Substitution and Interchangeability: Explaining the Terms

Substitution^*,†	Practice wherein the pharmacist may dispense an alternative biologic for a prescribed biologic.¹ No prior approval from the prescriber is required.¹
Automatic substitution of biosimilars	Replacing one biologic with a biosimilar at the pharmacy level without consulting the prescriber.^2,‡
Switching	Practice wherein a prescriber decides to exchange a biosimilar for another medicine with the same therapeutic intent.²
Interchangeability	In the US, “interchangeable” is a term defined by statute to mean the product may be substituted for the reference product without the intervention of the prescribing healthcare provider. An interchangeable product must be expected to produce the same clinical result as the reference product in any given patient, and for products administered more than once, the risk of switching between the interchangeable product and the reference product must not be greater than using the reference product without such switching. Most US state pharmacy laws only permit biosimilar substitution of biosimilars that the FDA has deemed interchangeable.^3,4 According to the European Commission Consensus Information Document, interchangeability means, “the medical practice of changing one medicine for another that is expected to achieve the same clinical effect in a given clinical setting and in any patient on the initiative or with the agreement of the prescriber.”¹

^*In some US states, there is ongoing dialogue regarding post-dispensing notification and documentation.
^†Private organization management of substitution may vary based on formulary decisions and other factors.
^‡Prescribers may indicate “Dispense As Written” and patients may request the originally prescribed biologic medicine.

References: 1. European Commission. What you need to know about biosimilar medicinal products. www.medicinesforeurope.com/wp-content/uploads/2016/03/biosimilars_report_en.pdf. Accessed October 29, 2019. 2. European Medicines Agency. Biosimilars in the EU: information guide for healthcare professionals. www.ema.europa.eu/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. Accessed October 29, 2019. 3. US Food and Drug Administration. Considerations in demonstrating interchangeability with a reference product. www.fda.gov.downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm537135.pdf. Accessed October 29, 2019. 4. US Food and Drug Administration. Biosimilar and interchangeable products. www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products. Accessed October 29, 2019.