FDA issues draft guidance clarifying differences between ANDAs and 505(b)(2) applications
The US Food and Drug Administration (FDA) has updated its seven-year-old guidance to clarify the differences among abbreviated approval pathways and the data it will accept for these applications. These pathways include the traditional Abbreviated New Drug Application (ANDA) process under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the 505(b)(2) pathway.
“Many potential drug product developers are not familiar with the different abbreviated approval pathways for drug products under the FD&C Act described in sections 505(j) and 505(b)(2) of 21 the FD&C Act (21 U.S.C. 355(b)(2), respectively) or the types of data and information that are permitted to support approval under those pathways,” states a notice announcing the guidance.
The draft guidance replaces a former version issued in May 2019. The agency notes that “changes from the 2019 version include providing additional information on duplicates and eligibility for approval under section 505(j) of the FD&C Act, as well as other updates that are intended to clarify FDA's recommendations to industry” (RELATED: When to Submit an ANDA vs. a 505(b)(2)? FDA Explains, Regulatory Focus 9 May 2019).
In the guidance, FDA outlines four different categories of applications:
- The 505(b)(1) is the stand-alone pathway for new drug applications under section 505(c) of the FD&C Act that requires full reports of investigations of safety and effectiveness for new drugs that were conducted by or for the applicant or for which the applicant has a right of reference or use.
- A 505(b)(2) application is an NDA submitted 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 or use. Drugs that can be submitted through the 505(b)(2) pathway include new versions of approved drugs that differ in the reference listed drug (RLD) in terms of active ingredient, dosage form, strength, route of administration, formulation, or when there is a new indication.
- The 505(j) pathway is for a product that is a duplicate of a previously approved drug product. An ANDA relies on FDA’s finding that the previously approved reference listed drug (RLD) is safe and effective. An ANDA generally must contain information to show that the proposed generic drug product is the same as the RLD with respect to the active ingredients, conditions of use, route of administration, dosage form, strength, and labeling, and its bioequivalence to the RLD.
- 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 suitability petition, that studies are not necessary to establish the safety and effectiveness of the proposed drug product.
In the guidance, FDA explains some of the regulatory considerations for these pathways. FDA will approve a suitability petition for an ANDA unless it determines 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 the drug product is approved in an NDA or a 505(b)(2) application.
The agency will not accept a 505(b)(2) application for a drug product that is a duplicate of a listed drug. Such duplicate drugs are only approvable under the full ANDA pathway under Section 505(j).
An applicant seeking approval for multiple drug products containing the same active ingredient may submit a single application under the 505(j) pathway. The guidance states that “an applicant seeking approval for multiple strengths of the same dosage form of a drug product, only some of which are duplicates of previously approved drug products 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.”
FDA states that applications submitted under section 505(j) require that an applicant’s proposed generic drug product be demonstrated to be the same as the RLD with respect to the active ingredient. If the active ingredient is different, the applications should not be submitted as an ANDA.
Under the section 505(j) pathway, the agency will allow certain differences in inactive ingredients for parenteral drugs. This would include preservatives, buffers, and antioxidants. Yet all other inactive ingredients must be qualitatively and quantitatively identical (Q1/Q2 same) to those in the RLD.
The deadline for submitting comments is 19 October. Comments should be sent to www.regulations.gov and reference Docket No. FDA-2017-D-5974.
