Drug Master File (DMF) Part 1: Definition & Types

INTRODUCTION

A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs, or

A Drug Master File (DMF) is a submission to the FDA of information, usually concerning the Chemistry, Manufacturing and Controls (CMC) of a component of a drug product, to permit the FDA to review this information in support of a third party’s submission.  Drug product information or other non-CMC information may be filed in a DMF.

The submission of a DMF is not required by law or FDA regulation. It is submitted solely at the discretion of the holder. The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, or amendments and supplements to any of these.

A DMF is NOT a substitute for an IND, NDA, ANDA, or Export Application. It is not approved or disapproved. Technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application.

DMF's are generally created to allow a party other than the holder of the DMF to reference material without disclosing to that party the contents of the file. When an applicant references its own material, the applicant should reference the information contained in its own IND, NDA, or ANDA directly rather than establishing a new DMF.

As of January 6, 2007, there were 19784 DMFs and the percentage has remained constant over the past three years.

TYPES OF DRUG MASTER FILES

There are five types of DMF’s:

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

• A Type I DMF is recommended for a person outside of the United States to assist FDA in conducting on-site inspections of their manufacturing facilities. The DMF should describe the manufacturing site, equipment capabilities, and operational layout.

• A Type I DMF is normally not needed to describe domestic facilities, except in special cases, such as when a person is not registered and not routinely inspected.

•  The description of the site should include acreage, actual site address, and a map showing its location with respect to the nearest city. An aerial photograph and a diagram of the site may be helpful.

•  A diagram of major production and processing areas is helpful for understanding the operational layout. Major equipment should be described in terms of capabilities, application, and location.

•  A diagram of major corporate organizational elements, with key manufacturing, quality control, and quality assurance positions highlighted, at both the manufacturing site and corporate headquarters, is also helpful.

 

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

A Type II DMF should, in general, be limited to a single drug intermediate, drug substance, drug product, or type of material used in their preparation.

1. Drug Substance Intermediates, Drug Substances, and Material Used in Their Preparation

• Summarize all significant steps in the manufacturing and controls of the drug intermediate or substance.

     2. Drug Product

• Manufacturing procedures and controls for finished dosage forms should ordinarily be submitted in an IND, NDA, ANDA, or Export Application. If this information cannot be submitted in an IND, NDA, ANDA, or Export Application, it should be submitted in a DMF

Type III: Packaging Material

• Each packaging material should be identified by the intended use, components, composition, and controls for its release. The names of the suppliers or fabricators of the components used in preparing the packaging material and the acceptance specifications should also be given. Toxicological data on these materials would be included under this type of DMF.

 

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.

• Toxicological data on these materials would be included under this type of DMF.

• Usually, the official compendia and FDA regulations for colour additives (21 CFR Parts 70 through 82), direct food additives (21 CFR Parts 170 through 173), indirect food additives (21 CFR Parts 174 through 178), and food substances (21 CFR Parts 181 through 186) may be used as sources for release tests, specifications, and safety. 
  
  Type V: FDA Accepted Reference Information
• FDA discourages the use of Type V DMF's for miscellaneous information, duplicate information, or information that should be included in one of the other types of DMF's.