U.S. DMF eCTD Format Details

Inquiry

Submission of DMFs to FDA is typically in the electronic Common Technical Document (eCTD) format. In this article, we detail the submission requirements for Type II and Type IV DMFs in the eCTD format.

Background

The U.S. Drug Master File (DMF) is categorized into five types, of which Type II and Type IV are the most common, covering active pharmaceutical ingredients (APIs) and pharmaceutical excipients, respectively.

Type II DMFs cover detailed information about APIs used in drug manufacturing, including the API's manufacturing process, quality control, purity standards, stability data, etc. These DMFs are usually prepared by the API manufacturer. This type of DMF is typically submitted by the API manufacturer to protect intellectual property and to allow the FDA to evaluate related drug applications such as NDAs and ANDAs.

Type IV DMFs contain information about pharmaceutical excipients used in the manufacture of a drug product, including the source of the excipient, the manufacturing process, quality control, safety data, etc. These excipients can be any material that is not directly used in the manufacture of the drug product. These excipients can be any substance that does not directly play a pharmacological role, such as stabilizers, fillers, solvents, etc.

Module I

(1) Cover letter (eCTD section 1.2)

FDA recommends using the template for submissions on CDER's DMF web page.

(2) Administrative information (eCTD section 1.3)

DMF holder

DMF holders should provide their name and address and only one company should be listed as the DMF holder. Joint submissions are not acceptable.

Contact person or agent

DMF Holders should provide the name, telephone and facsimile numbers, e-mail address, and specific responsibilities of the contact person and agent.

To facilitate communication, FDA strongly encourages foreign DMF holders to designate a representative, preferably in the United States, who is familiar with FDA regulations, guidance, and procedures. The agent may submit DMFs or sign on behalf of the DMF holder, except as follows:

Proxy appointment letter
Statement of commitment
Name change
Transfer of the holder
New holder acceptance letter
DMF closure request

Manufacturer

The DMF holder should provide the manufacturer's name, site address, contact name, phone number, fax number, and e-mail address.

Prohibition on certification

The DMF holder is listed in the category of "Persons Serving in Any Capacity in the Application" as required by Section 306(k)(1) of the FD&C Act, and the DMF holder may submit its debarment certification in the eCTD Section 1.3.3.

(3) References (eCTD section 1.4)

Letter of authorization (LOA)

List of authorized persons incorporated by reference

The list shall contain the following information for each authorized party:

Name of the authorized party
Date of the LOA
The specific product, program, or process cited, including submission date, eCTD section number, and page number
Application number of the cited DMF (optional)

(4) Application status (eCTD section 1.5)

(5) Meetings (eCTD section 1.6)

(6) Revision of information (eCTD section 1.11)

(7) Information not covered in Modules 2 to 5

In general, changes reported in eCTD Section 1.11 should only include a summary of changes to Modules 2 to 5 or changes that do not fit into Modules 2 to 5. eCTD documentation in Section 1.11 should include references and links to all parts of Modules 2 to 5 that have been changed. For example, changes to API specifications should be referenced in eCTD section 1.11, but should also be changed in sections 2.3.S.4.1 and 3.2.S.4.1.

(8) Additional information (eCTD section 1.12)

The DMF holder shall include in its DMF a commitment to operate its facility in accordance with applicable environmental laws.

(9) Labeling (eCTD section 1.14)

For DMFs related to pharmaceuticals, APIs, API intermediates covered by Type II DMFs, and excipients covered by Type IV DMFs, the DMF holder shall provide a copy of the label in the labeling section.

(10) Risk assessment and mitigation strategies (eCTD section 1.16)

Module II

Module II summarizes the corresponding Module III section (and IV and V, if applicable).

Module III

Detailed technical documentation:

Type II DMF involves API manufacturing, control, stability data, etc.
Type IV DMF covers excipient manufacturing, specifications, test methods, purity, stability, etc.

View the relevant reference guide.

Module IV

This module is not required for DMFs unless the DMF contains a non-clinical evaluation. Detailed information on Module IV:

For DMFs Containing Nonclinical Assessments
Used to support non-clinical assessments of excipient safety in Type IV DMF Module III CMCs
Used to support non-clinical assessment of the safety of impurities in Type II DMF Module III CMCs

Module V

Module V submits clinical information only.

Summary

Similarities and differences

Although the Type II and Type IV DMFs differ in content and purpose, with Type II focusing on the active ingredient and Type IV dealing primarily with excipients, the structure of their submissions in the eCTD format is similar, with the main difference being the specific technical data in Module III.

eCTD tools

With the help of professional eCTD tools, you can effectively shorten the preparation cycle of eCTD files and improve the efficiency of DMF submission. For example, Highthink eCTD is a professional eCTD submission system jointly developed by IT experts, programming team, big data experts, data management experts, statistics experts, GMP-GLP-GCP-ICH regulation experts and other interdisciplinary professionals.

Highthink eCTD is applicable to the submission of data in China, the United States, the European Union and other regions, and provides professional, enterprise and expert editions for different user groups.

Learn more about Highthink eCTD.

Although the FDA does not mandate the submission of DMF, it is necessary for manufacturers of raw and auxiliary packages who want to enter the U.S. market to file DMF. Proregulations has studied the U.S. drug regulations in depth, familiarized itself with the content and formatting requirements of the DMF, as well as the key points of the FDA's review, and provided customized DMF production services for global pharmaceutical companies. If you are interested in our services or need more details, please contact us.