The types of DMFs are:
? Type I 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(no longer applicable)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 ? Type III Packaging Material
? Type IV Excipient, Colorant, Flavor, Essence, or Material Used in Their
Preparation
? Type V FDA Accepted Reference Information
All files zipped (2.7 MB) (updated 11/15/2005)
Excel New Changes All All Active Type II Active Type III Active Type IV Active Type V Active New Changes All All Active Type II Active Type III Active Type IV Active Type V Active ASCII “A” = Active “I” = Inactive
“N” = Not an assigned number “P” = DMF Pending Filing Review
INACTIVATION AND RETIREMENT OF DMFs The criteria for judging a DMF to be inactive include:
1. The holder requested that the DMF be retired, closed, inactivated., or withdrawn
2. DMFs filed before September 30, 2002 which have had no activity since they were filed or have
had no activity since September 30, 2002.
Note that the status “Inactive” in the list does not distinguish between these two categories.
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.”
As discussed in the \Guideline for Drug Master Files\holders should update their DMFs annually.
FDA is in the process of sending “Overdue Notification Letters” (ONLs) to DMF holders that have not been updated in three years. If a DMF holder does not respond to this letter within 90 days, the DMF is retired and is unavailable for review.
Some DMFs may be listed as inactive which are, in fact, still active. Every effort will be made to correct any errors.
Please address ALL comments or questions regarding DMFs to dmfquestion@cder.fda.gov. All inquiries MUST have an entry in the \e-mail. Due to concerns about viruses and the amount of \received by this account, e-mails with subject fields containing meaningless text strings, only questions marks, or left blank will not be opened.
Other inquiries unrelated to DMFs should go to druginfo@cder.fda.gov. GUIDANCES
DMF Guideline The version posted on the web is the current version. No revision is planned for the immediate future. Please address question regarding the DMF Guideline to dmfquestion@cder.fda.gov. Type I DMFs
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
Type II DMFs may be submitted in the format for \Guidance for Industry M4Q: The CTD - Quality\Note that this is not required.
Module 1 should contain the following administrative information:
Addresses of DMF holder and manufacturing and testing facilities Name and address of contact persons and/or agents Agent Appointment letters Letters of Authorization.
Drug Substance:
The current Guideline for Drug Substances cited in the DMF Guideline is in the process of being revised. Draft Guidance for Industry: Drug Substance: Chemistry, Manufacturing, and Controls Information was posted on January 6, 2004 Drug Product:
There is a draft Guidance for Industry: Drug Product: Chemistry, Manufacturing, and Controls Information.
Type III DMFs
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 DOCUMENTATION” and Questions and Answers. Type V DMFs
DMFs to describe Manufacturing Site, Facilities, Operating Procedures, and Personnel for sterile manufacturing plants may be filed as Type V DMFs. It is not necessary to request prior clearance from FDA before filing such DMFs. See Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products.
Similarly DMFs to describe contract facilities for the manufacture of biotech products may be filed as Type V Master Files without prior clearance from FDA. See Draft Guidance for Industry: Submitting Type V Drug Master Files to the Center for Biologics Evaluation and Research
ELECTRONIC DMFS
See Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Human Pharmaceutical Product Applications and Related Submissions. To make sure you have the most recent versions of the specifications referenced in this guidance please check Electronic Common Technical Document (eCTD). Companies are encouraged to submit their DMFs in electronic form, including updating current paper DMFs.
See Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Human Pharmaceutical Product Applications and Related Submissions. To make sure you have the most recent versions of the specifications referenced in this guidance please check Electronic Common Technical Document (eCTD).
AGENTS
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. According to a Federal Register Notice, November 27, 2001 (Vol. 6, No. 228),
http://www.fda.gov/ohrms/dockets/98fr/112701a.htm, 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.
All “Agent Appointment Letters” 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.
FDA recommends that all letters appointing a new agent, notifying FDA of a change in the agent’s name or rescinding the appointment of an agent be sent as separate amendments, rather than being included in an Annual Report or other amendment. If a company acting as an agent changes its name, FDA recommends that the DMF holder issue a new Agent Appointment Letter.
HOLDER NAMES
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 should notify FDA in a separate amendment, rather 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.
ANNUAL REPORTS
According to the DMF Guideline, Annual Reports are NOT to be used to report changes in the DMF. (Emphasis added)
Section VII.C.
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. [see below], 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.
All changes to a DMF should be reported as amendments. VII. B.1.
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 number.
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Date created: April 17, 2001; updated October 26, 2005