Drug Master Files
Important Guidance Information
This site contains lists of
Drug Master Files (DMFs) as well as information concerning
submission of DMFs. The list is updated quarterly, although there may be delays of up to a month. See below for information regarding the current
QUESTIONS OR COMMENTS ABOUT DMFs
Please address ALL comments or questions regarding DMFs to email@example.com. All inquiries MUST have an entry in the "Subject" field of the e-mail. Due to concerns about viruses and the amount of "spam" received by this account, e-mails with subject fields that are blank or contain meaningless text strings or contain only question marks will not be opened. Other inquiries unrelated to DMFs should go to firstname.lastname@example.org.
The list of DMFs is current as of July 31, 2008, through DMF 21823. Changes to the DMF activity status, DMF type, holder name, and subject made since the last update of March 31, 2008 are included.
People who downloaded the previous list (through DMF 21536 March 31, 2008) and do not wish to download the entire updated lists can use the following lists:.
- New DMFs since the
- A list of changes
in DMF activity status, DMF type, holder name, and subject.
The lists are
available in Microsoft Excel and in ASCII (tab-delimited). Please
note that only ACTIVE DMFs have been sorted into different types.
For the Excel
files, the following lists are provided as different worksheets
within one Excel file.
- All DMFs
- Active DMFs
- Active Type II
- Active Type III
- Active Type IV
- Active Type V
The following lists are still
provided as separate files.
- New DMFs since
the last list
The types of DMFs
Manufacturing Site, Facilities, Operating Procedures, and Personnel
(no longer applicable)
Type II Drug
Substance, Drug Substance Intermediate, and Material Used in Their
Preparation, or Drug Product
IV Excipient, Colorant, Flavor, Essence, or Material Used in Their
Type V FDA
Accepted Reference Information
All files zipped (2.6 MB)
“A” = Active. This means that the DMF was found acceptable for filing, administratively, and is up-to-date.
“I” = Inactive
“N” = Not an assigned
“P” = DMF Pending
INACTIVATION AND RETIREMENT OF DMFs
There are three reasons for a DMF to be listed as inactive:
- By the holder: The holder requested that the DMF be retired, closed, inactivated, or withdrawn.
- By the FDA: The holder did not respond to an Overdue Notification Letter within 90 days to update the DMF.
- OVERDUE FOR UPDATE:
A DMF is considered “Overdue” when
- There have been no amendments or annual reports submitted
since it was filed
- There have been no technical amendments or annual reports submitted since June 30, 2005. DMF.
Note that submission of a Letter of Authorization, a change in holder name or an agent appointment is not sufficient to update a DMF.
Note that the status “Inactive” in the list does not distinguish
among the reasons listed above.
According to the regulations regarding DMFs (21 CFR 314.420(c)):
“Any addition, change, or deletion of information in a drug master file (except the list required under paragraph (d) of this section) is required to be submitted in two copies and to describe by name, reference number, volume, and page number the information affected in the drug master file.”
discussed in the "Guideline
for Drug Master Files" (September 1989), DMF holders
should update their DMFs annually (see below under
FDA is in the process of sending “Overdue Notification Letters” (ONLs) to DMF holders for DMFs that are OVERDUE FOR UPDATE (see above). If a DMF holder does not respond to this letter within 90 days, the DMF will be considered “Closed by FDA.” It will then be retired by the FDA and it will be unavailable for review. Note that there is a backlog in sending out ONLs. DMF holders can forestall the sending of an ONL by updating their DMFs, following the procedure below under “Reactivating a DMF.” Some DMFs may be listed as inactive which are, in fact, still active. Every effort will be made to correct any errors. Some DMFs may be listed as inactive which are, in fact, still
active. Every effort will be made to correct any errors.
Reactivating a DMF
A DMF holder that wants to reactivate a DMF that is listed as Inactive and that was not closed by the holder should use the following decision tree:
1. Have there been changes to the technical information in the DMF?
- If ”No”, go to #3 below.
- If “Yes” submit an amendment listing all the changes. This includes technical information usually submitted on a periodic basis (e.g., stability updates). Go to #4 below.
2. Have there been changes to the administrative information in the DMF?
- If ”No”, go to #3 below.
- If “Yes” submit an amendment listing all the changes (It is not necessary to submit any changes to the administrative information except the name and address of the holder and the manufacturing facility and the contact person.) Go to #4 below
3. If there have been no changes, submit an Annual Report stating that no changes have been made to the DMF. Include a list of all companies authorized to reference the DMF. (Authorized parties)
4. If there have been changes that were reported in the amendment(s) (see above), submit an Annual Report listing:
a. the date(s) of the amendment(s)
b. the subject(s) of the amendment(s)
c a list of Authorized parties.
There may be a lag time between inactivation of a DMF (either by lack of timely response to an ONL or closure by the holder) and its retirement by FDA. DMF holders who wish to reactivate an inactive DMF should contact email@example.com to determine whether the DMF has been retired by FDA.
Reactivating a Closed DMF
DMFs that have been closed either because the holder has not responded to an ONL within the 90 day time period or because the DMF was closed by the holder may have been retired by FDA and may require a complete resubmission. Note that a DMF will not be retired by FDA unless an ONL has been sent AND there was no response within 90 days. DMF holders who wish to reactivate a closed DMF should send an inquiry to firstname.lastname@example.org.
DMF Guideline The version posted on the web is the current
version. Note that the address for submitting DMF documentation to the FDA in the Guidance has been superseded by the Beltsville address below. No revision is planned for the immediate future. Please
address question regarding the DMF Guideline to
Note: FDA regulations require that all submissions to INDs and NDAs that are in a foreign language have “complete and accurate translations.” The same is true for DMFs. A “certified” translation is not required.
MORE INFORMATION ABOUT DMFs
The recommendations in the DMF Guidance are, in general, still applicable. However the information below provides additional information or clarification of the recommendations in the Guidance. This information provided below falls into three categories
- Recommendations that are no longer applicable due to changes in regulations or guidances.
- Additional clarification of recommendations in the Guidance.
- New information for aspects of DMF filing that were not in effect when the Guidance was written.
Address for Filing Original DMFs and Subsequent DMF Documents (Category 3)
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Road
Beltsville MD 20705-1266
Format and Content of the Chemistry, Manufacturing, and Controls Section of an Application (Category 1)
The “Guideline for the Format and Content of the Chemistry, Manufacturing, and Controls Section of an Application” cited in the DMF Guidance has been withdrawn. DMFs may be submitted following the format recommended in the "Guidance for Industry M4Q: The CTD - Quality".
TYPES OF DMFs
Type I DMFs (Category 1)
Type I DMFs are no longer accepted per a Final Rule published
January 12, 2000 (65 FR 1776). See Type V DMFs below.
Holders of Type II, III, and IV DMFs should not place information
regarding facilities, personnel or operating procedures in these
DMFs. Only the addresses of the DMF holder and manufacturing site
and contact personnel should be submitted.
Type II DMFs
The "Guideline for the Format and Content of the Chemistry, Manufacturing, and Controls Section of an Application" is no longer available. (Category 1)
Type II DMFs may be submitted in the format for "Drug substance" in the "Guidance for Industry M4Q: The CTD - Quality".(Category 3)
See the current Guideline for Submitting Supporting Documentation in Drug Applications for the Manufacture of Drug Substances.
For Type II DMFs filed in CDT-Q format, Module 2 is expected.
See the Guideline For Submitting Supporting Documentation In Drug Applications For The Manufacture Of Drug Products.
Type III DMFs
The "Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics." is no longer available. (Category 1)
The applicable Guidance for Type III DMFs is the “Guidance
for Industry: Container Closure Systems for Packaging Human Drugs
and Biologics: CHEMISTRY, MANUFACTURING, AND CONTROLS
Questions and Answers.
Type V DMFs (Category 3)
The following types of DMFs may be filed as Type V DMFs without
requesting prior clearance from FDA.
For other submissions as Type V DMFs, holders may send their request to email@example.com, explaining the necessity for filing the information in a Type V DMF.
ELECTRONIC DMFs (Category 3)
Guidance for Industry: Providing Regulatory Submissions in
Electronic Format — Human Pharmaceutical Product Applications and
Related Submissions Using the eCTD Specifications
. To make sure you have the most
recent versions of the specifications referenced in this guidance
Electronic Common Technical Document (eCTD). Companies are
encouraged to submit their DMFs in electronic form, including
updating current paper DMFs. Note that all applications to CDER, including DMFs, that are submitted in electronic format MUST be in ECTD format, unless a waiver is granted. http://www.fda.gov/cder/regulatory/ersr/waiver.htm
All Letters of Authorization for electronic DMFs should specify that the DMF has been submitted in electronic format.
Module 1 should contain the following information
Section 1.2: Cover Letter and Statment of Commitment
Section 1.3: Administrative Infromation
1.3.1 Contact/sponsor/Applicant information
22.214.171.124 Change of address or corporate name
Can be used to supply addresses of DMF holder and manufacturing and testing facilities
126.96.36.199 Change in contact/agent
Can be used to supply the name and address of contact persons and/or agents, including Agent Appointment Letter
Section 1.4.1: Letters of Authorization
Section 1.12.14 Information regarding the Environmental Analysis
Companies that wish to submit an annual report or amendment in
electronic format may do so. However, once the DMF holder has made
an electronic submission every subsequent submission must be in
electronic format. In such cases DMF holders are advised to resubmit
the entire DMF in CTD format as an amendment. This allows the DMF to
be reviewable in its entirety using the electronic DMF rather than
mixing paper and electronic formats. If there are any changes in the
technical content of the DMF as a result of the reformatting, e.g.
addition of new information, the cover letter for the amendment
should specify what areas of technical information have been
DMFs that cover multiple items e.g. Type III DMFs for components of container-closure systems or Type IV DMFs for flavors, can be submitted in ECTD format. Note that this format simply provides the backbone for the submission and a guide as to where to place information. It is not necessary to submit all Modules nor is it necessary to submit all sections within a Module. However, Module 1 is required for all eCTD submissions, as it contains the necessary administrative information to identify the DMF. The technical information can be in Module 3, following the outline in the Drug Substance Section. The different sections within 3.2.S. can be populated as appropriate. Each product e.g. different flavors, would have a different name e.g. 3.2.S.[Flavor 1], 3.2.S.[Flavor 2]. Information that is common to different products e.g. analytical procedures can be accessed by links from the relevant section for that product e.g. 3.2,S.4.2 [Flavor 1].
Products manufactured at separate facilities do not need to be filed as separate sections unless the manufacturing processes are different.
Electronic signatures are accepted for electronic DMFs.
LETTERS OF AUTHORIZATION (Category 2)
All Letters of Authorization (LOAs) must be submitted in two copies to the DMF. A copy of the LOA must then be sent by the DMF holder to the Authorized Party (company or individual authorized to incorporate the DMF by reference). Failure to submit the LOA to the DMF may result in a delay in review of the DMF.
AGENTS (Category 2)
There is no regulatory requirement for an agent for any DMF, foreign or domestic. An agent for DMF purposes is not the same as an agent for the purposes of the Drug Listing and Registration System. (DRLS). According to a Federal Register Notice, November 27, 2001 (Vol. 6, No. 228), effective May 24, 2002, all foreign drug establishments are required to register with the Food and Drug Administration (FDA). As published, foreign firms are required to register and identify a United States agent.
If possible, the word “Agent” should be used for the legal entity (whether a company or an individual) who is authorized to act on behalf of the DMF holder. The word “Representative” should be used for an individual who is employed by the Agent or Holder as the contact point for FDA. Agent Appointment Letters or notifications rescinding the appointment of an Agent should be sent as separate documents, rather than being included in an Annual Report or other amendment. If a company acting as an Agent changes its name, the DMF holder should issue a new Agent Appointment Letter. A change in Representative does not need to be reported in a separate amendment.
All “Agent Appointment Letters” for DMFs should be sent by the holder. FDA recommends that such letters include the phrase “appoint AGENT NAME as the agent for DMF” rather than “authorize AGENT NAME to act as the agent for DMF,” since the latter can be confused with a “Letter of Authorization”. An “Agent Appointment Letter” may be included in an original DMF.
A different agent can be appointed for different DMFs submitted by the same holder.
HOLDER NAMES (Category 2)
When the company that owns a DMF (DMF holder) changes its name, whether through sale of the company or simply a change in the company’s name, the DMF holder must notify FDA. This should be done in a separate
amendment, rather than including the information in an Annual Report or
other amendment. See Section VII.E. in the Guideline for DMFs for
further recommendations on the procedure for transferring ownership. A change in the name of a company for registration purposes under
DRLS will not change the DMF holder name.
In general FDA expects the manufacturer to be the holder. If a
manufacturer (Company A) of a MATERIAL wishes to have the DMF
submitted by another company (Company B) and Company B wishes to act
as the holder, the DMF should include statements from both companies
that Company B takes full responsibility for all the information in
the DMF and for all the processes and testing performed by the
manufacturer. The title of the DMF which will appear on the list of
DMFs will be “MATERIAL manufactured by COMPANY A in LOCATION OF
COMPANY A for COMPANY B.”
ANNUAL REPORTS (Category 2)
According to the DMF Guideline, Annual Reports are NOT to be used to
report changes in the DMF. Note that
Annual Reports to DMFs are not REQUIRED by law or regulation.
The holder should provide an annual report on the anniversary date
of the original submission. This report should contain the required
list as described in B.1. and should also identify all changes and
additional information incorporated into the DMF since the previous
annual report on the subject matter of the DMF.“
A DMF is required to contain a complete list of persons authorized
to incorporate information in the DMF by reference [21 CFR
314.420(d)]. The holder should update the list in the annual update.
The updated list should contain the holder's name, DMF number, and
the date of the update. The update should identify by name (or code)
the information that each person is authorized to incorporate and
give the location of that information by date, volume, and page
The list of authorized parties in the Annual Report should be a complete list of authorized parties rather than a list of authorized parties added since the previous update. See discussion above under "reactivating a DMF" for recommendations on what information should be in an Annual Report and what information should be in an amendment.
Note that an “Annual Update” and an “Annual Report” are the same thing.
BIOLOGICS MASTER FILES (Category 3)
Master Files submitted in support of products regulated by the Center for Biologics Evaluation and Research (CBER) should be submitted as
BB-MFs. See the CBER web site for the products regulated by CBER.
BINDERS (Category 2)
See ”FDA IND, NDA, ANDA, or Drug Master File Binders These are actually covers. One copy of the DMF should use the blue cover and one should use the red cover. Fasteners must be obtained separately. 2 Piece Prong Fasteners, 8 1/2" Center to Center, 3 1/2" Capacity
FEES (Category 3)
There are no fees or charges for filing a DMF.
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Date created: April 17, 2001; updated August 8, 2008