What is a Drug Master Files?

What Is a Drug Master Files(DMF) ?

A Drug Master File (DMF) is a submission to regulatory agencies, that contains critical information about the chemistry, manufacturing, and control (CMC) aspects of a pharmaceutical product or active pharmaceutical ingredient (API). DMFs are an essential resource for the regulatory process, as they provide detailed insights into the facilities and processes used in the production, processing, packaging, and storage of drugs that can be referenced by  pharmaceutical companies who wish to seek product approval.

The information within a DMF can support various regulatory applications such as Investigational New Drug Applications (INDs), New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), export applications, and amendments or supplements to these documents. It's important to note that a DMF is not a substitute for the aforementioned regulatory applications. Instead, it serves to protect the confidentiality of intellectual property related to the manufacturing process, benefiting the DMF holder.

Drug Master File submissions are typically submitted by API manufacturers to regulatory authorities and are designed to support the registration of finished pharmaceutical products that utilize the API. DMFs are not standalone applications and do not receive approval or disapproval on their own. They are reviewed and assessed only in conjunction with a drug application or export application. Regulatory authorities may use DMFs to assess claims made by applicants in support of their applications.

Types of Drug Master File (DMFs)

There are five types of DMFs, each containing specific information:

Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel

Description of the manufacturing site, equipment, and operational layout.

Information about major production and processing areas.

Organizational elements within the manufacturing site and corporate headquarters.

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

Detailed information about drug substances, intermediates, or materials used in their preparation.

Compliance with guidelines for drug substances and intermediates.

Type III: Packaging Material

Identification of suppliers or fabricators.

Organizational elements within the manufacturing site and corporate headquarters.

Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation

Identification and characterization of additives used in drug preparation.

Inclusion of toxicological data if necessary.

Type V: FDA Accepted Reference Information

Generally discouraged and used for specific information not covered by other Drug Master File types.

All new and existing DMFs must be submitted in eCTD format. Submissions not meeting this requirement are rejected. This move towards electronic submissions enhances efficiency, accessibility, and data security in the regulatory process.

DDReg’s Capabilities

DDReg provides expert regulatory affairs services to pharmaceutical companies, helping companies navigate the process of DMF submissions and drug product registrations:

Devising comprehensive regulatory submission strategy for all DMF types

Provide support in reviewing the development report with Quality by Design

Deep subject-matter expertise in impurity evaluations, assessments from genotoxicity perspective

Expert advisory in selection of key starting materials, route of synthesis, establishing impurity limits for starting materials and intermediates.

Preparation, review, and submission of DMF per GDUFA and competent authority assessments including support for fee compliance.

Real time repository of global API regulations, DMF requirements, API eCTD development and publishing