Stakeholders Want Changes to Interchangeability Guidance
Stakeholders are commending FDA for a draft guidance on considerations in demonstrating interchangeability with a reference product and recommending additional items to be included in the document. Pharmaceutical Research and Manufacturers of America (PhRMA) says the guidance “provides welcome insights into FDA’s current thinking” and would benefit from several revisions. It says the guidance should further explain the difference between biosimilarity and interchangeability, explaining that interchangeability is a high standard that requires additional data beyond that needed to show biosimilarity.
PhRMA also says the guidance should provide additional detail on the data and information needed to establish interchangeability and strengthen the recommendation that sponsors of proposed interchangeable products demonstrate interchangeability for all conditions of use approved for the reference products. The association’s final overall request is that the agency provide guidance on naming and labeling issues for interchangeable products and on exclusivity for first interchangeable biological products.
The Alliance for Safe Biologic Medicines says it “agrees with all elements outlined in the draft guidance and suggests adding the following points for consideration.” It calls for changes in the general principles, factors impacting the type and amount of data and information needed to support a demonstration of interchangeability, use of a U.S.-licensed reference product in a switching study or studies; and considerations for developing presentations for proposed interchangeable products.
AbbVie’s comment letter lists five issues it says FDA should correct in the final guidance: (1) giving explicit, independent meaning to the separate provisions of the statutory interchangeability standard to ensure the safe use of interchangeable biological products; (2) prescribing more robust interchangeability study endpoints and statistical methods than those recommended for use in the draft; (3) seeking robust postmarketing data to support interchangeability determinations for most biological products; (4) recommending human factors data assessing the impact of switching between the reference and proposed interchangeable biological product presentations; and (5) requiring labeling to ensure safe use of interchangeable biological products when multiple biosimilar products have been found interchangeable with the same reference product.
Merck says there is a need for clarification and flexibility by FDA for several key foundational elements: definitions, use of U.S.-licensed reference products in a switching study or studies, efficacy endpoints, endpoints analysis, and exclusivity.
Finally, Johnson & Johnson’s Janssen unit says it supports many aspects of the guidance, such as the agency’s strong expectation that a U.S. reference product be used in switching studies. It says the draft can be significantly improved by expecting that switching studies include immunogenicity as a primary endpoint and by addressing additional topics such as label statements about interchangeability, nonproprietary naming of interchangeable products, and the durability of interchangeability determinations given post-determination changes to the reference product and, for both products, manufacturing changes and drift.