FDA publishes draft guidance on determining whether to submit an ANDA or a 505(b)(2) application

In a new draft guidance document, the US Food and Drug Administration (FDA) explains both the pathways by which abbreviated new drug applications (ANDAs) and 505(b)(2) applications can be submitted. The guidance document includes information to assist applicants in determining which type of application is appropriate.

The draft guideline provides the definitions for various application types: an ANDA for a duplicate or generic drug, a petitioned ANDA and a 505(b)(2).

A ‘generic’ ANDA is an “application for a duplicate of a previously approved drug product that was submitted and approved under section 505(j) of the FD&C Act. An ANDA relies on FDA’s finding that the previously approved drug product, i.e., the reference listed drug (RLD), is safe and effective”.  Such an application usually requires that the proposed generic drug and the RLD are the same with respect to their active ingredient(s), dosage form, route of administration, strength, indications and labelling (with certain exceptions). An ANDA must also contain data demonstrating bioequivalence between the products.

In contrast, a petitioned ANDA is a type of ANDA for a drug product that differs from the RLD in its dosage form, route of administration, strength or active ingredient and for which FDA has determined, in response to a petition submitted under section 505(j)(2)(C) of the FD&C Act, that studies are not necessary to establish the safety and effectiveness of the proposed drug product. FDA will approve a suitability petition unless, among other things, (i) the agency decides that the safety and effectiveness of the proposed change from the RLD cannot be adequately evaluated without data from investigations that exceed what may be required for an ANDA or (ii) the petition is for a drug product for which a pharmaceutical equivalent has been approved in an NDA.

A 505(b)(2) application is an “NDA submitted under section 505(b)(1) and approved under section 505(c) of the FD&C Act that contains full reports of investigations of safety and effectiveness, 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“.

It is important to understand that the FDA generally will refuse to file a 505(b)(2) application for a drug that is a duplicate of a listed drug and eligible for approval under section 505(j) of the FD&C Act. If the FDA approves a duplicate drug product after submission of a 505(b)(2) application, but it is approved, that application would remain eligible for approval.

In a situation where an applicant wishes to submit applications for more than one strength of a drug containing the same active ingredient, and only some strengths would qualify for the 505(b)(2) route, bundling is allowed.  Bundling permits the submission of a single 505(b)(2) application for all strengths in a single NDA.

The draft guidance also offers various scientific considerations for both types of applications including:

  • Limited confirmatory studies
  • Active ingredient sameness evaluation
  • Drug product and RLD differences
  • Differences in bioequivalence and/or bioavailability
  • Differences in conditions of use and other differences.

Click here to access the full draft guidance document.