The document discusses submission documents for regulators like DMFs, CTDs, and eCTDs. It provides details on the contents required for a Drug Master File submission to the FDA, including transmittal letters, administrative information, and specifics on the five types of DMFs. Type I covers manufacturing facilities and procedures, Type II covers drug substances and products, Type III packaging materials, Type IV excipients, and Type V is for reference information accepted by the FDA. Guidance is provided on environmental assessments and stability studies to include.

1. Presented By:-
Machhi Dhruvi Anilkumar
1st Sem. M.Pharm.
Department of Pharmaceutical Quality Assurance
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav-vapi
Topic:- Submission Documents for
regulators DMFs, as CTD & eCTD
Subject Name:- Quality Control & Quality Assurance
Subject Code:- MQA103T
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1. Introduction
2. Transmittal Letters
3. Administrative Information
4. Drug Master File Contents
5. References

3. Drug Master File (DMF)
 A Drug Master File (DMF) is a submission to the Food and Drug
Administration (FDA) that may be used to provide confidential detailed
information about facilities, processes, or articles used in the manufacturing,
processing, packaging, and storing of one or more human drugs.
 The submission of a DMF is not required by law or FDA regulation.
 A DMF is submitted solely at the discretion of the holder.
 The information contained in the DMF may be used to support an Investigational New
Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug
Application (ANDA), another DMF, an Export Application, or amendments and
supplements to any of these.
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4. SUBMISSIONS TO DRUG MASTER FILES:-
 Each DMF submission should contain a transmittal letter, administrative information
about the submission, and the specific information to be included in the DMF.
 The DMF must be in the English language. Whenever a submission contains
information in another language, an accurate certified English translation must also be
included.
 Each page of each copy of the DMF should be dated and consecutively numbered. An
updated table of contents should be included with each submission.
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5. Submission to DMF includes
A. Transmittal Letters
1. Original Submissions
2. Amendments
B. Administrative Information
1. Original Submissions
2. Amendments
C. Drug Master File Contents
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6. 2. TRANSMITTAL LETTERS
The following should be included:
2.1 Original Submissions
(a) Identification of submission: Original, the type of DMF & 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, & all relevant
document numbers.
(c) Signature of the holder or the authorized representative.
(d) Typewritten name and title of the signer.
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7. 2.2 Amendments
(a) Identification of submission: Amendment, the DMF number, type of DMF, & 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)Typewritten name & title of the signer.
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8. 3. ADMINISTRATIVE INFORMATION
Administrative information should include the following:
3.1 Original Submissions
(a) Names and addresses of the following:
(i) DMF holder.
(ii) Corporate headquarters.
(iii) Manufacturing/processing facility.
(iv) Contact for FDA correspondence.
(v) Agent(s), if any.
(b) The specific responsibilities of each person listed in any of the categories
(c) 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.
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9. 3.2 Amendments
a. Name of DMF holder.
b. DMF number.
c. Name and address for correspondence.
d. Affected section &/or page numbers of the DMF.
e. The name & 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, & Export Application that relies on
the subject of the amendment for support, if known.
g. Particular items within the IND, NDA, ANDA, DMF, & Export Application that are
affected, if known.
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10. 4. DRUG MASTER FILE CONTENTS
4.1 Types of Drug Master Files
4.1.1 Type I: Manufacturing Site, Facilities, Operating Procedures, & Personnel
4.1.2 Type II: Drug Substance, Drug Substance Intermediate, and Material Used in
Their Preparation, or Drug Product
(i) Drug Substance Intermediates, Drug Substances, and Material Used in Their
Preparation
(ii) Drug Product
4.1.3 Type III: Packaging Material
4.1.4 Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
4.1.5 Type V: FDAAccepted Reference Information
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11. 4. DRUG MASTER FILE CONTENTS
4.2. General Information & Suggestions
4.2.1 Environmental Assessment
4.2.2 Stability
4.2.3 Format, Assembly & Delivery
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12. 4.1 TYPES OF DRUG MASTER FILES
4.1.1 Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel
4.1.2 Type II: Drug Substance, Drug Substance Intermediate, and Material Used in
Their Preparation, or Drug Product
4.1.3 Type III: Packaging Material
4.1.4 Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
4.1.5 Type V: FDAAccepted Reference Information
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13. 4.1.1 TYPE I: MANUFACTURING SITE, FACILITIES,
OPERATING PROCEDURES, & PERSONNEL
 It 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 &
- operational layout.
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14. 4.1.2 TYPE II: DRUG SUBSTANCE, DRUG SUBSTANCE
INTERMEDIATE, & MATERIAL USED IN THEIR
PREPARATION, OR DRUG PRODUCT
 A Type II DMF should, in general, be limited to a single drug intermediate, drug
substance, drug product, or type of material used in their preparation.
 It is further divided in two parts
4.1.2.1 Drug Substance Intermediates, Drug Substances, and Material Used in Their
Preparation
4.1.2.2 Drug Product
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15. 4.1.2.1 DRUG SUBSTANCE INTERMEDIATES, DRUG
SUBSTANCES, & MATERIAL USED IN THEIR PREPARATION
Type II DMF for drug substances and intermediates may be found in the following
guidelines:
Guideline for Submitting Supporting Documentation in Drug Applications for the
Manufacture of Drug Substances.
Guideline for the Format and Content of the Chemistry, Manufacturing, and Controls
Section of an Application.
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16. 4.1.2.2 DRUG PRODUCT
When a Type II DMF is submitted for a drug product, the applicant/sponsor should
follow the guidance provided in the following guidelines:
Guideline for the Format and Content of the Chemistry, Manufacturing, & Controls
Section of an Application.
Guideline for Submitting Documentation for the Manufacture of & Controls for Drug
Products
Guideline for Submitting Samples & Analytical Data for Methods Validation
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17. 4.1.3 TYPE III: PACKAGING MATERIAL
 Each packaging material should be identified by the intended use, components,
composition, & controls for its release.
 The names of the suppliers or fabricators of the components used in preparing the
packaging material & the acceptance specifications should also be given.
 Data supporting the acceptability of the packaging material for its intended use should
also be submitted as outlined in the "Guideline for Submitting Documentation for
Packaging for Human Drugs & Biologics."
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18. 4.1.4 TYPE IV: EXCIPIENT, COLORANT, FLAVOR,
ESSENCE, OR MATERIAL USED IN THEIR
PREPARATION
 Each additive should be identified and characterized by its method of manufacture, release
specifications, & testing methods.
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19. 4.1.5 TYPE V: FDAACCEPTED REFERENCE
INFORMATION
 FDA discourages the use of Type V DMF's for miscellaneous information, duplicate
information, or information that should be included in one of the other types of
DMF’s.
 If any holder wishes to submit information & supporting data in a DMF that is not
covered by Types I through IV, 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.
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20. 4.2 GENERAL INFORMATION &
SUGGESTIONS
4.2.1 Environmental Assessment
4.2.2 Stability
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21. 4.2.1 ENVIRONMENTALASSESSMENT
 Type II, Type III, and Type IV DMF's should contain a commitment by the firm that
its facilities will be operated in compliance with applicable environmental laws. If a
completed environmental assessment is needed, see 21 CFR Part 25.
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22. 4.2.2 STABILITY
 Stability study design, data, interpretation, & other information should be submitted,
when applicable, as outlined in the “Guideline for Submitting Documentation for the
Stability of Human Drugs & Biologics.”
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23. 5. REFERENCES:-
 Drug Master Files: Guideline Center for Drug Evaluation and Research Food and
Drug Administration Department of Health and Human Services, September 1989
(https://www.fda.gov/drugs/guidances-drugs/drug-master-files-guidelines )
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24. Thank
you
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