This document provides information about Drug Master Files (DMFs), which are documents submitted to regulatory authorities containing information about active pharmaceutical ingredients, drug products, and other materials. It discusses the DMF processes in the United States and Europe. In the US, there are five types of DMFs that differ based on the content. The European DMF, also called the European Drug Master File or Active Substance Master File, contains confidential and public portions. DMFs allow proprietary information to remain confidential while supporting regulatory applications and maintaining quality and safety.

1. GUIDED BY:-
Mrs. FALGUNI TANDEL
Assist. Prof.
PREPARED BY:-
DINESH KUMAR
M.Pharm.:-2nd SEM. QA.
IST Shift
Enroll. No.:- 132330804003

2. TABLE OF CONTENTS:-
 INTRODUCTION
 UNITED STATE DMF
TYPE OF USDMF
FORMAT OF USDMF
REVIEW OF USDMF
SUBMISSIONS TO DRUG MASTER FILES
 EUROPEAN DMF
CONTENT OF THE ACTIVE SUBSTANCE
MASTER FILE
USE OF THE ACTIVE SUBSTANCE MASTER
FILE PROCEDURE
 ADVANTAGE OF DMF
 REFERENCES

3. INTRODUCTION:-
 DMF is a document prepared by a
pharmaceutical manufacturer and
submitted to the appropriate regulatory
authority in the intended drug market.
 DMF is a document containing complete
information on an API / drug substance,
intermediate of drug substance, packaging
material, excipient or drug product.
 The DMF contains complete information on
quality aspect such as chemistry,
manufacture, purity, impurity profile,
packaging, stability etc.

4. UNITEDSTATE DMF:-
 In the United States, DMFs are submitted
to the Food and Drug Administration
(FDA).
OBJECTIVE :-
 To support regulatory requirements.
 To prove the quality, safety and efficacy of
the medicinal product for obtaining an
Investigational New Drug Application
(IND), a New Drug Application (NDA), an
Abbreviated New Drug Application
(ANDA),and an Export Application.

5. TYPE OF USDMF:-
 In US there are five types of DMF's:
 Type I Manufacturing Site, Facilities,
Operating Procedures, and Personnel
 Type II Drug Substance, Drug Substance
Intermediate, and Material Used in Their
Preparation, or Drug Product
 Type III Packaging Material
 Type IV Excipient, Colorant, Flavor,
Essence, or Material Used in Their
Preparation
 Type V FDA Accepted Reference
Information

6. Type I Manufacturing Site, Facilities, Operating Procedures, and
Personnel
 Its is recommended for a person outside of
the United States to assist FDA in
conducting on site inspections of their
manufacturing facilities.
 The DMF should describe the
manufacturing site, equipment capabilities,
and operational layout.
 The site should include actual site address,
and a map showing its location with
respect to the nearest city.

7. Type II Drug Substance, Drug Substance Intermediate, and Material
Used in Their Preparation, or Drug Product
 It should be limited to a single drug
intermediate, drug substance, drug
product, or type of material used in their
preparation.
 It Summarize all significant steps in the
manufacturing and controls of the drug
intermediate or substance.
Type III Packaging Material
 Each packaging material should be
identified by the intended use,
components, composition, and controls for
its release.

8.  Data supporting the acceptability of the
packaging material for its intended use
should also be submitted.
TypeIV Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
 Each additive should be identified and
characterized by its method of manufacture,
release specifications, and testing methods.
TypeV FDAAccepted Reference Information
 It consists miscellaneous information,
duplicate information, or information that
should be included in one of the other types
of DMF's.

9. FORMAT OF DMF:-
 Different countries have different
requirement for format and submission of
DMF.
 The United States Food and Drug
Administration require two copies of each
Type DMF in the CTD format, but not in
CTD module form.
 FDA requires continuous document in the
CTD format.
 There are no different sections as an
"Applicant's Part" or "Restricted Part" such
as Europe.

10. REVIEWOF DMF:-
 After receiving DMF is reviewed for
administrative content.
 This may take 2-3 weeks.
 If DMF is ok with administrative content
then acknowledgement letter will be
issued, and notice has been sent to holder
of the DMF.
 If DMF is not ok with administrative point
of view, the holder will be notified with
letter of deficiency.

11. SUBMISSIONS TO DRUG MASTER FILES:-
A. Transmittal Letters:-
 The following should be included:
A.1. Original Submissions:-
a. Identification of submission: the type of
DMF as classified in Section III, and its
subject.
b. Identification of the applications, if
known, that the DMF is intended to
support including the name and address of
each sponsor, applicant, or holder, and all
relevant document numbers.

12. A. 2. Amendments
a. Identification of submission:
Amendment, the DMF number, type of
DMF, and the subject of the amendment.
b. A description of the purpose of
submission, e.g., update, revised formula,
or revised process.
c. Signature of the holder or the authorized
representative.
d. Type written name and title of the signer.

13. B. Administrative Information:-
 Administrative information should include
the following:
B.1. Original Submissions:-
a. Names and addresses of the following:
(1) DMF holder.
(2) Corporate headquarters.
(3) Manufacturing/processing facility.
(4) Contact for FDA correspondence.
(5) Agent(s), if any.

14. b. The specific responsibilities of each
person listed in any of the categories in
Section a.
c. Statement of commitment.

15. B.2. Amendments:-
a. Name of DMF holder.
b. DMF number.
c. Name and address for correspondence.
d. Affected section and/or page numbers of
the DMF.

16. e. The name and address of each person
whose IND, NDA, ANDA, DMF, or Export
Application relies on the subject of the
amendment for support.
f. The number of each IND, NDA, ANDA,
DMF, and Export Application that relies on
the subject of the amendment for support,
if known.
g. Particular items within the IND, NDA,
ANDA, DMF, and Export Application that
are affected, if known.

17. EUROPEANDMF:-
 Commonly known as the European Drug
Master File (EDMF).
 ASMF is the older name of EDMF.
 The content and the format for drug
master file used in United States differs
from that used in European Countries to
obtain market authorization (MA).
OBJECTIVE:-
 To support regulatory requirements of a
medicinal product to prove its quality,
safety and efficacy.
 This helps to obtain a Marketing
Authorization grant.

18. CONTENT OF THE ACTIVE SUBSTANCE MASTER FILE:-
 The overall content of the EDMF should
contain detailed scientific information to
Applicants for Marketing Authorizations
for Medicinal Products in the Member
States of the European Union.
 EDMFs linked to human medicinal
products should be presented in the form
of the Common Technical Document
(CTD). EDMFs for veterinary medicinal
products may also be presented in CTD
form after consultation with the
Competent Authorities/EMEA.

19.  The scientific information in the EDMF should
be physically divided into two separate parts,
namely the Applicants Part (AP) and the
Restricted Part (RP).
i. The AP contains the information that the
EDMF holder regards as non-confidential to
the Applicant/MA holder.
 That can be submitted by anyone to third
parties without the written consent of the
EDMF holder.
 In all cases the AP should contain sufficient
information.

20.  The RP contains the information that the
EDMF holder regard as confidential.
 The RP may contain the remaining detailed
information on the individual steps of the
manufacturing method (reaction
conditions, temperature, validation and
evaluation data of critical steps).

21.  Use of the Active Substance Master File Procedure:-
 The ASMF procedure can be used for the
following active substances (except biological
active substances)
A. New active substances.
B. Existing active substances not included in
the European Pharmacopoeia.
C. Pharmacopoeial active substances included
in the Pharmacopoeia Europe.
• The ASMF procedure cannot be used for
biological active substances.

22. The ASMF holder should submit to the
Applicant/MA holder:-
 a copy of the latest version of the AP.
 a copy of the QOS on the latest version of
the AP.
 a copy of the Letter of Access where this
letter has not been submitted earlier for
the product concerned.

23. ADVANTAGE OF DMF:-
 DMF maintain confidentiality of proprietary
information (e.g. manufacturing
procedure) for the holder.
 Number of applicants can refer the
information.
 Finished product manufacturing companies
consider API manufacturer having DMF
number / CEP (certificate of suitability)
more reliable in terms of quality and
regulatory stand.

24.  REFERENCES:-
 http://en.wikipedia.org/wiki/Drug_Master_Fi
le
 http://www.ema.europa.eu/docs/en_GB/doc
ument_library/Scientific_guideline/2012/07/
WC500129994.pdf
 http://www.tga.gov.au/pdf/euguide/qwp227
02rev1.pdf
 http://www.fda.gov/Drugs/GuidanceComplia
nceRegulatoryInformation/Guidances/ucm12
2886.htm
 http://pharmatreasures.blogspot.in/2011/10
/drug-master-file-dmf.html