What Is A Drug Master File (DMF)?
What Is A Drug Master File (DMF)?
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 other components used in the manufacturing, processing, packaging, and storing of one or more human drug(s.) The submission of a DMF is not required by law or FDA regulation.
A DMF is submitted solely at the discretion of the holder. The information contained in the drug master file 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.
Types Of DMFs
- Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel
- 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
Regulatory bodies outside of FDA also accommodate submission of confidential detailed information supporting drug application. In some cases, these submissions are called DMFs. For example, the Common Technical Document (CTD,) allows for a “Closed Section,” which contains comparable information to a DMF, and is sometimes referred to as a DMF.
What Should Be Included In A Drug Master File?
A DMF is a document that contains information about the manufacturing, controls, storage, distribution, and stability of a drug substance, active pharmaceutical ingredient, excipient, or other element of a drug product. It is submitted to regulatory authorities to help them assess the safety and efficacy of a drug product.
The contents of a DMF vary depending on the country in which it is filed and the type of DMF filed. In general, the DMF should contain information to support the consistent manufacturing through the life cycle of the substance. A typical Type II DMF includes:
- Molecular structure and properties
- Component controls and specifications
- Manufacturing Controls and specifications
- Analytical procedures and controls
- Impurity profile
- Container/closure suitability and controls
- Distribution controls
- Qualification and validation information for equipment, manufacturing, and analytical methods
- Stability
- Batch analyses
- Environmental Assessment
- An authorization letter to the firm referencing the DMF
Why Is A Drug Master File Important?
A DMF allows a manufacturer to share information about its products with regulatory authorities without disclosing trade secrets. 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.
The DMF is an important tool for ensuring the safety and efficacy of pharmaceutical products. It helps to ensure that products are manufactured according to Good Manufacturing Practices (GMPs), and that they meet all quality control specifications. It also helps to ensure that products are safe for human use and that they meet all regulatory requirements.
How Is A Drug Master File Submitted To The FDA?
A DMF is a voluntary submission and, therefore, has no mandatory requirements for format or content. FDA does offer guidance.
A DMF IS NEVER APPROVED OR DISAPPROVED BY THE FDA.
An original DMF submission will be examined on receipt to determine whether it meets minimum guidance requirements for format and content. If the submission is administratively acceptable, FDA will acknowledge its receipt and assign it a DMF number.
The technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application.
FAQs on DMFs
What happens when you don’t complete a drug master file correctly?
If the submission is administratively incomplete or inadequate, it will be returned to the submitter with a letter of explanation from the Drug Master File Staff, and it will not be assigned a DMF number.
If FDA reviewers find deficiencies in the information provided in a DMF, a letter describing the deficiencies is sent to the DMF holder. At the same time, FDA will notify the person who relies on the information (e.g. the NDA holder) that the DMF is deficient and that additional information is needed in the supporting DMF.
When should you have an expert help in creating your drug master file?
A drug master file can be a complex and time-consuming process. It is therefore important to ensure that all information included in the DMF is accurate and up to date. An expert can help you to create a drug master file that meets all the elements needed to support a drug application.
An expert can also navigate the requirements for the specific types of DMFs and the particular information and formats required by various regulatory bodies.