FDA Releases Draft Guidance on Insulin Biosimilars, Interchangeable Insulins

The FDA today released draft guidance for industry on clinical immunogenicity considerations for biosimilar insulins and interchangeable insulins. The guidance document provides recommendations as to whether—and when—comparative clinical immunogenicity studies will be needed to support an application to the FDA for insulin products under the biosimilar approval pathway.

As of March 2020, insulins will be regulated as biologics, and as such, developers will be able to seek licensure for subsequent-entry insulins under the biosimilar approval pathway after that time, whereas they are currently treated as follow-ons.

In the past, the FDA has generally advised that clinical studies should be provided to evaluate potential risks from immunogenicity with insulin products. The FDA has also taken the stance that data from a comparative clinical immunogenicity study may be needed to evaluate risk and clinical impact of a proposed biosimilar or interchangeable insulin.

In the current guidance, the FDA reports that, in its current thinking, if a comparative analytical assessment demonstrates that products are highly similar, “there would be little or no residual uncertainty regarding immunogenicity.”

In such cases, explains the guidance, a proposed biosimilar or interchangeable insulin would be expected to have “minimal or no risk” of clinical impact from immunogenicity, and a comparative immunogenicity study would likely be unnecessary. Studies would still be needed in cases in which there is uncertainty raised by such factors as differences in certain impurities or novel excipients, however.

The updated recommendation is based on a multidisciplinary evaluation that considered the relatively small structure of insulin compared with other biologics, extensive experience with immunogenicity in insulins, experience with insulin products, public comments to the FDA, updated recommendations from the European Medicines Agency, and the published scientific literature.

The FDA expects Biologics License Applications for biosimilar and interchangeable insulins to include adequate chemistry, manufacturing, and control information; a comprehensive comparative analytical assessment; a comparative clinical pharmacology study; and an immunogenicity assessment that shows why a comparative clinical study is not needed.

Interchangeable insulins will not generally need switching studies, says the guidance, as long as statutory criteria for licensure are otherwise met.

The FDA will receive comments on the guidance for the next 60 days on the Federal Register.