Biosimilars: FDA draft guidance addresses manufacturing changes
The US Food and Drug Administration (FDA) on Monday issued a draft guidance specifying how manufacturers should report postapproval manufacturing changes for licensed biosimilar and interchangeable products.The draft is in a question-and answer format and addresses “commonly asked questions” on postapproval manufacturing changes. FDA said the guidance fulfills a commitment made in the 2022 reauthorization of the Biosimilar User Fee Act (BsUFA III) for fiscal years 2023 through 2027.
The draft also replaces a question (Q.I.20) in a previous guidance issued in September 2021 on biosimilar development. (RELATED: FDA finalizes more Q&As on biosimilar development, Regulatory Focus 20 September 2021)
The earlier question did not address manufacturing changes for interchangeable products because at that time the agency had “limited knowledge and experience” with these products. Yet since then, FDA has “determined that the principles that apply to manufacturing changes for biosimilars are relevant to interchangeable biosimilar products.”
The Q&A addresses the different postapproval reporting categories; FDA differentiates post-approval changes into three categories: major changes requiring the filing of a prior approval supplement (PAS); moderate changes require the filing of a changes being effected-30 days supplement (CBE-30); and minor changes requiring only the filing of an annual report.
The guidance also discusses the type of reference materials applicants should submit to compare pre- and post-change material. It states that manufacturers should use a “well-qualified, in-house reference material” comparability studies to evaluate the effect of the change on biosimilar or interchangeable biosimilars.
Also covered is how to introduce a biosimilar and interchangeable product into a multiproduct manufacturing area or a multiproduct contract manufacturing facility. The guidance states that “risks associated with introducing a licensed biosimilar or a licensed interchangeable biosimilar into a multiproduct manufacturing area or a multiproduct contract manufacturing facility depend on the type of product being introduced and the potential addition of further control measures to ensure that the product meets its intended quality characteristics, including purity. Identity testing is one tool used to detect and control such risks.”
FDA advises sponsors to consult three guidances on reporting manufacturing changes for these products. These include the 1997 guidance Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products, CMC Postapproval Manufacturing Changes for Specified Biological Products to be Documented in Annual Reports issued in December 2021, and the agency’s recent Chemistry, Manufacturing, and Controls Changes to an Approved Application: Certain Biological Products guidance issued in June 2021.
Lastly, the guidance advises applicants to adhere to the International Council for Harmonization’s (ICH) Q5E guidance on biotech comparability issued in June 2005 when making manufacturing changes to a licensed biosimilar or interchangeable biosimilar.
Draft guidance; Federal Register notice
