Regulatory Pathway

The FDA evaluation of the evidence

The regulatory pathway for biosimilar medicines is a unique and thoughtful process. It is designed to help ensure the development and approval of high-quality biosimilar medicines. Approved biosimilar medicines have no clinically meaningful differences in terms of safety and efficacy from the relevant reference product, based on the totality of evidence from analytical, nonclinical, pharmacokinetic, and clinical studies. The totality of evidence represents a new approach by the FDA to the development of a new biologic product.

Robust standards for quality, efficacy, and safety: a closer look at the totality of evidence

  • Robust analytical testing, including comparative structural and functional characterization, to establish high similarity of the biosimilar and the reference product
  • Nonclinical testing to evaluate the toxicity and safety profiles of the biosimilar
  • Comparative human pharmacokinetic and pharmacodynamic studies and clinical immunogenicity assessment
  • If residual uncertainty exists, comparative trials may be required (based on recent approvals, the FDA has required studies)

The “totality of evidence” approach to determining biosimilarity

The aim of biosimilar drug development is to establish similarity to the reference product in terms of quality, benefit/risk profile, and efficacy using a stepwise approach that includes analytical, nonclinical, and clinical comparability studies. In certain cases, additional comparative clinical studies may be warranted to help ensure that there are no clinically meaningful differences between the products.