Late last week, FDA released a final guidance titled “Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFA” 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. 

This guidance expands upon the information in the “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027” (GDUFA III commitment letter). Specifically, it provides information and recommendations on when a DMF early assessment, also referred to as a DMF prior assessment, could be requested and the conditions that must be met for FDA to commence such an assessment of Type II API DMFs six months prior to the submission of an ANDA or PAS referencing the DMF. For example, FDA states the following information must be provided when requesting an early assessment: 

• at least one Letter of Authorization with one pre-assigned ANDA number; 
• documentation that the DMF holder has paid a GDUFA DMF fee; and
• when the request is to support an original ANDA, reference to the corresponding reference listed drug listed in FDA’s Approved Drug Products With Therapeutic Equivalence Evaluations (the Orange Book).

FDA also provides a checklist containing elements the Agency recommends be included in the cover letter of the early assessment request and recommends that the DMF holder clearly state the basis on which it believes the request qualifies for such early assessment. 

It is important to note that FDA clarified that these requests should be limited to one DMF per API for each application. If the drug product has multiple APIs, and the DMF holder wishes for multiple early assessments, then a separate request must be submitted for each API. Moreover, FDA emphasized that this guidance does not apply to Type II API DMFs used to support new drug applications (NDAs), submissions related to ANDAs that are not described within the guidance itself, or any other types of DMFs.