A Drug Master File (DMF) is a confidential submission to the FDA containing detailed information about the manufacturing and quality control of human drugs, though it is not mandatory. DMFs support applications like IND, NDA, and ANDA, and help establish the credibility of API manufacturers. The submission includes various types covering manufacturing sites, drug substances, packaging, excipients, and requires an annual update to confirm the information remains current.

1. DRUG MASTER
FILE
BY- SHRUTI SHYAM MOTWANI
(M.PHARM)

2. Drug Master File(DMF): It is a submission to
the United States Food and Drug
Administration(USFDA) or to the concerned
regulatory authority, that may be used to
provide confidential and detailed information
about manufacturing, processing, packaging or
storing of one or more human drugs.
DMF SUBMISSION IS NOT
MANDATORY BY LAW OR FDA
REGULATIONS.

3. SALIENT FEATURES
 DMF is not a substitute for an:
IND: Investigational New Drug
Application.
NDA: New Drug Application.
ANDA: Abbreviated New Drug
Application.
 DMF is submitted by API
Manufacturers.
 The information in DMF is used to
support IND, NDA, ANDA, other DMF
or Export application.

4.  DMF’s are only reviewed when an ANDA
or NDA references them.
 DMF AS A PROOF OF RELIABILITY :
API manufacturers with large number of
DMF’s are often considered more reliable in
terms of quality, regulatory standing, and
ability to meet C-GMP requirements.
 DMF is considered as a degree of
credibility(when any API manufacturers
are willing to sell there product in U.S or
other regulated markets.)

5. WHO MUST FILE A DMF?
NOBODY!
THERE IS NO REGULATORY REQUIREMENT
TO FILE A DMF.
IT IS A SUBMISSION THAT INDICATES THAT
THE PRODUCT OF ONE’S COMPANY IS A
QUALITY PRODUCT AND MEETS THE
REQUIRED STANDARDS.

6. SUBMISSION OF DMF
 Each DMF submission contains:
1. A Transmittal letter.
2. An Adequate administrative
information.
3. Drug specific information.
 It must be written in English.
 Each page of DMF should be dated
and consecutively numbered along
with updated table of contents.

7. TYPES OF DRUG MASTER FILE
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, flavour, essence, colorant and material
used in the preparation.
V. FDA accepted reference information.

8. TYPE 1: Manufacturing Site, Facilities, Operating Procedures and
Personnel:
• It is recommended for a person outside the
united states to assist FDA conducting on site
inspections of their manufacturing facilities.
• This DMF shall describe manufacturing site
including acreage, site address, map showing
exact location, equipment capabilities,
application location and operational layout.
• A diagrammatic presentation of major
production and processing areas of
organisation, may be given to ease the process.
• Making of model is required only when
apparatus is unique.

9. TYPE 2: DRUG SUBSTANCE, DRUG SUBSTANCE INTERMEDIATE AND
MATERIAL USED IN THEIR PREPARATION OR DRUG PRODUCT:
• It should be limited to single drug
intermediate, drug substance, drug product and
drug materials used in their preparation.
• It shall summaries all significant steps of
manufacturing and controls of the drug
intermediates substance.
• Manufacturing procedures and controls for
finished dosage forms shall be submitted here if
not submitted in INDA, NDA, ANDA or Export
Application.

10. TYPE 3: PACKAGING MATERIAL:
• It should include the intended use, components
and composition controls for the packaging
material.
• The names of the suppliers or fabricators of the
components of packaging material should also be
included.
• The relevant data supporting the acceptability of
packaging material for its intended use shall also
be submitted.
• Toxicological data on these materials is also
added.

11. TYPE 4: EXCIPIENT, COLORANT, FLAVORS, ESSENCE OR
MATERIAL USED IN PREPARATION:
• Each additive should be identified by
its method of manufacture, release
specification, and testing methods.
• Toxicological data would be included.
• After the submission, the regulatory
department acts as a bridge between
the company(who has submitted the
DMF) and reviewing agency(who is
willing to refer that DMF) in replying
to queries and questions raised by the
agency within a specific span of time.

12. TYPE 5: FDA ACCEPTED REFERENCE INFORMATION:
• FDA discourages the use of Type-5 DMFs for
miscellaneous information, duplicate
information, or information that should be
included in one of the other types of DMFs.
• If any holder wishes to submit any supporting
information in a DMF that is not covered by
Types 1,2,3 and 4, then he must submit a
letter of intent to the FDA.(FDA may contact
the holder to discuss the proposed
submission.)

13. General Information and Suggestions
(a)Environmental Assessment :
Type 2, Type 3, and Type 4 DMFs should contain a
commitment by the firm that its facilities will be operated
in compliance with applicable environmental laws.
(b) Stability :
Stability study design, data, interpretation, and other
information should be submitted, when applicable, as
outlined in the “Guideline for Submitting Documentation for the
Stability of Human Drugs and Biologics.”

14. (c) Format, Assembly and Delivery :
• An original and a duplicate copies are to be submitted
for all DMF submissions.
• The original and duplicate copies must be collated, fully
assembled and individually jacketed.
• Each volume of a DMF should in general, be not more
than 2 inches thick.
• For multi volumes submissions, number each volume.
Ex. :for a 3 volume submission, each would be
numbered as 1 of 3, 2 of 3 and 3 of 3 resp.
• U.S. standard paper size(8-1/2 by 11 inches) is
preferred.
• Paper length should not be less than 10 inches and not
more than 12 inches.(larger size paper may be used to
present floor plan, synthesis diagram, batch formula,
etc.)

15. (d) Delivery to FDA:
Drug Master File submissions should be
addressed as follows:-
Food and Drug Administration
Centre for Drug Evaluation and
Research
Central Document Room
5091-B Ammendale road
Beltsville, MARYLAND 20705-1266
U.S.A

16. LETTER OF AUTHORIZATION TO FDA (LOA)
LOA: A written statement by the holder or designated agent or
representative permitting FDA to refer to information in the DMF
in support of another person’s submission.
The letter of Authorization includes the following:
1. The date.
2. Name of DMF holder.
3. DMF number.
4. Name of person(s) authorized to incorporate information in
the DMF by reference.
5. Specific product(s) covered by the DMF.
6. Submission date(s) of the above.
7. Section numbers and/or page numbers to be referenced.
8. Statement of commitment that the DMF is current and that
the DMF holder will comply with the statements made in it.
9. Signature of authorizing official.
10.Typed name and title of official authorizing reference to the
DMF.

17. REVIEW OF DRUG MASTER FILE
• A DMF IS NEVER APPROVED OR
DISAPPROVED.
• The agency will review information in a DMF
only when an IND sponsor, an applicant for an
NDA,ANDA or Export Application or another
DMF holder incorporates material in the DMF
by reference.
• The incorporation by reference must be
accompanied by a copy of the DMF holder’s
letter of authorization.

18. Annual Update
The holder should provide an annual
report on the anniversary date of the
original submission.
If the subject matter of the DMF is
unchanged, the DMF holder should
provide a statement that the subject
matter of the DMF is current.

19. DMF IS SUBMITTED IN CTD FORMAT( i.e common technical
document)
CTD format of DMF contains—
(a)Open part
(b)Closed part(confidential)
Module no. Data module
2.0 CTD summaries
2.3.S Quality overall summary
3.0 Quality(chemical and pharmaceutical
information)
3.2.S Drug substance
3.2.S.1 General information
3.2.S.2 Manufacturer
3.2.S.3 Characterization
3.2.S.4 Control of drug substance
3.2.S.5 Reference standards
3.2.S.6 Container and closure systems
3.2.S.7 Stability
Open
part:

20. Closed part:
Module no. Data module
3.2.S.2 Manufacturer
3.2.S.5 Reference standards
3.2.S.6 Container and closure
systems.

21. Applications(INDA,NDA
,ANDA)
DMF
Comes under regulatory
states and must be filed.
DMF submission is not
mandatory or come under
regulatory requirements.
Submitted to a particular
review division in FDA
Submitted to drug master file
staff.
Reviewed by FDA on filing DMF’s are reviewed only
when referenced by
application.

22. THANK
YOU