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# Insulin Product Clinical Immunogenicity Guidance Comments
- URL: https://www.fdaweb.com/insulin-product-clinical-immunogenicity-guidance-comments/
- Published: 2020-01-30T12:00:00.000Z
- Updated: 2026-09-14T16:00:42.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5145973

The U.S. Pharmacopeia says it agrees with FDA’s position in a draft guidance on clinical immunogenicity considerations for biosimilar and interchangeable insulin products that a comparative clinical immunogenicity study generally will not be necessary to support a demonstration of biosimilarity or interchangeability. The comment [letter](https://www.regulations.gov/document?D=FDA-2019-D-5255-0011&ref=fdaweb.com) says the agency position is based on “extensive product understanding, scientific data, and clinical evidence.” It says the recommendation on immunogenicity studies should effectively reduce the burden for potential BLA holders to bring new biosimilar and interchangeable insulin products to market.

Amgen [says](https://www.regulations.gov/document?D=FDA-2019-D-5255-0012&ref=fdaweb.com) that although the draft presents reasonable scientific justifications regarding the general lack of need for comparative clinical immunogenicity data to support a demonstration of biosimilarity or interchangeability for insulin products, it recommends that the final guidance clarify and emphasize that the omission of comparative immunogenicity studies, or other clinical studies, does not mean that FDA is applying a lesser standard to the demonstration of biosimilarity or interchangeability of insulin products.

The American Pharmacists Association’s [letter](https://www.regulations.gov/document?D=FDA-2019-D-5255-0006&ref=fdaweb.com) says the group appreciates FDA’s efforts to streamline efforts to support licensure of proposed biosimilar and interchangeable insulins and suggests that FDA also review opportunities to streamline the approval process and increase competition while maintaining safety. It encourages the agency to take a similar approach for other components of a 351(k) BLA.

The Lilly comment [letter](https://www.regulations.gov/document?D=FDA-2019-D-5255-0009&ref=fdaweb.com) says FDA should clarify **(1)** that the immunogenicity testing policy in the draft guidance does not apply to new insulin-related products with structures that differ meaningfully from current marketed products and native human insulin; **(2)** whether the draft guidance policy applies only to 351(k) applications for transition insulin products supported by clinical immunogenicity data as required for their original approval under section 505(b)(2) or also applies to section 351(k) applications for insulin products that were not previously approved and thus were not studies clinically for immunogenicity; and **(3)** that the draft guidance does not address considerations for biosimilarity and interchangeability of devices and presentations, including connected systems.

The Association for Accessible Medicines and its Biosimilars Council say they support the FDA thinking in the draft guidance and also say they believe it is important that the agency ensures that its approach to biosimilar and interchangeable insulin products is consistent with its approach to biosimilars and interchangeable biologic products broadly.

Novo Nordisk [tells](https://www.regulations.gov/document?D=FDA-2019-D-5255-0010&ref=fdaweb.com) FDA of an instance of unexpected immunogenicity in response to a new insulin analog that was encountered during its clinical development. It says the hypersensitivity was rectified by adjusting only the amounts of well-known excipients. The company says its experience exemplifies the unpredictable nature of immunogenic reactions in response to insulin formulations and suggests the need for caution in applying the broad assumption included in the draft guidance.