USFDA Guidance: Review of Drug Master Files in Advance of Certain ANDA Submissions

U.S. Food and Drug Administration announced yesterday (17 October 2024) a final guidance, "Review of Drug Master Files in Advance of Certain ANDA Submissions" that is intended for holders of Type II active pharmaceutical ingredient (API) drug master files (DMFs) that will be referenced in an abbreviated new drug application (ANDA), or a prior approval supplement (PAS) to an ANDA.

Drug Master File (DMF): A submission to the FDA that contains confidential detailed information about the manufacturing, processing, packaging, and storage of drug substances or APIs.

In this guidance, a DMF holder can request an early assessment, or a "DMF prior assessment," as well as the circumstances in which FDA will initiate an early assessment of Type II API DMFs 6 months in advance of an ANDA or PAS referencing the DMF, as well as suggestions for such DMF holders.

The guidance does not apply to Type II API DMFs used to support new drug applications (NDAs), submissions related to ANDAs that are not described above, or any other types of DMFs.

Under GDUFA, DMF holders are required to pay a DMF fee to be eligible for review. This fee must be paid before the DMF review can begin. If the fee has not been paid or the DMF does not meet FDA standards, the DMF will not be reviewed until compliance is achieved.

DMF holders can submit their DMFs 6 months before an ANDA or ANDA amendments. This timeline provides enough opportunity for the FDA to review the DMF and communicate any deficiencies to the DMF holder, giving them time to correct the issues before the ANDA is submitted. The GDUFA III Commitment Letter, to be eligible for this assessment, a DMF holder would submit with its request the following:

a. At least one Letter of Authorization (LOA) with one pre-assigned ANDA number;

b. A reference to the corresponding reference listed drug (RLD)10 listed in FDA’s Approved Drug Products With Therapeutic Equivalence Evaluations (the Orange Book);

c. Documentation that the DMF holder has paid a GDUFA DMF fee

In cases where a Prior Approval Supplement (PAS) is being submitted to add a new API source to an approved ANDA, the DMF for the new API source can also be submitted for early assessment. The timeline for submission is the same — 6 months in advance of the planned PAS submission. This process ensures that the DMF for the new API source is reviewed in advance, allowing for the timely approval of the PAS without API-related delays.

For more detailed information, refer to the full guidance document.