Last week, FDA published new guidance, Determining Whether to Submit an ANDA or a 505(b)(2) Application (CDER, 2019), to help Sponsors select the best abbreviated approval pathway for their product. While the guidance does not provide any monumental new initiatives, policies or approaches, here are four key takeaways on 505(b)(2) and abbreviated new drug application (ANDA) regulatory pathways.

1. FDA distinguishes not 3 but 4 regulatory pathways in the guidance

Interestingly, FDA begins by distinguishing four regulatory pathways:

• A “stand-alone NDA” application (submitted under section 505(b)(1))
• A 505(b)(2) application
• An ANDA
• A petitioned ANDA

A petitioned ANDA is one in which the Sponsor seeks to submit an application that differs from the reference listed drug (RLD) in dosage form, route of administration, strength or active ingredient (in cases where the proposed product is a fixed combination product and the Sponsor wishes to change one of the active ingredients).

Although not mentioned specifically in the guidance, this fourth application category can overlap with the 505(b)(2) pathway. The name derives from the requirement that a suitability petition be submitted to and approved by FDA before the ANDA may be submitted. The guidance excludes the 505(b)(1) pathway from further discussion.

2. Requirements and considerations are outlined for each type of submission

The guidance effectively lays out Regulatory (Section IV.A.) and Scientific (Section IV.B.) requirements and considerations for each type of submission.

For example, if a proposed product is considered a “duplicate”, it must be filed as an ANDA; it cannot be filed as a 505(b)(2). A “duplicate” is a product that has the same active ingredient(s), dosage form, route of administration, strength, conditions of use and labeling (with the allowable labeling variations).

3. A useful but seldom used approach known as “bundling” is described

In some instances, applicants may submit one 505(b)(2) application for multiple drug products permitted to be bundled in a single NDA:

“In some circumstances, an applicant may seek approval for multiple drug products containing the same active ingredient(s) when some of these products would qualify for approval under the section 505(j) pathway and some would qualify for approval under the 505(b)(2) pathway. In these circumstances, FDA has permitted an applicant to submit a single 505(b)(2) application for all such multiple drug products that are permitted to be bundled in a single NDA. For example, an applicant seeking approval for multiple strengths of a product, only some of which are included in the Orange Book as listed drugs, would not have to submit both an ANDA for the strengths listed in the Orange Book and a 505(b)(2) application for the new strengths; instead, the applicant may submit one 505(b)(2) application for all of the proposed strengths.”

4. FDA has broad discretion when evaluating active ingredient sameness

The guidance also has a useful, if somewhat murky, description of the importance of the “sameness” requirement for the active pharmaceutical ingredient for an ANDA compared to the associated RLD:

“FDA has broad discretion to determine whether an ANDA applicant has submitted information sufficient for the Agency to reasonably conclude that the proposed drug product’s active ingredient is the same as the active ingredient in the RLD. That is, the statutory provisions outlining the contents of an ANDA do not describe the type or amount of information that an ANDA applicant must submit to demonstrate that the active ingredient in the proposed generic drug product is the same as the active ingredient in the RLD.”

This description is followed by a caveat and recommendation to contact the Office of Generic Drugs (OGD) with questions:

“In some instances, current limitations of scientific understanding and technology may preclude approval of an ANDA with the data permitted for submission in an ANDA, including, for example, with respect to establishing active ingredient sameness of a given product. As scientific understanding and technology evolve, though, FDA may be able to receive, review, and approve ANDAs where it previously lacked the scientific basis to do so. We therefore recommend that a prospective ANDA applicant with questions about determining active ingredient sameness contact OGD prior to submission of the application.”

Determining the right pathway for your product

Beyond these four takeaways, the guidance also discusses the impact of formulation differences, bioequivalence issues, any required studies, and the presence of device constituents when determining whether a new product application is appropriately classified as an ANDA or 505(b)(2).

If you need help determining the best regulatory pathway for your product, Premier Consulting delivers deep experience with customized pharmaceutical R&D strategies to identify and execute the optimal path to better outcomes. Contact us to learn more.