This guidance provides recommendations to holders of biologics license applications (BLAs) for specified biological products regarding the types of changes to an approved BLA to be documented in an annual report under 21 CFR 601.12. Specifically, the guidance describeschemistry, manufacturing, and controls (CMC) postapproval manufacturing changes that FDA generally considers to have a minimal potential to have an adverse effect on product quality.
Under FDA regulations, postapproval changes in the product, production process, quality controls, equipment, facilities, or responsible personnel that have a minimal potential to have an adverse effect on product quality must be documented by applicants in an annual report.3
This guidance applies to biological products, as defined in 21 CFR 600.3(h), that fall under one of the following categories specified in 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, and therapeutic recombinant DNA-derived products.
It also applies to combination products licensed under a BLA, where the biological product constituent part falls under one of these categories specified in 21 CFR 601.2(a). The guidance does not apply to blood or blood components, blood-derived products, in vitro diagnostics, cellular and gene therapy products, or vaccines and related products ; however, a BLA holder for any other naturally derived biological product should discuss with FDA whether the recommendations in this guidance apply to his or her BLA.
This guidance focuses on reporting mechanisms. For information about change management within the pharmaceutical quality system, see International Council for Harmonisation (ICH) guidances for industry Q9 Quality Risk Management (June 2006), Q10 Pharmaceutical Quality ystem (April 2009), and Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (September 2016).
The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.