Biosimilars in the Next Era: Hope or Hype for Biosimilar Monoclonal Antibodies in the Near Future?

Abstract

Biosimilars, defined as biological medicinal products comparable in quality, safety and efficacy to reference products, follow the independent regulatory pathway in the EU for marketing authorizations after the patent expirations of the reference products. With the recent advent of biosimilar monoclonal antibodies (mAbs), the evolving EU guidelines on biosimilars are about to have a new regulatory landscape. The development of guideline on biosimilar mAbs is considered as a regulatory challenge due the tremendous complexity of mAbs. MAbs are highly complex molecules with secondary and tertiary structures subject to post-translational modifications, which are often heterogeneous and vulnerable to slight change in manufacturing process. Thus, to what extent of the similarity a biosimilar mAb should demonstrate, compared with its reference product, is currently the most controversial regulatory issue. This review discusses this issue by raising the questions in tiers of quality, non-clinical, clinical issues. In principle, the similarity issue on mAbs will be extensively discussed and justified on case-by-case basis. Most importantly, evaluation of biosimilar mAbs should be conducted with a holistic approach, i.e. rigorous interpretation between structure-function relationships to reduce unnecessary clinical trials while providing comprehensive post-marketing risk management plans. In the long run, biobetters might be gradually taking over biosimilars on the established regulatory track and leading to better access to biological medications.