Section 21 SAHPRA Applications: Accessing Unregistered Medicines in South Africa

What a Section 21 authorisation is

Section 21 of the Medicines and Related Substances Act 101 of 1965 empowers SAHPRA to authorise, in writing, the sale during a specified period, to a specified patient, of a specified quantity of a medicine that is not registered in South Africa. This is why it is often called named-patient access: the authorisation is tied to one identified patient, one medicine, one quantity and one period.

The word "unregistered" carries real weight. An unregistered medicine has not been evaluated by SAHPRA for safety, efficacy or quality. A Section 21 authorisation is permission to access the medicine — it is not a finding that the medicine works or is safe. That assessment falls to the responsible practitioner and to the evidence assembled in the motivation.

When Section 21 applies — and when it does not

Section 21 exists for the patient whose condition cannot be adequately treated, diagnosed or prevented with medicines registered in South Africa: the registered options have been considered and ruled out, have failed, are unsuitable for the particular patient, or are not available as marketed products.

A medicine that is registered in another jurisdiction but not in South Africa is still unregistered here, and accessing it requires Section 21 authorisation. Conversely, prescribing a registered South African medicine outside its registered indication (off-label use) is not a Section 21 matter, because the medicine itself is registered — that is a separate clinical-governance question.

• Registered therapies have failed or are clinically unsuitable for this specific patient
• No product registered in South Africa exists for the condition
• The registered product is not available as a marketed product — for example, during a supply interruption
• The medicine is registered abroad but not in South Africa — Section 21 is still required

Who applies — and who carries responsibility

The application is submitted by the health care provider responsible for the patient's care — in practice the treating practitioner, applying under their HPCSA registration number and registered specialty. By applying, the practitioner accepts responsibility for the use of the medicine, including monitoring its safety and the patient's response to an unevaluated product.

The SAHPRA portal distinguishes named-patient applications (one identified patient) from multiple-patient applications (a group of patients who need the same unregistered medicine). The Section 21 guideline also provides for bulk stock authorisations, typically held by licensed institutions anticipating need; these carry their own record-keeping duties, including dispensing records submitted to SAHPRA every six months and when the stock is depleted.

This is not a delegable signature. Pharmacists, hospitals and suppliers support the process, but the clinical responsibility named in the application sits with the practitioner who signs it.

How to apply: the SAHPRA portal, fees and turnaround

Section 21 applications are submitted online through the SAHPRA Engagement Portal (portal.sahpra.org.za) under E-Services > Section 21 Applications. The application captures the practitioner's details, the patient, the medicine and quantity requested, and the supporting documents. Proof of payment of the application fee is uploaded with the application — R400 at the time of writing (effective 13 February 2025); always check SAHPRA's latest fee schedule.

SAHPRA's Section 21 guideline records an aim to respond to individual named-patient applications within 24 hours, and the portal's own guidance states that processing takes up to three working days, excluding any time an application spends in a queried state. In practice, urgent cases move fastest when the application is complete on first submission.

• The prescription for the unregistered medicine
• The clinical motivation: diagnosis, registered alternatives considered, and the evidence base
• Proof of the patient's informed consent
• Product information — the professional information or prescribing information from the source jurisdiction
• Peer-reviewed literature supporting the intended use, where the product information alone does not carry the motivation
• The practitioner's HPCSA registration details
• A GMP certificate for the manufacturer, where applicable
• Proof of payment of the application fee

Building the clinical motivation

The motivation is the heart of the application, and it must establish three things with credible clinical evidence. First, the diagnosis, with the clinical findings that justify treating now. Second, why the registered alternatives are unsuitable or exhausted — each relevant registered option named, with the specific reason it failed, is contraindicated, or is unavailable for this patient; generic statements do not carry an application. Third, the evidence base for the unregistered medicine itself.

Acceptable evidence includes an investigator's brochure, the approved prescribing information from another jurisdiction, or peer-reviewed literature. The strength of the evidence should match the stakes of the treatment, and the motivation should state what the evidence shows and no more — the medicine has not been evaluated by SAHPRA, and overstating the case helps neither the application nor the patient. An honest, specific motivation is also the fastest one, because it pre-empts the queries.

• Diagnosis confirmed, with the clinical picture that justifies treatment now
• Each registered alternative named, with the patient-specific reason it failed or is unsuitable
• The evidence base attached: investigator's brochure, foreign prescribing information, or peer-reviewed literature
• Dose, quantity and duration requested — matched to the specified period the authorisation will cover

Informed consent: a required document, not a formality

Proof of the patient's informed consent is a required supporting document in a Section 21 application. The consent must reflect what makes Section 21 different: the patient is agreeing to a medicine that has not been evaluated by SAHPRA for safety, efficacy or quality, on the strength of the evidence the practitioner has put before them.

The consent discussion should cover the medicine's unregistered status and what that means, the evidence for and against its use, the alternatives — including no treatment — and the monitoring and reporting that will follow. Document the discussion and upload the signed proof with the application.

• The medicine is unregistered: not evaluated by SAHPRA for safety, efficacy or quality
• The evidence supporting its use, stated honestly, including what is unknown
• The alternatives considered, including registered options and no treatment
• The monitoring plan and the practitioner's reporting duties during use

After authorisation: your reporting duties

Authorisation is where the duties begin, not where they end. The pharmacovigilance obligations of regulation 40(3) apply equally to authorised unregistered medicines, and the practitioner who applied is the one who carries them.

The authorisation also covers only the specified quantity and the specified period. If treatment must continue beyond that, a new application is required — supported by a progress report on the patient's response to date. Progress reports are due every six months from commencement in any event, so a well-kept treatment record serves both duties at once.

• Serious adverse reactions: report to SAHPRA within 15 days — within 7 days if the reaction is fatal or life-threatening
• Progress reports: every 6 months from commencement of use
• Completion: a report within 30 days after the use of the medicine is completed or terminated
• Continuation beyond the authorised period: a fresh application, supported by the progress report

Why applications stall: the queried-application loop

Applications that raise questions or lack documents are placed in a queried state: SAHPRA returns specific questions to be answered and documents to be attached before a decision is made. Time spent in query is excluded from the stated processing turnaround, so an incomplete application is the slowest kind — a real cost when the patient needs the medicine this week.

The avoidable triggers map directly onto the required elements: proof of informed consent missing, proof of payment not uploaded, product information absent, or a generic motivation that does not name the registered alternatives or attach the evidence it relies on. If a detail on a valid approval later needs to change, SAHPRA's guidance is to resubmit the application on the portal with the amended details.

How Sphygmos helps

Sphygmos drafts Section 21 motivation letters with the SAHPRA framework built in — the diagnosis, the registered alternatives considered, the evidence base and the informed-consent record, structured the way the Section 21 guideline expects. Every motivation is produced as a draft for the responsible practitioner to review, correct and confirm before anything is submitted, and Sphygmos never fabricates evidence or claims that an unregistered medicine is safe or effective — those judgements remain the practitioner's, made on the actual evidence.

See Sphygmos — the clinical operating system for South African doctors

Frequently asked questions

Sources

• SAHPRA — Guideline for Section 21 Access to Unregistered Medicines (SAHPGL-CEM-S21-02)
• SAHPRA — Section 21 Application FAQs
• SAHPRA Engagement Portal — Section 21 applications
• Medicines and Related Substances Act 101 of 1965 (gov.za)
• Medicines and Related Substances Act 101 of 1965 — consolidated text (SAFLII)

This guide is general information for healthcare practitioners, not medical, legal, or regulatory advice. SAHPRA guidelines change — verify current requirements on sahpra.org.za before applying.

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