FDA provided a window into its thinking on biosimilars last week in the New England Journal of Medicine. The article, titled "Developing the Nation's Biosimilar's Program" co-authored by FDA officials, updated the medical community on the progress of FDA's implementation of the Biologics Price Competition and Innovation Act ("the BPCIA"). While the BPCIA has been in effect for over a year, FDA has kept a low profile so far on biosimilarity standards.
The article replete with guideposts that could help industry stakeholders predict future agency action. It comes as no surprise that FDA advocated the use of a "totality of the evidence" approach to determine biosimilarity and eschewed any "one size fits all" systematic assessment. Indeed, the BPCIA itself appears to require biosimilar applications to include some combination of analytical and clinical studies. The article confirmed that FDA will rely on its past experiences with protein products (both BLA and NDA) as well as the European experience to determine biosimilarity standards.
FDA also appeared to take a sliding scale approach to the balance of clinical versus non-clinical data. For example, the more rigorous the analytical assessment, the less clinical data that the Agency will likely need. Here, FDA cites its experience with enoxaparin, a complex non-biologic low molecular weight heparin product. FDA used highly-sensitive analytic techniques to compare the "fingerprint" of the reference listed drug with the generic enoxaparin. FDA would not go so far as to say that advanced analytical technology would eliminate the need for clinical studies ("for the foreseeable future"), but it would state that using advanced techniques could reduce the clinical burden.
In addition, FDA acknowledged that the unique challenges posed by biosimilars may necessitate a new approach to interaction with applicants; in FDA's words, "a new paradigm." It appears that FDA is considering a two-tiered approach where FDA first reviews analytical data and then provides guidelines on the necessary analytical data. Given this new approach, FDA is also considering the appropriate fee structure.
It is interesting to note that interchangeability occupies only two paragraphs of discussion at the end of the article. Many commentators have noted that interchangeability presents a lofty and unlikely goal for a biosimilar applicant. FDA's sparse and largely aspirational discussion of interchangeability appears to confirm this notion.
