Without enforcement, a master files guidance would be wasted effort, CRN says

The Food and Drug Administration’s plan to issue a master files guidance for new ingredients is misguided if the agency doesn’t plan to enforce it, the Council for Responsible Nutrition (CRN) has stated. CRN believes other priorities should come first.

CRN made its position public via a letter addressed to Cara Welch, Ph.D., the head of FDA’s Office of Dietary Supplement Programs (ODSP). The letter was delivered last week.

In July, FDA released an update of priority guidance topics for the foods program to complete during 2023. The updated list included draft guidance on dietary supplement master files.

Many ingredients on market without having gone through NDI process

Over the years, various current and former FDA officials have observed that only a fraction of new ingredients on the dietary supplement market have complied with the new dietary ingredient notification (NDI) requirement. This topic was the subject of a four-part series of articles published in 2020 by Natural Products Insider and republished this month in a 49-page regulatory report.

Other novel ingredients may claim to have self-affirmed GRAS (generally recognized as safe) status, while still others seem to have neither, yet have been marketed to consumers.

Disincentives for filing NDI Notifications

Related:FDA proposes new office combining ‘food chemical safety’ with ‘supplements’

Industry stakeholders have noted significant disincentives to filing NDI notifications. These include a lack of clarity about what exact information FDA is looking for in terms of safety.  Also unclear is whether the use of new manufacturing methods might mean an ingredient has become different enough from its progenitor that a new evaluation of safety is required.

Another big sticking point is how, and whether, companies can protect trade secrets regarding their manufacturing and other considerations.

A host of nutritional ingredients in the U.S. market purport to resemble NDIs that FDA has reviewed and acknowledged without objections, but these so-called me-too ingredients have not filed notifications with FDA.

Would FDA guidance fix the issue?

An FDA master files guidance could perhaps improve the situation. The basic idea is companies that file an NDI notification with FDA could grant licenses to others to use the same novel ingredient while protecting against the disclosure of proprietary information.

Under the concept, for example, an ingredient company would submit to FDA an NDI master file containing proprietary data; other ingredient suppliers or finished-product brands with authorization to use the same ingredient could reference the master file.

“Adding a master file component to the NDI notification process could protect the intellectual property of NDI manufacturers and facilitate the supplement industry and FDA in fulfilling NDI-related goals and, ultimately, promote consumer access to safe dietary supplements,” Haiuyen Nguyen, CRN’s vice president of regulatory and nutrition policy, wrote in a 2020 article published by Regulatory Focus, a publication of the Regulatory Affairs Professionals Society (RAPS).

Now, there is no way to tell if me-too ingredients are truly equivalent to those that have gone through the NDI notification process. Since that process is focused exclusively on safety, that’s a big gap in the regulatory picture, Steve Mister, president and CEO of CRN, told Natural Products Insider.

Mister said there is no way to know if those me-too ingredients meet the same level of safety as the NDIs they are copying.

CRN: guidance unlikely to be effective sans enforcement

However, in the past, FDA has viewed this issue as a commercial dispute akin to patent infringement, and thus not within the purview of a federal regulatory agency. If that continues to be the case, Mister said, the new guidance would be just so much hot air.

“It is just baffling to us why FDA will be moving ahead on master files when they sat down three years ago with us and said they will not put any enforcement around master files,” Mister said.

Mister was alluding to a master files framework that CRN, along with the Consumer Healthcare Products Association and the United Natural Products Alliance, submitted to FDA in May 2020. 

In the letter to Welch, CRN laid out the conditions under which a new master files provision could improve safety for consumers. That would hinge on an enforcement approach that goes beyond the mere issuance of warning letters.

“NDI master files can only succeed when FDA commits to rigorous enforcement of its use,” the letter states. “This means FDA must be willing to allocate resources to identifying and prosecuting bad actors who ignore their obligation under the law to submit their own NDI notification and instead claim that their ingredient is identical to the innovator company’s ingredient. Effective deterrence requires FDA to prosecute some of these offenders to establish that a negative consequence may result from flouting the requirements.”

“Without meaningful enforcement, FDA guidance on master files does little to support responsible companies desiring to innovate, to protect investment while doing so, and to fairly compete; and bad actors will continue to circumvent the law thereby posing risk to public safety,” CRN concluded in the letter.

Mister said other priorities should come first. Chief among those would be specifying the standard of safety for an NDI. In the view of CRN and other stakeholders, those goalposts have moved over the more than 20 years of the NDI process.

Keeping priorities straight

It’s especially important, Mister said, to keep priorities straight during this time of regulatory uncertainty. Even though FDA Commissioner Robert Calif, M.D., assured the industry that dietary supplements won’t diminish in importance despite a proposed reorganization of its foods programs, CRN doesn’t agree. FDA has proposed creating an Office of Food Chemical Safety, Dietary Supplements and Innovation (OFCSDSI) as part of its broader plans to transform its myriad food programs into a unified Human Foods Program.

“This reorganization, despite what FDA has said, will definitely mean even more deprioritization of dietary supplement issues,” Mister said.

FDA did not immediately respond to a request for comment.