The document provides information about Drug Master Files (DMFs), including:
1. A DMF contains confidential information about the manufacturing and controls of a drug product or component submitted to the FDA. There are currently four types of DMFs.
2. A DMF is not required to be filed but can provide information to support applications like an IND, NDA, or ANDA. The holder submits the DMF and is responsible for updating it annually or when changes occur.
3. A DMF is only reviewed when referenced by an application through a Letter of Authorization from the holder. The FDA communicates deficiencies only to the holder, keeping the contents confidential.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
An abbreviated new drug application (ANDA) contains data which is submitted to FDA for the review and potential approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, lower cost alternative to the brand-name drug it references.
To reduce the price of the drug. To reduce the time development. Increase the bioavailability of the drug in comparison to reference list drug.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
An abbreviated new drug application (ANDA) contains data which is submitted to FDA for the review and potential approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, lower cost alternative to the brand-name drug it references.
To reduce the price of the drug. To reduce the time development. Increase the bioavailability of the drug in comparison to reference list drug.
DRUG MASTER FILE
Presented by :
RUSHIKESH D MENDHE
Roll no - 511
Mpharm Ist Year
(Department of Pharmaceutics)
Content : :
INTRODUCTION
TYPES OF DMF
DMF FORMAT & ASSEMBLY
DELIVERY OF DMF TO FDA
SUBMISSION OF DMF
THE MECHANISM OF A DRUG MASTER FILE
CTD & ELECTRONIC DMFS
UPDATES TO DMF
CLOSURE OF A DRUG MASTER FILE
APPLICATION OF DMF
REFERENCE
INTRODUCTION :
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.
This guideline does not impose mandatory requirements.
Objectives :
Main Objective of the DMF is to support regulatory requirements
To prove the quality, safety and efficacy of the medicinal product
TYPES OF DMF :
DMF FORMAT & ASSEMBLY :
The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs
Multiple volumes are numbered, and the paper must be standard paper size
Paper length should not be less than 10 inches nor more than 12 inches.
Each volume of a DMF should be not more than 2 inches thick
DELIVERY OF DMF TO FDA :
DMF should be submitted at following address :
Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA
SUBMISSION OF DMF :
The DMF must be submitted in two copies, one with a blue cover and one with a red cover.
Each page of each copy of the DMF should be dated and consecutively numbered.
Each DMF submission should contain :
• A Transmittal letter
• Administrative information about the submission
• Other specific information
A. Transmittal Letter :
i) Original Submissions :
• Identification of submission: Original, the type of DMF as classified in Section III, and its subject.
• 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.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
ii) Ammendments :
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.
• A description of the purpose of submission, e.g., update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
B. Administrative information about the submission:
This presentation gives an overview of the Drug Master File, a document submitted by the company or pharmaceutical industry to the regulatory authorities. It indicates that the company's product meets the desired quality standards. A brief introduction followed by types of DMF, its reviewing procedure and applications may give you a better understanding about Drug Master File.
Investigational medical product dossierSachinFartade
Investigational medical product dossier is document made to apply for clinical trial application in European Union. European Medical Agency is regulatory body for drug approval in European Union.
DRUG MASTER FILE
Presented by :
RUSHIKESH D MENDHE
Roll no - 511
Mpharm Ist Year
(Department of Pharmaceutics)
Content : :
INTRODUCTION
TYPES OF DMF
DMF FORMAT & ASSEMBLY
DELIVERY OF DMF TO FDA
SUBMISSION OF DMF
THE MECHANISM OF A DRUG MASTER FILE
CTD & ELECTRONIC DMFS
UPDATES TO DMF
CLOSURE OF A DRUG MASTER FILE
APPLICATION OF DMF
REFERENCE
INTRODUCTION :
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.
This guideline does not impose mandatory requirements.
Objectives :
Main Objective of the DMF is to support regulatory requirements
To prove the quality, safety and efficacy of the medicinal product
TYPES OF DMF :
DMF FORMAT & ASSEMBLY :
The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs
Multiple volumes are numbered, and the paper must be standard paper size
Paper length should not be less than 10 inches nor more than 12 inches.
Each volume of a DMF should be not more than 2 inches thick
DELIVERY OF DMF TO FDA :
DMF should be submitted at following address :
Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA
SUBMISSION OF DMF :
The DMF must be submitted in two copies, one with a blue cover and one with a red cover.
Each page of each copy of the DMF should be dated and consecutively numbered.
Each DMF submission should contain :
• A Transmittal letter
• Administrative information about the submission
• Other specific information
A. Transmittal Letter :
i) Original Submissions :
• Identification of submission: Original, the type of DMF as classified in Section III, and its subject.
• 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.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
ii) Ammendments :
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.
• A description of the purpose of submission, e.g., update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
B. Administrative information about the submission:
This presentation gives an overview of the Drug Master File, a document submitted by the company or pharmaceutical industry to the regulatory authorities. It indicates that the company's product meets the desired quality standards. A brief introduction followed by types of DMF, its reviewing procedure and applications may give you a better understanding about Drug Master File.
Investigational medical product dossierSachinFartade
Investigational medical product dossier is document made to apply for clinical trial application in European Union. European Medical Agency is regulatory body for drug approval in European Union.
A Drug Master File (DMF) is a confidential submission to the FDA containing detailed information about the manufacturing, processing, packaging, and storing of a pharmaceutical product. It is submitted by a drug manufacturer to support a regulatory application, such as a New Drug Application (NDA) or an Abbreviated New Drug Application (ANDA), without disclosing the information to the applicant. The DMF system helps streamline the regulatory review process while protecting proprietary information.
A Drug Master File (DMF) is a submission to the USFDA or to the concerned regulatory authority, 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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
2. CONTENTS:-
Introduction
Some basic terminologies.
Types of DMFS with their contents.
Submissions to drug master files
Authorization to refer to a drug master file
Processing and reviewing policies
Holder obligations
Major reorganization of a drug master file
Closure of a drug master file
2
2
3. DRUG MASTER FILES
A Drug Master File (DMF) is a submission to the FDA of
information, usually concerning the confidential detailed
information about Chemistry, Manufacturing and Controls
(CMC) of a drug product or a component of a drug Product.
Other non CMC – information (like packaging, storing)
may also be filed in a DMF.
3
I. Introduction
3
4. TYPES OF DMFS
Originally Five Types…
I Plant information
and material used in
II Drug substance, drug product, intermediates
their manufacturing.
III. Packaging
IV. Excipients.
V. Other information which is generally not covered by type I to type
IV drug master files.
(Usually clinical, toxicity data are covered.)
4
4
5. CURRENT TYPES OF DMFS
Now Four Types:
TYPE I DMF WITHDRAWN.
(Numbering retained to avoid confusion)
II.Drug substance, drug product, intermediates and material used
in their manufacturing.
III.Packaging IV Excipients
V Other information which is generally not coverd by type I to
type IV drug master files. 5
5
7. WHO MUST FILE ADMF?
7
NOBODY
There is no legal or regulatory requirement
to file a DMF. A DMF may be filed to
provide CMC information that the FDA
reviews.
The information contained in DMF may be
used to support an IND / NDA /ANDA
,another DMF,an export application or
amendments and supplements of any of
these.
Remember that,
DMF is NOT a substitute for IND / NDA /
ANDA or export application.
review of IND /NDA /ANDA or an export application.
7
8. II. SOME BASIC TERMINOLOGIES
HOLDER: The person /company who submits DMF.
AGENT : The person / company who represents a DMF HOLDER. (Also called
Representative.)
APPLICANT / CUSTOMER / AUTHORISED PARTY (AP ) :The person / company
who references the DMF.
APPLICATION:Investigational New Drug Application (IND), New Drug Application
(NDA), Abbreviated New Drug Application (ANDA)
SUPPLEMENT TO AN ANDA / NDA: A report of change in an approved ANDA /
NDA.
AMENDMENT TO AN APPLICATION: Additional information to… an existing IND,
a pending ANDA / NDA
a pending ANDA / NDAsupplement.
8
8
9. III. TYPES OF DMFS WITH THEIR
CONTENTS
Type I : plant information
Points included:
Manufacturing site Equipment capabilities Operational layout
Actual site address
A map showing its location with respect to the nearest city
Corporate headquarters
As per Jan. 12, 2000 FR notice : Elimination of Type I DMFs
done by July 10, 2000.
9
9
10. TYPE II DMF
10
CONTENTS:
(1)Drug Substance Intermediates, Drug Substances, and Material Used in Their
Preparation.
It Summarizes all significant steps in the manufacturing and controls of
the drug intermediate or substance.
Detailed guidance on what should be included in a Type II DMF for drug substances
and intermediates may be found in the following guidelines:
1.Guideline for Submitting Supporting Documentation in Drug
Applications for the Manufacture of Drug Substances.
2.Guideline for the Format and Content of the Chemistry, Manufacturing,
and Controls Section of an Application.
10
11. (2) Drug Product (finished dosage forms)
11
Manufacturing procedures and
controls for finished dosage
forms
should
ordinarily be
submitted in an
IND, NDA,
ANDA, or
Export
Application.
If can not be
submitted to
above
documents
It should be submitted in a DMF
11
12. For a drug product, the applicant/sponsor should follow
the guidance provided in the following guidelines:
1.Guideline for the Format and Content of the Chemistry,
Manufacturing, and Controls Section of an Application.
2.Guideline for Submitting Documentation for the
Manufacture of and Controls for Drug Products.
3.Guideline for Submitting Samples and Analytical Data for
Methods Validation.
12
12
13. GENERAL POINTS INCLUDED IN TYPE II DMF
13
Manufacturing Quality
Controls
Validations Stability
data
Impurities Packaging &
Labeling
Inputs Finished Drug
Substance
Raw
materials
Packaging
materials
(1) (2) (3) (4) (5) (6)
Section
a. b. c.
a.1
Intermediates
a.2 & In-process
13
14. TYPE III: PACKAGING MATERIAL
Contents:-
Packaging material intended for which use.
Its components and composition.
Names of the suppliers or fabricators of the components
used in preparing the packaging material.
Acceptance specifications.
Toxicological data on these materials.
FOLLOW THE GUIDELINE: "Guideline for Submitting
Documentation for Packaging for Human Drugs and Biologics."
14
14
15. BUT REMEMBER THAT,
Responsibility for compatibility and safety of packaging components
in finished drug product is the responsibility of the AUTHORISED
PARTY(AP).
It is not the responsibility of DMF HOLDER.
15
15
16. EXCIPIENTS
CMC for a compendial excipient is usually not
reviewed and therefore a DMF is not necessary.
Exceptions: New route of administration or total
dosing that may affect safety and efficacy.
E.G..RESPITOSE, lactose for dry powder inhalation
products.
CMC requirements for a novel excipient should be
submitted same as type II DMF.
16
16
17. TYPE V DMF
FDA discourages the use of Type V DMFs for
miscellaneous information, duplicate information, or
information that should be included in one of the other
types of DMFs.
TO SUBMIT THE DATA
WHICH IS NOT COVERED
IN TYPE I TO IV DMF
(CLINICAL / TOXICITY DATA)
A holder
must first submit
a letter of intent
to the drug master file staff
FDA will then contact the
holder to discuss the17
proposed submission.
17
18. I
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DRUG MASTER FILES
Holder sends the DMF (NO FEE two copies) to Central
Document Room
Center for Drug Evaluation and Research 5901-B
Ammendale Road
Beltsville, MD 20705-1266
Containing:
1 – Transmittal (cover) letter
2 – Administrative information 3 – Technical
information
Follow the Guideline at www.fda.gov/cder/guidance/dmf.htm
Binders recommended
http://www.fda.gov/cder/ddms/binders.htm18
NEW ADDRESS
18
19. 1. TRANSMITTAL (COVER) LETTER
19
Original Submissions and Amendments
Identification of submission.
(Original /supportive to original DMF / Amendment)
Type of DMF and subject (update, revised formula, or revised
process)
The name and address of each sponsor, applicant, or holder, and
all relevant document numbers.
Signature of the holder or the authorized representative.
Typewritten name and title of thesigner
19
20. 2. ADMINISTRATIVE INFORMATION
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.
b.The specific responsibilities of each person listed in any of the categories in
Section a.
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.
20
20
21. 2 – ADMINISTRATIVE INFORMATION
21
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.
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.
21
22. DMF reviewed for administrative purposes ONLY
by Central Document Room (CDR) staff.
DMF entered into DMF DATABASE, assigned a
number, and a letter sent to the HOLDER.
If no response from FDA side,…
DMF HOLDER can put a query on the e-mail:
dmfquestion@cder.fda.gov
22
22
23. Letter sent by FDA to DMF HOLDER consists of …
• Number given to DMF in database and Type.
• Reminder of obligations (responsibilities) of holder :
–Submit all changes as amendments.
–Notify FDA of change in holder name or address.
–Notify FDA of change in agent/representative.
–SUBMIT ANNUAL UPDATE (Annual Report).
–Submit Letter of Authorization (LOA) for each item
referenced.
23
23
24. LETTER OF AUTHORIZATION (LOA)
The DMF will be reviewed ONLY when it is referenced in an Application or
another DMF.
24
DMF HOLDER
US FDA Send a letter to
remind holder
obligations
Send 2 copies of LOA to the FD A
1 copy of LOA to the APPLICANT
The applicant submits THIS copy
of LOA in their Application.
24
25. IMPORTANCE OF LOA
Sending LOA is the only mechanism which triggers the review
procedure of DMF.
A letter of authorization permits the FDA to reference the
DMF.
If the holder cross references its own DMF, the holder should
supply following information in a LOA.
-DMF number
-Specific product(s) covered by the DMF
-Section numbers and/or page numbers to be referenced
In Europe, the permission to reference a DMF is called a Letter of
Access. 25
25
26. REVIEW OF THE DMF
REVIEWER
When reviewer receives an application
(IND/NDA/ANDA) that
references a DMF
Requests the DMF from
the CDR (central document room)
but Delivery of DMF
can take a couple of days.
This review procedure of DMF
is in Contrast with
APPLICATION, where
document is delivered
automatically to reviewer.
26
Next slide
26
27. 27
After getting DMF,the
Reviewer starts the
review procedure
If Reviewer found
any deficiency in the
content of DMF,
The DETAILED DEFICIENCIES
are communicated to the holder.
The APPLICANT is also notified
but, the nature of the deficiencies is
not communicated to the applicant.
If no deficiencies, no letter, applicant not notified.
HOLDER should submit the
REQUESTED INFORMATION to
the DMF in response to the
agency's
deficiency letter along with
transmittal letter having subject
matter.
27
29. Applications DMFs
1. COMES UNDER REGULATORY
STATUS.MUST BE FILED BY
APPLICANT.
1.NOT COME UNDER REGULATORY
STATUS.IT IS NOT MANDATORY
TO FILE A DMF.
2. EACH APPLICATION AND ITS
SUPPLEMENT ARE ENTERED
INTO A COMMON DATABASE.
2. DMFs ARE ENTERED IN TO
DATABASE AS PER THEIR TYPES.
(SEPARATE DATABASE FOR EACH
TYPE OF DMF)
3.SUBMITTED TO A PARTICULAR
REVIEW DIVISION.
3.SUBMITTED TO CDR.
4. ASSIGNMENT TO A REVIEWERAND
EACH SUBMISSION HAS A DUE DATE.
4.NO ASSIGNMENT TO A REVIEWER,
NO DUE DATE.
5.REVIEW PROCEDURE QUITE
DIFFERENT THAN DMF.
5.DMFs ARE REVIEWED ONLY WHEN
REFERENCED BY APPLICATION
OR ANOTHER DMF
6.IF THE ANNIVERSARY DATE FOR
ANNUAL UPDATE IS MISSED
F2D9A WILL NOT SEND A
REMINDER.
6.IF THE ANNIVERSARY DATE FOR
ANNUAL UPDATE IS MISSED FDA
SENDS A REMINDER.
29
30. ANNUAL UPDATE OF DMF
The holder should provide an annual report on the
anniversary date of the original submission.
If the subject matter of the DMF is unchanged, the DMF
holder should provide a statement that the subject matter
of the DMF is current.
Failure to update can cause delays in FDA review of a
pending IND, NDA, ANDA or any amendment or
supplement to such application; and FDA can initiate
procedures for closure of the DMF.
30
30
31. RETIRING DMFS
If a DMF has no activity (amendment or
annual report) in three years FDA will initiate
retirement procedure.
Note: LOA is not counted for activity.
31
31
32. DMF RETIREMENT PROCEDURE
FDA sends overdue notice letter (ONL) to holder and/or
agent using most recent address.
If no response in 90 days, one copy of DMF is sent to
Federal Records Center (FRC) and the other is
destroyed.
32
32
33. CHANGES IN DMF SYSTEM
Over the past decade, there have been some changes in
the DMF system to help make it work better.
However some things remain the same.
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34. CHANGES IN THE DMF
SYSTEM AND PROCEDURES
(INTERNAL)
Creation of Review Cover Form
Creation of Type II Review Format
Implementation of Re-review Policy
Creation of Central Review File
Revision of Database View
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35. CHANGES IN THE DMF SYSTEM AND
PROCEDURES (EXTERNAL)
Elimination of Type I DMFs
Post-Approval Changes Guidance and
Creation of DMF List Website
Creation of DMFQUESTION
Establish Position of DMF Expert 35
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36. UNCHANGED THINGS OF DMF
No review of DMFon receipt of it.
Review only when referenced in application.
All of the DMF is still confidential.
DMFs are neither approved nor disapproved.
The holder still has the responsibility to notify
customer of changes.
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37. SUMMARY
The DMF system presents challenges for both the
industry and the FDA.
Some of the changes have made the system
smoother
(hopefully for both industry and FDA).
Problems can be minimized:
–With full understanding of their responsibilities and adherence
to Guidances on the part of holders and applicants.
–With adherence to policies and procedures on the part of
reviewers.
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38. NOW,…
WHAT EUROPEAN DRUG MASTER FILE
PROCEDURE FOR ACTIVE SUBSTANCES SAYS
ABOUT THE DMF…
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CONTENT OF DRUG MASTER FILE
APPLICANT’S PART OF DMF
F
ASM RESTRICTED PART OF DM
2
PARTS
OPEN PART CLOSED PART
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39. APPLICANT’S PART OF DMF
OPEN PART
( AVAILABLE TO APPLICANT)
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ACTIVE SUBSTANCE
MANUFACTURER
SUPPLIES INFORMATION
TO THE APPLICANT
THIS INFORMATION INCLUDES:
-outline of the manufacturing method
-impurities originating from the manufacturing method,
isolation procedure and degradation
-information on the toxicity of specific impurities
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40. The applicant’s part of a DMF is provided by the ASM to the
applicant directly and becomes part of the application for
marketing authorization.
The applicant’s part of the DMF is still a confidential
document which cannot be submitted to third parties without
the written agreement of the ASM.
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41. ASM RESTRICTED PART OF
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DMF
CLOSED PART
( NOT AVAILABLE TO THE APPLICANT)
IT INCLUDES:
Detailed information about…
Individual steps of the manufacturing method such
as reaction conditions, temperature,
Validation and evaluation data for certain critical
steps of the manufacturing method,etc.
Such information is supplied to the authorities only.
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