A Systematic Review of U.S. Biosimilar Approvals: What Evidence Does the FDA Require and How Are Manufacturers Responding?

Journal Article (Journal Article;Review;Systematic Review)

BACKGROUND: Biosimilars undergo an abbreviated licensure pathway called 351(k), which was created by the Biologics Price Competition and Innovation Act of 2009. This approval process is different from the 351(a) pathway for original biologic approval and, as of August 2017, has been used to approve 5 biosimilars in the United States. OBJECTIVE: To identify the types and quantities of evidence required by the FDA for biosimilar approval and the corresponding evidence manufacturers have provided in their 351(k) biosimilar approval applications. METHODS: To collect data for this review, we searched through drug-specific FDA approval documents and approval-related FDA webcasts for approval indications and dates; reference product names; formulations; postmarketing requirements and commitments; evidence used for extrapolation claims; advisory committee votes; and evidence on similarity in analytical and functional characteristics, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. RESULTS: All biosimilars approved in the United States provided a large evidence base to demonstrate similarity in analytical and functional characteristics-3 to 5 clinical studies showed similarity in pharmacokinetics and pharmacodynamics, and 1 to 2 clinical studies demonstrated efficacy. Safety and immunogenicity were evaluated across all clinical studies. All biosimilars were compared with either the U.S.-licensed reference product or the reference product licensed by the European Union. Extrapolation allowed biosimilars to be approved for indications in which clinical studies were not conducted. The few indications for which biosimilars did not share approval with the reference product were due to market exclusivity protection. None of the 5 biosimilars have been approved as interchangeable in the United States. CONCLUSIONS: The approval process for the first 5 biosimilars on the market in the United States provides a baseline understanding of what type and degree of evidence is required for biosimilar approval. DISCLOSURES: There was no external funding for this study. Hung reports employment as a pharmacist for CVS Health, an AHRQ F32 grant, and meeting/accommodation/travel support from AACP, DIA, and ISPOR, all outside the submitted work. Vu and Mostovoy have nothing to disclose. Study concept and design were contributed by Hung and Mostovoy, along with Vu. Hung and Vu collected the data, and data interpretation was performed primarily by Hung, along with Mostovoy. The manuscript was written by Hung and Vu and revised by all the authors. Some of the study results were previously presented as a poster at the ISPOR 22nd Annual International Meeting; May 20-24, 2017; in Boston, Massachusetts.

Full Text

Duke Authors

Cited Authors

  • Hung, A; Vu, Q; Mostovoy, L

Published Date

  • December 2017

Published In

Volume / Issue

  • 23 / 12

Start / End Page

  • 1234 - 1244

PubMed ID

  • 29172975

Electronic International Standard Serial Number (EISSN)

  • 2376-1032

Digital Object Identifier (DOI)

  • 10.18553/jmcp.2017.23.12.1234


  • eng

Conference Location

  • United States