Today, the FDA issued the final guidance titled Evaluation of Therapeutic Equivalence (here). The guidance is essentially identical to one with the same title issued in July 2022. There are only a few changes from the draft guidance, which include revisions to reflect an additional process by which applicants of certain 505(b)(2) applications may request TE codes. Minor changes were also made to improve clarity and to update the guidance.

The document describes the fundamentals of therapeutic equivalence (TE) including pharmaceutical equivalence, bioequivalence, and note that in order to be therapeutically equivalent, two products must be expected to have the same clinical effects and safety profile.

It outlines the FDA’s process for determining TE for ANDAs, 505(b)(1) and 505(b)(2) applications and the differences among the way in which TE codes are established including an explanation of why single source products (both NDAs and ANDAs) do not have an associated TE code in the Orange Book.

The guidance also has a section that describes how and why the FDA may change TE codes once assigned.

The guidance outlines the petition process for requesting an assignment of a TE code for a 505(b)(2) application but also describes the process that an “application holder may use the process described in section 505(j)(7)(A)(v)(I) to request that FDA make a therapeutic equivalence evaluation for a prescription drug in a 505(b)(2) application where the sole difference from a listed drug relied upon in the application is a difference in inactive ingredients not permitted under 21 CFR 314.94(a)(9)(iii)-(iv)”. In such cases, FDA will reach a therapeutic equivalence determination for such products “at the time of approval of such application or not later than 180 days after the date of such approval”. The use of the petition process for this type of specific change came under a lot of scrutiny due to the significant delays in responding to those petitions. The change in the law identified above was made to address that very specific issue. The petition process for other instances of TE determinations for 505(b)(2) applications is still in play.

There is also an interesting question and answer section in the guidance document.