Regulatory glossary

Drug Master File (DMF): Types, Letters of Authorization, and Fees

A Drug Master File is a submission to FDA containing confidential detailed information about facilities, processes or articles used in manufacturing, processing, packaging and storing human drugs.

It exists to solve a commercial problem, not a scientific one. An API manufacturer needs FDA to see its process in full. It does not want its customer, the drug product applicant, to see the same detail. The DMF lets the supplier file directly with FDA and authorise the customer to reference it without ever receiving it.

A DMF is never approved

This is the point people miss most often.

FDA does not approve or disapprove a DMF. It is not an application. It sits there until an application references it, and only then does FDA review its contents, as part of reviewing that application.

So "our supplier has a DMF" is not a statement about quality or acceptability. It means a file exists. Whether it supports your application is determined when your application is reviewed, and deficiencies in the DMF become deficiencies in your submission.

The types

Type I, which covered manufacturing sites and facilities, was discontinued in 2000. You will still see it referenced in old documents and templates.

Type II is the overwhelming majority, and the one that carries a fee.

Letters of Authorization

The mechanism that makes the whole thing work.

The DMF holder writes a Letter of Authorization to FDA naming the applicant who may rely on the file, the specific application, and the material or section being referenced. The applicant includes a copy in their submission.

Where this goes wrong:

• The LOA is too vague. It must identify what is being authorised specifically enough that FDA knows which parts of the DMF apply.
• The LOA is stale. DMFs are amended. An LOA referencing an old version, or an applicant who never learns the DMF changed, produces a mismatch found during review.
• The applicant assumes visibility. You still have to know enough about the material to write your own sections and answer questions, and you cannot see the DMF. That gap has to be closed by the supplier through a quality agreement, not assumed away.

The GDUFA fee and completeness assessment

Under GDUFA, a Type II API DMF referenced in a generic submission must have paid its fee and passed a completeness assessment before it is deemed available for reference.

Two practical consequences. A DMF that has not paid or not passed is not usable by your ANDA, and finding that out at filing is late. And the completeness assessment is administrative rather than scientific: passing it says the file has the required sections, not that FDA finds the process acceptable.

FDA publishes a list of DMFs available for reference, and checking your supplier's status against it before you rely on them is a five-minute job that prevents a filing problem.

Where DMF reliance goes wrong

• Treating the DMF as due diligence. It is a filing mechanism, not a quality signal.
• No visibility into changes. The holder can amend the file. Your quality agreement should require notification of changes affecting your product.
• Assuming a foreign supplier's DMF covers inspection readiness. A DMF describes the process. The facility still gets inspected, and an unsatisfactory inspection becomes an approvability issue on your application.
• Relying on a DMF for something Type II does not cover. Packaging is Type III, excipients are Type IV, and the distinction matters when the LOA is written.