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. Retiring DMFs A DMF can be retired only if it is closed. A retired DMF is unavailable for review. Retaining DMF activity A DMF holder that wants to retain the activity of a DMF listed as Inactive and not closed must submit an annual report (two copies). This is also the process used to respond to an ONL. The cover letter must specify that it is an annual report. Reactivating a closed DMF A company can return a closed DMF to active status only by submitting a reactivation. The reactivation must contain a complete re-submission of the DMF, updated to meet current guidance. Guidance For drug master files, the version posted on the web is the current version. The address for submitting DMF documentation to the FDA in the Guidance is dmfquestion@cder.fda.gov. FDA regulations require that all foreign language submissions to INDs and NDAs have complete, accurate translations. The same is true for DMFs. The FDA does not require a certified translation. More information about DMFs DMF guidance recommendations, in general, still apply. However, the information below provides additional information or clarification in three categories: Category 1: Recommendations no longer applicable due to changes in regulations or guidances Category 2: Additional clarification of recommendations in the Guidance Category 3: New information for DMF filing aspects not in effect when the company wrote the Guidance Mailing address for filing original DMFs and all subsequent DMF documents (Category 3): Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901-B Amendale Road Beltsville MD 20705-1266 Companies send two paper copies of all submissions to an existing paper DMF to the address above. The FDA does