Drug Master Files: Do you really know what they are and if you need them?

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The FDA recently announced that beginning May 5, 2017 all new Drug Master File (DMF) submissions will have to be done electronically. By shifting away from paper submissions, the FDA hopes the new system will facilitate processing and record-keeping of DMFs.

For many pharmaceutical and cell therapy companies, the new rules will be a welcome change. For those who have not yet been involved with the submission of Drug Master Files, here is a quick refresher on what they really are, who they are for, when they are needed and how to get help with them.

There are five categories of Drug Master Files, and typically API manufacturers fall within Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product.

The following information refers to DMFs within the context of drug manufacturing.

So, what are Drug Master Files?

Simply put, a Drug Master File is a confidential document prepared by a drug manufacturer (any pharmaceutical or biotechnology company) and submitted by said company to the FDA which outlines, in detail, the manufacturing process for the drug or API which the DMF is being submitted for.

What do you mean by “confidential”?

The Drug Master File is submitted at the sole discretion of the API manufacturer, and its contents are only shared between the manufacturer and the regulatory agency (FDA).

Who are the parties involved in the submission of a Drug Master File?

The company who submits a DMF is the holder. The holder is represented by an agent (optional), while the company who references the DMF is the applicant or the authorized party.

When is a Drug Master File required?

Never. There is no legal requirement to submit a Drug Master File.

What do you mean – so why would I bother submitting one?

A holder would submit a Drug Master File when they wish to keep the contents of the DMF confidential from a third party that wishes to make use of the DMF as part of a new product application.

So I cannot be requested to submit or have one on file?

No. While Drug Master Files show a company’s commitment to its quality systems by evidencing compliant manufacturing practices, the submission of a DMF is at the sole discretion of said company and its contents are not to be shared with any other party other than the FDA.

When would one file a Drug Master File?

Drug Master Files are submitted in conjunction with a new product application.

Is there a benefit of having Drug Master Files on file with the FDA?

The FDA only reviews Drug Master Files in conjunction with a new product application (e.g. when an NDA is filed that references the DMF in question), so having them on file with the FDA does not provide any apparent benefit.

What happens when a Drug Master File is submitted?

Technical contents of a DMF are reviewed only in connection with the review of a new application for product registration.

DMFs are reviewed only when referenced.

What happens when a DMF is reviewed?

When a DMF is reviewed, there are three possible outcomes: if deficiencies are found, the review board sends an Information Request (IR), otherwise it classifies the DMF as Approvable (AE), or Not Approvable. Technical amendments are done according to FDA guidelines.

Guidelines on submission of DMFs are provided here: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/DrugMasterFilesDMFs/UCM2007046

I am a drug/API/other manufacturer, and I am interested in knowing if a particular company has a DMF on file. How do I go about finding that out?

A list of DMFs are available from the FDA. This list only includes DMFs that have been reviewed and/or approved as part of a submission such as an NDA, so it does not necessarily include DMFs that have been submitted but not reviewed. If you are interested in a company’s DMF status, contact the company directly.

Be aware that a DMF holder is under no requirement – nor should they – share the contents of a DMF with a third party.

However, information that a manufacturer can provide through DMFs can be provided via alternative methods (batch records and/or audits), and no one other than the holder should make decisions as to whether a DMF should be filed.

Does Akron have DMFs?

Akron Biotech has on file DMFs for a variety of our products that are available to be filed should this be a suitable option for a particular application.

Do you need more help with DMFs? We would be happy to answer and help you file yours — or provide information about ours. Contact us here.



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