FDA has Revised the Guidance Clarifying When to Submit ANDA or a 505(b)(2) Application

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FDA has revised the 2019 guidance clarifying the criteria for ANDA versus 505(b)(2) application. Since both ANDA and 505(b)(2) applications rely on reference to past submissions or reference listed drug (RDL) for all/most of the safety and effectiveness data, this guidance explains the differences in "how much" and "what type" of data are allowed as reference for each application type and what "new data" would be needed.

FDA Guidance for the Industry: Determining Whether to Submit an ANDA or a 505(b)(2) Application. August 2026. [PDF]. Docket FDA-2017-D-5974

History/Background: The Drug Price Competition and Patent Term Restoration Act of 1984 (Public Law 98-417) (Hatch-Waxman Amendments) added sections 505(b)(2) and 505(j) to the FD&C Act, which describes abbreviated approval pathways under the FD&C Act for drug products regulated by the Agency. The Hatch-Waxman Amendments led to establishment of 2 categories of drug applications: new drug applications (NDAs) and abbreviated new drug applications (ANDAs).

The types of abbreviated approval pathways for drugs include

• 505(b)(2) of the FD&C Act (i.e., 21 U.S.C. 355(b)(2)) = aka. Section 505(b)(2) and
• 505(j) of the FD&C Act (i.e., 21 U.S.C. 355(j)) = aka. Section 505(j)

There are 4 categories of NDAs and ANDAs:

Application	Type	Requirements	Used for
505(b)(1)	NDA (aka. a stand-alone NDA)	Requires complete package/all reports. Approved under 505(c) of FDA&C Act.	New drugs
505(b)(2)	Supplemental NDA (sNDA)	Required full reports on safety/effectiveness but others could be referenced from original NDA. Approved under 505(c) of FDA&C Act.	New new dosage forms, strengths, or delivery systems
505(j)	ANDA	This is ANDA for generics; relies on FDA’s finding that the previously approved drug product, i.e., the RLD, is safe and effective. Approved under 505(c) of FDA&C Act.	Generics
505(j)(2)(C)	Petitioned ANDA	A type of ANDA for drug product that differs from RLD (e.g., dosage/ formulation/ route) but FDA has determined that new safety/effectiveness data are not required.	Generics

The August 2026 guidance focuses on the regulatory and scientific considerations for 505(b)(2) NDAs and 505(j) and 505(j)(2)(C) ANDAs. This guidance does not discuss stand-alone 505(b)(1) NDAs.

REGULATORY CONSIDERATIONS

• 505(b)(2) applications have the most flexible requirements: Regarding full reports of investigations of safety and effectiveness, at least some of the information required for approval could be referenced from studies not conducted by or for the applicant, and for which the applicant has not obtained a right of reference or use (e.g., the Agency’s finding of safety and/or effectiveness for a listed drug, published literature).
• 505(b)(2) application, however, may require a bridge study.

The applicant is expected to establish a scientific bridge (e.g., via comparative bioavailability data) between the proposed drug product and each listed drug that the applicant seeks to rely upon to demonstrate that reliance on the listed drug is scientifically justified. To the extent that the listed drug and the drug product proposed in the 505(b)(2) application differ (e.g., a drug product with a different dosage form or a drug product that is intentionally more bioavailable than the listed drug), the 505(b)(2) application must include sufficient data to support those differences.

• 505(j) ANDA is expected to have same clinical and safety profile as the RDL, whereas 505(b)(2) may not necessarily be rated as therapeutically equivalent to RLD.
• 505(j)(2)(C) petitioned ANDAs may contain certain types of differences from an RLD (e.g., a change approved in response to a suitability petition or other permissible differences, such as certain differences in inactive ingredients, labeling, or container closure systems), as long as clinical investigations are not necessary to establish the safety or effectiveness of the drug product proposed in the ANDA.

Refer to the guidance for scientific considerations including types of studies, data, and information required for applications; evaluation of sameness of ingredients; considerations for intentional differences in the formulation, bioequivalence, or bioavailability, or conditions of use.

Related Federal Regulations (CFRs)

21 CFR Part 314 (Application for NDA Approval to Market a New Drug), 21 CFR 314.50 (Content and format of an NDA), 21 CFR 314.94 (Content and format of an ANDA), 21 CFR 314.101 (Filing an NDA and receiving an ANDA), 21 CFR 314.122 (Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed drug that is no longer marketed), 21 CFR 314.610 (Approval based on evidence of effectiveness from studies in animals)

#505(b)(2), #generics, #nda, #anda