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Drug Master Files (DMFs) and it submission

Drug Master Files (DMFs) and it submission

Drug master files (DMFs) are submissions to FDA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products. They:

  • Allow parties to reference material without disclosing DMF contents to those parties.
  • Are not required by statute or regulation.
  • Are neither approved nor disapproved. Instead, FDA reviews the technical contents of DMFs in connection with the review of applications that reference them (e.g., NDAs, ANDAs, INDs, BLAs)

(a) A drug master file is a submission of information to the Food and Drug Administration by a person (the drug
master file holder) who intends it to be used for one of the following purposes:
To permit the holder to incorporate the information by reference when the holder submits an investigational new
drug application under part 312 or submits an application or an abbreviated application or an amendment or supplement to them under this part, or to permit the holder to authorize other persons to rely on the information to
support a submission to FDA without the holder having to disclose the information to the person.

FDA ordinarily neither independently reviews drug master files nor approves or disapproves submissions to a drug master file. Instead, the agency customarily reviews the information only in the context of an application under part
312 or this part.

A drug master file may contain information of the kind required for any submission to the agency, including information about the following:
(1) [Reserved] (2) Drug substance, drug substance intermediate, and materials used in their preparation, or drug product;
(3) Packaging materials;
(4) Excipient, colorant, flavor, essence, or materials used in their preparation;
(5) FDA-accepted reference information. (A person wishing to submit information and supporting data in a
drug master file (DMF) that is not covered by Types II through IV DMF’s must first submit a letter of intent to
the Drug Master File Staff, Food and Drug Administration, 5901–B Ammendale Rd., Beltsville, MD 20705–
1266.)

FDA will then contact the person to discuss the proposed submission.

(b) An investigational new drug application or an application, abbreviated application, amendment, or supplement may incorporate by reference all or part of the contents of any drug master file in support of the submission if the holder authorizes the incorporation in writing. Each incorporation by reference is required to describe the incorporated material by name, reference number, volume, and page number of the drug master file.

(c) A drug master file is required to be submitted in two copies. The agency has prepared guidance that provides information about how to prepare a well organized drug master file. If the drug master file holder adds, changes, or deletes any information in the file, the holder shall notify in writing, each person authorized to reference that information. 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.

(d) The drug master file is required to contain a complete list of each person currently authorized to incorporate by
reference any information in the file, identifying by name, reference number, volume, and page number the information that each person is authorized to incorporate. If the holder restricts the authorization to particular drug products, the list is required to include the name of each drug product and the application number, if known, to which the authorization applies.

(e) The public availability of data and information in a drug master file,including the availability of data and
information in the file to a person authorized to reference the file, is determined under part 20 and §314.430.

Types of Drug Master Files (DMFs)

Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation; or Drug Product

The Generic Drug User Fee Amendments (GDUFA) include provisions for DMF fees, a completeness assessment, and communications with DMF holders for Type II DMFs for drug substances (active pharmaceutical ingredients (APIs)) used to support ANDAs. These provisions do not apply to other types of DMFs or to Type II DMFs used to exclusively support NDAs or INDs. For more information about GDUFA as it relates to Type II DMFs, see:

For submissions of sterility assurance information, see:

Additional Resources

Type III Packaging Material

FDA does not require that packaging information be submitted in a DMF. NDA, ANDA, or BLA applicants or IND sponsors who receive information from the manufacturer of a packaging component or material of construction may include that information directly in the application. If, however, the manufacturer does not wish to share information with the applicant or sponsor (i.e., because it is considered proprietary), it may be placed in a Type III DMF and incorporated into the application by a manufacturer’s letter authorizing reference to the DMF.

For submission requirements related to Type III DMFs, see guidance for industry Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (Rev.6).  Revision 7 of this guidance has been issued as a draft for public comment and includes a proposed exemption for Type III DMFs. When final, this guidance will represent FDA’s current thinking on this topic.

For submissions of sterility assurance information, see:

Additional Resource

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, and testing methods.

Additional Resource

Type V FDA-Accepted Reference Information

For submissions of sterility assurance information, see:

Additional Resources

List of Drug Master Files (DMFs)

The list of DMFs, which is updated quarterly, contains DMFs received by June 30, 2020, for which acknowledgment letters were sent before June 9, 2020. The list is current through DMF 034984. Changes to the DMF activity status (A=active; I=inactive), DMF type, holder name, and subject (title) made since the last update of March 31, 2020, are included.

Drug Master File (DMF) Templates

The following templates recommend elements to include in certain DMF submissions:

In these letters, list the submission type and, if applicable, the amendment type as laid out below:

DMF Submission and Amendment Types
Submission Type Amendment Type
Original (New)
Administrative Amendment
  • Change of Agent/Address/Contact Person
  • Change of Holder/Address/Contact Person
  • Change of DMF Subject (Title)
  • Change of DMF Type
  • Agent Appointment
Annual Report
Letter of Authorization
Withdrawal of Letter of Authorization
Meeting
  • Meeting Package
  • Meeting Request
Quality Amendment
  • Controls Information
  • Facility Information
  • Formulation Information
  • Manufacture Information
  • Microbiology Information
  • New Item*
  • Packaging Information
  • Stability Information
Response to Administrative Filing Issue
Response to Deficiency, Complete Response, Information Request or Additional Comments Letter
REMS—Risk Evaluation and Mitigation Strategy
  • REMS Final
  • REMS Assessment
  • REM Assessment Methodology
  • REMS Revision
  • REMS Modification—Due to Safety Labeling Changes
  • REMS Modification—Major
  • REMS Modification—Minor
  • REMS Proposal—Standard
  • REMS Correspondence

 

 

About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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