FDA breaks silence on biosimilars with long-awaited proposal

For years, the FDA has been unveiling its plan for regulating knockoffs of blockbuster biologics in fits and starts, this week outlining just how it wants to define biosimilarity for would-be copycat drugs.

In a nonbinding draft guidance, the agency spelled out four tiers of possible similarity between an under-review treatment and the approved biologic it hopes to replace. In the best-case scenario, biosimilar developers would need only targeted animal or human studies to prove their drugs match their references, while those deemed not similar would not be further considered without changes to their manufacturing processes.

The FDA is floating its recommendations in hopes of drawing industry feedback, giving drug developers until Aug. 12 to weigh in on the proposal. Defining biosimilarity is among many outstanding questions in the FDA's years-long effort to figure out how it will approve copies of biologic medicines, something Europe has been doing since 2006. The agency is also yet to come down on naming regulations for biosimilars and on when a knockoff can be used interchangeably with its reference drug.

For now, the industry has plenty to chew over with the FDA's latest announcement, which explains how the agency will require drugmakers to submit analytical data comparing biosimilar candidates to their forebears. Depending on what differences those analyses find, the FDA will file each submitted treatment into one of four categories:

  • Highly similar with fingerprint-like similarity, in which a submission is deemed nearly identical to its reference product, "based on integrated, multi-parameter approaches," according to the FDA. Such drugs would need only "targeted and selective" further study to demonstrate their biosimilarity.
  • Highly similar, which also meets the statutory standard for similarity but falls short of the above-mentioned gold standard.
  • Similar, a label that applies to drugs whose analyses were inconclusive, demanding further data or studies to figure out whether changes in manufacturing or formulation might help demonstrate similarity.
  • Not similar, the draft's most self-explanatory tier, applies to products that don't measure up to their references.

Meanwhile, the long-forecast multibillion-dollar market for biosimilars remains on hold as the FDA metes out its rules. The eventual stateside debut of biosimilars, considered a threat to the bottom lines of biologic heavyweights like Amgen ($AMGN) and AbbVie ($ABBV), is expected to slash the cost of some the most widely used drugs by nearly half.

But the industry is hardly standing pat. In the four years since Congress authorized the agency to suss out an approval pathway for biologic copies, many makers of proprietary drugs have started investing in their own biosimilar operations, including Amgen, Merck ($MRK) and Biogen Idec ($BIIB).

- read the draft guidance (PDF)