Knowyourindustry.
in
KYI/Draft 01/29/08/2025
Module 4
Drug Master File (DMF)
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Drug Master File (DMF)
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A Drug Master File (DMF) is a submission of information to the FDA
to permit the FDA to review this information in support of a third party’s
submission without revealing the information to the third party.
DMFs usually cover the Chemistry, Manufacturing and Controls (CMC)
of a component of a drug product e.g. drug substance, excipient,
packaging material.
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Current Types of DMFs
II Drug substance, drug product, intermediates and material
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used in their manufacture
III Packaging
IV Excipients
V Other
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Regulatory Basis of Drug Master Files
The submission of a DMF is not required by law or FDA regulation but is
only submitted at the discretion of the holder.
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Once submitted, a DMF is not approved or disapproved; the contents of a
DMF are reviewed only in connection with the review of an application such as
an IND, NDA, ANDA and supplements/amendments.
Additionally, information will also get reviewed when an IND sponsor, an
applicant for an NDA, ANDA or another DMF holder incorporates material in
the DMF by reference.
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Comparison of DMF’s of USA, Europe and Canada
DMF USA EUROPE CANADA
Requirements
Health Authority U.S. Food And Drug European Medicines Agency Health Canada
Administration
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Types of DMF Type II - Drug substance, Active Substance Master File Type I - Active Substance
drug substance (ASMF) Master Files (ASMFs)
intermediate, and materials Type II - Container Closure
used in their preparation, or System Master Files (CCS
drug product MFs)
Type III - Packaging Type III - Excipient Master
material Files
Type IV - Excipient, Type IV - Dosage Form
colorant, flavor, essence, or Master Files (Dosage Form
material used in their MFs)
preparation Type V - Facilities and
Type V - FDA-accepted Equipment Master
reference information Files (FMFs)
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Comparison of DMF’s of USA, Europe and Canada
DMF USA EUROPE CANADA
Requirements
Format eCTD format eCTD format eCTD format
Fees FY 2022 Not applicable Fee as of April 1, 2022
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$ 74,952 (New Master File
Registration)
$1,324
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DMF - USFDA
Module 1 Administrative Documents
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Module 2 Summarizes the appropriate module 3 sections
Module 3 CMC
Module 4 This module is not necessary for DMFs unless nonclinical
evaluations are included in the DMF.
Module 5 Module 5 should be submitted for clinical information only,
such as in a Type V DMF
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DMF - USFDA
DMF SUBMISSIONS
eCTD format
Pre-assigned
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Cover letter and complete administrative and technical information in the appropriate eCTD modules
Letter of authorization (LOA)
LOA to the authorized party
Module 1 – Administrative documents
Module 2 - Summarizes the appropriate module 3 sections (and 4 and 5, if applicable)
Module 3 – Chemistry and Manufacturing Controls
Module 4 - not necessary for DMFs unless nonclinical evaluations are included in the DMF
Module 5 - should be submitted for clinical information only, such as in a Type V DMF
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EMA - Active Substance Master File
Active Substance Master File (ASMF), formerly known as the European Drug
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Master File (EDMF)
Common Technical Document (CTD)
Applicant’s Part (AP) and the Restricted Part (RP)
Submitted in support of an MAA or MAV
The ASMF holder may have an ASMF as well as a Certificate of Suitability (CEP)
issued by EDQM for a single active substance.
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The ASMF
procedure can New active substances;
be used for the
following active
substances,
including
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herbal active
substances/prep
Existing active substances not included in
arations. i.e.: the European Pharmacopoeia (Ph. Eur.) or
the pharmacopoeia of an EU Member State;
Pharmacopeial active substances included in
the Ph. Eur. or in the pharmacopoeia of an
EU Member State.
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Health Canada - Master Files (MFs)
Type I to V MFs
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eCTD format
Applicant’s Part and the Restricted Part.
MFs are filed no more than one year but no less than 2 months prior to the filing
of a drug submission.
MFs will only be reviewed in conjunction with an Applicant’s drug submission
English or French - Official language of correspondence
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Conclusion
The quality of drug
substances or Active
Pharmaceutical
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Ingredients plays an
important role in the
manufacturing of Any changes in the
effective and safe drug DMF is a critical
approved DMF must
products. Hence, the document, which is
be notified as it affects
registration used to support drug
requirements for API the drug product
product application.
should be provided application as well.
completely in detail and
the approval of an API
(Drug Master File) must
be achieved with utmost
care and confidentiality.
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Module 5: Organization of
the common technical
document for the registration
of pharmaceuticals for
human use
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