Interchangeability and Exclusivity
Equally challenging for FDA is to define interchangeability testing requirements and whether clinical switching studies will
be required to meet that standard. An interchangeable designation is important because the first follow-on biologic so deemed
by FDA enjoys a year of market exclusivity, during which FDA may not approve another similar interchangeable product.
Biosimilar makers note that switching studies are not required for innovator manufacturers to document comparability following
post-approval changes. Yet, innovators maintain that clinical studies in multiple populations are necessary to ensure safety
and efficacy with product switching. Amgen vice president Anthony Mire-Sluis pointed out that head-to-head studies are needed
to compare immunogenicity between reference and follow-on products, and that product labels should explicitly state approved
indications and whether the biosimilar is interchangeable for that indication.
Although the BPCI authorized 12 years' exclusivity for innovator biologics, that has not ended the exclusivity debate. In
addition to the 12 years when FDA cannot approve another product based on innovator data, biosimilars sponsors have to wait
four years after BLA licensing to even submit a 351(k) application. Innovators claim these protections are needed to spur
investment in R&D, but critics claim that 12 years is too long. The Obama administration recently proposed reducing exclusivity
to seven years, largely to cut spending, but also to prevent patent "evergreening." Biosimilars makers fear that innovators
will seek to extend protections by modifying a reference product's safety, purity, or potency sufficiently to make it "new."
The change has to be significant, says Kozlowski of CDER: "I don't think that 'slightly better purity' is enough to extend
exclusivity," he observed at the DIA/FDLI conference.
As with conventional generics, everyone is bracing for extensive legal maneuvering over patent and exclusivity issues. The
BPCIA took FDA out of the patent-listing arena, but set up an even more complex process for dealing with patent disputes:
Biosimilars makers have to provide the reference product sponsor with a full dossier on its process and product so that the
innovator can determine which patents it feels may be infringed. This "hokey-pokey process," explained Sidley Austin attorney
Jeffrey Kushan, was designed to promote early agreement on which patents are worth fighting about, but appears likely to create
a highly competitive legal environment. Biosimilars makers fear that too many parties will gain access to their confidential
filings, while BLA-holders stand to lose protection if they miss a deadline.
If the biosimilars regulatory process appears too complex and costly, it may limit the value of the 351(k) procedure and make
the traditional BLA route to market—and its 12 years' exclusivity—the more attractive option for copycat biotech developers.
Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at email@example.com