Table 1

Key Terms and Definitions Related to Therapeutic Interchange/Substitution

TermDefinition
BioavailabilityThe rate and extent to which a drug's active ingredient is absorbed from the drug product and becomes available at its site of action.
BioequivalenceThe absence of a significant difference in bioavailability between a drug product and its innovator when administered at the same molar dose under similar conditions in an appropriately designed study.
BiologicsBiological agents that are derived from living sources such as cultures of bacteria, viruses, or human or animal tissue and may have either a therapeutic or diagnostic intent.
Biosimilars“Generic” biologics that are copies of a therapeutic protein, not manufactured by an innovator company, and approved through an abbreviated process.
Critical dose drugsDrugs in which comparatively small differences in dose or concentration may lead to serious therapeutic failures and/or serious drug reactions.
Generic substitutionThe act of switching between a branded drug and its therapeutically equivalent generic version.
Narrow therapeutic index drugsDrugs identified as having less than a 2-fold difference between the median lethal and the median effective dose, having less than a 2-fold difference between the minimum toxic and minimum effective concentrations in the blood, and where safe and effective use of the drug requires careful titration and patient monitoring.
Orange Book (i.e., Approved Drug Products with Therapeutic Equivalence Evaluations)An FDA publication that identifies drug products approved on the basis of safety and effectiveness. It contains information as to whether generic versions of medications are considered to be therapeutic equivalents to the drugs manufactured by the innovator company (1).
Pharmaceutical equivalentsDrug products that contain the identical amounts of the same active ingredient in the same dosage form and route of administration, as well as meet compendia or other applicable standards of strength, quality, purity, and identity.
Reference innovatorThe initially FDA-approved drug in this category.
Therapeutic equivalentDrug products that are approved as safe and efficacious; are pharmaceutical equivalents; are bioequivalent; and are manufactured in compliance with current Good Manufacturing Practice regulations.
Therapeutic interchangeThe act of dispensing, with the authorization of the initial prescriber, an alternative drug that is believed to be therapeutically similar but may be chemically different, in a different category, with different pharmacokinetic properties. This interchange is based on the premise that the substituted drug will provide a similar clinical efficacy, desired outcome, and safety profile.
Therapeutic substitutionThe act of therapeutic interchange that occurs without the prior authorization of the initial prescriber.

FDA indicates U.S. Food and Drug Administration.