The U.S. Food and Drug Administration’s (FDA) current interpretation of “strength” does not allow a biological product to be licensed as a biosimilar and/or interchangeable product if there is any variation in inactive drug volume, even if it has the same amount of active drug content as the reference product. This article discusses challenges in reconciling this new thinking with the agency’s stated views relative to biosimilar regulation and the generally accepted “totality of evidence” standard as discussed in the agency’s guidance document, “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.” This contrast between strength, on the one hand, and potency (clinical function), on the other, is also important to consider relative to the implications of the intent of the Biologics Price Competition and Innovation Act of 2009 (BPCIA)—and how existing legislative ambiguities can be addressed and amended.
A Very Short History of the Biologics Price Competition and Innovation Act
The Biologics Price Competition and Innovation Act of 2009 (BPCIA) gave FDA authority to create a regulatory pathway for “biosimilar” biological products. The BPCIA amended the Public Health Service (PHS) Act to create an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.
The development of this legislation included many different legislative iterations and scientific approaches. Two key issues, however, laid the groundwork for final passage: 1) that the intent of the legislation was to expedite the introduction of biosimilars into the U.S. market in order to expand patient access to lower cost, safe, and effective biologics; and 2) to maintain FDA’s regulatory flexibility in determining the scientific “rules of the road.” As Dr. Jay Siegel (former Office Director, Office of Drug Evaluation Sciences at FDA) commented at a March 8, 2007 hearing of the Senate Health, Education, Labor and Pensions (HELP) Committee, “any proposed pathway should not constrain the FDA’s ability to request data and studies in support of sound scientific decisions.”
While Congress creates statutory framework, it is often left to the regulatory agency (in this case, FDA) to further develop regulations and guidance. In the case of the BPCIA, the law lays out the intent but allows FDA to create both the ground rules and the guardrails. Such a flexible approach helps to empower the agency and stakeholders to develop creative, nimble, and dynamic regulatory approaches with which to build the global standards for innovative biosimilar regulatory science.