FDA has published a draft guidance on new dietary ingredients notification master files

The U.S. Food and Drug Administration (FDA) published a draft guidance on the submission of new dietary ingredient notification (NDIN) master files. The master file concept helps ease the burden of submitting multiple NDINs containing the same ingredient. For example, an ingredient manufacturer can create a master file for its ingredient and authorize its clients to refer to the master file in their own NDIN.

Industry stakeholders have advocated for the master file system for years. In 2020, the Council for Responsible Nutrition (CRN; Washington, D.C.), Consumer Healthcare Products Association (CHPA; Washington, D.C.), and the United Natural Products Alliance (UNPA; Salt Lake City, UT) submitted to FDA a proposed framework for a master file system. This proposed framework was proposed framework is modelled after the U.S. Drug Master File.

The publication of this guidance is a positive step, and offers some more clarity on the NDIN process following the publication of FDA’s first final guidance on NDIN. That guidance failed to address many of the outstanding questions regarding the NDIN process, one of which was whether or not a master file system would be implemented. Of course, industry still emphasizes the need for FDA to enforce NDIs. Enforcement would help to prevent companies from unlawfully piggybacking on others’ NDINs, and encourage companies to comply with submitting NDINs without fear of compromising trade secrets or intellectual property, or wasting the money required to successfully submit a NDIN.

"It's a positive development to see the FDA moving ahead with this draft guidance. 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,” said Steve Mister, president and CEO of CRN, in a 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. 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 So, while we welcome this draft guidance, we, at the same time, strongly urge FDA to publicly announce its resolve to enforce the proper use of master files."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 issue still remains that any of this without enforcement is sort of a moot point,” says Daniel Fabricant, PhD, president and CEO of the Natural Products Association (NPA; Washington, D.C.). He points to a letter received by the Natural Alternatives International (NAI) in response to its request that FDA take enforcement action against generic beta-alanine products being imported into the country without having submitted NDINs. FDA’s Cara Welch, PhD, director of FDA’s Office of Dietary Supplement Programs in the Center for Food Safety and Applied Nutrition basically said in that letter that FDA did not have evidence that beta-alanine even required a NDIN, nor was there evidence that these generic products posed a risk to public safety. In that case, NAI’s NDIN and a master file on its beta-alanine does not confer much benefit to them or their clients while other beta-alanine manufacturers continue to operate without a NDIN. FDA has not even established a comprehensive list of ingredients exempt from NDIN to inform any enforcement efforts.

CHPA’s senior vice president of dietary supplements, Duffy MacKay offered a more positive view of the 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,” said MacKay, 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.”

He added that CHPA is still reviewing the guidance in detail, and echoed his peers in emphasizing the importance of enforcement of NDI regulation “for the master file system to realize its full potential.”