Section 21 SAHPRA Applications: Accessing Unregistered Medicines in South Africa

Updated 2026-07-05 · Written for South African healthcare practitioners by Sphygmos.

Section 21 of the Medicines and Related Substances Act 101 of 1965 is the legal route by which a South African practitioner obtains an unregistered medicine for a specific patient. This guide covers what the Act allows, when Section 21 applies, who applies and carries responsibility, what SAHPRA requires in support of an application, the portal, fee and turnaround facts, and the reporting duties that continue after authorisation.

What a Section 21 authorisation is

Section 21 of the Medicines and Related Substances Act 101 of 1965 allows 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 put before SAHPRA.

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. 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.

The SAHPRA portal, fee 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 records 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.

The guideline requires the clinical motivation to be supported by credible evidence, and names the acceptable forms: an investigator's brochure, the approved prescribing information from another jurisdiction, or peer-reviewed literature. The supporting documents SAHPRA requires are:

The prescription for the unregistered medicine
The clinical motivation, covering the diagnosis, the registered alternatives considered and the evidence base for the medicine
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

Informed consent is a required document

Proof of the patient's informed consent is a required supporting document in a Section 21 application. The consent reflects 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.

Because the medicine is unevaluated, the consent proof carries more weight than a routine treatment consent: it is the record that the patient accepted an unregistered medicine on the evidence available. An application submitted without it is placed in a queried state rather than decided.

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.

Serious adverse reactions: report to SAHPRA within 15 days, or 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

What a queried or refused application costs

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 turnarounds, so a queried application has no clock running on it, and the patient who needed the medicine this week waits on the query loop instead.

The documented triggers are missing documents and unsupported motivations: proof of informed consent not attached, proof of payment not uploaded, product information absent, or a 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 that the application is resubmitted on the portal with the amended details.

How Sphygmos helps

Sphygmos drafts Section 21 motivation letters with SAHPRA's 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 and ready for the responsible practitioner's review. Every motivation is a draft until you confirm it, and Sphygmos never fabricates evidence or claims that an unregistered medicine is safe or effective; those judgements stay with the practitioner, made on the actual evidence.

See Sphygmos, the clinical operating system for South African doctors

Frequently asked questions

What is a Section 21 application?

A Section 21 application asks SAHPRA to authorise, in writing, the sale of a specified quantity of an unregistered medicine to a specified patient for a specified period, under Section 21 of the Medicines and Related Substances Act 101 of 1965. It is the named-patient route to medicines not registered in South Africa. The authorisation permits access; it is not a SAHPRA finding that the medicine is safe or effective.

How long does SAHPRA take to decide a Section 21 application?

SAHPRA's Section 21 guideline records an aim to respond to individual named-patient applications within 24 hours. The application portal states that processing takes up to three working days, excluding any time the application spends in a queried state. Time in query does not count against either figure, so a queried application takes longer than both.

Who can apply for Section 21 authorisation in South Africa?

The health care provider responsible for the patient's care submits the application, using their HPCSA registration number and registered specialty on the SAHPRA Engagement Portal. By applying, the practitioner accepts responsibility for the use of the medicine, including monitoring its safety and the patient's response. The responsibility is not delegable to the pharmacy or supplier.

What documents does a Section 21 application need?

The core set is the prescription, the clinical motivation, proof of the patient's informed consent, the product information or prescribing information from the source jurisdiction, and proof of payment of the application fee. Peer-reviewed literature supporting the intended use is required where the product information alone does not carry the motivation, and a manufacturer GMP certificate applies in some cases. SAHPRA requires the motivation to cover the diagnosis, the registered alternatives considered, and the evidence base for the medicine.

How much does a Section 21 application cost?

SAHPRA's published application fee is R400, effective 13 February 2025, with proof of payment uploaded as part of the online application. Fees are revised from time to time, so check the latest fee schedule on sahpra.org.za before submitting.

Can I use Section 21 for a medicine that is registered overseas but not in South Africa?

Yes. A medicine registered in another jurisdiction but not in South Africa is unregistered here, so Section 21 authorisation is required to access it. The approved prescribing information from the other jurisdiction is one of the evidence forms SAHPRA accepts in the motivation. It remains a medicine SAHPRA has not evaluated, so the responsibility and reporting duties apply in full.

What must I report to SAHPRA after a Section 21 approval?

Regulation 40(3) reporting applies equally to authorised unregistered medicines. Serious adverse reactions must be reported within 15 days, or within 7 days if fatal or life-threatening; progress reports are due every 6 months from commencement of use; and a report is due within 30 days after use is completed or terminated. Continuing treatment beyond the authorised period requires a new application supported by a progress report.

Sources

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.