FDA’s NEW draft Drug Master Files Guidance for Industry explained

What you need to know about FDA’s NEW draft Drug Master Files Guidance for Industry

BY Lynne Ensor, Vice President, Technical, Parexel - 10.25.19 -

Drug Master Files (DMFs) may be submitted to the FDA to provide confidential and often proprietary information regarding facilities, processes, or components used in the manufacturing, processing, packaging, or storing of drug products.  Since it has been 30 years since the FDA released its DMFs: Guidelines in September 1989, the FDA posted the long-awaited, reorganized draft DMFs Guidance for Industry (GFI) for public comment on October 21, 2019.  

Following the public comment period, once finalized this GFI will represent the FDA’s, specifically the Center for Drug Evaluation and Research’s and the Center for Biologics Evaluation and Research’s, current thinking on the topic.  

Overall, the draft DMFs GFI provides information regarding the preparation and submission of DMFs.  It also describes DMF types, required information for a DMF, and the FDA’s DMF review process.  Although most of the original technical information contained in the 1989 guidance has remained unchanged, the guidance was reorganized and updated to include Generic Drug User Fee (GDUFA) considerations for Abbreviated New Drug Applications (ANDAs) and electronic common technical document (eCTD) format references, as these were not in existence when the GFI was originally released three decades ago.  

Some of the highlights from the updated DMFs GFI are:

  • DMF eCTD considerations (electronic submission requirements under section 745A of the Food, Drug, and Cosmetic Act which apply to certain DMFs and were not implemented at the inception of the original DMFs GFI)
    • eCTDs are required for all DMFs, excluding Type III (Packaging Material) DMFs.  Type III DMFs may still be submitted in paper format, although electronic submission is preferable to the agency
    • DMFs must have a pre-assigned number prior to their submission (refer to draft GFI line 117 for details on how to obtain a pre-assigned DMF number)
  • Updates for ANDA referenced submissions to reflect GDUFA commitments, which were not in place when the GFI original published
  • Improved details regarding how to submit an original DMF verses an amendment
  • An updated FDA DMF website:
    • to align to the current draft GFI, since the website not synchronized with the original, older guidance previously
    • will contain an ‘active’ Frequently Asked Question section, which will be constantly updated to address repetitive, voluminous, or critical formal inquiries received by FDA
  • Removal of Type I DMFs (which were discontinued in 2000)
  • An updated FDA contact person for the guidance

The DMFs GFI has a public comment period of 60 days (comments due by December 20, 2019) and can be found here.  Be mindful that DMFs are neither approved or disapproved by FDA.  DMF submissions are entirely at the discretion of the holder and they are not required by statue or regulation.  They are reviewed by FDA when specifically referenced in a drug application (new drug application, ANDA, investigational new drug applications, and biologics license applications).  

It is strongly advised that the authorized application specifically references, in the DMF’s Letter of Authorization, sections of the DMF which pertain to that specific application.  These references direct FDA assessors to the exact information and/or data pertinent to the specific drug product and its manufacturing process.  Directly referencing DMF information typically expedites the review process for both the DMF and referenced drug application, so it is a win-win for both the DMF holder and drug product applicant.  

We are always available for a conversation.


We are always available for a conversation.


Communication Preference

Communication Preference