New FDA Guidance: Review of DMFs in Advance for ANDA Submissions

The USFDA has published a new guidance titled “Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFA,” intended for holders of Type II active pharmaceutical ingredient (API) drug master files (DMFs). DMF holders can request an early assessment of their DMF six months prior to the planned submission date of an abbreviated new drug application (ANDA) or a prior approval supplement (PAS) that references the DMF.

The DMF prior assessment request must be submitted by the DMF holder and should include:

• A valid Letter of Authorization (LOA) with a pending ANDA number.
• Reference to the corresponding reference listed drug (RLD).
• Documentation confirming payment of the GDUFA DMF fees.

The guidance specifies the conditions under which a DMF holder can request a prior assessment, at least one of which must be met:

• All patents and exclusivities will expire within 12 months of the planned submission date of the ANDA.
• There are no more than 3 approved ANDAs in the Orange Book; the ANDA applicant should not be seeking approval for less than all conditions of use and is not seeking to “carve out” any conditions of use from the approved RLD.
• The submission is for a drug product that could help mitigate or resolve a drug shortage.
• The submission is for a drug product that could help address a public health emergency.
• The submission is for a drug product for which there is only one approved drug product listed in the Prescription Drug Product List.

The DMF prior assessment route is available only for API information submitted in a DMF and not for the review of drug substance information included in the ANDA. Prior assessment is limited to one DMF (one source) per API for an ANDA; however, for fixed combination products, one DMF prior assessment can be submitted for each API.

The guidance does not apply to API DMFs used to support new drug applications (NDAs).

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