Challenges and approaches in demonstrating comparability of a well-characterized biotechnology product after manufacturing changes can be as varied and complex as the products themselves. Participants at the January 2005 CMC Strategy Forum sought to discuss and agree on common implementation strategies for different manufacturing change scenarios (1). Development of flexible, comprehensive approaches in strategy development addressed evaluation of critical product characteristics, appropriate process steps to test, numbers of lots and levels of testing required, and assessment of product comparability. The change scenarios discussed can occur throughout the life cycle of a product from early development through postapproval manufacturing.
Early stage development is where the foundation for assessing comparability begins, and the effects of good or poor development will carry throughout a product life-cycle. Sufficient process and product knowledge is required for reliably predicting and assessing the impact of a change and ensuring that a product will consistently meet approved specifications and standards. Efforts required to assess comparability are inversely proportional to a manufacturer’s understanding of its manufacturing process, product quality attributes, and capability of the analytical methods used. An assessment of comparability should show that products are highly similar before and after a manufacturing change occurred. Comparability does not mean that products are identical, but that their physicochemical and biological properties are sufficiently similar to ensure no adverse impact on their quality, safety, or efficacy.
The fifth CMC Strategy Forum was held on 9 January 2005 at the Renaissance Mayflower Hotel in Washington, DC. Its purpose was discussion of issues related to demonstrating comparability for well-characterized biotechnology products in early and late development phases and postapproval. As with previous forums, the California Separation Sciences Society (CASSS; www.casss.org) sponsored this event. John Towns (Eli Lilly) and Keith Webber (CDER/FDA) moderated more than 130 attendees representing large and small companies, consulting firms, government agencies, and academic organizations.
Morning Session: Webber provided opening comments regarding the FDA’s current regulatory guidelines and perspective. Michael Klein of Amgen provided an example of preapproval comparability evaluation by pointing to elements crucial to successful design and implementation of demonstrating comparability for product changes preapproval. Attendees then received three questions related to preapproval comparability that facilitated discussion for the remainder of the session.
Afternoon Session: Tina Norsell of Novo Nordisk described two case studies on the investigation of impurities in a biopharmaceutical product. Genentech’s John O’Conner followed on demonstrating comparability for products manufactured at different global facilities. Allison Wolf of Eli Lilly gave a case study for successfully reducing a product’s reporting category with a comparability protocol. Attendees then received three questions relating to postapproval comparability that facilitated discussion for the remainder of this session.
1 Towns J, Webber K. Demonstrating Comparability for Well-Characterized Biotechnology Products: Early Phase, Late Phase, and Post Approval. BioProcess Int. 6(2) 2008.