In the draft guidance, which was published in the Federal Register on 18 January 2017, FDA outlines its requirements for biosimilar makers looking to prove that their versions are interchangeable with the originator biologicals.

FDA makes it clear that biosimilars makers will first have to prove that their product is ‘biosimilar’ to the reference biological. Then, in order to claim ‘interchangeability’ for the biosimilar, additional information must be submitted that shows that the biological product ‘can be expected to produce the same clinical result as the reference product in any given patient’ and that ‘for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch’.

Considerations in demonstrating interchangeability with a reference product
Date: January 2017
www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf

The draft guidance presents recommendations regarding the data and information needed to support interchangeability, as well as considerations for switching study design and analysis. However, FDA also points out that the data and information required may be dependent on and influenced by multiple factors and will therefore vary based on the product submitted. The agency gives the following two examples:

• Product A has relatively low structural complexity, has been demonstrated to have meaningful fingerprint-like analytical similarity to the reference product as a part of demonstrating biosimilarity, and has a low incidence of serious adverse events related to immunogenicity. Here, data derived from an appropriately designed switching study may be sufficient to support a demonstration of interchangeability.
• Product B has high structural complexity, has been demonstrated to be highly similar to the reference product as a part of demonstrating biosimilarity but has no demonstration of meaningful fingerprint-like analytical similarity, and has known serious adverse events related to immunogenicity. Here, post-marketing data for the product as a licensed biosimilar, in addition to an appropriately designed switching study may provide additional data and information necessary to support a demonstration of interchangeability.

Switching studies, FDA states, ‘should evaluate changes in treatment that result in two or more alternating exposures (switch intervals) to the proposed interchangeable product and to the reference product’. However, the agency does add that if the product is only intended to be administered once, sponsors may instead provide a justification for not needing to conduct a switching study.

The bar seems to have been set rather high for biosimilars makers to demonstrate interchangeability, with a requirement for multiple switches. Although, recent positive data from the NOR-SWITCH study and data from Sandoz’s EGALITY study on multiple switching may provide hope that this is not an insurmountable hurdle [1].

FDA has released the draft for a comment period of 60 days, i.e. until 20 March 2017. Comments on the draft guidance can be posted to the Division of Dockets Management (DDM) under Docket FDA-2007-D-0369-0015. This can be done via the website www.regulations.gov or written comments can be mailed to DDM (HFA-305), FDA, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

Related article
NOR-SWITCH study finds biosimilar infliximab not inferior to originator

Reference
1.  GaBI Online - Generics and Biosimilars Initiative. NOR-SWITCH study finds biosimilar infliximab not inferior to originator [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jan 20]. Available from: www.gabionline.net/Biosimilars/Research/NOR-SWITCH-study-finds-biosimilar-infliximab-not-inferior-to-originator

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