NDIs and the Burden of ProofNDIs and the Burden of Proof
While DSHEA was designed to balance consumer access to dietary supplements with a relative degree of safety, the new dietary ingredient (NDI) guidance appears to shift both the burden of proof and degree of safety substantiation required.
July 18, 2011
by Steve Mister
Much is made in our judicial system of the burden of proofwho has it and what the weight of that burden is. In criminal cases, the State has the burden of proof: innocent until proven guilty. In libel cases, the celebrity defendant must prove actual malice by the media outlet that defamed him. In contract cases, the plaintiff must prove a contract was breached, but the standard is only a preponderance of the evidence. In other words, a 51-percent likelihood that the defendant did as alleged.
The same legal concept is at the heart of dietary supplement law: who has the burden of proof to demonstrate safety, and how much evidence is enough to satisfy that safety standard? When the Dietary Supplement Health & Education Act (DSHEA) was enacted in 1994, it provided a clear division of responsibility. DSHEA would provide a certain assurance of safety for consumers of dietary supplements, but it was not intended to provide 100-percent certainty of safety. Not even pharmaceuticals that have undergone years of clinical investigation and FDA approval can assure that. (Drug recalls, anyone?) DSHEA purposefully sought to balance consumer access to products with a relative degree of safety. As then-Deputy FDA Commissioner Dr. Joshua Sharfstein pointed out at the Council for Responsible Nutritions (CRN) conference in late 2010, there is an inherent tension between access and safety. He acknowledged that, for the most part, DSHEA seemed to get that balance just right.
For products that were already on the market prior to 1994, the presumption of safety stayed with manufacturers. Thats not to say FDA couldnt remove one of those ingredients from the marketplace; but, to do so, the burden would be on the agency. And if FDA could demonstrate a product carried an unreasonable or significant risk of injury or illness, it could remove that product from the market. FDA did just that with ephedra.
What about new dietary ingredients (NDIs) that would come to market after 1994? Under DSHEA, the burden of proof would lie with the manufacturer or distributor. Manufacturers would be required to submit evidence to FDA before the new ingredient entered the market. Failing to do so, or marketing a new ingredient in the face of FDAs objection, was supposed to cause the product to be adulterated and subject to prosecution. At least, that was what DSHEA envisioned.
But what level of proof would be required? DSHEA answered that question, too, requiring that in an NDI notification, the submitter must demonstrate a reasonable expectation of safety in the new ingredient. In the early 1990s, the industry watched as FDA tried to restrict products such as black currant oil from being sold as supplements by holding them to the safety standard of a food additivea reasonable certainty of safetyclearly a higher burden of proof on the manufacturer. The NDI standard was intended to create a new standard that still required some amount of safety data for review (with the burden on manufacturer, not FDA), but would allocate the burden of proof differently so as to lessen the requirements of proof, and adjust the balance between safety and consumer access. DSHEA was about ensuring consumers would have access to a wide variety of innovative nutrients and natural health products with a reasonable expectation of their safety.
A Changing Burden of Proof?
Fast-forward to 2011 and the just-released draft NDI guidance. The crux of the issue is who should have the burden of proof when it comes to safety of a particular ingredientthe industry or FDA?
Heres the breakdown:
First, the scrimmage line between new dietary ingredients and old ones has been moved, and industry is calling off sides. In the draft guidance, FDA stated the burden of proof should switch from FDA to the manufacturers of even long-time ingredients if the manufacturer changes the method of extraction, concentration or manner of production that changes the chemical composition or structure in any regard. It basically freezes the marketplace in time at October 1994. Any advances in technology of existing ingredients will flip the burden of proof to the other side. Likewise, use of an new dietary ingredient along with an old one will flip the burden of proof to the manufacturer to prove the safety of the old as well as the new ingredient in this new matrix.
In addition, there are apparently other issues that will remove ingredients from consideration altogether. If the ingredient has been the subject of an Investigational New Drug Application (thats an IND, not to be confused with an NDI), that could remove it from being a dietary ingredient completely. Likewise, a synthetic version of a botanical substance cannot be a dietary ingredient either, according to the draft guidance, even if it is nature-identical to a plant material and the commercialization of the plant material is not commercially viable. No amount of safety data will escape that conundrum.
At the same time FDAs new guidance is changing who has the burden of proof of safety, the level of that burden is shifting toosort of like going from a preponderance of the evidence to guilty beyond a shadow of a doubt. The draft NDI guidance lays out what FDA expects from a manufacturer to satisfy this burden to demonstrate a reasonable expectation of safety, setting some pretty daunting standards for providing chronic safe use and even intermittent safe use. After all this time, its starting to look like the agency is trying to impose the food-additive burden of proof on the dietary supplement industry once again. With such high expectations from FDA to issue a no objection letter for an ingredient, one begins to think only the most scrupulous (or masochistic?) manufacturers will go to the trouble to file the NDI notification at all. When you set the bar too high, some folks wont even try to jump it. Thats not an encouraging scenario for an industry whose reputation is already tarnished by companies who dont bother to take on current regulatory burdens.
Surely this is not what Congress intended when it set up the NDI process in DSHEA 17 years ago. The differences between a reasonable expectation and certainty of safety were supposed to mean different burdens of proof for manufacturers. The dividing lines between old and new ingredients were supposed to carve out truly new ingredients for the higher safety substantiation, and ingredients with a history of safety were to get the benefit of the doubt. The rather remarkable safety profile of the dietary supplement industry, now evidenced over the past four years by the mandatory adverse event reporting law, demonstrates a strong safety track record in spite of whatever new concentrations, extractions and production methods have been employed since 1994. Shouldnt that count for something in the allocation of proof?
Finally, the law sets up not one, but three ways for FDA to remove products from the market when the burden of proving safety rests with it. The scales that balance consumer access with consumer safety were pretty even before the NDI guidance came out. Now FDA seems to have tilted them too far in its direction. Maybe its time we put our thumb on the dish to balance them out once again. The burden of proof didnt just change hands, it may have become insurmountable.
Steve Mister is the president and CEO of the Council for Responsible Nutrition (CRN), which is sponsoring a Sept. 14 webinar with VIRGO, FDAs NDI Guidance Document and Its Impact on the Dietary Supplement Industry." For more information or to register, visit NaturalProductsINSIDER.com/Webinars .
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