Today, the FDA has published revision 1 (here) of the draft guidance Determining Whether to Submit an NDA or a 505(b)(2) Application issued in May 2019. Its purpose is to further define which abbreviated pathway, ANDA, or a 505(b)(2) application, is the appropriate submission type for the market application.

The guidance first defines what a standalone NDA is (i.e., one that relies on full reports of safety and efficacy), then describes the 505(b)(2) as an application which also relies on full reports of safety and efficacy but “where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use application”. The guidance then goes on to define the ANDA as a duplicate of an existing Reference Listed Drug (RLD) for the underlying basis for safety and efficacy (and relies on the RLD’s data) and also meets the other applicable requirements for an ANDA including bioequivalence, full chemistry, manufacturing, and controls to demonstrate it is the same as that of the RLD. An ANDA cannot contain clinical studies other than bioequivalence studies to support its safety or efficacy. The guidance also describes a petitioned ANDA submitted under section 505(j)(2)(C) of the Act. Such an application may differ from the Reference Listed Drug (RLD) in dosage form, strength, route of administration, or an ingredient within the same pharmacological class that has a known equipotent dose relationship in a fixed-combination drug product, while still being expected to have the same therapeutic effect as the RLD on which the petition is based.

An ANDA must be shown to be therapeutically equivalent to the RLD upon which it relies whereas the 505(b)(2) “application allows greater flexibility as to the characteristics of the proposed drug product”. A drug product approved in a 505(b)(2) application will not necessarily be rated therapeutically equivalent to the listed drug it references.

The guidance document then goes on to describe the scientific considerations for ANDAs and 505(b)(2) applications which may impact on the type of filing that may be required:

  • Types of studies, data, and information submitted in ANDAs
  • Active ingredient sameness evaluation
  • Intentional differences between the proposed drug product and the RLD such as differences in formulation, difference in bioequivalence and/or bioavailability, differences in conditions of use and other differences with the exception of acceptable difference permitted by regulation.
  • Device constituents, and;
  • Labeling

The guidance also has a section that can help applicants decide how and where to seek FDA guidance for the appropriate application submission type. Once finalized, this draft guidance will replace the guidance issued in 2019 with the same title.