SAHPRA’s Biological Medicines Amendment Guideline - A Critical Update for Biologic Product Sponsors

The South African Health Products Regulatory Authority (SAHPRA) has released the sixth version of its Biological Medicines Amendment Guideline in May 2025, offering comprehensive instructions on how changes to registered biological products should be evaluated, reported, and submitted for regulatory review. The guideline applies to a wide range of products—from vaccines and monoclonal antibodies to gene therapies and plasma-derived products.

The guideline applies to all biological medicines registered in South Africa and outlines regulatory procedures for post-approval quality, safety, efficacy, and labeling changes.

It includes both reporting categories and submission procedures based on the type and potential impact of the change.

Key document sections include:

• Definitions and glossary (e.g., comparability protocol, seed lots, MCB/WCB)

• Categorization of amendments (Type IA, IAIN, IB, II)

• Procedures for COVID-19 and influenza vaccine strain updates

• Appendices outlining data requirements for specific changes

Reporting Categories for Changes

Amendments are grouped by risk level into four categories:

• Type II (Major changes): Must be approved by SAHPRA before implementation. Examples include changes in manufacturing facilities or introduction of new cell banks.

• Type IB (Moderate changes): Must be submitted for review, but if SAHPRA does not object within 60 working days, they are deemed accepted.

• Type IA (Minor changes): May be implemented without prior approval, but SAHPRA must be notified within 12 months.

• Type IAIN: Minor but require immediate notification.

If a change doesn't fit any category, it can be submitted under a “Z” code with proper justification.

All amendment submissions should include:

• A cover letter with a description and rationale of the change

• A Medicines Submission Application Form

• Supporting GMP documentation

• Comparative quality, safety, and efficacy data

• Revised PI and PIL if applicable

The format must comply with SAHPRA's electronic submission standards (ZA eCTD or ZA CTD).

For Type II amendments, SAHPRA may request additional data or issue a non-compliance letter if the change affects product integrity. Approval must be received before distribution.

When a change may affect a product’s safety or efficacy, bridging studies—either clinical or non-clinical—may be necessary. These include:

• Switching to new cell banks or bioreactor systems

• Modifying fermentation or purification steps

• Changing seed lots or master files (e.g., PMF/VAMF)

SAHPRA encourages a case-by-case evaluation using quality comparability and scientific rationale. The appendices offer actionable templates and classification tables, such as:

• Appendix 1: Review timelines (e.g., 120 days for Type II changes)

• Appendix 2: Changes to active substances

• Appendix 3: Final product changes

• Appendix 4: PMF and VAMF handling

• Appendix 5: Sample format for cover page

This makes it easier for applicants to determine what documents to include for each type of change.

For a complete understanding of the requirements and procedures, stakeholders are encouraged to consult the full Biological Medicines Amendment Guideline on the SAHPRA website.