Considerations in the early development of biosimilar products

•Development of a biosimilar is more rigorous than for a generic small molecule drug.•The first biosimilar development guidelines were published by the EMA in 2005.•Early clinical development of biosimilars focuses on PK/PD, safety and immunogenicity.•A strategic, early clinical biosimilar program informs a targeted Phase III program.

The widespread use and patent expiration of many biologics have led to global interest in development of biosimilar products. Because the manufacture of biologics, including biosimilars, is a complex process involving living systems, the development of a biosimilar is more rigorous than the development of a generic small molecule drug. Several regulatory agencies have established or are proposing guidelines that recommend a stepwise process to ensure the efficacy and safety of a biosimilar are highly similar to the reference product. This article also explores the early clinical phase of biosimilar development, which is particularly important to resolving any uncertainties that might remain following in vitro and in vivo evaluations and to enable a selective and targeted approach to Phase III clinical efficacy and safety investigation.