FDA Drug Master File (DMF) Type III
A Drug Master File (DMF) is a confidential submission to the U.S. Food and Drug Administration (FDA) that contains detailed information about the facilities, processes, and components used in the manufacturing, processing, packaging, and storage of human drugs. Although not mandatory under FDA regulations, submitting a DMF is at the discretion of the holder. DMFs are often used to support regulatory filings such as Investigational New Drug Applications (INDs), New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), other DMFs, export applications, and supplements.
For DMF Type III, which specifically covers packaging materials, the FDA has implemented the Manual of Policies and Procedures (MAPP 5015.5) to guide reviewers. This document instructs FDA reviewers to assess packaging data directly from the main drug application (IND, NDA, ANDA) wherever possible, reducing unnecessary DMF reviews. This streamlining helps applicants include packaging details directly, unless proprietary concerns necessitate a separate DMF submission.
Flexible packaging materials are widely used in the pharmaceutical industry, particularly for oral tablets and powder sachets—accounting for nearly 75% of drug packaging in the U.S. To ensure quality, the 21 CFR and USP 34 NF 29 set strict standards for packaging components. The FDA also recognizes DMF Type III submissions for these materials, especially for registration and audit readiness.
Many Indian packaging manufacturers are upgrading their facilities and documentation to align with US FDA compliance. Submitting a Type III DMF not only secures market access but also safeguards proprietary packaging information while supporting global regulatory submissions.
DMFs also enable third-party reference without disclosing confidential data. However, when applicants reference their own materials, it’s preferable to include the data directly within their IND, NDA, or ANDA instead of filing a new DMF.
Types of Drug Master Files (DMF) Explained
Understanding the different types of Drug Master Files (DMFs) is essential for pharmaceutical manufacturers, packaging suppliers, and regulatory consultants aiming for FDA compliance. Each DMF type serves a specific purpose in supporting drug applications such as IND, NDA, ANDA, and BLA.
Type I DMF – Facility & Site Information
Type I DMFs contain information about the manufacturing facility, operating procedures, site infrastructure, and personnel not tied to any specific active pharmaceutical ingredient (API) or drug product.
Type II DMF – Drug Substance & Intermediate
This is the most commonly submitted DMF type. Type II DMFs include detailed data about:
- Drug substances
- Drug intermediates
- Material used in the formulation of the drug product
It’s frequently used when a contract manufacturer supplies active ingredients for another company’s product, especially in support of an ANDA (Abbreviated New Drug Application).
Type III DMF – Packaging Materials
Type III DMFs cover packaging components such as:
- Caps, closures, bottles, vials
- Blister packs, PVC, foil laminates
- Any material that comes into direct contact with the drug product
While submission of a Type III DMF is not mandatory, it is recommended when proprietary packaging information must be kept confidential. The FDA’s updated guidance clarifies when and how Type III DMFs should be submitted:
- The applicant of an NDA, ANDA, BLA, or IND is responsible for providing complete packaging material information.
- If the manufacturer does not wish to disclose sensitive information directly, they can submit a Type III DMF and provide a Letter of Authorization (LOA) to the applicant.
- Alternatively, if there are no proprietary concerns, the data can be submitted directly within the main application without the need for a separate DMF.
DMF Type III: Key Information and Regulatory Positioning
Position of Packaging Information
- Information related to packaging parts or materials must be clearly stated in either the application (e.g., IND, NDA, ANDA, BLA) or in the Type III DMF.
- The holder’s conclusion framework (such as validation, testing approach, or material specifications) should be identified and described within the application.
Objective of DMF Type III
- The primary purpose of a Type III DMF is to provide confidential, detailed packaging material data that supports regulatory applications filed under 21 CFR 314.420.
- A DMF cannot substitute a regulatory application—it serves only as a supporting document.
DMF Type III Review Process
- A Letter of Authorization (LOA) is required to reference a DMF in any application.
- FDA reviews the submitted DMF data to support:
- An existing application
- Another DMF
- A modification or amendment
- A DMF may contain complete data on packaging parts.
- DMF deficiencies are communicated only to the DMF holder, not to the applicant referencing it.
Location: DMF
- Single Containers
- Pressurized Containers
- Bulk Containers
- Liners
- Inner Seals
- Valve Closure Systems
Location: Application
- Complete Container-Closure System
Details of DMF Type III
- Description of willful use (voluntary submission)
- Detailed data on substances used
- Accepting specifications for incoming materials
- Release specifications for finished products or substances
Required Data Submissions
- Relevant packaging information must be included in the original product application or referenced through the DMF.
- The application must include a note referencing the DMF and a Letter of Authorization.
- Duplicate copies of the LOA must also be included in the DMF.
Responsibilities of a DMF Type III Holder
- Notify applicants of any relevant changes to the DMF contents.
- Submit an annual update including:
Duplicate copies of LOAs
List of companies or individuals authorized to reference the DMF - Declare any transfer of ownership of the DMF to FDA and referencing applicants.
Other Drug Master File Types
Type IV DMF
Contains information related to excipients, such as:
- Binding agents (e.g., starch, cellulose)
- Colorants
- Flavors
- Essences
- Other non-active materials used in drug preparation
- Binding agents (e.g., starch, cellulose)
Type V DMF
Covers any information related to the drug not included in Types I–IV, including:
- Toxicological data
- Clinical study data
- Environmental impact reports
- Miscellaneous support documents
- Toxicological data
Is a License Required from Indian FDA for Primary Packaging Material?
In India, primary packaging material manufacturers are not required to obtain a license from the Indian FDA. However, if the packaging material is intended for use with pharmaceutical products especially for export compliance with international regulatory standards becomes essential.
To meet global market requirements, it is highly recommended that manufacturers of primary packaging materials obtain:
- Type III Drug Master File (DMF) for USFDA compliance
- ISO 15378 certification, which integrates GMP principles specifically for pharmaceutical packaging materials
Having a robust Quality Management System (QMS) in place not only ensures compliance but also simplifies the process of exporting primary packaging materials to regulated markets such as the U.S., EU, and others.
What is the Definition of Primary Packaging Materials?
Primary packaging materials are the materials that come into direct contact with pharmaceutical products, such as tablets, capsules, liquids, or powders. Their main role is to protect the drug from contamination, physical damage, and chemical degradation during storage, transportation, and use.
In the pharmaceutical industry, packaging is categorized into three levels:
- Primary packaging (direct contact with the product)
- Secondary packaging (outer labeling and bundling)
- Tertiary packaging (bulk transport handling)
Purpose of Primary Packaging
The primary objectives of primary packaging include:
- Containment of the drug
- Protection against physical, chemical, and environmental factors
- Portion control for accurate dosage
- Security from tampering and contamination
Also known as sales packaging, primary packaging plays a critical role not just in protection but also in consumer usability and product presentation. Since it directly touches the product, any defect in packaging can affect drug stability and safety potentially harming the end user.
