The FDA issued a final guidance on the pathway for interchangeable biosimilar drugs. The guidance is intended to assist sponsors in demonstrating the interchangeability of a proposed therapeutic protein with a reference product, the pathway for which is created by the Public Health Services Act (“PHS Act”) §351(k), and amended in the Biologics Price Competition and Innovation Act of 2009 (“BPCI Act”).
The PHS Act defines interchangeability as a biosimilar product that “can be expected to produce the same clinical result as the reference product in any given patients,” and further that “for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.” The determination of interchangeability is a significant one, as an interchangeable product may be substituted for the reference product “without the intervention of the health care provider who prescribed the reference product.”
The guidance is divided into the following topics:
Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability.
Product-dependent factors that may impact the data needed to support a demonstration of interchangeability include product complexity and the extent of comparative and functional characterization (for example, a product that has a single target receptor may require less data than that required for a product that has multiple target receptors), and the product-specific immunogenicity risk.
Biosimilar product postmarketing data that may impact the data needed to support a demonstration of interchangeability includes safety data, particularly as it relates to immunogenicity-related adverse events. However, postmarketing data alone will not likely be sufficient to support a demonstration of interchangeability.
Data and information needed to support a demonstration of interchangeability.
Considerations for the design and analysis of a switching study or studies need to support a demonstration of interchangeability, including study endpoints, study design and analysis, study population, condition(s) of use to be studied, and the route of administration.
Extrapolation of data, in which a product that meets the statutory requirements for interchangeability for one condition, can additionally be found interchangeable for additional conditions.
Considerations regarding the comparator product in a switching study or studies, include evaluating whether switching between the reference product and the interchangeable product will affect clinical response in terms of safety or diminished efficacy.
Considerations for developing presentations for proposed interchangeable products. For example, if the reference product is marketed as a vial and prefilled syringe, a sponsor should not seek licensure for the proposed interchangeable product with a different presentation, such as an auto-injector.
Postmarketing safety monitoring considerations. For example, rare safety risks may not be detected during preapproval clinical testing because the size of the population may be too small to assess rare events. In these cases, such risks may need to be evaluated through postmarket surveillance or studies.
Acting US Food & Drug Administration (“FDA”) Commissioner Ned Sharpless said this guidance will “provide clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act.” Sharpless also added that the FDA “plays an important role in helping to address the high cost of medicines” and that the policies in the guidance are intended to improve competition and access to high-quality, lower cost interchangeable biologics.06