Biosimilars: The Need, The Challenge, The Future

The FDA Perspective

Michael S. Epstein MD, FACG, AGAF; Eli D. Ehrenpreis, MD; Prasad M. Kulkarni MD, FACG


Am J Gastroenterol. 2014;109(12):1856-1859. 

In This Article

FDA Regulation of Biosimilars

The Biologics Price Competition and Innovation Act[8] (BPCI Act) was passed as part of the Affordable Care Act that President Obama signed into law on 23 March 2010. The BPCI Act creates an abbreviated licensure pathway (known as the 351k path) for biological products shown to be "highly similar" to or interchangeable with an FDA-licensed reference product.

A biosimilar product is one with "no clinically meaningful differences" from its reference product with regard to safety, purity, and potency, as supported by data from analytical, animal, and clinical studies. Applicants under 351(k) must demonstrate that the new product is biosimilar to the reference product, utilizes the same mechanism(s) of action for the proposed condition(s) of use, and has the same route of administration, dosage form, and strength. Interchangeability must be supported by data showing that the product is biosimilar to and likely to produce the same clinical results as the reference product. Interchangeable biosimilars must have the ability to be switched for or alternated with the reference produce in any given patient without introducing new risks in terms of safety and reduced efficacy. A product meeting interchangability standards may be substituted for the reference product without the authorization of the health-care provider.[9]

In Feburary 2012, the FDA issued new guidance documents[10] to reflect input and questions from regulatory meetings on biosimilar product development. The guidelines describe a stepwise process required to demonstrate biosimilarity, beginning with comprehensive stuctural and functional analyses, followed by animal studies to assess toxicity and clinical studies on pharmacokinetics, pharmacodynamics, and immunogenicity. The draft guidance also suggests that the FDA may allow extrapolation across indications given sufficient scientific justification. The quality guidelines list physiochemical considerations that may be relevant to assessing biosimilarity, including manufacturing process, impurities, and product stability.

In the absence of product-specific guidance, drug developers will need to determine the analytical tools and study end points with which they can demonstrate similarity. New analytical technologies are currently in development to assess protein aggregation, post-translational modifications, and other product-related factors known to cause immunogenicity.[11] However, only clinical studies will be able to account for the interplay between the potential immunogenicity of the drug itself and other factors such as mode of delivery, dosing, and patient characteristics.[11]