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FDA is pushing forward with new initiatives targeting enhancements to the Generic Drug User Fee Amendments (GDUFA) program as announced in a November 2021 commitment letter to industry. The current and third iteration of the GDUFA program, known as GDUFA III, enables FDA to continue assessing and collecting GDUFA fees that fund the Agency’s review programs for generic drugs.

Two new initiates under the GDUFA III program, both announced in October 2022, include a Draft Guidance for Industry that aims to streamline reviews of Drug Master File (DMF) submissions in advance of certain Abbreviated New Drug Applications (ANDA), and a Draft Guidance detailing criteria FDA will use to assign a goal review date based on a facility’s readiness for an inspection as certified on FDA Form 356h submitted as part of an original ANDA application.

Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFA

The first Draft Guidance for Industry focuses early assessment requests for holders of type II active pharmaceutical ingredient (API) DMFs that will be referenced in an ANDA or a prior approval supplement (PAS) to an ANDA. It does not apply to Type II API DMFs used to support new drug applications (NDAs) related to ANDAs.

DMF assessments six months prior to a planned ANDA or ANDA amendment submission may be requested in cases where FDA has not previously conducted a substantive DMF assessment and the DMF supports:

  • an original ANDA;
  • an ANDA amendment that contains a response to a Complete Response Letter (CRL);
  • an amendment seeking approval of an ANDA that previously received a tentative approval.

Additionally, holders of a DMF may submit a request for assessment of the DMF six months prior to the planned submission date for a PAS that requests to add a new API source in cases when the drug could alleviate or help to prevent drug shortages or when the drug will address a public health emergency.

Prior assessment requests should be limited to one DMF per API for each application. An appendix including required items to be submitted as part of the request is included in the Draft Guidance’s appendix.

During FDA’s review, DMF holders should continue close communication with the ANDA applicant to ensure all appropriate materials are provided in support of FDA’s review. These include:

  • At least one Letter of Authorization (LOA) with one pre-assigned ANDA number;
  • A reference to the corresponding reference listed drug (RLD) in FDA’s “Orange Book” if the request is to support an original ANDA ;
  • Verification that the DMF holder GDUFA DMF fee payments are current.

Facility Readiness: Goal Date Decisions Under GDUFA

FDA and industry are incentivizing ANDA applications that include inspection ready facilities to facilitate timely assessments. Inspection readiness includes compliance with FDA current good manufacturing practices (CGMP), and use of operations, methods and formulations consistent with those listed in the ANDA application, including facility data. Facilities must also be ready for commercial manufacturing at the time of inspection.

Under GDUFA III, FDA has committed to a goal of 15 months for original ANDAs. That includes any facility listed on Form FDA 356h as not inspection ready. Form FDA 356h includes a “yes” / “no” checkbox indicator for inspection readiness, but even so, FDA has experienced cases where facilities were unaware that they were listed on Form FDA 356h, and thus were unprepared for an FDA inspection.

In cases where facilities listed on Form 356h are not ready for inspection, FDA will assign a 15-month goal data expiration. In cases when facilities are still not prepared for an inspection 30 days before the 15-month goal date expiration, FDA will reset the goal date for an additional 15 months (i.e., 30 months from the date of original ANDA submission). Applications can be amended once all facilities are ready for inspection and the goal date may be reset to a standard or priority assessment, as applicable. To facilitate the date reassignment, FDA recommends including “Facility Ready For Inspection” as part of the cover letter requesting such change.

For questions on how this draft guidance may affect you, contact EAS Consulting Group.


Posted in Drugs.