After months of anticipation, FDA issued guidances last month that outlines  its recommendations for developing and approving biosimilar therapies. The  announcement came the same day that FDA officials discussed new user fees for  biosimilars and generic drugs at a Congressional hearing. Three separate draft  guidances map out the scientific considerations, quality analytical factors and  other regulatory issues for bringing to market new therapeutic proteins that  are similar, “but not the same” as a reference product.

  The documents describe a step-wise approval pathway, starting with extensive  analytical, physico-chemical and biological characterization data that can  demonstrate a high degree of similarity. FDA will evaluate that data and then  provide advice to the sponsor on the extent and scope of animal and human  testing needed to show biosimilarity. FDA will consider multiple factors in  making study determinations, including product complexity, formulation,  stability, structure-function relationships, manufacturing process, and  clinical experience with the reference product.

  Unlike European regulators, FDA decided not to issue guidances for  developing biosimilars in different drug product classes. If a specific issue  arises with a specific class, we may write guidance, explained Rachel Sherman,  director of the Office of Medical Policy in FDA’s Center for Drug Evaluation  and Research. But so far, she said at a press briefing, “this has not been seen  at the most efficient route.”

  To avoid redundant and unnecessary animal and clinical testing, FDA will  permit sponsors to use a non-US licensed comparator in certain studies, with  appropriate bridging data. Most applications, though, will require some additional  clinical trials, and Sherman expects that all will need immunogenicity studies.

  Once FDA determines that a product is biosimilar, the sponsor can opt to  demonstrate interchangeability. That will require additional switching studies  to show that changing to the new product does not affect safety and efficacy.  Interchangeability is a separate determination, and it’s sequential, Sherman  emphasized. “It would not look like the generic drug model at all.”

  FDA expects to be inundated with comments of these proposals and plans a  public meeting to hear from stakeholders. Meanwhile, staffers are holding  dozens of pre-IND meetings with sponsors and encouraging all prospective  biosimilar makers to seek early advice. Nine INDs for biosimilars have been  filed so far, and the agency is anticipating a full 351(k) application soon.

News

After months of anticipation, FDA issued guidances last month that outlines its recommendations for developing and approving biosimilar therapies.