Comparison: South Africa and Uganda
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
For a detailed list of sources per topic, see the single country view.
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South Africa
Uganda
QUICK FACTS
English Clinical trial application language English
Yes Regulatory authority & ethics committee review may be conducted at the same time No
Yes Clinical trial registration required Yes
No In-country sponsor presence/representation required Yes
Under 18 Age of minors Under 18
Yes Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: July 23, 2020

Overview

As stated in the MRSA, Proc20of2017, and ZAF-9, the South African Health Products Regulatory Authority (SAHPRA) (formerly the Medicines Control Council (MCC)) is the regulatory authority overseeing medicines and clinical research, as well as medical devices and radiation safety. Per ZAF-39, SAHPRA assumed the roles of the MCC and the Directorate of Radiation Control (DRC), which were housed at the National Department of Health (NDOH). As stated in the MRSA, GRMRSA, and ZAF-10, SAHPRA is responsible for clinical trial oversight, approval, and inspections in South Africa. It 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 ensuring that all clinical trials of both non-registered medicines and new indications of registered medicines comply with the essential requirements for safety, quality, and efficacy.

Per the MRSA and as described in ZAF-4, 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 NDOH. For details on the Board appointments, see ZAF-39 and ZAF-38. As delineated in the MRSA, the CEO will be appointed for a term of five (5) years and may be reappointed for one (1) additional term. Reporting to the Board, the CEO will appoint and supervise staff and determine the structure and policies for SAHPRA. When fully established, SAHPRA will conduct the monitoring, evaluation, regulation, investigation, inspection, registration, and control of clinical trials. Among other functions, SAHPRA will ensure that clinical trial protocols are being assessed according to prescribed ethical and professional criteria and standards.

As described in ZAF-10, SAHPRA is reorganizing into a program structure that comprises:

  • Corporate Services Program
  • Health Product Authorization Program
  • Inspectorate and Regulatory Compliance Program
  • Evaluation for Registration Program
  • Medical Devices and Radiation Control

ZAF-10 describes the Health Product Authorization Program as the core of SAHPRA’s regulatory functions. Sponsors (also referred to as applicants) will interact with portfolio coordinators, whose roles will be to steer applications through the prescribed processes. Per ZAF-1, SAHPRA’s Clinical Trials Committee (CTC) will continue to provide scientific expertise and support. ZAF-36 states that CTC operates within SAHPRA’s Clinical Trial Unit, 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 medicine for the purpose of conducting clinical trials.

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.

South African Health Products Regulatory Authority Contact Information:

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

Physical Address:
CSIR
Reception Building 38a
Meiring Naudé Road
Brummeria
Pretoria
South Africa

Clinical Trial Unit Emails

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

New Clinical Trial Applications (CTA) and Responses to Reviews of CTAs: ctcresponses@sahpra.org.za

Protocol Amendments during Conduct of Clinical Trials: ctcamendments@sahpra.org.za

Additional Investigators and Sites during Conduct of Clinical Trials: ctcinvestigators@sahpra.org.za

Bioequivalence Studies: ctcbeprotocols@sahpra.org.za

Notifications and Notification Studies: ctcnotifications@sahpra.org.za

Individual Serious Adverse Events: ctcsaes@sahpra.org.za

Clinical Evaluation – Pre-Registration Contact:
Tohlang Sehloho
Phone: 012 842 7589
082 302 0222

Clinical Evaluation – Post-Registration Contact:
Linda Thomson
Phone: 079 914 2033

Clinical Trials Contact:
Dorah Diale
Phone: 012 842 7606
060 548 4332

eCTD: ectd@mccza.com

Pharmacovigilance Contact:
Florah Matlala
Phone: 012 842 7610
083 387 3358

For General Enquiries:
enquiries@sahpra.org.za (For general, non-product specific enquiries only.)

Last content review/update: November 11, 2020

Overview

As per the NDPA CTReg, the G-CTConduct, and the G-TrialsGCP, the National Drug Authority (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-31, the Clinical Trials Unit in the NDA’s Directorate of Product Safety is specifically responsible for reviewing and approving the clinical trial applications.

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

Contact Information

National Drug Authority
Secretariat Office Kampala
Plot 19 Lumumba Avenue
P.O. Box 23096
Kampala, Uganda
Phone: +256 [0]417 788 100 (Reception) / +256 [0]417 788 124 (Directorate of Product Safety) / +256 [0]417 788 129 (Directorate of Inspectorate Services)
Fax: (+256) 41 255758 / 343921
Email:
ndaug@nda.or.ug

Uganda National Council for Science and Technology (UNCST)

As delineated in the NDPA CTReg, the NGHRP, the G-CTConduct, and UGA-31, 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 Uganda National Council for Science and Technology (UNCST), or from an institution authorized by the UNCST.

Established in 1990 by the UNCST Act, the UNCST is a semi-autonomous government agency, operating under the Ministry of Finance, Planning and Economic Development, whose role is to develop and implement strategies for integrating science and technology (S&T) into the national development process, provide advice to the government on S&T policies, and to oversee and coordinate research and development in Uganda.

As per the NGHRP and the UNHRO Act, the UNCST collaborates with the Uganda National Health Research Organisation (UNHRO) to register all health research protocols, and liaises with the Research Secretariat in the Office of the President of Uganda to register and clear 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. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for submission requirements.)

Contact Information

The Executive Secretary
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 or via the UNCST Contact page.

Regulatory Authority > Scope of Assessment
Last content review/update: December 16, 2020

Overview

As stated in the MRSA, Proc20of2017, ZAF-36, and ZAF-10, 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. In accordance with the GRMRSA, the SA-GCPs, and the G-Clin, the 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.

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. Any amendments required during the conduct of the study must be approved by SAHPRA. As per G-GenInfo, the CTU is specifically charged with evaluating the following:

  • Clinical trial applications and clinical trial amendments
  • Adverse event reports arising from a clinical trial
  • Applications for named patient use (compassionate use) of unregistered medicines
  • Applications for the use of unregistered medicines for clinical trial purposes

The SA-GCPs’ clinical trial evaluation checklist states that the review should evaluate previous research relating to the safety and potential benefit of intervention, assess trial methods, and consider ethical issues.

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. Mandatory training in Good Clinical Practice (GCP) forms a part of capacity building. To support transformation and capacity building, SAHPRA requires 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.

Clinical Trial Review Process

As indicated in the SA-GCPs, the Clinical Trials Committee (CTC) within the CTU will consider the scientific, medical, and ethical issues of the applications, and ensure that the submissions provide proof of safety, quality, and efficacy of the investigational product for both unregistered and registered medicines. Prior to this committee review, per ZAF-36, there is a preliminary screening by the CTU, which 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 submission of the application. The applicant must respond within seven (7) working days after receipt of the screening review. Responses must be sent by hard copy to SAHPRA reception and emailed to ctcresponses@sahpra.org.za. 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 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 2021 dates). Clinical trial reviews will result in one 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

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.

(See the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed submission requirements.)

Last content review/update: November 11, 2020

Overview

In accordance with the NDPA Act, the NDPA CTReg, the G-CTConduct, the NGHRP, 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-2, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the local ethics committee (EC) (research ethics committee (REC) in Uganda) and the Uganda National Council for Science and Technology (UNCST) approvals in the application. Therefore, the NDA and 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.

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

Clinical Trial Review Process

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. Applications verified as complete will undergo internal (either expedited or routine), expert, or joint review. Complete applications are given a Clinical Trial Application code, and the NDA issues a Clinical Trial Certificate (CTC) once the application is approved. 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.

According to the C-CTCFormat, the NDA has adopted a new format for the CTC to align with the NDPA Act and the NDPA CTReg.

As per the NDPA CTReg, an application for deviation from a condition of a clinical trial must use Form 36 and must be accompanied by evidence of ethical approval of the amendment to the clinical trial protocol, where applicable. Per the G-CTConduct, the application for amendment of the conditions of a clinical trial can also be found in Appendix III of this guideline, and on the NDA website (UGA-19). The proposed changes must be listed in a cover letter signed by the applicant, and a clear step-by-step justification for each proposed change(s) must be provided. The possible consequences with regard to the benefit/risk balance for participants already enrolled in the trial must also be summarized in the cover letter.

(See the Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Timeline of Review subtopics for detailed submission requirements and review processes.)

Uganda National Council for Science and Technology

According to the NDPA CTReg, the G-CTConduct, the G-TrialsGCP, and the G-UNCSTreg, an applicant must also submit a research proposal for review and approval to the UNCST. Per the G-UNCSTreg, the UNCST receives and reviews research protocols for their scientific merit, safety, and ethical appropriateness, and when satisfied, issues permits to conduct the research in Uganda. The research permit is granted at a national level to facilitate access to research resources within the country. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for submission requirements.)

Uganda National Health Research Organisation

The UNHRO Act authorized the Uganda National Health Research Organisation (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 UNCST.

Regulatory Authority > Regulatory Fees
Last content review/update: June 18, 2020

Overview

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 G-GenInfo, the MRSA-Fees, and ZAF-37, applicants are responsible for paying several non-refundable fees to submit a clinical trial application. The various fee types include the following:

  • Authorization of the use of an unregistered medicine requires an application fee payable with the full submission of the application: company-sponsored trial fee (9,900 South African Rand (ZAR)); institution-sponsored trial fee (4,950 ZAR); any other clinical trial fee (2,420 ZAR)
  • Registration fee, payable when the application complies with all the registration requirements, and which is payable prior to a registration certificate being issued
  • Annual retention fee to maintain a manufacturing license (2,200 ZAR)
  • Clinical trial amendments - (i) technical amendments (2,310 ZAR per amendment); (ii) administrative amendment (715 ZAR per amendment)
  • Manufacturing site inspection(s) - local manufacturing site (715 ZAR per hour); international manufacturing site (4,400 ZAR per hour)
  • Manufacturing New license (23,980 ZAR)
  • Manufacturing Renewal license (20,900 ZAR)

Instructions for Payment of Clinical Trial Application Fees

The G-SAHPRAFees delineates that applicants should transfer fees directly into SAHPRA’s bank account by electronic or manual deposit. Check payments should not be made. As soon as the deposit has been made, an email confirmation of such deposit should be sent to naazneed.babamia@health.gov.za. This confirmation must also clearly indicate the reference for the deposit—screening fee for application number xxxxx, as well as a deposit reference number. For administrative purposes, SAHPRA requests one (1) payment per transaction. If payments for more than one (1) item are made per transaction, a clear breakdown must be supplied with the proof of payment. Electronic transfers must include a reference to at least the applicant’s name and telephone number, the product application number, or purpose of the payment. In the reference field, preference should be given to the telephone number if space is an issue.

Bank and account details are:

Account name: South African Health Products Regulatory Authority
Special Name: The Medicines Control Council Account
Account type: Cheque 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

Further details regarding procedures for payment are available in the G-SAHPRAFees and the G-GenInfo.

Last content review/update: November 11, 2020

Overview

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. The fee must be paid in the form of a check or electronic transfer to the order of the National Drug Authority (NDA) in U.S. dollars (USD) or the equivalent in Ugandan shillings.

In addition, according to the G-UNCSTreg, applicants are responsible for paying fees to the Uganda National Council for Science and Technology (UNCST) for the research permit and for the ethics committee (EC) (research ethics committee (REC) in Uganda) review.

NDA Fees

As set forth in the NDPA FeesReg, the following non-refundable application 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

UGA-22 also states that the NDA fee ranges from $1,000-$4,000 USD, but can be waived in special cases (e.g., for students who are not supported by a university or sponsored by industry).

UNCST Registration Fee

As delineated in the G-UNCSTreg, the 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 Ugandan students registered for study in local institutions, are responsible for paying this fee. Ugandan students are only required to pay a fee of $50 USD.

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-2, the research fees are as follows:

Amount: $300 USD or $50 USD for Ugandan students (or an equivalent in Ugandan shillings)
Bank: any branch of 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

Ethics Committee > Ethics Committee
Last content review/update: June 18, 2020

Overview

South Africa has a centralized registration process for ethics committees (ECs). (Note: ECs are referred to as health research ethics committees (HRECs) in South Africa). Per ZAF-31 and ZAF-33, the National Health Research Ethics Council (NHREC) is a statutory body established under the NHA. NHREC gives direction on ethical issues relating to health and develops guidelines for the conduct of research involving humans and animals. Further, NHREC observes and advises on international developments in health ethics issues with relevant international organizations. 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 norms and standards for conducting 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

Section 73 of 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 NHREC website provides a list of registered ECs and the application form to register an EC, which are also available through ZAF-28 and ZAF-14, respectively. Please refer to Authorizing Body subtopic for additional information.

EC Composition

As delineated in the SA-GCPs and the G-EthicsHR, 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.

Specifically, the EC composition should:

  • Represent the communities served and reflect its demographic profile
  • Have at least nine (9) members, with 60% representing a quorum; if there are more than 15 members, the quorum may be 33%
  • Have a chairperson
  • Include members of both genders; not more than 70% of its members should be one (1) gender
  • Include at least one (1) lay person; however, the SA-GCPs, an older guideline, requires two (2) lay persons who have no affiliation with the institution, are not currently involved in medical, scientific, or legal work, and are preferably from the community in which the research is to take place
  • Include at least one (1) member with knowledge of and current experience in areas of research likely to be regularly considered by the EC
  • Include at least one (1) member with knowledge of and current experience in the medical profession, counseling, and/or treatment of people
  • Include at least one (1) member who has professional training in both qualitative and quantitative research methodologies
  • Include at least one (1) member who is legally trained
  • Ensure that the membership is equipped to address all relevant considerations arising from the research areas likely to be submitted
  • Be adequately informed on all aspects of a research protocol, including its scientific and statistical validity, that are relevant to deciding whether the protocol is ethically acceptable

Terms of Reference and Review Procedures

In addition to complying with composition requirements, an institution or organization must select EC members according to prescribed recruitment and appointment procedures. As stated in the SA-GCPs and the G-EthicsHR, 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.

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. For detailed EC procedures and information on other administrative processes, see Sections 4 and 5 of the G-EthicsHR and Section 8 of the SA-GCPs.

Last content review/update: May 05, 2020

Overview

Uganda has a centralized registration process for ethics committees (ECs), the majority of which are based at academic institutions or hospitals (ECs are referred to as research ethics committees (RECs) in Uganda). The Uganda National Council for Science and Technology (UNCST), operating under the Ministry of Finance Planning and Economic Development as mandated by the UNCST Act, oversees and coordinates research and development in Uganda as well as EC registration and accreditation.

Per the G-RECs and the NGHRP, an EC is accredited for a three (3)-year period and is not permitted to commence its activities until authorization is received from the UNCST. For multicenter or collaborative trials using the same clinical protocol, the participating institutions may enter into a joint EC review arrangement. See Section 4.2 of the NGHRP for details on EC establishment requirements.

EC 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 in 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 his/her insights about the community from which participants are likely to be drawn

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

Terms of Reference, Review Procedures, and Meeting Schedule

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

  • Meet at least once every three (3) months
  • At least 50% of members, including one (1) member representing community interests, must be present to conduct reviews
  • Project approval requires a simple majority of those members present at the meeting
  • Conduct initial and periodic reviews of research projects, including site visits, at intervals corresponding to the degree of risk, but not less than once a year
  • Respond to any allegations of ethical violations in approved or rejected research projects
  • Liaise with other ECs within and outside the country to better carry out its functions
  • Submit annual performance reports to the UNCST

See Sections 4.5.1 and 4.9 of the NGHRP for additional review requirements.

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

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

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

Ethics Committee > Scope of Review
Last content review/update: June 18, 2020

Overview

In accordance with the NHA, the SA-GCPs, and the G-EthicsHR, 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:

  • Review protocols to ensure that research involving human participants will promote health, and prevent or cure disability and disease
  • Ensure that human participants’ rights are protected, that they are treated with dignity, that their safety and well-being is not compromised, and that informed consent is obtained
  • Grant approval for research where the protocols meet the ethical standards of the institution, agency, or establishment

An EC must also pay special attention to protecting the welfare of certain classes of participants deemed to be vulnerable (See Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations).

Role in Clinical Trial Approval Process

As per the G-EthicsHR, 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.

Please see ZAF-33 for detailed information on issues that the EC should consider when reviewing a proposed study.

The National Health Research Ethics Council (NHREC) is responsible for establishing a research tracking system for the ECs. According to ZAF-32 and ZAF-40, the PI or the sponsor must register his/her clinical trial information on the South African Human Research Electronic Application System (Ethicsapp) website, and then the system will generate an NHREC application/registration number. Once the EC or SAHPRA approval is obtained, the PI or the sponsor should enter these regulatory approval numbers using the NHREC number on the South African National Clinical Trials Register (SANCTR) website. The National Department of Health (NDOH) then issues the SANCTR National Register Number. The SANCTR number will be generated within two (2) working days. This will be done either by email or fax and will be sent to both the relevant EC(s) and the PI or the sponsor. Receipt of the SANCTR number provides the research team with the authority to commence the study pending the approval of other relevant clearances, such as provincial and hospital approvals. See ZAF-32 and ZAF-40 for detailed registration instructions.

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 on the Application for Protocol Amendment to an Approved Trial (ZAF-20).

Last content review/update: November 11, 2020

Overview

In accordance with the NGHRP, the central scope assessed by 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 Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses, and Neonates; Prisoners; and Mentally Impaired for additional information about these populations).

According to the NGHRP, the EC must approve informed consent documentation, and may also require the investigator to administer a comprehension test to ensure participants understand the consent information being provided. Also, an EC may waive some of, or all of, the requirements for the researcher to obtain informed consent in certain situations, including if the research could not practicably be carried out without the waiver. See Section 5.5 of the NGHRP for additional information.

Role in Clinical Trial Approval Process

As per the G-CTConduct, the NGHRP, and the G-TrialsGCP, the National Drug Authority (NDA) approval, the Uganda National Council for Science and Technology (UNCST) registration, and the EC approval of a clinical trial application are mandatory before a study may commence.

Per the NDPA CTReg and UGA-2, proof of the local EC and UNCST approvals must be submitted in the application to the NDA. However, the G-TrialsGCP states 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. The NGHRP further indicates that the EC also has a continuing responsibility to regularly monitor the approved trial(s) to ensure ethical compliance throughout the study duration.

Per the NDPA CTReg, an application to the NDA for deviation from a condition of a clinical trial must be accompanied by evidence of ethical approval of the amendment to the protocol.

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.

Per the G-UNCSTreg, researchers interested in continuing a study using an approved protocol beyond the UNCST research permit expiration date should make a written request for an extension or renewal of the permit to the UNCST Executive Secretary. The request should be accompanied by a progress report, the EC approval, and any other institutional approvals, where applicable. See the G-UNCSTreg for detailed submission information.

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

Ethics Committee > Ethics Committee Fees
Last content review/update: June 18, 2020

Overview

Based on the G-EthicsHR, and the SA-GCPs, ethics committees (ECs) may independently decide whether to charge fees for a protocol review. The EC procedures section of both the G-EthicsHR and the SA-GCPs state that an EC should establish and record working procedures concerning fees charged, if any.

Although South African ECs may decide on their own whether to charge a research review fee, ECs typically only charge to review research funded outside of the institution or industry-sponsored research. No charge is assessed to review investigator-driven research conducted for academic purposes within the institution.

Last content review/update: May 05, 2020

Overview

According to the G-RECs, ethics committees (ECs) (research ethics committees (RECs) in Uganda) may independently decide what fee to charge for a protocol review. The only instruction provided is that an EC must indicate its fee policy and structure in its self-assessment report submitted to the Uganda National Council for Science and Technology (UNCST) to meet its accreditation requirements. However, per the G-UNCSTreg, research applicants are required to pay the UNCST fees to obtain research clearance (See the Regulatory Authority topic, Regulatory Fees subtopic for UNCST fee requirements).

Ethics Committee > Authorizing Body
Last content review/update: June 18, 2020

Overview

Per ZAF-31, the National Health Research Ethics Council (NHREC) is the central statutory body responsible for the registration and auditing of ethics committees (ECs) in South Africa. As per the terms of Section 72 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.

As delineated in the NHA, the SA-GCPs, and the G-EthicsHR, the NHREC’s core responsibilities center on promoting, ensuring, and monitoring compliance by ECs. This includes conducting the following activities:

  • Determining guidelines for EC operations
  • Registering and auditing ECs
  • Setting norms and standards for conducting research on humans and animals, including norms and standards for conducting clinical trials
  • Adjudicating complaints about the functioning of ECs and handling researcher discrimination complaints

NHREC Composition

According to the NHA and the G-EthicsHR, the Minister of Health is authorized to appoint 15 members to the NHREC and the NHREC elects its own chairperson. The Council meets four (4) times per year, and submits an annual report to advise the Minister about policy. The Council is also provided with secretariat support from the National Department of Health (NDOH)’s Research Directorate. For additional information on the NHREC, see the NHA and the NHREC website.

Registration and Auditing

As delineated in the NHA, the G-EthicsHR, and the SA-GCPs, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study. (See ZAF-14 for the application form.) The EC registration is then recorded and publicly listed by the NHREC. The NHREC then performs an audit of the application, and depending on the EC’s structure and function, will categorize the committee as either a Level 1 or Level 2 EC. Level 1 ECs include those that have the capacity to assess straightforward research designs involving minimal risk to human participants. These include research proposals that do not involve drug research, biomedical research involving human tissues, high-budget research, or high-technology research. Level 2 ECs comprise those that may review all types of research proposals.

The NHREC’s categorization of ECs is based on the principles set forth in the SA-GCPs, the Declaration of Helsinki (ZAF-44), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27). The NHREC audits occur as part of an annual review process. EC categorization may change based on these annual reviews to reflect new ethical concerns or standards that have arisen in South Africa or internationally. The Council will publish any additional requirements that emerge on its website. See G-EthicsHR for detailed information on the NHREC registration, auditing, and categorization process.

Last content review/update: May 05, 2020

Overview

The Uganda National Council for Science and Technology (UNCST) is the central statutory body responsible for the registration, auditing, and accreditation of ethics committees (ECs) (research ethics committees (RECs) in Uganda). As per section 4 of the UNCST Act, the UNCST was created by the Ministry of Finance Planning and Economic Development to provide ethical oversight of clinical research and to safeguard the rights and welfare of human participants involved in clinical studies.

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

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

Registration, Auditing, and Accreditation

As per the NGHRP, the G-RECs, and UGA-27, the UNCST must register and accredit all ECs. An Accreditation Committee for RECs in Uganda (ACRECU), comprised of five (5) members appointed by the UNCST Executive Secretary, carries out the accreditation process. Members of the ACRECU are appointed on a three (3) year renewable term limit.

UNCST accreditation involves a two-stage process in which the EC conducts a self-assessment and submits a report along with an accreditation application. The ACRECU then reviews the application and inspects the institution. The outcome of the ACRECU reviews are communicated to the EC and the institution within 14 working days from the site inspection date. Accreditation is granted for three (3) years. In order to apply for renewal, an EC must follow the same procedures as in its initial application. The renewal application must be submitted three (3) months prior to the accreditation expiration date. See the G-RECs for additional details on the UNCST accreditation process. A list of UNCST-accredited ECs is also available through UGA-27.

Clinical Trial Lifecycle > Submission Process
Last content review/update: December 16, 2020

Overview

Per ZAF-23, 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. Per ZAF-20, the same process applies to the review and approval of an amendment to the protocol. In addition, 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).

Submitting the Clinical Trial Application

Per ZAF-36, researchers must submit a completed application on predetermined dates (ZAF-11) and obtain proof of delivery (see below in Delivery Address for information on proof of delivery). SAHPRA’s Clinical Trial Unit (CTU), which includes the Clinical Trials Committee (CTC), 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 CTU receives, processes, and evaluates the applications for approval to conduct the study within South Africa. G-CTA-Electronic delineates the electronic submission and communication process in SAHPRA’s 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 and proof of payment. In the subject of the e-mail, provide type of application, protocol number, and SAHPRA predetermined cycle (See ZAF-11). Per ZAF-36, during the preliminary screening, SAHPRA’s 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 submission of the application. The applicant must respond within seven (7) working days after receipt of the screening review. Hardcopy responses must be delivered to SAHPRA Reception and emailed to ctcresponses@sahpra.org.za. If an application is rejected, no response is required; the screening checklist should be used as guidance for resubmission during the next review cycle.

For phase IV trials of approved products, the applicant must notify SAHPRA following the instructions provided in ZAF-35.

Next, the CTC (which includes an expert committee of specialists, as needed) reviews the proposed clinical trial pursuant to SAHPRA’s schedule (ZAF-11 for 2021 dates). CTC 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, the next cycle
  • 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

Applicants will 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. To respond to the review recommendation letter from the expert CTC, the applicant should submit all responses to SAHPRA Reception and obtain proof of delivery. Subsequently, the applicant should submit copies of the documents including the proof of delivery to the CTU by e-mail to ctcresponses@sahpra.org.za. In the subject of the email, the applicant should provide the type of application, protocol number, and SAHPRA database tracking number. These email submissions should comply with the following requirements:

  • Responses submitted to CTC’s recommendation in MS Word format
  • All other accompanying documents submitted in Portable Document Format (PDF) (See G-CTA-Electronic for specific PDF settings)
  • The maximum size of documents allowed per e-mail is 5 MB

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. (See the Submission Content and Special Circumstances/Emergencies subtopics 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 conduct of clinical trials, bioequivalence studies, notifications and notification studies, and individual serious adverse events. (Also see Sponsorship topic, Site/Investigator Selection subtopic and Clinical Trial Lifecycle topic, Safety Reporting subtopic for information about these submittal processes.)

Delivery Address for Clinical Trial Application

As indicated in the G-GenInfo and ZAF-36, clinical trial applications and correspondence should be delivered to SAHPRA Reception:

South African Health Products Regulatory Authority

Chief Executive Officer
CSIR
Reception Building 38a
Meiring Naude Road
Brummeria
Pretoria
South Africa

Per ZAF-36, upon receipt of the clinical trial application at the 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.

Per the G-GenInfo, all applications and correspondence should be clearly coded as specified in the following list:

  • TGC – General correspondence
  • TCA – Application to conduct a clinical trial
  • TCV – Amendment of an existing clinical trial
  • TCR – Response to CTC resolution
  • TAE – Report of adverse drug events arising from a clinical trial
  • TUM – Applications related to unregistered medicines as per the MRSA

Assembly and Number of Copies

ZAF-23, ZAF-20, and ZAF-17 delineate the following requirements for the assembly and number of copies for a clinical trial application.

  • Two (2) hard copies of the cover letter (letter of application)
  • Two (2) hard copies of the proof of payment
  • Two (2) Compact Discs (CDs) containing the complete clinical trial application with all the required documents
  • One (1) USB flash drive containing the complete clinical trial application with all the required documents

The following requirements apply to the CDs:

  • Include complete clinical trial application documents, including the cover letter (one (1) signed in PDF and one (1) in MS-Word format) and two (2) completed copies of the clinical trial application (ZAF-23 and ZAF-20)—one (1) signed in PDF and one (1) in MS-Word format.
  • Include the following statement in the letter of application, after having confirmed that the submission is virus-free: “We confirm that the CD burning session is closed and the submission is checked with an up-to-date and state-of-the art virus checker: [name of the antivirus software and version of the virus checker] and is virus-free". CD (CD-ROM) conforming to ISO 9660 or ISO 13346 can be accepted.
  • The use of re-writable disks is discouraged. When using a re-writable disk, all open sessions must be closed before sending the CD.
  • The CD should be packed adequately to prevent damage to the media.
  • Each CD should include the following label information, clearly presented and printed on the media: the applicant’s name, the protocol number, and the submission date (MM-YYYY).
  • The data on the CD should not be packed into a zip-file, rar-file, or any other file format that has been compressed.
  • One-time security settings or password protection is not acceptable during transportation from the applicant to SAHPRA.

The following requirements apply to the USB flash drive:

  • Include complete clinical trial application documents, including the cover letter (one (1) signed in PDF and one (1) in MS-Word format) and two (2) completed copies of the clinical trial application (ZAF-23 and ZAF-20)—one (1) signed in PDF and one (1) in MS-Word format.
  • The packaging should include the following label information, clearly presented and printed on the packaging: the applicant’s name, the protocol number, and the submission date (MM-YYYY).
  • The data on it should not be packed into a zip-file, rar-file, or any other file format that has been compressed.
  • One-time security settings or password protection are not acceptable during transportation from the applicant to SAHPRA.

Clinical Trial Application Language Requirements

As per the G-GenInfo and 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.

Last content review/update: November 11, 2020

Overview

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

Per the NDPA CTReg and UGA-2, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the EC and UNCST approvals in the application. Therefore, the NDA and 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.

The online application for UNCST permission to conduct research in Uganda is provided in UGA-28, and EC approval is obtained through the National Research Information Management System (NRIMS) (UGA-33).

According to the NDPA CTReg, an application to the NDA for authorization to conduct a clinical trial shall be made 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 submit a power of attorney verifying his/her appointment as an agent or a letter of authorization (see Form 30 in the NDPA CTReg). Applicants may apply for renewal of the NDA’s clinical trial approval with the Application Form for Renewal of Authorisation of Clinical Trial (UGA-32).

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. The PI should be a Uganda resident and should be licensed by a relevant body in Uganda.

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

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

  • Administrative clearance from the institution where the trial will be conducted
  • Primary EC review and approval
  • UNCST research clearance and approval
  • NDA authorization to import the investigational product

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

Delivery Address for Clinical Trial Application

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

Assembly and Number of Copies

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.

Details for registering with the UNCST are available in the Clinical Trial Lifecycle topic, Submission Content subtopic.

Clinical Trial Application Language Requirements

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 English translation.

Clinical Trial Lifecycle > Submission Content
Last content review/update: June 18, 2020

Overview

In accordance with the NHA, the SA-GCPs, the G-EthicsHR, and the NHA Participants, a sponsor (or the principal investigator when there is no sponsor) must apply to the South African Health Products Regulatory Authority (SAHPRA) and an accredited ethics committee (EC) to conduct a clinical trial for a non-registered drug or a registered drug for new indications.

SAHPRA Requirements

As per ZAF-23, the following documentation must be submitted to the SAHRPA:

  • Two (2) hard copies of the cover letter (letter of application)
  • Two (2) hard copies of the proof of payment
  • Two (2) Compact Discs (CDs) containing complete clinical trial application documents with all the required documents
  • One (1) USB flash drive containing complete clinical trial application documents with all the required documents

The CDs and flash drive must contain these completed documents:

  • Two (2) cover letters (one (1) signed in PDF and one (1) in MS-Word format)
  • Two (2) completed copies of the clinical trials application (one (1) signed in PDF and one (1) in MS-Word format)
  • Checklist
  • Protocol
  • Patient information leaflets and informed consent forms (PIL/ICF); include standardized SAHPRA contact details (Annex 1 of ZAF-23)
  • Relevant questionnaires
  • Investigators Brochure (IB)/SAHPRA and other regulatory authorities’ approved professional information (Package insert(s))
  • Certificate of analysis of the product
  • Signed investigator(s) Curriculum Vitae(s) (CV) in SAHPRA format (Annex 2 of ZAF-23)
  • Signed declaration by co- or principal investigator(s) (PI) (Annex 3 of ZAF-23)
  • Signed joint declaration by sponsor/national PI (Annex 4 of ZAF-23)
  • Signed declaration by applicant
  • 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 (Annexes 2 and 6 of ZAF-23)
  • Proof of application to register the trial on the South African National Clinical Trials Register
  • Active insurance certificate for clinical trial
  • Proof of sponsor indemnity for investigators and trial site(s) (Annex 7 of ZAF-23)
  • Good Clinical Practice Certificates (not more than three (3) years old)
  • 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)
  • EC approval letter or copy of letter submitted to EC
  •  Study budget
  • Citations
  • Proof of payment

In addition, as outlined in ZAF-23, a sponsor is required to include the following investigational product (IP) information in the clinical trial application:

  • Name(s) and details of IP(s)
  • Properties of IP, such as mechanism of action
  • Summary of pre-clinical findings
  • Summary of clinical findings
  • Name(s) and details of comparator product(s)
  • Name(s) and details of concomitant medication(s) including rescue medications required in the protocol
  • Registration status of IP
  • Estimated quantity of trial material (each drug detailed separately) for which exemption will be required
  • If any of the above drugs are available in South Africa, an explanation for not using what is available in South Africa
  • Details of IP supply management and accountability (e.g., receipt from supplier, storage, dispensing, packaging, and labelling)
  • Details of the manufacture, quality control, and stability of the IP
  • Details of intention to register and justify if registration is not planned
  • Previous studies using this IP that have been approved by SAHPRA (or its predecessor Medicines Control Council) and include SAHPRA approval number, title, protocol number, date of approval, national PI, principal investigator, date(s) of progress report(s), and date of final report.

See ZAF-36 for additional information. For phase IV trials of approved products, the application 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 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.

EC 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-41, and ZAF-42 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 Informed Consent topic, Children/Minors subtopic 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
  • National Health Research Ethics Council (NHREC) trial registration form
  • Declaration of trialists (PI and subinvestigators) in SAHPRA format
  • Insurance certificate

Clinical Protocol

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

  • General information
  • Background information
  • 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
  • Ethical and administrative issues
  • Data and safety monitoring plan
  • Data handling/recordkeeping
  • Statistical measures
  • Financing/insurance
  • Publication policy

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

Last content review/update: November 11, 2020

Overview

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

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

NDA Requirements

As per Appendices I and II of the G-CTConduct and UGA-1, the following documentation must be submitted to the NDA:

  • Proof of payment
  • Applications for import and/or export of biological materials (if required)
  • Clinical Trial Application Form
  • Trial Protocol
  • Investigators Brochure
  • Participant Information Leaflet and informed consent (IC)
  • Certificate of Good Manufacturing Practice (GMP) manufacture of the trial medicine or other evidence of manufacture quality, safety and consistency
  • Package insert(s) for other trial medicines
  • Certificate of GMP manufacture 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 NDA
  • Signed and completed declarations by all investigators
  • Approval of ECs for the protocol
  • UNCST approval
  • Full, legible copies of key, peer-reviewed published articles supporting the application
  • Sample of the label for the imported products
  • Letter of authorization from the manufacturer/product owner
  • Pharmaceutical data on dosage form
  • Duly signed declaration of the monitor
  • Clinical Trial Agreement between the sponsor and the principal investigator (PI)
  • Other supporting documents

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. 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.

UNCST Requirements

As delineated in the G-UNCSTreg and UGA-2, the PI is also required to register the research proposal for approval with the UNCST. Applications must be submitted online through UGA-28. As per UGA-2, the PI should have soft copies of the following documents ready before making a submission:

  • A copy of the stamped research proposal, approved by the EC
  • A copy of stamped data collection instruments
  • A copy of stamped informed consent documents, where applicable
  • An approval letter from the EC
  • 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 and/or initialed on each page
  • Proof of payment of research administration and clearance fees for the study

The proposed research project should at a minimum have a title, introduction, objectives, study design and methods, version, date, budget, and the estimated duration. Special permits must be obtained from the UNCST to export and import plant or animal specimens for further investigations abroad. See UGA-2 for detailed application requirements.

EC Requirements

According to 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 the minimum, the requirements should include:

  • Research protocol with version and date
  • IC 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.

Clinical Trial Lifecycle > Timeline of Review
Last content review/update: December 16, 2020

Overview

Based on ZAF-23, 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.

In addition, as described in the G-EthicsHR 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. While the submission requirements differ for each provincial health committee, generally, upon receipt of EC approval, the sponsor or investigator should register the study online at the National Health Research Database (ZAF-43).

SAHPRA 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 would be sent within 10 weeks of submission due date. There are cases where this turnaround time might be prolonged, such as unfamiliar investigational product which may be referred to external reviewers or other SAHPRA committees for input.

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 submission of the application. The applicant must respond within seven (7) working days after receipt of the screening review. Hardcopy responses must be sent to SAHPRA Reception and emailed to ctcresponses@sahpra.org.za. 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 CTC reviews the proposed clinical trials. Per ZAF-9, the CTC meets on a 6-weekly basis and typically reviews approximately between 20-40 studies during each cycle (approximately 240 per year). ZAF-11 provides the dates of the 2021 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-36 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.

EC 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 various EC procedures.

Last content review/update: November 11, 2020

Overview

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

Per the NDPA CTReg and UGA-2, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the EC and UNCST approvals in the application. Therefore, the NDA and 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.

NDA Approval

According to UGA-24, the NDA will acknowledge receipt of a clinical trial application within five (5) working days. The NDA will provide feedback on the initial screening of an application within 10 working days, and reach a decision on the application within 70 working days. When a request is made to an applicant for additional information or clarification, the NDA clock stops until the response is received.

As per the G-CTConduct, NDA reviews for clinical trials 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. When a clinical trial application is submitted to the NDA, the application is first screened for completeness. Per C-IncompleteCTA, the NDA registry will not receive incomplete submissions. All submissions deemed incomplete will be returned with a checklist indicating the missing regulatory requirements. According to the G-CTConduct, the applicant must submit his/her responses in writing or in any other format as advised by the NDA, and in the timeframe determined by the NDA. 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.

The G-CTConduct states that any new information that becomes available regarding the product must be submitted to the NDA as soon as possible. The NDA may request supplementary information or documentation when appropriate, which should be submitted within the stated timeline, usually four (4) weeks. If the requested information is not submitted, the application will be archived within 50 working days. The application will need to be resubmitted for it to be reviewed.

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 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, under which a regulatory decision is given to the applicant within 30 working days, is only 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; or
  • 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

The NDA’s decision shall be communicated to the applicant in writing. Once the application is approved, the NDA issues a Clinical Trial Certificate, which is valid for one (1) year from the date it is awarded. Applicants may apply for renewal of this approval with the Application Form for Renewal of Authorisation of Clinical Trial (UGA-32).

See the G-CTConduct for detailed NDA review procedures.

EC Approval

An applicant must also submit the clinical trial protocol for review and approval by a UNCST-accredited local 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.

UNCST Approval

As per the G-UNCSTreg and UGA-2, the principal investigator (PI) must register the research proposal for approval with the UNCST. The UNCST provides feedback on the registration status within 10 working days from the submission date. According to the NGHRP, the UNCST registration process is normally completed within 14 working days.

As per the NGHRP and the UNHRO Act, the UNCST also collaborates with the UNHRO to register all health research protocols, and liaises with the Research Secretariat in the Office of the President of Uganda to register and clear all research intended to be carried out in the country. The collaborative UNCST/UNHRO registration process is conducted centrally at UNCST.

Clinical Trial Lifecycle > Trial Initiation
Last content review/update: June 18, 2020

Overview

In accordance with the GRMRSA, the SA-GCPs, the G-EthicsHR, 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, 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’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.

South African National Clinical Trials Register (SANCTR) Recording Requirements

According to the SA-GCPs, NHAParticipants, ZAF-32, and ZAF-40, once the trial has obtained approval from the SAHPRA and the EC, the sponsor or the PI must register his/her clinical trial information on the South African Human Research Electronic Application System (Ethicsapp) website (ZAF-40), and then the system will generate a National Health Research Ethics Council (NHREC) application/registration number. Once the ethics or SAHPRA approval is obtained, the PI or the sponsor should enter these regulatory approval numbers using the NHREC number on the South African National Clinical Trials Register (SANCTR) website. The National Department of Health (NDOH) then issues a unique SANCTR National Register Number. The SANCTR number will be generated within two (2) working days. This will be done either by email or fax and will be sent to both the relevant EC(s) and the PI or the sponsor. Receipt of the SANCTR number provides the research team with the authority to commence the study pending the approval of all other relevant regulatory clearances. See ZAF-32 and ZAF-40 for detailed registration instructions.

In addition, per the SA-GCPs, because multi-center trials and multi-sponsor trials are susceptible to duplicate registration, sponsors must be attentive when registering the trials. For multi-sponsored trials, the lead sponsor should take responsibility for registration. It is critical that investigators and sponsors work together to ensure that a trial is registered only once with SANCTR.

Per ZAF-2, SANCTR is not an International Committee of Medical Journal Editors (ICMJE)-recognized register. The ICMJE will only consider publishing reports of trials in a register that is part of the World Health Organization (WHO) registry network (e.g., Pan African Clinical Trials Registry). Therefore, if sponsors want their trial results published, they must also register in a WHO-affiliated registry.

Clinical Trial Agreement

According to the SA-GCPs, before the trial begins, a sponsor must prepare a written agreement, which includes any information not covered in the protocol. The agreement must be signed by the sponsor and the PI, and any other parties involved (e.g., institutions) with the trial to confirm the contract terms.

The sponsor should also obtain the investigator's agreement to:

  • Conduct the trial in compliance with the SA-GCPs, the SAHPRA requirements, 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, 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.

EC Confirmation of Review

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:

  • EC member profiles (names and addresses)
  • Documented approval of EC’s favorable opinion
  • Copy of EC recommendations in case it has based its approval on change(s) in any aspect of the study (e.g., protocol modifications, written informed consent form, or any other written information or other procedures)

The sponsor should also obtain from the PI documentation and dates relating to any EC re-evaluations, re-approvals, withdrawals, or suspensions of approval. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on EC review process).

Last content review/update: November 11, 2020

Overview

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

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

Per the NDPA CTReg and UGA-2, the NDA’s review and approval of a clinical trial application is dependent upon the applicant submitting proof of the local EC and UNCST approvals in the application. Therefore, the NDA and 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.

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. The trial must be conducted in compliance with the NDPA CTReg, the G-CTConduct, the G-TrialsGCP, and the NGHRP. As per the G-TrialsGCP, all investigators should possess appropriate qualifications, training, and experience.

According to the NGHRP, a care package for research participants should be stated 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. The duration and sustainability of care and treatment for the research participant after the study should be negotiated before initiation of the study. Also, the sponsor and researcher shall put in place a mechanism for compensating research related injury at the commencement of a study. For more information, see Section 6 of the NGHRP.

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). 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.

In addition, according to the G-TrialsGCP, the sponsor should ensure that the protocol or other written agreement specifies that the investigator(s)/institution(s) will permit trial-related monitoring, audits, EC review, and regulatory inspection(s), providing direct access to source data/documents. A signed agreement between involved parties (such as the PI/institution and sponsor; the PI/institution and CRO; and the sponsor and CRO), is also considered an essential document before a clinical trial can commence.

EC Confirmation of Review and Approval

The NDPA CTReg, the G-TrialsGCP, and the G-CTConduct mandate that the sponsor or the PI receive written confirmation of EC review and approval of the protocol and submit this approval to the NDA prior to the trial’s commencement. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review process).

Clinical Trials 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.

Data and Safety Monitoring Board

As set forth in the NGHRP and the NDPA CTReg, the sponsor is also required to establish a Data and Safety Monitoring Board (DSMB) prior to a trial’s commencement, and submit its composition to the EC and the UNCST. 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 and the NDPA CTReg.

Clinical Trial Lifecycle > Safety Reporting
Last content review/update: June 18, 2020

Overview

In accordance with the SA-GCPs, the G-EthicsHR, 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 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 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.

Reporting Requirements for AEs/ADRs

As specified in the SA-GCPs and the G-EthicsHR, the principal investigator (PI) must inform the sponsor, within the time specified in the protocol, of any unexpected SADRs/SAEs occurring during the study. The initial SAE/SADR 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. According to an in-country subject matter expert, investigators may forward reports directly to the ethics committee (EC) as relevant and as permitted by the EC’s standard operating procedures.

As delineated in the GRMRSA, the SA-GCPs, and the G-EthicsHR, the sponsor is required to report all expected or unexpected SAEs/SADRs on an expedited basis to all concerned parties, including 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)
  • Final Safety Report
  • Final Study Report

Per ZAF-18, the following must be reported and signed by the PI and the sponsor as part of the six-month progress reports:

  • All SAEs and SUSARs for studies in South Africa (and any other issues of special concern outside South Africa) for all participants per site in a line listing format
  • All critical and major protocol violations at each site in a line listing format
  • PI comment on other major safety concerns, including information impacting the risk-benefit profiles such as changes in the nature, severity, or frequency of risk factors

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. These reports should be in a line listing format.
  • 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.
  • A progress report should be submitted six (6) months after the initial approval of the clinical trial and every six (6) months thereafter (ZAF-18).
  • The final progress report should be submitted within 30 days of the completion or termination of the clinical trial; the final study report should be submitted within 180 days of the completion or termination of the clinical trial.
  • The annual DSURs must be submitted annually.

If the study is multi-centered, the SA-GCPs states that the sponsor should ensure that all SAEs/SADRs occurring at any study site are reported without delay to the investigator(s)/institution(s), the SAHPRA, and the ECs.

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 should be used to complete SAE/ADR reports—for both initial and follow-up safety reports. The G-SafetyRpt indicates that the safety reports during a clinical trial should be reported to the Clinical Trial Unit of SAHPRA:

Chief Executive Officer
SAHPRA
CSIR Campus
Brummeria
Pretoria 0001
South Africa
Tel: (012) 842 7602/7606
E-mail:
ctcsaes@sahpra.org.za

Safety information for post-marketing studies must be sent to the Vigilance Unit of SAHPRA:

Chief Executive Officer
SAHPRA
CSIR Campus
Brummeria
Pretoria 0001
South Africa
Tel: (012) 842 7609/7610
E-mail:
adr@sahpra.org.za

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
Last content review/update: November 11, 2020

Overview

In accordance with the NDPA CTReg, the NDPA PVReg, 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)

Reporting Requirements for AEs/ADRs

Per UGA-31, the National Drug Authority (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).

Investigator Responsibilities

As per the NDPA CTReg and the G-TrialsGCP, all SAEs/SADRs must also be reported by the principal investigator (PI) 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 NDA, and the 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 reportable 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 AEs/ADRs related to trials 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.

Data and Safety Monitoring Board

As set forth in the NGHRP and the NDPA CTReg, the sponsor is required to establish an independent group of experts known as a Data and Safety Monitoring Board (DSMB) to review safety data during a clinical trial. A DSMB’s role is to ensure that the trial is conducted in accordance with the protocol provisions and to monitor AEs/ADRs and safety data. A DSMB must be established prior to a trial’s commencement, and its composition must be submitted to the EC and the UNCST. 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 and the NDPA CTReg.

The G-TrialsGCP further indicates that a DSMB (also referred to as an Independent Data-Monitoring Committee (IDMC)) 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.

Clinical Trial Lifecycle > Progress Reporting
Last content review/update: June 18, 2020

Overview

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 date of approval of an application and 30 days after the completion or termination of the clinical trial. The SA-GCPs requires the principal investigator (PI) to submit progress reports as required by the sponsor, the SAHPRA, and/or the relevant ethics committee(s) (ECs) on the status of a clinical trial.

Progress Reports

Per the GRMRSA and ZAF-18, the SAHPRA requires the sponsor to submit a six-month progress report from the date of approval of the clinical trial by SAHPRA. This six-month report (ZAF-18) requires the following:

  • SAHPRA database tracking number
  • Study title
  • Protocol number
  • Details of the sponsor
  • List of all active trial sites, addresses, and PIs
  • Trial information, including date of approval of study, treatment hold (if applicable), and expected date of completion
  • Number of participants per site
  • Sponsor comment on progress to date
  • Summary Data Safety Monitoring Board or Safety Committee recommendations
  • Serious adverse events and suspected unexpected serious adverse reactions for all participants per site in this study in South Africa
  • Any safety issues of special concern outside of South Africa
  • Line listing of all critical and major protocol violations and resolutions/actions taken at a site
  • PI comment on other major safety concerns
  • Signature of the PI
  • Signature of the sponsor

As per the SA-GCPs, the PI is obligated to submit progress reports to the sponsor, SAHPRA, and the ECs. These reports should contain the following information:

  • Study status
  • Number of participants included in relation to the number expected
  • Number of dropouts and withdrawals
  • Adverse events/adverse drug reactions
  • If the planned time schedule is still appropriate

Final Study Reports

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 the completion or termination of the clinical trial.

In addition, per the SA-GCPs, upon the trial’s end, the PI, where applicable, should provide the EC, the SAHPRA, and other relevant regulatory authorities with a summary of the trial’s outcomes, and a statement that the trial has been conducted in accordance with the GRMRSA and the SA-GCPs.

The SA-GCPs also specifies that the protocol, statistical, and clinical aspects of the trial be integrated to obtain a final study report that is consistent with the study data generated. Essential elements to include are:

  • Baseline comparisons between the treatment groups
  • 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 using tables, graphs, test variables, and statistical parameters as appropriate
  • An assessment of between-group differences with confidence intervals

In multicenter studies, an evaluation of the center effect may also be included, and should always be conducted where significant center variation is suspected.

An account must also be made of missing, unused, or spurious data during statistical analyses. All omissions of this type must be documented to enable review to be performed. The sponsor or the PI is responsible for recording the final study results in the South African National Clinical Trials Register (SANCTR) within one (1) year of the study’s completion.

Last content review/update: November 11, 2020

Overview

In accordance with the NDPA CTReg, the G-CTConduct, the NGHRP, and the G-TrialsGCP, the principal investigator (PI) and the sponsor share responsibility for submitting progress reports on the status of a clinical trial, and for submitting a comprehensive final report. Schedule 2 of the NDPA CTReg contains the form for submitting a clinical trial report.

Interim/Progress Reports

As per the G-TrialsGCP, the PI is obliged to submit progress reports as required by the sponsor, the 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, and
  • If the planned time schedule is still appropriate

The format and frequency of reporting shall be 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, researchers should electronically submit annual progress reports to the UNCST within four (4) weeks following every 12 months of the study for informational purposes only. Failure to do so may result in termination of the research.

Final Report

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

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 researcher’s obligation to submit final reports of his/her research projects to the UNCST. Researchers 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. Researchers who are foreign nationals are required to submit a study completion report before returning to their countries.

Sponsorship > Definition of Sponsor
Last content review/update: June 18, 2020

Overview

As defined in the SA-GCPs, a sponsor is the person or organization responsible for the initiation, management and 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 PI. A sponsor may be domestic or foreign.

Per the SA-GCPs and the Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (ZAF-27), a sponsor may transfer any or all of his/her trial-related duties and functions to a contract research organization (CRO). However, he/she 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 the conduct of a clinical trial, 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.

For 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.

Last content review/update: May 05, 2020

Overview

As defined in the NDPA CTReg, the G-CTConduct, the G-GMPMedicinalAnnexes, and the G-TrialsGCP, a sponsor is the person, company, institution, or organization that takes responsibility for the initiation, management, or financing of a clinical trial. The NGHRP specifically assigns responsibility to the sponsor for providing all the necessary financial support to initiate and complete a research study. Further, the G-GMPMedicinalAnnexes states that sponsors are required to assume ultimate responsibility for all aspects of the clinical trial including the quality of investigational medicinal products. The increased complexity in manufacturing operations requires a highly effective quality system.

The NDPA CTReg also specifies that in order for the sponsor to submit a clinical trial application, he/she must be one of the following:

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

Per NDPA CTReg, in the case of foreign sponsors, a local company in Uganda must submit a letter of authorization from the licensed person or manufacturer of the drug to be the agent in the clinical trial and is responsible for all matters pertaining to the NDA clinical trial certificate (See UGA-18). The G-CTConduct further 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 PI who is the representative of the in-country sponsor. The PI should be a resident of Uganda and should be licensed by a relevant body in Uganda. The qualifications of the PI should be in line with the proposed study with careful consideration of the population and the product.

Sponsorship > Trial Authorization
Last content review/update: June 18, 2020

Overview

In accordance with the SA-GCPs, a sponsor or his/her designated contract research organization (CRO) is responsible for submitting a clinical trial application to the South African Health Products Regulatory Authority (SAHPRA) to obtain approval to conduct a study. As indicated in ZAF-23, if there is no sponsoring organization, the principal investigator (PI) must clearly state in the protocol who will be assuming the sponsor’s role of initiating, managing, or funding the clinical trial.

To complete the clinical trial application package, a sponsor must use the SAHPRA’s Application to Conduct Clinical Trials form (CTF1) listed in ZAF-23. In addition to the completed application, a sponsor must also provide the protocol, the patient information leaflet and informed consent form, a signed joint declaration by the sponsor and PI, a financial declaration signed by the sponsor, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic. It is both the sponsor’s and the PI’s responsibility to ensure that the protocol satisfies the requirements of the protocol checklist in ZAF-23. For more information on SAHPRA’s clinical trial application process, see ZAF-36.

Last content review/update: November 11, 2020

Overview

In accordance with the NDPA CTReg and the G-CTConduct, the sponsor or the principal investigator (PI) is responsible for submitting a clinical trial application to the National Drug Authority (NDA) to obtain approval to conduct a study, and for registering the study with the Uganda National Council for Science and Technology (UNCST). The sponsor must be one of the following:

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

Per the NDPA CTReg, in those cases where a local agent submits the clinical trial application, the agent must submit a power of attorney verifying his/her appointment as an agent or a letter of authorization (see Form 30 in the NDPA CTReg or UGA-18). The agent is responsible for all matters pertaining to the NDA Clinical Trial Certificate (CTC). The G-CTConduct further indicates that based on the Clinical Trial Agreement between the sponsor and the PI, the NDA will liaise with the PI who is the representative of the in-country sponsor. The PI should be a resident of Uganda and should be licensed by a relevant body in Uganda. The qualifications of the PI should be in line with the proposed study with careful consideration of the population and the product.

According to the C-CTCFormat, the NDA has adopted a new format for the CTC to align with the NDPA Act and the NDPA CTReg.

To complete the clinical trial application package, the applicant must use the NDA’s clinical trial application form (see Appendix I of the G-CTConduct).

In addition to the completed NDA application, the applicant must also provide the clinical protocol, the participant information leaflet and informed consent form, a signed declaration by the investigators, a certificate of good manufacturing practice for the manufacture of the trial medicine, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.

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

Sponsorship > Insurance
Last content review/update: June 18, 2020

Overview

As set forth in the G-Insurance, all sponsors and investigators of clinical trials 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 Association of the British Pharmaceutical Industry’s (ABPI) guidelines (ZAF-26 and ZAF-25) to comply with South Africa’s clinical trial insurance requirements. A sponsor must ensure that he/she has obtained insurance and indemnity to cover his/her liability in a clinical trial.

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. Notwithstanding the absence of a legal commitment, the sponsor should pay compensation to all participants including healthy volunteers suffering bodily injury, including death, in accordance with the G-Insurance. The following should be considered in compensation of participants:

  • If, on the balance of probabilities, the injury is attributable to the administration of an investigational product (IP) or any clinical intervention or procedure provided for by the protocol that would not have occurred but for the inclusion of the participant in the trial.
  • Compensation should be paid for a child injured in-utero through the participation of the biological parent in a clinical trial as if the child were a patient-volunteer with the full benefit of SAHPRA guidelines.
  • Compensation should only be paid for a serious injury of an enduring or disabling nature (including exacerbation of an existing condition) and not for temporary pain or discomfort or less serious occurrences.
  • Where there is an adverse reaction to an IP under trial 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 under trial.
  • The sponsor is under strict liability in respect of injuries caused by the IP or procedures provided for by the protocol that would not have occurred but for the inclusion of the participant in the trial, regardless of whether the participant is able to prove negligence on the part of the sponsor or that the IP is defective.

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 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
Last content review/update: May 05, 2020

Overview

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.

In accordance with the NGHRP, the sponsor and researcher shall put in place a mechanism for compensating research-related injury at the commencement of a study. The mechanism, which may include, inter alia, insurance, and medical care, should be acceptable to the ethics committee (EC) (research ethics committee (REC) in Uganda).

Sponsorship > Compensation
Last content review/update: June 18, 2020

Overview

As specified in the G-TIECompensation, the sponsor or his/her designated representative is responsible for providing compensation to research participants. ZAF-23 states that the South African Health Products Regulatory Authority (SAHPRA) must be given details of compensation to clinical trial participants. Per the G-EthicsHR and the G-TIECompensation, compensation should be based on time, inconvenience, and expenses. In addition, the G-EthicsHR also addresses researcher requirements to budget for participant travel and other expenses. (See the G-EthicsHR for detailed information).

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.

As per the SA-GCPs, the sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (ZAF-26 and ZAF-25) to comply with South Africa’s participant compensation and treatment requirements due to trial-related injuries.

The guidelines state that the sponsor should furnish written assurance to the investigator that he/she will agree to pay compensation to participants and/or his/her legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committee(s).

The G-PostCTAccess guides sponsors in when to consider post-trial or continued access (PTA/CA) to the investigational product (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 IP.

Compensation Principles

The SA-GCPs and ZAF-26 provide several basic principles to guide sponsors in fulfilling their compensation obligations. Compensation should be paid as follows:

  • When it can be demonstrated that a causal relationship exists between a participant’s injury and his/her participation in a trial
  • When a child is injured in utero through his/her mother’s participation in a clinical trial
  • 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 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 him/her from being eligible for compensation. (See the aforementioned guidelines and the Informed Consent topic, Compensation Disclosure subtopic for additional information on a participant’s right to compensation).

Payment Procedures and Requirements

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

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 his/her 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 the SA-GCPs and 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.

Last content review/update: May 05, 2020

Overview

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 researcher 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.

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.”

In the event of any trial-related injuries, the sponsor is required to ensure that the research participants are not asked to waive their legal rights to seek compensation.

The sponsor and researcher 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 ethics committee (EC) (research ethics committee (REC) in Uganda). The EC, research participant, and/or researcher may initiate the compensation process. The EC, sponsor, and researcher shall agree on an appropriate mechanism for arbitration.

In the clinical trial application made to the National Drug Authority (NDA), the applicant must explain how he/she will compensate the participant(s) for their time and other inconveniences, in accordance with the G-CTConduct.

In addition, per the NGHRP, participants must be 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. 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 also 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.

(See the Informed Consent topic, Compensation Disclosure subtopic for additional information.)

Sponsorship > Quality, Data & Records Management
Last content review/update: June 18, 2020

Overview

As clinical trial oversight manager, the sponsor must implement and maintain quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol and the SA-GCPs. 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. Agreements made by the sponsor with the principal investigator and any other involved parties should be in writing either as part of the protocol or in a separate agreement. 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, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Data Protection

Per the POPIA, the sponsor (known as the “responsible party” in data protection legislation), 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)

For additional information about consent, see the Informed Consent topic, Documentation Requirements and Required Elements subtopics.

Electronic Data Processing System

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 he/she maintains SOPs for using these systems. Refer to the SA-GCPs for detailed information on electronic trial data systems. 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.

Independent Data Monitoring Committee

The sponsor is permitted to establish an Independent Data Monitoring Committee (IDMC) to assess the trial’s progress. The IDMC would review the safety data and critical efficacy endpoints at intervals, and recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should also have written SOPs and maintain written records of all its meetings.

Record Management

As set forth in the SA-GCPs, the sponsor should inform the investigator(s) and institution(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.

Following the trial’s completion, a sponsor should retain copies of all study-related documentation that does not contain participant identifying information. The files should also include information on study site personnel responsible for maintaining the participant lists, and those responsible for archiving investigator documents. These documents should be saved for 15 years after the trial’s termination, and preferably for the product’s commercial lifetime. Refer to the SA-GCPs for additional record retention requirements.

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.

Audit Requirements

As part of its QA system, the sponsor should perform a clinical trial audit. No specific timeframe is provided for the audit process. The audit should be conducted separately and independently from other routine monitoring or QC functions. It should evaluate study conduct and compliance with the protocol, the SOPs, and the SA-GCPs. The sponsor may appoint qualified external auditors who have appropriate documentation. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs, that the auditor observations are archived, and that data is available as needed for the South African Health Products Regulatory Authority (SAHPRA) and ethics committee (EC) review. The person responsible for auditing must submit a report to the SAHPRA when evidence of Good Clinical Practice non-compliance exists.

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

If a trial is prematurely terminated or suspended, a sponsor must promptly notify the investigator(s), the institution(s), the EC, and the SAHPRA accordingly. The notification should document the reason(s) for the termination/suspension. The sponsor is also responsible for ensuring that the South African National Clinical Trials Register (SANCTR) is updated as well.

Multicenter Studies

In the event of a multicenter clinical trial, the sponsor must make administrative arrangements to ensure the protocol is followed by investigators at different institutions. Some of the tasks requiring special consideration include:

  • Ensuring strict adherence to the protocol
  • Confirming case report forms (CRFs) are designed to capture the required data at all multi-center trial sites
  • Documenting the responsibilities of coordinating investigator(s) and the other participating investigators
  • Supplying investigators with instructions on following the protocol, on complying with a uniform set of standards to assess clinical and laboratory findings, and on completing the CRFs
  • Facilitating communication between investigators
Last content review/update: November 11, 2020

Overview

As stated in the G-GMPMedicinalAnnexes, the sponsor is responsible for the initiation, management, and/or financing of a clinical trial in Uganda. The sponsor should also have access to the quality system standard operating procedures (SOPs) that the manufacturer or importer has designed, established, and verified.

The NDPA CTReg also 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 Clinical Trial Lifecycle topic, Safety Reporting subtopic contains information regarding reporting.

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 Section 4.3 of the G-TrialsGCP.

As per the G-GMPMedicinalAnnexes, the sponsor is responsible for sending a written order to the manufacturer to process, package, and/or ship investigational products (IPs) for a clinical trial. This order should be formally authorized and refer to the product specification file and the relevant clinical trial protocol.

In addition, during the shipping process, the sponsor maintains control of the IP until certification by the manufacturer’s authorized person and the fulfillment of relevant requirements on:

  • Batch records
  • Production conditions
  • Validation status of facilities, processes, and methods
  • Examination of finished packs
  • Results of any analyses or tests performed after importation, where relevant
  • Source and verification of conditions of storage and shipment
  • Audit reports concerning the quality system of the manufacturer
  • Documents certifying that the manufacturer is authorized to manufacture IPs or comparators
  • Regulatory requirements

The sponsor must ensure that the IP is consistent with the details in the clinical application and NDA’s authorization. This can be achieved through a change control process for the product specification file and defined in a technical agreement between the sponsor and the authorized person. The sponsor should record and retain all relevant documentation. Per the G-GMPMedicinal, the manufacturer should retain IP documentation for at least five (5) years after the completion or formal discontinuation of the last clinical trial in which the IP was used.

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 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.

Record Management

As per the NDPA CTReg, the G-CTConduct, and the G-TrialsGCP, the sponsor and the investigator(s) are responsible for ensuring the safety of all trial-related documentation. The sponsor should retain documents for a minimum period of 20 years and inform the National Drug Authority (NDA) in writing prior to destroying any documents.

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

According to the NGHRP, collaborating research partners must agree on appropriate data access and use rights before commencement of the study. Researchers 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 researchers must have unrestricted access rights to data sets collected through a collaborative research project. Lastly, researchers 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.

Audit Requirements

According to the NGHRP, the sponsor or PI must conduct audits or inspections of the trial as prescribed in the study protocol. The NDA may conduct an inspection or audit of the clinical trial to ensure the protocol and all applicable regulatory requirements are followed.

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 ethics committee (EC) (research ethics committees (RECs) in Uganda) and the NDA. The audit report should be submitted to the NDA if evidence of good clinical practice (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 UGA-5. The notification must give reasons for the termination, indicate the disposal process for the unused IP, 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.

Multicenter Studies

The G-TrialsGCP indicates that where necessary, site-investigators for multicenter trials should develop site-specific SOPs or a site implementation plan to guide the respective sites on implementation of the protocol at that site. The sponsor should ensure that:

  • All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and which received EC and NDA approvals
  • 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
Sponsorship > Site/Investigator Selection
Last content review/update: June 18, 2020

Overview

As set forth in the SA-GCPs, the sponsor is responsible for selecting the investigator(s) and institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must ensure that the investigator(s) are qualified by training and experience, and that they have adequate resources to properly conduct the 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 and ZAF-16 for more information on investigator workload.

Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the involved parties with the protocol and an up-to-date investigator’s brochure, and allow them sufficient time to review this documentation. The sponsor must also define and allocate all study related duties and responsibilities to the respective identified person(s) and organization(s) prior to initiating the study. In addition, if a multi-center trial is going to be conducted, the sponsor must organize a coordinating committee or select coordinating investigator(s).

In addition, per ZAF-21, to add or change investigators and/or for 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, delegation of trial responsibilities, analysis, and reporting of the trial. 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 his/her 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 his/her 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.

In the case of a multi-country study, the sponsor must ensure that any differences in trial designs between the South African site and other sites must be clearly documented and explained in the study protocol and related documents.

Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Last content review/update: May 05, 2020

Overview

Based on the NDPA CTReg and the G-TrialsGCP, the sponsor oversees the selection of the investigator(s) and the institution(s) for the clinical trial. According to the G-CTConduct and the G-TrialsGCP, the principal investigator (PI) should be a resident of 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. The investigator should also be given sufficient time to review the protocol and the information provided.

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 National Drug Authority (NDA), and the protocol agreed upon by the sponsor and given approval by the relevant ethics committee (EC) (research ethics committee (REC) in Uganda)
  • 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

As delineated in the NDPA CTReg and the G-CTConduct, before the trial begins, the sponsor must sign a clinical trial agreement with the PI. 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. In addition, according to the G-TrialsGCP, a signed agreement between involved parties (such as the PI/institution and sponsor; the PI/institution and CRO; and the sponsor and CRO) is also considered an essential document before a clinical trial can commence. 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.

According to the NDPA CTReg, an application for additional investigators, additional clinical trial sites, or for change of the investigators must be made using UGA-13 and must be accompanied by evidence of ethical approval of the amendment to the clinical trial protocol, where applicable, and the prescribed fees. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for additional information on clinical trial application requirements.)

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.

Foreign Investigator Responsibilities

In accordance with the G-UNCSTreg, all researchers who are foreign nationals are required to identify and become affiliated with a local organization appropriate for their type of research in Uganda. Researchers arrange the affiliation themselves with the local organization. The researcher should obtain a letter of recommendation from the local organization, which they submit to the Uganda National Council for Science and Technology (UNCST). Per NDPA CTReg, the local company in Uganda must submit a letter of authorization from the licensed person or manufacturer of the drug to be the agent in the clinical trial and is responsible for all matters pertaining to the NDA clinical trial certificate (See UGA-18).

Data and Safety Monitoring Board

In addition, according to the NGHRP and the NDPA CTReg, the sponsor is responsible for establishing a Data and Safety Monitoring Board (DSMB) prior to the trial’s commencement. 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 and the UNCST. (See the Clinical Trial Lifecycle topic, Trial Initiation subtopic for additional information.)

No additional information is available regarding the sponsor’s role in selecting the EC or overseeing multicenter trials.

Informed Consent > Documentation Requirements
Last content review/update: June 18, 2020

Overview

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, 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 Informed Consent topic, Required Elements subtopic 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 his/her 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 ICF content should be briefly and clearly presented, without coercion or unduly influencing a potential participant to enroll in the clinical trial.

According to the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the G-GPHlthCare-IC, in all cases, both written informed consent must be obtained. The SA-GCPs also states that verbal consent must be obtained. Where the participant is illiterate and/or his/her 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.

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.

Language Requirements

According to the SA-GCPs, the G-EthicsHR, and the G-GenInfo, the ICF and any patient information sheet(s) should be written in English and in the 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.

Documentation Copies

As stated in the SA-GCPs, the G-EthicsHR, 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, his/her 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 for his/her record. 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. The SA-GCPs also requires contact information for the EC and for the SAHPRA be provided in the ICF.

Last content review/update: May 05, 2020

Overview

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.

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 ethics committee (EC) (research ethics committee (REC) in Uganda) and provided to the National Drug Authority (NDA) with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)

The investigator(s) should provide research study information to the participant and/or his/her 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 ICF content should be brief and clearly presented without coercion or unduly influencing a potential participant to enroll in the clinical trial.

Participant information may be presented in written or oral form, and should be communicated in a language and form understandable to the participant and/or his/her legal representative(s) or guardian(s). The participant and/or the participant’s legal representative(s) or guardian(s), and the investigator(s) must personally sign the ICF. In situations in which the research participant prefers not to execute a written ICF, the investigator must obtain oral informed consent and document that it has been obtained. The participant or his/her legal representative(s) or guardian(s) may sign the form using his/her thumbprint to indicate that he/she has read and understood and agrees to participate in the study.

Re-Consent

According to the NGHRP and the G-TrialsGCP, any change to the research study that may impact the participant’s willingness to continue requires a new ICF to be approved by the EC and submitted to the NDA before such changes are implemented. The participant and/or his/her legal representative(s) or guardian(s) will also be required to sign the revised ICF.

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.

Documentation Copies

The NGHRP states that the participant and the investigator(s) should sign the ICF. If the participant is incapable of giving an informed consent, his/her legal representative(s) or guardian(s) should sign and date the ICF. In cases where oral consent is allowed, the investigator must document that the consent was obtained.

The investigator(s) should retain a copy of the signed ICF, and one (1) copy should be offered to the participant for his/her record.

Informed Consent > Required Elements
Last content review/update: June 18, 2020

Overview

As delineated in the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, prior to beginning a research study, the principal investigator (PI) is required to obtain ethics committee (EC) approval for the written informed consent form (ICF), and for all information being provided to the research participant and his/her legal representative(s) or guardian(s).

Information should be presented in an easily understandable and unambiguous language in both written and oral form. Adequate time should be given to the participant and/or his/her legal representative(s) or guardian(s) to inquire about the details of the study, and have all questions answered to his/her satisfaction. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Per the POPIA, and the POPIA-Regs, personal information may only be processed if the data subject and/or his/her legal representative(s) or guardian(s) consents to the processing. The responsible party (sponsor) bears the burden of proof for the consent. The data subject and/or his/her 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.

No Coercion

None of the oral or written information concerning the study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or his/her representatives from his/her liabilities for any negligence.

ICF Required Elements

Based on the informed consent essential elements checklists in the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the NHAParticipants, the ICF should include the following statements or descriptions, as applicable:

  • The study involves research and an explanation of its nature and purpose
  • The procedures to be followed
  • The participant’s responsibilities
  • Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
  • 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 anticipated prorated payment, if any, to the participant for participating in the trial
  • PI and co-investigator(s) contact information
  • The sponsor’s identity, and any potential conflicts of interest
  • The consequences of a participant's decision to withdraw from the study
  • Alternative procedures or treatment that may be available to the participant
  • The study has been approved by an accredited South African-based EC, and EC contact information
  • The approximate number of participants in the research study
  • The expected duration of the participant's participation
  • Information regarding a multicentered study, if applicable
  • An explanation of whom to contact in the event of research-related injury
  • Additional costs to the participant that may result from participation in the study
  • Foreseeable circumstances under which the investigator(s) may remove the participant without his/her consent
  • The participant and/or his/her 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
  • If the research involves collecting biological materials, participants must be provided with an explanation on how the specimens will be managed at the end of the study. If samples will be stored for future use, separate consent should be obtained

See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics as well as the Specimens topic, Consent for Specimen subtopic for further information.

Last content review/update: May 05, 2020

Overview

As delineated in the NGHRP and the G-TrialsGCP, prior to beginning a research study, the investigator(s) is required to obtain ethics committee (EC) (research ethics committee (REC) in Uganda) approval for the written informed consent form (ICF), the patient information leaflet, and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s).

Information should be presented in easily understandable language that is as non-technical as practical, and may be presented in written and/or oral form. Adequate time should be given to the participant and/or his/her legal representative(s) or guardian(s) to inquire about the details of the study and have all questions answered to his/her satisfaction.

No Coercion

None of the oral and written information concerning the study, including the written ICF, should contain any coercive language. In addition, it should not release or appear to release the investigator(s), the institution, the sponsor, or his/her representatives from his/her liabilities for any negligence.

ICF Required Elements

Based on the NGHRP, the NDPA CTReg, and the G-TrialsGCP, the ICF should include the following statements or descriptions, as applicable (Note: The regulatory sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

  • The study involves research and an explanation of its nature and purpose
  • The procedures to be followed
  • The expected duration of the trial
  • The trial treatment(s) and the probability for random assignment to each treatment (where appropriate)
  • The participant's responsibilities
  • Those aspects of the trial that are experimental
  • Any reasonably foreseeable risks or discomforts to the participant, and whether the project involves more than minimal risk
  • Any benefits to the participant or to others that may be reasonably expected from the research; if no benefit is expected, the participant should also be made aware of this
  • The disclosure of specific appropriate alternative procedures or therapies available to the participant
  • The extent to which confidentiality of records identifying the participant will be maintained and who will have access to the participant’s medical records
  • For research involving more than minimal risk, the policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury
  • The extent of the investigator’s responsibility, where applicable, to provide medical services to the participant
  • The nature, form, and extent of compensation for participation
  • The identity of a sponsor and any potential conflict of interests
  • The sponsors’ and the investigators’ institutional affiliation(s)
  • A contact name and number of the principal investigator and/or site investigator
  • Participation is voluntary, the participant can withdraw from the study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled
  • The participant and/or his/her legal representative(s) or guardian(s) will be notified in a timely manner if significant new findings develop during the study which may affect the participant's willingness to continue
  • A witness may represent vulnerable populations during the informed consent process, if applicable
  • The study has been approved by an accredited Ugandan-based EC
  • 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 his/her 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

(See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopic as well as the Specimens topic, Consent for Specimen subtopic for further information.)

Informed Consent > Compensation Disclosure
Last content review/update: June 18, 2020

Overview

In accordance with the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, the informed consent form (ICF) should contain a statement describing the compensation or benefits a participant may receive for participating in a clinical trial. In addition, as specified in the SA-GCPs, sponsors and investigators must also comply with the Association of the British Pharmaceutical Industry’s (ABPI) guidelines relating to participant compensation and treatment requirements due to trial-related injuries (See ZAF-26 and ZAF-25). Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Compensation for Participation in Research

As per the SA-GCPs, the ICF should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. The ICF should also contain a statement indicating whether any compensation and medical treatment will be made available if injury occurs.

Per the SA-GCPs and the G-GPHlthCare and as described in ZAF-5, the sponsor must ensure that participants are reimbursed for all reasonable costs incurred by their participation in the trial. As described in the G-EthicsHR and ZAF-5, the researcher should reimburse participants using a fair rate calculated using a formula that accounts for time, inconvenience, and expenses to determine costs. However, any compensation or incentive to participants must not be so excessive that it may unfairly influence participants, or cause them to overlook important facts and risks.

If the studies are multicentered, information regarding incentives to be given to participants at the different sites must be provided, and the differences across sites must be explained.

The G-PostCTAccess guides sponsors in when to consider post-trial or continued access (PTA/CA) to the investigational product (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, ICF, and patient information leaflet. See Sponsorship topic, Compensation subtopic for additional considerations.

Compensation for Injury

As per the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, the G-Insurance, ZAF-5, and ZAF-26, a statement must be included in the ICF regarding compensation or treatment for research-related injuries available to the participant(s). If applicable, this should include a statement regarding compensation for any potential injury received by a child in utero or a nursing child, through the mother’s participation in a research study.

The South African Health Products Regulatory Authority (SAHPRA) and the ethics committee(s) (ECs) require a sponsor to provide comprehensive insurance for injury and damage to all trial participants as described in the SA-GCPs, ZAF-26, and ZAF-25. A sponsor must furnish written assurance to the investigator that he/she will agree to pay compensation to participants who incur research-related injuries or death. The investigator, in turn, communicates this information to the relevant EC(s).

The SA-GCPs and ZAF-26 also provide the following basic principles to guide compensation payment to participants:

  • A causal relationship exists between a participant’s injury and his/her participation in a trial
  • A child is injured in utero through his/her mother’s participation in a trial, and should be treated as if he/she were a participant
  • For more serious injuries of an enduring and disabling nature, and not for temporary pain or discomfort, or less serious or curable complaints
  • An adverse drug reaction (ADR) occurs to a participant using a medicinal product under trial, and injury is caused by a procedure adopted to deal with that ADR. The injury should be treated as if it were caused directly by the medicinal product under trial
  • Any trial-related injuries, regardless of the participant’s ability to prove that the sponsor has been negligent in relation to the research or development of the medicinal product under trial, or, that the product is defective

The participant should be eligible for compensation even if he/she freely consented (in writing or otherwise) to participate in the trial, or he/she was aware that there was a likelihood of an ADR. (See the aforementioned guidelines and the Sponsorship topic, Compensation subtopic for additional information on sponsor compensation responsibilities; the Informed Consent topic, Required Elements subtopic for additional details on what should be included in the ICF.)

Last content review/update: May 05, 2020

Overview

In accordance with the NGHRP and the G-TrialsGCP, the informed consent form (ICF) should contain a statement describing the compensation or benefits a participant may receive for participating in a clinical trial.

Compensation for Participation in Research

As stated in the NGHRP, the ICF should contain a statement with a description of the nature, form, and extent of compensation for study participation, including any reimbursement for transportation, time, and meals. Research participants shall be fairly compensated for inconveniences, time spent, and expenses incurred. Research participants may also receive free medical services.

However, the compensation or medical services must not be so excessive that it may unfairly influence participants or cause them to overlook important facts or risks. The G-TrialsGCP further specifies that the sponsor must ensure that participants are reimbursed for all reasonable costs incurred by their participation in the trial.

Compensation for Injury

As per the NGHRP, the ICF should include a statement advising the participant about compensation and medical treatment(s) available in the event of any trial-related physical, social, economic, or psychological injury; what they consist of; and where further information may be obtained. In Uganda, injuries are classified according to their relationship to the trial as follows:

  • Definitely – An injury directly caused by trial participation
  • Probably – When the injury is most likely explained by trial participation, but no definite proof of causality is evident
  • Possibly – When an explanation for the injury is equally due to trial participation or other cause
  • Unlikely – When the injury is more likely explained by a cause other than trial participation
  • Not related – When the injury is clearly due to a cause other than trial participation

(See the Sponsorship topic, Compensation subtopic for additional details on compensation requirements.)

Informed Consent > Participant Rights
Last content review/update: June 18, 2020

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, 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 Informed Consent topic, Required Elements and Vulnerable Populations subtopics 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 his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she 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 Informed Consent topic, Required Elements subtopic 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.

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. For more information about the sponsor’s (called the “responsible party” in South Africa) data protection requirements, see the Sponsorship topic, Quality, Data & Records Management subtopic.

The Right of Inquiry/Appeal

Per the G-GPHlthCare-IC, the research participant and/or his/her 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 his/her rights. It is also required that the South African Health Products Regulatory Authority (SAHPRA) address and contact information be provided. (See the Informed Consent topic, Required Elements subtopic 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.

Last content review/update: May 05, 2020

Overview

Uganda’s ethical standards promote respect for all human beings and safeguard the rights of research participants, including the right of their autonomy, culture, beliefs, and values. In addition, participants also have the right to receive the nationally available standard of health care, and the right to report any trial-related abuses to the investigator(s), the ethics committee (EC) (research ethics committee (REC) in Uganda), the National Drug Authority (NDA), and the Uganda National Council for Science and Technology (UNCST). 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 Informed Consent topic, and the subtopics of Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired 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 in the instance of a participant from a vulnerable population, his/her legal representative(s) or guardian(s)—should be informed that participation is voluntary, that he/she 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

A potential research participant and/or his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

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

The research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the investigator(s) and the EC to address trial-related inquiries in the event of any injury and/or to appeal against a violation of his/her rights. (See the Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The NGHRP and the NDPA CTReg clearly state that a research participant’s right to safety and the protection of his/her health and welfare must take precedence over the objectives of biomedical research.

Informed Consent > Special Circumstances/Emergencies
Last content review/update: June 18, 2020

Overview

The NHA, the SA-GCPs, and the G-EthicsHR make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances can be medical emergencies, or when a research participant is mentally incapacitated, or has physical impairments requiring special considerations. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Medical Emergencies

As per the SA-GCPs and the G-EthicsHR, the ethics committee (EC) may approve emergency medical research when informed consent cannot be obtained from the participant or his/her legal representative(s) or guardian(s) if the investigator(s) ensures the protocol meets the following requirements:

  • Reasonable steps are being taken to ascertain the participant’s religious and cultural sensitivities
  • The participant’s condition precludes giving consent
  • Inclusion in the trial is not contrary to the interests of the patient
  • The research is intended to be therapeutic, and poses no more risk than is inherent to the participant’s condition, or would be caused by alternative treatments
  • The participant, his/her 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 participant will be informed, and consent obtained, once he/she has undergone the necessary emergency procedures and regained consciousness
  • 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.

Research Involving Unconscious Persons

The SA-GCPs, the G-EthicsHR, 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), include any relevant statutory authorities, on that person's behalf. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive observational research.

Last content review/update: May 05, 2020

Overview

The NGHRP and the G-TrialsGCP make provisions to protect the rights of a research participant during the informed consent process when special circumstances complicate the procedure.

Medical Emergencies

The NGHRP allows the ethics committee (EC) (research ethics committee (REC) in Uganda) to waive some or all of the informed consent requirements in instances of medical emergencies where consent cannot be reasonably obtained from the individual or his/her representative.

The G-TrialsGCP further states that in emergency situations, when prior consent of the participant not possible, the consent of his/her legal representative(s), if present, should be requested. When prior consent of the participant is not possible and his/her legal representative(s) is not available, enrollment of the participant should require measures 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 his/her legal representative(s) should be informed about the trial as soon as possible, and consent to continue and other consent as appropriate should be requested.

Waiver of Consent

An EC may waive some or all of the requirements for the investigator to obtain an informed consent or a signed/thumb-printed informed consent form (ICF) for some or all of the participants of a study if the EC determines that the research being conducted meets one of the following conditions:

  • It involves only minimal risk
  • The study could not be carried out without the waiver or alteration
  • In cases where deception needs to be applied to achieve the objectives of the study
  • The only record linking the participant and the study would be the ICF, and the principal risk to the participant would be potential harm resulting from a breach of confidentiality
  • When it is necessitated in emergency situations where no proxy consent can be taken

If the EC grants a waiver of written informed consent, each participant should be asked whether he/she wishes to have documentation that links him/her with the study, and the participant’s wishes must be followed. In situations in which the participant prefers not to complete a written ICF, the investigator must obtain oral informed consent and document that it has been obtained.

Informed Consent > Vulnerable Populations
Last content review/update: June 18, 2020

Overview

In all South African clinical trials, research participants from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

The NHA, the SA-GCPs, the G-EthicsHR, 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, and other vulnerable groups such as collectivities, and persons in dependent relationships. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

The ethic committees (ECs) must pay special attention to protecting participants from vulnerable populations. The ECs may impose additional measures such as requiring post-research investigations to be conducted. 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 risk are assessed and minimized, and appropriate consent procedures are followed

See Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations. Information on the other vulnerable populations specified in the SA-GCPs and the G-EthicsHR is provided below.

Persons in Dependent Relationships or Hierarchical Situations

Participants whose proposed involvement in research arises from dependent or hierarchical relationships need additional attention, and the EC must be satisfied 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

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 his/her medical treatment.

Terminally Ill Patients

Terminally ill patients require additional protection as they are more vulnerable to developing unrealistic expectations of benefits. Investigators must ensure that the prospective benefit from participation is neither exaggerated nor used to justify a higher risk than that involved in the patient’s current treatment. Investigators must also respect the participants’ wishes to spend time as they choose, particularly with family members.

The Elderly

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

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
Last content review/update: November 11, 2020

Overview

In all Ugandan clinical trials, research participants from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. According to the NGHRP, 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, and pregnant women.

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.

Per the NGHRP, the ethics committee (EC) (research ethics committee (REC) in Uganda) must carefully consider and approve the mode of consent for participants from vulnerable populations. ECs must ensure that:

  • Selection of the particular community is justified by the research goals
  • Research is relevant to the needs and priorities of the community in which it is to be conducted
  • Research is beneficial to that community
  • The community can access products of the research
  • Where appropriate, feedback of results relevant to the community is provided
  • Participants are fully aware that they are participating in the research, and provide informed consent. It is essential that special attention be paid to the content and language of the informed consent form, the procedures for obtaining informed consent, and any precautions such as monitoring the process and testing comprehension.

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 Informed Consent topic, and the subtopics of Children/Minors; and Pregnant Women, Fetuses & Neonates subtopics for additional information about these vulnerable populations.

Informed Consent > Children/Minors
Last content review/update: June 18, 2020

Overview

The SA-GCPs state that a minor is a person under 21 years of age and that assent from the minor should be obtained where he/she is capable of understanding.

On the other hand, 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.

According to the NHA, the G-EthicsHR, 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 where he/she 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, 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 he or she is capable of understanding

See the NHAParticipants for detailed application requirements.

In addition, 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 SA-GCPs, the G-EthicsHR, 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. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Assent Requirements

The SA-GCPs and the G-EthicsHR 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 he/she fails to object during the informed consent process. It is necessary for the minor/child and his/her legal representative(s) or guardian(s) to be in agreement on participation. The minor’s/child’s refusal to participate is final.

Conflict in Laws Regarding Minors/Children

As per the G-GPHlthCare, South African law has been inconsistent in its approach to addressing the capacity of minors/children to consent. Currently, there are no clear legal statutes specifying when children can independently consent to research.

Data Protection

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.
Last content review/update: May 05, 2020

Overview

The NGHRP defines a child as a person below the age of 18. While consent from the child’s parent or guardian is required in most cases, the NGHRP does allow for mature and emancipated minors, as described below, to provide consent.

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

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

Assent Requirements

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

Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: June 18, 2020

Overview

As per the NHA, the SA-GCPs, and the G-EthicsHR, any research studies involving pregnant women, women who may become pregnant, or fetuses, required 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 potential for additional health concerns that may arise during pregnancy, and the need to avoid unnecessary risk to the fetus.

The following conditions are required for research to be conducted involving pregnant women and fetuses:

  • Appropriate studies on animals and non-pregnant individuals have been completed
  • The risk to the fetus is minimal and is the least possible risk for achieving the study’s objectives, except where the purpose of the study is to meet the health needs of the mother and the fetus, and the foreseeable benefits outweigh the potential risks
  • Individuals engaged in the study have no part in deciding the timing, method, and procedures to be used to terminate the pregnancy, or in determining the viability of the fetus at the termination of the pregnancy

Pregnant women and fetuses may not be involved as research participants unless the mother and the fetus will be placed at risk to the minimum extent necessary to achieve the study’s health objectives, the purpose of the research is to meet the mother’s health needs, and the mother is legally competent, and has given informed consent after having been fully informed about the possible impact on the fetus.

In certain circumstances, recognition should be given to the interests of the father of the fetus to participate in decision making. However, the father's informed consent is not required if the purpose of the research is to meet the mother’s health needs, the father’s identity or whereabouts cannot reasonably be ascertained, the father is not reasonably available, or the pregnancy is a result of rape.

Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27). (See the Informed Consent topic, Required Elements subtopic for general informed consent form requirements).

Last content review/update: May 05, 2020

Overview

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 the purpose of the study is primarily to meet the mother's health needs, the father's identity or whereabouts are unknown, the father is not reasonably available, or the pregnancy resulted from rape or incest.

(See the Informed Consent topic, Required Elements subtopic for general informed consent form requirements.)

Informed Consent > Prisoners
Last content review/update: June 18, 2020

Overview

According to the NHA, the SA-GCPs, the G-EthicsHR, and the NHAParticipants, a prisoner may not, even with his/her consent, participate in any scientific experimentation, research study, or clinical trial except under limited conditions . A research study may involve a prisoner as a participant only after the ethics committee (EC) has ensured that the clinical trial involves the following:

  • The study of the possible causes, effects, and processes of incarceration, and of criminal behavior
  • No more than minimal risk and inconvenience to the participants
  • The study of prisons as institutional structures or of prisoners as incarcerated persons
  • Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on diseases that may be more prevalent in prisons, and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) only after appropriate experts have been consulted
  • Research on practices, both innovative and accepted, that have the intent and probability of improving the health or well-being of prisoners
  • The rights of prisoners, including but not limited to the rights to dignity, privacy, bodily integrity, and equality, will be protected
  • The Department of Correctional Services’ procedures and guidelines will be followed

An EC reviewing the protocol involving prisoners must also ensure that:

  • A majority of the EC members have no association with the prisoner(s) involved
  • Where possible, a prisoner or an ex-prisoner should be an EC member
Last content review/update: May 05, 2020

No relevant provisions

Informed Consent > Mentally Impaired
Last content review/update: June 18, 2020

Overview

According to the NHA, the SA-GCPs, the G-EthicsHR, 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.

Research involving these populations must conform to the following requirements:

  • Be relevant to mental disabilities or substance abuse related disorders so that it is necessary to involve people who have a mental disability or a substance abuse related disorder(s)
  • Justify the involvement, as the study population of institutionalized persons with mental disabilities
  • Ensure appropriate evaluation procedures for ascertaining the participants’ ability to give informed consent. If participants are deemed unable to understand or to make a choice, then an appropriate individual who is able to consent on their behalf must be identified
  • Ensure that consent is free from coercion and risk to participants
  • Ensure that only minimal risk is involved, and that the risk is outweighed by the anticipated benefits for the participants, and by the importance of the knowledge that will be gained from the research

In addition, persons with mental or intellectual impairment should not participate in research that might be conducted equally well with persons without those impairments. Consent to conduct research must be obtained from:

  • The participant, whenever he/she is competent to give informed consent
  • The participant’s legal representative(s) or guardian(s) where the participant is deemed not competent to do so
  • An authority, organization, or person having that responsibility by law

Consent cannot be given for participation in research that is contrary to the interests of the person with the mental or intellectual impairment. The mentally or intellectually impaired person's refusal to participate in research must always be respected. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Last content review/update: May 05, 2020

No relevant provisions

Investigational Products > Definition of Investigational Product
Last content review/update: June 18, 2020

Overview

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

Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Last content review/update: May 05, 2020

Overview

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.

This includes:

  • A registered product when used or assembled (formulated or packaged) in a way different from the approved form
  • When used for an unapproved indication
  • When used to gain further information about an approved use
Investigational Products > Manufacturing & Import
Last content review/update: July 23, 2020

Overview

According to the SA-GCPs and the GRMRSA, the South African Health Products Regulatory Authority (SAHPRA) is responsible for authorizing the manufacture of investigational products (IPs) in South Africa. In addition, IPs which are unregistered medicines may only be brought into the country after the clinical protocol has been approved by the SAHPRA.

The SA-GCPs states that the clinical trial application approval document issued by the SAHPRA also serves as the importation permit for the unregistered IP under MRSA. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics and Regulatory Authority topic, Regulatory Fees subtopic for detailed application requirements).

Pursuant to the SA-GMPs, South Africa adopted the PIC-S-GMP-Guide for the manufacturing of therapeutic goods. In addition, as per ZAF-29 and ZAF-13, the SAHPRA requires a Certificate of Analysis to be issued by the manufacturer for all IPs to be used in a clinical trial. Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

The G-PostCTAccess guides sponsors in 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. See Sponsorship topic, Compensation subtopic for additional considerations.

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.

Last content review/update: November 11, 2020

Overview

According to the NDPA CTReg, the G-CTConduct, the G-GMPMedicinal, and the G-TrialsGCP, the National Drug Authority (NDA) is responsible for authorizing the manufacture of investigational products (IPs) in Uganda. The NDA will only approve the manufacture of an IP after approval of the clinical trial application. The NDPA CTReg indicates that if the IP is to be manufactured in Uganda, the holder of the clinical trial certificate must apply to the NDA for a manufacturing license. Per the G-GMPMedicinal, the NDA issues a manufacturing authorization, which requires the holder to ensure he/she manufactures IPs in compliance with the requirements of the clinical trial authorization.

The NDA is also 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. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics, and Regulatory Authority topic, Regulatory Fees subtopic for detailed application requirements).

The G-GMPMedicinalAPIs indicates that once drug development reaches the stage where the active pharmaceutical ingredient (API) is produced for use in IPs intended for clinical trials, manufacturers should ensure that APIs are manufactured in suitable facilities using appropriate production and control procedures to ensure the quality of the API. The production of APIs for use in clinical trials should be documented in laboratory notebooks, batch records, or by other appropriate means.

As per the G-GMPMedicinalAnnexes, the sponsor is responsible for sending a written order to the manufacturer to process, package, and/or ship IPs for a clinical trial. This order should be formally authorized and refer to the Product Specification File and the relevant clinical trial protocol. The Product Specification File is a reference file that contains all of the information necessary to develop written instructions on processing, packaging, quality control testing, batch release, and shipping of an IP.

The sponsor must ensure that the IP is consistent with the details in the clinical application and NDA’s authorization. This can be achieved through a change control process for the Product Specification File and defined in a Technical Agreement between the sponsor and the Authorized Person. The sponsor should record and retain all relevant documentation.

In addition, the G-GMPMedicinal and the G-GMPMedicinalAnnexes require the manufacturer to create and/or maintain the following documentation:

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

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.

Investigational Products > IMP/IND Quality Requirements
Last content review/update: June 18, 2020

Overview

The SA-GCPs states that the information required to support the quality of the investigational product (IP) in South Africa is based upon the principles set forth in Section 7 (Investigator’s Brochure (IB)) of the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (ZAF-27).

IB Content Requirements

The SA-GCPs and ZAF-27 require the IB to provide coverage of the following areas:

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

See Section 7 of ZAF-27 for detailed content guidelines.

The sponsor is also accountable for supplying the IP, including the comparator(s) and placebo, if applicable. As defined in the SA-GCPs, he/she must ensure that the products are manufactured in accordance with the good manufacturing practices as prescribed in Annex 13 of the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs). (See Investigational Products topic, IMP/IND Quality Requirements subtopic for additional information on IP supply, storage, and handling requirements).

In addition to including the IB with the clinical trial application submission, the South African Health Products Regulatory Authority (SAHPRA) also requires the application to provide a detailed review of the IPs to be used in the study. As indicated in ZAF-23, the following information must be furnished:

  • IP name(s) and details (e.g., formulation(s) and strength(s))
  • Comparator product(s) name(s) and details
  • Concomitant name(s) and details including rescue medications
  • Estimated quantity of trial material (each drug detailed separately) for which exemption will be required
  • 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
  • Date SAHPRA registration applied for or envisioned date of application for trial medication; explain if registration is not envisioned
  • Registration status of entity, for the indication to be tested in this trial, in other countries

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

Certificate of Analysis

As stated in the Manufacturing & Import subtopic, the SAHPRA requires a Certificate of Analysis (CoA) to be issued by the manufacturer for all IPs to be used in a clinical trial. The CoA should identify the compound, dose, batch numbers, expiration dates, excipients, stability information (if available), and include a statement that the product is manufactured according to any applicable good manufacturing practices as described in the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs). For the placebo group, the CoA must demonstrate that no active component exists in the formulation. If a comparator drug product is to be used in the trial, the CoA should confirm the appearance, dose, composition, expiration dates, stability (if available), and batch numbers for the product.

Last content review/update: May 05, 2020

Overview

In accordance with the NDPA CTReg, the G-CTConduct, the NGHRP, and the G-TrialsGCP, the sponsor is responsible for preparing the Investigator’s Brochure (IB), which is a compilation of the clinical and non-clinical data on the investigational product(s) (IPs). The IB must contain all of the relevant information on the IPs including chemical, pharmaceutical, toxicological, pharmacokinetic, and pharmacodynamic data obtained from studies in animals as well as in humans, and the results of earlier clinical trials, if applicable.

Per the G-GMPMedicinalAnnexes, the sponsor has the ultimate responsibility for all aspects of the clinical trial including the quality of IPs and associated manufacturing operations. However, according to the NDPA CTReg, the principal investigator (PI) is responsible and accountable for the IP.

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

IB Content Requirements

The G-TrialsGCP 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 guidelines, and UGA-14 or Schedule 2 of the NDPA CTReg for the format of the IB.

Certificate of Analysis and GMP Certificate

Per the G-GMPMedicinal, the manufacturer is required to provide a certificate of analysis that contains a summary of testing results on samples of products or materials together with the evaluation for compliance to a specification. In addition, the National Drug Authority (NDA) conducts periodic good manufacturing practice (GMP) inspections of all manufacturers of medicinal products within and outside Uganda. The NDA will issue a GMP compliance certificate to manufacturers that are GMP compliant. Further, as specified in the G-GMPMedicinalAnnexes, the manufacturer must establish a quality system that is described in written procedures and available to the sponsor. This system should take into account GMP principles and guidelines that apply to IPs.

According to the G-CTConduct and the G-TrialsGCP, the sponsor must ensure that the IP(s) is manufactured in accordance with GMP and is coded and labeled in a manner that protects the blinding, if applicable. The G-CTConduct further indicates that evidence of manufacture under GMP standards must be submitted with the clinical trial application to the NDA.

As per the G-CTConduct, 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.

(See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements).

Investigational Products > Labeling & Packaging
Last content review/update: June 18, 2020

Overview

Investigational product labeling in South Africa must comply with the requirements set forth in the SA-GCPs, the GRMRSA, and the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs). The GRMRSA states that for an investigational product (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.

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, specialised 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.

In addition, the SA-GCPs state that the IP be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Last content review/update: May 05, 2020

Overview

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

As per the NGHRP, the G-TrialsGCP, and the G-GMPMedicinalAnnexes, the sponsor is responsible for ensuring the proper packaging and labeling of the IPs. The IPs and comparator products must be labeled in conformity with the clinical protocol, and the labeling must state that the product is for investigational purposes only.

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:

  • The name, address, and telephone number of the sponsor or manufacturer; the G-GMPMedicinalAnnexes specifies the investigator or contract research organization could also be the main contact for IP information, clinical trial, and emergency unblinding
  • The pharmaceutical dosage form, route of administration, quantity of dosage units, and strength of active substance
  • The batch number
  • A trial reference code allowing identification of the trial, site, investigator, and sponsor, if not given elsewhere
  • The trial participant identification number or treatment number and, where relevant, the visit number
  • The investigator’s name (if not already provided on the label) (the G-GMPMedicinalAnnexes)
  • The product name or unique code (if blinded)
  • The storage conditions and storage temperature
  • The instructions for use
  • The period of use (use-by date, expiration date, or re-test date), in month/year format
  • The product is a clinical trial material (e.g., For Clinical Trial Use Only)

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

The G-TrialsGCP requires that IPs be packaged to prevent contamination and unacceptable deterioration during transport and storage. 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).

Investigational Products > Product Management
Last content review/update: June 18, 2020

Overview

In accordance with the SA-GCPs, the sponsor is responsible for providing the investigator(s) with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) including chemical, pharmaceutical, toxicological, pharmacokinetic, and pharmacodynamic data obtained from studies in animals as well as in humans, and the results of earlier clinical trials, if applicable. The information provided should be accurate and adequate to justify the nature, scale, and duration of the proposed trial, and to evaluate the potential safety and need for special precautions. Moreover, a sponsor must bring any new and relevant information arising during the study to the attention of the principal investigator(s) (PI(s)) and the ethics committee(s) (ECs), and update the IB, as required. The sponsor should also include all of the information contained in the IB in the clinical protocol. Refer to the Clinical Trial Lifecycle topic, Submission Content subtopic for additional IP requirements.

Per the SA-GCPs, the sponsor should also follow the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27).

Investigational Product Supply, Storage, and Handling Requirements

As defined in the SA-GCPs, the sponsor must also supply the PIs/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable. The sponsor should not supply the PI(s)/institution(s) with the IP(s) until the sponsor obtains approvals from the South African Health Products Regulatory Authority (SAHPRA) and the EC. The SAHPRA approval is also a written authorization document to import unregistered drug products under MRSA.

The sponsor must provide the PI(s)/institution(s) with written procedures to follow for IP(s) handling and storage. The sponsor must ensure the following:

  • Timely delivery of IP(s) to the PI(s)/institution(s)
  • Maintenance of records documenting IP(s) shipment, receipt, disposition, return, and destruction
  • Maintenance of a system for retrieving IPs and documenting this retrieval
  • Maintenance of a system to dispose of unused IP(s) and corresponding documentation
  • Ensuring the IP(s) are stable over the period of use
  • Maintenance of sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary
  • Maintenance of records of batch samples analyses and characteristics

The sponsor must also ensure that the products are manufactured in accordance with any applicable Good Manufacturing Practices which are described in the PIC-S-GMP-Guide (which South Africa adopted pursuant to the SA-GMPs), and are coded and labeled in a manner that protects the blinding, if applicable. IP labeling should comply with the PIC-S-GMP-Guide labeling requirements. 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.

In blinded trials, 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. 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 available prior to its use in the clinical trial. Refer to the SA-GCPs for detailed sponsor-related IP requirements.

Record Requirements

The sponsor is required to retain essential documents for at least 15 years, or, until at least two (2) years after the last approval of a marketing application and until there are no pending or contemplated marketing applications, or, at least 15 years have elapsed since the formal discontinuation of clinical development of the IP. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or if needed by the sponsor.

The sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial related records are no longer needed.

Last content review/update: November 11, 2020

Overview

In accordance with the NDPA CTReg, the G-CTConduct, the NGHRP, and the G-TrialsGCP, the sponsor is responsible for providing the investigator(s) with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) including chemical, pharmaceutical, toxicological, pharmacokinetic, and pharmacodynamic data obtained from studies in animals as well as in humans, and the results of earlier clinical trials, if applicable. The information should be presented in a concise, simple, objective, balanced, and non-promotional form that enables a clinician, or potential investigator, to understand it and make his/her own unbiased risk-benefit assessment of the appropriateness of the proposed trial.

According to the NDPA CTReg and the G-TrialsGCP, the sponsor should update the IB as new information becomes available. 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 ethics committee(s) (ECs) (research ethics committees (RECs) in Uganda) and/or regulatory authorities before it is included in a revised IB. The sponsor is responsible for ensuring that an up-to-date IB is made available to the investigator(s), and the investigator(s) is responsible for providing the up-to-date IB to the responsible ECs and the National Drug Authority (NDA).

As specified in the G-GMPMedicinalAnnexes, the sponsor has ultimate responsibility for all aspects of the clinical trial including the quality of the IPs. The increased complexity in manufacturing operations requires a highly effective quality system. However, according to the NDPA CTReg, the principal investigator (PI) is responsible and accountable for the IP.

Investigational Product Supply, Storage, and Handling Requirements

As defined in the NDPA CTReg, the G-TrialsGCP, and the G-CTConduct, the sponsor must also supply the investigator(s)/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable.

The G-TrialsGCP states that the sponsor should not supply the investigator(s)/institution(s) with the IP(s) until the sponsor obtains NDA and EC approvals. The sponsor is responsible for ensuring that the products are manufactured in accordance with Good Manufacturing Practices (GMPs). Furthermore, the sponsor should ensure that written procedures include instructions that the investigator/institution should follow for the handling and storage of IP(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from participants, and return of unused IP(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the NDA approved protocol and/or where available, applicable regulatory requirement(s)).

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

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

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

Record Requirements

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

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

The G-TrialsGCP and the G-CTConduct state that the sponsor and the PI are responsible for archiving and ensuring the safety of all trial-related documentation. The holder of the clinical trial certificate should inform the NDA in writing prior to destroying the documents. Per the NDPA CTReg, trial records for unregistered IPs should be kept for 20 years following the study's completion. Documentation for trials involving IPs to be registered should be kept for two (2) years after the registration of the IP.

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

Investigational Product Importation and Release Requirements

According to the NDPA CTReg, the G-TrialsGCP, and the G-CTConduct, the sponsor should document the shipment and receipt of IPs. The G-CTConduct further indicates that the pharmacist of record must maintain instructions for handling of IP(s) and trial related materials, if not indicated in the protocol or IB). The pharmacist must also maintain shipping records for the IP(s) and trial related material, as well as for receipt date(s) of product delivery and quantity.

As per the G-GMPMedicinalAnnexes, the sponsor is responsible for sending a written order to the manufacturer to process, package, and/or ship IPs for a clinical trial. This order should be formally authorized and refer to the product specification file and the relevant clinical trial protocol. The product specification file is a reference file that contains all of the information necessary to develop written instructions on processing, packaging, quality control testing, batch release, and shipping of an IP.

In addition, during the shipping process, the sponsor maintains IP control until certification by the manufacturer’s authorized person and release following fulfillment of relevant requirements on:

  • Batch records
  • Production conditions
  • Validation status of facilities, processes, and methods
  • Examination of finished packs
  • Results of any analyses or tests performed after importation, where relevant
  • Source and verification of conditions of storage and shipment
  • Audit reports concerning the quality system of the manufacturer
  • Documents certifying that the manufacturer is authorized to manufacture IPs or comparators
  • Regulatory requirements

The sponsor must ensure that the IP is consistent with the details in the clinical application and the NDA’s authorization. This can be achieved through a change control process for the product specification file and defined in a technical agreement between the sponsor and the authorized person. The sponsor should record and retain all relevant documentation.

Specimens > Definition of Specimen
Last content review/update: June 18, 2020

Overview

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, 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 follows the G-EthicsHR 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 defines “human biological materials” with the same definition as is used for “biological specimen.”

In addition, the NHABlood&Cells generally refers to substances of human origin as biological substances.

Please refer to the G-EthicsHR, the NHABiol, the NHA, the NHABlood&Cells 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.

Last content review/update: May 05, 2020

Overview

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, the following:

  • Blood
  • Urine
  • Stool
  • Saliva
  • Hair
  • Nail clippings
  • Skin
  • Microorganisms
  • Other associated bio-products
Specimens > Specimen Import & Export
Last content review/update: June 18, 2020

Overview

As delineated in the GRMRSA, the SA-GCPs, and the NHAParticipants, to conduct a clinical trial using biological substances, a sponsor or his/her designated contract research organization (CRO) must submit a clinical trial application to receive approval from the South African Health Products Regulatory Authority (SAHPRA) and the local accredited ethics committee(s) (ECs). In addition, per the NHA, the NHABlood&Cells, 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 SAHPRA approval letter and the NDOH import/export permit must be included with each biological substance shipment. See also the Clinical Trial Lifecycle topic, Submission Content subtopic for information on completing a clinical trial application.

NDOH Application Requirements

As set forth in the NHA, the NHABlood&Cells, 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 NHABlood&Cells, 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 NHABlood&Cells 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 he/she is satisfied that the submission meets the NHA, the NHABlood&Cells, 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 NHABlood&Cells 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 NHABlood&Cells 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 NHABlood&Cells. 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 NHABlood&Cells 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.
Last content review/update: May 05, 2020

Overview

A permit must be obtained from the Uganda National Council for Science and Technology (UNCST) to conduct a clinical trial using a human biological substance in Uganda.

UNCST Application Requirements

As set forth in the NGHRP and the G-UNCSTreg, when a host institution demonstrates that it lacks the capacity to conduct an adequate investigation of a human biological substance in Uganda, an investigator must submit a request to the UNCST to obtain permission to transfer, export, or exchange samples abroad for research purposes. The request must be accompanied by a Material Transfer Agreement (MTA) between the host institution in Uganda and the recipient institution abroad. 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
  • The governing law in the form of a Memorandum of Understanding (MOU) should be provided
  • 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 collaboration and benefit sharing
  • A framework for accessing and sharing data
  • Restrictions to third party transfer
  • 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
  • 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
  • Specific restrictions for recipient organization should be described
  • 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”
  • The process by which the recipient institution provides annual reports to the host institution and the UNCST on the status of the samples

See Section 10.4 of the NGHRP for detailed MTA requirements.

The investigator must comply with the following requirements:

  • Be a legal resident of Uganda, or be affiliated with a locally recognized institution in Uganda
  • Obtain UNCST registration and approval for the research proposal that involves the transfer, export, or exchange of the human biological substance
  • Submit a letter to the Executive Secretary of the UNCST to obtain permission
  • Submit the MTA and any other documents related to the request

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.

All exchanges and transfers, including importation and exportation of materials for research purposes, require UNCST clearance, except for the exchange of human materials between organizations within Uganda.

Future studies using UNCST approved human biological materials must include a Ugandan scientist as an investigator.

(Refer to the NGHRP and the G-UNCSTreg for additional information.)

Specimens > Consent for Specimen
Last content review/update: June 18, 2020

Overview

In accordance with the NHA, the NHASpecAmend, and the NHABiol, prior to removing or withdrawing any biological material from the body of a living person for research purposes, consent must be obtained from that person in writing, before a competent witness. In the event that the person is a minor, the parents or guardians of that person must provide consent. Furthermore, when withdrawing blood, the NHASpecAmend requires written consent from persons older than 16 years.

The NHABiol specifically states that when taking biological samples from a child, where the person is younger than 18 years, Part 3, Section 129 of the Children’s Act must be followed.

Additionally, the NHABiol requires the following consent for the removal or withdrawal of biological samples to treat a person with mental illness:

  • His/her consent, if he/she is capable;
  • A court appointed curator, spouse, next of kin, parent or guardian, major child, brother, or sister, partner or associate, if the mentally ill person is incapable of giving consent; and
  • The head of the health institution in the case of an emergency

Similarly, the NHA and the NHABiol include consent provisions for the donation of human bodies and the tissue of deceased persons. These documents state that any person who is competent to make a will may donate his/her body or any specified tissue to be used after his/her death for medical and dental purposes, as long as he/she signs the will in the presence of at least two (2) competent witnesses. The person may also give consent to a post-mortem examination of his/her body for research purposes, and may select an institution or person as the recipient. In the absence of a donation as described above, the individual’s spouse, child over 18 years, parent, guardian, or brother/sister over 18 years may donate his/her body or any specific tissue to an institution or person for research purposes. Please refer to the NHA, and the NHABiol for detailed requirements. (See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent).

Human Tissue Sample Consent Requirements

The G-EthicsHR presents separate consent provisions for the use of human tissue samples. With reference to human tissue samples, donor consent should be obtained where it is proposed to use tissue samples that have been held:

  • in storage following, or in association with, clinical investigations
  • in archives or banks, or removed during a clinical study, or used in research that may lead to harm, benefit, or injustice to a donor of such tissue

This guideline also requires that consent be voluntary and specific to the purpose for which the tissue is to be used. The participant must be given full information about the study, be advised on storage and future use of samples, and be assured of data related confidentiality and privacy.

In addition, per the NHATissue, tissue banks are required to develop donor record management systems in which the tissue donor register contains the full identity and relationship of the consenting person. The system will also document tissue banking processes, including the process of obtaining informed written consent.

Human Stem Cell Consent Requirements

The NHAStemCell similarly states that authorized stem cell banks must retain a record of the donor’s written informed consent. Further, no person shall use stem cells or its therapeutic research products for educational purposes unless he/she is authorized by the National Department of Health (NDOH) and complies with the following requirements:

  • Has obtained the donor’s informed written consent even in the case of residual tissue, blood or blood products; and
  • Is certain the donor has donated voluntarily and it is properly documented

The NHA also indicates that the NDOH Minister may permit research on stem cells and zygotes that are not more than 14 days old on a written application, and if the applicant documents the research for record purposes, and prior consent is obtained from the donor.

Human Genetic Research Consent Requirements

The G-EthicsHR states that the investigator or institution must obtain consent for human genetic research. Investigators and institutions must comply with numerous requirements to ensure participant consent, protection, and privacy rights are upheld with regard to the storage of genetic materials. See the G-EthicsHR for consent requirement details.

Consent Waivers

In reference to both human tissue sample and genetic research consent, the G-EthicsHR indicates that an ethics committee may sometimes waive the consent requirement in cases where there is minimal risk of commercial exploitation or privacy violations. For additional details, see section 3.3 of the G-EthicsHR.

Last content review/update: May 05, 2020

Overview

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

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

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

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

The investigator must also give the research participant the right to choose whether his/her samples should or should not be stored for future studies.

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