On December 22, 2017, FDA issued a draft guidance to assist applicants and manufacturers of certain licensed biological products in determining which reporting category is appropriate for a change in chemistry, manufacturing, and controls (CMC) information to an approved biologics license application (BLA) as specified in 21 CFR 601.12 (i.e., post-approval changes). This guidance describes general and administrative information on reporting and evaluating changes and recommendations for reporting categories based on a tiered-reporting system for specific changes under 21 CFR 601.12. When finalized, this guidance will supersede the guidance entitled “Guidance for Industry: Changes to an Approved Application: Biological Products” dated July 1997.
FDA is updating this guidance to accommodate advances in manufacturing and testing technology, and to clarify FDA’s current thinking on assessing reportable changes. FDA has revised the recommendations for reporting categories by reclassifying the risks associated with specific changes, and have provided additional examples of manufacturing changes to provide further guidance to applicants and manufacturers and assist with making more informed decisions when reporting and implementing post-approval changes. In some instances, these updated recommendation will result in a less burdensome approach for reporting changes.
Licensed biological products that are within the scope of this guidance include:
- naturally-derived protein products (e.g., enzymes, toxins, etc.)
- vaccines and allergenic products
- plasma-derived products
- antitoxins, antivenins, and venoms
- IVDs regulated under the Public Health and Safety (PHS) Act
- Other biological products licensed under the PHS Act subject to the exceptions listed below
The guidance applies to combination products licensed under a BLA, unless the biological product constituent part is a specific biological product described in 21 CFR 601.2(a) (see below).
Biological products that are not within scope of this guidance include specified biologics products described in 21 CFR 601.2(a), which include monoclonal antibody products for in vivo use, therapeutic NDA plasmid products, therapeutic recombinant DNA-derived products, and therapeutic synthetic peptide products of 40 or fewer amino acids.
This guidance does not apply to certain specified biotechnology products listed in 21 CFR 601.2(c), recombinant DNA-derived protein/polypeptide products approved under the Federal Food, Drug, and Cosmetic Act (FDCA) and complexes or conjugates of a drug with a monoclonal antibody approved under the FDCA. Information on changes to an approved application for specified biotechnology products (and specified synthetic biological products) can be found in FDA July 1997 final guidance “Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products“.
Other key information:
- This draft guidance includes a section on implementing changes to approved established conditions, defined by FDA as “the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy, as defined in an application, that assure process performance and quality of an approved product”. This section references the May 2015 FDA draft guidance “Established Conditions, Reportable CMC Changes for Approved Drug and Biologic Products” for additional information on this topic.
- The draft guidance discusses certain manufacturing changes that may also require revision of the approved labeling. These changes are outside the scope of this document.
- The draft guidance includes a section on special considerations, which discusses how to address changes in process parameters and suppliers of raw materials.
- The draft guidance includes a 4-page glossary section and 2-1/2 pages of references. The bulk of the draft guidance is the Appendix, where FDA provides examples of post-approval manufacturing changes and their recommended reporting categories (prior approval supplement, CBE30, or annual report) organized by the appropriate CMC section of the regulatory submission.
FDA is accepting comments on this draft guidance through March 22, 2018.