Demonstrating Comparability for Well-Characterized Biotechnology Products

LEVEL: INTERMEDIATE C hallenges 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. 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 (e.g., trending analysis, additional characterization studies, accelerated stability data). The change scenarios we 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. It does not mean the products are identical, but that their physicochemical and biological properties are sufficiently similar to ensure no adverse impact on their quality, safety, or efficacy.