On November 27, 2019, FDA issued draft guidance on Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products. On March 23, 2020, NDAs for insulin products will be deemed licenses and will be available to be used as reference products by applicants seeking licensure of proposed biosimilar and interchangeable insulin products. The draft guidance provides recommendations as to whether and when comparative clinical immunogenicity studies may be needed to support licensure of proposed biosimilar and interchangeable insulin products for patients with Type 1 or Type 2 diabetes mellitus.

In the past, FDA generally has advised that clinical studies to evaluate potential risks from immunogenicity associated with proposed insulin products may be necessary to support NDA approval. Additionally, FDA previously advised that data from a comparative clinical immunogenicity study would likely be needed to evaluate the potential risk and clinical impact of immunogenicity of proposed biosimilar and interchangeable insulin products.

In this guidance, FDA describes its updated thinking that, generally, if a comparative analytical assessment supports a demonstration of “highly similar” for a proposed biosimilar or interchangeable insulin product, “there would be little or no residual uncertainty regarding immunogenicity,” and a comparative clinical immunogenicity study generally would be unnecessary to support licensure of a proposed biosimilar or interchangeable product. However, FDA notes that there still may be limited cases where immunogenicity studies would be required. For example, FDA adds that a study may be necessary to support licensure of a proposed biosimilar or interchangeable insulin product for which differences in certain impurities or novel excipients give rise to residual uncertainty related to immunogenicity.

FDA recommends that a BLA for a biosimilar or interchangeable insulin product contain: adequate chemistry, manufacturing, and control information; a comprehensive and robust comparative analytical assessment; a comparative clinical pharmacology study; and an immunogenicity assessment justifying why an immunogenicity comparative clinical study is not necessary to support biosimilarity. Furthermore, FDA states that an applicant for a proposed interchangeable insulin product would not need to conduct a comparative clinical immunogenicity study to support licensure so long as the statutory criteria for licensure as an interchangeable are otherwise met.