DRUG MASTER FILE (DMF)
Presented by
Renaldy Donlang Nongbet
M.Pharm 1st sem
Pharmaceutics
Contents
Introduction
DMF Requirements
Types of DMF
DMF Submissions
How the US DMF System Works
Letter of Authorization to FDA
Reference
Introduction
A Drug Master File (DMF) is a submission to the United States Food and Drug Administration
(USFDA) or to the concerned regulatory authority that may be used to provide credential and
detailed information on facilities, processes, packaging or storing of one or more human drugs.
DMFs can contain other types of information as well (e.g., toxicology information, shared system
REMS (risk evaluation and mitigation strategy)).
DMFs are submitted solely at the discretion of their holders and are not required by statute or
regulation. They are not typically submitted for nonproprietary materials. Ordinarily, FDA neither
independently reviews nor approves DMF submissions. Instead, FDA customarily reviews the
technical contents of DMFs only in connection with the review of applications that reference them.
Contd…
DMFs can be used to support (but are not substitutes for) applications reviewed by FDA. This
guidance focuses on the following submissions to the Center for Drug Evaluation and
Research (CDER) and the Center for Biologics Evaluation and Research (CBER):
• DMFs under 21 CFR 314.420 that are used to support new drug applications (NDAs),
abbreviated new drug applications (ANDAs), and investigational new drug applications
(INDs) under the Federal Food, Drug, and Cosmetic Act (FD&C Act).
• DMFs and other master files under 21 CFR 601.51(a) that are used to support biologics license
applications (BLAs) under the Public Health Service Act (PHS Act).
DMF Requirements
Each DMF submission should contain
1. A transmittal letter,
2. Administrative information about the submission, and
3. The specific information to be included in the DMF
The DMF must be in the English language. Whenever a submission contains information in
another language, an accurate certified English translation must also be included.
Each page of each copy of the DMF should be dated and consecutively numbered. An updated
table of contents should be included with each submission.
TYPES OF DMF
Type Essential Content
I Manufacturing site, facilities, operating procedures and personnel
II Drug substance, drug substance intermediate, drug material used
and drug product
III Packing Material
IV Excipient, flavor, essence, colorant and materials used in the
preparation
V FDA accepted reference information
TYPE I : PLANT AND INFORMATION
This type of DMF includes
Mfg plant
Equipment capabilities
Operational layout
Actual plant address
A map showing its location.
TYPE II: INORMATION ON DRUGS
It includes
1) Drug substance intermediates, drug substance and material used in their preparation.
2) Finished drug product : Mfg procedures and controls for finished dosage form. General
points included in type II DMF areoMfg section
3) Quality control: Raw material, Packaging material, Intermediates, In process Q.C, Finished
Drug Substance
4) Validations
5) Stability data
TYPE III, TYPE IV
TYPE III : PACKAGING MATERIAL
• Packaging material intended for which use.
• Its components and compositions.
• Names and suppliers.
• Toxicological data on these materials.
TYPE IV : EXCIPIENTS
• CMC (Chemistry, Mfg, & controls) requirements for a novel excipients should be submitted
same as Type II DMF.
• It includes excipients such as colorants, flavors, essence etc. or, materials used in their
preparations.
TYPE V : OTHER INFORMATION
• Other information which is generally
not covered by Type I to IV DMF.
• Such as miscellaneous information.
Fig: Showing DMF Sample
DMF SUBMISSIONS
A. Format and Delivery
• DMF submissions are subject to the electronic submission requirements as set forth in
guidance 89 implementing section 745A of the FD&C Act.
• A DMF submissions must have a DMF number, must be submitted in the electronic format
specified in such guidance, and, if 10 gigabytes or smaller, must be submitted through the
Electronic Submissions Gateway (ESG). Submissions over 10 gigabytes can be submitted
through ESG or they can be submitted on physical media (e.g., CD-ROM) accompanied by a
cover letter as described below and with prepaid delivery charges. The standard electronic
format for DMFs is electronic common technical document (eCTD) format.
DMF SUBMISSIONS
B. Original Submissions
• Before submitting an original DMF in eCTD format, DMF holders must obtain a pre-
assigned number.
• For CBER submissions, send requests for application numbers via secure email to
mailto:cberrims@fda.hhs.gov and include the sponsor/applicant name and address, point
of contact name and number, product name, and anticipated submission date.
• Original submissions should contain a cover letter and complete administrative and
technical information in the appropriate eCTD modules. Although some eCTD module
section headings refer to change and sponsor/applicant, they are applicable to original and
subsequent submissions to DMFs.
DMF
Table 2 : Essential contents of Transmitted letters
Sl Content Details
No.
1 Original • Name and address of each sponsor, applicant or holder
Submission • Signature of the holder or authorized representative
• Typewritten name and title of the signer
2 Amendments • The DMF number, type of DMF and the subject of the
amendments.
• Short description of the purpose of admission like update
revised formula or press.
• Signature of the holder or authorized representative.
• Typewritten name and title of signer
DMF
Table 3 : Essential contents of Administrative Information
Sl Content Details
No.
1 Original • Name, address and specific responsibilities of DMF holder,
Submission corporate headquarter manufacturing facility, contact of
correspondence and agent
• State commitment
• A signed statement by the holder certifying that the DMF is
current and that the DMF hold will comply with the statement
made in it.
2 Amendments • Name of DMF holder, DMF number, name and address of
correspondence affected section and/ or page number of the
DMF
• Name and address of each person whose IND, NDA, ANDA,
DMF or export applications relies on the subject of the
amendment for support.
How the US DMF System Works
Filing the DMF DMF review procedure
• Holder sends two copies of the DMF to FDA • The DMF is reviewed only if referenced by an
• DMF is reviewed for administrative purposes Applicant or another DMF
only by Central Document Room staff
• If the reviewer finds deficiencies in the DMF,
• DMF entered into database, assigned a number
and acknowledgment letter sent to holder the deficiencies are detailed in a letter to the
• A DMF is neither approved or disapproved Holder
• If deficient, the Applicant will be notified, but
the nature of the deficiencies are not
communicated to the Applicant
Letter of Authorization to FDA
• FDA will not review a DMF until the DMF holder submits a letter of authorization (LOA) to the
DMF regarding a specific application or other DMF.
• The LOA permits FDA to review the DMF and permits the authorized party (i.e., the company or
individual who submits an application or another DMF) to incorporate information into an
application or another DMF by reference (eCTD section 1.4.1).
• he DMF holder should send a copy of the LOA to the authorized party.
• The authorized party must include a copy of the LOA in its application or DMF (eCTD section
1.4.2).
• An LOA does not give an authorized party permission to view or access a DMF
Letter of Authorization to FDA
The LOA should include the following
Date, name, DMF number of the DMF holder
Name of person authorized to incorporate information in the DMF reference
Specific products covered by he DMF, submission date
Section or page numbers to be referenced
Statement of commitment that the DMF is current and the DMF holder to comply with it
Signature of the authorizing official
Typed name and title o authorizing reference to the DMF.
References
1. Drug Regulatory affairs by Mr. Sachin C. Itkar and Dr. N.S. Vyawahare (Page No.s 7.1-
7.10).
2. https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs.
Accessed on 01/09/2023.
3. https://www.fda.gov/drugs/guidances-drugs/drug-master-files-guidelines#:~:text=A%20Dru
g%20Master%20File%20%28DMF%29%20is%20a%20submission,is%20not%20required
%20by%20law%20or%20FDA%20regulation.
Accessed on 01/09/2023
THANK
YOU
