FDA sketches a complex instruction manual for biosimilars

A group of top FDA regulators has penned an article in the New England Journal of Medicine intending to give drug developers a clearer picture of the agency's thinking on the "abbreviated pathway" lawmakers demanded for biosimilars. But anyone hoping for a simple instruction manual with crystal clear goals and relatively low-cost data demands will be sorely disappointed. The regulations for developing biosimilars will come with its own complex set of customized instructions, complete with demands on animal and human data and new ground rules for initial talks with regulators.

Drawing off the European biosimilar regulations established in 2005 as well as its own experience on abbreviated reviews for protein therapeutics, the regulators--a group which includes Janet Woodcock--say that there will be no "one size fits all" systematic assessment for biosimilars. Instead developers will need to integrate various types of evidence "since it seems possible to exceed a current state-of-the-art analytic characterization by evaluating more attributes and combinations of attributes at greater sensitivities with multiple complementary methods."

It is possible that a "fingerprint" approach to protein structures can be used, they add. While fingerprinting wouldn't eliminate the need for animal as well as human studies, those studies could be reduced in scope. And the FDA likes the EMA's approach to monoclonal antibodies, with its emphasis on "populations, pharmacodynamic markers, and end points that are sensitive to the potential differences between products."

All developers are familiar with the INDA process, where they hope to glean some initial idea of the kind of data that will be needed to gain an approval for a new drug. But the FDA warns it will need to create a new "paradigm" for its initial discussions with biosimilar developers, with a more extensive product review to detail the additional data needed for a biosimilar approval. Rules on interchangeability, which would allow doctors to switch a branded biologic for a biosimilar, are still in the works.  

It's been well over a year since the law passed and biosimilar regulations are still very much a work in progress. But the FDA is clearly establishing a daunting set of clinical demands for biosimilar developers. That will limit the number of players taking the field, significantly raising the bar for researchers and pushing R&D costs to painfully high amounts.

- read the article in the New England Journal of Medicine
- here's the Reuters story