FDA Guidance on CMC Change Management for Biologics and Notifications published

Recommendation

7/8 May 2024

Annex 2 & Co. - GMP Compliance for Biopharmaceuticals - Live Online Training
Regulatory Requirements and Practical Implementation

If changes in the Chemistry, Manufacturing, Controls (CMC) of an already authorised biological product become necessary, these must of course be reported to the authority. To provide guidance to holders of marketing authorisations or applications (Biologics License Application - BLA) for these products, the FDA has published the guidance document "CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports". 

The document comprises recommendations regarding the types of changes to an approved BLA that are to be documented in an annual report in accordance with 21 CFR 601.12. The focus is specifically on post-approval CMC changes that the FDA believes to have potential to affect product quality. Current FDA regulations state that an applicant must document changes to the product, production process, quality controls, equipment, facilities or responsible personnel that have minimal potential to affect product quality in an annual report.

This guidance, published in December, applies to biological products under 21 CFR 600.3(h) that fall into one of the following categories under 21 CFR 601.2(a): 

• Therapeutic DNA plasmid products, 
• Therapeutic synthetic peptide products of 40 or fewer amino acids,
• Monoclonal antibody products for in vivo use
• Therapeutic recombinant DNA-derived products.

It also applies to BLA-approved combination products if the component of the biological product falls within one of the categories under 21 CFR 601.2(a). However, it does not cover:

• Blood or blood components, 
• Blood-derived products, 
• in vitro diagnostics, 
• cellular and gene therapy products or vaccines and related products.

However, the holder of a BLA for a naturally derived biological product should in any case contact FDA to determine whether the recommendations in this guidance apply to their BLA.

The focus of this guidance is therefore on notification procedures. In contrast, information on change management within the pharmaceutical quality system can be found in the International Council for Harmonisation (ICH) industry guidance documents Q9 Quality Risk Management (June 2006), Q10 Pharmaceutical Quality System (April 2009) and Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (September 2016).