生物分析与生物医学杂志

Overcome Challenges to Successful Manufacture of Biosimilars through Media and Feed Screening and Cell Culture Process Optimization

Abstract

Min Zhang and Timothy Hill

In the journey of drug development through regulatory approval, product quality attributes of a biosimilar protein must compare within defined limits to those of the innovator product. Unlike small molecule drugs, whose structure can usually be completely defined and entirely reproduced, biologicals are typically more complex and consist of heterogeneous populations not entirely identical to an innovator product. Therefore, biosimilarity is generally demonstrated as having matched product quality attributes, comparable in vitro biological activity, and no clinically meaningful differences between the biosimilar drug and innovator product. The complexity of recombinant protein manufacturing processes, including expression systems (i.e., host cell line, expression vector, cell line development process), cell culture process conditions and related nutrient systems, such as cell culture media and feeds, present significant challenges to achieve the required product quality for biosimilars. To address these challenges, a systematic approach combining media toolbox methodology and bioprocess “knowhow” has been developed to screen and optimize manufacturing conditions that promote the desired product quality profiles of recombinant proteins. Results using this strategy are presented to highlight the efficacy of this approach and successful implementation in manufacture of biosimilar recombinant monoclonal antibodies.