FDA releases draft guidance on NDI master files

The Food and Drug Administration on April 3 released a draft guidance for the dietary supplement industry on NDI master files. This is the second document published since early March focused on a safety-related notification requirement in the Dietary Supplement Health and Education Act of 1994 (DSHEA).

While not required by statute or regulation, new dietary ingredient notification (NDIN) master files can be used to facilitate the submission of certain information to FDA for its use in evaluating a potential future premarket ingredient notification, FDA explained in a constituent update. These details in a master file may include NDI-related identity, manufacturing and/or safety information.

Release of the draft guidance came in response to the industry’s requests for specific guidance on recommendations about master files for NDINs, according to the constituent update.

“The intent of the guidance, once finalized, will be to help industry comply more easily with the NDIN requirement by providing recommendations on the content, submission and use of master files,” FDA added.

FDA in March released final guidance on NDIN procedures and timeframes. The guidance “provides clarification” on the NDI submission and review processes, Cara Welch, Ph.D., director of FDA’s Office of Dietary Supplement Programs (ODSP), explained in an interview in March. The guidance will “ideally” help notifiers prepare a notification that is “comprehensive” and “well laid-out,” she added.

Related:FDA NDI guidance: Five key takeaways

FDA published the final guidance 30 years after then-President Bill Clinton signed into law DSHEA. Subject to an exemption some critics have described as the GRAS loophole, a manufacturer or distributor must demonstrate a new dietary ingredient (NDI) “will reasonably be expected to be safe” when used under the conditions recommended or suggested in the labeling of the dietary supplement.

Since passage of DSHEA, the supplement market has grown from roughly 4,000 products in 1994 to over 100,000 products today, according to FDA estimates. But outside regulatory experts — and FDA — suspect that many novel ingredients subject to the notification requirement circumvent the agency's review. FDA typically responds to fewer than 50 notifications a year.

FDA is expected to release additional final NDI guidance documents, as part of its efforts to break up final guidance into smaller, more manageable documents than a 102-page draft guidance published in 2016.

Industry reaction to master files guidance

Steve Mister, president and CEO of the Council for Responsible Nutrition, described as a "positive development" FDA's release of the draft guidance on NDI master files.

Related:Most NDI notifications to FDA receive good day letter in FY23

"In 2020, CRN developed an NDI master file framework for dietary supplements to protect our members' investments and intellectual property, and this is clearly a step in the right direction, incorporating many of the elements we put forward," Mister said in an emailed statement.

"But as we have previously stated, meaningful enforcement alongside guidance is crucial in supporting responsible companies desiring to innovate, to protect investment while doing so, and to fairly compete," he added. "FDA must deter bad actors who circumvent the law thereby posing risk to public safety. So, while we welcome this draft guidance, we, at the same time, strongly urge FDA to publicly announce its resolve to enforce the proper use of master files." 

The Consumer Healthcare Products Association (CHPA) also welcomed FDA’s NDI master files guidance.

 “We have been a longtime supporter of a master file system for NDINs that will establish a framework to safeguard scientific data supporting an NDIN on a specific ingredient, preventing its unauthorized use by firms marketing similar, but not identical, ingredients,” CHPA’s SVP of Dietary Supplements Duffy MacKay said in a statement. “A well implemented master file system has the potential to benefit both industry and FDA by increasing submissions, enhancing public safety, and spurring product innovation and investments in science. Overall, this system should encourage companies to increase investments in research that demonstrate the safety of new ingredients and finished products."

Related:FDA ‘can’t promise special enforcement preferences’ for NDI master files

Like Mister, MacKay also underscored the importance of FDA enforcement.

“CHPA is currently reviewing the draft guidance in detail, but is generally pleased with the concept, while also recognizing FDA enforcement of the NDI regulation is critical for the master file system to realize its full potential,” he said. “We appreciate FDA's ongoing efforts to advance this guidance, which will foster innovation and scientific development.”