Biosimilars and Future Biotherapeutics

Interchangeability and Substitution Policies

Interchangeability and substitution policies play a pivotal role in the broader adoption and integration of biosimilars into clinical practice. These policies define the conditions under which a biosimilar can be substituted for its reference biologic without the intervention of the prescribing healthcare provider. While biosimilars are approved based on their similarity to reference products in terms of safety, efficacy, and quality, interchangeability is a higher regulatory standard in some regions—particularly the United States—requiring additional data to demonstrate that switching between the biosimilar and its reference product does not result in diminished safety or efficacy. In the U.S., the Food and Drug Administration (FDA) defines an interchangeable biosimilar as one that may be substituted at the pharmacy level, similar to how generic drugs are handled, provided the biosimilar meets rigorous criteria through switching studies. These studies are designed to evaluate whether alternating between the reference product and the biosimilar causes any adverse effects or compromises therapeutic outcomes. Although several biosimilars have gained FDA approval, only a few have been designated as interchangeable, highlighting the stringent nature of the process and the regulatory caution applied to biologic therapies. In contrast, the European Medicines Agency (EMA) does not grant an interchangeability designation per se; instead, it leaves the decision to individual EU member states.