International Journal of Pharmaceutical Research and Applications

Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

Compressive Review of Drug Master File (Dmf) in Regulatory

Affair
Ms.Amruta Dipak Pawara*, Mr. Atish B. Velhal, Prof. (Dr) V.K.Redasani.
Ms.Komal Ramesh Lohar Ms. Divya Ravindra Pawar
Yashoda Shikshan Prasarak Mandal,Yashoda Technical Campus, Faculty of Pharmacy (B.Pharmacy),Wadhe,
Satara – 415001

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Submitted: 25-05-2023 Accepted: 05-06-2023
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ABSTRACT regulatory bodies like DMF USFDA, European
A Drug Master File (DMF) is highly confidential Medicines Agency (EMA) etc. DMFs are used only
information that describes secondary elements and to support marketing applications such as NDAs,
error-free information about the final API and ANDAs, and Biologics License Applications
dosage forms. It consists of two parts. One is the (BLAs). By using the DMF, applicants can comply
open side and the other is the restricted side. The with legal requirements while maintaining the
open part contains information about the quality of confidentiality of information.(4)
the drug for the holder of the registration
certificate. The restricted section, a closed section Role of DMF :-
that protects confidential and unofficial product  The DMF documents the purity, strength and
manufacturing information, is repeated before suitability of the drugs in the Chemistry,
respected regulatory authorities. When several Manufacturing and Control (CMC)
people are involved in the production of a drug. department.
The drug master file contains general information  Drug registration/approval document support.
about the product quality, shelf life and purity of  To protect Confidential and Proprietary
the drug. The Drug Master File supports Information.(2)
Investigational New Drug (IND) applications,
Abbreviated New Drug Applications (ANDA) Current Types of DMF’s:
applications, and NDA applications. All country Now four types are present, they are:
has its personal medication refill format and I. Pharmaceutical products, formulations,
content. In the current competition, different intermediates and materialsused in production
countries apply for Master of Medicine, and the
content and format of Master of Medicine II. Packaging Material
application respects the country. This review III. Excipients, Colorant, Flavour, Substance or
revealed about DMF , it’s parts contents , role & Material Used in theirPreparation
it’s mechanism of filling procedure. IV. Other Sterile Plants, Biotech Contracts,
KEYWORDS – Drug Master File , DMF Types , clinics, toxins(18)
Mechanism of DMF , DMF in Various Country ,
DMF Filling in Various Country DMF PROCEDURE:-
 Module-1
I. INTRODUCTION Regional & Administrative Information
A Drug Master File (DMF) is a document
prepared by a drug or excipient manufacturer and  Module-2
submitted to the regulatory authorities of the target QUALITY OVERALL SUMMARY (QOS)
market. It contains information on the chemistry,
stability, purity, excipient profile and packaging, as  Module-3
well as cGMP status of each API. (3) QUALITY (1)
It is not a mandatory requirement for

DOI: 10.35629/7781-080320792084 | Impact Factor value 7.429 | ISO 9001: 2008 Certified Journal Page 2079
 International Journal of Pharmaceutical Research and Applications
Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

Flow chart for Mechanism of Drug Master File(3) :-

DMF are classified into 2 parts - about drugs and pharmaceuticals to regulatory
1. Open part (Applicant’s part): authorities in India. A DMF can be sent for bulk or
Production, possible additives, production systems, prescription drugs. (7)
etc.
2. United States –
2. Closed Part (Restricted part): In the United States, Drug Master File
It includes extractions, validations, processes, are submitted to the USFDA. The primary
solvents used, reactions, temperatures, conditions, purpose of a DMF is to support regulatory
critical manufacturing steps and more. Contains requirements and demonstrate the quality, safety
API manufacturing confidential information such and efficacy of pharmaceutical products to receive
as.(16) IND applications, NDA applications, ANDA
applications, other DMFs or export applications.(14)
DMF in Various Country :-
1. India – Types of DMF in United States :-
There are no guidelines for drug master Type I - Manufacturing Site, Facilities, Working
documents issued by the Central Drug Standards Procedures, and Personnel. This is no longer
Organization. The DMF format is commonly used accepted by the FDA.
in the United States to deliver confidential data Type II – Pharmaceutical products, intermediats

DOI: 10.35629/7781-080320792084 | Impact Factor value 7.429 | ISO 9001: 2008 Certified Journal Page 2080
 International Journal of Pharmaceutical Research and Applications
Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

and susbstances or agents used in their United States DMF Filling System :-
manufacture. Latest Updates on USFDA DMF You can
Type III – Packaging submit an e-CTD through the Electronic
Type IV – Excipients, Colors, Flavors, Essences or Submission Gateway (ESG). The deadline to
Ingredients Used in Preparation. Type V – FDA transition from paper to e- CTD format is May 5,
approved references are Used for sterile 2017, and all NDA, ANDA, BLA and master file
manufacturing.(17) submissionsmust be submitted in eCTD format.(5)

Comparative Study Of DMF in India and US(7) :-

Requirement US FDA India

RegulatoryAuthority Food And Drug AdministrationCentral Drug and Standard

(FDA) ControlOrganization
(CDSCO)
Use Of DMF in IND, NDA,ANDA MAA
Support of Application
Provide Information Drug Substance Intermediate, DrugAPI, Drug Products, Flavors,
Products , Flavors Colorants, Etc.
Etc
Fees For ANDA Case Only No Fee
Assessment

Forms For DMFFilling Not ApplicableExcept Not Applicable

Type Ii DMF, Form
FDA 3794
Letter Of Applicable Applicable
Authorization
Electronic eCTD eCTD
Submission

3. Australia – Australia DMF Filling system:-

The purpose of the Drug Master File The Australian DMF registration system contain of
is to provide the Food and Drug Administration the following steps.
(FDA) with detailed information about the  Phase 1: Pre - Shipment
facilities, processes, or materials used in the  Phase 2: Transmission phase
manufacture, processing, packaging, and storage of  Phase 3: First step in evaluation
one or moredrugs for human use. Providing a DMF  Phase 4: Response period for combined
is not essential through law or FDA regulations. applicaton under section 31
Awarded at the pleasure of the DMF owner.
 Phase 5: Second evaluation period
Current work provides detailed information on how
drug master files are submitted in Australia.(6)  Phase 6: Evaluation period of expert advice
 Phase 7: The decision-making phase
Types of DMF in Australia :-  Phase 8: Positioning(9)
Type 2: Drug substance and substance
intermediate. 4. Canada –
Type 3: Packaging material. A drug master file is a reference file that
Type 4: Inactive substance, colorant, flavour, deliver data about particular procedures or
essence or ingredients used in theirpreparation. constituents used in the manufacture, processing
Type 5: FDA accepted correct reference and packaging of pharmaceutical products. DMF is
information.(6) useful for providing information to healthcare
organizations where that information is proprietary
and not existing to the formulary manufacturer or

DOI: 10.35629/7781-080320792084 | Impact Factor value 7.429 | ISO 9001: 2008 Certified Journal Page 2081
 International Journal of Pharmaceutical Research and Applications
Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

participating sponsors.(10) File (CCSMF)

c) Type 3- Excipient Master File (EMF)
Types of DMF in Canada - Includes information related to excipient, coating
A) Type 1- Active Substance Master File (ASMF) ingredients, colorants, flavorsand other additives.
For pharmaceuticals, it includes API in the d) Type 4- Dosage Form Master File
manufacturing of a drug substance. (DFMF)
For biologics, it includes process intermediates, Includes information related to dosage form & their
vaccines antigens, excipient ofbiological origin. intermediates(12)
b) Type 2- Container Closure System Master

Comparison of DMF’s of Canada and Australia(8) :-

DMF CANADA AUSTRALIA
Requirement

Health Authority Health Canada Australian

government- TGA
Definition of DMF A DMF is In the case of anAPI used
aninformative definition by a producer for a
for a medicine whose origin is a
particular process or thirdparty
component used in the manufacture, manufacturer, dataabout its
processing fabrication, quality control and
and stability can be presented by a
packaging of pharmaceutical DMF.
products.
Types of DMF Type I-Active Substance No type for drugmaster file.
Master Files
(ASMFs) Type II-Container
Closure System Master Files (CCS
MFs)
Type III-Excipient

Master Files(ExcipientMFs)
Type IV-Dosage
Form Master
Format MFs must followthe filing The currently approved form is
and formatting requirements the CTD format.
outlined in the
Guidance Document Preparation
ofDrug
Regulatory Activities in
the ―Non-eCTD Electronic-
Only
(NeeS)‖ Format.

Letter of Letter of Access is Letter of Access is

Authorization required. required.

DOI: 10.35629/7781-080320792084 | Impact Factor value 7.429 | ISO 9001: 2008 Certified Journal Page 2082
 International Journal of Pharmaceutical Research and Applications
Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

Fees The revised fee structure New chemicalentity is $46,900.

increases the cost of filing a new No cost for filing aletter of Access.
DMF to $424 (Canadian), and the
cost of filing a Letters of Access to
$191(Canadian).
Updation Bi- annually Five years once

5. EU – such as manufacturing technology information.(15)

The European DMF was established in
1989-1991 and revised in 2005. After the DMF Filling in various country :-
introduction of the CTD in the EU, it became the The following parameters have been selected to
Active Substance Master File (ASMF). ASMF in understand and navigate the regulatory
Europe is regulated by Directive 2001/83/EC. The requirements for DMF submissions in different
ASMF application aims to protect intellectual countries.
property while giving applicants full responsibility • Get detailed information on the regulatory
for quality control of active substances.(3) requirements for issuing DMFs in your chosen
market.
Types of DMF in EU :- • Addressing regulatory challenges in emerging
EDMF or ASMF scientific information is markets (China, Brazil and
physically divided into two parts according to Korea) and underlines the strict requirements of
European archiving procedures. regulated markets (US) and emergingauthorities.(13)

A. Restricted part (Closed part) II. CONCLUSION :-

This information is considered confidential and is DMF is a document prepared by the drug
provided only to authorizedorganizations. products manufacturer or excipient and submitted
Manufacturer(s)/site of manufacture to the targeted market's regulatory authority. DMF is
Detailed description of the production process and a submission to the FDA (Food Drug and
process control Administration) covering information and
Materials management (API raw materials, chemistry, stability, purity, impurity profile, and
reagents, solvents and other materialsused) packaging and cGMP status of any API.We have
Control of critical and intermediate steps Process seen the role of DMF , it’s types and procedure in
verification and/or evaluation Manufacturing this project.We also studied a comparison of DMF
process development accross different countries.

B. Applicant’s part (Open part) ACKNOWLEDGEMENT-

Information that is not confidential and must be I would like to express a specially thanks
disclosed to applicants.The information is provided to my guide Ms.Atish B. Velhal for his affectionate
to the authorities as part of the DMF service. encouragement, inspiring guidance and never
• These section include: Common information ending enthusiasm.. An ostentatious use of words
Characterization Control of API will not be sufficient to express my heartiest thanks
Standards or reference material Container closure to Prof.Dashrath Sagare (President), Prof. Ajinkya
system Stability(11) Sagare (Vice President). Prof. (Dr) V.K.Redasani
(Principal, Yspm YTC, Satara) for their
6. Japan – constructive suggestions, motivation.At last but not
Manufacturers of pharmaceutical the least I am humbly grateful to all the team
substances may, at the option of the owner, register members who directly orindirectly played the role
information about the quality and manufacturing of a catalyst to bring out the lovely reaction of this
method of their products with the PMDA through work.
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Volume 8, Issue 3 May-June 2023, pp: 2079-2084 www.ijprajournal.com ISSN: 2249-7781

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DOI: 10.35629/7781-080320792084 | Impact Factor value 7.429 | ISO 9001: 2008 Certified Journal Page 2084