FDA Gives Biosimilars Update

Published on: 

Rachel Sherman, MD, Associate Director for Medical Policy, within FDA’s Center for Drug Evaluation and Research, gave a press briefing today. Below is a summary.

Rachel Sherman, MD, Associate Director for Medical Policy, within FDA’s Center for Drug Evaluation and Research, gave a press briefing today. Below is a summary.

In terms of background, the BPCI Act was passed in March 2010 as part of Affordable Care Act, and it creates an abbreviated licensure pathway for biological products shown to be biosimilar or interchangeable with an FDA-licensed reference product (section 351k of Public Health Service Act). FDA is eager to have an informational discussion on this topic because with the new pathway program, the agency is “essentially launching an entirely new regulatory paradigm” and public needs to understand this, said Sherman.

The BPCI Act adds “protein” to the definition of a biological product which currently includes terms such as a virus, toxin, and blood. Historically, proteins have been approved as drugs under the FD&C Act (505) and under the PHS Act (351). Proteins (except for any chemically synthesized polypeptide) will be regulated going forward under PHS.


FDA can rely on some existing information about the reference product when considering a proposed bisimilar product. Specifically, “biosimilar” means the product has the same mechanism of action as the reference product; the condition of use in proposed labeling has been previously approved for reference product; and has the same route of administration, dosage form, and strength as reference product.

The agency has to decide whether the biosimilar product is highly similar to the reference product and ensure that there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency. A doctor can provide product A or B, for example, and expect the same result. The doctor cannot go back and forth between Product A and B, however (see below), noted Sherman.

The BPCI Act requires FDA to look at three buckets of information for the 351(k) pathway: analytical studies to show that the biosimilar is highly similar to the reference product; animal studies (including toxicity, and as needed); and clinical study(ies) to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed (including, among others, pharmacokinetics and immunogenicity).

A common question: biosimilars are not identical to the reference product but are close-how close? As Sherman explained it, each study adds a piece of information to understand what the biosimilar product is and shows what more is needed to fully understand it. The method is similar to a fingerprint like approach to closely identify the product. There is no one size fits all assessment. Another approach FDA may take is to use the totality of evidence in assessing the biosimilar. Europe has a similar way of evaluating biosimilars. To provide the best advice on required animal and human studies to the biosimilar applicant, FDA should have competed a thorough review of data from structural and functional analyses.

Interchangeability. This term means that the biosimilar product produces the same clinical result as the reference product in any given patient, AND for a product administered more than once, the safety and reduced efficacy risks of alternating or switching are not greater with repeated use of reference product without alternating or switching. An interchangeable biosimilar product may be substituted for reference product without authorization of a healthcare provider. NOTE: Biosimilarity is a prerequisite for interchangeability.

Discussions happening at FDA: The agency is thinking about ways to consider non-US licensed comparator products; the definition of protein (including chemically synthesized polypeptides); standards for interchangeability; naming and tracking standards for biosimilars and interchangeable products; exclusivity issues; and pediatric assessment requirements.

FDA will also be thinking about product class under the Act’s transition provisions. By 2020, every biological product will need to be approved under 351 of the PHS Act versus the FD&C Act.

To date, there have been 35 Pre-IND meeting requests for proposed biosimilars to 11 reference products. 21 PRE IND sponsor meetings held, and 9 INDs received

As for the FDA guidance on biosimilars…. Sherman says it’s still in final stages. No details on timeline specifics.