Last week, the US Food and Drug Administration (“FDA”) released a draft guidance which provides recommendations regarding the need for comparative clinical immunogenicity studies to support biosimilar insulin applications. The draft, entitled Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products, is intended to “facilitate the development of, and improve patient access to, life-saving insulin products.”
Insulin is currently regulated as a drug. However, on March 23, 2020, approved New Drug Applications (“NDAs”) directed to insulin products will be deemed to be approved biologics license applications (“BLAs”). After this transition, the approved insulin product can be used as a “reference product” to support approval of a proposed biosimilar insulin product. To obtain approval, the applicant must meet certain requirements to demonstrate biosimilarity, including an immunogenicity assessment to “investigate[s] the presence of an immune response to the therapeutic protein and its clinical impact, which can influence whether the therapy will work well and be safe.”
The draft guidance provides the following recommendations:
Comparative clinical immunogenicity study generally not necessary when the “risk of clinical impact from immunogenicity … [is] minimal.” That is, if the application “contains a robust and comprehensive analytical assessment demonstrating that the proposed insulin is ‘highly similar’ to its proposed reference product with very low residual uncertainty regarding immunogenicity.” Instead, the applicant should include a scientific justification addressing why an immunogenicity study is not necessary.
Comparative clinical immunogenicity may be needed when there is “residual uncertainty regarding immunogenicity.” For example, residual uncertainty may exist when the proposed biosimilar contains impurities or novel excipients, when compared to the reference product.
The FDA notes that this guidance is based on characteristics that are specific to insulin, including that the molecule is “relatively small, structurally uncomplicated, and well characterized,” extensive experience that confirms minimal or no immunogenicity related to insulin use, and scientific thinking on the lack of clinical impact of immunogenicity with insulin use. The FDA added that the science and technology of biologics protein manufacturing has advanced “considerably,” leading to an “evolution in the understanding and extensive characterization of protein products,” and that this particularly true with insulin products.
The release of the draft guidance comes amid a torrent of criticism about the skyrocketing cost of insulin products. The FDA expects that biosimilar competition should help address that issue, noting that the “availability of approved biosimilar and interchangeable insulin products … [should] increase access and reduce costs of insulin products.” Comments are due by January 27, 2020.