Clinical Trials and Clinical Investigations under Regulation 16 in South Africa

1. Key takeaways

South Africa has dedicated provisions for medical device clinical trials and clinical investigations: Notice 1515 Regulation 16 (Conduct of clinical trials and clinical investigations) governs how they are carried out. The accompanying requirements include: the registration application must state the name and physical address of the clinical investigation site (where applicable) (Regulation 8(5)(b)(vii)); the authorised representative (AR) is, by definition, responsible for compliance with the conditions of clinical trials or clinical investigations; and SAHPRA also lists clinical trial approvals among the regulatory activities to which reliance may apply in its reliance guidance (SAHPGL-MD-22). Three practical threads run through these requirements. The definitions in Regulation 1 distinguish clinical trials of devices from clinical performance studies of IVDs, and the two serve different evidentiary aims even though Regulation 16 governs both. The reporting timelines for trial adverse events follow the same three bands as post-market vigilance, namely 48 hours, 10 calendar days and 30 days, so a single SOP framework can serve both phases. And because the compliance responsibility for trial conditions cannot be contracted away, any outsourcing to a CRO or hospital must preserve the AR’s access to complete study records.

2. Legal basis

3. Expert insights

Insight 1: Regulation 1 defines clinical trials and IVD clinical performance studies as distinct categories. The definitional provision sets out clinical investigation or clinical trial, concerning devices and involving human or animal subjects to discover or verify safety or clinical performance, and clinical performance study of an IVD, to establish or confirm the clinical performance of an IVD. Both are governed uniformly under Regulation 16, but their evidentiary aims differ, and companies should make clear at protocol design stage which category a study belongs to. The category determines the endpoints, the statistical expectations and the evidence the study is meant to generate for the dossier, so an early misclassification propagates through ethics applications, monitoring plans and the eventual evaluation report.

Insight 2: Clinical investigation site information enters the registration application. Regulation 8(5)(b)(vii) requires the application form to state the name and physical address of the clinical investigation site. This design links clinical research directly to product registration, and it means SAHPRA can trace the source sites of the data and, where necessary, conduct inspections of development and manufacturing sites; Regulation 8(5)(b)(vi) likewise requires the name and physical address of the original manufacturer to be reported. Companies should treat site data as regulated submission content with the same change discipline as any other dossier field, updating it when studies move or add sites.

Insight 3: The AR’s scope of responsibility expressly includes clinical trial conditions. Under the definitions in Notice 1515, the AR is responsible for all aspects of the device, including performance, quality and safety, and compliance with registration conditions, clinical trials or clinical investigations. This means that even where the study is executed by a CRO or a hospital, the compliance responsibility still rests with the AR, and companies that outsource must ensure the AR can obtain complete study records. Contract terms should give the AR a documented right of access to the investigator site file, monitoring reports and safety listings, so that the responsibility is matched by information.

Insight 4: Adverse events in clinical trials have their own reporting timelines. Under SAHPGL-MD-03 v4 and SAHPRA’s frequently asked questions: events constituting a serious health threat are reported within 48 hours; unexpected serious adverse device reactions (USADE) and serious adverse events leading to death or serious deterioration in health are reported within 10 calendar days; other serious adverse events and device deficiencies are reported within 30 days. These three bands match the timeline structure of post-market vigilance, and companies can adopt the same SOP framework for the study phase, adjusting only the study-specific routing and responsibilities.

Insight 5: Clinical trial approvals can also be relied upon. SAHPGL-MD-22 expressly lists clinical trial approvals among the regulatory activities to which reliance may apply. Practical estimate: a trial protocol already approved by a reference regulatory authority can be expected to reduce duplicate review in South Africa, but SAHPRA reserves the right to require supplementary information. Sponsors should still file the full protocol, approvals and ethics documentation, and should expect questions on local ethics review and site suitability even where the scientific assessment is largely carried over.

4. Practical recommendations

1. First determine whether the study is a clinical trial or an IVD clinical performance study: based on the definitions in Regulation 1.
2. Obtain SAHPRA approval under Regulation 16 before starting: do not conduct first and report afterwards.
3. When outsourcing studies, ensure the AR can obtain complete records: the responsibility cannot be transferred.
4. Build the study-phase adverse event reporting process on the three time bands of 48 hours, 10 days and 30 days.
5. Keep clinical investigation site information consistent with the registration submission.
6. Assess the applicability of the reliance pathway to trial approvals and document the foreign approvals relied upon.

5. Verification checklist

• □ The study type has been determined (clinical trial or IVD clinical performance study)
• □ SAHPRA approval has been obtained under Regulation 16 before the study starts
• □ The name and physical address of the clinical investigation site have been recorded (Regulation 8(5)(b)(vii))
• □ The AR has been expressly informed of its responsibility for compliance with clinical trial conditions
• □ The study-phase adverse event reporting process has been established on the three bands of 48 hours / 10 days / 30 days
• □ Outsourced study contracts provide the AR’s right of access to records
• □ The applicability of the reliance pathway to trial approvals has been assessed
• □ Study records have been archived and can be cited for subsequent registration and inspection

Regulatory information verified as of 29 October 2026. The regulations, guidance documents and effective dates described in this article are limited to the official sources listed under Legal basis as published on that date; where official documents are subsequently updated, the latest published version prevails.

• South Africa local resources: GRZAN assists manufacturers from the Chinese mainland and overseas with SAHPRA medical device establishment licence (MDEL) applications and product registration preparation, including authorised representative (AR) scheme design, ISO 13485 certification pathway planning and CAB selection, GMDN coding and classification determination, technical dossier preparation, and the setup of vigilance and adverse event reporting mechanisms.
• Service capabilities: product attribute determination and risk classification (Class A/B/C/D), establishment licence applications and renewals, reliance pathway justification, technical dossier and Essential Principles conformity argumentation, labelling and IFU localisation in English, and support for post-market vigilance and annual compliance information submissions.
• Contact: info@grzanglobal.com; hito.lin@grzan.cn; website www.grzan.cn.