A biosimilar should be highly similar to the reference product with regard to structure, and biological and physicochemical properties. The manufacturing process for the reference product is not disclosed, therefore the first step of biosimilar development is to establish the manufacturing process. Manufacturing methods, including host cells used, cell culture conditions and purification procedures, impact the quality of biotechnological products, so a comparability assessment of the biosimilar with the reference product is critical. The comparability assessment is based on the principles applied for evaluating the impact of a change in the manufacturing process of a biotechnological product (ICH Q5E guideline). A stepwise approach is used, consisting of comparative quality, non-clinical and clinical studies.

Comparative quality studies assess differences in quality attributes between the biosimilar and the reference product using analytical methods. Next, in vitro and in vivo non-clinical studies evaluate the impact of such differences on the efficacy and safety of the biosimilar. Following this, comparative clinical studies are performed to ensure that these differences do not lead to any clinically meaningful differences between the biosimilar and reference product. These comparative clinical studies are usually stepwise procedures beginning with pharmacokinetic (PK) and, if feasible, pharmacodynamic (PD) studies, followed by clinical efficacy and safety trials or in some cases, confirmatory PK/PD studies for demonstrating clinical biosimilar comparability. Without surrogate markers for efficacy, it is usually necessary to demonstrate comparable clinical efficacy in randomized clinical trials using efficacy endpoints.

Conflict of interest
The authors of the research paper [1] declared that there was no conflict of interest. This study was supported in part by the 'Research on Regulatory Science of Pharmaceuticals and Medical Devices' from the Japan Agency for Medical Research and Development (AMED).

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Reference
1. Ishii-Watabe A, Kuwabara T. Biosimilarity assessment of biosimilar therapeutic monoclonal antibodies. Drug Metab Pharmacokinet. 2019;31(1):64-90.

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