On May 10, the Food and Drug Administration (FDA) published its final guidance for manufacturers seeking to demonstrate interchangeability in biosimilar products. FDA defines interchangeability to mean that “the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Unlike generic small-molecule drugs that can be substituted after FDA approval, pharmacists cannot substitute a biosimilar for its reference product unless the FDA has approved the biosimilar as interchangeable. Absent final guidance on the issue, manufacturers have been hesitant to seek an interchangeability designation. ASHP has voiced concerns that lack of interchangeability may impede biosimilar uptake and reduce product competition, so we are pleased that the FDA has taken action on this issue.
The end goal for manufacturers looking to get an interchangeability determination is to show that the biosimilar “can be expected to produce the same clinical result as the reference product in any given patient.” The final guidance clarifies the studies and data required to meet that standard. Determinations will be based on supporting data and information including critical quality attributes, product-specific immunogenicity, and design and analysis of “switching studies.” The switching studies, which focus on the clinical impact of switching between a reference product and its biosimilar, will supplement rather than replace the clinical studies/trials required to demonstrate biosimilarity.
To avoid confusion, the FDA is encouraging sponsors, when possible, to apply for interchangeability for all the reference product’s conditions of use. Manufacturers cannot apply for conditions of use outside of the reference product’s nor can they use presentations for which the reference product is not also licensed (e.g., if the reference product is only available as a prefilled syringe, the interchangeable should not be presented in an auto-injector). Finally, FDA expects robust postmarket surveillance programs for interchangeable drugs but does not specify requirements for those programs in this guidance.
What Happens Next?
FDA anticipates that the additional clarity provided by the guidance will increase the number of applications for interchangeability. At present, only one company has submitted an application for an interchangeable biosimilar. FDA is also hoping that the guidance will spur the development of biosimilar and interchangeable insulin products to generate competition and lower prices for diabetic and insulin-dependent patients. FDA recently held a public meeting on insulin biosimilars and ASHP plans to submit comments.