On May 9, 2019, FDA issued final guidance titled, “Determining Whether to Submit an ANDA or a 505(b)(2) Application.” FDA intends the guidance to assist applicants in determining which abbreviated approval pathway is appropriate when filing a drug marketing application. The final guidance is nearly identical to FDA’s draft guidance of the same name from October 2017. Finnegan’s IP FDA Blog post on the draft guidance can be found here.

The guidance draws various comparisons between ANDAs and 505(b)(2) applications. For example, an ANDA applicant must demonstrate that the proposed generic product is therapeutically equivalent to the applicable RLD, while a 505(b)(2) applicant need not demonstrate this. An ANDA applicant must also show that the proposed generic drug product and RLD are the same with respect to their active ingredient(s), dosage form, route of administration, strength, conditions of use, and labeling (with certain exceptions), while this is not required for a 505(b)(2) application. Additionally, an ANDA relies on FDA’s findings of safety and effectiveness for an RLD, while a 505(b)(2) application may rely on FDA’s findings of safety and/or effectiveness for a listed drug only to the extent the proposed product shares characteristics with it (e.g., active ingredient, dosage form, route of administration, strength, indication or other conditions of use). To the extent a 505(b)(2) drug and a listed drug differ (e.g., a product with a different dosage form), the 505(b)(2) application must support the differences with sufficient data, such as clinical investigations.

FDA provides three regulatory considerations when deciding whether to file an ANDA or 505(b)(2) application:

  1. Duplicates. FDA generally will refuse a 505(b)(2) application for a drug that is a duplicate of an RLD and eligible for approval through an ANDA.
  2. Petitioned ANDAs. An applicant may petition FDA for permission to submit an ANDA for a generic drug product that differs from an RLD in its route of administration, dosage form, or strength or that has one different active ingredient in a fixed-combination drug product. FDA generally grants these petitions unless it determines (1) additional data or studies are necessary to determine the safety and effectiveness of the proposed drug product, or (2) the petition is for a drug product for which a pharmaceutical equivalent has been approved in an NDA, in which case a petitioned ANDA is not needed.
  3. Bundling. An applicant may be able to use a bundled 505(b)(2) application for multiple drug products containing the same active ingredient(s) when some of the products would qualify for approval via ANDAs and others would qualify under 505(b)(2).

FDA also provides three scientific considerations:

  1. Types of Studies, Data, and Information Submitted in ANDAs. ANDA applicants and 505(b)(2) applicants generally have significant flexibility in the types of studies, data, and information they may submit to FDA in support of their applications. However, 505(b)(2) applicants may submit clinical investigations to establish safety and/or effectiveness, while ANDA applicants may not.
  2. Active Ingredient Sameness Evaluation. ANDAs generally must demonstrate that a proposed generic product is the same as the RLD with respect to active ingredient(s). FDA has adopted a flexible approach in making these types of determinations.
  3. Intentional Differences Between the Proposed Drug Product and the RLD. Permissible differences between an ANDA product and the RLD may include, for example, differences in formulation, i.e., inactive ingredients, or differences in conditions of use, i.e., the ANDA labeling carves out conditions of use approved for the RLD because of patents or regulatory exclusivity.