to the protocol.

Regulatory Submission

Per ZAF-36, researchers must submit a completed application (ZAF-23) and the prescribed fee on predetermined dates (ZAF-11) and obtain proof of delivery. The proof of delivery, proof of payments, and cover page must be sent to SAHPRA via email. The G-CTA-Electronic delineates the electronic submission and communication process in SAHPRA’s Clinical Trial Unit (CTU). For new clinical trial applications (excluding bioequivalence studies), upon submission at SAHPRA Reception, applicants are requested to alert the CTU via e-mail at ctcresponses@sahpra.org.za and include a copy of the proof of delivery, proof of payment, and proof of insurance. In the subject of the e-mail, provide type of application, protocol number, SAHPRA predetermined cycle (see ZAF-11), and email number in case of multiple emails (e.g., “email 1 of 5”). Note that the submission email must include organized zipped folders for various sections of the clinical trial application. Individual site documents for each staff member must be uploaded into one (1) document and labelled with the staff name and arranged in folders according to the site which they belong to.

Per G-CTA-Electronic, to respond to SAHPRA’s screening checklist or to CTU’s expert committee review, the applicant must submit all responses by e-mail to ctcresponses@sahpra.org.za and include labelled attachments to the required documents. In the subject of the email, the applicant should provide the type of application, protocol number, and SAHPRA database tracking number. Responses to the CTU’s expert committee recommendations can be in MSWord or PDF formats. All other accompanying documents should be in PDF format v1.4, 1.5, 1.6, or 1.7 and legible with the Acrobat Reader search plugin or any other freeware viewer. PDF files should be saved as “Optimized” to reduce the size and allow faster opening when viewed online. The use of additional software to navigate and work with the files is not acceptable. If PDF files are not produced from an electronic source document but from scanned paper, readability and file size should be balanced; the following is recommended: resolution 300 dpi (photographs up to 600 dpi), avoid grayscale or color where possible, use only lossless compression techniques. The file must be searchable (OCR scanned). In addition, the maximum size of documents allowed per e-mail is 5 MB. As per arrangement with CTU, in case of a big file of documents and documents that need to be couriered, the waybill should indicate the type of application, protocol number, and SAHPRA database tracking number.

Per G-CTA-Electronic, for bioequivalence studies, the application and accompanying documents should be emailed to ctcbeprotocols@sahpra.org.za. The clinical trial application form should be in MS Word format and all other accompanying documents in PDF, as described above. As per arrangement with CTU, in case of a big file of documents and documents need to be couriered, the waybill should indicate the type of application, protocol number and SAHPRA database tracking number. The email subject should include the type of application, protocol number, and SAHPRA database tracking number. See the G-CTA-Electronic for specific examples of labeling the emails.

Per the G-CTAPHEmerg, during a public health emergency, applicants should use the modified clinical trial application form in G-CTAPHEmerg. This form recognizes the constraints on the availability of information posed by the emergency. SAHPRA may accept clinical trial applications with reduced information together with a commitment to update and complete the required information as soon as possible. However, all documents submitted must be organized with zipped folders according to the checklist in G-CTAPHEmerg and correctly labelled to ensure easy validation by SAHPRA (See the Submission Content and Emergencies sections for more details).

The G-CTA-Electronic provides instructions on submitting protocol amendments during the conduct of clinical trials, for additional investigators and sites during the conduct of clinical trials, bioequivalence studies, notifications and notification studies, and individual serious adverse events. The applicant must submit to SAHPRA the application for amendment to an approved trial (ZAF-20), as well as notify and get EC approval. (Also see Site/Investigator Selection and Safety Reporting sections for information about these submittal processes.)

The G-CTA-Electronic and ZAF-23 state that the clinical trial application must be sent to SAHPRA in a submission email (per directions above). However, ZAF-1 provides the following address for delivery of clinical trial applications to SAHPRA Reception:

South African Health Products Regulatory Authority
SAHPRA reception – 2nd floor
Loftus Park, Building A
402 Kirkness St, Arcadia
Pretoria, 0007
South Africa

Per ZAF-1, upon receipt of the clinical trial application at SAHPRA Reception, an acknowledgement of receipt in the form of a stamp and signature will be issued. The waybill from a courier company does not suffice as proof of delivery. SAHPRA’s CTU requires a document, referred to as the ‘stamp page,’ which includes the SAHPRA trial reference number, protocol number, and study title. This document will then be date-stamped and signed by SAHPRA’s Administrative Department and returned as proof.

As per the GRMRSA, all applications and supporting data submitted to the SAHPRA should be presented in English. Original documents that are not in English must be accompanied by an English translation.

Ethics Review Submission

Each EC has its own required submission procedures, which can differ significantly regarding the number of copies to be supplied and application format requirements. Refer to each EC’s website for specific submission procedures (Note: ECs are referred to as health research ethics committees (HRECs) in South Africa).

3-7
Where Do I Submit a New Clinical Trials Application?, How Do I Make Sure My Hard Copy Application Gets to the Right Place?, and What Should an Acceptable Proof of Delivery Look Like?
2.6 and 6.2
Application for the Registration of a Medicine – Part 16 (4)
Last content review/update: February 9, 2024

Overview

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

Per the NDPA-CTReg and UGA-20, the NDA’s review and approval of a clinical trial application are dependent upon the applicant submitting proof in the application of institutional EC approval and a research permit from the UNCST. UGA-33 further notes that for clinical trials involving human participants, approval must be obtained through the institutional EC portal (the National Research Information Management System (NRIMS) (UGA-33)) before NDA approval. 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.

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.

The NDPA-CTReg further indicates that an application for deviation from a condition of a clinical trial must use Form 36, and an application for additional investigators, additional clinical trial sites, or for change of the investigators must use Form 37 (see Schedule 1 of the NDPA-CTReg).

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. In the cover letter, a clear step-by-step justification for each proposed change(s) must be provided, and the possible consequences with regard to the benefit/risk balance for participants already enrolled in the trial must be summarized. The subject of the cover letter must be “Application to amend CTA XXX” where XXX is the Clinical Trial Application code assigned by the NDA upon authorization of the clinical trial and indicated on the clinical trial certificate. Only one (1) copy of the completed form must be sent to the NDA.

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 UGA-33.

Per UGA-33, NRIMS is an online platform that supports the NDA, the Uganda National Health Research Organisation (UNHRO), the UNCST, and institutional ECs in the regulatory oversight of clinical research. The system provides researchers with an interface with the regulatory agencies in the data capture, data management, data validation, quality control, and overall regulatory compliance related to clinical research management processes. See UGA-33 for more information.

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

Introduction, 4.2-4.3, 4.5-4.7, 7.1, and Appendices I and III
1.6-1.7
6.0 and 8.0
2.2 and 3.1-3.4
Part II (3-8 and 10) and Schedule 1 (Forms 29, 30, 36, and 37)

Submission Content

Last content review/update: December 18, 2023

Regulatory Authority Requirements

As per ZAF-23, the following documentation must be submitted to the South African Health Products Regulatory Authority (SAHPRA):

  • The clinical trial application form (ZAF-23)
  • Two (2) cover letters (one (1) signed in PDF and one (1) in MS-Word format)
  • Two (2) completed copies of the clinical trial application (one (1) signed in PDF and one (1) in MS-Word format) (ZAF-23 and ZAF-20 (for amendments))
  • Checklist
  • Protocol
  • Patient information leaflets (PILs) and informed consent forms (ICFs); include standardized SAHPRA contact details (Annex 1 of ZAF-23)
  • Copy(ies) of recruitment advertisement(s) (if applicable) and questionnaires
  • Investigator’s Brochure (IB)/SAHPRA and other regulatory authorities’ approved professional information (Package insert(s))
  • Summary of previous trials with the investigational product(s) (IP(s)), if applicable
  • Certificate of analysis of the product
  • Signed investigator(s) Curriculum Vitae(s) (CV) in SAHPRA format (Annex 2 of ZAF-23)
  • Signed declaration(s) by all investigator(s) (Annex 3 of ZAF-23)
  • Signed joint financial declaration by sponsor and principal investigator (PI) or national PI (Annex 4 of ZAF-23)
  • Signed declaration by applicant and national PI
  • Signed declaration by national PI (See page 4 and Annex 3 (ZAF-23)
  • Signed declaration by sub-investigators (Annex 5 of ZAF-23)
  • CV(s) and signed declaration by regional monitor(s) (Annexes 2 and 6 of ZAF-23)
  • Proof of application to register the trial on the South African National Clinical Trials Register (SANCTR) (ZAF-48)
  • Active insurance certificate for clinical trial
  • Proof of sponsor indemnity for investigators and trial site(s) (Annex 7 of ZAF-23)
  • Active Good Clinical Practice (GCP) Certificates
  • Workload forms for investigators (Annex 8 of ZAF-23)
  • Proof of registration with professional statutory bodies
  • Proof of professional indemnity (malpractice insurance) of trialist(s)
  • Ethics committee (EC) approval letter or copy of letter submitted to EC
  • Study budget
  • Electronic copies of key peer reviewed publications following International Committee of Medical Journal Editors (ICMJE) recommendations to support the application (if applicable)
  • Proof of payment (bank validated)
  • Certificate of good manufacturing practice (GMP) for manufacture of the IP(s) (including placebo and comparator)
  • Evidence of accreditation/certifications of the designated laboratories
  • Data Safety Monitoring Board charter and composition (where applicable)

See ZAF-36 for additional information on submissions. For phase IV trials of approved products, the applicant must notify SAHPRA following the instructions provided in ZAF-17.

ZAF-20 delineates the contents and requirements for submitting an application for protocol amendment to an approved clinical trial.

Per the G-CTAPHEmerg, SAHPRA states that during a public health emergency, new and experimental treatments may become necessary and clinical trials are essential to provide the evidence to develop appropriate policies for patient treatments. Under these circumstances, there may be limited information available. However, applications need to contain a certain minimum of information to enable a meaningful evaluation and regulatory decisions. To address this, SAHPRA provides an information grading system in the G-CTAPHEmerg wherein required information is labelled. Applicants must attempt to provide the information listed below and justify when this is not available. The required information is graded as follows:

  • Essential – Application will not be considered without this
  • Important – Necessary information that must be provided later and must be justified if not available
  • Not essential – May be omitted from this preliminary application

All incomplete information must be explained, justified, and provided to SAHPRA as a complete application (ZAF-23), when available. This means that repeat evaluations of an application may be necessary.

Ethics Committee Requirements

Each EC has its own application form and clearance requirements which can differ significantly regarding the number of copies to be supplied and application format requirements. However, the requirements list provided below is basically consistent across all South African ECs.

The following list was compiled from ZAF-24, ZAF-22, ZAF-45, ZAF-42, and ZAF-49, to exemplify the common elements shared by the various application forms:

  • Cover letter
  • Completed EC-specific application form
  • Protocol
  • Protocol synopsis
  • PIL(s) and ICF(s) and process for obtaining informed consent
  • Separate assent form required for adolescents/children under the age of 18 (See Children/Minors section for additional information)
  • IB and package insert(s) (if applicable)
  • SAHPRA approval letter or letter of application and notification
  • Approval letter from institution’s scientific committee (if applicable)
  • Copy of completed clinical trial application signed by all participating investigators
  • All questionnaires and diaries to be used in the study
  • Advertisement(s) (if applicable)
  • Trial site information (address, telephone numbers, PI names, etc.)
  • Trial payment schedule and budget schedule per site/draft financial contract and additional funding details
  • Proof of submission fees payment
  • Current investigator(s) CVs
  • GCP training certificates for PIs and subinvestigators
  • Information on registration with SANCTR (ZAF-48)
  • Declaration of trialists (PI and sub-investigators) in SAHPRA format
  • Insurance certificate

Further, per the MTA-Human, all the providers and recipients of human biological material for use in research or clinical trials under the auspices of ECs must use the “Material Transfer Agreement of Human Biological Materials” in MTA-Human. The agreement must be signed by the research institution’s authorized representative and the EC. (For additional details, see Specimens topic.)

Clinical Protocol

As delineated in ZAF-23 and the SA-GCPs, the clinical protocol should contain the following information (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

  • General information
  • Background information
  • Study rationale and motivation
  • Trial objectives, purpose, and endpoints (with justifications)
  • Trial design and methodology
  • IP information
  • Participant eligibility, selection, and withdrawal
  • Participant treatment
  • Efficacy assessment
  • Safety assessment
  • Statistics
  • Direct access to source data/documents
  • Quality control/quality assurance
  • Data and safety monitoring plan
  • Data handling/recordkeeping
  • Statistical measures
  • Financing/insurance
  • Publication policy

Per the SA-GCPs, the protocol must also provide details on ethical and administrative issues, including how the following matters are addressed:

  • Compliance of multi-center/national trials with all South African regulatory requirements
  • The trial design must be customized appropriately for the local setting to ensure that local realities are considered and appropriately integrated into the design
  • For multi-national trials, whether a reasonable proportion of significant project team members, including scientists and health care professionals, are South African researchers, including those from previously disadvantaged backgrounds
  • If South Africa is selected as a clinical trial site but the country of origin or other high-income countries are not, an explanation and reason for this with a clear ethical justification

For detailed information on protocol elements, please refer to ZAF-23 and the SA-GCPs.

Submission Documents
2.6, 6.2, 7.1-7.16
Cover page, 3, and Annexure A
Last content review/update: February 9, 2024

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: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

  • Proof of payment
  • Applications for import and/or export of biological materials (if required)
  • Clinical Trial Application Form (See Appendix I of the G-CTConduct)
  • Trial protocol
  • Investigator’s Brochure (See UGA-4 or Schedule 2 of the NDPA-CTReg)
  • Participant Information Leaflet and informed consent form
  • Certificate of Good Manufacturing Practice (GMP) of the trial medicine or other evidence of manufacturing 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.

As per the NDPA-CTReg, an application for deviation from a condition of a clinical trial must use Form 36, and an application for additional investigators, additional clinical trial sites, or for change of the investigators must use Form 37 (see Schedule 1 of the NDPA-CTReg).

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

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.

4.6, 7.1, and Appendices I-V
4.8
Part II (10), Schedule 1 (Forms 29-34 and 36-37), and Schedule 2

Timeline of Review

Last content review/update: December 18, 2023

Overview

Based on ZAF-23 and the SA-GCPs, the review and approval of clinical trial applications by the South African Health Products Regulatory Authority (SAHPRA) and an accredited ethics committee (EC) may be conducted in parallel. The applicant must notify each regulatory body of the other’s approval once it has been received.

Regulatory Authority Approval

In general, per ZAF-36, SAHPRA’s Clinical Trial Unit (CTU) aims to process new applications and issue a screening checklist within three (3) weeks of receipt. After that, the expert Clinical Trials Committee (CTC) recommendations will be sent within 10 weeks of the submission due date. There are cases where this turnaround time might be prolonged, such as an unfamiliar investigational product which may be referred to external reviewers or other SAHPRA committees for input.

Per ZAF-1, during the preliminary screening, the CTU screens the application and sends an official letter to the applicant with the outcome and follow-up questions on a screening checklist. The applicant receives the screening checklist within 15 working days after application submission. The applicant must respond within seven (7) working days after receipt of the screening review.

Next, the CTC reviews the proposed clinical trials. ZAF-11 provides the dates of the 2024 CTC meetings and the SAHPRA submission due dates. It is advisable to submit clinical trial applications before these due dates. Once the reviewer approves the application, the CTC presents the committee’s/reviewer’s recommendations to the SAHPRA. ZAF-1 states that applicants receive a response within 10 working days from the CTC meeting, and they must send an answer within seven (7) working days after receipt of comments. If an applicant would like to request a meeting with the CTC, the request should be submitted through the SAHPRA Chief Executive Office pursuant to the procedures in the G-ConsultMtg.

Ethics Committee Approval

As earlier stated, an applicant must also submit the clinical trial application for review and approval by an accredited local EC. Review timelines vary per an individual EC’s procedures.

Governance

In addition, as described in the G-EthicsHR-ZAF and ZAF-6, all clinical trials must obtain site-specific provincial and/or hospital approval to assess the impact the clinical trial will have on the resources of the establishment hosting the trial.

Chapter 4 – South Africa (MCC, HREC, Provincial/Hospital) (full ebook only available for purchase)
How Will I Know If My Application has been Received and Reviewed?, What is the Timeline for Receipt of Screening Checklist?, What is the Timeline for Response of Screening Checklist?, What is the Expected Timeline for Response from Clinical Trial Committee Review?, and What is the Timeline for Submitting Responses from Expert Committee Review?
5.5
4.4
Last content review/update: February 9, 2024

Overview

Per the NDPA-CTReg and UGA-20, the National Drug Authority (NDA)’s review and approval of a clinical trial application are dependent upon the applicant submitting proof in the application of institutional ethics committee (EC) (research ethics committee (REC) in Uganda) approval and a research permit from the Uganda National Council for Science and Technology (UNCST). UGA-33 further notes that for clinical trials involving human participants, approval must be obtained through the institutional EC portal (the National Research Information Management System (NRIMS) (UGA-33)) before NDA approval. 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 further 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.)

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

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

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.

5.0, 5.3-5.5, and 7.0
1.6 and 2.2
6.0
3.2 and 4.9
Part II (3-8)

Initiation, Agreements & Registration

Last content review/update: December 18, 2023

Overview

In accordance with the GRMRSA, the SA-GCPs, the G-EthicsHR-ZAF, and the NHAParticipants, a clinical trial can only commence in South Africa once an applicant receives approval from the South African Health Products Regulatory Authority (SAHPRA) and from an accredited local ethics committee (EC). There is no waiting period required following the applicant’s receipt of these approvals.

In addition, the principal investigator (PI) for each study site must be a South African-based scientist (resident of South Africa), and should have the appropriate qualifications, training, and experience to assume responsibility for the proper conduct of a trial. The trial must be conducted in compliance with the SA-GCPs, the G-EthicsHR-ZAF, and the GRMRSA. Also, per the SA-GCPs, all clinical trials must be conducted in a laboratory complying with Good Laboratory Practices (GLP). See ZAF-46 for the World Health Organization (WHO)’s handbook on GLPs.

Per the SA-GPPs, pharmacists must be involved in clinical trials, including for example, assisting in the development of protocols, overseeing medicine supplies, monitoring administration protocols, and maintaining registries.

Clinical Trial Agreement

According to the SA-GCPs, all parties involved in the conduct of a trial should be familiar with guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27) and other international guidelines. Before the trial begins, a sponsor must prepare a written agreement. The agreement must be signed by the sponsor and the PI, and any other parties involved (e.g., institutions and contract research organizations) with the trial to confirm the contract terms. Both the sponsor and the PI must commit to providing safety information between each other. The sponsor should also obtain the investigator's agreement to:

  • Conduct the trial in compliance with the SA-GCPs, the SAHPRA requirements, ZAF-27, and the EC approved protocol
  • Comply with data recording/reporting procedures
  • Permit monitoring, auditing, and inspection
  • Retain the trial-related essential documents until the sponsor informs the investigator(s) and institution(s) that these documents are no longer needed

In addition, per the SA-GCPs, the financial aspects of the trial should be documented in the agreement. A declaration must be signed by the sponsor and PI stating that sufficient funds are available to complete the study. The sponsor is also responsible for securing agreements 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.

Clinical Trial Registration

According to the SA-GCPs, NHAParticipants, and ZAF-32, the PI or the sponsor must enter the trial information in the South African National Clinical Trials Register (SANCTR) (ZAF-48). The SA-GCPs indicates that the National Department of Health (NDOH) then issues a unique SANCTR National Register Number. ZAF-32 has instructions for registering either online or via email.

ZAF-48 states that SANCTR fulfills the requirements of the International Committee of Medical Journal Editors (ICMJE) publication mandates and has a formal partnership with the Pan African Clinical Trials Registry (ZAF-50), which is recognized by the WHO.

General Objectives and Requirements of Pharmaceutical Services
4 and 5
1.2, 2.6, 4.4, 6.1-6.2, 6.4, 6.9, 7.11, and 9.2
3
Part 30 (2)
Last content review/update: February 9, 2024

Overview

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

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

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

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.

Introduction, 4.3, 4.6, 4.8, 10.0-10.1, and Appendix I
3.1-3.4, and 4.8
6.0-7.0
1.6-1.7, 4.4-4.5, 4.9, 6.10, and 10.3
Part II
Part II (3-9) and Schedule 1 (Form 29)

Safety Reporting

Last content review/update: December 18, 2023

Safety Reporting Definitions

In accordance with the SA-GCPs, the G-EthicsHR-ZAF, and the G-SafetyRpt, the following definitions provide a basis for a common understanding of South Africa’s safety reporting requirements:

  • Adverse Event/Experience (AE) – Any untoward medical occurrence that may present during treatment with a medicine, but which does not necessarily have a causal relationship with this treatment
  • Adverse Drug Reaction or Adverse Reaction (ADR) – A noxious and unintended response to a medicine in humans or animals, including lack of efficacy, and which occurs at any dosage and can also result from overdose, misuse, or abuse of a medicine
  • Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life-threatening, requires patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
  • Unexpected Adverse Drug Reaction – One in which the nature, specificity, severity, and outcome is inconsistent with the applicable product information (i.e., with the approved package inserts for registered medicines, the investigator’s brochure, or other product information for unregistered medicines being used)

Furthermore, ZAF-30 provides clarification on the definition of a serious suspected unexpected adverse reaction (SUSAR), which is a reporting requirement in the updated G-SafetyRpt. Per ZAF-30, a SUSAR is an adverse reaction that is unexpected but suspected to be drug related. It must fulfil the criteria for “serious” as per the definition of SAEs. In addition, all SUSARs are SAEs but not all SAEs are SUSARs.

Per the G-EmergencyProc, all clinical trial sites must have an emergency standard operating procedure that should be available for inspection by the South African Health Products Regulatory Authority (SAHPRA). In addition, each clinical trial site should have adequately trained investigators to manage medical emergencies. Further, there must be an emergency 24-hour contact number for trial participants who experience an unexpected AE.

Safety Reporting Requirements

Investigator Responsibilities

As specified in the SA-GCPs and the G-EthicsHR-ZAF, the principal investigator (PI) must inform the sponsor immediately, or within the time specified in the protocol, of any serious and/or unexpected AEs occurring during the study. The initial reporting form and any relevant follow-up information should be sent to the sponsor. The G-SafetyRpt directs the investigator to report AEs to the sponsor in a manner defined in the protocol. Per the SA-GCPs, AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations must be reported to the sponsor in accordance with the reporting requirement and within the time periods specified in the protocol. In the case of participant deaths, the PI must supply the sponsor, the ethics committee (EC), and SAHPRA with any additional information, as requested. The initial and follow-up reports must identify the affected participants by the participant identification code.

Sponsor Responsibilities

As delineated in the GRMRSA and the G-EthicsHR-ZAF, the sponsor is required to report all expected or unexpected SAEs/SADRs on an expedited basis to all concerned parties, including the investigator(s) and institution(s), the SAHPRA, and the ECs. Pursuant to the G-SafetyRpt, the sponsor is required to submit the following safety reports to SAHPRA:

  • Reports of SUSARs occurring in the clinical trial using the SAHPRA SAE form (ZAF-19), CIOMS form (ZAF-15), or Annex B of G-SafetyRpt
  • Reports of all SUSAR and trends occurring with the investigational product (IP) in South Africa
  • Six-month progress report
  • Annual Development Safety Update Reports (DSURs) that includes information gathered from all clinical experience with the IP, whether in South Africa or elsewhere
  • Final Progress Report
  • Final Study Report

The SA-GCPs states that the sponsor is responsible for performing an ongoing safety evaluation of the IP and must promptly provide written notification to the investigator and SAHPRA of findings that may adversely affect the safety of participants or the conduct of the trial, and/or change the EC's approval to continue the trial. The commitment to provide safety information must be included in the clinical trial agreement signed between the sponsor and the investigator.

The G-SafetyRpt delineates the following reporting timeframes:

  • The sponsor should initially report all fatal or life-threatening SAEs in local reports within seven (7) calendar days after first knowledge, using CIOMS format (ZAF-15)/SAHPRA SAE form (ZAF-19). The follow-up report should be submitted within an additional eight (8) calendar days.
  • All fatal or life-threatening SAEs in foreign reports should initially be reported within 30 calendar days after first knowledge by the sponsor. The follow-up report should be submitted within an additional six (6) months as part of the progress report. If the SAEs result in premature study closure, the reporting times are shorter—seven (7) days for the initial report and within an additional eight (8) days for the follow-up report. These reports should be in a line listing format. Note that these reporting requirements also cover foreign reports of “special concern,” which is a significant safety issue defined for each clinical trial that requires urgent attention from the regulatory authority. An adverse reaction of special concern from a foreign jurisdiction should be based on the decision of its regulatory authority. A safety issue leading to international regulatory action is considered to be significant at all times and hence reportable.
  • Local reports of other serious events (unexpected, not fatal or life threatening) within 15 calendar days of the event and every six (6) months in the CIOMS format (ZAF-15)/SAHPRA SAE form (ZAF-19)
  • A line listing of all local reports—serious (unexpected and expected) AEs—and any other issues of special concern outside South Africa should be submitted every six (6) months (using the progress report form in ZAF-18).
  • An initial detailed report of new information impacting the risk-benefit profile of the IP or conduct of trial should be submitted within three (3) calendar days; a follow-up report should be submitted within an additional six (6) months.
  • An initial detailed report of other major safety concerns (e.g., changes in nature, severity, or frequency of risk factors) should be submitted within 15 days of knowledge of the concern; a follow-up report should be submitted within an additional six (6) months.
  • DSURs should be submitted within one year from approval of the study and annually thereafter.

In addition, SAHPRA reserves the right to impose additional reporting timelines on an individual protocol basis, and it may require expedited reporting of AEs of special interest, whether serious or not.

See the G-SafetyRpt for details on the contents of the reports and other safety report requirements.

Form Completion & Delivery Requirements

Per the G-SafetyRpt and ZAF-19, the SAHPRA’s Safety Reporting During Clinical Trials Form (ZAF-19) should be used to complete SAE/ADR reports—for both initial and follow-up safety reports. The G-SafetyRpt indicates that adverse drug reactions occurring during post-marketing studies (Phase 4 and observational studies) should be reported to the Vigilance Unit of SAHPRA, and adverse drug reactions occurring during the use of concomitant and/or comparator medicine in a clinical trial should be reported to the Clinical Trial Unit of SAHPRA. Reportable safety information must be sent to:

As per ZAF-47, the following is the contact information for pharmacovigilance-related submissions:

G-CTA-Electronic details the requirements for electronic submission of individual SAEs. All SAEs should be submitted to ctcsaes@sahpra.org.za with a cover letter detailing:

  • The title of the study
  • The SAHPRA reference number
  • Protocol number
  • Name of site
  • Patient study ID
  • Cause of SAE
  • Causality and SAE reporting form
  • Other applicable information

The email subject line should include the following information: SAE, protocol number, and SAHPRA database tracking number.

Part B
Clinical Evaluation and Management (Pharmacovigilance)
1, 2, and 6
4.5.1 and Appendix 1
8
4.1-4.2, 4.6-4.7, 5.2, 6.1-6.4, and 7.1-7.3
5.12, 6.4, 6.9, and 12
1 and 30(7)
Last content review/update: February 9, 2024

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).

2.0 and 9.1
1.1, 3.4, 3.13, and 4.18-4.19
7.1-7.2 and 9.1-9.4
Part I (2), Part III (18-19), and Part IV (21-22)
2-3, 6, and Schedule (Format of Report on Suspected Adverse Drug Reactions for Human Drugs)

Progress Reporting

Last content review/update: December 18, 2023

Interim and Annual Progress Reports

In accordance with the GRMRSA, the person authorized by the South African Health Products Regulatory Authority (SAHPRA) to conduct a clinical trial (i.e., the sponsor) must submit progress reports to the SAHPRA every six (6) months from the application approval date. The SA-GCPs requires the investigator to submit written progress reports to the ethics committee (EC) annually and to SAHPRA every six (6) months. ECs and SAHPRA may request reports more frequently.

Per the GRMRSA, the SA-GCPs, and G-SafetyRpt, the six-month report (ZAF-18) must include the following (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • SAHPRA database tracking number
  • Study title
  • Protocol number
  • Details of the sponsor
  • Progress to date or the outcome in case of completed research
  • Whether participant follow up is still active or has been completed
  • List of all active trial sites, addresses, and principal investigators (PIs)
  • Trial information, including date of approval of study, treatment hold (if applicable), and expected date of completion
  • Number of participants per site and current enrollment status
  • Sponsor comment on progress to date
  • Summary Data Safety Monitoring Board or Safety Committee recommendations and relevant safety data
  • Serious adverse events and suspected unexpected serious adverse reactions for all participants per site in South Africa, including identification of previous safety reports submitted to SAHPRA concerning a similar suspected adverse reaction and an analysis of their connection
  • Any safety issues of special concern outside of South Africa
  • Line listing of all critical and major protocol violations/noncompliance and resolutions/actions taken at a site or conditions of approval
  • Principal investigator (PI) comment on other major safety concerns
  • Signature of the PI
  • Signature of the sponsor

Note that the SA-GCPs directs the investigator to promptly provide written reports to the sponsor/applicant, the EC, and where applicable, the institution on changes that significantly affect trial conduct and/or increase the risk of participant harm.

Final Report

The sponsor is required to submit a final progress report to the SAHPRA 30 days following the trial’s completion as stated in the GRMRSA and the G-SafetyRpt. Further, per G-SafetyRpt, a final study report should be submitted within 180 days of clinical trial completion or termination.

In addition, per the SA-GCPs, upon the trial’s end, the investigator must inform the institution (if applicable), the EC, and SAHPRA and provide them with a summary of the trial outcome and other required reports.

The SA-GCPs specifies that the sponsor must ensure that trial results and outcomes are reported to the investigators, SAHPRA, and the National Department of Health (NDOH) via the South African National Clinical Trials Register (SANCTR) (ZAF-48) within one (1) year of the study’s completion. The sponsor and the PI are responsible for appropriate dissemination of the trial findings.

6.1-6.2 and 7.3.1
5.5, 5.11, 5.14, and 6.15
Part 30 (6)
Last content review/update: February 9, 2024

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.

9.4-9.5
1.7, 3.15, and 5.2
14.1 and 14.4
7.2
Part II (12) and Schedule 2 (Format for the Clinical Trial Report)

Definition of Sponsor

Last content review/update: December 18, 2023

As defined in the SA-GCPs, a sponsor is the person or organization responsible for the initiation, management, or financing of a clinical trial. A sponsor can be a pharmaceutical company, the principal investigator (PI), a funding body, or an individual or organization designated by the funding body or academic institution. An applicant can be an individual, company, institution, or organization that acts on behalf of the sponsor to initiate and manage the trial as its local representative. In the case of an international sponsor, a local applicant designated by the sponsor is responsible for initiation and management of the trial in the local context.

Per the SA-GCPs, a sponsor may transfer any or all trial-related duties and functions to a contract research organization (CRO). However, the sponsor is always ultimately responsible for the study data quality and integrity. Further, per the G-Monitor, the sponsor is solely responsible for adequate oversight of clinical trial conduct, including the justification for and selection of monitoring methods. Any trial-related responsibilities transferred to and assumed by a CRO should be specified in writing. The sponsor retains those responsibilities not specifically transferred to and assumed by a CRO.

1
6
Last content review/update: February 9, 2024

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.

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

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

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

2.0
Annex 13 (Glossary to Annex 13)
1.1 and 4.5
7.2
Part I (2), Part II (4), and Schedule 1 (Form 30)

Site/Investigator Selection

Last content review/update: December 18, 2023

Overview

As set forth in the SA-GCPs, the sponsor is responsible for using qualified individuals (e.g., biostatisticians, clinical pharmacologists, and physicians), as appropriate, throughout all stages of the trial process. Sponsors should select investigator(s) who are qualified by training and experience and have adequate resources to conduct the proposed clinical trial. Further, per the G-Monitor, the sponsor should consider previous experience with the investigator or site, workload of the investigator, and resource availability at the study site during investigator and site selection. Per the G-Capacity, clinical trial applications should include evidence and activity plans to build capacity at each study site as well as enhancing research activities and skills of professionals from historically disadvantaged groups. Mandatory training in Good Clinical Practice (GCP) forms a part of capacity building. To support transformation and capacity building, the South African Health Products Regulatory Authority (SAHPRA) states that the sponsor must have a policy on “Capacity Building and Transformation in Clinical Research in SA” in place, and preferentially select sites that are compliant. See G-Capacity, for detailed information on actions that will comply with this requirement.

According to the SA-GCPs, the sponsor must also define and allocate all study related duties and responsibilities to the investigator prior to initiating the study.

In addition, per ZAF-21, to add or change investigators and/or additional sites to an approved clinical trial, the sponsor must submit a signed application to SAHPRA. See ZAF-21 for details.

Per the G-CTInvestigators, SAHPRA will recognize and approve categories of investigators for trial leadership. The principal investigator (PI) must be a South Africa-based scientist, who has sole or joint responsibility for the design, conduct, and delegation of trial responsibilities, analysis, and reporting. The PI is accountable to the sponsor and regulatory authorities. The PI can designate and supervise sub-principal investigator(s) (Sub-PI) of which at least one (1) must be a clinician and registered with the appropriate statutory entity to provide clinical oversight within their scope of practice. Further, the SAHPRA recognizes a category of co-principal investigator (co-PI), which allows for a team consisting of two (2) co-PIs to lead a study at a site. At least one (1) of the co-PIs must be a clinician registered with the appropriate statutory body and qualified to provide clinical oversight within their scope of practice. For multi-center studies, there must be a national PI appointed, who may or may not be a site PI. The national PI must have appropriate experience and expertise in that field and must be responsible for the application to the SAHPRA to conduct the study. The national PI must meet all other requirements to be a PI and sign a declaration accepting the responsibility as national PI and sign off on the clinical trial application. For more information on PI requirements, roles, and responsibilities, see the G-CTInvestigators.

Per the SA-GCPs, all parties involved in the conduct of a trial should be familiar with the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27) and other international guidelines. Additionally, the investigator must agree to conduct the trial in compliance with the SA-GCPs, ZAF-27, SAHPRA requirements, and the ethics committee approved protocol. In the event of an interpretation conflict between the SA-GCPs and an international guideline, the SA-GCPs take precedence.

Foreign Sponsor Responsibilities

As required in the SA-GCPs, if South Africa is selected as a clinical trial site but the country of origin or other high-income countries are not, the sponsor must explain the reason(s) why and provide a clear ethical justification. Further, multi-national trials should ensure that a reasonable proportion of project team members are South African researchers, including scientists and health care professionals and those from previously disadvantaged backgrounds.

Data and Safety Monitoring Board

Per the SA-GCPs, the sponsor may establish an independent Data Safety Monitoring Board (DSMB) to assess the progress of a clinical trial, including safety data and critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The DSMB must have written standard operating procedures and must maintain written records of all its meetings.

Multicenter Studies

Per the SA-GCPs, if the trial is a multicenter and/or multi-country trial, any differences in trial designs between the South African and other sites must be clearly documented and explained in the trial protocol and/or related documents. In addition, international research groups must comply with South African regulatory requirements, and researchers must adapt the trial design and informed consent procedures to take into account local conditions and characteristics.

1.25, 5.5, and 5.6
5
3 and 4
1.2, 5.9, 6.2, 6.4, and 7.12
Last content review/update: February 9, 2024

Overview

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

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
4.3
1.6, 3.0, 3.2, 4.8-4.9, and 4.25
8.0
3.6
Part II (4, 7, and 10) and Schedule 1 (Forms 30, 35, and 37)

Insurance & Compensation

Last content review/update: December 18, 2023

Insurance

As set forth in the G-Insurance and the SA-GCPs, all clinical trial sponsors and investigators must obtain adequate insurance and indemnity to cover any liability claims during the conduct of a clinical trial, in accordance with the responsibilities described in the SA-GCPs. As delineated in the SA-GCPs and G-Insurance, a sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s (ABPI) guidelines (ZAF-26 and ZAF-25) to comply with South Africa’s clinical trial insurance requirements. Per the SA-GCPs, research participants should not bear any financial cost to rectify harms that occur as a result of trial participation. The insurer pays the medical costs of necessary treatment to restore the previous position of the participant, if possible, when bodily or other injury is attributable to trial participation. Only bodily injuries of an enduring and disabling character (including exacerbation of an existing condition) and/or death are covered by the insurance. Temporary pain or discomfort or less serious or curable complaints are generally not regarded as trial-related, bodily injury. In the case of an in-utero injury due to the mother’s participation, payment for medical expenses proceeds as though the unborn child is a research participant. For additional details on limitations on liability, dispute resolution, weighting of risk factors, and insurance settlements, see the SA-GCPs.

Per the G-Insurance, the application to conduct a clinical trial must include evidence of comprehensive no fault insurance for serious injury and harm and/or death. In addition, the sponsor must provide indemnification for all investigators and trial sites involved in their clinical studies on compliance with the protocol requirements. In cases where the investigators/site staff were negligent and/or did not comply with the protocol requirements, personal malpractice insurance would apply.

As delineated in the G-Insurance and ZAF-23, an insurance certificate and indemnity must be included in the clinical trial application submitted to the South African Health Products Regulatory Authority (SAHPRA). Per the G-Insurance, the sponsor must include details of the insurance, including the following:

  • Name and local address of the insurance company, including contact name and telephone number
  • Title and protocol number of the clinical trial
  • Date of commencement and termination of coverage
  • Liability limit – per occurrence and total per occurrence and total for the study. Note that the limit should be adequate enough to cover extended stay in an intensive care unit or hospital
  • Date of issuance of the insurance policy and expiry thereof
  • Original or electronic signature of the insurer
  • Special conditions if any. It is unacceptable to have special conditions which may invalidate or abate the clinical trial cover
  • Any additional coverage
  • Declaration of compliance with the SA-GCPs and ABPI guidelines on the certificate and in the patient information leaflet
  • Where the insurance is not provided by a local company, a local insurance vendor must be identified with full details
  • Insurance policy number
  • The amount insured

Compensation

Injury or Death

As set forth in the G-Insurance, all clinical trial sponsors and investigators must have adequate insurance to cover any liability claims during the conduct of a clinical trial, in accordance with the responsibilities as described in the SA-GCPs. As delineated in the SA-GCPs and G-Insurance, a sponsor must follow the principles set forth in the ABPI guidelines (ZAF-26 and ZAF-25) to comply with South Africa’s participant compensation and treatment requirements for trial-related injuries. The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or their legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committee (EC).

The SA-GCPs, the G-Insurance, and ZAF-26 provide several compensation principles to guide sponsors in fulfilling their obligations (Note: the sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • Compensation should be paid when it can be demonstrated that a causal relationship exists between a participant’s injury and their participation in a trial
  • Compensation should be paid when the injury results in permanent injury or disability to the participant
  • When there is an adverse reaction to a medicinal product under trial, and injury is caused by a procedure adopted to deal with that adverse reaction
  • The sponsor/applicant is under strict liability with respect to injuries caused by the investigational product (IP), and research participants should not bear any financial cost to rectify harms that occur as a result of trial participation
  • The insurer should pay the medical costs of necessary treatment to restore the previous position of the participant, if possible
  • In the case of an in-utero injury due to the mother’s participation, payment for medical expenses proceeds as though the unborn child is a research participant
  • In principle, only bodily injuries of an enduring and disabling character (including exacerbation of an existing condition) and/or death are covered by the insurance; temporary pain or discomfort or less serious or curable complaints are generally not regarded as trial-related, bodily injury
  • Where there is an adverse reaction to an IP and the injury is caused by a procedure adopted to deal with that adverse reaction, compensation should be paid for such injury as if it were caused directly by the IP
  • Payment for medical expenses is made without acknowledgement of any legal liability and is thus to be understood to be an ex-gratia payment
  • The provision of insurance cover and payment of medical expenses does not mean that an injured participant may not pursue legal action against the sponsor for loss or harm not covered by the insurance; however, an argument that pain and suffering, loss of income, and other possible claims should be paid for by the sponsor’s insurer is not sound in South African law and will not succeed
  • The likelihood of an adverse reaction, or the fact that the participant has freely consented (whether in writing or otherwise) to participate in the trial should not exclude the participant from being eligible for compensation

According to the SA-GCPs and ZAF-26, the amount of compensation to be paid to the participant should be appropriate to the nature, severity, and persistence of the injury. The compensation should also be generally consistent with the amount of damages commonly awarded for similar injuries. The amount paid in compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):

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

ZAF-26 provides that in any case where the sponsor agrees to pay the participant, but the two (2) parties differ on what is the appropriate level of compensation, it is recommended that the sponsor agree to seek, at the sponsor’s own cost, the opinion of a mutually acceptable independent expert. This opinion should then be made available to the participant(s), and the expert’s opinion should be given substantial weight by the sponsor in reaching a decision on the payment amount.

Additionally, any participant claims pursuant to ZAF-26 should be made to the sponsor, preferably via the investigator. The participant should include details on the nature and background of the claim, which the sponsor should review expeditiously. The review process may be delayed if the participant requests an authority to examine any medical records relevant to the claim.

Trial Participation

As specified in the G-TIECompensation and the SA-GCPs, the sponsor or the designated representative is responsible for providing compensation to research participants. The SA-GCPs state that before the clinical phase of the trial commences, the EC must approve the documentation on participant compensation. Per the G-EthicsHR-ZAF, the SA-GCPs, and the G-TIECompensation, compensation should be based on time, inconvenience, and expenses. In addition, the G-EthicsHR-ZAF and the SA-GCPs also address researcher requirements to budget for participant travel and other expenses. (See the G-EthicsHR-ZAF for detailed information). See ZAF-5 for an analysis of ethical considerations regarding payment of trial participants in South Africa.

The G-TIECompensation guides sponsors of approved clinical trials and proposes a model for minimum compensation that can be paid. It is not intended as an exclusive approach and the SAHPRA reserves the right to request any additional information. In addition, G-TIECompensation is not applicable to Phase I clinical trials, which pose a higher risk for participants and should be compensated on a different scale.

Post-Trial Access

The G-PostCTAccess guides sponsors on when to consider post-trial or continued access (PTA/CA) to the IP following the trial’s conclusion. Only those participants who derive benefit from the IP will be considered (this excludes participants on standard of care, placebo, and registered medicines). Where appropriate and available, the possibility of PTA/CA should be disclosed to and discussed with potential participants during the initial informed consent process or via a separate consent process. Where appropriate and/or available, details of potential PTA/CA should be included in the clinical trial application form, informed consent form, and patient information leaflet. Additional considerations include the following:

  • PTA/CA is not applicable for Phase I and II studies. However, PTA/CA may be necessary for particular diseases (e.g., cancer or rare diseases).
  • PTA/CA should be considered for Phase III studies when there is no registered and marketed standard of care in South Africa, provided that data from interim or final analyses shows that access is clinically justifiable.
  • PTA/CA is not applicable to Phase IV studies
  • A minimum of four (4) years after completion of the study is recommended as the acceptable time period to provide PTA/CA to the participants, unless there are compelling reasons for determining otherwise.
  • During the PTA/CA period, the sponsor must ensure monitoring and oversight of participants using the IP.
3 and 4
Cover, 1 and 2
1-5 and 7
3.1.7
1.2, 2.7, 6.2, 7.14, 9.2, and 10.2
Last content review/update: February 9, 2024

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

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

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

Injury or Death

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

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

  • Definitely: When injury is directly caused by participation in a research project
  • Probably: When injury is most likely explained by participation in a research project but when no definite proof of causality is evident
  • Possibly: When explanation for injury is equally due to participation in a research project or other cause
  • Unlikely: When injury is more likely explained by another cause other than participation in a research project

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

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

Trial Participation

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

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.

4.6 and Appendix I
3.0 and 7.0
3.12, 4.11, and 4.12
2.2, 6.1, 6.3-6.6, and 7.2
Part III (15) and Schedule 1 (Form 29)

Risk & Quality Management

Last content review/update: December 18, 2023

Quality Assurance/Quality Control

Per the SA-GCPs, the sponsor is responsible for implementing a quality management system to manage quality throughout the design, conduct, recording, evaluation, reporting, and archiving of clinical trials. This quality management system should adopt a risk-based approach for risk identification, evaluation, control, communication, and reporting. The sponsor should focus on trial activities that promote human participant protection and reliability of trial results, which include using qualified individuals, designating qualified medical personnel to respond to trial-related medical questions, and ensuring all aspects of the trial are operationally feasible and avoiding unnecessary complexity, procedures, and data collection. With respect to quality assurance (QA) and quality control (QC), the sponsor is responsible for implementing and maintaining QA and QC 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, and the applicable regulatory requirement(s).

Per the G-Monitor, the responsibility for adequate oversight of the conduct of a clinical trial, including the justification for and selection of monitoring methods, remains that of the sponsor solely.

Per the SA-GCPs, all parties involved in the conduct of a trial should be familiar with guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27) and other international guidelines. Additionally, the investigator must agree to conduct the trial in compliance with the SA-GCPs, ZAF-27, South African Health Products Regulatory Authority (SAHPRA) requirements, and the ethics committee (EC) approved protocol. In the event of an interpretation conflict between the SA-GCPs and an international guideline, the SA-GCPs take precedence.

Monitoring Requirements

In accordance with the SA-GCPs, the sponsor must conduct an independent audit to evaluate trial conduct and compliance with the protocol, procedures, good clinical practice, and the applicable regulatory requirements. The sponsor must appoint individuals who are independent of the clinical trials to conduct the audits and ensure that the auditors are qualified by training and experience to conduct audits properly. The sponsor's audit plan and procedures for a trial audit must be guided by the number of participants in the trial, the type and complexity of the trial, the level of risks to the trial participants, and any identified problem(s). Observations and findings of the auditors must be documented. The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, and reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities.

In addition, per the G-Monitor, the sponsor’s monitoring plan should include planned audits to ensure that monitoring activities are in accordance with the monitoring plan, applicable regulations, guidance, and sponsor’s plans and policies.

Premature Study Termination/Suspension

Per the SA-GCPs, if a trial is prematurely terminated or suspended for any reason, the investigator must promptly inform the trial participants and ensure appropriate therapy and follow-up for them. If the investigator, sponsor, institution, SAHPRA, or the EC terminate or suspend a trial, the investigator must promptly inform the other parties with a detailed written explanation for the termination or suspension. The sponsor is also responsible for ensuring that the South African National Clinical Trials Register (SANCTR) (ZAF-48) is updated as well.

1.65, 5.0-5.2, 5.5, 5.18, 5.19, 5.21, 5.23, 6.10, and 8
1 and 4
Introduction, 1.2, 5.10, 5.13, 6.1, 6.4, and 6.12
Last content review/update: February 9, 2024

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.

5.6
1.7, 3.9, 4.3-4.4, 4.20, 4.21
Part II (12), Part III (15), and Schedule 2 (Format of Report for Terminated Clinical Trial)

Data & Records Management

Last content review/update: December 18, 2023

Electronic Data Processing System

Per the SA-GCPs, the sponsor must ensure that the electronic data processing system conforms to the specific documented requirements for completeness, accuracy, reliability, and consistency of intended performance, and that standard operating procedures for using these systems are maintained. In addition, the sponsor must:

  • Ensure that the systems are designed to document data changes without deleting previously entered data (i.e., maintain an audit trail)
  • Maintain a security system that prevents unauthorized access to the data
  • Maintain a register of persons authorized to make data changes
  • Maintain adequate data backup
  • Ensure that blinding, if any, is maintained during data entry and processing
  • Ensure the integrity and confidentiality of data, including any that describe the context, content, and structure of the data – especially when making changes to computerized systems
  • If data are transformed during processing, it must be possible to compare the original data and observations with the processed data
  • Use an unambiguous participant identification code that allows identification of all data reported for each participant
  • Report any transfer of ownership of the data to South African Health Products Regulatory Authority (SAHPRA)

Per the G-Monitor, when developing a study’s monitoring plan, the sponsor should consider how it uses electronic data capture (EDC) systems. EDC systems that are capable of assessing quality metrics in real time will help identify high-risk sites that need more intensive monitoring.

Records Management

As set forth in the SA-GCPs, the sponsor should inform the investigator(s) in writing of the need for record retention, and should notify these parties in writing when the trial related records are no longer needed. The sponsor, or other data owners, must retain all the sponsor-specific essential documents pertaining to the trial for not less than 10 years or until at least two (2) years have elapsed since the formal discontinuation of clinical development of the investigational product (IP).

4
Introduction, 1.2, 5.10, 6.4
Last content review/update: February 9, 2024

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 also describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use.

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

Records Management

The G-TrialsGCP and the G-CTConduct state that the sponsor and the PI are responsible for archiving and ensuring the safety of all trial-related documentation. Per the NDPA-CTReg, documents and information provided to the National Drug Authority (NDA) along with a clinical trial application for unregistered investigational products (IPs) should be kept for 20 years following the trial's completion. Documentation for trials involving IPs to be registered should be kept for two (2) years after the registration of the IP. The NDPA-CTReg and the G-CTConduct further state that the holder of the clinical trial certificate should inform the NDA in writing prior to destroying the documents. Per the G-CTConduct, documents may be stored in electronic (soft and scanned) or hard copies.

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

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

9.5
4.8, 5.1, and 5.3-5.5
11.2
Part II (4) and Part III (18)

Personal Data Protection

Last content review/update: December 18, 2023

Responsible Parties

For the purposes of data protection requirements, the POPIA provides that the “responsible party” is a public or private body or any other person that, alone or in conjunction with others, determines the purpose of and means for processing personal information.

Data Protection

Per the POPIA, participants have the right to privacy, which includes a right to protection against the unlawful collection, retention, dissemination, and use of personal information by public and private bodies. This right to privacy is subject to justifiable limitations that are aimed at protecting other rights and interests (e.g., the right of access to information). Additional information on the rights of data subjects is provided in the POPIA.

The POPIA states that the responsible party must protect the constitutional right to privacy by safeguarding personal information when it is processed. The law provides conditions under which personal information may be gathered and processed.

  • Accountability – The responsible party must ensure that the conditions and all the measures in the POPIA are complied with at the time of the purpose and means of processing is determined
  • Processing limitation – Personal information may only be processed in a fair and lawful manner and only with the consent of the data subject
  • Purpose specification – Personal information may only be processed for specific, explicitly defined, and legitimate reasons
  • Further processing limitation – Personal information may not be processed for a secondary purpose unless that processing is compatible with the original purpose
  • Information quality – The responsible party must take reasonable steps to ensure that the personal information collected is complete, accurate, not misleading, and updated where necessary
  • Openness – The data subject whose information you are collecting must be aware that you are collecting such personal information and for what purpose the information will be used
  • Security safeguards – Personal information must be kept secure against the risk of loss, unlawful access, interference, modification, unauthorized destruction and disclosure
  • Data subject participation – Data subjects may request whether their personal information is held, as well as the correction and/or deletion of any personal information held about them

The POPIA establishes a duty requiring a public or private body to register its Information Officer with the Information Regulator (South Africa). Per the POPIA, the Information Officer is responsible for compliance with lawful processing of information and working with and responding to requests by the Regulator. Per the POPIA-Regs, the Information Officer has further responsibilities to:

  • Develop, implement, monitor, and maintain a compliance framework
  • Conduct a personal information impact assessment to ensure compliance with the conditions for the lawful processing of personal information
  • Develop, monitor, and maintain a manual; and make it available upon request by any person, provide copies of the manual to any person upon request and payment of a fee to be determined by the Information Regulator from time to time
  • Develop internal measures and systems to process requests for information or access
  • Conduct internal awareness sessions on protection of personal information requirements
  • Provide reasonable assistance free of charge to the data subject in objecting to processing of personal information (using Form 1 in the POPIA-Regs) and/or correcting or revising a record of personal information (using Form 2 in the POPIA-Regs)

The POPIA provides that records of personal information for research may be retained longer than is necessary for achieving the purpose for which the information was collected or processed if the responsible party has established appropriate safeguards against the records being used for any other purposes.

For additional guidance on processing personal data, including guidance on “special personal information” (e.g., health history) and personal information of children, see the Information Regulator website.

Consent for Processing Personal Data

Per the POPIA and the POPIA-Regs, personal information may only be processed if the data subject and/or the legal representative(s) or guardian(s) consents to the processing. The responsible party bears the burden of proof for the consent. The data subject and/or the legal representative(s) or guardian(s) may withdraw consent at any time if the lawfulness of the processing of personal information will not be affected.

Preamble, Chapter 1 (1-2), Chapter 2 (4-5), Chapter 3, and Chapter 5 (55-56)
2-4
Last content review/update: February 9, 2024

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: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

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

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

Children

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

Part I (2), Part II (3), Part III, Part VI, and Part V
Parts III, VI, and VIII

Documentation Requirements

Last content review/update: December 18, 2023

Obtaining Consent

In all South African clinical trials, a freely given, written informed consent is required to be obtained from each participant in accordance with the principles set forth in the NHA, the Declaration of Helsinki (ZAF-44), the SA-GCPs, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

As per the SA-GCPs, the G-EthicsHR-ZAF, and the G-GPHlthCare, the informed consent form (ICF) and patient information sheet(s) are essential documents that must be reviewed and approved by an accredited ethics committee (EC) based in South Africa and provided to the South African Health Products Regulatory Authority (SAHPRA) with the clinical trial application. (See the Required Elements section for details on what should be included in the form.) The principal investigator (PI), or a person designated by the PI, should provide research study information to the participant and/or the legal representative(s), or guardian(s). When drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education. The informed consent document should be non-technical and understandable to the participant and in a participant’s preferred written language. The ICF content should be briefly and clearly presented, without coercion or unduly influencing a potential participant to enroll in the clinical trial.

The SA-GCPs directs that none of the oral or written information concerning the study, 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 their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or the representatives from the sponsor’s liabilities for any negligence.

Re-Consent

The G-GPHlthCare-IC states that the participant must be informed of any relevant new findings over the course of the study, and be given the choice to continue to participate or withdraw from the study. Per the SA-GCPs, written informed consent documentation and other participant-related information should be revised when new information that may be relevant to a participant’s consent or willingness to continue to participate in the trial becomes available. Any revisions must be submitted for ethics review and approval before implementation. Communication of the new information to participants must be documented.

Language Requirements

According to the SA-GCPs and the G-EthicsHR-ZAF, the ICF and any patient information sheet(s) should be written in English and in a vernacular language that the participant is able to understand. The G-GPHlthCare states that the researchers should provide information to the participants in a language that the participant understands and in a manner that takes into account the participant’s level of literacy, understanding, values, and personal belief systems.

Documenting Consent

As stated in the SA-GCPs, the G-EthicsHR-ZAF, and the G-GPHlthCare, the ICF should be signed by the participant and the PI, or the person designated by the PI. If the participant is incapable of giving an informed consent, the legal representative(s) or guardian(s) should sign the ICF. The original signed ICF and patient information sheet(s) should be retained by the investigator and a copy should be given to the participant. The SA-GCPs requires an additional copy of the signed ICF and a source document identifying the study and recording the participation dates should be placed in the participant’s medical records. According to the SA-GCPs, the G-EthicsHR-ZAF, the G-GPHlthCare, and the G-GPHlthCare-IC, in all cases, written informed consent must be obtained. Where the participant is illiterate and/or the legal representative(s) or guardian(s) is illiterate, verbal consent should be obtained in the presence of and countersigned by a literate witness. The participant and/or the participant’s legal representative(s) or guardian(s), the PI or person designated by the PI, and if applicable, a literate witness must personally sign the ICF. Further, the SA-GCPs states that the participant should indicate willingness to participate by making a mark (either a cross or a fingerprint). The witness signs to affirm that the participant willingly consented to participate. The witness dates the mark and signature.

Waiver of Consent

No information is currently available regarding conditions for waiving consent.

3, 4.4, 4.8, and 6
3.4 and 6.3
11, 12.3, and 15.1.3
1.3-1.6, 2.3, 3.1, 3.2, 4.3, and 5.2
2.5 and 5.9
Chapter 9 (71)
Last content review/update: February 9, 2024

Obtaining Consent

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

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

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

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

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

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

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

Re-Consent

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

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

Language Requirements

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

Documenting Consent

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

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

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

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

Waiver of Consent

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

  • The research project carries no more than minimal risk (risk that is no more than the risks encountered in normal daily life in a stable society)
  • The research project could not practicably be carried out without the waiver or alteration (whenever appropriate the research participants will be provided with additional pertinent information after participation)
  • Deception needs to be applied to achieve the objectives of the study
  • The only record linking the research participant and the research project would be the ICF and the risk to the research participant would be potential harm resulting from a breach of confidentiality
  • The research participant is involved in an emergency situation and informed consent cannot be reasonably obtained from the individual or the representative
4.6 and 4.7
3.7 and 4.25
4.5, 4.7-4.8, 5.1-5.2, and 5.4-5.5
Part II (4) and Part III (14)

Required Elements

Last content review/update: December 18, 2023

Based on the informed consent essential elements in the SA-GCPs, the G-EthicsHR-ZAF, the G-GPHlthCare, and the NHAParticipants, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: the regulations 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
  • Why the potential participant has been approached and their responsibilities
  • The aspects of the clinical trial that are experimental
  • Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant; information should include the probability and magnitude of the foreseeable risks of harm
  • Any benefits to the participant or to others that may reasonably be expected from the research; if no benefit is expected, the participant should also be made aware of this
  • A disclosure of appropriate alternative procedures or treatments, and their potential benefits and risks
  • The probability for random assignment to each treatment
  • Participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
  • Compensation and/or medical treatment available to the participant in the event of a trial-related injury
  • The planned incentives, if any, to attract the participant and the planned reimbursements, if any, for time, inconvenience, and expenses
  • The extent to which confidentiality of records identifying the participant will be maintained, the possibility of record access by the sponsor, the ethics committee (EC), or the South African Health Products Regulatory Authority (SAHPRA)
  • EC contact details for information and concerns regarding the trial participants’ rights
  • The sponsor’s identity
  • Potential conflicts of interest of the principal investigator (PI)
  • The consequences of a participant's decision to withdraw from the study
  • Information about approval from the EC and SAHPRA
  • The approximate number of participants in the research study, locally and globally
  • The expected duration of participation
  • An explanation of whom to contact in the event of research-related injury
  • Foreseeable circumstances under which the investigator(s) may remove the participant without consent
  • The participant and/or the legal representative(s) or guardian(s) will be notified if significant new findings developed during the study which may affect the participant's willingness to continue

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

6.3
2.3.6 and 3.3.6
1.2, 2.5, 5.9, and 6.2
5
Last content review/update: February 9, 2024

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: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

  • 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 or legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant's willingness to continue
  • A witness may represent vulnerable populations during the informed consent process, if applicable
  • The study has been approved by an accredited Ugandan-based 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.

3.7 and 4.12
5.1-5.4
Part III (14)

Participant Rights

Last content review/update: December 18, 2023

Overview

South Africa’s ethical standards promote respect for all human beings and safeguard the rights of research study participants. In accordance with the principles held forth in the Declaration of Helsinki (ZAF-44), the SA-GCPs, the G-EthicsHR-ZAF, the G-GPHlthCare, the G-GPHlthCare-IC, the NHAParticipants, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (ZAF-27), a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. Below are the basic rights for participants in clinical research studies. (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

According to the NHA and the NHAParticipants, everyone has the right to participate in any decision affecting their health or treatment, including research. The participant and/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 G-GPHlthCare-IC, a potential research study participant has the right to be fully informed on the nature and purpose of the research study, its anticipated duration, the sponsor and investigator(s), any potential benefits or risks, study procedures, any compensation for participation, injury and/or treatment, and any significant new information regarding the research study. (See the Required Elements section for a more detailed list.)

Per POAIA, a participant may seek access to their clinical trial records, pursuant to their constitutional right of access to any information held by the State or by another person.

The Right to Privacy and Confidentiality

Per the G-GPHlthCare-IC, participants have the right to privacy and confidentiality, and the ICF must provide a statement identifying this right. It is the responsibility of the investigator to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

Per the G-GPHlthCare-IC, the research participant and/or the legal representative(s) or guardian(s) should be provided with contact information for the investigator(s), and the ethics committee to address clinical trial-related queries, in the event of any injury and/or to appeal against a violation of the participant’s rights. It is also required that the South African Health Products Regulatory Authority (SAHPRA) address and contact information be provided. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The SA-GCPs and ZAF-44 clearly state that research participants have the right to safety and well-being, which must take precedence over the interest of science and society. The NHA and the NHAParticipants safeguard the rights of all South Africans including vulnerable populations.

2-4, and 6
1-3
1.1, 2.3, and 3.1
2.4-2.5 and 4.3
2 and 5
Chapter 1 (2), Chapter 2 (8 and 11), and Chapter 9 (71)
Act, Preamble, and Chapter 2
Last content review/update: February 9, 2024

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

The Right to Information

According to the NGHRP and the G-TrialsGCP, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

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

The Right to Safety and Welfare

The NGHRP 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.

3.7
1.1, 1.3-1.4, 2.2-2.3, and 5.1-5.4
Part II (4) and Part III (14)
Last content review/update: December 18, 2023

The NHA and the G-EthicsHR-ZAF make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies. As per the G-EthicsHR-ZAF, the ethics committee (EC) may approve a delay in obtaining informed consent for emergency medical research if:

  • Inclusion in the trial is not contrary to the interests of the patient
  • The research poses no more risk than is inherent to the participant’s condition, or would be caused by alternative treatments
  • The participant, the participant’s next of kin, and/or legal representative(s) or guardian(s) will be informed as soon as is reasonably possible of the participant’s inclusion in the study, and have the option to withdraw from the study at any time
  • The research is based on valid scientific hypotheses, and offers a realistic possibility of benefit over standard care

Per the G-CTAPHEmerg, the South African Health Products Regulatory Authority (SAHPRA) states that during a public health emergency, informed consent and the patient information sheet(s) remain essential documents that must be reviewed and approved by an EC and provided to the SAHPRA with the clinical trial application.

11.5-11.6 and Annex 1
3.1, 3.2, and 3.4
Chapter 2 (7, 8, and 9)
Last content review/update: February 9, 2024

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

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

3.7
5.5 and 8.1

Vulnerable Populations

Last content review/update: December 18, 2023

Overview

The NHA, the SA-GCPs, the G-EthicsHR-ZAF, the G-GPHlthCare, and the NHAParticipants require special considerations for vulnerable populations, and characterize them by limited education, limited economic resources, inadequate protection of human rights, discrimination due to health status, limited ability to provide informed consent, limited availability of health care and treatment options, or an inadequate understanding of scientific research. Vulnerable populations include children/minors, mentally and physically disabled, pregnant women, substance abusers, prisoners, armed forces, the homeless, the elderly, members of a group with a hierarchical structure, patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, nomads, refugees, and other vulnerable groups such as persons in dependent relationships.

The SA-GCPs state that ethics committees (ECs) must pay special attention to protecting participants from vulnerable populations. The ECs may impose additional measures such as imposing additional protective measures for the informed consent process or requiring increased monitoring and interim reporting on the participants’ welfare. As per the NHAParticipants, research with vulnerable participants must comply with the following requirements:

  • Involve vulnerable persons only when non-vulnerable persons are not appropriate for inclusion
  • Not systematically avoid inclusion of vulnerable participants because it is unfairly discriminatory, and would prevent this population from benefiting from relevant research
  • Be responsive to health needs and priorities of vulnerable persons, and
  • Provide special attention in the ethical review to ensure research-related risks are assessed and minimized, and appropriate consent procedures are followed

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

Persons in Dependent Relationships or Hierarchical Situations

As indicated in the SA-GCPs and the G-EthicsHR-ZAF, participants whose proposed involvement in research arises from dependent or hierarchical relationships need additional attention, and particular attention should be given to ensuring that their consent is both adequately informed and voluntary. In addition, per the NHAParticipants, research is appropriate when research-related risks of harm are minimized. These types of relationships include, but are not limited to, those who are in junior or subordinate positions in hierarchically structured groups, such as prisoners and prison authorities, older persons and their caregivers, and patients and healthcare professionals.

Persons Highly Dependent on Medical Care

Per G-EthicsHR-ZAF, participants who are highly dependent on medical care may have a limited capacity to provide informed consent due to the gravity of their medical condition. In addition, their medical condition may require invasive measures resulting in greater risk. There may also be a perception of coercion if a participant is reluctant to refuse consent for fear that it may compromise the medical treatment. The EC may approve a delay in obtaining informed consent for research participants highly dependent on medical care if the following conditions are met:

  • Research is based on valid scientific hypotheses that support a reasonable possibility of more benefit than that offered by standard care
  • Participation is not contrary to their medical interests
  • Research interventions pose no more risk of harm than that inherent in the participant’s condition or alternative methods of treatment
  • As soon as reasonably possible, the participant must be informed and give delayed consent and advised of the right to withdraw from the research without any reduction in quality of care

Persons with Physical Disabilities

As described in the G-EthicsHR-ZAF, recruitment strategies for research participation in general should be sensitive to the possibility that persons with physical disabilities may wish to volunteer and therefore should ensure that there are no unintended barriers to such participation (e.g., the absence of ramps or a lift for wheelchair-bound potential participants). Research involving participants with physical disabilities should anticipate possible barriers and include measures to minimize them.

Elderly Persons

As per the G-GPHlthCare, research involving elderly persons requires consent to be provided by the participant’s legal representative(s) or guardian(s) on that person's behalf. Because of their vulnerability, the elderly should not be included in research unless the research is necessary to promote the health of this population and unless this research cannot instead be performed on legally competent persons.

Research Involving Collectivities

Per the G-EthicsHR-ZAF, a collectivity is a distinct group characterized by common beliefs, values, social structures, and other features identifying them as a separate group. Investigators are required to obtain EC approval for research involving a collectivity when any of the following conditions apply:

  • Property or information private to the group as a whole is studied or used
  • Research requires the permission of people occupying positions of authority, or involves members acknowledged as representatives to participate
1, 2.4.6, 3.1, 4.1.2, 4.1.3, and 6.3
1.3, 2.3, 3.1, 3.2, 3.4, and 4.5
1.2, 3.1, 3.4, 6.2, and 12
1 and 4
Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), and Chapter 9 (70(2)(d) and 71)
Last content review/update: February 9, 2024

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.

1.1 and 2.3
4.7 and 8.0

Children/Minors

Last content review/update: December 18, 2023

The SA-GCPs stipulate that minors are younger than 18 years old and are regarded as vulnerable persons due to their lack of legal capacity. The G-GPHlthCare-IC states that a person over the age of 18 years is an adult and is legally competent to decide on all forms of treatment and medical procedures. However, a child who is 12 years of age and older is legally competent to consent to a proposed investigation if the child is of sufficient maturity and is able to understand the benefits, risks, social, and other implications of the research. A minor's/child’s refusal to participate in research must be respected.

Per the SA-GCPs, documented permission from the legal representative(s) or guardian(s) must be obtained in advance prior to approaching the minor to request participation. According to the NHA, the G-EthicsHR-ZAF, the SA-GCPs, the G-GPHlthCare, and the G-GPHlthCare-IC, consent for minors/children to participate in research must be obtained from:

  • The legal representative(s) or guardian(s) in all but exceptional circumstances (such as emergencies)
  • The minor/child who is competent to make the decision
  • Any organization or person required by law (defined in the NHA)
  • Where the minor/child is not competent, assent from the minor/child and consent from the legal representative(s) and/or guardian(s)

According to the NHA, where research or experimentation is to be conducted on a minor for therapeutic purposes, the study may only be conducted when:

  • It is in the best interests of the minor/child
  • It is carried out in such manner and on such conditions as may be prescribed
  • The consent of the minor’s parent or guardian is provided

Where research or experimentation is to be conducted on a minor for non-therapeutic purposes, the NHA, the NHAParticipants, the SA-GCPs, and the G-MinisterConsent state that a study may only be conducted when:

  • It is carried out in such manner and on such conditions as may be prescribed
  • The consent of the Minister of Health is provided, or, where appropriate, consent from a delegated authority
  • The consent of the minor’s parent or guardian is provided
  • The consent of the minor is provided when the minor is capable of understanding

See the NHAParticipants for detailed application requirements.

In addition, per the G-MinisterConsent, the Minister of Health may not give consent if any of the following circumstances apply:

  • The study objective(s) can also be achieved if conducted on an adult
  • The research is unlikely to significantly improve scientific understanding of the minor’s/child's condition, disease, or disorder to such an extent that it will result in significant benefit to the minor(s)/child(ren)
  • The reasons for the consent to the research by the parent or guardian and, if applicable, the minor/child, are contrary to public policy
  • The research poses a significant risk to the health of the minor
  • The risk to the health or well-being of the minor is not significantly outweighed by the potential benefit

For more information on ministerial consent for non-therapeutic health research with minors, see the operational guidelines at the G-MinisterConsent.

As delineated in the G-EthicsHR-ZAF and the NHAParticipants, the following additional criteria must be met to conduct clinical trials with minors/children:

  • The research study presents minimal risk
  • The research study presents more than minimal risk, but potentially direct or anticipated benefit for the participant outweighs the risk
  • The research presents more than minimal risk (minor increase), and may not have a direct benefit to the participant, but has a high probability of producing important and relevant information, and that benefit may outweigh the risk
  • Adults are not appropriate participants for the research

In all cases, there should be sufficient reasons to justify why minors/children should be included as participants.

Assent Requirements

The SA-GCPs and the G-EthicsHR-ZAF require the ethics committee (EC) to ensure that adequate steps outlined in the clinical protocol are used to obtain a minor’s assent when, in the EC’s judgment, the minor is capable of providing such assent. When the EC determines that assent is required, it must also indicate whether and how such assent should be documented. A minor’s/child’s assent should not be assumed simply because of failure to object during the informed consent process. It is necessary for the minor/child and the legal representative(s) or guardian(s) to be in agreement on participation. The minor’s/child’s refusal to participate is final.

Consent for Processing Personal Data

Per the POPIA, there is a general prohibition on the processing of personal information of children. However, a responsible party may process personal information concerning a child for research purposes to the extent that:

  • The purpose serves a public interest, and the processing is necessary for the purpose; or
  • It appears to be impossible or would involve a disproportionate effort to ask for consent, and sufficient guarantees are provided to ensure that the processing does not adversely affect the individual privacy of the child to a disproportionate extent.
5, 6.3, and 8.5
8.5
1-6 and Appendices 1-3
3.2
1.2, 2.5, 3.2, and 6.2
4 and 7
Chapter 9 (71)
Chapter 3 (35)
Last content review/update: February 9, 2024

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

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

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

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

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

Assent Requirements

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

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

3 and 4.1
5.6, 5.8, and Glossary

Pregnant Women, Fetuses & Neonates

Last content review/update: December 18, 2023

As per the NHA and the G-EthicsHR-ZAF, any research studies involving pregnant women, women who may become pregnant, or fetuses, require additional safeguards to ensure the research conforms to appropriate ethical standards and upholds societal values. The ethics committee (EC) must provide particular attention to these participants due to the potential for additional health concerns that may arise during pregnancy, and the need to avoid unnecessary risk to the fetus.

The SA-GCPs stipulates that pregnant women, women planning to become pregnant, or breastfeeding women are usually excluded from human clinical trials where a new chemical entity (NCE) or medicines with no information on safety in pregnancy/lactation are investigated for treatment of a particular disease/condition or disorder. However, when safety and other relevant information is available, pregnant or breastfeeding women should be included in clinical trials to ensure that appropriate knowledge about NCEs for this group is developed.

3.2
1.2, 6.2, and 10.7
Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), Chapter 9 (70(2)(d) and 71), and Chapter 11 (90(1)(s) and 90(2))
Last content review/update: February 9, 2024

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

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

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

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

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

3 and 4.1
5.7
Last content review/update: December 18, 2023

According to the NHA, the G-EthicsHR-ZAF, and the NHAParticipants, a prisoner may not, even with consent, participate in any scientific experimentation, research study, or clinical trial except under limited conditions. Per the G-EthicsHR-ZAF, prisoners are considered a vulnerable class of persons because of the potential effect of incarceration on the voluntariness of the decision to participate in research. Neither coercion nor undue influence is acceptable in the informed consent process. Researchers should pay attention to whether their intended participants are prisoners who are awaiting trial or are convicted as different ethical issues arise for each group. The recruitment strategy design must pay careful attention to how coercion and undue influence will be avoided. Similarly, persons administering questionnaires or conducting interviews must be conscious of environmental factors that may influence voluntariness. The ethics committee (EC) should include, at least on an ad-hoc basis, a member with experience and knowledge of working with prisoners when deliberating on the protocol.

Per the G-EthicsHR-ZAF, research should be conducted on prisoners only if:

  • Their participation is indispensable to the research
  • The research cannot be conducted with non-prisoners
  • The research concerns a problem of relevance to prisoners
  • Sound informed consent processes can be ensured
  • Engagement with relevant role players about the proposed research has occurred

Generally, it is unlikely that independent consent by minor prisoners will be justifiable.

3.2
4
Chapter 2 (7, 8, and 11) and Chapter 9 (71)
Last content review/update: February 9, 2024

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.

2.3

Mentally Impaired

Last content review/update: December 18, 2023

According to the NHA, the SA-GCPs, the G-EthicsHR-ZAF, the G-GPHlthCare, and the NHAParticipants, sufficient justification must be provided for any research or treatment involving a participant who has a mental or intellectual impairment or substance abuse related disorder, and the research must be relevant to the mental disability or substance abuse disorder.

Per the G-EthicsHR-ZAF, research involving these populations must conform to the following requirements:

  • The research, including observational research, is not contrary to the best interest of the participant
  • The research, including observational research, places the incapacitated adult at no more than minimal risk
  • The research involves greater than minimal risk but provides the prospect of direct benefit for the incapacitated adult; the degree of risk must be justified by the potential benefit
  • The research, including observational research, involves greater than minimal risk, with no prospect of direct benefit to the incapacitated adult, but has a high probability of providing generalizable knowledge
  • The legally appropriate person gives permission for the person to participate
  • Where appropriate, the person will assent to participation (Note that the incapacitated person’s refusal or resistance to participate, as indicated by words or behavior, takes precedence over permission by a proxy)

The G-EthicsHR-ZAF and the G-GPHlthCare state that research involving unconscious persons requires consent to be provided by the participant’s legal representative(s) or guardian(s) on that person's behalf. Unconscious persons should not be included in research unless the research is necessary to promote the health of the population represented and unless this research cannot instead be performed on legally competent persons.

4 and 6.3
2.3 and 3.2
1.2, 3.3, and 6.2
4
Chapter 2 (7, 8, and 11), and Chapter 9 (71)
Last content review/update: February 9, 2024

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.

2.3

Definition of Investigational Product

Last content review/update: December 18, 2023

As delineated in the SA-GCPs and the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs), an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes:

  • A product with a marketing authorization when used or assembled (formulated or packaged) in a different way from the approved form
  • When used for an unapproved indication
  • When used to gain further information about an approved use
2
Annex 13
1.2, 6.2, and 12
Last content review/update: February 9, 2024

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 product with a marketing authorization 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
2.0
Annex 13 (Glossary to Annex 13)
1.1
Glossary
Part I (2)

Manufacturing & Import

Last content review/update: December 18, 2023

Manufacturing

According to the SA-GMPs and the GRMRSA, the South African Health Products Regulatory Authority (SAHPRA) is responsible for authorizing the manufacture of investigational products (IPs) in South Africa. As delineated in the G-ManuImpExp, a manufacturer’s license for IPs is required for both total and partial manufacture, and for the various processes of dividing up, packaging, or presentation, in accordance with the MRSA. To obtain a license, the application form (ZAF-55) should be emailed to SAHPRA at gmplicensing@sahpra.org.za, accompanied by the following information:

  • Proof of payment
  • Existing SAHPRA license for renewal and amendment applications
  • Cover letter
  • Site Master File
  • Signed declaration
  • SAHPRA inspection resolution
  • Intellectual property documentation
  • Department of Health premises license
  • Registration of responsible pharmacist
  • South African Pharmacy Council (SAPC) Record of a Pharmacy
  • SAPC Record of a Pharmacy Owner
  • Municipal Approval/Zoning Certificate

Per ZAF-55, the license is valid for five (5) years and the application to renew the license must be submitted at least 180 days before the expiration of the current license.

In addition, per ZAF-23, a clinical trial application to SAHPRA must include a certificate of good manufacturing practice (GMP) for manufacture of the IP(s). The SA-GCPs also states that the sponsor must ensure that the IP (including active comparator and placebo, if applicable) is manufactured in accordance with applicable GMP standards.

Pursuant to the SA-GMPs, South Africa adopted the PIC-S-GMP-Guide for the manufacturing of therapeutic goods. The PIC-S-GMP-Guide includes requirements for a Certificate of Analysis to be issued by the manufacturer for all IPs to be used in a clinical trial. For GMP agreements with competent international regulatory authorities, the SA-GMPs states that these agreements do not permit automatic acceptance but may be used to enhance regulatory oversight and compliance. SAHPRA may request additional documentation and/or schedule an inspection to ensure GMP compliance. The following conditions demonstrate GMP compliance:

  • The site has been approved by a recognized regulatory authority (RA) within the previous three (3) years
  • The dosage form of the IP within the application is within the same dosage form grouping as the dosage form approved by the RA
  • The product type applied for is the same as the product type approved by the recognized RA
  • The activities applied for by the applicant are the same activities that have been approved by the recognized regulator

Import

The SA-GCPs states that IPs may be imported into South Africa only after approval of the protocol by SAHPRA. Samples of the IP to be imported before trial approval require a SAHPRA license under MRSA. The sponsor must ensure that the IP (including active comparator and placebo, if applicable) is manufactured in accordance with any applicable GMP standards. Per G-ManuImpExp to import an IP, the applicant must submit an application form (ZAF-55) to SAHPRA.

Per the G-ImprtPorts, SAHPRA’s Regulatory Compliance Unit is responsible for ensuring that health products at ports of entry meet importation requirements under MRSA, including for IPs. Imported IPs must be accompanied by the certificate of registration that proves authorization under the MRSA.

Please note: South Africa is party to the Nagoya Protocol on Access and Benefit-sharing (ZAF-8), 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 ZAF-34.

1.1 and 3.1.2, and Appendices 1-2
3
Annex 13
1.2, 5.7, 6.2, and 6.6
21 and 22C
23
Last content review/update: February 9, 2024

Manufacturing

According to the NDPA-CTReg, the G-CTConduct, and the G-TrialsGCP, the National Drug Authority (NDA) is responsible for authorizing the manufacture of investigational products (IPs) in Uganda. The NDA will only approve the manufacture of an IP after approval of the clinical trial application. The NDPA-CTReg indicates that if the IP is to be manufactured in Uganda, the holder of the clinical trial certificate must apply to the NDA for a manufacturing license.

Uganda follows the G-GMPMedicinal, the G-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-GMPMedicinalAnnexes further states that for manufacturers to be able to apply, and comply with, GMP for IPs, cooperation between manufacturers and sponsors of clinical trials is required. This cooperation should be described in a technical agreement between the sponsor and manufacturer.

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

See the G-GMPMedicinal, the G-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.

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

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

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

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

Please note: Uganda is party to the Nagoya Protocol on Access and Benefit-sharing (UGA-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see UGA-21.

10.0-10.2
Terms and Definitions, 11.0, and 14.0
4.15
Annex 13 (Introduction)
Introduction and Chapters 1 and 4
19
Part II (9) and Schedule 1 (Form 30)

Quality Requirements

Last content review/update: December 18, 2023

Investigator’s Brochure

In accordance with the SA-GCPs, the sponsor is responsible for ensuring an up-to-date Investigator’s Brochure (IB) is available to the investigator; investigators must provide it to the responsible ethics committee (EC). In the case of an investigator-sponsored trial, the sponsor-investigator must determine whether an IB is available from the commercial manufacturer.

The SA-GCPs states that the IB should contain the following sections, each with literature references where appropriate:

  • Table of Contents
  • Summary: A brief summary (preferably not exceeding two (2) pages) to highlight the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information available that is relevant to the stage of clinical development of the investigational product (IP)
  • A brief introductory statement with the chemical name (and generic and trade name for an approved product) of the IP, all active ingredients in the IP, its pharmacological class and expected position within this class (e.g., advantages), the rationale for conducting research with the IP, and the anticipated prophylactic, therapeutic, and/or diagnostic indications. Also include a description of the general approach to be followed in evaluating the IP.
  • Physical, chemical, and pharmaceutical properties and formulation parameters
  • Pre-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
  • Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and postmarketing experiences)
  • Summary of data and guidance for the investigator(s)

Quality Management

As defined in the SA-GCPs, the sponsor must ensure that IPs are manufactured in accordance with good manufacturing practices (GMPs), including the requirements in Annex 13 of the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs). (See Product Management section for additional information on IP supply, storage, and handling requirements). As indicated in ZAF-23, the following information must be furnished in the clinical trial application:

  • Whether the IP contains an active substance of chemical origin or of biological/biotechnological origin
  • IP name(s) and details (e.g., formulation(s) and strength(s))
  • Properties of the IP (e.g., mechanism of action)
  • Summary of pre-clinical findings (e.g., laboratory, animal, toxicity, or mutagenicity)
  • Summary of clinical findings
  • Comparator product(s) name(s) and details
  • Concomitant name(s) and details including rescue medications
  • Registration status of IP, concomitant, and/or comparator medicine(s); include the IB, South African Health Products Regulatory Authority (SAHPRA)-approved principal investigator (PI), and other international professional information (package inserts) if not approved in South Africa, and a Certificate of Analysis (CoA)
  • Whether the IP is modified in relation to its original registration for the purpose of the clinical trial
  • Estimated quantity of trial material (each drug detailed separately) for which exemption will be required, including for concomitant medicines to be imported
  • Explanation for use of imported drugs when the same product is available in South Africa
  • Details of receiving the drugs from supplier including storage, dispensing, and packaging of drugs
  • Details of intention to register the IP or explain if registration is not envisioned
  • Details of the manufacture, quality control, and stability of the IP (including IP destruction process) and include certificate of good manufacturing practice (GMP)
  • Previous studies using this medicine that have been approved by SAHPRA, including the SAHPRA approval number, study title, protocol number, date of approval, national PI/PI, date(s) of progress report(s), and date of final report

See ZAF-23 for detailed instructions on IP submission requirements.

Per the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs), the release of IPs should not occur until after the authorized person has certified that the relevant requirements have been met. CoAs should be issued for each batch of intermediate or active pharmaceutical ingredient, on request. CoAs should be dated and signed by authorized personnel of the quality unit(s) and should show the name, address, and telephone number of the original manufacturer. See the PIC-S-GMP-Guide for certification requirements.

2
Part II (11.4) and Annex 13
1.2, 5.7, 6.2, 6.5, 6.7, and 8
Last content review/update: February 9, 2024

Investigator's Brochure

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

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

The G-TrialsGCP, the NDPA-CTReg, and UGA-4 require the IB to provide coverage for the following areas:

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

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

Quality Management

Uganda follows the G-GMPMedicinal, the G-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, GMP ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the clinical trial authorization. The forementioned documents must be used for periodic GMP inspection of all manufacturers of medicinal products within and outside Uganda whose products are registered or subjected to registration in the country. Manufacturers that are GMP compliant will be issued GMP compliance certificates.

According to the G-CTConduct and the G-TrialsGCP, the sponsor must ensure that the IP(s) is manufactured in accordance with GMP. The G-CTConduct further indicates that evidence of manufacture under GMP standards must be submitted with the clinical trial application to the NDA. In cases where the 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-GMPMedicinalAnnexes, the manufacturer should establish and maintain a quality control system placed under the authority of a person who has the requisite qualifications and is independent of production. Quality control of the IP, including that of the comparator product, should be performed in accordance with the information submitted in the application for the clinical trial. See the G-GMPMedicinal and the G-GMPMedicinalAnnexes for more information on quality control requirements.

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

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

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

4.6, 10.2, and 10.5
4.15 and 7.0-7.3
Annex 13 (2 and 7)
Introduction and Chapters 1 and 4
Part I (2), Part III (15 and 18), and Schedule 2 (Format for Investigator’s Brochure)
Last content review/update: December 18, 2023

Investigational product (IP) labeling in South Africa must comply with the requirements set forth in the SA-GCPs, the GRMRSA, MRSA, and the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs). The GRMRSA states that for an IP to be used in a clinical trial, it must be properly labeled in English and at least one (1) other official language, and should appear in clearly legible and indelible letters. As set forth in the PIC-S-GMP-Guide, the following labeling information must be included on both the outer packaging and the immediate container:

  • The name, address, and telephone number of the sponsor, contract research organization (CRO), or investigator
  • The pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
  • The batch and/or code number to identify the contents and packaging operation
  • A trial reference code allowing identification of the trial, site, investigator, and sponsor (if not given elsewhere)
  • The trial participant identification number/treatment number and where relevant, the visit number
  • The investigator name (if not already included above)
  • Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
  • “For clinical trial use only” or similar wording
  • The storage conditions
  • The period of use (use-by date, expiration date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
  • “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by the participant

In addition, precautions against mislabeling should be intensified by trained staff (e.g., label reconciliation, line clearance, and in-process control checks by appropriately trained staff).

The SA-GCPs specify that in blinded trials, the IP should be coded and labeled in a manner that protects the blinding. The IP(s) coding system should include a mechanism that permits rapid IP(s) identification in case of a medical emergency but does not permit undetectable breaks of the blinding.

2
Annex 13
1.2 and 6.6
35
10 and 30 (9)
Last content review/update: February 9, 2024

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

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

According to the NDPA-CTReg and the G-CTConduct, the IP must be labelled as specified in UGA-7 or Form 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: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

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

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

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

4.6, 10.3, and Appendix I
Annex 13 (6.4 and 6.6)
4.15
7.2
Part III (17) and Schedule 1 (Form 38)

Product Management

Last content review/update: December 18, 2023

Supply, Storage, and Handling Requirements

As defined in the SA-GCPs, the sponsor is responsible for supplying a sufficient quantity of the investigational product (IP) after the sponsor obtains study approvals from the South African Health Products Regulatory Authority (SAHPRA) and the ethics committee (EC). The sponsor must ensure that written procedures include instructions and relevant documents for the investigator to follow for handling and storage of the IP for the trial. The procedures must address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from participants, and return of unused IP to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the SAHPRA-approved protocol). In addition, the sponsor must:

  • Ensure timely delivery of the IP to the investigator
  • Maintain records that document shipment, receipt, disposition, return, and destruction of the IP
  • Maintain a system for retrieving the IP and then documenting such retrieval (e.g., for deficient product recall, reclaim after trial completion, and expired product reclaim)
  • Maintain a system for disposal of unused IP and for its documentation
  • Take steps to ensure that the IP is stable over the period of use
  • Maintain sufficient quantities of the IP used in the trials to reconfirm specifications, if necessary, and maintain records of batch sample analyses and characteristics; to the extent that IP stability permits, samples should be retained until analyses of trial data are complete or as required by the applicable regulatory requirement(s), whichever is longer
  • Provide and maintain a system for retrieving and disposing of trial-related waste (e.g., syringes and needles)

Per the SA-GCPs, the sponsor should determine acceptable temperatures, conditions, times for IP storage, reconstitution fluids/procedures, and devices for product infusion, if any, that comply with the SA-GPPs. The sponsor must inform all parties involved (e.g., monitors, investigators, pharmacists, storage managers) of these determinations.

The SA-GCPs specify that if significant formulation changes are made in the IP(s) or comparator product(s) during the course of clinical development, the results of any studies of the newly formulated product(s) should be made available prior to its use in the clinical trial. Refer to the SA-GCPs for detailed sponsor-related IP requirements.

Regarding packaging, the PIC-S-GMP-Guide indicates that IPs are normally packed individually for each participant in the clinical trial. The number of units to be packaged should be specified prior to the start of the packaging operations, including units necessary for carrying out quality control and any retention samples to be kept. Sufficient reconciliations should take place to ensure the correct quantity of each product required has been accounted for at each stage of processing. During packaging, the risk of product mix up must be minimized by using appropriate procedures and/or, specialized equipment as appropriate and relevant staff training. The packaging must ensure that the IP remains in good condition during transport and storage at intermediate destinations. Any opening or tampering of the outer packaging during transport should be readily discernible. Similarly, the SA-GCPs state that the IPs must be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Record Requirements

Per the SA-GCPs, the sponsor, or other data owners, must retain all essential documents pertaining to the trial for not less than 10 years or until at least two (2) years have elapsed since the formal discontinuation of clinical development of the IP. In addition, the sponsor should obtain the investigator’s agreement to retain trial-related essential documents until the sponsor informs the investigator/institution that these documents are no longer needed.

Annex 13
1.2, 5.7, 6.2, 6.6-6.7, and 8.1-8.2
Last content review/update: February 9, 2024

Supply, Storage, and Handling Requirements

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

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

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

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

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

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

Record Requirements

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

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

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

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

10.5
Chapter 4
Annex 13 (5, 6.5, 8, and 11)
4.14-4.16
Part III (15-16 and 18)

Definition of Specimen

Last content review/update: December 18, 2023

In South Africa, the NHARegMicroLabs refers to a specimen as a “diagnostic specimen,” and defines it as any human or animal material, including excreta, secreta, blood and its components, tissue or tissue fluids, that is to be used for the purpose of diagnosis, but does not include live infected animals. The G-EthicsHR-ZAF, in turn, refers to a specimen as a “biological specimen,” and defines it as material from a person including blood and blood products, DNA, RNA, blastomeres, polar bodies, cultured cells, embryos, gametes, progenitor stem cells, small tissue biopsies, and growth factors.

The term “specimen” appears to be used interchangeably with “biological material” in South Africa. The NHABiol and the MTA-Human follow the G-EthicsHR-ZAF definition of biological specimen, defining “biological material” as material from a human being including DNA, RNA, blastomeres, polar bodies, cultured cells, embryos, gametes, progenitor stem cells, small tissue biopsies, and growth factors from the same. The G-EthicsHR-ZAF defines “human biological materials” with the same definition as is used for “biological specimen.”

In addition, the NHABloodCells generally refers to substances of human origin as biological substances.

Please refer to the G-EthicsHR-ZAF, the NHABiol, the NHA, the NHABloodCells, the NHATissue, and the NHAStemCell for more specific definitions of selected terms including blood, cultured cells, embryonic tissue, human tissue, plasma, stem cell, and genetic material.

Chapter 3 (3.3) and Appendix 1
1
1
1
2.9
1
1
1
Last content review/update: February 9, 2024

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.

10.0

Specimen Import & Export

Last content review/update: December 18, 2023

Import/Export

Per the NHA, the MTA-Human, the NHABloodCells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, a permit must also be obtained from the National Department of Health (NDOH) Director General to import or export biological substances. Both the South African Health Products Regulatory Authority (SAHPRA) approval letter and the NDOH import/export permit must be included with each biological substance shipment. See also the Submission Content section for information on completing a clinical trial application.

As set forth in the NHA, the NHABloodCells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, the NDOH Director-General, as delegated by the NDOH Minister, is responsible for establishing regulations related to the import and export of biological substances. In addition, only the Minister can authorize an institution or hospital to import or export biological substances for research purposes.

In accordance with the NHA, the NHABloodCells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, the NDOH Director-General reviews and approves all import or export requests by an institution or hospital. These requests must be submitted in writing using the application forms that may be obtained by contacting the NDOH Permit Programme at importexportpermit@health.gov.za. The forms also appear as Annexures 1-6 in the NHABloodCells and Form 1 in the NHARegMicroLabs.

Upon review of the application, the Director-General will issue a permit or certificate authorizing the import or export request if the Director-General is satisfied that the submission meets the NHA, the NHABloodCells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell requirements, as applicable. The permit will contain an expiration date for the approved biological substance(s).

General Import/Export Requirements for Biological Substances

The NHABloodCells states that each biological substance to be imported into South Africa must be accompanied by a certificate from the supplier stating that the substance has been exported in terms of the originating country’s applicable laws and regulations.

As per the NHABloodCells and ZAF-7, export permits for biological substances may only be issued by the Director-General to a Southern African Development Community (SADC) member state or to a South African citizen, provided that the country’s market requirements have been met. An applicant must also be registered with the Health Professions Council of South Africa (HPCSA) and operating in South Africa in order to apply for a permit to import or export biological substances. The applicant must also provide the Director-General with written information on stock levels for this substance along with the export application.

Applicants to whom a permit has been issued must keep a record of the import or export and submit this information using the register forms listed in Annexures 4, 5, and 6 of the NHABloodCells. The forms must be submitted to the Director-General annually before the end of February, for the preceding calendar year.

Import/Export Requirements for Specific Biological Substance Categories

The NHABloodCells provides details on unique application requirements for specific types of biological substances as outlined below:

  • Import of tissues being used for therapeutic purposes: application must be accompanied by donor health status
  • Export of tissues or gametes: application must include written proof that the donated biological substance complies with the NHA requirements
  • Import or export of placenta tissue, embryonic or fetal tissue, embryonic, fetal or umbilical stem cells: applications will only be approved with the Minister’s written consent
  • Import or export of blood or blood products: applications must be accompanied by a national blood transfusion service certificate and test results. If no documentation is included, the applicant must submit a letter to the Director-General explaining the reason. The Director-General will decide whether tests must be conducted, and the Minister is authorized to determine whether the applicant’s institution can be exempted from these requirements.

Material Transfer Agreement

Per the MTA-Human, all the providers and recipients of human biological material for use in research or clinical trials under the auspices of ethics committees (ECs) must use the “Material Transfer Agreement of Human Biological Materials” in MTA-Human. The agreement must be signed by the research institution’s authorized representative and the EC. The EC’s obligations are to:

  • Review and approve research proposals and protocols that require the transfer of human biological materials
  • Review and approve the material transfer agreement and ensure it adequately safeguards human biological material and ethical requirements
  • Review and approve all secondary use research if the material is to be transferred

The EC must be the last party to sign the agreement after all the provisions of MTA-Human have been satisfied.

2-13 and Forms 1 and 2
Chapter 8 (54, 57, 60, and 68)
2-5, 7, and Annexures 1-6
Cover page, 3, 4.1, and Annexure A
1 and 2
1, 3, and 16
Last content review/update: February 9, 2024

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.

4.6 and Appendices I and II
15.0
10.0

Requirements

(Guidance) Application to Conduct a Clinical Trial - Guidance in Conditions of a Public Health Emergency (G-CTAPHEmerg) (Version 2) (Effective June 1, 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Capacity Building and Transformation in Clinical Research in South Africa (G-Capacity) (Version 2) (October 2022)
South African Health Products Regulatory Authority
(Guidance) Clinical Guideline (G-Clin) (Version 3) (August 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Clinical Trial Investigators (G-CTInvestigators) (Version 3) (Effective October 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Electronic Submission of Clinical Trial Documents (Amendments, Bioequivalence Studies, Responses, Notifications, and Serious Adverse Events) (G-CTA-Electronic) (Version 3) (September 5, 2022)
South African Health Products Regulatory Authority
(Guidance) Emergency Procedures for Clinical Trial Sites (G-EmergencyProc) (Version 3) (August 2022)
South African Health Products Regulatory Authority
(Guidance) Ethics in Health Research: Principles, Processes and Structures (G-EthicsHR-ZAF) (2015)
National Department of Health
(Guidance) General Information Guideline (G-GenInfo) (Version 12) (December 2023)
South African Health Products Regulatory Authority
(Guidance) Good Pharmacy Practice in South Africa (SA-GPPs) (2018)
South African Pharmacy Council
(Guidance) Guideline for Clinical Trial Participant Time, Inconvenience & Expense (TIE) Compensation Model (G-TIECompensation) (Version 2) (Effective August 1, 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Post Clinical Trial Access (PTA)/Continued Access (G-PostCTAccess) (Version 4) (August 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Release of Import Health Products at Ports of Entry (G-ImprtPorts) (Version 2) (June 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for the Procedure of Consultation Meetings with Clinical Trial Applicants (G-ConsultMtg) (Version 2) (August 3, 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline on How to Apply for a License to Manufacture, Import, and/or Export Medicines and Scheduled Substances (G-ManuImpExp) (Version 3) (June 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline on the Payment of Fees to SAHPRA (G-SAHPRAFees) (Version 7) (September 2022)
South African Health Products Regulatory Authority
(Guidance) Guidelines for Good Practice in the Health Care Professions: General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa
(Guidance) Guidelines for Good Practice in the Health Care Professions: Seeking Patients’ Informed Consent: The Ethical Considerations, Booklet 4 (G-GPHlthCare-IC) (September 2016)
Health Professions Council of South Africa
(Guidance) Liability Insurance for Clinical Trials (G-Insurance) (Version 3) (August 2022)
South African Health Products Regulatory Authority
(Guidance) Ministerial Consent for Non-therapeutic Health Research with Minors: Operational Guidelines (G-MinisterConsent) (2015)
National Health Research Ethics Council, National Department of Health
(Guidance) Oversight and Monitoring in Clinical Trials (G-Monitor) (Version 4) (August 2022)
South African Health Products Regulatory Authority
(Guidance) PIC/S Guide to Good Manufacturing Practice for Medicinal Products, PE009-17 (PIC-S-GMP-Guide) (August 25, 2023)
The Pharmaceutical Inspection Co-operation Scheme
(Guidance) Guideline on Good Manufacturing Practice for Medicines (SA-GMPs) (Version 8) (September 2022)
South African Health Products Regulatory Authority
(Guidance) Guideline for Safety Reporting During Clinical Trials in South Africa (G-SafetyRpt) (Version 5) (October 2022)
South African Health Products Regulatory Authority
(Guidance) South African Good Clinical Practice: Clinical Trial Guidelines (SA-GCPs) (3rd edition) (2020)
National Department of Health
(Legislation) Children’s Act 38 of 2005 (ChildrensAct) (Effective April 1, 2010)
Parliament
(Legislation) Medicines and Related Substances Act (Act No. 101 of 1965) (MRSA) (Amended 2015)
Parliament
(Legislation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to Research with Human Participants (No.R.719) (NHAParticipants) (September 19, 2014)
Parliament
(Legislation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to the Registration of Microbiological Laboratories and the Acquisition, Importation, Handling, Maintenance and Supply of Human Pathogens (No.R.178) (NHARegMicroLabs) (March 2, 2012)
Parliament
(Legislation) National Health Act, 2003 (Act No. 61 of 2003) (NHA) (Amended 2013)
Parliament
(Legislation) Promotion of Access to Information Act (Act No. 2 of 2000) (POAIA) (Amended 2019)
Parliament
(Legislation) Protection of Personal Information Act, 2013 (Act No. 4 of 2013) (POPIA) (Effective July 1, 2020)
Parliament
(Regulation) Regulations Regarding Fees Payable in Terms of the Provisions of the Medicines and Related Substances Act, 1965 (Act No. 101 of 1965) (No. R. 1379) (MRSA-Fees) (December 22, 2020)
National Department of Health
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Material Transfer Agreement of Human Biological Materials (MTA-Human) (July 20, 2018)
National Department of Health
(Regulation) Medicines and Related Substances Act, 1965 (Act No. 101 of 1965): General Regulations (No. 859) (GRMRSA) (August 25, 2017)
National Department of Health
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Regarding the General Control of Human Bodies, Tissue, Blood Products, and Gametes: Amendment (NHASpecAmend) (April 26, 2017)
National Department of Health
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to Stem Cell Banks (No. R.183) (NHAStemCell) (March 2, 2012)
National Department of Health
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to the Import and Export of Human Tissue, Blood, Blood Products, Cultured Cells, Stem Cells, Embryos, Foetal Tissue, Zygotes and Gametes (No.R.181) (NHABloodCells) (March 2, 2012)
National Department of Health
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to the Use of Human Biological Material (No.R.177) (NHABiol) (March 2, 2012)
Parliament
(Regulation) National Health Act, 2003 (Act No. 61 of 2003): Regulations Relating to Tissue Banks (No. R.182) (NHATissue) (March 2, 2012)
National Department of Health
(Regulation) Regulations Relating to the Protection of Personal Information, 2018 (No.R.1383) (POPIA-Regs) (Effective July 1, 2021)
Department of Justice and Constitutional Development
(Circular) No. 009 - Certification of Premises Used to Supply Restricted Drugs within Institutions Conducting Clinical Trials (C-InstitutionCert) (February 27, 2018)
National Drug Authority
(Circular) No. 26 – Incomplete Clinical Trial Application Submissions (C-IncompleteCTA) (December 6, 2018)
National Drug Authority
(Guidance) Guidelines for the Conduct of Clinical Trials in Uganda (G-CTConduct) (Effective October 14, 2019)
National Drug Authority
(Guidance) Guidelines for the Provision of Insurance Cover for Research Participants in Clinical Trials in Uganda (G-InsuranceCover) (Effective October 14, 2019)
National Drug Authority
(Guidance) Guidelines on Good Clinical Practice in the Conduct of Clinical Trials Involving Human Participants (G-TrialsGCP) (Effective October 18, 2019)
National Drug Authority
(Guidance) Guidelines on Good Manufacturing Practice for Medicinal Products - Annexes (Revision No. 3) (G-GMPMedicinalAnnexes) (Effective September 6, 2023)
National Drug Authority
(Guidance) Guidelines on Good Manufacturing Practice for Medicinal Products Part I - Basic Requirements for Medicinal Products (Revision No. 4) (G-GMPMedicinal) (Effective September 6, 2023)
National Drug Authority
(Guidance) Guidelines on Good Manufacturing Practice for Medicinal Products Part II – Basic Requirements for Active Pharmaceutical Ingredients (Revision No. 1) (G-GMPMedicinalAPIs) (Effective September 6, 2023)
National Drug Authority
(Guidance) National Guidelines for Research Involving Humans as Research Participants (NGHRP) (July 2014)
Uganda National Council for Science and Technology
(Guidance) National Research Biobanking Guidelines (G-Biobank) (January 2021)
Uganda National Council for Science and Technology
(Guidance) Research Registration and Clearance Policy and Guidelines (G-UNCSTreg) (July 2016)
Uganda National Council for Science and Technology
(Legislation) National Drug Policy and Authority Act 1993, (Ch 206) (NDPA-Act) (December 3, 1993)
Parliament
(Legislation) The Data Protection and Privacy Act, 2019 (NITA-U-PrivAct) (May 3, 2019)
Parliament
(Legislation) The Uganda National Health Research Organisation Act, 2011 (UNHRO-Act) (June 10, 2011)
Parliament
(Legislation) Uganda National Council for Science and Technology Act 1990 – Chapter 209 (UNCST-Act) (June 1, 1990)
Parliament
(Regulation) The Data Protection and Privacy Regulations, 2021 (NITA-U-PrivReg) (March 12, 2021)
National Information Technology Authority - Uganda
(Regulation) The National Drug Policy and Authority (Conduct of Clinical Trials) (Amendment) Regulations, 2021 (NDPA-CTRegAmdt) (July 2, 2021)
Ministry of Health
(Regulation) The National Drug Policy and Authority (Conduct of Clinical Trials) Regulations, 2014 (S.I. 2014/32) (NDPA-CTReg) (March 28, 2014)
Ministry of Health
(Regulation) The National Drug Policy and Authority (Fees) Regulations, 2022 (S.I. 2022/5) (NDPA-FeesReg) (Effective March 1, 2022)
Ministry of Health
(Regulation) The National Drug Policy and Authority (Pharmacovigilance) (Amendment) Regulations, 2021 (NDPA-PVRegAmdt) (July 2, 2021)
Ministry of Health
(Regulation) The National Drug Policy and Authority (Pharmacovigilance) Regulations, 2014 (S.I. 2014/37) (NDPA-PVReg) (March 28, 2014)
Ministry of Health
(Guidance) National Guidelines for Community Engagement in Research (NGCER) (February 2022)
Uganda National Council for Science and Technology
(Guidance) Registration Classification and Guidance Note for Application for Registration/Renewal of Registration (PDPO-Note) (Version 1.3) (December 2021)
Personal Data Protection Office
(Correspondence) Request to Review Templates for Materials Transfer Agreements and Data Sharing Agreements (UNCST-RevTemp) (April 19, 2021)
Uganda National Council for Science and Technology
(Guidance) Guidelines on the Verification of Applications for the Importation and Exportation of Drugs and Pharmaceutical Raw and Packaging Materials (Revision No. 1) (G-VerImprtExprt) (Effective September 6, 2023)
National Drug Authority
(Guidance) Guidelines on the Conduct of Clinical Trials in Children, Pregnant and Lactating Women in Uganda (G-CTChldrnWmn) (Effective July 10, 2023)
National Drug Authority

Additional Resources

(Article) Human Tissue Legislation in South Africa: Focus on Stem Cell Research and Therapy (ZAF-3) (August 2015)
M S Pepper, South African Journal of Bioethics and Law
(Article) Payment of Trial Participants in South Africa: Ethical Considerations for Research Ethics Committees (ZAF-5) (2012)
National Health Research Ethics Council
(Document) A Comprehensive and Practical Guide to Clinical Trials (ZAF-6) (2017)
The Clinical Research Centre at the University of Cape Town
(Document) Biological Substances Export/Import Permits (ZAF-7) (Date Unavailable)
TNT and South African Clinical Research Association (SACRA)
(Document) Clinical Trials Committee Meeting and Submission Dates for 2024 (ZAF-11) (Version 1) (October 6, 2023)
South African Health Products Regulatory Authority
(Document) Nagoya Protocol on Access and Benefit-sharing (ZAF-8) (2011)
Convention on Biological Diversity, United Nations
(Document) Safety Reporting in Clinical Trials (ZAF-30) (November 29, 2019)
Ruff, Paul, University of the Witwatersrand, Member of SAHPRA Clinical Trials Committee
(Document) 2020/21 - 2024/25 Strategic Plan (ZAF-9) (January 2022)
South African Health Products Regulatory Authority
(Document) Clinical Trial Compensation Guidelines (ZAF-26) (2014)
Association of the British Pharmaceutical Industry, United Kingdom
(Document) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (ZAF-25) (2nd Edition) (June 2012)
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research Association, United Kingdom
(International Guidance) Declaration of Helsinki (ZAF-44) (October 19, 2013)
World Medical Association
(International Guidance) Handbook - Good Laboratory Practice (GLP): Quality Practices for Regulated Non-clinical Research and Development (ZAF-46) (2nd Edition) (January 1, 2009)
World Health Organization
(International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (ZAF-27) (Step 4 Version) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(Webpage) Clinical Trials Ethics in South Africa (ZAF-51) (Current as of December 18, 2023)
South African Clinical Research Association
(Webpage) Clinical Trials (ZAF-36) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) Country Profile: South Africa (ZAF-34) (Current as of December 18, 2023)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) Research Ethics Office (ZAF-49) (Current as of December 18, 2023)
South African Medical Research Council
(Webpage) Ethics Resources (ZAF-42) (Current as of December 18, 2023)
Pharma-Ethics Independent Research Ethics Committee
(Webpage) Fees (ZAF-37) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) National Health Research Ethics Council (ZAF-52) (Current as of December 18, 2023)
Department of Health
(Webpage) Pan African Clinical Trials Registry (ZAF-50) (Current as of December 18, 2023)
Pan African Clinical Trials Registry
(Webpage) South African Health Products Regulatory Authority - About Us (ZAF-39) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) South African Health Products Regulatory Authority - Our Offices (ZAF-35) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) South African Health Products Regulatory Authority - Key Contacts (ZAF-47) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) South African National Clinical Trial Register - How to Register a Trial (ZAF-32) (Current as of December 18, 2023)
National Department of Health
(Webpage) The SAHPRA Board (ZAF-38) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Webpage) The South African National Clinical Trials Register (ZAF-48) (Current as of December 18, 2023)
South African National Clinical Trials Register
(Webpage) FAQs – Clinical Trials (ZAF-1) (Current as of December 18, 2023)
South African Health Products Regulatory Authority
(Document) Accredited Research Ethics Committee in Uganda (UGA-11) (2022)
Uganda National Council for Science and Technology
(Document) Format for Investigator’s Brochure (UGA-4) (Effective August 20, 2018)
National Drug Authority
(Document) Format of Clinical Trial Report (UGA-6) (Effective August 20, 2018)
National Drug Authority
(Document) Format of Report for Terminated Clinical Trial (UGA-5) (Effective August 20, 2018)
National Drug Authority
(Document) Initial CTA Screening Checklist (UGA-1) (Rev No. 2) (Effective September 14, 2021)
National Drug Authority
(Document) Labelling Investigational Drug Products for Clinical Trial (UGA-7) (Date Unavailable)
National Drug Authority
(Document) Nagoya Protocol on Access and Benefit-sharing (UGA-3) (2011)
Convention on Biological Diversity, United Nations
(Webpage) The National Research Clearance Process (UGA-20) (Date Unavailable)
Uganda National Council for Science and Technology
(Document) Format for Clinical Trial Protocol (UGA-12) (Date Unavailable)
National Drug Authority
(Not Available Online) NIAID Communication with Makerere University (February 2022) (UGA-31)
(Webpage) Application for Permission to Conduct Research in Uganda (UGA-28) (Current as of February 9, 2024)
Uganda National Council for Science and Technology
(Webpage) Country Profile: Uganda (UGA-21) (Current as of February 9, 2024)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) Directorate of Product Safety (UGA-29) (Current as of February 9, 2024)
National Drug Authority
(Webpage) National Drug Authority – Contact Us (UGA-23) (Current as of February 9, 2024)
Ministry of Health
(Webpage) National Drug Authority – Innovation & Research Desk (UGA-10) (Current as of February 9, 2024)
Ministry of Health
(Webpage) National Drug Authority – Service Delivery Timelines (UGA-24) (Current as of February 9, 2024)
National Drug Authority
(Webpage) National Research Information Management System (NRIMS) (UGA-33) (Current as of February 9, 2024)
Uganda National Council for Science and Technology
(Webpage) Uganda National Council for Science and Technology – Contact Us (UGA-25) (Current as of February 9, 2024)
Uganda National Council for Science and Technology
(Webpage) Uganda National Council for Science and Technology – Who We Are (UGA-30) (Current as of February 9, 2024)
Uganda National Council for Science and Technology
(International Guidance) Declaration of Helsinki (UGA-27) (October 19, 2013)
World Medical Association
(Webpage) Uganda National Health Research Organisation – Contact Us (UGA-26) (Current as of February 9, 2024)
Uganda National Health Research Organisation
(Webpage) National Drug Authority: Management Information System (NDAMIS) (UGA-34) (Current as of February 9, 2024)
National Drug Authority

Form

(Form) Annual Report Form for Human Research Ethics Committees Registered with the National Health Research Ethics Council (ZAF-54) (Version 2.21) (May 13, 2021)
National Health Research Ethics Council
(Form) Application for Additional Investigator(s) or Change of Investigator(s) and Application for Additional Sites (ZAF-21) (Version 4) (September 2022)
South African Health Products Regulatory Authority
(Form) Application for a Protocol Amendment to Approved Trial (ZAF-20) (Version 4) (September 2022)
South African Health Products Regulatory Authority
(Form) Application to Conduct a Clinical Trial (ZAF-23) (Version 8) (Effective September 18, 2023)
South African Health Products Regulatory Authority
(Form) Application Form to Register a Human Research Ethics Committee with the National Health Research Ethics Council (ZAF-53) (Version 2.21) (May 13, 2021)
National Health Research Ethics Council
(Form) Application to the Human Research Ethics Committee: (Medical) - For Clearance of Research - For Pharmaceutical/Grant/Donor Sponsored Clinical Trials Involving Drugs/Devices (ZAF-45) (Version 9.1) (2019)
Human Research Ethics Committee, University of the Witwatersrand, Johannesburg
(Form) Biomedical Research Ethics Committee Application Form (ZAF-24) (Version 2) (2017)
Biomedical Research Ethics Committee, University of Kwazulu-Natal
(Form) CIOMS Form I (ZAF-15) (Date Unavailable)
Council for International Organizations of Medical Sciences
(Form) License Application to Manufacture, Import, or Export (HCR) Medicines and Scheduled Substances Including Contract Testing Laboratories (ZAF-55) (Effective August 26, 2022)
South African Health Products Regulatory Authority
(Form) Notification Studies: Phase IV (ZAF-17) (Version 5) (Effective October 1, 2023)
South African Health Products Regulatory Authority
(Form) Research Ethics Committee Application Form (ZAF-22) (Version 3) (January 2022)
Human Sciences Research Council (HSRC), South Africa
(Form) Six Monthly Progress Report Form for Clinical Trials (ZAF-18) (Version 5) (Effective September 22, 2023)
South African Health Products Regulatory Authority
(Form) Safety Reporting During Clinical Trials Form (ZAF-19) (Version 4) (Effective October 26, 2022)
South African Health Products Regulatory Authority
(Form) Application Form for REC Accreditation (UGA-9) (January 2022)
Uganda National Council for Science and Technology
(Form) Application for Additional Investigators, Change of Investigator or Additional Clinical Trial Sites (UGA-13) (Date Unavailable)
National Drug Authority
(Form) Application Form for Amendment of Conditions of a Clinical Trial (UGA-19) (Effective August 20, 2018)
National Drug Authority
(Form) Application Form for Renewal of Authorization of Clinical Trial (UGA-32) (Effective August 13, 2020)
National Drug Authority
(Form) CIOMS Form I (UGA-8) (Date Unavailable)
Council for International Organizations of Medical Sciences
(Form) Declaration by Monitor (UGA-17) (Date Unavailable)
National Drug Authority
(Form) Declaration by Principal Investigator (UGA-16) (Date Unavailable)
National Drug Authority
(Form) Declaration by Sponsor and Principal Investigator of Funds of the Clinical Trial (UGA-15) (Date Unavailable)
National Drug Authority
(Form) Letter of Authorization from Holder of Patent of Drug, Licensed Person or Manufacturer of Drug (UGA-18) (Effective October 18, 2019)
National Drug Authority
(Form) Pharmaceutical Data on Dosage Form (UGA-14) (Date Unavailable)
National Drug Authority
(Form) CTA Amendments Screening Form (UGA-22) (Effective March 23, 2020)
National Drug Authority
(Form) CTA Screening Renewal Form (UGA-2) (Effective April 17, 2018)
National Drug Authority
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