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.2,3,‡
Automatic substitution of biosimilars
  • Replacing one biologic with a biosimilar at the pharmacy level without consulting the prescriber.2,‡
Switching
  • Practice wherein a physician decides to exchange a biosimilar for a biologic with the same therapeutic intent.
  • In the EU, in the context of biosimilars, the term “switching” is often used synonymously with the term “interchangeable.”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 prescriber. 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 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.”5

*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. EuropaBio. Guide on Biosimilars in Europe. When Science Meets Policy. www.europabio.org/sites/default/files/europabio_guide_to_biosimilars_europe_2014.pdf. Accessed January 10, 2019. 2. CADTH. Environmental Scan: International Policies on the Appropriate Use of Biosimiliar Drugs. www.cadth.ca/sites/default/files/pdf/es0333_international-policies-on-use-of-biosimilar-drugs.pdf. Accessed January 10, 2019. 3. US Food and Drug Administration. FDA. Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Published April 2015. Accessed January 10, 2019. 4. National Conference of State Legislatures. State Laws and Legislation Related to Biologic Medication and Substitution of Biosimilars. www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. Accessed January 10, 2019. 5. European Commission. What You Need to Know about Biosimilar Medicinal Products. www.medicinesforeurope.com/wp-content/uploads/2016/03/biosimilars_report_en.pdf. Accessed January 10, 2019.