Development of biosimilars presents considerable challenges due to their complex structure and specialized manufacturing processes that could have clinical implications; similarity of structural and functional characteristics of the proposed biosimilar to the reference product forms the foundational first step in the totality of evidence for biosimilarity demonstration.

The goal of the biosimilar clinical development program is not to demonstrate efficacy and safety per se but rather to confirm similarity with the reference product based on pharmacokinetic/pharmacodynamic equivalence and a confirmatory comparative pivotal clinical study in a representative indication evaluating safety, efficacy, and immunogenicity.

Regulatory guidance allows for extrapolation to all indications of use for which the reference product is approved with scientific justification centered around the totality of evidence that supports similarity between the proposed biosimilar and the reference product based on same mechanisms of action while simultaneously considering the physiology of each disease.