DMF: International Regulatory Affairs and requirements.

1. NAILA KANWAL
Sr. Officer Regulatory Affairs
The SEARLE Company Limited
DRUG MASTER FILE (DMF)
&
Global Regulatory Requirements

2.  Drug Master Fileor DMF is a document
prepared by a pharmaceutical manufacturer
and submitted solely at its discretion to the
appropriate regulatory authority in the
intended drug market.
 The document provides the regulatory
authority with confidential, detailed
information about facilities, processes, or
articles used in the manufacturing, processing,
packaging, and storing of one or more human
drugs.
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3.  Typically, a DMF is filed when two or more
firms work in partnership on developing or
manufacturing a drug product.The DMF
filing allows a firm to protect
its intellectual property from its partner
while complying with regulatory
requirements for disclosure of processing
details.
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1.
The DMF
contains factual
and complete
information on a
drug product's
chemistry,
2-
Manufacture
4-
Purity
3-
Stability 6-
Packaging.
5-
Impurit
y
profile,

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C. CHARACTERISATION
1. Eluciation of
Structure and other
characteristics
A. GENERAL
INFORMATION
B. 1. General
properties
2. Structure
3. Nomenclature
C. CHARACTERISATION
1. Elucidation of
Structure and other
characteristics
2. Impurities
a) Sources of
Potential Impurities.
b)Types of
impurities. c)Test
Procedure for
determining
impurities
B. MANUFACTURE
1. Manufacture(s)
2. Description of Manufacturing
Process and ProcessControl a)
Flow Chart of Manufacturing
Process b) Synthetic Route of
Manufacturing Process c)
Manufacturing Method.
3. Control of Material a) List of
Materials. b) Specification and
routine tests of the Raw Materials.
4. Control of Critical Steps and
Intermediates.
a) Critical Steps. b) Process
Validation and/or evaluation.
5. Specifications andTest method for
the Intermediates.
6. Manufacturing
ProcessDevelopment

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E. REFERENCE STANDARDSOF MATERIAL
F. CONTAINER CLOSURE SYSTEM
G. STABILITY
1. Stability summary and
Conclusions
2. Post-Approval Stability protocol
and Stability Commitment.
3. Stability data
a) Accelerated Stability
b) LongTerm Stability Studies
c) Forced Degradation Studies
H. MATERIAL DATA SAFETY
SHEET
I. APPENDICES
1. FACILITIES AND
EQUIPMENTS
a) Building and Utilities
2. EQUIPMENTS DESIGN
AND
LOCATION
a. Equipment List
b. Equipment Flow
Chart
3. ADVENTITIOUSAGENTS
SAFETY EVALUATIONS
STATEMENT OF COMMENT
D. CONTROLOF
DRUG SUBSTANCES
1. Specifications
2. Analytical
procedure
3.Validation of
Analytical
procedure
4. Batch Analysis
a) Description of
Batches
b) Certificate of
Analysis
5. Justification of
Specification

8.  DMFs Globally :
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9.  DMFs in the United States
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10. 1-DMFs in the United States
 In the United States, DMFs are submitted to the
Food and Drug Administration FDA).
 The Main Objective of the DMF is to support
regulatory requirements and to prove the quality,
safety and efficacy of the medicinal product for
obtaining an Investigational New Drug Application
(IND), a New Drug Application (NDA),As an
Abbreviated New Drug Application (ANDA), another
DMF, or an Export Application.
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11.  A US: drug master file comprises two parts:
 The Applicant’s Part
1- (USA: Open Part)
Which contains all the information that the licence-
holder needs to assess the quality and submit a
licence or amendment application.
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12. 2- Restricted Part (USA: Closed Part):
Which contains confidential information about
the manufacturing procedure only disclosed to
the authorities.
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 TYPES OF DMFs
The types of DMFs are:
 Type I :
Manufacturing Site, Facilities, Operating
Procedures, and Personnel (no longer applicable).
 Type II :
Drug Substance, Drug Substance Intermediate, and
Material Used inTheir Preparation, or Drug Product.

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 TYPES OF DMFs
 Type III :
Packaging Material.
 Type IV :
Excipient, Colorant, Flavor, Essence, or Material
Used inTheir Preparation.
 TypeV :
FDA Accepted Reference Information.

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2- DMFs in Europe

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DMFs in Europe
 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).The Main Objective of the EDMF is to support
regulatory requirements of a medicinal product to
prove its quality, safety and efficacy.This helps to
obtain a Marketing authorisation grant.

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 The DMF contains information which includes valuable
know-how which should be kept confidential and
submitted to the authorities only.
 Therefore, it should be divided into 2 parts – an
applicant’s part and an ASM Restricted Part.
 The applicant’s part of a DMF is provided by the ASM
(Active Substance Manufacturer) to the applicant
directly and becomes part of the application for
marketing authorization. Both the applicant’s part and
the ASM Restricted Part of the DMF are submitted to
the authorities.

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 Applicant’s part of a DMF – opening part
 The applicant must be supplied by the ASM with sufficient
information to be able to take responsibility for an
evaluation of the suitability of the active substance
specification to control the quality of the substance.This
normally includes a brief outline of the manufacturing
method, information on potential impurities originating
from the manufacturing method, from the isolation
procedure (natural products) or from degradation and,
where applicable, information on the toxicity of specific
impurities.

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 ASM Restricted Part of DMF – closing part
 Detailed information on the individual steps of the
manufacturing method such as reaction conditions,
temperature, validation and evaluation data for certain
critical steps of the manufacturing method, etc. and on
quality control during manufacture may contain valuable
know-how. Such information may therefore be supplied
to the authorities only.

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 Other DMF Systems:
 1- Canada
 2- Australia

22. 3-DMFs in Canada:
 Canada has 4Types of DMFs,
 Type 1: Used for Active Pharmaceutical
Ingredients (APIs)
 Type II: used for packaging materials
 Type III: used for excipients
 Type IV: used for products
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23. 3-DMFs in Canada:
Type I & 4 have two sections
 Sponsor's (Open)
 Restricted (Closed)
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24. 4-DMFs in Australia:
 In the case of an API used by a
producer for a medicine who’s origin is
a third party manufacturer, data about
its fabrication, quality control and
stability can be presented by a Drug
Master File (DMF).
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25. 4-DMFs in Australia:
 The Europena style relavent for the procedure of
a Active Substance Master File, adopted by
Austrailia’s Therapeutic Goods Administration
(TGA), are available on theTGA website.
 A DMF format used by the US (FDA) is
acceptable if the DMF is prepared according to
the CommonTechnical Document (CTD) format
or the older European format if this is not
available.
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26. Global DMFTrends:
NotYet Harmonized !!!!!!
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• Consumer• Pharmaceutical
Manufacturer /
MAA
• API / Excipient
Manufacturer
/Packaging
Supplier
• National
Regulatory
Authorities
Safety /
Efficacy
/ Quality
Secrecy
Cost /
Results
Speed
to
Market

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