From DCAT Value Chain Insights (VCI)
The US Food and Drug Administration has issued draft guidance, Considerations in Demonstrating Interchangeability With a Reference Product, to assist sponsors in demonstrating that a proposed therapeutic protein product is interchangeable with a reference product for the purposes of submitting a marketing application or supplement for biological products shown to be biosimilar or interchangeable with an FDA-licensed biological reference product.
The purpose of demonstrating interchangeability is so that sponsors can submit a marketing application or supplemental application for the proposed therapeutic under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) amends the PHS Act and other statutes to create an abbreviated licensure pathway in Section 351(k) of the PHS Act for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product. Although the 351(k) pathway applies generally to biological products, this draft guidance focuses on therapeutic protein products and gives an overview of scientific considerations in demonstrating interchangeability of a proposed therapeutic protein product with a reference product.The draft guidance outlines the data and information for showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product. Key elements include: (1) the identification and analysis of the critical quality attributes; (2) the identification of analytical differences between the reference product and the proposed interchangeable product, and, in addition, an analysis of the potential clinical impact of the differences; (3) an analysis of mechanism(s) of action in each condition of use for which the reference product is licensed, which may include the following: the target receptor(s) for each relevant activity/function of the product; the binding, dose/concentration response, and pattern of molecular signaling upon engagement of target receptor(s); the relationship between product structure and target/receptor interactions; and the location and expression of target receptor(s); (4) the pharmacokinetics and biodistribution of the product in different patient populations (5) the immunogenicity risk of the product in different patient populations; (6) differences in expected toxicities in each condition of use and patient population (including whether the expected toxicities are related to the pharmacological activity of the product or to off-target activities); and (7) any other factor that may affect the safety or efficacy of the product in each condition of use and patient population for which the reference product is licensed. The draft guidance also specifies that where applicable, the data and information should include a scientific justification as to why any differences that exist between the reference product and the proposed interchangeable product do not preclude a showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in any given patient.
Source: US Food and Drug Administration
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