Understanding interchangeable biosimilars at the federal and state levels

Though biologic medications have improved the treatment landscape by providing the solution to many unmet medical needs, biologics cost much more than small-molecule chemical medications. Biosimilars are cost-effective alternatives that are highly similar to originator/reference biologics in terms of efficacy and safety, yet the uptake of biosimilars in the United States has been gradual in part due to provider- and patient-related barriers. To improve biosimilar uptake and adoption, the FDA has established an interchangeable designation for biosimilars. This review discusses the FDA biosimilar and interchangeable biosimilar approval pathway requirements, FDA regulations, and state-specific requirements regarding the dispensing and administration of biosimilars and interchangeable biosimilars. For FDA approval, a biosimilar must demonstrate that it is highly similar to the reference product and that there are no clinically meaningful differences between the reference biologic and the proposed biosimilar. Interchangeable biosimilars are recommended to undergo additional studies to demonstrate that there is no change in efficacy or safety after 3 switches between the proposed interchangeable biosimilar and the reference product. Most states permit the substitution of a reference product for an interchangeable biosimilar without the approval of the prescribing physician. The time frame required for communication to the prescriber about such substitutions varies by state. This review highlights the importance of understanding the regulation of interchangeable biosimilar products in each state.