Explaining biosimilars and how reverse engineering plays a critical role in their development

Abstract

ABSTRACT Introduction Biologicals are protein-based therapeutics consisting of larger and more complex structures than small molecule medicines. As the patents for originator biological therapeutics expire, biosimilar products are licensed for the same indications as their marketed reference biologics across different specialities. Owing to the complex nature of the manufacturing process for a biological therapy compared to conventional chemically synthetized medicines, the development of biosimilars is more complicated and costly than the manufacture of generic small molecules. Areas covered The manufacturing process of the originator biologic is in most cases largely unknown to biosimilar developers and therefore reverse engineering through extensive analysis of the originator is a fundamental and critical step for successful biosimilar development. In this review, the authors examine the abbreviated roadmap for biosimilar approval which must be underpinned by the same rigorous standards that apply to all biological medicines. They discuss various aspects of biosimilar manufacturing with a focus on reverse engineering. Expert opinion The biosimilar approval pathway places a greater emphasis on preclinical assessments in comparison to the development of originator biologics. Multiple comparative clinical studies add little to the confirmation of the efficacy of the molecule under study whilst adding considerably to the cost and time of bringing a biosimilar into clinical use. A successful demonstration of biosimilarity to the reference product is therefore essential at a structural and functional level but this could not be achieved without well-designed and quality-driven reverse engineering of the originator production process.