What a Drug Master File Is, and Why You Cannot Read One

Answer first: it is a filing cabinet, not a decision

The regulation defines it by what the person filing it intends it to do.

A drug master file is a submission of information to the agency by a person, the holder, who intends it to be used for one of two purposes.

The first is self-serving in the ordinary sense. To permit the holder to incorporate the information by reference when it submits its own investigational application, application, abbreviated application, amendment or supplement.

The second is the interesting one. To permit the holder to authorize other persons to rely on the information to support a submission to the agency, without the holder having to disclose the information to that person.

Read that twice. The whole point of the arrangement is that a customer can use a supplier's data without ever seeing it.

The sentence that disposes of most marketing claims

Two sentences in the same paragraph settle what a file does and does not signify.

The agency ordinarily neither independently reviews drug master files nor approves or disapproves submissions to a drug master file.

Instead, the agency customarily reviews the information only in the context of an application.

So the existence of a file is not a review, not an approval and not a disapproval. It is a submission sitting in a system until somebody's application points at it.

A claim that a supplier holds one is a claim about paperwork existing. It is not a claim that anybody at the agency has looked at what is in it.

What can be in one

The regulation says a file may contain information of the kind required for any submission, and then lists types.

The list's first numbered entry is reserved, so it begins at the second.

Drug substance, drug substance intermediate, and materials used in their preparation, or drug product.

Packaging materials.

Excipient, colorant, flavor, essence, or materials used in their preparation.

And a category for information the agency has accepted that does not fit the others. Someone wishing to submit information not covered by the other types must first send a letter of intent to the drug master file staff, and the agency then makes contact to discuss the proposed submission.

How a customer uses a file it cannot see

Incorporation by reference is the mechanism, and it has a written gate and a citation format.

An application, abbreviated application, amendment or supplement may incorporate by reference all or part of the contents of any file in support of the submission — if the holder authorizes the incorporation in writing.

That written authorization is what people mean when they talk about a letter of authorization. The holder controls it.

The reference has to be precise. Each incorporation by reference is required to describe the incorporated material by name, reference number, volume and page number.

So the customer's application cites a page it has never read, in a file it does not hold, with the holder's written permission.

The holder has to keep a list of who may point at it

One paragraph creates a record that answers a question people often assume is unanswerable.

The file is required to contain a complete list of each person currently authorized to incorporate by reference any information in it.

The list identifies, by name, reference number, volume and page number, the information each person is authorized to incorporate.

And it can be scoped. If the holder restricts the authorization to particular drug products, the list is required to include the name of each drug product and the application number, if known, to which the authorization applies.

That list exists inside the file. Whether anyone outside can see it is a separate question, answered in the last paragraph of the section.

When the file changes, the customers get told

There is a notification duty and it runs from the holder outward.

If the holder adds, changes or deletes any information in the file, the holder must notify in writing each person authorized to reference that information.

Any addition, change or deletion is itself submitted in the prescribed number of copies and must describe, by name, reference number, volume and page number, the information affected.

The authorization list is carved out of that submission requirement, which makes sense: the list changes whenever a customer is added or removed.

The practical effect is that a company relying on a supplier's file is supposed to learn when the underlying information moves. That is a channel between two businesses, not a public announcement.

Whether anyone can read it

The section does not answer this itself. It points elsewhere, and the pointer is the answer.

The public availability of data and information in a file is determined elsewhere. It is decided under the agency's public information regulations and the section governing disclosure of application files, and that reaches availability to a person authorized to reference it.

Note the phrase in the middle. Including the availability of data and information in the file to a person authorized to reference the file.

So even an authorized customer's access is governed by those disclosure rules rather than by the authorization itself. Being allowed to cite a file is not the same as being allowed to read it.

The agency's general disclosure regulations withhold trade secrets and confidential commercial or financial information, which is the category most of a manufacturing file would sit in.

What this changes about a sourcing question

This is the practical payoff, and it reframes a question buyers ask constantly.

Asking where an active ingredient comes from often runs into this structure. The detail lives in a file the seller may be authorized to cite and not authorized to disclose.

That is a real constraint rather than an evasion, and it is worth separating from the questions that do have answers.

What is answerable: which entities are named on the product's own labeling, what registrations and listings exist for the establishments involved, and what the seller is willing to state in writing.

What a file's existence never establishes: that the agency reviewed the contents, approved them, or made any finding about the material at all. The regulation says the agency ordinarily does neither.

What this page does not tell you

Two boundaries, stated where you can see them.

Everything above is drawn from one section of the federal drug application regulations. No supplier or seller was examined, and nothing here says whether any company holds or references such a file.

The section points at two other regulations for public availability, and those are described only to the extent this section points at them. The disclosure rules for an approved application file, and the agency's general public information regulations, are covered on their own pages.