Considerations related to comparative clinical studies for biosimilars.

Biosimilar medicines have transformed the healthcare landscape by providing improved access to life-saving medicines at a lower cost. Biosimilars are a distinct category of biologic therapeutics that enter the market after patent expiration of a reference molecule. Regulatory bodies worldwide have developed guidance to expedite the approval and entry of these drugs to the market. Biosimilar approval is based on a totality of the evidence approach, demonstrating similarity between the biosimilar and the originator in terms of physicochemical properties, quality characteristics, biological activity, safety, and efficacy. This article provides an overview of the biosimilar regulatory guidelines and discusses the importance and considerations of comparative clinical studies that are performed during biosimilar development. Two review assessment reports, one each from the EMA and the FDA, are presented. The discussed case studies illustrate the importance of pharmacokinetic and pharmacodynamic studies in the regulatory approval of biosimilars. It is crucial for biosimilar developers to judiciously determine clinical parameters including biomarkers, endpoints, and acceptance criteria before executing clinical studies.