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NDI Draft Guidance Chance to Prove Critics Wrong

NDI Draft Guidance Chance to Prove Critics Wrong

<p>The NDI draft guidance provides industry and FDA the opportunity to hit &#8220;reset," and make the NDI notification system truly work to deliver safe, efficacious new products to consumers.</p>

After more than five years of waiting, the new new dietary ingredient (NDI) draft guidance is out.

Is it everything the industry could have wanted? Of course not, but we didn’t expect that. What we got is a substantially revised document that the dietary supplement industry should be able to live with. We need to embrace it, provide meaningful comments to FDA on the remaining issues of contention, and finally get down to the business of demonstrating to FDA—and to consumers—that NDIs are reasonably expected to be safe.

For the past 22 years, dietary supplements have lived under the myth that dietary supplements are not subject to premarket review, that NDIs just appear on the market, and that the law requires nothing more than a wink and a promise that supplements are harmless. It’s a myth the critics have perpetuated.

Of course, that’s not what the Dietary Supplement Health & Education Act of 1994 (DSHEA) permits at all. From the start, the law recognized two kinds of ingredients: “grandfathered ingredients" and NDIs. Grandfathered ingredients (those that were already on the market prior to October 1994 and for which the market already had evidence of their safety by virtue of actual use) now enjoy an additional 22 years of demonstrated post-marketplace safety, thanks most recently to the extra surveillance tools that the mandatory adverse event reporting (AER) law imposed in 2008. The law required then, as it does now, that companies must notify FDA of any NDIs (anything introduced in the food supply after 1994) at least 75 days before the ingredients  appear on the market, and that manufacturers must demonstrate that the new ingredients, as well as the finished products in which they appear, are reasonably expected to be safe.

The statute was explicit: failure to file an NDI notification is grounds for making a supplement containing an NDI adulterated as an administrative matter and subject to recall, seizure and prosecution. To be candid about the law, it does contemplate that a marketer might disagree with FDA about how much evidence creates a reasonable expectation of safety, and, having filed the notification, the company could continue to market over the FDA’s objection. In that situation, the burden falls on FDA to challenge the ingredient and argue in court that the notification it received was inadequate to be considered “reasonably safe." But DSHEA absolutely requires that FDA be given notice and opportunity to review the marketer’s safety data, and to make its own determination.

This was a grand compromise that carefully balanced FDA’s mandate to protect public health and safety with industry’s need to innovate. Without the promises of exclusivity and patent protection afforded to new chemical entities (i.e., drugs), manufacturers of naturally occurring dietary ingredients could hardly afford multi-million dollar clinical trials. NDIs that are vitamins, minerals, herbs, amino acids and similar substances that already occur to some degree in the human diet shouldn’t necessitate that level of scrutiny. The NDI provision of DSHEA was a reasonable middle ground.

The problem has been that neither FDA nor the industry has fully honored this provision. For years, FDA largely ignored the NDI notification requirement, rejecting a great many of the notifications it received, but rarely calling out manufacturers that failed to file the notification for a new ingredient. Prior to 2012, FDA had issued only a handful of warning letters companies for failing to file an NDI notification—and those were for androstenedione. Since then, FDA has accelerated its attention to “unnoticed" NDIs, issuing at least 45 warning letters for NDIs without a notification for ingredients such as aegeline, DMAA (1,3-dimethylamylamine), BMPEA (&#946;-methylphenethylamine )and Acacia rigidula.

For its part, the industry has been less than diligent about its obligations under the law, too. FDA grossly mischaracterizes the matter when it contrasts the more than 5,560 new products each year with the approximately 750 NDI notifications it has received since 1994—many of these new products are simply new combinations of grandfathered ingredients, new delivery forms of old ingredients (e.g., gelcaps, chewables, gummies and drink mixes), and others are new brands entering the market with the same ingredients. Additionally, until this new draft guidance was released, many firms interpreted the law to require notification only of the new ingredient, not each unique finished product containing the NDI. But putting the extent of the disparity aside, one must acknowledge that over the past 22 years, numerous new ingredients have appeared without the requisite notification to FDA that is arguably required.

This new draft guidance offers the opportunity to push “reset." While industry will certainly disagree about some of the specifics, the new draft guidance provides the clearest articulation to date of how the agency interprets the requirements of the law and what it expects should be included in a notification. It reflects real progress in the conversation between industry and its regulators over such issues as the standard for a “reasonable expectation" of safety (more flexible than the previous version) and the ability of an ingredient manufacturer to establish a master file that eases the notification burdens for its customers and opens new opportunities to protect its investments in science. Even where the guidance doesn’t deliver completely satisfying answers, industry should remember it is only a guidance—the “current thinking" of the agency on the topic—not a regulation that impedes further evolution of FDA’s position.

The new guidance provides a chance for industry to finally make the NDI provision of DSHEA work. The law recognized when it was enacted that new ingredients may present new risks to consumers and should undergo the appropriate safety evaluation. Even without imposing the burdensome pre-market approval system for pharmaceuticals, FDA was indisputably charged with protecting consumers from new and untested ingredients.

Consumers of dietary supplements expect as much today. If industry and FDA actually commit to implement the NDI requirements espoused in this new draft guidance, it will unequivocally demonstrate that FDA does review the safety of dietary supplements containing new ingredients before they go to market. That honors the aspirations of DSHEA’s founders and engenders confidence among consumers. It’s a moment to reset that we shouldn’t miss.

Steve Mister is the president/CEO of the Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement and functional food industry.

Looking for more insight about the draft guidance and what’s next? CRN and INSIDER are offering a webinar, Navigating FDA's 2016 NDI Draft Guidance: Expert Overview & Analysis, on Wednesday, Sept. 7, at 2pm EDT. CRN’s Duffy MacKay, N.D., will moderate the event with speakers including FDA’s Cara Welch, Ph.D.; Miriam J. Guggenheim, J.D., Covington & Burling LLP; and Ricardo Carvajal, J.D., M.S., Hyman, Phelps & McNamara, P.C.

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