Interchangeability

Interchangeability refers to the exchange of one medicine for another medicine that is expected to have the same clinical effect.¹ In the context of biosimilars, this means an approved biosimilar can be used instead of its reference product (or vice versa), or one biosimilar can be replaced with another biosimilar of the same reference product.¹

REGIONAL DIFFERENCES IN SUBSTITUTION POLICY
While the scientific principles underpinning biosimilar approval are somewhat harmonised on a global scale, how interchangeability is implemented varies widely. This is because substitution policies are shaped not only by regulatory designations, but also by national laws and healthcare system structures within different markets.³ Some regions allow prescribers full control over switching decisions, while others allow pharmacists to substitute at the point of dispensing without consulting the prescriber.^2,4,5

The EMA and HMA consider biosimilars interchangeable with their reference product once approved, but switching or substitution should be based on approved use and national policies. Decisions on how interchangeability is applied, by prescribers or at the pharmacy level, are made by individual EU member states, not the EMA.⁴

An interchangeable biosimilar can be substituted for the reference biologic at the pharmacy without prescriber consultation, similar to generics, subject to state laws. Both biosimilars and interchangeable biosimilars are proven to be as safe and effective as the original biologic and can be prescribed in its place.⁵

REFERENCES

Abbreviations: EMA, European Medicines Agency; FDA, Food and Drug Administration; HMA, Human Medicines Agency.

1. European Medicines Agency. Biosimilars in the EU: Information Guide for Healthcare Professionals. Published 2017. Accessed October 2025. Available at: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf.
2. Afzali A, et al. The automatic substitution of biosimilars: definitions of interchangeability are not interchangeable. Adv Ther. 2021;38(5):2077–2093.
3. Knox RP, et al. Biosimilar approval pathways: comparing the roles of five medicines regulators. J Law Biosci. 2024;11(2):1-27.
4. European Medicines Agency. Statement on the scientific rationale supporting the interchangeability of biosimilar medicines in the EU. Published September 19, 2022. Accessed October 2025. Available at: https://www.ema.europa.eu/en/documents/public-statement/statement-scientific-rationale-supporting-interchangeability-biosimilar-medicines-eu_en.pdf.
5. U.S. Food and Drug Administration. Biosimilar and interchangeable biologics: more treatment choices. Published July 28, 2021. Accessed October 2025. Available at: https://www.fda.gov/consumers/consumer-updates/biosimilar-and-interchangeable-biologics-more-treatment-choices.

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