Drug Master File

Drug Master File or DMF is a document prepared by a pharmaceutical manufacturer and submitted solely at its discretion to the appropriate regulatory authority in the intended drug market. There is no regulatory requirement to file a DMF. However, the document provides the regulatory authority with confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Typically, a drug master file is filed when two or more firms work in partnership on developing or manufacturing a drug product. The DMF filing allows a firm to protect its intellectual property from its partner while complying with regulatory requirements for disclosure of processing details.

INACTIVE STATUS OF DMFs

There are three reasons to list a DMF as inactive:

  • The holder requested that the DMF be closed (or retired, closed, inactivated, or withdrawn) by submitting a closure request.
  • The FDA closed the DMF because the holder did not respond to an overdue notification letter within 90 days by updating the DMF.
  • The DMF was overdue for update. The FDA considers DMFs submitted before March 31 overdue for update when the company has submitted no annual reports since that date. The FDA considers only an annual report sufficient to prevent them sending an overdue notice letter (ONL).

The status Inactive in the list does not distinguish among the reasons listed above.

DMFs must be current at the time of review. According to FDA regulations regarding DMFs (21 CFR 314.420(c)):

“Any addition, change, or deletion of information in a drug master file (except the list required under paragraph (d) of this section) is required to be submitted in two copies and to describe by name, reference number, volume, and page number the information affected in the drug master file.”

The Guideline for Drug Master Files (September 1989), recommends that DMF holders update their DMFs annually (see below under Annual reports).

To ensure DMFs are current, the FDA sends overdue notification letters (ONLs) to DMF holders for DMFs that are overdue for update (see above). If a DMF holder does not respond to this letter within 90 days by submitting an annual report, the FDA considers the DMF closed by the FDA, and retired.

Note that the FDA has a backlog sending out ONLs. DMF holders can forestall the sending of an ONL by updating their DMFs, following the procedure below under Retaining the activity of a DMF.