Drug Master Files: Guidelines

A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. 

The submission of a DMF is not required by law or FDA regulation. A DMF is submitted solely at the  discretion of the holder. The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, or amendments and supplements to any of these.

A DMF is NOT a substitute for an IND, NDA, ANDA, or Export Application. It is not approved or disapproved. Technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application.

This guideline does not impose mandatory requirements (21 CFR 10.90(b)). It does, however, offer guidance on acceptable approaches to meeting regulatory requirements. Different approaches may be followed, but the applicant is encouraged to discuss significant variations in advance with FDA reviewers to preclude spending time and effort in preparing a submission that FDA may later determine to be unacceptable.

Drug Master Files are provided for in 21 CFR 314.420. This guideline is intended to provide DMF holders with procedures acceptable to the agency for preparing and submitting a DMF.

The guideline discusses types of DMF's, the information needed in each type, the format of submissions to a DMF, the administrative procedures governing review of DMF's, and the obligations of the DMF holder. DMF's are generally created to allow a party other than the holder of the DMF to reference material without disclosing to that party the contents of the file. When an applicant references its own material, the applicant should reference the information contained in its own IND, NDA, or ANDA directly rather than establishing a new DMF.

Drug master file is a valuable and important part of regulatory affairs in pharmaceuticals. Proper submission of DMF plays an important role of product approval by regulatory authorities.

The guidance document discusses the preparation and submitting of drug master files as well as FDA’s review process.

FDA announced the publication of draft guidance on drug master files on October 18, 2019. The new guidance revises the agency’s September 1989 guidance, Drug Master Files: Guidelines and details the preparation and submission of drug master files (DMFs).

1. Meaning of a Drug Master File

• DMF stands for Drug Master File which is a voluntarily submission at the holder’s discretion to help the customers.

2. Drug Master Files’ Regulatory Basis

• It is not a necessity by law to submit DMF, on the other hand, it is submitted at the holder discretion. Upon submission, DMF isn't endorsed or objected; its contents are checked in reference to the application’s review.

3. DMF Submission Contents

• Each submission has particular requirements including a transmittal letter, information about the administration and the information necessary to be covered in the DMF which should be written only in English.
• No different forms should be submitted alongside the DMF apart from the user fee. DMF number must be included in all Letters of Approval.
• Every single page of DMF’s copy should be continuously numbered and dated of which any update should incorporate a table of contents which is updated.

4. Electronic Entries

• As from 5th May 2018, each new entry into the current DMF should be amassed and entered in eCTD form. In the event that a current DMF happens to be in the paper format then a similar entry should be submitted again in eCTD format. The Agency will automatically reject DMF's not submitted in eCTD format.
• Electronic entries 10 GB or less should be entered through the Electronic Submission Gateway and entries more than 10 GB might be presented on physical media.

5. US Food and Drug Administration Agents

• It is a requirement from the US FDA each firm from another country doing business under the FDA regulatory, use U.S. Agents when conducting its business. The agents act as intermediaries between the firm and the FDA. All DMF entries must include the agent’s contacts’ details updates more so the agent’s information. In a case whereby the FDA analysts have queries in regards to the DMF; they will definitely contact the agent with those inquiries notwithstanding the submitter and give a course of events in which those answers should be given.
• DMF should be updated each time new data pops up. The new data could be another softener for a compartment, a new course of the union, a change to a dose shape, or whatever other change that has the capacity for trading off the security of the pharmaceutical.
• Drug Master File (DMF) is a classified report used to give the point by point data about offices, procedures or particulars utilized in the assembling procedure, bundling and putting away of at least one human medication. The DMF might be used either by the holder who sets up the record or by at least one extra gatherings in help innovation from its accomplice while conforming to administrative prerequisites of their application.
• The DMF recording enables a firm to shield its protected for the indulgence of preparing subtle elements. The survey incorporates different kinds of
• DMFs, the essential viewpoints in recording and handling.
• There are guidelines which should be adhered to in submission of the DMFs and failure to do so may lead to unnecessary compromises.