Biosimilars: The US Regulatory Framework

Annu Rev Med. 2017 Jan 14:68:243-254. doi: 10.1146/annurev-med-051215-031022. Epub 2016 Oct 28.


With the passage of the Biologics Price Competition and Innovation Act of 2009, the US Food and Drug Administration established an abbreviated pathway for developing and licensing biosimilar and interchangeable biological products. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a "totality of the evidence" that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. Although questions and concerns about the biosimilars pathway remain and may slow uptake, a robust scientific program has been put in place. With three biosimilars already licensed and numerous development programs under way, clinicians can expect to see many new biosimilars come onto the US market in the coming decade. [Note added in proof: Since the writing of this article, a fourth biosimilar has been approved.].

Keywords: biologic; biosimilar; interchangeable.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal
  • Biosimilar Pharmaceuticals* / standards
  • Drug Approval / legislation & jurisprudence*
  • Drug Labeling / legislation & jurisprudence
  • Drug Substitution
  • Humans
  • Quality Control
  • United States
  • United States Food and Drug Administration


  • Antibodies, Monoclonal
  • Biosimilar Pharmaceuticals