Navigating Drug Master File/Master File Requirements for Pharmaceutical Excipients

04 Mar 2026

What Excipient Manufacturers Need to Know About Drug Master Files/Master Files in the United States and Canada

Pharmaceutical excipients may be called “inactive” or “non-medicinal” ingredients, but their impact on drug product quality, stability, and performance cannot be overlooked. For chemical companies that manufacture excipients, entering regulated markets like the United States and Canada means understanding how regulators—specifically the Food and Drug Administration (FDA) and Health Canada, respectively—classify and evaluate excipients. Of utmost importance to excipient manufacturers is protecting proprietary knowledge while still supporting drug manufacturers and sponsors, and that’s where a Drug Master File (DMF) or Master File (MF) comes in as a powerful, strategic tool.

What Is a Drug Master File/Master File?

A DMF in the United States or a MF in Canada is a detailed, confidential dossier submitted to a regulatory authority that contains information about active substances, intermediates, drug products, excipients, packaging materials, and manufacturing facilities or equipment. With regard to excipients, key details include an excipient’s:

• Structure, characterization and impurities;
• Manufacturing processes (including raw materials, controls, facilities, and equipment);
• Specifications and analytical methods; and
• Packaging and stability.

Through a DMF/MF, an excipient manufacturer can provide sensitive, proprietary information directly to the regulatory authority without the need for full disclosure to drug manufacturers or sponsors. This helps protect intellectual property while still ensuring regulatory compliance. Drug manufacturers or sponsors can simply reference the excipient’s DMF in their drug applications.

The Business Case for Excipient Drug Master Files/Master Files

Although DMFs are not legally required, in practice they are often essential for doing business in regulated pharmaceutical markets. Excipient DMFs/MFs can:

• Protect a company’s proprietary excipient data and knowledge;
• Provide a mechanism for drug manufacturers or sponsors to cross-reference excipient data for drug applications; and
• Demonstrate that the excipient manufacturer/chemical company adheres to the applicable regulatory authority’s quality standard.

Not only this, but the filing of excipient DMFs/MFs to regulatory bodies like the FDA or Health Canada comes with commercial advantages. An excipient DMF/MF demonstrates that the ingredient is held to a high quality standard, building customer confidence. Drug manufacturers and sponsors feel more confident that the excipient will hold up under regulatory scrutiny, reducing the risk of deficiencies encountered in the drug application process. In competitive excipient markets, regulatory reliability is often what separates preferred suppliers from backup options. For novel, complex, or function-critical excipients, a DMF/MF is often the difference between being considered or ignored for use by a drug manufacturer or sponsor.

Excipient Drug Master Files in the United States

In the United States, Type IV – Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation DMFs are applicable to excipients.

1. Preparing the documentation: Prepare the documentation according to the FDA regulations.
2. Submitting the DMF to the FDA: Submit the DMF electronically in eCTD format through the Electronic Submissions Gateway (ESG). The submission undergoes an administrative review by the FDA to ensure the information meets their standards. The technical review of the excipient DMF typically occurs when referenced in a drug submission. The excipient manufacturer will then be informed as to whether the DMF is acceptable or whether further clarification is needed.

Once filed, any drug manufacturer or sponsor that uses the excipient must have a Letter of Authorization to reference the excipient DMF.

Maintaining Drug Master Files With the Food and Drug Administration

In the United States, DMFs must be maintained. Excipient manufacturers are required to:

• Submit an annual report to keep the DMF active, even if no changes have been made; and
• Submit a DMF amendment for any significant change to the excipient.

It is important to note that outdated DMFs can delay or block a sponsors drug application review and/or approval.

Excipient Master Files in Canada

In Canada, Type III – All excipients including those of biological origin (such as albumin), capsule shells, coating ingredients, colourants, flavours and other additives (such as gelatin, alum and growth media) MFs are applicable to excipients.

Health Canada uses a split format for MFs as follows:

• Applicant’s part (open part): Non-confidential data shared with the drug sponsor; and
• Restricted part (closed part): Proprietary manufacturing and control information filed by the MF holder to Health Canada directly.

Preparing and Filing Master Files for Submission to Health Canada

The essential steps involved in preparing an MF for submission to Health Canada include:

1. Gathering data and preparing the documentation: Health Canada typically requires similar documentation as that required by the FDA.
2. Submitting the MF to Health Canada: Health Canada prefers electronic submission of excipient MFs in eCTD format via the ESG, but excipient MFs can also be submitted in non-eCTD electronic format. The excipient MF is reviewed only when referenced in a drug submission. The applicant will then be informed as to whether the MF is acceptable or whether further clarification is needed.

Once filed, any drug manufacturer or sponsor that uses the excipient must have a Letter of Access to reference the excipient MF.

Maintaining Master Files With Health Canada

Health Canada recommends maintaining MFs by submitting annual reports. Any changes to the excipient must be communicated clearly.

Quick Comparison Between Drug Master Files/Master Files in the United States and Canada

Feature	United States	Canada
Regulatory Authority	Food and Drug Administration (FDA)	Health Canada
File Type	Type IV	Type III
Mandatory	No	No
Format	eCTD required	eCTD preferred; non-eCTD accepted
Confidentiality	Single confidential file	Open + restricted parts
Annual Updates	Required	Recommended
Customer Access	Letter of Authorization	Letter of Access

Best Practices for Excipient Manufacturers

If you, as an excipient manufacturer, want to compete in regulated pharmaceutical markets, here’s what you need to know:

• Treat your excipient like a pharmaceutical-grade ingredient;
• Build documentation aligned with ICH CTD Module 3;
• Work with a regulatory partner to help navigate the requirements, prepare, and file submissions, as needed;
• Maintain a well-defined quality system;
• Carefully track Letters of Authorization and Letters of Access/customer references;
• Update your DMF/MF when changes occur.

Intertek Can Help!

For chemical companies that manufacture pharmaceutical-grade excipients, DMFs/MFs are not just paperwork—they are strategic assets. Whether you are entering the market in the United States, Canada, or both, a well-built and well-maintained DMF/MF can unlock new customers, protect your technology, and position you as a trusted partner in the pharmaceutical supply chain.

If you are planning to file a DMF or MF in the United States or Canada, Intertek is happy to help you prepare and submit the documentation per the regulatory requirements. Contact us to discuss all your DMF/MF needs!