Drug Master File

1. DRUG MASTER FILE
(DMF)
School Of Pharmaceutical Sciences,
Rajiv Gandhi Proudyogiki Vishwavidyalaya
Presented By-
Shreeharsh Sharma
M.Pharm 1st Sem
Pharmaceutical Quality Assurance
0001PY23MP20
Submitted to-
Dr. Farhad Mehta
Assistant Professor

2. What is DMF
❖ The Drug Master File (DMF) is a confidential, detailed file submitted by drug owners
to the U.S. Food and Drug Administration (FDA).
❖ It comprises complete information of the manufacturing, chemistry, packaging,
processing, and storing of drug products intended for human use.
❖ The information contained in the DMF may be used to support IND, NDA, ANDA, and
another DMF.
What is need of DMF
• The main objective of the DMF is to support regulatory requirements.
• To prove the quality, safety and efficacy of the medicinal product.

3. Some Important Terminology
❖ Agency means Food and Drug Administration.
❖ Agent means any person who is appointed by a DMF holder to serve as the contact for
holder.
❖ Holder means a person who owns a DMF.
❖ Drug product means finished dosage form, for example tablet, capsule, or solution.
❖ Letter of Authorization means a written statement by the holder or designated agent
permitting FDA to refer to information in the DMF in support of another person’s
submission.
❖ Person includes individual, partnership, corporation and association

4. Types of Drug Master File
Type 1 Type 2 Type 3 Type 4 Type 5
Plant
Information
Drug
Substance
Packaging
Material
Excipient FDA Accepted
Reference
Information

5. Type 1 :- Plant Information
It includes -
• Manufacturing Site
• Equipment information
• Operation layout
• Actual Site address
• A map showing its location with respect to the nearest city corporate
headquarters.
As per Jan. 12, 2000 FR notice: Types 1 DMFs was withdrawn by July 10,
2000

6. Type 2 :- Drug Substance and Material
used in their preparation
• DMFs for drug substance states that the material covered by the DMF is
manufactured under current good manufacturing practices.
• It summarizes all significant steps in the manufacturing and controls of the
drug intermediate or substance.
• Guideline for submitting supporting documentation in drug application for
the manufacture of drug substance.
• Guideline for the format and content of the chemistry, manufacturing and
controls section of an application.

7. Type 3 :- Packaging Material
It generally includes –
❖Component and composition of packing material.
❖Packing material intended for which use.
❖Name of the suppliers or fabricators of the components used in
preparation of packing material.
❖Toxicological data of those material.

8. Type 4 :- Excipient, Colorant, Flavor,
Essence or material used in their
preparation
• Submission of DMF is required for new excipients for which CMC and
safety information is not accessible in appropriate regulation.
• Each additive should be identified and characterized by its method of
manufacture, release specification and testing methods.
• Toxicological data on these material would be included under this
type of DMF, if not otherwise available by cross reference to another
document.

9. Type 5 :- FDA Accepted Reference
Information
• FDA discourage the use of type 5 DMF’s for miscellaneous
information, duplicate information or information that should be
included in one of the types of DMF’s .
• If any holder wishes to submit information and supporting data in a
DMF that is not covered by type 1 through 4, a holder must first submit
a letter of intent to the drug master file staff. FDA will then contact
the holder to discuss the proposed submission

10. Submission of Drug Master File
The DMF must be submitted in two copies, one with a blue
cover and one with red cover.
Each page of each copy of the DMF should be dated and
consecutively numbered.
The Drug Master File submission should contain:
❖ A Transmittal Letter,
❖ Administrative information about the submission,
❖ Technical Information

11. Transmittal Letter
1.) Original Submissions:
• Identification of submission: Original, the types of DMF, and its subject.
• Identification of the application, that the DMF is intended to support, including the name and
address of each sponsor,
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
2.) Amendments
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the
amendment.
• A description of the purpose of submission, eg: update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.

12. Administrative Information
1.) Original Submission
❖ Name and Addresses of the following:
• DMF Holder
• Corporate headquarter
• Manufacturing/processing facility
• Contact for FDA correspondence
• Agent (if any)
❖ Statement of commitment.
❖ A signed statement by the holder certifying that the DMF is current
and that the DMF holder will comply with the statements made in it.

13. 2.) Amendments
• Name of DMF holder
• DMF number
• Name and address for correspondence
• Affected section or page number of the DMF
• The name and address of each person whose dossier relies on the subject
of the amendment for support.
• The number of each dossier that relies on the subject of the amendment
for support
Administrative Information

14. Other Specific Information
• An original and duplicate are to be submitted for all DMF submissions.
• The original and duplicate copies must be collected, fully assembled.
Each volume of a DMF should, in general, be no more than 2 inches thick. For multivolume submission,
number each volume. For example: for a 4 volume submission, the volumes would be numbered 1 of 4,
2 of 4, 3 of 4 etc.
• US standard paper size (8-1/2 by 11”) is preferred.
Paper length should not be less than or more the preferred size, however, occasionally individual
pages can be larger than standard size to represent floor plan, diagram etc. Those pages should be
folded and mounted to allow the page to be opened for review without damage.
• Delivery to FDA.

15. Specification of page
for filing DMF
• The left margin should at least
three fourth of an inch to assure
that text is not obscured.
• The right margin should be at
least one half inch.
• The submitter should punch holes
8-1/2 inches apart in each page.

16. Mechanism of DMF
FDA assesses whether all parts of the DMF are included and in correct order.
if
passes
the holder will be
informed
The holder then must satisfactorily
respond to any deficiencies for the DMF
Undergo Administrative review
if fails
if
passes
Office of Pharmaceutical Quality (OPQ) sends an acknowledgement letter for review of the technical content.
if fails
OPQ sends Administrative
Filling Issue(AFI) letter
Required to resolved within 2-3 weeks

17. Submission of
DMF
Screening Evaluation
Completion / Cancellation
New
DMF
Update
Proceed
Lifecycle of Drug Master File

18. • DMF are to update be annually, the updates shall be reported as
“Annual Report”, and the annual report date will be from on the
anniversary date of the original submission.
• Failure to submit an annual report to the DMF in past three years, FDA
will send “ Overdue Notification Letter” (ONL) to DMF holder.
• If a DMF holder does not respond to this letter within 90 days with the
submission of an annual report, the DMF may be closed by the FDA.
Updates To DMF

19. • A holder who wishes to close a DMF should submit a request to the
Drug Master File Staff stating the reason for the closure.
• The agency may close a DMF that does not contain an annual update
of authorized for past three years to incorporate information in the
DMF.
• The Holder will be notified of FDA’s intent to close the DMF.
Closure of a DMF

20. Conclusion
• Drug Master File is invaluable tool in the pharmaceutical industry,
promoting regulatory compliance, safeguarding intellectual property.
• The main purpose of DMF is to support regulatory requirement and to
prove the quality, safety and efficacy of medicinal product.
• DMF’s are not just about compliance but about enhancing the lives of
patient.

21. Reference
• Kumar P, Mangla B, Singh S, Rana A. DRUG MASTER FILE: GLOBAL
REGULATORY ISSUES AND CHALLENGES. European Journal of
Biomedical. 2018;5(01):623-6.
• https://www.fda.gov/drugs/forms-submission-requirements/drug-
master-files-dmfs.
• https://www.fda.gov/drugs/guidances-drugs/drug-master-files-
guidelines.
• https://en.wikipedia.org/wiki/Drug_Master_File.