The US Food and Drug Administration (FDA) has issued its final guidance on making therapeutic equivalence evaluations and assigning therapeutic equivalence (TE) codes. The guidance is the final version following the release of the draft guidance in 2022.
As defined in 21 CFR 314.3(b), therapeutic equivalents are described as ‘approved drug products that are pharmaceutical equivalents for which bioequivalence has been demonstrated, and that can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labelling’.
These therapeutic equivalence evaluations have been prepared to promote public education in cost-effective drug product selection for State health agencies, prescribers and pharmacists. Assigned TE codes are listed in the Agency’s Orange Book and indicate a drug’s bioequivalence to a reference-listed drug (RLD).
The final guidance, entitled ‘Evaluation of Therapeutic Equivalence’ explains that the scientific and regulatory foundation for the evaluation of therapeutic equivalence of prescription drug products is based on:
1. Pharmaceutical equivalence
2. Bioequivalence, and
3. Same expected clinical effect and safety profile when administered to patients under the conditions specified in the labelling.
It states that: ‘the FDA believes products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product will have the same clinical effect and safety profile as the prescribed product when administered to patients under the conditions specified in the labelling’.
Specifically, Section B of the guidance discusses products evaluated for therapeutic equivalence. The FDA states that the guidance primarily applies to abbreviated new drug applications (ANDAs). Sponsors must show that the proposed generic product is the same as the RLD with respect to the active ingredient, conditions of use, route of administration, dosage form, strength and labelling, and that the drug is bioequivalent to the RLD.
The FDA states in the guidance that it does not typically conduct TE evaluations for new drug applications (NDAs) submitted under Section 505(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) or for products submitted via the hybrid 505(b)(2) application pathway.
The issue of this guidance reinforces the FDA’s commitment to informing relevant parties about cost-effective drug-product selection.
