South Africa SAHPRA’s Guidelines: Section 21 Access to Unregistered Medicines and Quality & Bioequivalence Requirements

Sharan Murugan
Nov 1
2 min read

On 23rd October 2025, the South African Health Products Regulatory Authority (SAHPRA) continues to strengthen its regulatory framework to ensure that all medicines—whether registered, imported, or accessed under exceptional circumstances—meet the highest standards of safety, quality, and efficacy. Two of SAHPRA’s most recent guidance documents, namely the Guideline for Section 21 Access to Unregistered Medicines and the Quality and Bioequivalence Guideline, play a pivotal role in achieving this mission.

1. Understanding Section 21 Access to Unregistered Medicines

The Guideline for Section 21 Access to Unregistered Medicines provides a comprehensive framework for authorising the use of unregistered medicines in South Africa.

Rooted in Section 21 of the Medicines and Related Substances Act (Act 101 of 1965), it empowers SAHPRA to grant time-bound approval for the sale and use of specific unregistered medicines under well-defined conditions.

Purpose and Scope

This guideline aims to ensure that access to unregistered medicines is:

Managed effectively and transparently,
Granted only when conventional therapies are unavailable or unsuitable, and
Always backed by credible safety and efficacy evidence.

The guidance clarifies that affordability alone is not a sufficient justification for approval. It also excludes access to veterinary medicines and medicines used solely for exhibition purposes.

Access Scenarios under Section 21

The guideline categorises access into five main scenarios:

Individual Named Patient Applications – For a single patient where standard therapies are ineffective or unavailable.
Multiple Patient Applications – For institutions requiring limited emergency stock, such as ICUs or oncology units.
State Procurement – For urgent public sector supply in critical health situations.
Public Health Emergency (PHE) – For unregistered medicines used to combat national outbreaks or pandemics.
Medicines Recognised by Other MRAs – Products authorised by internationally recognised regulatory agencies may be fast-tracked under Section 21.

For more details, refer to SAHPRA’s guidance: Section 21 Access to Unregistered Medicines

2. The Quality and Bioequivalence Guideline: Ensuring Scientific Rigor

The Quality and Bioequivalence Guideline, updated in October 2025, reflects SAHPRA’s commitment to aligning South African regulatory standards with those of the European Medicines Agency (EMA), the International Council for Harmonisation (ICH), and the Southern African Development Community (SADC).

Scope and Legal Basis

The guideline applies to:

New registration applications for small molecule new chemical entities (NCEs),
Generic medicines, and
Post-registration variations.

It does not apply to biologicals, complementary medicines, or medical devices.

SAHPRA has formally adopted a wide range of ICH and EMA quality and bioequivalence guidelines, including:

ICH Q1–Q14 series for quality and stability testing,
ICH M9 and M10 for biopharmaceutics classification and bioanalytical method validation,
EMA reflection papers on dissolution and bioequivalence studies.

Review Pathways under SAHPRA

Applications undergo one of four review types:

Full Review – Comprehensive assessment of all dossier modules.
Abridged Review – Reliance-based review for products approved by recognised regulatory authorities (RRAs).
Verified Review – Validation-focused review with minimal duplication of RRA assessments.
Recognition – Future pathway allowing automatic acceptance of products from trusted RRAs.

Reliance-Based Evaluation

Reliance is a cornerstone of modern regulatory efficiency. SAHPRA may partially or fully rely on evaluations from RRAs such as the EMA, US FDA, Health Canada, MHRA, Swissmedic, or TGA.Applicants must, however, submit:

Full assessment reports,
Certificates of registration,
Labels and patient information leaflets (PILs), and
A Declaration of Sameness ensuring the product mirrors the RRA-approved version

1. Understanding Section 21 Access to Unregistered Medicines

The Guideline for Section 21 Access to Unregistered Medicines provides a comprehensive framework for authorising the use of unregistered medicines in South Africa.

Rooted in Section 21 of the Medicines and Related Substances Act (Act 101 of 1965), it empowers SAHPRA to grant time-bound approval for the sale and use of specific unregistered medicines under well-defined conditions.

Purpose and Scope

This guideline aims to ensure that access to unregistered medicines is:

Managed effectively and transparently,

Granted only when conventional therapies are unavailable or unsuitable, and

Always backed by credible safety and efficacy evidence.

The guidance clarifies that affordability alone is not a sufficient justification for approval. It also excludes access to veterinary medicines and medicines used solely for exhibition purposes.

Access Scenarios under Section 21

The guideline categorises access into five main scenarios:

Individual Named Patient Applications – For a single patient where standard therapies are ineffective or unavailable.

Multiple Patient Applications – For institutions requiring limited emergency stock, such as ICUs or oncology units.

State Procurement – For urgent public sector supply in critical health situations.

Public Health Emergency (PHE) – For unregistered medicines used to combat national outbreaks or pandemics.

Medicines Recognised by Other MRAs – Products authorised by internationally recognised regulatory agencies may be fast-tracked under Section 21.

For more details, refer to SAHPRA’s guidance: Section 21 Access to Unregistered Medicines

2. The Quality and Bioequivalence Guideline: Ensuring Scientific Rigor

Scope and Legal Basis

The guideline applies to:

New registration applications for small molecule new chemical entities (NCEs),

Generic medicines, and

Post-registration variations.

It does not apply to biologicals, complementary medicines, or medical devices.

SAHPRA has formally adopted a wide range of ICH and EMA quality and bioequivalence guidelines, including:

ICH Q1–Q14 series for quality and stability testing,

ICH M9 and M10 for biopharmaceutics classification and bioanalytical method validation,

EMA reflection papers on dissolution and bioequivalence studies.

Review Pathways under SAHPRA

Applications undergo one of four review types:

Full Review – Comprehensive assessment of all dossier modules.

Abridged Review – Reliance-based review for products approved by recognised regulatory authorities (RRAs).

Verified Review – Validation-focused review with minimal duplication of RRA assessments.

Recognition – Future pathway allowing automatic acceptance of products from trusted RRAs.

Reliance-Based Evaluation

Reliance is a cornerstone of modern regulatory efficiency. SAHPRA may partially or fully rely on evaluations from RRAs such as the EMA, US FDA, Health Canada, MHRA, Swissmedic, or TGA.Applicants must, however, submit:

Full assessment reports,

Certificates of registration,

Labels and patient information leaflets (PILs), and

A Declaration of Sameness ensuring the product mirrors the RRA-approved version

For more details, refer to SAHPRA’s guidance: Quality and Bioequivalence Guideline

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