Enliven: Biosimilars and Bioavailability

For approval of a proposed biosimilar product, the United States Food and Drug Administration (FDA) requires totality-of-the-evidence be provided to support a demonstration of biosimilarity between the proposed biosimilar product and the US-licensed drug product. However, as indicated in Section 314.126 of 21 CFR (Code of Federal Regulation) that substantial evidence needs to be provided to support the claims of new drugs. In practice, although there is no clear distinction between the concept of substantial evidence (with legal basis) in new drug development and the concept of totality-of-the-evidence (without legal basis) in biosimilar drug product development, it is a concern whether the totality-of-the-evidence in terms of analytical similarity, pharmacokinetic (PK) and pharmacodynamic (PD) similarity and clinical similarity can provide substantial evidence to support the demonstration of biosimilarity between the proposed biosimilar product and the USlicensed drug product. A couple of recent regulatory submissions were presented to demonstrate the concern.