Background and Current State

A Drug Master File (DMF) is a submission of information to the U.S. FDA to permit the Agency to review information on a drug component (e.g., API, excipient and packaging material) in support of a third party’s drug application. DMFs usually cover the Chemistry, Manufacturing and Controls (CMC) and where appropriate, toxicology reports/summaries for a drug substance, excipient or packaging material.  The Drug Master File Guidance states “The submission of a DMF is not required by law or FDA regulation. A DMF is submitted solely at the discretion of the holder.[1]” The primary purpose for establishing a DMF is to maintain confidentiality of proprietary information.  Historically, excipient DMFs were submitted on paper; however, in May 2015 the U.S. FDA published a final guidance[2] which established a deadline of May 5, 2017 for DMFs (including excipients) to be submitted in the Electronic Common Technical Document (eCTD) format.  There is no requirement to convert existing paper DMFs into the eCTD format.  The new requirement only applies to submissions going forward.  It should be noted that eCTD requirements for drug applications [(Investigational New Drugs (INDs), New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Biologics License Applications (BLAs)] have been in place for years, therefore, the CTD structure and electronic format is not new for drug product manufacturers.  However, eCTD submission requirements for excipient DMFs place a significant burden on excipient suppliers since a majority of the excipient DMFs historically have not even followed the CTD format, and to convert the file content to CTD format could require the DMF holder to completely rewrite the file.  This may require significant resource, cost and time commitment that may not be justifiable from a business standpoint.  In addition, many excipient suppliers would not have the capability or information technology (IT) resources to convert the files to the necessary electronic format.

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