Biosimilars: the need, the challenge, the future: the FDA perspective.

OBJECTIVES: This article summarizes the brief history of the biosimilars industry, the FDA's regulations and guidance for biosimilars development, and the issues and challenges facing developers and regulators in bringing biosimilars to market.

METHODS: Current literature, regulations, and FDA guidance documents were summarized and interpreted to define biosimilars and to present their financial and clinical implications.

RESULTS: Some biologic agents that will lose patent protection during the next few years may be replaced with lower cost follow-on biologics. However, unlike generic drugs, biosimilars may be structurally and functionally different from the reference product they are designed to resemble. The FDA has yet to approve any agent via the abbreviated licensure pathway for biosimilars that was passed as part of the Affordable Care Act. The FDA has issued new guidance describing processes by which manufacturers may demonstrate either biosimilarity or interchangeability with an FDA-approved biologic agent, which is required for abbreviated licensure. Biosimilars approved in Europe consist of relatively small molecules; complex large-molecule biosimilars could be subjected to a rigorous and prolonged FDA approval process, which would defeat attempts to develop lower-cost versions of biologic drugs.

CONCLUSIONS: Biosimilar development is a consequence of the financial success of biologic therapies and their eventual patent expiration. The pharmaceutical industry must now develop complex biosimilars that resemble FDA-approved biologic agents and invent analytical tools and end points to demonstrate similarity to regulatory authorities. Already in development is a new wave of "biobetter" or "biosuperior" drugs that mimic but also improve upon a biologic drug's chemistry, formulation, or delivery.