With the introduction of H.R. 1427, the “Promoting Innovation and Access to Life-Saving Medicine Act,” Rep. Henry Waxman has set the stage for the latest debate on follow-on biologics. Waxman’s bill is not the only piece of legislation that merits attention, of course (a new draft bill from Rep. Eshoo is circulating, for example), but given his keen interest in the subject and his position as chair of the Energy & Commerce Committee, it will be an important reference point for all discussion. It is a complex bill that requires careful reading and re-reading – and we will be sending you more in-depth analyses as we do so – but as a start, this Update briefly raises a few thoughts we had on our initial review of the bill.

Approval of Biosimilars  

  • Biosimilarity or interchangeability would be demonstrated by (1) chemical, physical, and biological assays and other non-clinical laboratory studies, and (2) “necessary” clinical studies sufficient to confirm safety, purity, and potency. The U.S. Food and Drug Administration (FDA) determines what clinical studies, if any, are necessary, and the bill warns that any studies must be designed to avoid duplicative and unethical clinical testing. These provisions suggest that product- or process-specific assays may assume a greater role in an abbreviated approval pathway for biologics, which highlights the importance of taking appropriate steps to protect the intellectual property and trade secrets associated with such assays.  
  • The FDA may give a biosimilar the same official or nonproprietary name as the reference product, even if the two products are not found to be interchangeable. This may raise substitution issues under state pharmacy laws, given how prescriptions are written.  

Marketing Exclusivities  

  • A Biologics License Application (BLA) would be given five years of exclusivity if the product contains no “major substance” that has been approved in any previous BLA or that is highly similar to a major substance approved in a previous BLA. The circumstances under which five-year exclusivity would be awarded are not clear, given that “major substance” is not defined (although much of the orphan drug definition of a macromolecule “same drug” is imported to define what would not constitute differences that create a “new” major substance). Also, because the exclusivity would bar approval of an Abbreviated Biologics License Application (ABLA), but not its submission or its review by the FDA, the benefit to the innovator would be less than what is available under the Hatch-Waxman new chemical entity exclusivity.  
  • Three-year exclusivity would be available for a biologic that contains a major substance that was in a biologic previously-approved via a BLA, if new clinical investigations are required. However, the exclusivity would be rewarded only if the product represents a “significant therapeutic advance,” such as a “significant” new indication or subpopulation, other than a pediatric indication. An applicant could not receive three-year exclusivity for such innovations to its own product, unless they resulted in a product requiring submission of a new BLA (as opposed to a BLA supplement). Thus, the issue of whether a new BLA is required or permitted for a given change or improvement may take on even greater significance.  
  • An applicant would be able to extend its three- or five-year exclusivity by six months by obtaining approval of a BLA supplement that requires new clinical investigations and that incorporates a significant therapeutic advance. Only one 6-month extension would be allowed for any product, and the supplement would have to be approved before the final year of the exclusivity period. Additionally, if the product has annual U.S. sales greater than $1 billion, the extension would be reduced to three months. Taken together, these provisions indicate that it will be difficult for an applicant to obtain significant benefits from many product innovations.  
  • The equivalent of an authorized generic would be prohibited during the 180-day exclusivity given to the sponsor of the first approved ABLA for an interchangeable biosimilar. This is consistent with what seems to be a growing antipathy to authorized generics, and a response to FDA’s position that it lacks authority to prohibit authorized generics under the current statute.  

Patent Disputes  

  • Rather than relying on patent listings in the Orange Book or a similar publication, an ABLA applicant would, at any point in the development process, be able to ask the sponsor of a proposed reference product for information about relevant patents. This may give reference product sponsors fairly early notice that a biosimilar is in development. Also, the types of patents that the innovator would be identifying are broader than what is permitted to be listed in the Orange Book, and would include patents claiming unapproved uses and manufacturing process patents. Although these provisions likely would benefit innovators, the lack of a thirty-month stay for litigation likely would be a significant drawback, as would the provision allowing the ABLA applicant (and defendant in the lawsuit) to seek a transfer of any litigation to a more favorable venue.