New Dietary Ingredients: Will FDA protect consumers from pirates and piggybackers?
A “new dietary ingredient,” defined in the Dietary Supplement Health & Education Act (DSHEA), means a dietary ingredient that was not marketed in the United States before October 15, 1994, when DHSEA was enacted. We’ve been waiting so long for FDA to fully implement this provision that perhaps, for the sake of accuracy, we should just be calling them “post-DSHEA dietary ingredients” rather than “new.” Twenty-six years is a long time.
The NDI requirements established by DSHEA were intended to give consequence to the dividing line between grandfathered ingredients and ones introduced after the passage of the law. Dietary ingredients already on the market received a presumption of safety, but ingredients introduced after the law’s enactment would have to demonstrate they are reasonably expected to be safe.
DSHEA commands that a supplement containing a new dietary ingredient is adulterated unless it was already in the food supply in a form that has not been chemically altered or there is a history of use or other evidence that the ingredient, if used as recommended or suggested in the labeling, will reasonably be expected to be safe. The law further provides that the manufacturer or distributor provide FDA with the basis for concluding that the dietary ingredient will reasonably be expected to be safe in the form of an NDI notification. (21 USC 350b)
Moreover, DSHEA declared that a supplement is adulterated if it contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury. (21 USC 342(f)(1)(B)) It commands that introducing a dietary supplement into interstate commerce that is unsafe under the NDI provisions of the law is an expressly prohibited act. Public safety seems intrinsically intertwined with the new dietary ingredient requirements.
Over time, FDA has repeatedly touted the notification requirement associated with the NDI provision as “FDA's only opportunity to evaluate the safety of a new dietary ingredient before it becomes available to consumers.” The agency has lamented the paucity of NDI notifications it has received over the past 26 years as evidence that consumers may be at risk from un-notified and therefore, potentially unsafe, ingredients.
But FDA seems reluctant to enforce the law against products that ignore the NDI notification requirement—enforcement that would create deterrence and provide incentives for companies to file these notifications.
Enforcement of the NDI requirements is likewise the lynchpin of the master file system that FDA proposed in its 2016 draft guidance on NDIs. Master files would allow the filer of an NDI notification to protect its safety dossier and license it to its customers while assuring that competitors marketing their own versions of that ingredient would have to develop their own assurance of safety for the ingredient.
Since then, industry has embraced the concept of master files, not only for the protection of public health, but also for the additional benefit that it rewards the research investment of innovative ingredient developers. Master files would deter pirates who steal that intellectual property, fail to file their own notifications, and undersell the innovator because they don’t have to recover the costs of innovation.
Earlier this spring, CRN, along with three other trade associations, presented FDA with a detailed framework for how master files could be implemented. It requires the agency to police NDI notifications, and as DSHEA envisioned, ingredients marketed by piggybackers who fail to file their own notification would be deemed adulterated.
Since 2016, FDA has been silent on this issue. While lamenting the relatively few notifications filed by industry, the agency has not initiated a single enforcement action, not imposed a single import alert, nor recalled a single supplement for lack of an NDI notification. And the industry should worry that lack of action by the FDA signals that the master file concept, along with enforcement of NDIs, is not a priority at the agency.
The problem is that FDA may well view the development of master files, the pirating of ingredients, problem of piggybacking, and the calls for enforcement of NDI requirements as amounting to enlisting FDA to help protect a supplement manufacturers’ intellectual property. Industry’s enthusiasm that master files could provide incentives for research investment in supplements may be dissuading FDA from the public safety aspects. Adjudicating competitive disputes is not something FDA has ever considered high among its priorities, and certainly not for dietary supplements. FDA’s mission after all is to protect and promote public health, not to assist companies in their competitive battles.
But this ignores that NDI master files are a matter of public health as much as are FDA’s concerns about cannabidiol. Failure to file NDI notifications for new dietary ingredients creates public health gambles for consumers. When a competitor claims to be selling the same ingredient captured in an NDI notification, how does FDA know it is the same ingredient? How does FDA know it is concentrating the same constituents or properly identifying the requisite plant parts? That it is using the same solvents and extraction agents and properly removing them during production? That harmful contaminants have been eliminated? It doesn’t. As FDA has repeatedly noted, the NDI notification is FDA’s only opportunity to review the safety of new dietary ingredients.
The law leaves no doubt that Congress considered NDIs a matter of public health, not economic protectionism. NDI notifications and master files represent a method to give consumers an assurance of safety in these ingredients. It’s time FDA take the safety issues involved with NDIs as seriously as it does the safety issues it raises for CBD.
So while consumers wait for the arrival of CBD supplements, bogged down by FDA’s high requirements for safety, the industry also waits for enforcement of NDIs and a similar dedication to protecting consumers of products already on the market. NDI’s won’t work without enforcement.