The US approach to biosimilars: the long-awaited FDA approval pathway.

In the US, the Biologics Price Competition and Innovation Act (BPCI Act, 2009) provided the pathway to create an abbreviated licensure procedure for biologic products that are demonstrated to be biosimilar to or interchangeable with a Food and Drug Administration (FDA) licensed biologic product. In February 2012, the FDA issued three guidelines that list the requirements for biosimilar registration. The topics covered include scientific and quality considerations to demonstrate biosimilarity to a reference product and a guidance that clarifies the BPCI Act implementation. The sponsor application for the biosimilar approval must contain biosimilarity information based on data derived from analytical, animal, and clinical studies. Clinical studies should include an assessment of immunogenicity, pharmacokinetics, pharmacodynamics, and address one or more indications licensed for the reference product. To demonstrate biosimilarity the applicant is allowed to use comparative animal or clinical data with a non-US-licensed product. According to these guidelines, the FDA will consider different aspects when evaluating biosimilarity, such as product formulation, complexity, and stability which will have a risk-based approach and will depend on the degree of knowledge of the product characteristics, as well as clinical experience with the reference one. The FDA intends to use a risk-based and facts-focused approach for review of applications of biosimilars, although it faces several challenges. Once a biologic medicine has been demonstrated to be biosimilar to the reference product, an abridged development program for the biosimilar medicine can be carried out in a similar way to that established by the European Medicines Agency (EMA). In addition, FDA legislation goes a step further than the EMA, offering the possibility to adopt full interchangeability for biosimilars.