Why Excipient Suppliers Should Dump Most DMFs Prior To May Deadline

An excipient trade group said that converting paper drug master files to electronic DMFs is fraught with challenges and suggested some alternatives to ease the path for communicating proprietary information to US FDA. Agency guidance has set a May 5 deadline for conversion to eDMFs.

Excipient suppliers need to decide soon whether to convert their paper drug master files (DMFs) for existing drugs to electronic form or to inactivate them and consider alternative approaches for handling proprietary information. One such alternative would be to provide this information directly to manufacturers instead of FDA under confidential disclosure agreements.

So asserts a position paper just issued by the International Pharmaceutical Excipients Council. The paper outlines some of the challenges involved in converting paper DMFs to electronic files and offers some alternatives to the traditional DMF for disclosing proprietary information.

In May 2015 FDA published final guidance that established a deadline of May 5, 2017, for DMFs to be submitted in the electronic Common Technical Document format. The new requirement only applies to submissions going forward; there is no requirement to resubmit anything that has already been submitted in paper. A DMF is a submission of information to the US FDA to permit the agency to review information on a drug component in support of a third party’s drug application. The primary purpose for establishing a DMF is to maintain confidentiality of proprietary information.

IPEC said that while there is no requirement to convert existing paper DMFs into the eCTD format, it is “realistically impossible long-term for excipient suppliers to maintain paper DMFs since all future updates, amendments, annual reports and letters of authorization (LOAs) will be required to comply with eCTD format and electronic submission specifications (including XML backbone and submission through an approved FDA portal).” An LOA grants FDA the authorization to review the DMF.

There is also concern that drug product manufacturers may expect their suppliers to have eCTD compliant DMFs by May 2017.

The group also said that “many excipient suppliers do not have the software required for eCTD publishing, nor do they have systems that can communicate directly with the FDA computer system; therefore updating excipient DMFs to eCTD format would require significant resources that would need to be justified.”

To ensure their optimal use, DMFs should be used in the following situations:

• Excipient suppliers should only submit or maintain a DMF if they have confidential information on non-compendial, co-processed or novel excipients that they do not want to share directly with the customer.
• A DMF may also be submitted for a compendial excipient where proprietary toxicology information is necessary to support new routes of administration or higher levels of use than what was previously approved and the DMF holder chooses not to share the information directly with manufacturers.

IPEC suggested that DMFs be inactivated for compendial excipients and some types of non-compendial excipients such as simple mixtures of common excipients since they “often do not provide added value to regulators.”

David Schoneker, global regulatory affairs director for Colorcon, and a past president of IPEC, told the Pink Sheet that “a pretty high number” of excipient manufacturers use DMFs for communicating proprietary information, yet some also use confidentiality agreements with pharmaceutical manufacturers.

He further noted that the content of DMFs varies: while some may only be a few pages, others may be thousands of pages long. Some DMFs include full toxicology reports or quantitative formulations which can make them very large or they might only include a basic description of a key manufacturing step that is considered highly confidential.

He said that “there is no standard historically for the formatting, which is why it would be very difficult for many of the old DMFs to simply be converted into the eDMF format, which requires the information to be in CTD format. Most excipient DMFs have been around for years and are not in CTD format and many excipient companies have limited desire to do much work to convert the files since they only sell small amounts into the pharmaceutical industry.”

Excipient manufacturers should decide before May 5, 2017, whether to close or inactivate existing DMFs or convert them to an eDMF in the eCTD format.

From the editors of Gold Sheet.