On statistical evaluation for interchangeability of biosimilar products

Abstract

A biosimilar product is a biological product which is highly similar to an existing reference product in structure and function and has no clinically meaningful difference in terms of safety, purity or potency. Under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), the Food and Drug Administration (FDA)-approved interchangeable biosimilar products can be expected to produce the same clinical result as the reference product in any given patient. In practice, although it is impossible to demonstrate that a proposed interchangeable biosimilar can meet this criterion due to differences in physiological conditions of patients and subtle differences between products, it is possible to demonstrate that the interchangeable biosimilar can produce the same clinical result as the reference product in any given patient with certain assurance. In this article, we derived a statistical method, which we refer to as an interchangeability index, for evaluating of the interchangeability of a biosimilar product with a certain statistical assurance. The proposed method was evaluated via extensive simulation studies. The results indicate that when the ratio of mean clinical results produced by test and reference product is within a narrow limit and the clinical results have only moderate variability, higher interchangeability index would suggest the test products are likely to meet the criteria for biosimilar interchangeability.