How to Submit a DMF (Drug Master File)

A Drug Master File (DMF) is a confidential document submitted to the U.S. FDA that contains detailed information about the manufacturing, processing, packaging, and storage of drug substances, intermediates, or components.
It is not mandatory but is often used to support another company’s IND, NDA, ANDA, or export application without disclosing proprietary information to them.

Types of DMFs

1. Type I – Manufacturing Site, Facilities, Operating Procedures (discontinued for new submissions)

2. Type II – Drug Substance, Drug Substance Intermediate, or Drug Product

3. Type III – Packaging Material

4. Type IV – Excipient, Colorant, Flavor, Essence

5. Type V – FDA Accepted Reference Information

Steps for DMF Submission

1. Prepare DMF Content

• Follow FDA Guidance for Industry – Drug Master Files.

• Include:

  • Administrative Information (Cover Letter, Applicant, Agent)

  • Table of Contents

  • Body of the DMF:

    • Manufacturing process

    • Controls for raw materials and intermediates

    • Process validation data

    • Packaging system details

    • Stability data

  • References & Appendices

2. Assign a DMF Number

• Submit electronically via FDA’s Electronic Submissions Gateway (ESG).

• Upon acceptance, FDA assigns a DMF Number (e.g., DMF ######).

3. Submit Letter of Authorization (LOA)

• If the DMF supports another company’s application, provide an LOA to the applicant and to the FDA.

• LOA should:

  • Identify the DMF number

  • Authorize FDA to reference the DMF for the specific application

  • Be signed by the DMF holder

4. Maintain & Amend the DMF

• Annual Report is mandatory to keep DMF active.

• Amendments must be submitted for any:

  • Process changes

  • Facility changes

  • Specification updates

5. FDA Review

• FDA does not “approve” a DMF — it only reviews it when referenced in an application.

• If deficiencies are found, FDA issues an Incomplete Letter to the DMF holder.

✅ Quick Compliance Tips:

• Always submit electronically in eCTD format.

• Keep the LOA list updated.

• Ensure GMP compliance for all facilities mentioned.

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