Clinical Research Regulation For Canada and South Africa

Last content review/update: November 2, 2026

Overview

In accordance with the CanadaFDA, Health Canada (HC) reviews, evaluates, and approves applications for clinical trials using authorized therapeutic products. HC also approves the sale or importation of drugs for use in clinical trials. (See the Manufacturing & Import section for additional information on importation.) As delineated in the CanadaFDR and the G-CanadaCTApps, institutional ethics committee (EC) review is required for each clinical trial site and may occur in parallel with HC’s clinical trial application (CTA) review and approval. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. See CAN-23 for background information on how HC reviews drugs in Canada.

Per the CanadaFDA, a “therapeutic product” is defined as a drug or device, or any combination of drugs and devices, but does not include natural health products; and “therapeutic product authorization” refers to a license that is approved for the import, sale, advertisement, manufacture, preparation, preservation, packaging, labeling, storage, or testing of a therapeutic product. As per the G-CanadaCTApps, a drug is defined as a pharmaceutical, biologic, gene therapy, blood product, vaccine, and radiopharmaceutical for human use that is to be tested in a clinical trial. HC’s scope of assessment includes clinical trials (Phases I - III) using:

Drugs not authorized for sale in Canada in development and in comparative bioavailability studies
Marketed drugs where the proposed use of the drug for one (1) of the following is different: indication(s) and clinical use; target patient population(s); route(s) of administration; or dosage regimen(s)

Clinical Trial Review Process

As set forth in the G-CanadaCTApps and CAN-23, HC’s Health Products and Food Branch (HPFB) coordinates the CTA approval process. The G-CanadaCTApps and CAN-23 state that prior to initiating the trial, the sponsor must file a CTA to the appropriate HPFB Directorate. CTAs involving pharmaceutical drugs should be sent to the Pharmaceutical Drugs Directorate (PDD), and CTAs involving biologics and/or radiopharmaceuticals should be sent to the Biologic and Radiopharmaceutical Drugs Directorate (BRDD).

The G-CanadaCTApps indicates that upon receipt of a CTA, the HPFB Directorate (PDD/BRDD) screens the application package for completeness. If deficiencies are found, the Directorate sends the sponsor a Request for Clarification or a Screening Rejection Letter. If the Directorate finds the application complete, an acknowledgement letter is issued to indicate the 30-day default review period commenced on the date of receipt. See CAN-23 for more information.

Per the G-CanadaCTApps, once a clinical trial is authorized, the sponsor is allowed to sell or import a drug for use in a trial, if a CTA has been filed with HC and has not received an objection within 30 days. If the clinical trial is authorized, a No Objection Letter (NOL) is issued. If the CTA is rejected, a Not Satisfactory Notice (NSN) is issued. During the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals. See the Submission Process section for detailed application submission requirements. See CAN-23 for more information.

Per the G-CanadaCTApps, soon after HC issues an NOL, it will publish the following information about the clinical trial in HC’s publicly accessible database:

Protocol number
Protocol title
Drug name
Medical condition
Study population
Authorization date
Sponsor name
HC control number
Trial start and end dates, if known

The CanadaFDR and the G-CanadaCTApps also delineate that a clinical trial application-amendment (CTA-A) is required for proposed changes to a previously authorized study when the changes to clinical trial drug supplies affect the quality or safety of the drug, or when the changes to an authorized protocol alter the risk to clinical trial participants, or both. CTA-As must be authorized by HC prior to implementation of the changes. However, if the sponsor is required to immediately implement changes because the clinical trial or the use of the clinical trial drug endangers the health of participants or other persons, the sponsor may immediately make the amendment without prior review by HC. Sponsors must notify HC of this change, provide the relevant rationale in support of the immediate implementation, and file a CTA-A that clearly identifies the change and rationale for immediate implementation of the change within 15 days after the amendment implementation date. In addition, sponsors may make the following changes immediately if it notifies HC in writing within 15 days after the date of the change: a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug; or a change to the protocol that does not alter the risk to the health of a participant.

As per the G-Dcntrl, HC requires information about decentralized elements in the clinical trial application to review whether these elements were designed to minimize risk to participants, support appropriate oversight and monitoring throughout the trial, and help achieve trial objectives. Additionally, sponsors must attest that the trial, including all decentralized elements, will be conducted according to good clinical practice (GCP). Depending on the decentralized elements and activities within the proposed trial known at the time of application, HC will review how participant visits and clinical trial activities will be conducted (e.g., in person, by telephone or telehealth platform, or through third parties or vendors). See G-Dcntrl for more details about clinical trials with decentralized elements.

As delineated in the CanadaFDA and the G-Inspections, HC is authorized to implement an inspection strategy and to ensure compliance with CanadaFDA. The G-Inspections states that HC’s Regulatory Operations and Enforcement Branch (ROEB) monitors compliance, which is assessed through inspections and other compliance and enforcement activities, such as compliance verifications. Compliance verifications of clinical trials may be initiated when there are reasonable grounds to believe that non-compliance may have occurred or is occurring and that enforcement measures may be necessary (e.g., complaints received regarding specific trials, reports of adverse drug reaction(s), or reports from other regulatory authorities). The Clinical Trial Compliance Program within ROEB is responsible for clinical trial site selection for inspections in collaboration with the PDD and the BRDD. A risk-based approach is applied in the site selection process to minimize the potential health risks inherent to clinical trials involving human participants. The selection of sites for inspection is based on a variety of criteria to select sites throughout all levels of the drug assessment and regulatory approvals process. For clinical trial sites with decentralized elements, G-Dcntrl states that the main location of the clinical trial site associated with the qualified investigator (QI) is the primary point of contact for an inspection. HC inspectors may request documentation from sponsors and QIs to demonstrate adequate coordination, oversight, and monitoring of delegated parties, as well as the measures in place to protect participant safety. See the Risk-Insp for a risk classification guide used by ROEB; this guide describes how inspectors classify risk-based observations and assign a rating, promotes consistency, and provides examples of inspection observations.

Per the CanadaFDR, HC will suspend the authorization to sell or import a drug for clinical trial purposes if it has reasonable grounds to believe that:

The sponsor has contravened any relevant laws or regulations
Any information submitted in respect of the drug or clinical trial is false or misleading
The sponsor has failed to comply with GCP
The sponsor has failed to provide information or samples as required by the regulation

See the CanadaFDR for additional details on HC’s suspension and cancellation responsibilities.

Expanded Access Clinical Trial

The Expd-CTs explains that in Canada, an expanded access clinical trial is a type of clinical trial that provides access to investigational products (IPs) that have the potential to treat people living with medical conditions who do not qualify for other clinical trials or are not able to participate in one. When appropriate, expanded access clinical trials can use more flexible protocols and a decentralized model to facilitate access for a larger, potentially more diverse population of participants, in more accessible settings. Since expanded access clinical trials are a type of clinical trial under the CanadaFDR, they require a CTA for review by HC. HC will review applications for the sponsor’s evidence from previous studies that the proposed use of the IP would not endanger the health and safety of participants. HC assesses all CTAs on a case-by-case basis. CTAs for expanded access clinical trials follow the same review processes and timelines as other clinical trials. HC scientists and physicians review expanded access CTAs to assess whether:

The risks in using the drug in the trial are considered and would not endanger health and safety
The best interests of those taking part in the trial have been considered, including that drugs are used in the right way for the participants being studied
The goals of the trial can be met

Per the Expd-CTs, group-level access to a drug in Canada is available only through an expanded access clinical trial and not through the individual-patient Special Access Program. Therefore, sponsors wishing to include a Canadian arm in an international expanded access program for multiple patients must do so through an expanded access clinical trial.

1.1-1.3 and 3.2

1.2, 2.1, 2.3-2.7, and Appendix 1

3 and 4

2 and Part II (Sections 22 (1) and 30 (1.2))

Part C (Division 5 (C.05.001, C.05.002, C.05.005-.008, and C.05.016-.017))

What is the Health Products and Food Branch?

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

Clinical Guideline (Version 4, Effective June 2026)
SAHPRA’s Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

In accordance with the GRMRSA, the South African Health Products Regulatory Authority (SAHPRA) is responsible for reviewing and approving all clinical trial applications for an unregistered medicine, and for any new indication or dosage regimen of a registered medicine. The scope of the SAHPRA’s assessment includes all clinical trials (Phases I-IV) and bioequivalence/bioavailability studies. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and a registered ethics committee (EC) may be conducted in parallel. However, the G-EthicsHR-ZAF recommends that scientific review be completed prior to ethics review, and in cases where scientific review capacity is not available, the EC approval should be delayed until SAHPRA scientific approval has been provided.

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

Clinical Trial Review Process

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

As stated in ZAF-36, the CTU completes a preliminary screening of the application and sends an official letter to the applicant with the outcome and follow-up questions on a screening checklist. As indicated in ZAF-23, incomplete documentation or sub-standard submissions will be rejected. Additionally, applications submitted without clinical trial insurance will be rejected. Applicants will be allowed a maximum of two (2) rounds of queries to respond to, and if the responses are not satisfactory, the application will be rejected. Per ZAF-36, if an application is rejected, no response is required; the screening checklist should be used as guidance for resubmission during the next review cycle. Next, the CTU’s Clinical Trial Committee (CTC) (which includes an expert committee of specialists, as needed) reviews the proposed clinical trials pursuant to the schedule on SAHPRA’s website. (See CTCDates for 2026 dates). Per ZAF-1, clinical trial reviews will result in one (1) of the following outcomes:

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

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

Other Considerations

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

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

Checklist (Note for all applications), 3.1, Annex 3, Annex 5, and Appendix

Review of Clinical Trials (Expert Committee Review)

9.3.2

3.1

Part 30 (1)

Regulatory Fees

Last content review/update: November 2, 2026

According to CAN-56, there are no fees to submit a clinical trial application in Canada.

Fees

Last content review/update: March 19, 2026

South African Health Products Regulatory Authority

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

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

Clinical trial application (safety and efficacy): South African Rand (R)33 700
Clinical trial application (bioequivalence study): R31 700
Clinical trial application (postgraduate study) with pharmaceutical company involvement: R11 200
Phase 4 clinical trial application and any other clinical trial application, including university-involved postgraduate qualification and/or pre-consultation of clinical trials: R5 100

For amendments to clinical trials:

Technical amendment applications: R7 200
Administrative amendment applications: R4 200
Any other application except for the purpose of performing a clinical trial: R400

For licenses:

New manufacturing license: R26 200
New import/export license to the holder of certificate of registration: R15 600
Renewal of manufacturing license: R22 900
Renewal of import license to the holder of the certificate of registration: R9 600
Renewal of export license to the holder of the certificate of registration: R9 600
Annual retention of all licenses: R4 400

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

Manufacturing sites: R1 660 per hour per inspector, plus reimbursement for travel time
Desktop inspection, including good practice compliance status after license amendments: R2 200 per day per inspector

Payment Instructions

Per the G-SAHPRAFees, SAHPRA has initiated a process to phase in an electronic application system through various Application Portals that will create unique reference numbers for the application and relevant payment. When making payments, applicants should follow these guidelines:

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

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

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

Fee payment questions can be directed to finance@sahpra.org.za or 012 501 0470.

Sections 1-3 and Annexures A and B

35

Fees for Clinical Trials, Fees for New Licenses, and Fees for Inspections

Ethics Committee

Last content review/update: November 2, 2026

Overview

As indicated in the CanadaFDR and the G-CanadaCTApps, Canada has a decentralized process for the ethical review of clinical trial applications, and requires the sponsor to obtain institutional ethics committee (EC) approval for each participating trial site. (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information.

Per CAN-35 and CAN-13, all proposed or ongoing research involving human participants carried out by, funded by, or otherwise under the auspices of Health Canada (HC) or the Public Health Agency of Canada (PHAC) must obtain approval from a joint EC representing those two (2) agencies—as well as complying with the CanadaFDR and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. This joint EC is known as the HC-PHAC REB. Further, if an institution is conducting an HC- or PHAC-funded project, the HC-PHAC REB must review and approve the research even if it has been previously reviewed and approved by another EC. See CAN-35 for details on the HC-PHAC REB’s development, responsibilities, and composition. HC’s operational policy (CAN-13) outlines policies and procedures that the joint HC-PHAC REB must follow when reviewing clinical trials.

Institutional ECs are required to comply with the provisions delineated in the CanadaFDR, the G-CanadaCTApps, and CAN-52. Note that per CAN-50, HC-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. In addition, institutional ECs are guided by the G-TCPS2. Jointly developed by Canada’s three (3) federal research agencies: the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Social Sciences and Humanities Research Council (SSHRC), the G-TCPS2 is a policy that sets the ethical benchmark for all Canadian institutional ECs. However, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guideline as a condition of funding. According to CAN-14, the CIHR, the NSERC, and the SSHRC created the Panel on Research Ethics (PRE) to promote the ethical conduct of research involving human participants. The PRE develops, interprets, and implements the G-TCPS2.

Ethics Committee Composition

As delineated in the CanadaFDR and the G-CanadaCTApps, institutional ECs must have at least five (5) members representing a mixed gender composition, the majority of which are Canadian citizens or permanent residents, and must include:

Two (2) members from a scientific discipline, with broad experience in the relevant research methods and areas, one (1) of whom is from a medical or dental discipline
One (1) member knowledgeable in ethics
One (1) member knowledgeable in relevant Canadian biomedical research laws
One (1) member from a nonscientific discipline
One (1) community representative

The G-TCPS2 mirrors these EC composition requirements, and also requires a Chair who is responsible for ensuring that the ethics review process conforms to the requirements of G-TCPS2. The Chair provides overall leadership for the EC and facilitates the review process based on institutional policies and procedures and the G-TCPS2. The Chair should monitor the EC’s decisions for consistency and ensure that these decisions are recorded accurately and communicated clearly to researchers in writing as soon as possible by the Chair or designate. Institutions must provide the necessary resources and adequate administrative support to enable the EC Chair to fulfill their responsibilities. As mentioned earlier, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guidance as a condition of funding.

Also, see CAN-52 for additional guidance on EC composition, functions, and operations. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Terms of Reference, Review Procedures, and Meeting Schedule

According to G-TCPS2, institutions must have in place written procedures for the appointment, renewal, and removal of EC members, including Chairs. Further, institutions must have clear written policies describing the mandate of each EC. An institution may wish to use different models for the ethics review of research conducted under its auspices.

The G-TCPS2 states that an EC should have adequate expertise, experience, and training to understand the disciplines, methodologies, and approaches of the research that it considers for research ethics review. Institutions should ensure that all EC members receive appropriate education and training in ethics review of research involving humans, to enable them to fulfill their duties. This includes providing training opportunities for all members in core principles and understanding of the G-TCPS2, basic ethics standards, applicable institutional policies, and legal or regulatory requirements. It includes an understanding of the role and mandate of ECs and responsibilities of EC members. Training should be tailored to the types and complexities of the research that the EC reviews.

Per the G-TCPS2, when there is less than full attendance, decisions requiring full review should be made only when the members present have the specific expertise, relevant competence, and knowledge necessary to provide an adequate ethics review. Ad hoc advisors, observers, research ethics administration staff, and other attendees must not be counted toward quorum or permitted to vote; decisions made without quorum are not valid or binding. ECs must hold regular meetings and normally meet face to face to review research not assigned to delegated review. Where members are geographically dispersed or exceptional circumstances prevent attendance, participation by phone, videoconference, or other technology may be acceptable, provided quorum is maintained and the Chair ensures active participation. A schedule of EC meetings should be communicated to researchers, and ECs should establish a process for reaching decisions requiring full review, such as consensus or, where necessary, a vote.

G-TCPS2 indicates that proportionate review means the level of EC review is determined by the level of foreseeable risk to participants: the lower the risk, the lower the level of scrutiny through delegated review; the higher the risk, the higher the level of scrutiny through full-board review. Full EC review should be the default requirement for research involving humans. Where research is determined to involve minimal risk, an EC may authorize delegated review in accordance with its institutional policies and written procedures. Delegated reviewers may refer proposals to the full EC, and any proposed negative decision must be reviewed and endorsed by the full EC before it is communicated to the researcher. Delegated decisions must be well documented and formally reported to the full EC, which remains responsible for the ethics of all research involving humans within its jurisdiction. ECs must function impartially, provide researchers with a fair hearing, and provide reasoned and appropriately documented opinions and decisions. Approvals and refusals must be communicated in writing. Where members disagree, an effort should be made to reach consensus; if disagreement persists, the decision must be made in accordance with the EC’s agreed-upon and documented process. The EC makes the final determination regarding the nature and frequency of continuing research ethics review using a proportionate approach. At minimum, continuing review consists of an annual status report for multi-year projects and an end-of-study report for projects lasting less than one (1) year.

Regarding records, G-TCPS2 indicates that ECs must prepare and maintain comprehensive records, including all documentation related to the projects submitted to the EC for review, attendance at all EC meetings, and accurate minutes reflecting EC decisions. Where the EC denies ethics approval for a research proposal, the minutes must include the reasons for this decision. When deciding the retention period of their files, ECs should be guided by their institutional record-keeping policies and other relevant legal or regulatory requirements. Files, minutes, and other relevant documentation must be accessible to authorized representatives of the institution, researchers, sponsors, and funders when necessary to assist internal and external audits, or research monitoring, and to facilitate reconsideration or appeals. The minutes of EC meetings must clearly document the EC’s decisions, any dissents, and the reasons for them. EC decisions should be supported by clear references (e.g., date of decision, title of project), documentary basis for decision, the plan for continuing ethics review and timelines, reasons for decisions, and any conditions or limitations attached to the approval. Providing reasons for EC decisions is optional when ethics approval is granted. ECs should have written procedures for its management of record keeping and other submitted reports. EC must maintain reports and decisions on unanticipated issues or changes to approved research.

For examples of EC SOPs, see CAN-13 for the HC-PHAC REB operational policy.

1.2, 1.4, 2.1, and 2.7

Introduction and Chapter 6

Part C (Division 5 (C.05.001, C.05.002, C.05.005, C.05.006, and C.05.010))

2 and 3

About the REB and Policies, Guidelines, and Resources

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

As stipulated in the NHA and ZAF-52, ethics committees (ECs) in South Africa are governed by the National Health Research Ethics Council (NHREC), which is a statutory body established under the NHA. NHREC determines guidelines for the functioning of ECs and registers and audits ECs, among other functions. Further, NHREC gives direction on ethical issues relating to health and develops guidelines for the conduct of research involving humans and animals.

As delineated in the NHA, the G-EthicsHR-ZAF, and the SA-GCP, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study.

The NHA and the G-EthicsHR-ZAF require that every institution, health agency, and health establishment at which research is conducted establish an EC or have access to an independent EC that is registered with the NHREC. Per the G-EthicsHR-ZAF, researchers without affiliation to an institution or organization with an EC should approach a registered EC to request it to review their health research protocols.

Ethics Committee Composition

As delineated in the SA-GCP and the G-EthicsHR-ZAF, an EC must consist of members who collectively encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of all proposed research studies. Further, per the G-EthicsHR-ZAF, ECs should be independent, multidisciplinary, multi-sectoral, and pluralistic. In general terms, membership should include the following:

As many disciplines, sectors, and professions as possible, appropriate to the remit of the specific EC
Members from diverse age groups and academic or professional ranks
Ethnically and culturally diverse members and an appropriate mix of genders
Lay persons
Researchers who do not conduct human participant research or animal use research

The G-EthicsHR-ZAF states that subject to institutional requirements, a chairperson could be appointed or elected at the first meeting of a newly constituted EC. Alternatively, the chairperson could be appointed by the institutional leadership for a period of three (3) to five (5) years, renewable once, if so specified in the terms of reference. The chairperson must have experience in research methodology and research ethics, should have at least two (2) years’ experience as an EC member and should have leadership experience. If the chairperson is an external appointee, the institution must provide the chairperson with the necessary support and authority to perform the role. The chairperson should be assisted by at least one (1) deputy chairperson, who is elected by the EC members and assists the chairperson and serves as the role of chairperson when necessary.

As delineated in the G-EthicsHR-ZAF, the composition of ECs should promote optimal human participant welfare, research integrity (including data robustness and scientific validity), defendable significance of proposed research questions (including translatability of scientific findings into practice, where applicable), as well as legal, professional, and regulatory compliance. All EC members should have documented proof (i.e., evidence) of research ethics training, refreshed at least once. EC membership should consist of:

A minimum of nine (9) members with a quorum being a simple majority; where the number of members is more than 15, the quorum may be 33%
At least one (1) layperson
At least one (1) member with knowledge of, and current experience in, the professional care, counseling, or health-related treatment of people, (e.g., a social worker, nurse, psychologist, or medical practitioner)
At least one (1) member with professional training and experience in qualitative research methodologies
Members with professional training and experience in quantitative research methodologies
A member with expertise in biostatistics
A member with expertise in research ethics
At least one (1) member who is legally qualified and has extensive knowledge of family law, health law, and research ethics

Terms of Reference, Review Procedures, and Meeting Schedule

Per the G-EthicsHR-ZAF, when appointing EC members, institutions should be mindful of the need for ECs to develop institutional memory among the membership as well as to ensure succession planning. Members of ECs should be appointed formally for periods of three (3) to five (5) years, renewable once, after which the member should step down for at least one (1) term. Appointments should overlap so that no more than half the committee membership is new at any one appointment time. ECs should have standard operating procedures (SOP) that specify meeting attendance expectations, possible sanctions if attendance is poor, expectations for promptness of reviews, preparation for meetings, agenda, minutes, etc. ECs must define the review timelines in their SOPs. The appointment letter should describe the essential expectations of membership. ECs should provide induction training for new members that includes discussion of the role of EC members, the code of conduct, expectations of integrity, and confidentiality. Each EC should also have terms of reference that include the delegated and inherent authority as well as the scope of the EC's authority, its responsibilities, its relationship to non-affiliated researchers, its accountability responsibilities, and the mechanisms for reporting and remuneration, if any, for members. See the G-EthicsHR-ZAF for a sample terms of reference.

In addition, per the G-EthicsHR-ZAF, EC members are expected to familiarize themselves with the institutional documentation, as well as the national and relevant international research ethics guidelines, and should have documented proof of such familiarity, e.g., an assessment of training certificate, not a mere attendance certificate. See the G-EthicsHR-ZAF for additional training requirements. The SA-GCP stipulate that EC members who review clinical trial proposals should have research ethics training and good clinical practice training, evidenced by certificates issued in the last three (3) years.

The G-EthicsHR-ZAF states that it is important for ECs to have clear SOPs that clarify the expectations about EC members’ review responsibilities.

Per the G-EthicsHR-ZAF, institutions must have a Code of Conduct for EC members, which details the conduct and integrity expectations of members, including regular and punctual attendance at meetings, diligent performance of responsibilities, maintenance of confidentiality, and management of potential conflicts of interest. The induction process for new members should require that they sign the Code of Conduct to indicate they know and understand the expectations. (See A2.6 Code of Conduct for REC members sample.) Institutions must also ensure there is a formal appointment letter for EC members that sets out the term of office and the assurance that members are indemnified from personal liability against claims that may arise in the course of ordinary business of the EC.

Per the G-EthicsHR-ZAF, ECs should correspond primarily with the principal investigator (PI) or a delegated signatory, and not with the sponsor unless dictated by specific circumstances. EC members should disclose information that may lead to potential, actual, and perceptions of conflict of interest. EC members should not review or make decisions about research protocols in which they are involved personally (including as supervisor of a student) or financially. When such a protocol is to be discussed, the member concerned must declare the potential conflict and offer to recuse themselves from the meeting for that time. Should the member be permitted to remain for the discussion at the discretion of the chairperson (e.g., to facilitate clarifications), the member must leave the meeting for the duration of the final decision-making discussion concerning the application in question. EC members and ad-hoc reviewers must not use the ethics review process to impose personal biases, professional jealousy, or territorial protection conduct about an applicant's protocol, including about research methods or the topic. If applicants pay fees for the ethics review service, this must not negatively affect the rigor of reviews, the integrity of the process, or the capacity to monitor the research that the EC approves. The EC should be alert to whether an advocate for special interest groups of participants proposed for specific research would add value to the review process for informed responsible decision-making in the context. The EC should be alert to the potential for poor consent processes in the absence of appropriately translated materials and the availability of interpreters.

Regarding archiving and record keeping, the G-EthicsHR-ZAF states that ECs should keep written records of all research protocols received for review, including information sheets, consent forms, and relevant correspondence, in the form in which they were approved. Electronic records are acceptable, provided the signatures, especially on the final approved documentation, are properly documented and included in the record. EC records must provide a reliable and authoritative record of the business of the EC that will stand up to scrutiny in the event of queries, conflict, and audit. The record should include at least the following:

Name of PI
Protocol identification number
Title of the project
Date of approval or rejection
Duration of approval period (maximum 12 months, renewable)
Conditions of approval, if applicable
Whether approval was expedited
Copy of the signed final protocol or protocol approved
Whether and how consultation occurred
Records of adverse events
Records of amendments
Reports of adverse and serious adverse events and action taken
Other relevant information such as complaints from participants

Per the SA-GCP, the EC should retain all relevant records for a period of at least three (3) years or as per institutional requirement, whichever period is longer, after completion of the trial and make them available upon request from the applicable regulatory authority.

1.2, 1.6, 5, Appendix A2.5 and A2.6

4.3 and 12

Chapter 9 (72 and 73)

Scope of Review

Last content review/update: November 2, 2026

Overview

According to the CanadaFDR, the G-CanadaCTApps, and the G-TCPS2, the primary scope of information assessed by institutional ethics committees (ECs) (called Research Ethics Boards (REBs) in Canada) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. ECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable.

See the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which CAN-50 indicates that Health Canada (HC) has adopted, for additional EC responsibilities and requirements. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Role in Clinical Trial Approval Process

As per the CanadaFDR, HC must approve a clinical trial application (CTA) and an institutional EC(s) must give ethical clearance prior to a sponsor initiating a clinical trial. In addition, as delineated in the CanadaFDR and the G-CanadaCTApps, institutional EC review for each clinical trial site may occur in parallel with HC’s CTA review and approval. Once HC completes its review, the department issues a No Objection Letter (NOL) if the CTA is approved. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval for each participating trial site is submitted. The sponsor should use the Clinical Trial Site Information Form (CAN-6) to submit the required information. The CanadaFDR also states that the EC must review and approve any protocol amendments prior to those changes being implemented.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, requires EC review and approval of research involving living human participants and human biological materials. Further, ECs must have procedures in place to receive and respond to reports of new information, including, but not limited to, safety data, unanticipated issues, and newly discovered risks.

See TCPS2-InterpReview for the Panel on Research Ethics (PRE)’s interpretations of the G-TCPS2, including on the EC’s review of secondary use of non-identifiable information, delegated review of minimal risk studies, and ongoing review.

The G-TCPS2 lays out options, procedures, and considerations for the ethics review of multi-jurisdictional research either entirely within Canada, or in Canada and other countries. An institutional EC may approve alternative review models for research with multiple ECs and/or institutions but remains responsible for the ethics and conduct of research in its jurisdiction or under its auspices regardless of where the research is conducted. The SingleECRev provides guidance on the G-TCPS2’s single EC review model for multi-jurisdictional minimal risk, which seeks to streamline the research ethics review process where additional ethics reviews are not expected to add greater participant protections. In line with a proportionate approach to research ethics review, if research is of minimal risk and spans multiple jurisdictions, institutions that have approved the use of the single EC review model authorize the review of the research by one (1) EC. See the G-TCPS2 for more information about the various review models for multi-jurisdictional research.

Per CAN-8, an attestation must be completed by the EC that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested. (See the Submission Process section for detailed submission requirements.)

G-Dcntrl indicates that for clinical trials with decentralized elements a single EC can approve activities at a clinical trial site as well as decentralized trial elements. However, sponsors and qualified investigators may need to obtain their own additional provincial or institutional approvals or permissions, or meet community-specific requirements, to use institutional resources or gain access to specific locations or populations, such as Indigenous communities.

The G-TCPS2 directs the researcher to submit an annual report to enable the EC to evaluate the continued ethical acceptability of the research. Per the G-CanadaCTApps, if an EC terminates or suspends any prior approval or favorable opinion, it must document its views in writing, clearly identifying the trial, the documents reviewed, and the date for the termination or suspension.

1.2, 1.4, 2.1, 2.5, and 2.7

Research ethics board approval

Introduction, and Chapters 1-2, 6, 8, and 11

Part C (Division 5 (C.05.001, C.05.005, C.05.006, and C.05.010))

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA’s Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

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

Review protocols to ensure that research involving human participants has scientific merit and will promote health, and prevent or cure disability and disease; in addition, ensure the research has social merit in light of South Africa’s research priorities or is otherwise justified
Ensure clinical trials are governed by the ethical principles of beneficence and non-maleficence, distributive justice (equity), and respect for persons (dignity and autonomy)
Uphold the key norms for ethical research with human participants including relevance and value; scientific integrity; stakeholder engagement; fair selection of participants; informed consent; ongoing respect for enrolled participants; and researcher competence and expertise
Grant approval for research where the protocols meet the ethical standards of the institution, agency, or establishment
Determine whether and why randomization is relevant, and how this is addressed
Evaluate the appropriateness of the inclusion/exclusion criteria and the recruitment process in the South African context
Ensure the feasibility of obtaining meaningful results with the lowest possible risk of harm for participants and whether the risk of harm is appropriately weighed against anticipated benefits for participants or the class of persons from which they are drawn; high risk of harm may be justifiable where the anticipated benefit is of high importance to increase relevant knowledge and appropriate mitigating measures are in place to minimize harm to participants; and attention must be given to harms and benefits beyond the life of the trial itself, especially in respect to early phase studies and (pharmacovigilance) surveillance for chronic and life-threatening conditions
Protect the welfare of certain classes of participants deemed to be vulnerable (See the Informed Consent topic for additional information about these populations).

Role in Clinical Trial Approval Process

Per the G-EthicsHR-ZAF, the SA-GCP, and the NHAParticipants, the principal investigator (PI) or the sponsor must submit a clinical trial application to both the South African Health Products Regulatory Authority (SAHPRA) and a registered EC for review and approval before a study may commence. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and a registered EC may be conducted in parallel. However, the G-EthicsHR-ZAF recommends that scientific review be completed prior to ethics review and, in cases where scientific review capacity is not available, the EC approval should be delayed until SAHPRA scientific approval has been provided. Further, where site permissions are required, e.g., from Provincial Health Research Committees (PHRCs) or superintendents, to conduct research in health care facilities, ECs must delay granting full approval until these permissions are received. This is to prevent research from beginning before the facility knows it will happen.

The G-EthicsHR-ZAF indicates that after the deliberative review process, the EC should approve, require amendment to, or reject a research protocol. In considering a research protocol, the EC may seek assistance from experts who have no conflicts of interest. EC decisions should be recorded in writing and appropriately documented in the minutes. A decision to approve should include the conditions (e.g., the duration of the approval, the reporting requirements, etc.). Reasons for a decision to require an amendment or to reject a research protocol should be recorded and provide sufficient feedback to the applicant. Outright rejection should be avoided if a researcher can be advised to improve the protocol. Researchers should be encouraged to address the concerns and improve their protocols. In addition, feedback should include the expected return date to minimize delays to finalize the approval process. The maximum time for a return date should not exceed six (6) months. Should the applicant exceed the stipulated return date without communication to the EC, the application should be removed from the agenda, and a new application must be submitted. ECs should require researchers to report immediately if a project is terminated or suspended before the anticipated date of completion. ECs should require researchers to report immediately anything that might warrant reconsideration of ethical approval of the protocol, including but not limited to:

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

Per the G-EthicsHR-ZAF, to prevent unnecessary duplication of work, ECs may, at their own discretion, recognize the review and approval of a research protocol granted by another registered South African EC. Reciprocal recognition means that two (2) or more registered ECs decide to recognize each other’s review. This arrangement may involve formal agreements between the ECs explaining how the workload and responsibilities are shared and the basis on which recognition occurs. Alternatively, the committee may decide to use reciprocity recognition on a case-by-case basis. ECs that recognize reciprocal review agree on the nature of the documents to be filed at each office. The expectation is that ECs should communicate with each other, through their chairpersons, and agree on a way forward regarding review of a multi-site protocol when it is desirable to avoid duplication of effort. The possibility of reciprocal recognition of reviews should occur in a collaborative, harmonious manner, bearing in mind that each EC retains the responsibility of protecting the safety, rights, and interests of participants enrolled in the studies it has approved. For more details on reciprocal review, see the G-EthicsHR-ZAF.

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

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

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

Per the G-EthicsHR-ZAF and 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 SAHPRA using the Application for Protocol Amendment to an Approved Trial (ZAF-20).

As delineated in the G-EthicsHR-ZAF, ECs have the right to monitor the research it approves. The frequency and type of monitoring should reflect the degree and extent of risk of harm to participants. Monitoring types include passive and active measures. Active monitoring requires a site visit. Passive monitoring is generally paper, using reports and other information. A site visit is expected for investigation of adverse events, serious adverse events for high-risk research, as well as other occurrences that prompt concerns for ECs. The EC should ensure that appropriate feedback is given to the PI, with an opportunity to address any identified gaps within a negotiated timeline. ECs may recommend and adopt any additional appropriate mechanism for monitoring, including random inspection of research sites, welfare monitoring sheets, data and signed consent forms, and records of interviews. ECs should ensure information and consent materials indicate that such monitoring may take place. Further, ECs should request regular, at least annual, reports from PIs. See the G-EthicsHR-ZAF for more details including the report requirements.

The G-EthicsHR-ZAF states that where circumstances indicate that a project is non-compliant with the approved protocol and the interests of participants are at risk of harm, the EC may withdraw approval, after due process has been followed. A clear process should be followed that permits swift but proper investigation and decision-making to ensure protection of participants. The investigation should include interaction with the researchers and other interested parties to ensure a fair and transparent process. If the decision is to withdraw approval, the EC should inform the PI and other interested parties, including the institutional authorities, and recommend suspension (temporary stoppage) or termination (permanent stoppage) of the project. It should also recommend remedial action where appropriate. In the case of suspension, the PI must comply with the recommendations and any special conditions imposed by the EC.

Expedited Review

Per the G-EthicsHR-ZAF, expedited review applies, in principle, only to research that poses no more than minimal risk of harm. Generally, expedited review means that no fewer than two (2) EC members review the protocol and that deliberation in the full committee meeting is foregone, unless the reviewers believe there are issues that the EC should discuss. The nature of research that may be expedited should be described in the procedures. The outcomes of the expedited review process must be reported to the full committee, at least by being noted on the agenda, so that the record is complete.

Rapid Review

As delineated in the G-EthicsHR-ZAF, the rapid review process permits rapid but thorough processing of ethics review applications in circumstances that require accelerated preparation for a research study or project, for example when there is a national or localized emergency. The EC should carefully assess the nature of the research to determine the appropriate review process, bearing in mind that not all research during a major incident is necessarily urgent. Careful ethical reflection is essential, notwithstanding any perceived urgency. All the usual ethical norms and standards must be considered. The EC should have a review standard operating procedure (SOP) that allows a combination of rapid but thorough review and reciprocal recognition of review (see above) by other registered ECs. The SOP might stipulate that a small group of reviewers (3-5 persons) with appropriate expertise reviews the protocol. The deliberations and outcome of the process must be documented in minutes and reported to the full EC at its next meeting.

Joint Review

The G-EthicsHR-ZAF allows joint reviews wherein two (2) or more ECs review a multi-site research protocol together. The sites may be within South Africa or may include sites elsewhere on the African continent. A joint review is not the same as a reciprocally recognized review (described above). A joint review entails members of the ECs concerned communicating virtually or face-to-face to discuss their respective reviews and queries and come to conclusions. The joint review process permits efficiency of reviews, facilitation of capacity building, development of trust, and avoids unnecessary repetition of administrative work. When deliberations are completed and a decision to approve has been reached, each EC uses its own approval SOPs and processes. Joint review does not exempt any of the ECs involved from their responsibilities, including monitoring and looking after the interests of participants at their sites. The PIs concerned are responsible for informing their institutional EC of the fact of multi-site research, as well as the names of the other ECs with jurisdiction over other research sites. This information enables the chairs of the ECs to arrange a joint meeting of the ECs involved to review, deliberate on, and approve the protocol concerned simultaneously. Joint reviews involving South African and other African ECs can be used in a similar manner to facilitate the ethics review and approval processes. A memorandum of understanding is recommended between the ECs involved that outlines the process, the expectations, and the responsibilities.

Foreign Research Collaboration

The G-EthicsHR-ZAF indicates that where international research (multi-country studies) is conducted exclusively online or the online platform is used to recruit study participants, and the PI neither lives or works in South Africa, an exemption from ethics review and approval is possible. This is on the proviso that the PI can demonstrate to a local registered EC that permission has been obtained from the website owners and that a notice of research intent is posted on the relevant website. In addition, the PI must comply with the privacy policies and terms of website use, and with personal data protection requirements in the POPIA. (See the Personal Data Protection section for more information).

Artificial Intelligence

Per G-EthicsHR-ZAF, ECs must consider the following ethical considerations when reviewing protocols that involve the use of artificial intelligence (AI):

Transparency
Extent and communication of researchers’ interpretation of AI models
Responsibility and accountability of the researchers
Equity and fairness
Benefit sharing
Safety risks and attack vulnerabilities
Safety prioritization and risk mitigation strategies

See the G-EthicsHR-ZAF for detailed guidance on the above AI considerations.

3 (Part 4)

3.1 and Appendix

2.1-2.3, 3, 5.5, and 6.5

1.2, 2.1, 2.6, 4.3, and 9.2

Chapter 9, Sections 72 and 73

3

Ethics Committee Fees

Last content review/update: November 2, 2026

Institutional ethics committees (ECs) may independently decide whether to charge fees to conduct protocol reviews. For example, an institutional EC may require industry sponsors or other for-profit organizations to pay a fee. See specific examples of institutional fee requirements in CAN-3 and CAN-1.

REB Review Fees

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

As indicated in the G-EthicsHR-ZAF, ethics committees (ECs) may independently decide whether to charge fees for a protocol review for external researchers. Researchers without an affiliation to an institution or organization with an EC should approach a registered EC to request it to review their health research protocols. If the EC is willing to review external applications, a fee for service may be levied.

5.2 and 5.5

Oversight of Ethics Committees

Last content review/update: November 2, 2026

There are no applicable regulations or guidance regarding the registration, auditing, and accreditation of institutional ethics committees (ECs).

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

As stipulated in the NHA, ethics committees (ECs) in South Africa are governed by the National Health Research Ethics Council (NHREC), which is a statutory body established under the NHA. NHREC determines guidelines for the functioning of ECs and registers and audits ECs, among other functions. The NHREC was created by the Minister of Health to provide ethical oversight of clinical research and to safeguard the rights and welfare of human participants involved in clinical studies. According to ZAF-52, NHREC gives direction on ethical issues relating to health and develops guidelines for the conduct of research involving humans and animals. Further, NHREC oversees and supports ECs across the country, ensures that health research involving human participants upholds the highest ethical standards, and promotes alignment with international best practices through global collaboration.

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

Determine guidelines for the functioning of ECs
Register and audit ECs
Set norms and standards for conducting research on humans including clinical trials
Adjudicate complaints about the functioning of ECs
Refer professional misconduct to the relevant statutory councils
Recommend disciplinary action for violations of ethical research standards
Advise the national department and provincial departments on any ethical issues concerning research

Registration, Auditing, and Accreditation

As delineated in the NHA, the G-EthicsHR-ZAF, and the SA-GCP, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study. As indicated in the ECRegstrn, applications from ECs whose scope does not align with the mandate of the NHREC, as defined by the NHA, will not be accepted. The application form requires a clear description of the types of health or health-related research the EC reviews, or will review and monitor. The submission must demonstrate how these activities fall within the mandate of the NHREC. Only applications that clearly align with the NHA and the NHREC's scope will be considered for registration.

Registration information is available on the NHREC webpage (ZAF-12), and a list of ECs currently registered with NHREC is available at ZAF-13. The application to register an EC is at ZAF-53. ZAF-54 states that the EC registration is recorded and publicly listed by the NHREC.

Per the G-EthicsHR-ZAF, the criteria for the NHREC registration assessment and the eligibility audit for ECs are based on the G-EthicsHR-ZAF and other internationally recognized guidelines. ZAF-12 indicates that ECs must comply with the NHA and the G-EthicsHR-ZAF to be eligible for NHREC registration. As required in the G-EthicsHR-ZAF, members of the NHREC undertake the assessment and auditing to ensure that ECs comply with capacity and operational requirements. After the first pre-registration audit, guidance and recommendations for improvement are provided with specific timelines for improvements. Before the registration is completed and a registration number is issued, NHREC conducts a follow-up audit to ensure that required revisions have been completed. Voluntary deregistration can occur when an EC is no longer active and closes. Per ZAF-12, once approved, the EC is formally recognized as a NHREC-registered research EC. To maintain registration, RECs must submit annual reports (ZAF-54), implement any required improvements, and respond to audit outcomes.

The G-EthicsHR-ZAF states that the NHREC conducts a comprehensive quality assurance assessment and administrative audit of ECs on a five (5)-year cycle to check compliance with the various administrative and record-keeping standards. When an EC persistently fails to comply with expected standards, the NHREC must enforce the standards, e.g., to suspend operations until compliance is achieved or, in extreme cases, to revoke registration of the committee. If an EC is suspended, the NHREC informs the EC of the suspended registration status and outlines the steps to be taken to rectify matters so that a registered status may be reinstated. Capacity evaluation and enhancement for ECs is also an important function of the NHREC. During the period of suspension, the EC concerned may not review new protocols for health research and may not permit another registered EC to review on their behalf. Instead, they should refer applicants to another registered EC. An assessment of the implications for harm to participants will determine whether ongoing monitoring of approved studies is acceptable to the NHREC. Failure by the EC to respond to the required measures to reverse the status of suspended registration can lead to registration being revoked. In this case, a new application for registration is required.

Use of Information

1.2 and 6.4

4.1 and 12.0 (National Health Research Ethics Council)

Chapter 9 (72 and 73)

Submission Process

Last content review/update: November 2, 2026

Overview

In accordance with the CanadaFDR and the G-CanadaCTApps, Canada requires the sponsor to obtain clinical trial authorization from Health Canada (HC) prior to initiating the trial. The sponsor must file a clinical trial application (CTA) to the appropriate Directorate within HC’s Health Products and Food Branch (HPFB). In addition, as delineated in the CanadaFDR and the G-CanadaCTApps, the sponsor may submit a CTA for clinical trial authorization to the HC in parallel with its submission to an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) for a favorable ethical opinion. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form (CAN-6)) for each participating trial site is submitted. See CAN-30 for instructions on filling out and submitting CAN-6.

CAN-19 provides a full list of HC’s forms for drug-related applications and submissions. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Regulatory Submission

Per the G-CanadaCTApps, CTAs (CAN-4) should be sent directly to the appropriate HPFB Directorate for review—the Pharmaceutical Drugs Directorate (PDD) for pharmaceutical drugs or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) for biological drugs and radiopharmaceuticals.

The G-MDSA and the G-CanadaCTApps indicate that sponsors may request a pre-submission/application meeting with the appropriate directorate within HC if they have any questions or concerns prior to filing a CTA. Additional details on requesting a meeting and meeting procedures are available in the aforementioned guidance documents. According to CAN-4, the submission can be in French or English. For CTAs that use pharmacometric approaches, sponsors should consider the policy statements in G-Pharmacometrics. Pharmacometrics is the science of using quantitative analysis and modelling and simulation approaches to inform and enhance drug development and regulatory review. In addition, see the G-CTACell for guidance on preparing CTAs for use of cell therapy products in humans.

Per the CanadaFDR, an application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial must be submitted to HC, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer. The sponsor’s clinical trial attestation must be submitted with the application (CAN-4). For guidance on completing CAN-4, see the G-DrugApp.

Electronic Common Technical Document (eCTD) Electronic Submission

As indicated in the G-eCTD, clinical trial applications in electronic common technical document (eCTD) format are recommended, not mandatory. However, once a sponsor files a regulatory activity in eCTD format, all additional information and subsequent regulatory activities for the same dossier must be filed in eCTD format. CAN-36 explains that prior to filing the first regulatory transaction for a dossier in eCTD format, the sponsor must request a dossier ID using the online dossier ID request. Per the ElecSubms, CAN-20 is the request form for biological clinical trial dossiers and CAN-21 is for pharmaceutical clinical trial dossiers. A request for a dossier ID should be sent a maximum of eight (8) weeks prior to submitting the CTA. In addition, applicants should review the Rules-eCTD for validation rules before submission. (Note: As per ElecSubms, G-eCTD and CAN-36 are only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'Request for eCTD Guidance Document' is in the subject line of the email.)

Per the G-eCTD and CAN-28, all regulatory transactions in eCTD format must be sent via the Common Electronic Submissions Gateway (CESG) (CAN-25), except for those exceeding 10 gigabytes (GB) in size. The CESG allows users to submit secure regulatory transactions electronically to HC, including CTAs. The G-eCTD and CAN-36 describe how to file CTAs and other clinical trial regulatory transactions (e.g., CTA amendments, responses to requests for information, and other in-scope activities) in eCTD format to CESG. The G-eCTD clarifies that prior to using the CESG for sending transactions, sponsors must register as a trading partner. To access and use CESG, CAN-34 instructs sponsors to follow these steps:

Register as a trading partner with the U.S. Food & Drug Administration (FDA) at the FDA Electronic Submissions Gateway Next Generation (ESG NextGen) (CAN-51) to be able to send a regulatory transaction (Note: CAN-54 indicates that the new version of the platform, ESG NextGen, continues to support HC submissions.)
Send regulatory transactions to HC by selecting “HC” as the center on the FDA ESG system; CTAs intended for HC will be automatically redirected.

For detailed information on how to become a trading partner and send regulatory transactions, refer to CAN-54, CAN-51, and CAN-25.

As indicated in the G-eCTD, the following media formats are acceptable for eCTD transactions greater than 10 GB: Universal Serial Bus (USB) 2.0 or 3.0 drive; or portable external hard drive with USB 2.0 or 3.0 interfaces. (Contact HC at hc.ereview.sc@canada.ca for other media formats that may be acceptable at the time of filing.) A paper copy of the cover letter must accompany the media (unless otherwise indicated), and a pre-paid envelope must be provided if the media is to be returned. The complete regulatory transaction must be provided on a single drive, and the label on the drive should contain the following information:

Stakeholder Name
Brand Name
Dossier ID, which is based on the protocol number
Sequence (regulatory transaction) number

Media must be mailed to HC at the address below:

Health Canada
Finance Building
101 Tunney’s Pasture Driveway
Address Locator: 0201A1
Ottawa, Ontario
K1A 0K9

See the G-eCTD, CAN-54, CAN-34, CAN-36, CAN-25, and CAN-28 for details on registering as a trading partner for CESG transactions, how to use CESG, and submitting CTAs in eCTD format.

Non-eCTD Electronic Submission

For non-eCTD electronic submissions, G-Non-eCTD indicates that the CTA (CAN-4) must be provided in PDF format. Other files submitted should be in PDF format, unless otherwise specified in G-Non-eCTD. PDF documents should be generated from electronic source documents and not from scanned materials, except where access to an electronic source document is unavailable or where a signature is required. Documents that are more than 10 pages should be bookmarked. Sections, subsections, tables, figures, and appendices should be bookmarked, with no more than four (4) levels of bookmarks. Hyperlinks within the same PDF document are acceptable, but hyperlinks between different documents must not be used. Stakeholders are responsible for ensuring that hyperlinks function, and links must also include references to the applicable section or page. Documents that legally require signatures may be signed electronically, or the signature page may be printed, signed, scanned, and saved as a PDF. If only one (1) page of a multi-page document contains a signature, the scanned page should be included in the same location in the PDF. Each document should have only one (1) PDF file. The cover letter does not require a signature but should include the printed name, phone number, and email address of the contact person.

As explained in G-Non-eCTD, all regulatory transactions should be validated before being transmitted to HC. For the applicable requirements, including validation rules, see the Rules-Non-eCTD. Initial CTAs and CTA-As should be submitted on electronic media, accompanied by a paper copy of the cover letter, and sent directly to the Office of Clinical Trials within PDD for pharmaceuticals or the Office of Regulatory Affairs within BRDD for biologics and radiopharmaceuticals. The ElecSubms contains a zip file of the folder structure for clinical trial non-eCTD submissions. (Note: As per ElecSubms, G-Non-eCTD is only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'non eCTD Guidance Document' is in the subject line of the email.)

Per the G-Non-eCTD, CTA submissions to the appropriate Directorate within HC’s HPFB must be in one (1) of these accepted media formats:

Compact Disc-Recordable (CD-R) conforming to the Joliet specification
USB 2.0 or 3.0 drive
Digital Versatile Disc (DVD-RAM and DVD+R/-R) in Universal Disk Format (UDF) standard

All media should be labelled and contain the following information:

Stakeholder Name
Brand Name

Subsequent to burning the CD/DVD or transferring data to a drive, applicants should ensure that all files can be opened, files are not corrupted, and that "Thumb.db" files are removed.

As per the G-Non-eCTD, G-MDSA, CAN-18, and CAN-17, non-eCTD CTAs involving pharmaceutical drugs should be sent to PDD, and CTAs involving biologics and/or radiopharmaceuticals should be sent to BRDD at the addresses listed below (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Office of Clinical Trials
Pharmaceutical Drugs Directorate
Health Canada
5th Floor, Holland Cross, Tower B
1600 Scott Street
Address Locator: 3105A
Ottawa, Ontario, Canada
K1A 0K9
General Inquiries E-mail: oct.enquiries-requetes.bec@hc-sc.gc.ca

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate
Health Products and Food Branch
Ground Floor, Health Canada Building 6
100 Eglantine Driveway
Tunney’s Pasture
Address Locator: 0601C
Ottawa, Ontario, Canada
K1A 0K9

Telephone: 613-957-1722
E-mail: brdd.ora@hc-sc.gc.ca

Per the G-Non-eCTD, if an applicant submits a non-eCTD CTA via email, they should meet the following requirements:

The maximum email size accepted by the corporate mail server is 20 megabytes. If the clinical trial submission is larger than 20 megabytes, the submission may be split and sent as separate emails (e.g., an email for Module 1, and another email for Module 2/3). The subject line of the emails should clearly link to each other (e.g., "Email 1 of 2" in the relevant subject line)
A duplicate copy must not be provided by mail
The submission should be organized in folders and the body of the email should only contain the zipped regulatory submission
Zipped files and documents contained in the email should not be password protected

The G-Non-eCTD provides additional information on emailing other clinical trial submissions, including responses to a clarification request, responses to a no objection letter, notifications, and development safety update reports.

Ethics Review Submission

As indicated in the CanadaFDR and the G-CanadaCTApps, all research involving human participants in Canada must be reviewed by an institutional ethics committee (EC). (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements. Further, Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information. CAN-35 delineates submission requirements to the joint HC-Public Health Agency of Canada (PHAC)’s EC. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers on the premises or in collaboration with external researchers.

Guidance documents, notices, and supporting documents

1.2, 2.2, 2.3, and 2.7

2.3 and 9

3.1-3.4 and Appendix B

1.3 (Table 1), 3.2, and 5

Part C (Division 5 (C.05.002, C.05.004, C.05.005))

Research Ethics Board (Apply for Ethics Review)

Submissions (Does ESG NextGen support Health Canada)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026) 
SAHPRA’s Communication to Stakeholders: SAHPRA Clinical Trials Online Applications Platform (April 16, 2026)

Overview

As delineated in the SA-GCP, the sponsor and the investigator must obtain approval from the South African Health Products Regulatory Authority (SAHPRA) and a registered ethics committee (EC) to begin a clinical trial in South Africa. Per ZAF-23, the review and approval of clinical trial applications by SAHPRA and an accredited EC may be conducted in parallel. As indicated in ZAF-20, the same process applies to the review and approval of an amendment to the protocol. However, note that the G-EthicsHR-ZAF recommends that scientific review be completed prior to ethics review and, in cases where scientific review capacity is not available, the EC approval should be delayed until SAHPRA scientific approval has been provided.

Regulatory Submission

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

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

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

Per the ZAF-40, during a public health emergency, applicants should use the modified clinical trial application form in ZAF-40. This form recognizes the constraints on the availability of information posed by the emergency. SAHPRA may accept clinical trial applications with reduced information together with a commitment to update and complete the required information as soon as possible. However, all documents submitted must be organized with zipped folders according to the checklist in ZAF-40 and correctly labelled to ensure easy validation by SAHPRA (See the Submission Content and Emergencies sections for more details).

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

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

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

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

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

Ethics Review Submission

Each EC has its own required submission procedures, which can differ significantly regarding the number of copies to be supplied and application format requirements. Refer to each EC’s website for specific submission procedures.

3-7

Where Do I Submit a New Clinical Trials Application?, How Do I Make Sure My Hard Copy Application Gets to the Right Place?, and What Should an Acceptable Proof of Delivery Look Like?

3.1

2.6 and 6.2

Application for the Registration of a Medicine – Part 16 (4)

Submission Content

Last content review/update: November 2, 2026

Regulatory Authority Requirements

As set forth in the CanadaFDR and the G-CanadaCTApps, Health Canada (HC) requires the sponsor to apply for clinical trial authorization by submitting a clinical trial application (CTA) to HC. As specified in the G-CanadaCTApps and the G-QCM-PharmCTAs, the CTA should be organized into three (3) modules in Common Technical Document (CTD) format:

Module 1 - Administrative and clinical information about the proposed trial
Module 2 - Quality (Chemistry and Manufacturing) summaries about the drug product(s) to be used in the proposed trial
Module 3 - Additional supporting quality information

Per the CanadaFDR, the clinical trial application form (CAN-4) and the following information and documents must be submitted:

Protocol
Summary of potential risks/benefits
Clinical trial attestation that includes drug information (chemistry, names, classifications, dosage, therapeutic purpose, human-sourced excipient, drug identification number or notice of compliance, manufacturing information); sponsor’s contact information; if the drug is to be imported, contact information for the sponsor’s representative in Canada who is responsible for the sale of the drug; and contact information for the qualified investigator at each site, if known at the time of submittal
Contact information for each institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) that approved the protocol, if known at the time of submitting the application (provided in the required Clinical Trial Site Information (CTSI) form (CAN-6))
Contact information of any institutional EC that previously refused to approve the protocol, its reasons, and refusal date
Investigator’s Brochure (IB)
Informed consent form (ICF)
Information about use of a human-sourced excipient
Chemistry and manufacturing information
Proposed date for trial commencement at each site, if known

Per the Mdrn-CTFrmwrk, for multi-site trials operating within a streamlined multi-site ethics review process, sponsors sometimes identify the same EC for all clinical trial sites. When providing information on a new site through CAN-6, sponsors only need to include the contact information for an EC once, as long as:

The same EC has previously been identified as having approved other sites in that trial
The EC's contact information has already been provided to HC in the context of the clinical trial, and continues to be up to date

Accordingly, as indicated in the Mdrn-CTFrmwrk, the form's section on EC approval may only contain the name of the approving board and the date of its approval.

Refer to the CanadaFDR, the G-FDR-0100, the G-CanadaCTApps, the G-DrugApp, the G-QltyBioCTs, and the G-QCM-PharmCTAs for detailed submission information.

Ethics Committee Requirements

Each institutional 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.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, requires clinical trial researchers to submit their research proposals for EC review and approval of their ethical acceptability prior to the start of recruitment of participants, data collection, access to data or collection of human biological materials. Researchers must submit sufficient details to enable the EC to make an informed review of the ethical acceptability of the research. In addition, they should include a plan for monitoring safety, efficacy/effectiveness (where feasible), and validity in their proposal for EC review. This plan must describe:

How participant safety will be monitored and what actions will be taken in the event of a threat to participant safety
How intervention efficacy will be monitored (where feasible) and what actions will be taken if efficacy is found to be greater than expected
The criteria by which participants may be removed from a study for safety reasons
The study-wide stopping rules (if any) by which studies may be stopped or amended due to evidence of inferior safety, superior efficacy or futility
The reporting procedure that will be followed to ensure any information relevant to participant welfare or consent is reported clearly and in a timely fashion to the EC

See CAN-35 for submission requirements to the joint HC-Public Health Agency of Canada (PHAC)'s REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.

Clinical Protocol

The CanadaFDR requires submission of a clinical trial protocol. Per G-FDR-0100, a protocol should describe the objectives, design, methodology, statistical considerations and organization of a clinical trial, and it should be consistent with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52). The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. CAN-50 indicates that HC adopted CAN-52.

2.3 and 2.7

Introduction, Application and Authorization, and Appendix A (Glossary)

I Introduction, S Drug Substance, and P Drug Product

Chapter 6 (Article 6.11) Chapter 11 (Article 11.6)

1

Part C (Division 5 (C.05.001, C.05.004, and C.05.005))

Apply for Ethics Review

Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA’s Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Regulatory Authority Requirements

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

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

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

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

Per the ZAF-40, SAHPRA states that during a public health emergency, new and experimental treatments may become necessary and clinical trials are essential to provide the evidence to develop appropriate policies for patient treatments. Under these circumstances, there may be limited information available. However, applications need to contain a certain minimum of information to enable a meaningful evaluation and regulatory decisions. To address this, SAHPRA provides an information grading system in the ZAF-40 wherein required information is labelled. Applicants must attempt to provide the information listed below and justify when this is not available. The required information is graded as follows:

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

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

Ethics Committee Requirements

Per the G-EthicsHR-ZAF, each EC has its own application form and clearance requirements that can differ, but ECs must ensure that the submission content includes the following:

A description of the essential ethical elements: an explanation of the proposed research in plain language, information about potential participants (age range, vulnerabilities, etc.), and ethical implications of the research
Indication of whether it is a sub-study or parent study; each sub-study must be reviewed
Adequate consideration of participants’ welfare, rights, beliefs, perceptions, customs, and cultural heritage
All documents and other material to be used to inform potential participants, such as information sheets, consent forms, questionnaires, advertisements, videos, dramatizations, and letters
A description of the readability level to ensure that plain language is adapted to the anticipated literacy levels in the participant documentation
Evidence of community engagement and plans for ongoing consultation, as appropriate
Plans to implement benefit sharing, as appropriate to the context
Monitoring schedules, the responsible persons, and their contact numbers
Disclosure of any researcher conflicts of interest, financial interests, or information that may result in perceptions of conflict of interest
A data management plan (See the Personal Data Protection section for more details)

See ZAF-22 and ZAF-49 for example EC applications, which share some or all of following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

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

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

Clinical Protocol

Per the G-EthicsHR-ZAF, it is strongly recommended that a report on the scientific review should accompany the protocol in the EC application. If a separate scientific review capacity is not available, the EC must ensure that the science is satisfactorily explained in the protocol. As delineated in the G-EthicsHR-ZAF, the SA-GCP, and ZAF-23 the clinical protocol should contain the following information (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

General information
Background information
Study rationale and motivation
Trial objectives, purpose, and endpoints (with justifications)
Scientific design and methodology
IP information
Participant eligibility, selection, and withdrawal; inclusion and exclusion criteria
Selection of study population and sampling
Community and stakeholder engagement
Recruitment and enrollment
Risk/benefit analysis
Reimbursements and inducements for participants
Informed consent
Participant treatment
Participants’ interests in privacy and confidentiality
Efficacy assessment
Safety assessment
Statistics
Direct access to source data/documents
Research procedures and quality control/quality assurance
Data and safety monitoring plan
Data handling/recordkeeping
Statistical measures
Financing/insurance
How data records (written, audio, or visual) are to be secured, the length of time for which they will be retained, and who will be responsible for storage and/or final disposal
An explanation on why particular identifying information is required for the study that purports to collect data anonymously
Measures in place to assess whether notifiable activities might occur amongst participants, e.g., abuse of minors or notifiable diseases

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

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

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

Submission Documents

3.1 and 5.5

2.6, 6.2, 7.1-7.16

Cover page, 3, and Annexure A

Timeline of Review

Last content review/update: November 2, 2026

Overview

As delineated in the CanadaFDR and the G-CanadaCTApps, the review and approval of a clinical trial application (CTA) by Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) may be conducted in parallel. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form) for each participating trial site is submitted. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Regulatory Authority Approval

According to the CanadaFDR and the G-CanadaCTApps, an authorized clinical trial is one that has been filed with HC and has not received an objection within 30 days. All CTAs are subject to the 30-day default period from the date of receipt of the completed application at the appropriate Directorate within HC’s Health Products and Food Branch (HPFB). While the Directorates can establish shorter administrative targets of seven (7) days for the review of bioequivalence trials, the 30-day default system remains the regulatory requirement. Applications to conduct Phase I clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines, or reproductive and genetic technologies are not included in the seven-day target system. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals.

As specified in the G-CanadaCTApps and the G-MDSA, during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. The G-MDSA clarifies that, where warranted, HC can adjust the timelines to be longer or shorter based on the complexity of the request, communications with the sponsor, and/or circumstances of the review, including pausing the clock during the scientific review. The G-CanadaCTApps also states that HC will issue a Not Satisfactory Notice (NSN) if a timely response to requested information has not been provided. The G-MDSA indicates that the review of the submission will stop on the date the NSN is sent.

Ethics Committee Approval

The EC review and approval process timeline varies by institution. The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, recommends a proportionate approach to ethics review—the lower the level of risk, the lower the level of scrutiny (delegated review); the higher the level of risk, the higher the level of scrutiny (full board review). In either case, pursuant to the G-TCPS2, the institutional EC should make its decisions in an efficient and timely manner.

See CAN-35 for ethics review timelines with the joint HC-Public Health Agency of Canada (PHAC)'s EC. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.

2.1, 2.3.3, 2.5, and 2.7

4.1.3, 4.2 and 4.4

Chapter 2 (Articles 2.8 and 2.9) and Chapter 6 (Article 6.13)

Part C (Division 5 (C.05.005 and C.05.006))

Apply for Ethics Review

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

Based on ZAF-23 and the SA-GCP, 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. However, note that the G-EthicsHR-ZAF recommends that scientific review be completed prior to ethics review and, in cases where scientific review capacity is not available, the EC approval should be delayed until SAHPRA scientific approval has been provided. Also, where site permissions are required, e.g., from Provincial Health Research Committees (PHRCs) or superintendents, to conduct research in health care facilities, ECs must delay granting full approval until these permissions are received to prevent research from beginning before the facility knows it will happen.

Regulatory Authority Approval

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

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

Next, the CTC reviews the proposed clinical trials. CTCDates provides the dates of the 2026 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 SAHPRA. ZAF-1 states that applicants receive a response within 10 working days from the CTC meeting, and they must send an answer within seven (7) working days after receipt of comments. If an applicant would like to request a meeting with the CTC, the request should be submitted through the SAHPRA Chief Executive Office pursuant to the procedures in the G-ConsultMtg.

Ethics Committee Approval

Review timelines vary per each EC’s procedures. The G-EthicsHR-ZAF states that ECs must define the review timelines in their standard operating procedures.

How Will I Know If My Application has been Received and Reviewed?, What is the Timeline for Receipt of Screening Checklist?, What is the Timeline for Response of Screening Checklist?, What is the Expected Timeline for Response from Clinical Trial Committee Review?, and What is the Timeline for Submitting Responses from Expert Committee Review?

3.1 and 5.5

4.4

Initiation, Agreements & Registration

Last content review/update: November 2, 2026

Overview

In accordance with the CanadaFDR and the G-CanadaCTApps, a clinical trial can only commence after the sponsor receives authorization from both Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada). No waiting period is required following the applicant’s receipt of these approvals. CAN-30 specifies that for purposes of the Clinical Trial Site Information (CTSI) Form (CAN-6), the trial commencement date is the date when the clinical trial site is ready to enroll participants. The commencement date is a date after which the sponsor has both the HC authorization from the appropriate Directorate (date on the No Objection Letter (NOL) or the date of the Notice of Authorization) and approval from the relevant EC. Further, the commencement date would be the date when the sponsor implements the protocol, which includes the screening period that occurs prior to the check-in date. See the Scope of Review section for detailed institutional EC requirements, and the Submission Content section for additional HC approval information. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

In addition, per the G-CanadaCTApps, if a sponsor (Canadian or foreign) wants to import a drug into Canada to conduct a clinical trial, a copy of HC’s clinical trial authorization (i.e., the NOL) must be included with the drug shipment. According to the G-CanadaCTApps and CAN-32, if a sponsor plans to import investigational drugs directly to each trial site, then the sponsor must also authorize the importer (i.e., the clinical trial site) when submitting the clinical trial application using Appendix I of HC’s Drug Submission Application Form (CAN-4). See the Manufacturing & Import section for detailed import requirements.

Clinical Trial Agreement

Prior to initiating trial activities, as delineated in the G-FDR-0100, agreements made by the sponsor with the qualified investigator, institution, service providers, and any other parties (e.g., independent data monitoring committee or adjudication committee) involved with the clinical trial should be documented. The sponsor is also responsible for obtaining agreements from all involved parties to permit monitoring and auditing by sponsors, inspections by regulatory authorities (domestic and foreign) and review by ECs, including providing direct access to source records and facilities, including those of service providers. Any of the sponsor's trial-related activities that are transferred to and assumed by a service provider should be documented in an agreement. The sponsor's trial-related activities that are not specifically transferred to and assumed by a service provider are retained by the sponsor.

In accordance with the G-CanadaCTApps, prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form (CAN-37 or similar documentation that meets the CanadaFDR requirements) has been completed and is kept on file by the sponsor. Per the CanadaFDR, the form certifies that the QI will conduct the clinical trial in accordance with good clinical practice and will immediately inform trial participants and the institutional EC of trial discontinuance and the reason for this discontinuance. If there is a change in the QI at a site, a new CTSI Form must be submitted to HC, and a new QIU form must be maintained by the sponsor.

G-Dcntrl indicates that sponsors and QIs are responsible for ensuring that all agreements supporting decentralized trial activities clearly define roles, responsibilities, and oversight expectations. Trial-related activities delegated to service providers should be documented in written agreements that establish how tasks will be performed, supervised, and documented; investigational products and data will be managed; and compliance with regulations and good clinical practice will be maintained.

See CAN-6, CAN-8, and CAN-19 for additional clinical trial forms. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Clinical Trial Registration

As per the CT-Rgstrn, sponsors should register their clinical trial before it has opened for enrollment in Canada but no later than 21 calendar days after the date of enrollment of the first participant. HC considers the registration date as the date when the clinical trial registration materials are first submitted to a registry. For a multi-national clinical trial with one (1) or more Canadian sites, sponsors should add the Canadian site(s) to their existing registry record. Ideally, this should be done before opening for enrollment, but no later than 21 calendar days after the date of enrollment of the first participant at the Canadian site(s). Sponsors should register their clinical trial with an international clinical trial registry that complies with World Health Organization (WHO) international standards, including the International Clinical Trials Registry Platform (ICTRP) (CAN-60). Two (2) widely used registries that are publicly accessible and part of the WHO network are ClinicalTrials.gov (CAN-45), and the International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (CAN-46). Sponsors should include the protocol code/number in their registry record.

Also see HC’s Clinical Trial Search Portal (CAN-59), which is a search tool to find information about Canadian clinical trials. It is not a registry, but some of the information is collected directly from international registries.

Registration and Resources

1.2 and 2.7

Agreements

5.6

Part C (Division 5 (C.05.006))

Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

In accordance with the GRMRSA, the SA-GCP, the G-EthicsHR-ZAF, and the NHAParticipants, a clinical trial can only commence in South Africa once an applicant receives approval from the South African Health Products Regulatory Authority (SAHPRA) and from a registered ethics committee (EC). There is no waiting period required following the applicant’s receipt of these approvals. Note that the G-EthicsHR-ZAF recommends that scientific review be completed prior to ethics review and, in cases where scientific review capacity is not available, the EC approval should be delayed until SAHPRA scientific approval has been provided. Also, where site permissions are required, e.g., from Provincial Health Research Committees (PHRCs) or superintendents, to conduct research in health care facilities, ECs must delay granting full approval until these permissions are received to prevent research from beginning before the facility knows it will happen.

The trial must be conducted in compliance with the SA-GCP, the G-EthicsHR-ZAF, and the GRMRSA. Also, per the SA-GCP, all clinical trials must be conducted in a laboratory complying with Good Laboratory Practice (GLP). See ZAF-2 for the World Health Organization (WHO)’s handbook on GLP.

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

Clinical Trial Agreement

According to the SA-GCP, all parties involved in the conduct of a trial should be familiar with guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27) and other international guidelines. All clinical trials should be conducted in accordance with all ethical principles outlined in the Declaration of Helsinki (ZAF-44). Before the trial begins, a sponsor must prepare a written agreement. The agreement must be signed by the sponsor and the PI, and any other parties involved (e.g., institutions and contract research organizations) with the trial to confirm the contract terms. Both the sponsor and the PI must commit to providing safety information between each other. The sponsor should also obtain the investigator's agreement to:

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

In addition, per the SA-GCP, the financial aspects of the trial should be documented in the agreement. A declaration must be signed by the sponsor and PI stating that sufficient funds are available to complete the study. The sponsor is also responsible for securing agreements to ensure direct access to all trial-related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.

Clinical Trial Registration

According to the SA-GCP, NHAParticipants, and ZAF-32, the PI or the sponsor must enter the trial information in the South African National Clinical Trials Register (SANCTR) (ZAF-48). The G-EthicsHR-ZAF states that solely the sponsor must register all South Africa-based trials on SANCTR, and if the trial has no commercial sponsor, the PI must register the trial. According to the SA-GCP, the National Department of Health (NDOH) then issues a unique SANCTR National Register Number. ZAF-32 has instructions for registering either online or via email.

Governance

The G-EthicsHR-ZAF explains that research, especially that using state or provincial facilities and resources, should link to health care system priorities, and findings should be integrated into policy planning and management of health programs. PHRCs were established to liaise with researchers to ensure that the greatest health needs of each province are being addressed. As such, they perform a gate-keeping role by managing access to health facilities. While they accept ethics approval granted by a registered EC, they need to consider applications to use their facilities to manage potential interference with or interruption of services. It is thus important that PIs respect this role of the PHRCs. Some provinces have also registered provincial ECs, and these committees are important in areas of the country where other ECs are not active.

Part 2 (General Objectives and Requirements of Pharmaceutical Services)

3.1, 5.3, and 6.5

1.2, 2.1, 2.6, 4.4, 6.1-6.2, 6.4, 6.9, 7.11, and 9.2

Part 30 (2)

3

Safety Reporting

Last content review/update: November 2, 2026

Safety Reporting Definitions

According to the CanadaFDR and G-CanadaCTApps, the following definitions provide a basis for a common understanding of Canada’s safety reporting requirements:

Adverse Event (AE) – Any adverse occurrence in the health of a clinical trial participant who is administered a drug that may or may not be caused by the administration of the drug, and includes an adverse drug reaction.
Adverse Drug Reaction (ADR) – Any noxious and unintended response to a drug that is caused by the administration of any dose of the drug.
Serious Adverse Drug Reaction (SADR) or Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or causes a congenital anomaly/birth defect.
Serious, Unexpected ADR – A serious ADR that is not identified in nature, severity, or frequency in the risk information set out in the investigator’s brochure or on the label of the drug.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), requires researchers to promptly report new information revealed during the conduct of the trial that might affect the welfare or consent of participants to the EC, to a publicly accessible registry, and to other appropriate regulatory or advisory bodies. In addition, when new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers must work with their ECs to determine which participants must be informed, and how the information should be conveyed.

For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Safety Reporting Requirements

Investigator Responsibilities

Per the G-FDR-0100, the collection, assessment, and reporting of AEs is a critical component of the conduct of any clinical trial. The assessment of the site AEs should be done by the qualified investigator (QI) or the delegated sub-investigator(s) for seriousness, expectedness, and causality determination, when they become aware. All SAEs should be reported immediately (after the QI reasonably becomes aware of the event) to the sponsor. The QI should also include an assessment of causality. In accordance with applicable regulatory requirements, the protocol may identify SAEs not requiring immediate reporting; for example, deaths or other events that are endpoints. Subsequent information should be submitted as a follow-up report, as necessary.

Sponsor Responsibilities

As delineated in the CanadaFDR and the G-CanadaCTApps, the sponsor is required to expedite reports of ADRs to HC that meet these three (3) criteria: serious, unexpected, and having a suspected causal relationship. ADR reports that are expected or unexpected, but not serious, should not be reported to HC, but rather monitored and tracked by the sponsor. As specified in the G-CanadaCTApps, when evaluating whether an AE is serious and unexpected, the QI’s and sponsor’s determination of causality is important. Only serious and unexpected ADRs found to have a reasonable suspected causal relationship with the drug should be reported by the sponsor to HC.

Per the CanadaFDR and the G-CanadaCTApps, during a clinical trial, the sponsor is required to inform HC of any serious, unexpected ADR that has occurred inside or outside Canada. An ADR report must be filed in the following specified timelines:

When the ADR is neither fatal nor life-threatening, within 15 days after becoming aware of the information
When it is fatal or life-threatening, immediately when possible and, in any event, within seven (7) days after becoming aware of the information
Within eight (8) days after having informed HC of the ADR, submit a report that includes an assessment of the importance and implication of any findings

Other Safety Reports

The G-DSUR delineates that the development safety update report (DSUR) and the DSUR Checklist (CAN-38) should be provided when requested by HC. A DSUR may be submitted voluntarily to HC when important new safety information on a drug needs to be conveyed by a clinical trial sponsor. In these cases, a rationale/justification for the filing of the DSUR should be included in the cover letter. For additional details, see the G-DSUR.

The G-DSUR-CanUK describes the region-specific requirements for DSURs submitted to the regulatory authorities of Canada and the United Kingdom. This guidance applies to both marketed and non-marketed drugs that are used in clinical trials and applies to DSURs prepared by the manufacturer and/or marketing authorization holder of the investigational drug.

Form Completion & Delivery Requirements

As per the G-CanadaCTApps, all serious and unexpected ADRs should be reported individually to HC. According to CAN-48 (which Canada adopted pursuant to CAN-50), at a minimum, the report should include an identifiable patient, the name of a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. The G-CanadaCTApps requires the sponsor to complete the expedited reporting form (CAN-5) and the CIOMS Form I (CAN-7) and fax them to the appropriate HC Directorate: BRDD Fax: 613-957-0364; PDD Fax: 613-941-2121.

Additionally, the G-DSUR indicates that HC recommends that DSURs in electronic Common Technical Document (eCTD) format be submitted via the Common Electronic Submissions Gateway (CESG) (CAN-25). For information on eCTD format, refer to the ElecSubms. For technical questions on eCTD filings, contact ereview@hc-sc.gc.ca as instructed in the G-DSUR.

2.1 and 2.8

Notice, 1.2, and 2.4

Serious unexpected adverse drug reaction reporting

Chapter 11 (Article 11.8)

Part C (Division 5 (C.05.001 and C.05.014))

Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA communication noting that the E2B standard is the only acceptable method to submit SAEs to SAHPRA effective July 1, 2026
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Safety Reporting Definitions

In accordance with the SA-GCP 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)

The G-EthicsHR-ZAF defines SAE as an unforeseen harmful event related to the study (e.g., injury/death due to an experimental intervention), thereby negatively affecting the research participants and requiring an intervention.

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

Safety Reporting Requirements

Investigator Responsibilities

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

Per the G-EthicsHR-ZAF, researchers are expected to provide appropriate information to the EC to facilitate monitoring, including alerts. If an EC conducts a site visit, the evaluation should include inspecting documentation of AEs and SAEs. In addition, ECs should request regular, at least annual, reports from PIs on matters including a list of all AEs in the past 12 months.

Sponsor Responsibilities

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

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

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

The G-SafetyRpt delineates the following reporting timeframes:

The sponsor should initially report all fatal or life-threatening SAEs in local reports within seven (7) calendar days after first knowledge, using CIOMS format (ZAF-15)/SAHPRA SAE form (ZAF-19). The follow-up report should be submitted within an additional eight (8) calendar days.
All fatal or life-threatening SAEs in foreign reports should initially be reported within 30 calendar days after first knowledge by the sponsor. The follow-up report should be submitted within an additional six (6) months as part of the progress report. If the SAEs result in premature study closure, the reporting times are shorter—seven (7) days for the initial report and within an additional eight (8) days for the follow-up report. These reports should be in a line listing format. Note that these reporting requirements also cover foreign reports of “special concern,” which is a significant safety issue defined for each clinical trial that requires urgent attention from the regulatory authority. An adverse reaction of special concern from a foreign jurisdiction should be based on the decision of its regulatory authority. A safety issue leading to international regulatory action is considered to be significant at all times and hence reportable.
Local reports of other serious events (unexpected, not fatal or life threatening) within 15 calendar days of the event and every six (6) months in the CIOMS format (ZAF-15)/SAHPRA SAE form (ZAF-19).
A line listing of all local reports—serious (unexpected and expected) AEs—and any other issues of special concern outside South Africa should be submitted every six (6) months (using the progress report form in ZAF-18).
An initial detailed report of new information impacting the risk-benefit profile of the IP or conduct of trial should be submitted within three (3) calendar days; a follow-up report should be submitted within an additional six (6) months.
An initial detailed report of other major safety concerns (e.g., changes in nature, severity, or frequency of risk factors) should be submitted within 15 days of knowledge of the concern; a follow-up report should be submitted within an additional six (6) months.
DSURs should be submitted within one (1) year from approval of the study and annually thereafter.

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

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

Form Completion & Delivery Requirements

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

ctcsaes@sahpra.org.za for clinical trials (per ZAF-47, ctcsaes@sahpra.org.za should be used for individual patient SAEs and related queries)
adr@sahpra.org.za or e2b@sahpra.org.za for post-marketing studies
section21@sahpra.org.za for reporting of SAEs for medicines used under Section 21

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

ADR reports in an e2b in an xml format: e2b@sahpra.org.za
All other ADR reports: adr@sahpra.org.za
Pharmacovigilance related queries: pvqueries@sahpra.org.za
Documentation relating to identified safety concerns, responses to recommendations, and Risk Management Plans (RMPs): pvsubmissions@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

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

In addition, SAE-E2B states that SAHPRA’s Clinical Trials Unit encourages applicants to use the International Council for Harmonisation (ICH) Guideline E2B on Electronic Transmission of Individual Case Safety Reports (ICSRs) as an additional method for reporting SAEs during clinical trials. SAHPRA accepts both the E2B R2 or E2B R3 formats. See ZAF-31 for the ICH technical specifications for the R2 and R3 formats. For E2B submissions, the preferred encoding is ISO-8859-1 (with UTF-8 also acceptable), and SAHPRA is the organization identifier. In addition, applicants must attach a cover letter to the email that includes the SAHPRA reference number, medicine registration form number (if applicable), participant number, study title, protocol number, site name, investigator/reporter name, suspect study drug, AE, report type (initial or follow-up), and outcome. SAEs should be submitted by email to ctcsaes@sahpra.org.za and the subject line should include E2B, the SAHPRA database tracking number, the protocol number, and SAE (e.g., E2B_20220203_NER000_SAE). SAHPRA notes that the current SAE reporting methods using the ZAF-15 or ZAF-19 are still acceptable.

Part B

Clinical Evaluation and Management (Pharmacovigilance)

1, 2, and 6

8

4.1-4.2, 4.6-4.7, 5.2, 6.1-6.4, and 7.1-7.3

5.5 and Appendix 1 (A1.1)

5.12, 6.4, 6.9, and 12

1 and 30(7)

Progress Reporting

Last content review/update: November 2, 2026

Interim and Annual Progress Reports

Pursuant to the CanadaFDR and the G-CanadaCTApps, investigators and sponsors share responsibility for submitting interim and annual reports on the status of a clinical trial. The investigator is required to provide annual progress reports to the institutional ethics committee (EC) and submit interim progress reports to the EC and Health Canada (HC) if there are any significant changes affecting the trial or risk to participants. The sponsor is required to submit annual reports (in the form of an updated Investigator’s Brochure (IB)) to HC. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

According to the G-TCPS2, investigators must report new information that may affect the welfare or consent of participants to the institutional EC, HC, and other appropriate regulatory or advisory entities. When new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers should work with their ECs to determine which participants must be informed, and how the information should be conveyed. New information may comprise a range of issues, including, but not limited to:

Changes to the research design
Evidence of any new risks
Unanticipated issues that have possible health or safety consequences for participants
New information that decisively proves the benefits of one (1) intervention over another
New research findings, including relevant non-trial findings
Unanticipated problems
Closure of trials at other sites for reasons that may be relevant to the welfare or consent of participants in the ongoing trial

Final Report

While the CanadaFDR does not require submission of a final study report to HC, the CT-Rgstrn states that HC’s policy for reporting summary results aligns with international initiatives, including the Declaration of Helsinki (CAN-58). Sponsors should submit the summary results of their clinical trial within 12 months following primary study completion, which is the final study visit for collection of data on the primary outcome for the last participant in a global study, whether the clinical trial concluded according to the pre-specified protocol or stopped early. For clinical trials with more than one (1) primary outcome measure with different completion dates, the primary study completion is the date when data collection is completed for all primary outcome measures. In cases where submission of summary results within one (1) year of primary study completion will jeopardize the scientific integrity of the clinical trial, summary results may be submitted within one (1) year of study completion, which is the final study visit for collection of data on any remaining secondary outcome measures and adverse event information for the last participant in the global study, whether the clinical trial concluded according to the pre-specified protocol or stopped early. If a sponsor intends to apply for market authorization for the product studied or a new condition of use, the sponsor may defer submitting summary results until 30 calendar days after HC renders a decision on the application or the sponsor cancels or withdraws it, or up to 36 months following primary study completion, whichever is earlier. HC does not support deferral for products or new conditions of use that the sponsor does not intend to market or for which product development has stopped. Sponsors should submit the summary results of their clinical trial to the same registry where their trial is registered. (See Initiation, Agreements & Registration section for information on clinical trial registration.)

Per the G-CanadaCTApps, the sponsor should notify the HC Directorate when a clinical trial is completed or a clinical trial site is closed. A study is considered to be completed after the last participant globally completes the "end of study" visit as defined in the protocol. The "end of study visit" is the final visit for study-related tests and procedures, including the capture of any final potential study-related adverse events, and usually occurs after the participant has completed/discontinued study drug administration. The "end of study visit" is normally an in-person visit, but for some studies it can also be carried out over the telephone. There may be certain scenarios (e.g., gene therapies, drugs with very long half-lives) where a study may be ongoing well beyond the period of study treatment, i.e., where long-term safety monitoring and reporting would be required. The reporting requirements with regard to such long-term follow-up of safety are normally specified in the study protocol and agreed to between the sponsor and HC prior to the authorization of the clinical trial in Canada.

Reporting Results

2.8

Chapter 11 (Article 11.8)

Part C (Division 5 (C.05.012 and C.05.013))

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA’s Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Interim and Annual Progress Reports

In accordance with the GRMRSA, the person authorized by the South African Health Products Regulatory Authority (SAHPRA) to conduct a clinical trial (i.e., the sponsor) must submit progress reports to the SAHPRA every six (6) months from the application approval date. The SA-GCP requires the investigator to submit written progress reports to the ethics committee (EC) annually and to the SAHPRA every six (6) months. ECs and the SAHPRA may request reports more frequently. The G-EthicsHR-ZAF states that ECs should request regular, at least annual, reports from principal investigators (PIs) on matters including: progress; current enrollment status; whether participant follow-up is still active or completed; record maintenance and security; evidence of compliance with the approved protocol and any conditions of approval; negative reports from monitors or good clinical practice (GCP) inspectors; all adverse events in the past 12 months; and all amendments made in the past 12 months.

Per the GRMRSA, the SA-GCP, and G-SafetyRpt, the six-month report (ZAF-18) must include the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

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

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

Final Report

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

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

The G-EthicsHR-ZAF states PIs or research leaders must disseminate research results or findings, whether positive or negative, in a timely, accessible, responsible, and competent manner. This includes reporting back to participant communities where appropriate.

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

6.1-6.2 and 7.3.1

2.3 and 5.5

5.5, 5.11, 5.14, and 6.15

Part 30 (6)

Definition of Sponsor

Last content review/update: November 2, 2026

As per the CanadaFDR and the G-CanadaCTApps, a sponsor is defined as an individual, corporate body, institution, or organization that conducts a clinical trial. In accordance with the G-FDR-0100, a sponsor may transfer any or all of the sponsor's trial-related activities to a service provider in accordance with applicable regulatory requirements. However, the ultimate responsibility for the sponsor's trial-related activities, including protection of participants' rights, safety, and well-being and reliability of the trial data, resides with the sponsor.

According to the CanadaFDR and G-CanadaCTApps, a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer who is residing in Canada who will represent the sponsor, and sign and date the application and the clinical trial attestation form.

For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

2.1

Part C (Division 5 (C.05.001, C.05.005, C.05.015))

Last content review/update: March 19, 2026

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

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

1

6

Site/Investigator Selection

Last content review/update: November 2, 2026

Overview

Per the CanadaFDR and the G-FDR-0100, every sponsor must ensure that a clinical trial is conducted in accordance with good clinical practice (GCP) and must also ensure that:

At each clinical trial site, there is no more than one (1) qualified investigator (QI)
At each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the supervision of the QI
Each individual involved in the conduct of the clinical trial is qualified by education, training, and experience to perform the tasks

The G-FDR-0100 explains that the sponsor’s selection and oversight of QIs and service providers are fundamental features of the oversight process. As stated in Mdrn-CTFrmwrk, a "qualified investigator" may be:

A physician or dentist who is authorized under CanadaFDR to act as a qualified investigator
An individual who has the education, training, and experience required to conduct the clinical trial in accordance with regulatory requirements, despite not meeting the regulatory requirement to be a physician or dentist in CanadaFDR

Mdrn-CTFrmwrk further specifies that in clinical trials where the investigator is not a physician or dentist, medical decisions with respect to the trial that are outside the licensed scope of practice of the investigator must be made by a qualified physician or dentist on the clinical trial team who is:

Licensed to practice in the province or territory where the site is located
Responsible for medical oversight and participant care, including medical decisions with respect to the trial

In accordance with the G-CanadaCTApps, prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form (CAN-37) (or similar documentation that meets the CanadaFDR requirements) has been completed and kept on file by the sponsor; it should be retained by the sponsor for 15 years. Per the CanadaFDR, the form certifies that the QI will conduct the clinical trial in accordance with GCP, and, if the trial is discontinued, will immediately inform trial participants and the institutional ethics committee (EC) (known as Research Ethics Boards in Canada) of the discontinuance, and the reason for it. (See the Submission Content section for additional information on clinical trial application requirements). For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Per G-Dcntrl, for clinical trials with decentralized elements, sponsors and QIs should assess whether decentralized locations have sufficient funding, time, equipment, and staff to support trial conduct that complies with GCP. Considerations include local care and institutional practices, provincial or territorial requirements, training needs, and coordination and communication across locations. The main location and remote locations supervised by one (1) QI constitute a single clinical trial site. The main location must be identified on the Clinical Trial Site Information (CTSI) form (CAN-6) and receive EC approval before trial initiation.

For additional guidance on investigator selection, qualifications, and training, see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Per CAN-11, the Canadian Clinical Trials Asset Map (CCTAM) (CAN-26) is a pan-Canadian research inventory of investigators, clinical research sites, and other resources across the country. Sponsors can use CCTAM to identify potential sites and investigators, which may expedite study feasibility and start-up timelines. To view the CCTAM, the user must register and create an account.

Foreign Sponsor Responsibilities

According to the CanadaFDR and the G-CanadaCTApps, a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer residing in Canada to represent the sponsor, and sign and date the application and the clinical trial attestation form.

Data and Safety Monitoring Board

The G-TCPS2 provides the following considerations to help researchers and ECs determine whether a Data and Safety Monitoring Board (DSMB) (known as an Independent Data-Monitoring Committee in Canada) is needed:

The magnitude of foreseeable research-attributable harms to participants
Whether the circumstances of the participants make them vulnerable in the context of research
The feasibility of interim data analysis
The complexity of the study
Conflicts of interest

Also see CAN-52 for ICH guidance on DSMBs.

Multicenter Studies

The CanadaFDR and the G-CanadaCTApps, require the sponsor to complete and retain the Research Ethics Board (REB) Attestation (CAN-8) and Qualified Investigator Undertaking (QIU) (CAN-37) forms at each trial site, while submitting in electronic format CAN-6 to the appropriate HC Directorate for each trial site.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, provides that in multi-site clinical trials, a lead principal investigator (PI) is a designated PI who is responsible for the ethical conduct of the study for all sites. The lead PI is responsible for communicating any changes to the study, new information, and/or unanticipated events to the EC, to the sponsor, and to local site PIs.

Per CAN-50, Canada has implemented the ICH Guidance E17: Multi-Regional Clinical Trials (CAN-40), which describes general principles for the planning and design of multi-regional clinical trials with the aim of increasing the acceptability of these trials in global regulatory submissions. HC recognizes that the scope and subject matter of current HC guidance may not be entirely consistent with ICH guidance. In such circumstances, HC-implemented ICH guidance takes precedence.

2.1 and 2.7.2

Design considerations, Single and multi-site clinical trials, and Identifying clinical trial sites

Chapter 11 (Article 11.7)

2

Part C (Division 5 (C.05.005))

Canadian Clinical Trials Asset Map

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA’s Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

As set forth in the SA-GCP, the sponsor is responsible for using qualified individuals (e.g., biostatisticians, clinical pharmacologists, and physicians), as appropriate, throughout all stages of the trial process. Sponsors should select investigator(s) who are qualified by training and experience and have adequate resources to conduct the proposed clinical trial.

Per the SA-GCP, all parties involved in the conduct of a trial should be familiar with the guidance in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ZAF-27) and other international guidelines.

Capacity Building & Training

As described in 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.

The G-EthicsHR-ZAF states that researchers must be suitably qualified and technically competent (trained and supervised, in the case of student researchers) to carry out the proposed research. The principal investigator (PI) has primary responsibility to ensure the safety and well-being of participants, the scientific integrity of the protocol, research data management, and responsible implementation of that protocol. Competence is demonstrated mainly by academic qualifications, credentials, and scientific and technical competence, as evidenced in previous publications or testimonials. Competence includes research competence, which is assessed in terms of education, knowledge, certification, and experience. In addition, researchers must produce evidence of appropriate research ethics training within the previous three (3) years.

The SA-GCP prescribes mandatory GCP training with evidence of current (i.e., within three (3) years) GCP training and general research ethics training. To meet the required GCP training, the GCP-Trning indicates that virtual methods are acceptable (Zoom, Teams, etc.) for both basic and refresher training. Virtual training must be done properly, which includes monitoring interactive and active engagement of participants, and using a full-time facilitator (qualified to conduct training) available for the entire duration including questions and answers. To ensure inclusivity and fairness, consideration should be given to those who are unable to attend virtual training, especially in remote areas where internet accessibility remains a challenge. A hybrid model could be considered in this case. The duration of basic GCP training should be in alignment with the prescribed outcomes or unit standards (approximately two (2) days). The training content should be accredited by the Health Professions Council of South Africa (HPCSA).

Management of Investigators

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

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

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

Foreign Sponsor Responsibilities

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

Per the G-EthicsHR-ZAF, all international collaborative health research conducted in South Africa must undergo ethics review and approval by a South African registered EC and comply with the SA-GCP. In addition, if international collaborators are affiliated with a foreign research institution or university, they must provide evidence of ethics review and approval from their home institution. International researchers are expected to demonstrate sensitivity to and understanding of the local socio-economic and political conditions of the research context, as these may indicate vulnerabilities of potential participants. It is advisable to create appropriate memoranda of understanding (MOUs) and agreements to establish the expectations, roles, and contributions of the various parties, as well as the limitations of the collaborative relationship. An agreement should exist between the host research institution and the collaborating institution(s) regarding all aspects of the research, including management of the research itself; research data management that includes the fate of the data and samples after completion of the study; financial arrangements; approach to research output publications; infrastructure development; allocation of intellectual property rights; and dispute resolution mechanisms. Selection of study participants is expected to be based on distributive justice and fairness. Risk/benefit assessments must be properly conducted to ensure that foreseeable risks of harm are mitigated and that anticipated benefits of participation are distributed fairly.

Data and Safety Monitoring Board

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

Multicenter Studies

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

The G-EthicsHR-ZAF states that for international multi-site research, at least one (1) PI or co-PI must be physically in South Africa.

1.25, 5.5, and 5.6

5

3 and 4

2.3 and 3.3

1.2, 4.3, 5.9, 6.2, 6.4, and 7.12

Insurance & Compensation

Last content review/update: November 2, 2026

Insurance

The CanadaFDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. However, the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50, guides sponsors on providing insurance. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Compensation

Injury or Death

The Canadian regulations do not require compensation for trial participants in the event of trial-related injuries or death. However, the G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs) (known as Research Ethics Boards in Canada), provides that, during informed consent, participants should be given information about any payments, including compensation for injury.

Trial Participation

The Canadian regulations do not require compensation for trial participation. However, as per the G-TCPS2, the informed consent form (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. 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.

Also see CAN-52, which guides sponsors on providing compensation.

Chapter 3 (Article 3.2)

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA guidelines:

Guideline for Phase 2-4 Clinical Trial Participant Time, Inconvenience and Expense (TIE) Compensation Model (Version 3, Effective June 1, 2026)
Guideline for Remuneration of Volunteers in Phase 1 Clinical Trials (Effective June 1, 2026)
Pre-Clinical Testing Guidelines and Clinical Requirements for Phase I / First in Human (FIH) Studies (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026) 
Guideline for Liability Insurance for Clinical Trials (Version 4, Effective March 2026)

Insurance

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

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

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

Name and local address of the insurance company, including contact name and telephone number
Title and protocol number of the clinical trial
Date of commencement and termination of coverage
Liability limit – per occurrence and total per occurrence and total for the study. Note that the limit should be adequate enough to cover extended stay in an intensive care unit or hospital
Date of issuance of the insurance policy and expiry thereof
Original or electronic signature of the insurer
Special conditions if any. It is unacceptable to have special conditions which may invalidate or abate the clinical trial cover
Any additional coverage
Declaration of compliance with the SA-GCP 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

CTInsurance indicates that when applying to SAHPRA for approval of a new clinical trial, proof of active participant insurance cover for the trial must be included in the submission. The insurance quotation letters, letters of intent, or pro forma certificates are not acceptable. As indicated in the clinical trial application form (ZAF-23), applications submitted without an insurance certificate will be rejected at the screening phase and will not be accepted for review.

Compensation

Injury or Death

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

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

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

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

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

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

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

Trial Participation

As specified in the G-TIECompensation and the SA-GCP, the sponsor or the designated representative is responsible for providing compensation to research participants. The SA-GCP states that before the clinical phase of the trial commences, the EC must approve the documentation on participant compensation. Per the G-EthicsHR-ZAF, the SA-GCP, and the G-TIECompensation, compensation should be based on time, inconvenience, and expenses (TIE). In addition, the G-EthicsHR-ZAF and the SA-GCP also address researcher requirements to budget for participant travel and other expenses. (See the G-EthicsHR-ZAF 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.

The G-EthicsHR-ZAF explains that inducements (also known as incentives) may be offered in justified circumstances (e.g., where recruitment is anticipated to be difficult) to encourage participation and to express appreciation by offering gifts over and above reimbursement of expenses and compensation for time and inconvenience. Inducements are not necessarily cash but may take other forms like data or airtime vouchers, food vouchers, etc. Importantly, an inducement should not unfairly influence an informed choice about whether to participate or undermine a potential participant’s ability to assess the risk of harm. This is especially important for Phase I and First in Humans clinical trials where the circumstances may involve healthy people being offered significant payments over and above those outlined in the TIE method. All inducements should be clearly explained and justified to the EC. If there are community members on the EC, their input may be constructive regarding appropriate inducements.

Post-Trial Access

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

PTA/CA is not applicable for Phase I and II studies. However, PTA/CA may be necessary for particular diseases (e.g., cancer or rare diseases).
PTA/CA should be considered for Phase III studies when there is no registered and marketed standard of care in South Africa, provided that data from interim or final analyses shows that access is clinically justifiable.
PTA/CA is not applicable to Phase IV studies
A minimum of four (4) years after completion of the study is recommended as the acceptable time period to provide PTA/CA to the participants, unless there are compelling reasons for determining otherwise.
During the PTA/CA period, the sponsor must ensure monitoring and oversight of participants using the IP.

3 and 4

Cover, 1 and 2

1-5 and 7

3.1, 3.3, 3.4, and Appendix 2 (A2.2)

1.2, 2.7, 6.2, 7.14, 9.2, and 10.2

Risk & Quality Management

Last content review/update: November 2, 2026

Quality Assurance/Quality Control

As stated in the CanadaFDR, the sponsor must ensure that a clinical trial is conducted in accordance with good clinical practice and must ensure, among other things, that the trial is scientifically sound and clearly described in a protocol; the trial and use of the drug comply with the protocol and the CanadaFDR; and systems and procedures that assure the quality of every aspect of the trial are implemented. Regarding quality, the G-FDR-0100 explains that the sponsor is responsible for the establishment of a quality management system consisting of documented procedures (standard operating procedures (SOPs), protocol procedures, etc.) to assure the quality of every aspect of a clinical trial. The range and extent of oversight measures should fit the purpose and be tailored to the complexity of and risks associated with the trial. Quality management includes the design and implementation of efficient clinical trial protocols, including tools and procedures for trial conduct (including data collection and management), to ensure the protection of participants' rights, safety, and well-being, and the reliability of trial results. The sponsor should adopt a proportionate and risk-based approach to quality management, which involves incorporating quality into the design of the clinical trial (i.e., quality by design) and identifying those factors that are likely to have a meaningful impact on participants' rights, safety, and well-being, and the reliability of the results. The sponsor should describe the quality management approach in the clinical trial report.

In addition, G-FDR-0100 states that risks to critical-to-quality factors should be managed proactively and adjusted when new or unanticipated issues arise once the trial has begun. Risk review is a key component to risk-based quality management systems, and Health Canada (HC) expects that sponsors will be able to demonstrate that risk control measures are periodically reviewed and remain effective and relevant, considering emerging knowledge and experience throughout the trial.

Per G-Dcntrl, for trials with decentralized elements, sponsors and qualified investigators (QIs) should collaborate with trial sites and service providers to implement a quality management system covering decentralized activities and supporting compliance with HC regulations and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. Processes should identify, evaluate, control, communicate, and review risks affecting participant safety or the reliability of results, including risks arising from decentralized elements. Additional training, continuing quality checks, and competency assessments may be needed beyond SOPs. See G-Dcntrl for additional details.

Further, CAN-50, Canada implements the ICH Guidance E8(R1): General Considerations for Clinical Studies (CAN-49), which provides guidance on conduct during the clinical trial. Other relevant ICH guidance adopted per CAN-50 are the guidance on statistical principles for clinical trials (CAN-53) and the addendum on estimands and sensitivity analysis (CAN-39). The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Monitoring Requirements

As indicated in the G-FDR-0100, the sponsor should determine the appropriate extent and nature of monitoring based on identified risks. Factors to consider include the objective, purpose, design, complexity, blinding, number of trial participants, investigational product, current knowledge of the safety profile, and endpoints of the trial. Monitoring may include site monitoring (performed onsite and/or remotely) and centralized monitoring. The frequency of monitoring activities should also be determined based on identified risks. Monitoring activities and their frequency should be modified as appropriate using knowledge gained. Centralized monitoring processes provide additional monitoring capabilities that can complement and reduce the extent and/or frequency of site monitoring or be used on its own. Use of centralized data analytics can help identify systemic or site-specific issues, including protocol noncompliance and potential unreliable data. In addition to monitoring, a sponsor should perform audits in a manner that is proportionate to the risk associated with the conduct of the trial. See CAN-52 for additional guidance on sponsor responsibilities involving monitoring and auditing.

Further, per the G-FDR-0100, it is critical to include processes that will be followed to address situations of non-compliance, as well as to identify events that would require either a review or revision of the monitoring plan. HC expects these components to be clearly documented in risk-based monitoring plans. The sponsor should describe the requirements of monitoring reports (including their content and frequency) in the standard procedures. Reports of site and/or centralized monitoring should be provided to the sponsor in a timely manner for review and follow up. When needed, the report should describe findings requiring escalation for action and resolution. The sponsor should decide on the appropriate action to be taken, and these decisions and the resolution of the actions involved, where needed, should be recorded. For additional information on monitoring reports, refer to the U.S. Food & Drug Administration (FDA)’s Guidance for Industry: A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers.

Next, per the G-FDR-0100, if it is discovered that noncompliance significantly affects or has the potential to significantly affect human participant protection or reliability of trial results, the sponsor should perform a root cause analysis, implement appropriate corrective and preventive actions, and confirm their adequacy, unless otherwise justified. Where the sponsor identifies issues that are likely to significantly impact the rights, safety, or well-being of the trial participant(s) or the reliability of trial results (i.e., serious noncompliance), the sponsor should notify the HC and the institutional ethics committee (known as Research Ethics Boards in Canada).

Per the HCNotice-ICH-E19, HC adopted and implemented ICH guidance on selective safety data collection in specific late stage pre-approval or post-approval clinical trials (CAN-15). Selective safety data collection refers to the recording of certain data by investigators in case report forms. It does not affect the monitoring and clinical care of individual trial participants or documentation of their adverse events in medical records. See the HCNotice-ICH-E19 and the CAN-15 for more information.

Per G-Inspections, regulated parties (sponsors, qualified investigators, contract research organizations, and any other party involved in the conduct of clinical trials) have mandatory responsibilities under the CanadaFDA and can be inspected. Foreign entities that conduct regulated activities in Canada, or in relation to a product imported in Canada, are also subject to Canadian law. During an inspection or a compliance verification, a regulated party is required to provide all reasonable assistance and information necessary for the HC inspector to perform their duties, including providing evidence that its facility, equipment, and practices and procedures meet the applicable requirements. As indicated in G-Dcntrl, sponsors should oversee decentralized elements in clinical trials across all locations, including remote locations, with monitoring directed toward potential safety concerns, data quality, and reliable results. See the Risk-Insp for HC’s risk classification guide for observations related to inspections of clinical trials of human drugs.

Premature Study Termination/Suspension

The CanadaFDR and the G-CanadaCTApps state that if a trial is prematurely terminated or suspended, the sponsor should inform HC no later than 15 days after the termination or suspension. In addition, the sponsor should provide HC with the reason(s) for the termination or suspension and its impact on the proposed or ongoing clinical trials related to the drug in Canada by the sponsor. The sponsor should also promptly notify the qualified investigators of the termination or suspension and advise them in writing of any potential risks to the participants’ health. Further, the G-CanadaCTApps states that the sponsor’s notification to HC should include confirmation that the sale or importation of the drug to the discontinued sites has been stopped and that reasonable measures to ensure the return of all unused quantities of the drug will be taken. This notification must also be submitted for premature discontinuation of a clinical trial or clinical trial site outside Canada where there are ongoing trials with the drug in Canada. See G-FDR-0100 for additional information and interpretation of discontinuation, suspension, and cancellation. CAN-52 also provides guidance on premature termination or suspension.

2.8.1

Managing risk and Quality management systems

Discontinuation, Suspension and Cancellation, and Good Clinical Practices

2 and 4

Part C (Division 5 (C.05.007-008, C.05.010, and C.05.015))

Purpose and Scope, and Glossary

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Quality Assurance/Quality Control

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

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

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

Monitoring Requirements

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

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

As delineated in the G-EthicsHR-ZAF, researchers are expected to provide appropriate information to the EC to facilitate monitoring, including alerts and investigator brochures.

Premature Study Termination/Suspension

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

The G-EthicsHR-ZAF reiterates that if a project is terminated or suspended before the anticipated date of completion, then the researchers must report this immediately to the EC.

1.65, 5.0-5.2, 5.5, 5.18, 5.19, 5.21, 5.23, 6.10, and 8

1 and 4

5.5

Introduction, 1.2, 5.10, 5.13, 6.1, 6.4, and 6.12

Data & Records Management

Last content review/update: November 2, 2026

Electronic Data Processing System

The G-FDR-0100 states that systems and processes that aid in data capture, management, and analyses, as well as those that help ensure the quality of the information generated from the clinical trial, should fit the purpose of the trial, capture the data required by the protocol, and be implemented in a way that is proportionate to the risks to participants and the importance of acquired data. Quality should be addressed in the design or adaptation of electronic systems for clinical trial purposes to ensure the integrity of relevant trial data. Any electronic system used to capture, process, manage, and/or archive clinical trial information should be adequately validated, and evidence of validation should be retained and readily available for inspection by Health Canada (HC) inspectors. The approach for validation should be based on a risk assessment that considers the intended use of the system; the purpose and importance of the data/record that are collected/generated, maintained, and retained in the system; and the potential of the system to affect the well-being, rights, and safety of trial participants and reliability of trial results. The responsibilities of the sponsor, qualified investigator (QI), and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. The sponsor should periodically review the risk control measures to ascertain whether the implemented systems remain effective and relevant, considering experience and emerging knowledge.

Per the G-FDR-0100, any modifications or additions made to the electronic system (for example software upgrades or migration of data) can impact its intended functions by altering the quality of validated applications and the system itself. This may affect the integrity of electronic information and the reliability of the system. Therefore, adequate documented assessment and approval of changes to hardware or software during the clinical trial are required. The impact of such a change should be evaluated and documented, and partial validation of some components of the electronic system may be required.

G-Dcntrl states that computerized systems and digital health technologies used in decentralized activities should be suitable for their intended use and validated through a risk-based approach consistent with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. Sponsors should address data transfer integrity, security, interoperability, audit trails, and cybersecurity, with documented procedures and training supporting system development, maintenance, and use. See G-Dcntrl for additional details.

For additional information on computerized system validation and electronic records, see CAN-52. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Records Management

As set forth in the CanadaFDR and the CanadaFDR1024, the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR requires the sponsor to maintain all trial-related records for a period of 15 years. Per the G-FDR-0100, the electronic system should allow for the retrieval of records and the generation of complete and accurate paper copies of the electronic source data. The system should provide audit trails for the entire 15-year record retention period. Records created, maintained, and processed by outsourced systems are subject to the same requirements as the data/records generated by company-owned systems.

Pursuant to CanadaFDR1024, the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven (7) days of a request. Per CAN-8, an attestation must be completed by the institutional ethics committee (EC) (known as Research Ethics Boards in Canada) that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested.

G-Dcntrl states that records of agreements and contracts (paper or electronic) must be available or accessible from the main location of the clinical trial site. Per the Mdrn-CTFrmwrk, the sponsor is responsible for obtaining and retaining records for all EC approvals that may be required for participating sites, in accordance with applicable local requirements. The sponsor must retain records of all approvals for verification during clinical trial inspections. To meet this requirement, the sponsor must maintain complete and accurate records demonstrating EC approval for research undertaken at a clinical trial site.

Also see CAN-52 for additional guidance.

Requirements and oversight for digital systems and Agreements

Labeling and Records

1

Part C (Division 5 (C.05.012))

Regulatory Impact Analysis Statement

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Electronic Data Processing System

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

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

See the G-EthicsHR-ZAF for detailed ethical, legal, and security considerations for database storage and access.

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

Records Management

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

4

4.2

Introduction, 1.2, 5.10, 6.4

Personal Data Protection

Last content review/update: November 2, 2026

Responsible Parties

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), states that where researchers seek to collect, use, share, and access different types of information or data about participants, they should determine whether the information or data proposed in research may reasonably be expected to identify an individual. Researchers and ECs must consider whether information is identifiable or non-identifiable. Researchers, ECs, and institutions share the responsibility for protecting participant confidentiality.

Data Protection

Per CAN-42, the Office of the Privacy Commissioner of Canada provides advice and information for individuals about protecting personal information, and enforces the two (2) federal privacy laws that set out the rules for how federal government institutions and certain businesses must handle personal information, including health data. The PrivAct covers the personal information-handling practices of federal government departments and agencies in Canada, and the PIPEDA regulates private businesses’ data protection practices. In addition, some provinces and territories have laws that deal specifically with the protection of personal health information. See CAN-43 for a list of provincial and territorial privacy laws and webpages.

Per the G-TCPS2, in the research context, the most simplified method to protect participants is through the collection and use of anonymous or anonymized data. When anonymized data is not possible or desirable, a next best alternative is to use de-identified data, which is provided to the researcher in de-identified form and the existing key code is accessible only to a custodian or trusted third party who is independent of the researcher. Where it is not feasible to use anonymous or anonymized data for research, the ethical duty of confidentiality and the use of appropriate measures to safeguard information become paramount. Researchers should consult their ECs if they are uncertain about whether information proposed for use in research is identifiable (e.g., when proposing to link anonymized or coded data sets).

G-Dcntrl states that for decentralized data collection through wearables, digital platforms, or remote monitoring, sponsors should consider where data is stored, who may access it, and how to prevent unauthorized sharing or reuse.

Consent for Processing Personal Data

Both PIPEDA and the PrivAct require consent for the use of personal data, including health data, except under prescribed conditions, such as for research or during emergencies. Also see CAN-43 for provincial and territorial privacy laws.

The G-TCPS2 states that to seek broad consent for the storage and future unspecified use of data, researchers must provide prospective participants, or authorized third parties, with applicable information as set out in the informed consent requirements. See the Informed Consent topic, as well as the following details:

The type, identifiability, and amount of data being collected and stored for re-use, and for what potential purpose
The voluntariness of the participant’s consent, including any limitations on the feasibility of withdrawal
A general description of the nature and types of future research that may be conducted, including whether the research might be conducted outside of Canada (if known)
The risks and potential benefits of data storage and use in future unspecified research, including areas of uncertainty where risks cannot be estimated
Access to a general description of the repository and its governance
A statement regarding participants’ preference to being contacted for additional future research
Whether the data could be shared with researchers who are not subject to the G-TCPS2
Whether the research will (if known) or might include whole genome sequencing or similar technologies that may pose a substantial risk of re-identification of the participant or identification of material incidental findings (when appropriate)
Whether linkage of data gathered in the research with other data about participants – either contained in public or personal records – is anticipated
Separate options for consenting to participate in a specific research project and for consenting to the storage of data for future unspecified research

See Brd-Cnst for additional clarifications on broad consent for the storage and future unspecified use of data.

Per G-Dcntrl, when using digital tools for decentralized activities, there may be concerns about data storage, access, and reuse or sharing without consent. Sponsors and qualified investigators can work collaboratively with participants to ensure informed consent is maintained.

Data management plans and Equitable and participant-centred use of technology

Chapter 2 (Article 2.1), Chapter 3 (Article 3.13), and Chapter 5 (A. Key Concepts and 5.1)

Part I (2, 6.1, and 7)

3, 7, and 8

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Responsible Parties

For the purposes of data protection requirements, the POPIA provides that the “responsible party” is a public or private body or any other person that, alone or in conjunction with others, determines the purpose of and means for processing personal information. In addition, an "information officer" is the designated head or deputy of a public or private body responsible for fulfilling the duties and functions related to personal information.

Data Protection

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

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

Accountability – The responsible party must ensure that the conditions and all the measures in the POPIA are complied with at the time 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 G-EthicsHR-ZAF reaffirms that data protection measures should be aligned with the requirements of the POPIA, including the conditions for cross-border transfer and sharing of health data. To ensure data processing is lawful, fair, and transparent, researchers should submit a data management plan to the ethics committee (EC), which covers how data will be collected, stored, accessed, shared, and disposed of or retained. The data management plan should indicate how it complies with the POPIA, how data security will be maintained and the processes for possible data breaches. If data-sharing options include the use of open-access databases, the selected databases must meet the minimum legal, ethical, and security requirements. See the G-EthicsHR-ZAF for additional guidance and analysis. Also see the Specimen Import & Export section for details on sharing human biological material (HBM) and HBM data.

The POPIA establishes a duty requiring a public or private body to register its Information Officer with the Information Regulator (South Africa) on the eServices platform (ZAF-14). 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, maintain, and continually improve a compliance framework
Conduct a personal information impact assessment to ensure compliance with the conditions for the lawful processing of personal information
Develop internal measures and systems to process requests for information or access
Conduct internal awareness sessions on protection of personal information requirements

As indicated in the POPIA-Regs, a data subject may object to the processing of personal information at any time during office hours and free of charge. The objection must be made on a form substantially similar to Form 1 (in the POPIA-Regs), and the responsible party must make the form reasonably accessible by hand, fax, post, email, SMS, WhatsApp, or any other expedient means. The responsible party must notify the data subject of the right to object when collecting personal information. If an objection is made telephonically, it must be electronically recorded and made available to the data subject upon request. In addition, a data subject may request the correction, destruction, or deletion of personal information at any time and free of charge, where the information is inaccurate, irrelevant, excessive, out of date, incomplete, misleading, obtained unlawfully, or no longer authorized to be retained. Requests must be made on a form substantially similar to Form 2 (in the POPIA-Regs), which must be reasonably accessible through various means, including hand delivery, fax, post, email, SMS, WhatsApp, or any expedient manner. If a request is made telephonically, the responsible party must record it and make it available on request. The responsible party must also notify the data subject in writing within 30 days of the action taken in response to the request. Also see ZAF-4 for voluntary guidance on complying with the POPIA and the POPIA-Regs.

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

See ZAF-4 for voluntary guidance on complying with the POPIA, and ZAF-28 for more background on information officers. For additional guidance on processing personal data, including guidance on “special personal information” (e.g., health history) and personal information of children, see the Information Regulator website.

Consent for Processing Personal Data

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

As delineated in the G-EthicsHR-ZAF, consent to processing of personal information in terms of the POPIA requires a voluntary, specific, and informed expression of will, separate from the consent to participate in research. Special attention should be given to ensuring that computers and electronically stored data are protected from unauthorized access, inadvertent or accidental dissemination in the form of a ‘data dump’, etc. In general terms, a participant should know what personal information is being collected; why it is being collected; what will happen to it; how long it will be retained; whether it will identify the participant; whether it will be shared with others and why; whether it will be shared with third parties inside South Africa and why; and whether it will be sent outside South Africa and why. The participant should agree to these terms. Note that when processing some types of personal information, consent alone is insufficient as stipulated in the POPIA. Necessity must also be established with special personal information, such as information about a person’s race or ethnic origin, a person’s health or sex life, a person’s inherited characteristics (genetic makeup), biometric information, or children’s personal information.

Consent for Processing Personal Data of Minors

Per the POPIA, there is a general prohibition on the processing of personal information of a minor. However, a responsible party may process personal information concerning a minor if the processing meets one (1) of the following conditions:

It is carried out with the prior consent of a competent person
It is necessary for the establishment, exercise, or defense of a right or obligation in law
It is necessary to comply with an obligation of international public law
It is for historical, statistical, or research purposes to the extent that the purpose serves a public interest and the processing is necessary for the purpose concerned; or it appears to be impossible or would involve a disproportionate effort to ask for consent and the processing does not adversely affect the individual privacy of the child to a disproportionate extent
It is of personal information which has deliberately been made public by the minor with the consent of a competent person

As required in the G-EthicsHR-ZAF, when personal information about a minor (under 18 years) is to be processed, permission of a parent/legal guardian is required before data collection, even when permission is not required for the specific activity that gives rise to the information (e.g., donating blood). A minor aged 16 years or more may donate blood without parent/legal guardian permission, but the POPIA requires parent/legal guardian permission to process the information.

3.3 and 3.4.3

Preamble, Chapter 1 (1-2), Chapter 2 (4-5), Chapter 3, Chapter 5 (55-56), and Chapter 9 (72)

Schedule (2-4) and Forms 1 and 2

Documentation Requirements

Last content review/update: November 2, 2026

Obtaining Consent

In all Canadian clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in the CanadaFDR and the G-TCPS2. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

As per the CanadaFDR and the G-TCPS2, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) and provided to HC with the clinical trial application (CTA). (See the Required Elements section for details on what should be included in the form.)

The G-TCPS2 states that the qualified investigator (QI) must provide detailed research study information to the participant or legal representative/guardian. The ICF content should be in plain language (i.e., non-technical and easy to understand) and provided in a format that facilitates understanding. For example, written documentation may be supplemented with audio and/or visual aids. The participant and legal representative/guardian should also be given adequate time to consider whether to participate.

As stated in Mdrn-CTFrmwrk, HC is moving from “written” to “documented” informed consent to allow new approaches for obtaining consent (e.g., remote or electronic platforms, electronic signatures, and documentation of consent where it is provided orally). Informed consent requirements will be considered met by HC where processes:

Are appropriately documented
Comply with good clinical practice and CAN-52 principles
Ensure that consent is informed and given in accordance with the applicable laws governing consent

Per G-Dcntrl, sponsors must inform participants of the potential risks and anticipated benefits of any decentralized elements in a clinical trial. In designing and implementing consent processes across locations, sponsors should consider whether the approach may introduce additional cognitive or emotional demands for participants. Reasonable steps should be taken to minimize unnecessary burden while supporting informed and voluntary decision-making. Virtual meeting platforms and electronic signatures may make the informed consent process more efficient for those who live in remote areas. However, participants may face additional challenges in providing informed consent remotely. Sponsors and QIs should be careful not to create a disadvantage for those who face barriers such as reliable private internet access, digital literacy, or comfort with virtual tools, or prefer not to use virtual platforms. Trial-related documentation should support any proposed delegation of duties related to the informed consent process to trial personnel or other third party, any proposed virtual meeting to obtain informed consent, and the proposed medium of the documented record of participants providing their consent (for example, written, video, audio). The following should also be considered:

Providing different methods of informed consent to those who request them, including in-person consent meetings and physical copies of the ICF
Using virtual meeting platforms that include both audio and video features so that QIs (or delegated persons) and participants can take part in the informed consent process and discussion in real time, and interact virtually with a real person

Further, the G-FDR-0100 indicates that a clinical trial participant cannot be involved in any aspect of a clinical trial until they have gone through the informed consent process, with a trial staff member (doctor, study nurse, clinical trial coordinator, etc.) and signed the document indicating that they understand the information and have agreed to participate in the trial. Neither the QI, nor the QI site staff, should coerce or unduly influence a participant to participate or to continue their participation in a trial. A qualified physician should be available to answer any medical questions that the participant may have regarding their participation in the trial. Information should be as clear and concise as possible, use simple language, and avoid unnecessary volume and complexity. See CAN-52 for additional information.

For guidance from Canadian researchers on the core elements for obtaining consent to ensure transparency and improve participants’ understanding of their involvement in research studies, see CAN-57.

Re-Consent

Per the G-TCPS2, consent must be maintained throughout the research project. Researchers have a continuous duty to provide participants with all information relevant to their ongoing consent to participate in the research. Consent begins with the initial contact (e.g., recruitment) and carries through to the end of participation in the study. Throughout the clinical trial, researchers have a continuous responsibility to provide participants and ECs with all information relevant to participants’ ongoing consent to participate in the research. The researcher must also notify participants of any changes to the research project that may affect them. These changes may have ethical implications, may be relevant to their decision to continue in the study, or may be unique to the particular circumstances of individual participants. Specifically, researchers must disclose changes to the risks or potential benefits of the research.

The G-TCPS2 indicates that rather than an age-based approach to consent, researchers should use an approach based on decision-making capacity in compliance with any laws governing research participation. This includes those whose decision-making capacity is in the process of development, those whose decision-making capacity is diminishing or fluctuating, and those whose decision-making capacity remains only partially developed. Mechanisms should be in place from the outset to identify and address any changes that could affect consent. A change in participant capacity is an important element of ongoing consent.

Further, the G-TCPS2 states that within the limits of consent provided by the participant, researchers should disclose to the participant any material incidental findings discovered in the course of research. Incidental findings are considered to be material incidental findings if they are reasonably determined to have significant welfare implications for the participant or prospective participant. Where material incidental findings are foreseeable, researchers should inform participants during the initial consent process. In addition, researchers should develop a management plan for review by the EC. For more information on how to address material incidental findings, see G-ConsentMatIncFindings.

See CAN-52 for additional information.

Language Requirements

Per the G-FDR-0100, the ICF must be made available for each participant in either official language (French or English) or other language as appropriate. The G-TCPS2 requires the ICF to be presented in plain language that the participant is able to understand. If there is a language barrier, the QI should select an intermediary who has the necessary language skills to ensure effective communication.

Documenting Consent

As per the G-TCPS2, the participant or legal representative/guardian, as well as the QI, must sign and date the ICF. The G-FDR-0100 states that the QI should retain the signed ICF.

The G-TCPS2 further indicates that researchers can use a range of procedures to seek and document consent, including oral consent documented in field notes, and other forms of recording (e.g., a consent log, audio or video recordings, or other electronic means). Evidence of consent may also be documented via completed questionnaires (in person, by mail, by email, or other electronic means). ECs should consider the power relationship that might exist between researchers and participants, and whether a waiver of the requirement for signed written consent may affect the welfare of the participants. If researchers plan to obtain non-written consent, they must explain their strategy to the EC.

See CAN-52 for additional information.

Waiver of Consent

As explained in the G-TCPS2, there are research situations that call for alterations of consent. The EC may approve research that involves an alteration to the consent requirements if the EC is satisfied, and documents that all of the following apply:

The research involves no more than minimal risk to the participants
The change to consent requirements is unlikely to adversely affect the welfare of participants
It is impossible or impracticable to carry out the research and to address the research question properly, given the research design, if the prior consent of participants is required
In the case of a proposed alteration, the exact nature and extent of any proposed alteration is defined
There is a plan to brief participants and offer the option of refusing consent and/or withdrawing data and/or human biological materials

Informed consent process

Good Clinical Practices

Chapters 3 and 10

3

Part C (Division 5 (C.05.005, C.05.006, C.05.008, and C.05.010))

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Obtaining Consent

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

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

The SA-GCP directs that none of the oral or written information concerning the study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or the representatives from the sponsor’s liabilities for any negligence.

G-EthicsHR-ZAF explains that an important element of enabling an informed choice is the nature and quality of information made available to the potential participant, such as reading the information sheet and/or dialoguing with the participants, allowing for verbal consent, which is then recorded and transcribed or documented manually in the researchers’ notes. The process should permit sufficient time for consultation between the recruitment step and the time for deciding whether to participate. No person should be required to make an immediate decision. ECs should assess the proposed process for informed consent as well as the information that potential participants will be given and the measures to facilitate understanding. Considerations for assessment include whether:

The informed consent setting is sufficiently private and appropriate to minimize the possibility of undue influence
The person conducting the informed consent process is appropriately trained, independent, and bias-free
The text is in plain language and appropriate to the participants’ level of understanding with translations, as needed

Re-Consent

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

Per the G-EthicsHR-ZAF, informed consent should be a trust-based process and relationship between the researcher and the participants, groups, and communities that extends over time. Consent must be negotiated and renegotiated as the research continues and develops.

Language Requirements

According to the SA-GCP, the ICF should be provided in a participant’s preferred written language. 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.

The G-EthicsHR-ZAF states that informed consent material must be translated into the language(s) best suited for the population and context of the study. If appropriate, the consent documents can be translated. However, merely translating documents is insufficient to ensure that consent is informed because illiteracy is prevalent in some contexts, language dialects vary substantially across regions, some words and terminology are not easily translated, translated written materials may not be helpful to some participants, and/or professional translators are not content experts so mistranslation may occur. Therefore, it may be more useful to train a research assistant/interpreter who can explain information about the study verbally to potential participants in their language of choice and answer any questions they may have about the study.

Regarding the plain language text, the G-EthicsHR-ZAF indicates that the text should be appropriate to the participants’ level of understanding, which means:

Translated into the language(s) best suited for the population and context of the study
Has content, language(s), and procedures that are simplified and modified to accommodate any written or verbal language differences or impairments with which the participant may present
Free of jargon and unexplained acronyms
Clear and explains technical terminology

Documenting Consent

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

The G-EthicsHR-ZAF indicates that there may be circumstances where alternative forms of obtaining consent are allowed when it is not possible to have written consent. If it is ethically justifiable for the specific circumstances, then verbal consent may be approved. Usually, if verbal consent is permitted, a witness attests that the person did consent to participation after indicating understanding of the information provided. In addition, sometimes the nature of the research requires electronic data collection, or the potential participants may have an impairment that prevents a personal face-to-face consent process with written consent. Alternatives to face-to-face personal consent may not occur without sound justification approved by a registered EC. The justification for an alternate format of consent process must be evidenced by clear descriptions of why an alternative is justified in the circumstances and how the interests of the potential participant are properly protected.

Per the G-EthicsHR-ZAF, where electronic consent is proposed, the research protocol must describe in detail the method and process for obtaining consent. Electronic signatures are a functional equivalent of a paper-based signature with the same legal authority if it meets legal requirements including:

A typed name at the end of an email
A scanned image of a handwritten signature embedded into a document
A digital signature

Further, the G-EthicsHR-ZAF states that with regard to telephonic (verbal) and electronic informed consent, EC reviewers of research protocols must insist on a proper decisive description of how informed consent will be regarded as authentic. The following electronic methods of obtaining informed consent are recommended:

Telephonic recruitment for research that poses more than minimal risk of harm should be limited to screening for eligibility, followed by face-to-face informed consent, or virtual informed consent via an electronic platform
Telephonic research surveys are possible for minimal risk studies, and verbal agreement to participate serves as informed consent
For research that poses more than minimal risk of harm, different electronic platforms could be used for different purposes: a technology (e.g., email) to screen and obtain informed consent and another system to collect data

Waiver of Consent

Per the G-EthicsHR-ZAF, any decision by the EC to grant a waiver of participant or legal representative/guardian consent must be documented and must include the justification for the decision. A waiver of consent to conduct the research can be justified on two (2) grounds: if the waiver will not infringe upon any right of a participant, and obtaining consent is impracticable; or if the rights infringement is minimal and is outweighed by the expected social value of the research, and obtaining consent is impracticable. Any decision by the EC to grant a waiver of participant or legal representative/guardian consent must be documented and must include the justification for the decision. A waiver of consent is not automatic and requires a researcher to apply to the EC for approval to use someone's personal information or personal health information without obtaining consent from the individual. The application must explain why a waiver is requested and how one of the justification criteria above applies. The EC must assess the level of risk of harm associated with a waiver, which refers to the risk of harm flowing from researchers accessing identifiable private information and not to risk of harm concerning the whole research project. An alteration of requirements for informed consent (as opposed to a full waiver) is possible, e.g., when existence of a signed consent form might pose a risk of harm (breach of confidentiality) to the participant in studies involving illegal behavior. The alteration may take the form of permitting unsigned informed consent documentation.

3, 4.4, 4.8, and 6

Booklet 4 (11, 12.3, and 15.1.3)

3.4 and 6.3

3.1

2.5 and 5.9

Chapter 9 (71)

Required Elements

Last content review/update: November 2, 2026

Based on the CanadaFDR and the G-TCPS2, the informed consent form (ICF) should generally include the following statements or descriptions in plain language, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Information that the individual is being invited to participate in a research project
The study involves research and an explanation of its purpose and duration
The identity of the researcher and the funder/sponsor
The procedures to be followed
The participant’s responsibilities
Any reasonably foreseeable risks or anticipated benefits to the participant and in general
Information about any payments, including incentives for participants, reimbursement for participation-related expenses, and compensation for injury
An assurance that prospective participants are under no obligation to participate and are free to withdraw at any time without prejudice to pre-existing entitlements
An assurance that prospective participants will be given, in a timely manner throughout the course of the research project, information that is relevant to their decision to continue or withdraw from participation
An assurance that prospective participants will be given information on their right to request the withdrawal of data or human biological materials, including any limitations on the feasibility of that withdrawal
Information concerning the possibility of commercialization of research findings, and the presence of any real, potential, or perceived conflicts of interest on the part of the researchers, their institutions, or the research sponsors
The measures to be undertaken for dissemination of research results and whether participants will be identified directly or indirectly
The identity and contact information of a qualified designated representative who can explain scientific or scholarly aspects of the research to participants
The identity and contact information of the appropriate individual(s) outside the research team whom participants may contact regarding possible ethical issues in the research
An indication of what information will be collected about participants and for what purposes
An indication of who will have access to information collected about the identity of participants
A description of how confidentiality will be protected
A description of the anticipated uses of data
Information indicating who may have a duty to disclose information collected, and to whom such disclosures could be made
A statement to the effect that, by consenting, participants have not waived any rights to legal recourse in the event of research-related harm
Information on stopping rules and when researchers may remove participants from trial
All other aspects of the clinical trial that are necessary for a person to make the decision to participate in the clinical trial

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Chapter 3

Part C (Division 5 (C.05.010))

Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Based on the informed consent essential elements in the SA-GCP, the G-EthicsHR-ZAF, the G-GPHlthCare, G-PostCTAccess, and the NHAParticipants, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The study involves research and an explanation of its nature and purpose, including that it conforms to the protocol
The procedures to be followed and their purpose and nature
Why the potential participant has been approached, their responsibilities, and the research-related activities and procedures that the participant is being asked to consent to
Who the researchers are, the nature of their expertise, and their responsibilities
The aspects of the clinical trial that are experimental
Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant; information should include the probability and magnitude of the foreseeable risks of harm
The measures to be taken to minimize risk of harm
Any benefits to the participant or to others that may reasonably be expected from the research both during and after 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 without explanation or prejudice, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
Compensation and/or medical treatment available to the participant in the event of a trial-related injury
The planned incentives, if any, to attract the participant and the planned reimbursements, if any, for time, inconvenience, and expenses
The extent to which confidentiality of records identifying the participant will be maintained, the possibility of record access by the sponsor, the ethics committee (EC), or the South African Health Products Regulatory Authority (SAHPRA)
How the personal information of participants, including confidentiality of data collected during the research, will be protected
Who will have access to participants' information, biological samples and associated data, including whether samples will be shared with other researchers
That participants may request that corrections to their information be made or that their information or samples be deleted or destroyed; in cases where withdrawal of samples and information is not possible, the potential limitations and consequences of not withdrawing samples and data from research should be explained
Instances where a legal obligation to disclose information may arise
Statement that participants may contact the EC at the contact details provided if they have questions or complaints about their rights and welfare
The sponsor’s identity
Potential conflicts of interest of the principal investigator (PI)
The consequences of a participant's decision to withdraw from the study
Information about approval from a registered EC and SAHPRA
Information about the EC monitoring the clinical trial
The approximate number of participants in the research study, locally and globally
The expected duration of participation
Whether feedback about the study will be provided and, if so, how it will be provided
Whether biological samples will be used for commercial benefit
Where relevant, whether incidental findings will be shared with participants
An explanation of whom to contact in the event of research-related injury
A statement that participants may contact the researcher at the contact details provided if they have questions about the research project
Foreseeable circumstances under which the investigator(s) may remove the participant without consent
The research may be terminated early in particular circumstances
The participant or legal representative/guardian will be notified if significant new findings developed during the study which may affect the participant's willingness to continue
Information on post-trial or continued access (PTA/CA)
Whether data and/or samples can be used after the person’s death, especially if it is possible that the person may die during the study
Description of a measure to probe understanding and comprehension of the information is planned (e.g., a teach-back method), and how it proposes to do so especially for very vulnerable potential participants

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

6.3

3.1 and 5.5

1.2, 2.5, 5.9, and 6.2

5

Participant Rights

Last content review/update: November 2, 2026

Overview

In accordance with the CanadaFDR and the G-TCPS2, Canada’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-TCPS2 states that a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

The Right to Participate, Abstain, or Withdraw

As stated in the G-TCPS2, the participant or legal representative/guardian should be informed that participation is voluntary, that they may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the G-TCPS2, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to the G-TCPS2, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-TCPS2 states that the research participant or legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or the participant’s rights.

The Right to Safety and Welfare

The G-FDR-0100 upholds the Declaration of Helsinki (CAN-58), which states that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

Good Clinical Practices

Chapter 1 (Article 1.1), Chapter 2, and Chapter 3 (Articles 3.1 and 3.2)

Part C (Division 5 (C.05.001 and C.05.005))

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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 SA-GCP, the G-EthicsHR-ZAF, the G-GPHlthCare, the G-GPHlthCare-IC, the NHAParticipants, the Declaration of Helsinki (ZAF-44), and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (ZAF-27), a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. Below are the basic rights for participants in clinical research studies. (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

According to the NHA and the NHAParticipants, everyone has the right to participate in any decision affecting their health or treatment, including research. The participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

According to the G-GPHlthCare-IC, a potential research study participant has a right to information about any condition or disease from which they are suffering, and investigators must inform users of their health status (except where there is substantial evidence that disclosure would be contrary to the user’s best interests), the range of diagnostic procedures and treatment options generally available, the benefits, risks, costs and consequences generally associated with each option, and the user’s right to refuse health services and the implications, risks, and obligations of such refusal. (See the Required Elements section for a more detailed list of the ICF’s contents.

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-EthicsHR-ZAF and the G-GPHlthCare, participants have the right to privacy and confidentiality. The G-GPHlthCare states that the researcher must ensure that where personal information about research participants or a community is collected, stored, used, or destroyed, it is done in ways that respect the privacy or confidentiality of participants or the community and complies with any agreements made with the participants or the community.

The Right of Inquiry/Appeal

The SA-GCP indicates that potential participants must have the identity of the person(s) to contact for trial-related queries and injuries, the ethics committee’s contact details for information and concerns on the rights of trial participants, and the identity of the sponsor. The G-EthicsHR-ZAF also indicates that all research study-related information and consent documentation must include contact details for a participant to make a complaint about being a research participant.

The Right to Safety and Welfare

The SA-GCP 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.

Booklet 4 (1-3)

2-4 and 6

1.1, 2.1, 2.3, 3.1, and 5.5

2.4-2.5, 4.3, and 5.9

Chapter 1 (2), Chapter 2 (8 and 11), and Chapter 9 (71)

Act, Preamble, and Chapter 2

2 and 5

Emergencies

Last content review/update: November 2, 2026

G-FDR-0100 states that in emergency situations, when prior consent of the participant is not possible, the consent of the participant's legal representative/guardian (as defined by provincial requirements), if present, should be requested. When prior consent of the participant is not possible, and the participant's legal representative/guardian is not available, enrollment of the participant should require measures described in the protocol and/or elsewhere, with documented approval by the ethics committee (EC) (known as a research ethics board in Canada), to protect the participant's rights, safety, and well-being, and to ensure compliance with applicable regulatory requirements. The participant or the participant's legal representative/guardian should be informed about the trial as soon as possible, and consent should be requested as appropriate.

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Per G-TCPS2, research involving medical emergencies must be conducted only if it addresses the emergency needs of the individuals involved, and then only in accordance with criteria established in advance of such research by the EC. The EC may allow research that involves medical emergencies to be carried out without the consent of participants, or legal representatives/guardians, if all of the following apply:

A serious threat to the prospective participant requires immediate intervention
Either no standard efficacious care exists, or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care
Either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect of direct benefits to the participant
The prospective participant is unconscious or lacks capacity to understand the risks, methods, and purposes of the research project
Authorization from the legal representative/guardian cannot be secured in sufficient time, despite diligent and documented efforts to do so
No relevant prior directive by the participant is known to exist

The G-TCPS2 states that consent will not apply to public health activities undertaken by federal, provincial, and territorial public health officials operating under statutory powers during publicly declared health emergencies. The Ethcs-Emrgcy is an educational resource that provides ethical considerations, including for consent, to help institutions, ECs, and researchers protect participants and uphold public trust in the ethics review and conduct of research during publicly declared emergencies. It includes examples of practical applications from various publicly declared emergency contexts.

Good Clinical Practices

Chapter 3 (Articles 3.7-3.9) and Chapter 6 (D)

Information on ICH guidelines implemented by Health Canada and Efficacy Guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

The NHA and the G-EthicsHR-ZAF make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies. As per the G-EthicsHR-ZAF, there are emergency situations that merit use of deferred consent (also called delayed consent). Usually, the circumstances entail a temporary loss of decision-making capacity and a reasonably held prognosis that the person will regain the capacity within a predictable period (e.g., an unconscious patient in the Emergency Unit who is predicted to regain consciousness within hours). Deferred consent should be used only where the likelihood of obtaining personal informed consent after the research has begun is likely. The ethics committee (EC) may approve use of deferred consent if the following conditions are met:

The proposed research is based on valid scientific hypotheses that support a reasonable possibility of more benefit than that offered by standard care
The individual has a temporary loss of decision-making capacity
There is a reasonably held prognosis that they will regain the capacity within a predictable period
Participation is not contrary to the medical interests of the patient
When the individual regains capacity to make decisions, they must be informed that they have been enrolled in a research study (i.e., deferred consent must be obtained); if they object to having been enrolled in the study, this counts as a refusal to participate, and they should be asked whether their data already collected must be withdrawn

If death of the participant occurs before deferred consent can be obtained, it should not be assumed that continued use of the data and/or samples is ethical. The deceased’s wishes or those of their proxy or mandate holder should be ascertained.

Per the G-EthicsHR-ZAF, during disease outbreaks, potential participants must be assisted to understand the research proposed and the implications of enrollment, despite the situational duress and anxiety. The notion that informed consent is a process does not change because the research is being conducted in pandemic circumstances. Research during a public health emergency must adhere to standard research ethics principles including informed consent.

Per the ZAF-40, 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 SAHPRA with the clinical trial application.

11.5-11.6 and Annex 1

3.1 and 3.3

Chapter 2 (7, 8, and 9)

Vulnerable Populations

Last content review/update: November 2, 2026

Overview

Per the G-FDR-0100, the responsibility of an institutional ethics committee (EC) (known as a research ethics board in Canada) is to protect the rights, safety, and well-being of all human participants. An EC should pay special attention to trials that may include vulnerable human participants (elderly, children, mentally ill, prisoners, etc.). The G-TCPS2 states that in all Canadian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

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

Good Clinical Practices

Chapter 3 (Article 3.9) and Chapter 4 (Article 4.7)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Overview

The NHA, the SA-GCP, the G-EthicsHR-ZAF, the G-GPHlthCare, and the NHAParticipants require special considerations for vulnerable populations, and characterize them by limited education, limited economic resources, inadequate protection of human rights, discrimination due to health status, limited ability to provide informed consent, limited availability of health care and treatment options, or an inadequate understanding of scientific research. Vulnerable populations include children/minors, mentally and physically disabled, pregnant women, substance abusers, prisoners, armed forces, the homeless, the elderly, members of a group with a hierarchical structure, patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, nomads, refugees, and other vulnerable groups such as persons in dependent relationships. (Note: Each of the items listed above will not necessarily be found in all sources, which provide overlapping and unique elements).

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

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

Per the G-EthicsHR-ZAF, where factors usually associated with vulnerability are integral to the research, the protocol should demonstrate how vulnerability will be managed. In cases where the researcher is known to the community and speaks the local language and/or is accepted as part of that community, this may be seen as a positive element for the research context. Special care should be exercised before undertaking research involving participants in such communities, and ECs should ensure that:

Persons in these communities are not being involved in the research merely because they are expediently accessible, while the research is feasible to undertake in a less vulnerable community
Research is relevant to the needs and priorities of the targeted community
Research participants know they will take part in research and that the research will be carried out only with appropriate consent

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

Persons in Dependent Relationships or Hierarchical Situations

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

Persons Highly Dependent on Medical Care

Per G-EthicsHR-ZAF, individuals who are highly dependent on medical care deserve special attention when considering research participation. The gravity of their medical condition may require invasive measures that carry increased risk of harm. The quality of informed consent may be compromised by the effect the medical condition has on the participant’s decision-making or communication abilities. A patient may be reluctant to refuse consent for fear that this may compromise their medical treatment. Adequate provision must be made for informing patients and their relatives about the research to ensure that stress and other emotional factors do not impair their understanding. Their dependency on caregivers should not unfairly affect research participation decisions.

Persons with Physical Disabilities

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

Elderly Persons

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

Research Involving Collectivities

Per the G-EthicsHR-ZAF, a collectivity is a term used to distinguish some distinct groups from informal communities, commercial, or social groups. Collectivities are persons who participate in research in groups distinguished by common beliefs, values, social structures, and other features that identify them as a separate group; customary collective decision-making according to tradition and beliefs; the custom that leaders express a collective view; and members of the collectivity being aware of common activities and common interests. Research involves a collectivity when property or information private to the group as a whole is studied or used; permission of people occupying positions of authority is required; and participation of members acknowledged as representatives is involved. Among other requirements, research involving collectivities should include measures to ensure an informed consent process for individual participants.

1, 2.4.6, 3.1, 4.1.2, 4.1.3, and 6.3

3.2

1.2, 3.1, 3.4, 6.2, and 12

1 and 4

Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), and Chapter 9 (70(2)(d) and 71)

Children/Minors

Last content review/update: November 2, 2026

Per CAN-35, because the G-TCPS2 does not specify an age of consent for children, the decision on whether to seek consent from children is based on whether they have the capacity to understand the research and the risks and benefits of their participation. Youth who have not reached the age of majority (either 18 or 19 depending on the province or territory) may still be old enough to provide their own consent. For children who are not sufficiently mature to provide consent but are able to understand the nature of study participation, researchers must obtain the child’s assent in addition to the consent of an authorized third party. The decision of a child not to assent must be respected regardless of whether third-party consent was obtained. (Note: CAN-35 offers practical guidance that is consistent with the G-TCPS2, but it is only required for research reviewed by the joint Health Canada (HC)-Public Health Agency of Canada (PHAC) Research Ethics Board (REB).)

CAN-35 provides the following criteria for determining whether participants can provide their own consent, or whether an authorized third party should be involved:

The risk level associated with the research project
The legal requirements for age of consent in that jurisdiction
The characteristics of the research participant (e.g., maturity level)
In certain cases, the topic of the research itself

CAN-35 states that it is generally accepted that youth can consent to minimal risk studies at 16 years of age, and that assent should be sought from children beginning at approximately seven (7) years of age. However, it is ultimately up to the researcher to determine whether to obtain assent or consent from children, and to provide the rationale for this decision to the ethics committee (EC) (known as a Research Ethics Board in Canada). Researchers should also consider that within a single research project, some minors may be capable of consenting while others may not. See CAN-35 for additional details regarding obtaining consent from minors.

As per the G-TCPS2, when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. All pediatric participants, however, should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the ICF.

As stated in G-TCPS2, children should only participate in clinical studies when the research objective cannot be achieved with adult participants only. When considering the inclusion of children in research, the investigators and ECs must consider a child’s stage of physical, physiological, psychological, and social development to ensure adequate protections for the child’s welfare.

Assent Requirements

G-FDR-0100 states that if minors are to be included in a trial, the EC should review the assent information considering the age, maturity, and psychological state of the minor population intended to be enrolled, as well as applicable regulatory requirements. Where a minor is to be included as a participant, age-appropriate assent information should be provided and discussed with the minor as part of the consent process, and assent from the minor to enroll in the trial should be obtained as appropriate. A process for consent should be considered if, during the trial, the minor reaches the age of legal consent, in accordance with applicable regulatory requirements.

Per G-TCPS2, where a child has some ability to understand the significance of the research, the researcher must ascertain the wishes of that individual with respect to participation. Children—whose decision-making capacity is in the process of development—may be capable of verbally or physically assenting to, or dissenting from, participation in research. While their assent would not be sufficient to permit them to participate in the absence of consent by the child’s parent/legal guardian, their expression of dissent must be respected. See TCPS2-InterpCnsnt for additional information.

Further, according to CAN-12, which offers best practices and guidance to researchers and ECs in pediatric research and complements the G-TCPS2, provincial laws in Canada vary as to when a child is presumed to be legally competent to provide informed consent. Some provinces use age while others use a competence-based evaluation.

As per CAN-12, if the pediatric participant has the capacity for assent, then affirmative assent is required to participate in a study according to the participant’s level of development and capacities. When the child develops the legal capacity to provide informed consent or attains the legal age of majority (which depends on the province), researchers should obtain an informed consent. Regarding dissent, CAN-12 states that the researchers must respect the dissent of a child who is capable of understanding.

For more details and guidance about best practices for research involving pediatric participants, see CAN-12.

Good Clinical Practices

Chapter 3 (Article 3.10) and Chapter 4 (Article 4.4)

1

Guidelines III and IV

Consent Process (Key Considerations)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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

Per the SA-GCP, documented permission from the parent/legal guardian must be obtained in advance prior to approaching the minor to request participation. According to the NHA, the SA-GCP, the G-GPHlthCare, and the G-GPHlthCare-IC, consent for minors to participate in research must be obtained from:

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

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

Where research or experimentation is to be conducted on a minor for non-therapeutic purposes, the NHA, the NHAParticipants, the SA-GCP, 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/legal guardian is provided
The consent of the minor is provided when the minor is capable of understanding

The G-EthicsHR-ZAF further indicates that the following are minimum conditions for an ethics committee (EC) to approve research with minors:

Their participation is scientifically essential to the research and investigates a problem of relevance to minors, and the protocol should provide sufficient information to justify why minors should be included as participants
Minors should only participate in research where such research poses acceptable risks of harm
Research involving minors must be reviewed appropriately, including pediatric or child research specialists as reviewers
Registered ECs’ deliberations are properly documented in minutes and recorded and include EC members with appropriate minor research experience
Minors should participate in research only when the required written permissions from the parent/legal guardian have been obtained
When a parent/legal guardian gives permission for their minor to choose whether to participate in research, this permission is given based on a detailed description of all diagnostic and therapeutic interventions that will affect the minor in the study
The informed consent documentation must explain whether results of tests will be made known to minor participants and their parents
The minor’s interest in confidentiality must be respected
The minor’s privacy interests are considered
Research involving minors must respect their evolving capacity to give consent
Researchers must familiarize themselves with the legal obligations to report minor abuse and neglect

See the NHAParticipants and G-EthicsHR-ZAF for detailed application requirements.

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

The study objective(s) can also be achieved if conducted on an adult
The research is unlikely to significantly improve scientific understanding of the minor’s condition, disease, or disorder to such an extent that it will result in significant benefit to the minor(s)
The reasons for the consent to the research by the parent/legal guardian and, if applicable, the minor, 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.

Assent Requirements

The SA-GCP requires the 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 assent should not be assumed simply because of failure to object during the informed consent process. It is necessary for the minor and the parent/legal guardian to be in agreement on participation. The minor’s refusal to participate is final.

Per the G-EthicsHR-ZAF, the parent/legal guardian does not choose for the minor who has factual capacity to choose, rather, the parent/guardian gives permission for the minor to choose (i.e., to assent to participation). Where a minor is very young (less than seven (7) years old) or is factually incapable of exercising a choice, then the parent/legal guardian chooses whether the minor should participate. When ECs review protocols that involve minors, it is critical to consider whether the required written permissions have been obtained, including assent from the minor in writing preferably (i.e., agreement to participate) if they choose to participate.

See the Personal Data Protection section for requirements on processing personal data of minors.

5, 6.3, and 8.5

Booklet 4 (8.5)

1-6 and Appendices 1-3

3.2 and 3.3

1.2, 2.5, 3.2, and 6.2

4 and 7

Chapter 9 (71)

Pregnant Women, Fetuses & Neonates

Last content review/update: November 2, 2026

As per the G-TCPS2, studies involving women of childbearing age, or who are pregnant, require additional safeguards to ensure that the research assesses the risks to the women and the fetuses. The following guidance applies to research involving materials related to human reproduction:

Research using materials related to human reproduction in the context of an anticipated or ongoing pregnancy must not be undertaken if the information can reasonably be obtained by alternative methods
Materials related to human reproduction for research use must not be obtained through commercial transaction, including exchange for services

Per the G-TCPS2, research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if:

The research is intended to benefit the embryo
Research interventions will not compromise the care of the woman, or the subsequent fetus
Researchers closely monitor the safety and comfort of the woman and the safety of the embryo
Consent was provided by the gamete donors

According to the G-TCPS2, research involving embryos that have been created for reproductive or other purposes permitted by law, but are no longer required for these purposes, may be ethically acceptable if:

The ova and sperm from which they are formed were obtained in accordance with the G-TCPS2
Consent was provided by the gamete donors
Embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy
Research involving embryos will take place only during the first 14 days after their formation by combination of the gametes, excluding any time during which embryonic development has been suspended

Per the G-TCPS2, research involving a fetus or fetal tissue:

Requires the consent of the woman
Must not compromise the woman’s ability to make decisions regarding continuation of her pregnancy

Chapter 4 (Article 4.3) and Chapter 12 (Articles 12.6-12.9)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA’s Guidelines to Clinical Trials in Pregnancy and Lactation (Effective June 1, 2026)
South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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

The G-EthicsHR-ZAF states that any proposed exclusion of women participants must be justifiable in light of research priorities as well as the specific research question under consideration. Systematic class exclusion must be guarded against to avoid unfair participant selection. Additional health concerns arise during pregnancy, including the need to avoid unnecessary risk to the embryo, fetus, or infant; however, automatic exclusion of pregnant women should be avoided to prevent data inequities for pregnant and nursing women. Researchers and ECs should exercise extra caution when women participants are or may become pregnant. Exclusion of women from research may be justifiable to protect the health of the embryo, fetus, or infant, and if exclusion is scientifically supportable. The informed consent documents must explain carefully and fully what the effects of the research activities on the embryo, fetus, or infant might be. Usually, research involving pregnant women should be undertaken when:

The purpose of the proposed research is to meet the health needs of the mother of the embryos, fetuses, or infants
Appropriate studies on animals and nonpregnant women have been completed
The risk of harm to the embryo, fetus, or infant is minimal, when procedures or interventions have no potential individual benefit for the women or embryo, fetus, or infant
The risk of harm is outweighed by the prospect of potential individual benefit, when procedures or interventions have potential individual benefit for the women or embryo, fetus, or infant
In all cases, inclusion poses the least risk of harm possible for achieving the objectives of the research

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

3.2

1.2, 6.2, and 10.7

Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), Chapter 9 (70(2)(d) and 71), and Chapter 11 (90(1)(s) and 90(2))

Prisoners

Last content review/update: November 2, 2026

According to the G-TCPS2, prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study involving prisoners should ensure that these prospective participants are informed and are given the opportunity to make their own decisions without any interference from a higher authority.

Chapter 3 (Article 3.1) and Chapter 4 (Article 4.7)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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

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

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

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

3.2

4

Chapter 2 (7, 8, and 11) and Chapter 9 (71)

Mentally Impaired

Last content review/update: November 2, 2026

According to the G-TCPS2, the ethics committee (EC) (known as Research Ethics Board in Canada) must approve the participation of research participants who are mentally or physically incapable of giving consent.

The G-TCPS2 indicates that for research involving individuals who lack the capacity, either permanently or temporarily, to decide for themselves whether to participate, the EC must ensure that, at a minimum, the following conditions are met:

The researcher involves participants who lack the capacity to decide on their own behalf to the greatest extent possible in the decision-making process
The researcher seeks and maintains consent from the participant’s legal representative/guardian in accordance with the best interests of the persons concerned
The legal representative/guardian is not the researcher or any other member of the research team
The researcher demonstrates that the research is being carried out for the participant’s direct benefit, or for the benefit of other persons in the same category; if the research does not have the potential for direct benefit to the participant but only for the benefit of the other persons in the same category, the researcher must demonstrate that the research will expose the participant to only a minimal risk and minimal burden, and demonstrate how the participant’s welfare will be protected throughout the participation in research
When authorization for participation was granted by a legal representative/guardian, and a participant acquires or regains decision-making capacity during the course of the research, the researcher must promptly seek the participant’s consent as a condition of continuing participation

The G-TCPS2, the participant’s legal representative/guardian can provide consent for adults who lack the capacity to decide on their own behalf in accordance with the best interests of the persons concerned. In such cases, participants should still be involved to the greatest extent possible in the decision-making process, and their assent to participate must be obtained if they are capable of expressing their wishes in a meaningful way (whether verbally or physically). Importantly, when authorization for participation was granted by the participant’s legal representative/guardian and a participant acquires or regains decision-making capacity during the course of the research, the researcher must promptly seek the participant’s consent as a condition of continuing participation.

Chapter 3 (Article 3.7-3.10)

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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

Per the G-EthicsHR-ZAF, research involving adults with incapacity should be approved only if:

The research, including observational research, is not contrary to the best interest of the individual
The risk of harm assessment shows that the research, including observational research, places the incapacitated adult at no more than minimal risk
The research involves greater than minimal risk but provides the prospect of direct benefit for the incapacitated adult; the degree of risk must be justified by the potential benefit
The research, including observational research, involves greater than minimal risk, with no prospect of direct benefit for the incapacitated adult, but has a high probability of providing generalizable knowledge (i.e., the risk should be justified by the risk-knowledge ratio)
Greater than minimal risk must represent no more than a minor increase over minimal risk
Where appropriate, the person assents to participation (Note that the incapacitated person’s refusal or resistance to participate, as indicated by words or behavior, takes precedence over permission by a proxy)

As delineated in the G-EthicsHR-ZAF, proxy decision-makers for incapacitated adults are not permitted in South African law unless the proxy is a court appointed curator or holds a statutory mandate to make health care decisions for the now incapacitated person pursuant to the NHA. Incapacity may not be assumed but requires independent and objective assessment by appropriately trained persons. If the research participant regains capacity to make decisions, they must be informed that they have been enrolled in a research study. If they object to having been enrolled in the research study, this counts as a refusal to participate, and their data must be withdrawn. If the participant does not object, personal consent may be desirable depending on the length and complexity of the study.

4 and 6.3

3.1 and 3.2

1.2, 3.3, and 6.2

4

Chapter 2 (7, 8, and 11), and Chapter 9 (71)

Definition of Investigational Product

Last content review/update: November 2, 2026

As delineated in the CanadaFDR and the G-GMP-Annex13, 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, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form.

For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

5.1

Appendix A

Part C (Division 5 (C.05.001))

Last content review/update: March 19, 2026

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

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

2

Annex 13

1.2, 6.2, and 12

Manufacturing & Import

Last content review/update: November 2, 2026

Manufacturing

As specified in the CanadaFDR and the G-CanadaCTApps, Health Canada (HC) authorizes the manufacture of investigational products (IPs) in Canada. HC approves the manufacture of IPs as part of the clinical trial application (CTA) approval. The G-QCM-PharmCTAs provides guidance and templates to assist sponsors in completing the quality portion of the CTA, which in turn, enables HC to assess IP characteristics adequately. The G-GMP-Annex13 requires the sponsor to ensure that IPs for clinical trials are manufactured and imported in accordance with its provisions and with CanadaFDR requirements. Per the G-CanadaCTApps, sponsors must file amendments or notifications to a previously authorized CTA when manufacturing changes are proposed that may affect the quality or safety of the clinical trial drug or biologic supplies.

Per G-GMP-Annex13, during development, critical parameters and in-process controls should be identified, adapted based on production experience, and justified by the knowledge available at the time. Although the manufacturing process need not be validated to the extent necessary for routine production, premises and equipment are expected to be validated in accordance with applicable good manufacturing practice (GMP) principles. Manufacturers must identify process steps that ensure participant safety and the reliability and robustness of clinical trial data and maintain written cleaning procedures and analytical methods to prevent cross-contamination. For sterile products, controls and processes related to sterility should meet the same standards as those for marketed products; where required, virus inactivation/removal and removal of other biological impurities should be demonstrated, with enhanced attention to aseptic-process validation and operator training. If a drug is modified, data such as stability, comparative dissolution, or bioavailability should demonstrate that the changes do not significantly alter its original quality characteristics; the sponsor should justify an appropriate retest date, and a reference sample of the comparator product should be retained following repackaging or over-encapsulation. For blinded products, systems should maintain the blind while permitting rapid product identification when necessary; where the manufacturer generates randomization codes, unblinding information should be available to the person in charge of quality control before the drugs are supplied, and the expiry assigned to all products should correspond to that of the shortest-dated product. See the G-GMP-Annex13 for additional details.

Per CAN-55, HC is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) and meets international GMP standards.

Per CAN-50, Canada has implemented the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which provides additional guidelines on manufacturing IPs. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Import

Per the CanadaFDR and the G-FDR-0100, HC authorizes the sponsor to import an IP. A sponsor who is not based in Canada must have a Canadian representative who is responsible for the import of the IP and demonstrates compliance with the applicable regulatory requirements. This representative should be the sponsor’s senior medical or scientific officer residing in Canada and is responsible for providing an attestation with respect to the CTA at the time of filing. Per the G-CanadaCTApps, the G-DrugApp, and CAN-4, if clinical trial drugs are to be imported into Canada, the authorization template (Appendix 1) in CAN-4 should be completed and submitted for each importer in Canada. The G-DrugApp states that Canadian importer(s) must be located within Canada. As additional importers are identified, additional copies of the authorization template in CAN-4 should be provided to HC.

The G-FDR-0100 provides additional guidance on requirements if a sponsor plans to send the clinical trial IP(s) directly to each trial site:

A No Objection Letter (NOL) has been issued by HC authorizing the importation of the clinical trial material in Phase I-III trials; no clinical trial drugs should be imported prior to the NOL issuance and the NOL should accompany the package at the time of the importation
Each party, including individual Canadian clinical trial sites, importing drugs directly (i.e., receiving drug shipments directly from outside of Canada) is identified on Appendix 1 of the Drug Submission Application Form (HC/SC 3011 form) (CAN-4)
Clinical Trial Site Information (CTSI) forms (CAN-6) for each Canadian site conducting the clinical trial are submitted to HC for Phase I-III trials, prior to the start of the study
Systems are in place, when appropriate, to monitor the transportation and storage conditions from the foreign source to the various clinical trial sites across Canada
There is documented accountability of the imported drugs used in clinical trials and distributed to various clinical trial sites located in Canada, including the disposition of drugs returned from the clinical trial sites
A written agreement is in place between the sponsor and the qualified investigator (QI) describing their specific responsibilities, and this agreement is available at the clinical trial site
There is evidence that the drugs used in clinical trials conducted in Canada meet GMP requirements (e.g., certificates of manufacture, certificates of analysis, and/or evidence of approved lot release by a QI)

The G-CanadaCTApps, the G-HlthProdImprtExptReqs, the G-FDR-0100, and CAN-32 state that if a sponsor wants to import a drug into Canada for a clinical trial, a copy of HC’s authorization (i.e., the NOL) issued by either the Pharmaceutical Drugs Directorate (PDD) or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) must be included for the applicable trial with the shipment. A copy of this authorization must be provided at the port of entry. The G-HlthProdImprtExptReqs states that drugs without a Drug Identification Number may be imported where authorized for a Canadian clinical trial and a NOL was issued. The G-FDR-0100 further states that if 30 days have passed and the NOL was not issued, specific requests to import IPs should be directed to the Health Product Border Compliance Program at the following email account: hpbcp-pcpsf@hc-sc.gc.ca. Note that a sponsor does not have to submit a CTA for authorization to import an IP used in a Phase IV clinical trial.

Per CanadaFDR, the sponsor can make the following changes to the authorized use or importation of drugs if the sponsor notifies HC in writing within 15 days after the date of the change:

A change to the chemistry and manufacturing information that does not affect the quality or safety of the drug
A change to the protocol that does not alter the risk to the health of a clinical trial participant

Other changes must follow the amendment requirements delineated in the CanadaFDR. See the G-FDR-0100 for additional HC interpretations of the relevant provisions of the CanadaFDR.

2.3 and 2.7

Section # Block D and Appendix 1 Guidance

Application and Authorization and Good Clinical Practices

1.0 and 8.2-8.4

Importer’s Role, Table 1, and Human Drugs

I Introduction, S Drug Substance, and P Drug Product

Part C (Divisions 2-5)

Appendix 1

Drug Importation

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

SAHPRA has issued the following:

Guidelines for Good Manufacturing Practice of Medicines (Version 10, Effective April 2026)
Guideline on How to Apply for a License to Manufacture, Import, and/or Export Medicines and Scheduled Substances (Version 4, Effective March 2026)

Manufacturing

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

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

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

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

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

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

Import

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

The CTA-Import indicates that there have been delays in the release of IPs at the SAHPRA border control because the import licenses (clinical trial approval letters) have not specified the quantities of study medication authorized for importation. To address this problem, a protocol amendment application (ZAF-20) is required to request the approval of the remaining study medication to be imported for these specific trials. Applicants will be allowed six (6) months from the date of the CTA-Import (i.e., from September 19, 2024) to obtain the necessary approvals.

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

Please note: South Africa is party to the Nagoya Protocol on Access and Benefit-sharing (ZAF-8), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see ZAF-34.

1.1, 3.1.2, and Appendices 1-2

3

Annex 13

1.2, 5.7, 6.2, and 6.6

21 and 22C

23

Quality Requirements

Last content review/update: November 2, 2026

Investigator’s Brochure

In accordance with the CanadaFDR, the sponsor is responsible for providing the investigators with an Investigator’s Brochure (IB). The IB must contain all the relevant information on the investigational product(s) (IPs), including significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information. The sponsor must ensure that an up-to-date IB is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee. Per CAN-50, Canada has implemented the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which provides additional guidance on IB development and contents. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

The CanadaFDR requires 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; and regulatory and post-marketing experiences)
Summary of data and guidance for the investigator(s)

In accordance with the G-CanadaCTApps, the sponsor must submit annually to HC an updated IB, which serves as the annual report, including all safety information and global status. Revisions that are more frequent may be appropriate depending on the stage of development and the generation of relevant new information.

Quality Management

As specified in the G-GMP-CAN and G-GMP-Annex13, the sponsor must ensure that the products are manufactured in accordance with good manufacturing practice (GMP). The G-GMP-CAN requires a quality management system, incorporating GMP, to ensure that IPs are of the quality required for their intended use.

Per the G-GMP-Annex13, the manufacturer’s quality system should be described in written procedures and available to the sponsor, taking into account GMP principles and guidelines. The manufacturer should establish and maintain a quality control system placed under the authority of a person who has the requisite qualifications and is independent of production. Quality control of the clinical trial drug, including that of the comparator product or placebo, should be performed in accordance with the information submitted in the application for the clinical trial, as authorized by the relevant country. Verification of the effectiveness of blinding should be performed and recorded.

Per the G-FDR-0100, if a sponsor plans to send the clinical trial IP(s) directly to each trial site, there should be evidence that the drugs used in clinical trials conducted in Canada meet GMP requirements (e.g., certificates of manufacture, certificates of analysis, and/or evidence of approved lot release by a qualified individual).

2.8

4, 8.2, and 9.0

4

Part C (Division 5 (C.05.001, C.05.005, and C.05.012))

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: March 19, 2026

Investigator’s Brochure

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

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

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

Quality Management

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

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

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

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

2

Part II (11.4) and Annex 13

1.2, 5.7, 6.2, 6.5, 6.7, and 8

Labeling

Last content review/update: November 2, 2026

Investigational product (IP) labeling in Canada must comply with the requirements set forth in the CanadaFDR, the G-CanadaCTApps, and the G-GMP-Annex13. The CanadaFDR and the G-CanadaCTApps state that for an IP to be used in a clinical trial, it must be properly labeled in both official languages: English and French. The CanadaFDR requires that IPs be packaged and labelled under the supervision of personnel who have had satisfactory technical, academic, and other training. The packager and/or labeler must have written procedures and ensure that the IP is packaged, labelled, and tested in compliance with those procedures. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. Per CAN-50, Canada has implemented the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which provides additional guidelines on labeling IPs. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

As delineated in the CanadaFDR and the G-GMP-Annex13, the following information must be included on the IP label:

A statement indicating that the drug is an IP to be used only by a qualified investigator
Name, number, or identifying mark
Expiration date
Recommended storage conditions
Lot number
Sponsor’s name and address
Protocol code or identification
Radiopharmaceutical information, if applicable

Per the G-FDR-0100, a label includes any legend, word, or mark attached to, included in, belonging to, or accompanying any drug or package. The sponsor is responsible for ensuring that the labeling of a clinical trial drug meets the requirements of the CanadaFDR, and that the system in place is validated, traceable, and does not compromise participant safety or product quality. The required information must be attached to, included with, or accompany each container of the drug product. If a label provides all the required information in both official languages (English and French), it is considered to have met the requirements of the CanadaFDR. However, traceability to the manufacturing lot should be maintained on the label immediately attached to the IP (i.e., primary container) such that its identity can be determined, and, if necessary, which unit was dispensed to each participant. For blinded clinical trials the sponsor must ensure that labeling information does not compromise the blinding. Labeling of a clinical trial drug with a manufacturer's lot number may compromise a blinded clinical trial. Identifiers other than a "lot" or "(L)" number (for example a batch number, a kit number, or a bar code) may be considered compliant, provided traceability is maintained. Where a bar code is included as the identifier on the label, the code on the drug label should readily link to information (for example, lot number and expiration date) through a validated computerized system. During an inspection, HC may verify that there is a system of traceability in place to ensure participant safety and that the computerized system, if applicable, is fully validated. It is acceptable for a marketed drug used in a clinical trial as a comparator, to be labelled in accordance with its marketing authorization, provided that the label on the marketed drug is appropriate for the trial. However, a marketed comparator drug used off-label must comply with the IP labeling requirements.

With regard to the expiration date, the G-GMP-Annex13 states that if it becomes necessary to change the expiration date, an additional label should be affixed to the IP. This additional label should state the new expiration date and repeat the batch number. It may be superimposed on the previous expiration date, but for quality control reasons, not on the original batch number. This operation should be performed at an appropriately authorized manufacturing site. However, when justified, it may be performed at the investigational site by or under the supervision of the clinical trial site pharmacist or other health care professional in accordance with national regulations and with the sponsor’s requirements. Where this is not possible, it may be performed by the clinical trial monitor(s) who should be appropriately trained. The operation should be performed in accordance with good manufacturing practice (GMP) principles, operating procedures, and applicable contractual provisions, and should be checked by a second person. This additional labeling should be properly documented in both the trial documentation and in the packaging records.

As indicated in the G-FDR-0100, HC may verify that a clinical trial drug has a valid expiration date during an inspection. If stability studies to support the expiration date for an IP are still ongoing at the time of labeling, the following may be considered acceptable in lieu of an expiration date:

A re-test date on the label if the sponsor has data to support the extended shelf-life of the drug, and
A manufacturing date is listed on the label, as long as the clinical trial site where the drug is dispensed has a document from the sponsor documenting the shelf-life of the drug

The above process should be documented, and procedures and quality control systems should be in place and in accordance with the approved clinical trial application. This additional labeling information should be properly documented in both the trial documentation and in the packaging records.

2.8.7

Labelling and Records

8.6

Part C (Divisions 2 (C.02.006, C.02.011, C.02.015-016) and 5 (C.05.011))

Efficacy guidelines

Last content review/update: March 19, 2026

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

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

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

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

2

Annex 13

1.2 and 6.6

35

10 and 30 (9)

Product Management

Last content review/update: November 2, 2026

Supply, Storage, and Handling Requirements

Per CanadaFDR, drugs must be manufactured, handled, and stored in accordance with good manufacturing practice (GMP). For investigational product (IP) packaging, the G-GMP-Annex13 provides the following guidance:

The risk of product mix up must be minimized by using appropriate procedures, specialized equipment, and relevant staff training.
To prevent errors, particularly when IPs are blinded, use heightened precautions, such as label reconciliation, line clearance, and in-process control checks by appropriately trained staff.
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.

The G-Storage provides principles and interpretations on the environmental control of clinical trial drugs during storage and transportation, including packaging. See G-Storage for information regarding compliance with the CanadaFDA and the CanadaFDR, as it relates to packaging clinical trial drugs for human use, such as the role of environmental controls, quality risk management, and special considerations for active pharmaceutical ingredients.

G-Dcntrl states that for decentralized activities, sponsors and qualified investigators (QIs) must ensure GMP- and protocol-compliant transport, storage, and handling of IPs. Sponsors are responsible for preserving product integrity during transport and storage and addressing controlled-substance diversion risks. QI oversight may include maintaining accountability for the IP at decentralized locations. Sponsors should ensure that direct-to-home shipment and dispensing comply with applicable provincial and territorial requirements.

Per CAN-50, Canada has implemented the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which provides additional guidance on IP management. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Record Requirements

As set forth in the CanadaFDR, the G-FDR-0100, and the CanadaFDR1024, the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR states that the sponsor should maintain all trial-related records for a period of 15 years. Pursuant to CanadaFDR1024, the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to Health Canada (HC) within seven (7) days of a request.

Per the G-FDR-0100, drug accountability records should include the following information:

Date of arrival on site
Quantity received
Identification (batch/lot number)
Expiration date
Quantity and date dispensed and to whom
Quantity and date returned by participants
Quantity and date of destruction or return to sponsor

As explained in the G-FDR-0100, to ensure that participants receive the IP according to their randomization, qualified investigators (QIs) should maintain records. The QI and/or a pharmacist or other appropriate individual should maintain records of the product's delivery, the inventory, the use by each participant (including documenting that the participants were provided the doses specified by the protocol), and the return to the sponsor and destruction or alternative disposition of unused product(s). Drug accountability records are required for:

Drugs that are the subject of the clinical trial, and do not have market authorization
Drugs that are the subject of the clinical trial, have market authorization, but are used off-label
Comparator drug, if it does not have market authorization
Comparator drug, if it has market authorization, but its labeling was changed (for example for blinding purposes)
Comparator drug, if it has market authorization, but is used off-label (unless it was not considered to be investigational in the context of the particular clinical trial, based on the assessment of the application)

Further, per in the G-FDR-0100, drug accountability records are not required for:

Drugs that are the subject of a Phase IV clinical trial
Comparator drug, if it has market authorization, is used on-label, and has not been altered in any manner
Rescue or concomitant medications, authorized for sale in Canada, that may be used on or off-label but are not the subject of the clinical trial (for example, they are used as supportive medications for known clinical applications)

The G-Storage provides that when contracted parties, such as warehouses or commercial carriers, store or transport drugs, there should be a written agreement that outlines all relevant conditions.

See CAN-52 for additional guidance on IP record keeping.

Designing the trial, Quality management systems, and Roles and responsibilities

Labelling and Records

8.6

Part C (Division 5 (C.05.001, C.05.005, C.05.010, and C.05.012))

Regulatory Impact Analysis Statement

Efficacy guidelines

Last content review/update: March 19, 2026

Supply, Storage, and Handling Requirements

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

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

Per the SA-GCP, 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-GPP. The sponsor must inform all parties involved (e.g., monitors, investigators, pharmacists, storage managers) of these determinations.

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

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

Record Requirements

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

Annex 13

1.2, 5.7, 6.2, 6.6-6.7, and 8.1-8.2

Definition of Specimen

Last content review/update: November 2, 2026

In Canada, a specimen is referred to as “human biological material” or “biological material.” According to the G-TCPS2, human biological materials include tissues, organs, blood, plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva, and other body fluids. The term also comprises materials related to human reproduction, including embryos, fetuses, fetal tissues, and human reproductive materials. The G-TCPS2 breaks down human biological material further into the following categories: anonymized, anonymous, coded, and identified human biological materials. Refer to the G-TCPS2 for more detailed information on these categories.

In addition, CAN-2 defines biological material as pathogenic and non-pathogenic microorganisms, proteins, and nucleic acids, as well as any biological matter that may contain microorganisms, proteins, nucleic acids, or parts thereof. Examples include, but are not limited to, bacteria, viruses, fungi, prions, toxins, genetically modified organisms, nucleic acids, tissue samples, diagnostic specimens, live vaccines, and isolates of a pathogen (e.g., pure culture, suspension, purified spores).

Chapter 12 and Glossary

Glossary

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

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 NHABiol and the G-EthicsHR-ZAF define “human biological materials (HBM)” 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. The G-EthicsHR-ZAF states that blood and blood products are also included pursuant to NHASpecAmend. The NHABloodCells generally refers to substances of human origin as biological substances.

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

Appendix 1 (A1.1)

1

Specimen Import & Export

Last content review/update: November 2, 2026

Import/Export

According to the G-HlthProdImprtExptReqs, Health Canada (HC) does not have jurisdiction over human biological materials to be imported for testing or research purposes. The G-HlthProdImprtExptReqs further states that all blood samples as well as cultures, diagnostic specimens, or research tissue may be potential carriers of human or animal pathogens, and are regulated by the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA). Per CAN-24 and CAN-2, the PHAC’s Centre for Biosecurity oversees the licensing process under the authority of the HPTA and the HPTR. The HPTA states that a license must be issued by the Minister that authorizes the import or export of human pathogens or toxins.

As specified in the HPTA, the HPTR, and CAN-2, individuals planning to conduct controlled activities (including producing, possessing, handling, using, storing, providing access to, transferring, disposing of, releasing, abandoning, or importing/exporting) with a human pathogen or toxin, whether imported or domestically acquired, must obtain a license. Per CAN-2, because all human biological materials are potential carriers of human pathogens, the PHAC has categorized these materials by risk group based on risk to the individual/animal and risk to the community. Risk Group 1 consists of microorganisms, nucleic acids, or proteins that are unable or unlikely to cause human or animal disease so they are generally not considered to be pathogens, and are therefore exempt from the HPTA and the HPTR licensing requirements. Risk groups 2 through 4 are considered to be pathogens or toxins with moderate to high individual risk and low to high community risk, and are subject to the HPTA and the HPTR licensing requirements. See CAN-2 for detailed information and instructions on how to obtain a license for activities associated with Risk Groups 2 through 4.

Other Considerations

Per the G-TCPS2, institutions and researchers that maintain biobanks must ensure that they have or use appropriate facilities, equipment, policies, and procedures to store human biological materials safely, and in accordance with applicable standards. They must also establish appropriate physical, administrative, and technical safeguards to protect human biological materials and any information about participants from unauthorized handling. Procedures for storage and record keeping must include effective measures to ensure that participants’ identities are protected, including the security of facilities and effective procedures for data handling, record keeping, and regulating access to human biological materials and information. Appropriate governance of biobanks is also important for managing access to and use of stored biological materials. The appropriate governance structure and management of a biobank will vary depending on its size and usage. Organizations that maintain biobanks may have their own policies on privacy of, confidentiality of, and access to materials. Researchers should be aware of requirements for compliance with such policies. Identifiable data derived from human biological materials may be linked to other research or public databases. Researchers who propose to engage in data linkage must obtain ethics committee (EC) approval prior to carrying out the data linkage. Where data linkage involves or is likely to produce identifiable information, researchers must show that the data linkage is essential to the research, and appropriate security measures will be implemented to safeguard information.

Blood and blood components for transfusion

Chapter 5 (5.7) and Chapter 12 (12.5)

Purpose of the Act, Interpretation and Application, Obligation, Prohibitions, and Licenses

Licenses

Chapters 1 and 2

Last content review/update: March 19, 2026

New Info (Not Yet in Profile)

South African Ethics in Health Research Guidelines: Principles, Processes and Structures (3rd Edition, Version 3.2) (Effective May 2026)

Import/Export

Per the NHA, the MTA-Human, the NHABloodCells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, a permit must be obtained from the National Department of Health (NDOH) Director General to import or export human biological material (HBM). Both the South African Health Products Regulatory Authority (SAHPRA) approval letter and the NDOH import/export permit must be included with each HBM shipment. See also the Submission Content section for information on completing a clinical trial application. (Note that HBM is referred to as a “biological substance” in the older South African regulations (e.g., the NHABloodCells); this summary will hereinafter use HBM to refer to human biological material, specimens, and biological substances.)

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

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

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

Per the G-EthicsHR-ZAF, sharing HBM and data about HBM must comply with the POPIA and may not occur unless:

The recipient is in a country that has similar legal protections for processing of personal information
For situations where the recipient is in a country that does not have an adequate level of protection, prior authorization has been obtained or there is a code of conduct in place
The data subject has consented specifically to the intended transborder data sharing
The transfer is necessary in terms of a contract or for the benefit of the data subject

In addition, per the G-EthicsHR-ZAF, ethics committees (ECs) should consider the following during the review process for proposed HBM and HBM data sharing:

The recipient of such data should have the necessary research approvals to use the data for research purposes
The recipient should comply with the POPIA requirements, have clear processes to deal with possible data breaches, and must inform the provider and EC should a breach occur
The recipient must specify the timeframe for storage of the data and its destruction, where relevant
Any proposed re-use of the data not specified in the protocols should be subject to EC review and approval, as well as approval from the provider
Intellectual property rights must be specified
If the HBM and data are shared only for research purposes, such HBM and data cannot be used for commercialization
The researchers involved in HBM and data sharing must ensure that proper updated records are kept
Where data alone is shared, a Data Transfer Agreement (DTA) or Data Sharing Agreement (DSA) is necessary

General Import/Export Requirements for HBM

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

As per the NHABloodCells, export permits for HBM 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 HBM. The applicant must also provide the Director-General with written information on stock levels for this substance along with the export application.

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

Import/Export Requirements for Specific HBM Categories

The NHABloodCells provides details on unique application requirements for specific types of HBM 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 HBM complies with the NHA requirements
Import or export of placenta tissue, embryonic or fetal tissue, embryonic, fetal or umbilical stem cells: applications will only be approved with the Minister’s written consent
Import or export of blood or blood products: applications must be accompanied by a national blood transfusion service certificate and test results. If no documentation is included, the applicant must submit a letter to the Director-General explaining the reason. The Director-General will decide whether tests must be conducted, and the Minister is authorized to determine whether the applicant’s institution can be exempted from these requirements.

Material Transfer Agreement

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

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

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

The G-EthicsHR-ZAF indicates that the MTA covers the transport of HBM between institutions/organizations within the country and cross-border transfers to provide access by the recipient to that material. The MTA should provide guidance on key issues, such as:

Purpose of the transfer of the HBM
Obligations of the parties
Terms and conditions under which HBM may be used
Whether modifications to the HBM are permissible
Whether third-party transfers may happen
What the benefit-sharing arrangements are
The relevant intellectual property rights
The indemnity arrangements

Research institutions may tailor the content to suit their individual contexts. Although some MTAs may include clauses governing sharing of data, it is advisable, as part of data management, to enter into separate data sharing agreements to regulate sharing of one (1) or more data sets from the custodian/provider to a third party.

4.2

2-13 and Forms 1 and 2

Chapter 8 (54, 57, 60, and 68)

Chapter 9 (72)

2-5, 7, and Annexures 1-6

Cover page, 3, 4.1, and Annexure A

1 and 2

1, 3, and 16

Consent for Specimen