Access to affordable insulin can be a matter of life and death for Americans with diabetes. If not appropriately treated, diabetes can lead to serious and life-threatening complications, including heart disease, organ failure and blindness. And consistent, lifelong access to insulin is imperative to patient survival and quality of life. However, we are aware that the high cost of insulin raises serious concerns about the ability of many patients to access insulin products. This is an issue the FDA takes very seriously; therefore, today we are announcing new draft guidance that is intended to help facilitate the development of, and improve patient access to, life-saving insulin products.

The FDA is committed to continuing our efforts to help increase market competition among insulin products, which may potentially lower costs for patients and payors and increase access and product choice. This includes facilitating the development of safe and effective insulin products for the treatment of patients with type 1 and type 2 diabetes, including products that are biosimilar to, or interchangeable with, an approved insulin product.

To inform product developers who intend to seek the FDA’s approval of proposed insulin products that are biosimilar to, or interchangeable with, an approved insulin product, the FDA today issued a draft guidance for industry, “Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products.” This draft guidance is intended to help guide efficient product development by clarifying what data and information may—or may not—be needed to support a demonstration of biosimilarity or interchangeability for a proposed insulin product, as defined in the draft guidance. The draft guidance reflects, among other things, the FDA’s decades of experience with insulin products which, along with wide clinical use, has contributed to a robust scientific understanding of these products. The draft guidance also reflects consideration of stakeholder feedback provided at the FDA’s May 2019 public hearing on this topic at which stakeholders were invited to provide input on developing biosimilar and interchangeable insulin products.

Significantly, the FDA recommends in the draft guidance that, under certain circumstances, a comparative clinical immunogenicity study would not be necessary for approval of certain proposed biosimilar and interchangeable insulin products. In general, immunogenicity studies investigate 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.

In the circumstances described in the draft guidance, the FDA generally expects the risk of clinical impact from immunogenicity to be minimal for certain proposed biosimilar and interchangeable insulin products. As such, while applications for biosimilar and interchangeable insulin products would be expected to include an immunogenicity assessment, that assessment could include a scientific justification of why a comparative clinical study to assess immunogenicity is not necessary for that particular proposed insulin product.

The recommendations described in the draft guidance, which reflects extensive multidisciplinary evaluation of scientific considerations, may result in a more efficient development program that could ultimately bring biosimilar or interchangeable insulin products to the market more quickly.

Applications for proposed biosimilar or interchangeable insulin products need to meet strict statutory standards, and applicants will need to submit data and information sufficient to demonstrate biosimilarity or interchangeability, including, among other things, a comparative clinical pharmacology study, adequate chemistry, manufacturing and controls information, and a comprehensive and robust comparative analytical assessment. For some proposed biosimilar or interchangeable insulin products, a comparative clinical immunogenicity study may still be needed to address residual uncertainty regarding immunogenicity. For example, a comparative clinical immunogenicity study may be needed if there are differences in certain impurities or novel excipients, but that would be a case-by-case scientific determination in the context of individual applications.

On March 23, 2020, approved New Drug Applications (NDAs) for biological products will be deemed to be licenses for the biological products (i.e., approved Biologics License Applications (BLAs)) under section 351 of the Public Health Service Act. After an approved NDA for a biological product (such as an insulin product) is deemed to be an approved BLA, the product can be used as a “reference product” by an applicant seeking approval of a proposed biosimilar or interchangeable product. A reference product is the biological product, already approved by the FDA, against which a proposed biosimilar or interchangeable product is compared. This will enable, for the first time, submission of applications for products that are proposed as biosimilar to, or interchangeable with, the transition products. As such, the transition of insulin products from approved NDAs to deemed BLAs will open up those products to potential biosimilar and interchangeable competition. The availability of approved biosimilar and interchangeable insulin products is expected to increase access and reduce costs of insulin products, which millions of Americans take each day to maintain stable blood glucose.

The FDA is working now, in advance of the March 23, 2020 transition, to build a solid regulatory foundation for the review and approval of biosimilar and interchangeable insulin products.

The issuance of this draft guidance supports key goals in the FDA’s Biosimilars Action Plan, which aims to improve the efficiency of the biosimilar and interchangeable product development and approval process and to maximize scientific and regulatory clarity for the biosimilar product development community. We’ve accomplished many of the projects outlined in the Biosimilars Action Plan, and we’re continuing our work on others to enhance patient access to needed medicines. The FDA will begin accepting comments from the public on the draft guidance on November 29.