Industry offers reaction to the FDA NDI draft guidance, NDIN experiences and suggestions for proceeding until a finalized version is put forth.

Since the 1994 passing of the Dietary Supplement Health and Education Act (DSHEA), the industry has had limited guidance on the statute requiring the submission of new dietary ingredient notifications (NDINs) to the U.S. Food and Drug Administration (FDA); direction regarding the data required to be included in a successful notification as well as the determination of when a dietary ingredient might be new or old was not always straight forward and questions hung over the industry as it sought to bring innovative products to market.

So the issuance of the FDA’s NDI draft guidance in July of last year was, to some degree, welcomed by those seeking direction and definitive answers. However, what the FDA put forth not only left those questions unanswered, but created a rash of concerns, leaving the industry reeling at how far the Agency missed the mark.

“Everyone anticipated a guidance.Some within the industry asked for it with the hope it would help companies understand how to file NDINs and what information was required,” said Kevin Boot, legal and regulatory counsel for Iowa-based Embria Health Sciences, LLC, which had successfully completed an NDI for its EpiCor® immune health ingredient prior to the draft guidance being issued. “Unfortunately, the draft guidance went well beyond what was needed for just filing an NDI.” 

The Council for Responsible Nutrition (CRN) has been actively engaged with the FDA before the draft guidance was Released, and through to today, where it shares its members’ disappointment.

“We called on FDA to issue a guidance document so that the industry would have more clarity and transparency with regard to the agency’s interpretation of the statute and how it evaluates NDINs. We were hopeful to get a guidance that aided companies who file NDINs to improve their understanding of the process,” said Steve Mister, CRN president and CEO, noting that the association put together a task group of regulatory executives in its companies to develop the major themes for comments and to review successive drafts of the issues. The group met numerous times even before the guidance was released to anticipate what might be included. “But the draft guidance the agency issued last July is not the guidance we were looking for.It misinterprets the law and sets unrealistic hurdles for ingredient suppliers.That’s why we have called on FDA to withdraw the document and start over.”

Concerns 

While the industry submitted comprehensive comments, Paul Dijkstra, CEO of California-based InterHealth Nutraceuticals, boiled it down to three main sticking points.

“First, [FDA] should grandfather ingredients that were in the food supply prior to DSHEA’s enactment. Second, NDI should be required for ‘new’ ingredients, not for finished products. Third, safety requirements specified in the guidelines are too stringent and safety requirements should be based on reasonable safety evaluation of the dietary supplement ingredient,” he said, noting that InterHealth has an FDA-notified and published NDI for its UC-II® ingredient that supports joint comfort, mobility and flexibility. “As a research-based ingredient supplier dedicated to making people’s lives healthier, InterHealth shares a similar vision of our advocacy groups. We supported the trade organiZations to assist them in their efforts to engage in politics and policy.” 

One company that played a key role in CRN developing its comments was Florida-based Burdock Group, a full service food safety and regulatory compliance consulting firm offering customized solutions for FDA compliance needs. George Burdock, the company’s president, was likewise disappointed with what the FDA put forth, and offered strong criticism of the Agency.

“The proposed guidelines were gross overkill and an obvious attempt to pass the buck to the Office of Food Additive Safety, with the suggestion that a supplement might be determined GRAS before it is a supplement. This suggestion indicates that ONPLDS (Office of Nutritional Products Labeling and Dietary Supplements) has failed to Come to terms with the fact that although the safety standard is no different for GRAS and a supplement ingredient (i.e., one product cannot be more ‘safe’ than another), it is the ‘quantity and quality’ of supporting evidence of safety that is different between a food ingredient and a dietary supplement ingredient. There is a distinction and a difference,” he said.

“As a first draft, it’s expected that the document contain mistakes and shortcomings.However, it seems the FDA took this opportunity to add more regulation that goes beyond the original intent of DSHEA,” said Embria’s Boot.
“It’s as if the FDA considers the NDIN Notification akin to an approval process rather than what DSHEA described as being simply a notice requirement.Embria hopes the FDA will take the comments submitted into consideration and revise its guidance into a final format that puts consumer safety ahead of bureaucracy, follows DSHEA and is not an undue burden to the industry.”

One of the burdens highlighted in the industry’s comments is the timeframe estimation to generate data to meet the requirements of an NDIN. While the FDA suggested 20 hours would be all that time required, CRN members argued that 100 to 350 hours would be necessary to complete the process.Having extensive experience with the NDIN process, including securing a voluntary NDIN after the draft guidance was issued for Aker BioMarine Antarctic’s SuperbaTM Krill Oil, Melody Harwood, director of regulatory affairs for the Oslo, Norway-based company, explained how CRN’s estimate was Much more realistic.

“Unless a company had already compiled a master file of data for a similar submission in another jurisdiction, the timeframe of 20 hours suggested by the FDA would definitely be much shorter than the time that would actually be required to prepare a successful NDIN,” she said. “Having worked for 10 years as a scientific and regulatory consultant prior to joining Aker BioMarine, I was involved with the strategies for and submission of various NDIN and can confirm that, on average, the time spent from start to finish in preparing the data sufficient for a successful notification well exceeds 20 hours and more realistically approaches at least 50 hours for a straightforward notification, and to more than 100 hours for an NDI that may have complex properties/study results that merit significant detail and explanation.This timeframe is not withstanding any additional studies that may be determined to be required to meet the requirements of an NDIN (e.g., stability, pre-clinical or clinical data).”

In addition, Harwood noted that the scientific data requirements as stipulated in the draft guidance have understandably put the industry on edge.

“In outlining the scientific data requirements, there now appears to be a much more cumbersome process placed on companies selling NDIs into the U.S. dietary supplement industry,” she said. “However, in context, no legislative amendment has taken place and none of the requirements outlined in the draft guidance document are new to the NDIN requirements, as the safety of NDI has always been the focus of the notification process. Admittedly, some of the wording in the draft guidance is contrary to how the industry views the legislative requirements for an NDIN and hence, now is the time to provide suggested revisions to FDA so that a final guidance can be prepared that is satisfactory to all.”

Innovation & Regulation 

A significant concern expressed by many about the draft guidance is the wording and how it relates to finished products. Bob Green, president of New Jersey-based Nutratech, Inc., maker of the thermogenic weight-loss ingredient AdvantraZ®, sees the draft guidance as a method for potentially eliminating or restricting sales of certain dietary supplements, “particularly natural herbs and botanicals.”

“As drafted, the guidelines appear to lean toward product regulation rather than ingredient regulation, placing the burden on finished goods manufacturers to submit NDINs on every finished product,” he said. “Under these conditions, it seems that manufacturers will have to push this responsibility down to ingredient suppliers and require them to supply evidence of marketing prior to October 1994, or provide the necessary safety and toxicity data in their Standardized Information on Dietary Ingredients (SIDI) forms time and time again—requiring an inordinate number of resources from the manufacturer as well as the FDA.”

Nutratech has not had to submit an NDIN as its ingredients were marketed prior to October 1994. Yet, Green expressed that the company is actively preparing its operations to handle the onslaught of technical support needed from customers should the NDI guidance Document go through.

“The FDA must consider the cost versus reward for full compliance. Will NDI guidance truly make consumers any safer? I don’t think so. Our industry already has an excellent safety record,” Green added. “I’m very afraid that, as currently written, the NDI guidance will simply be too unwieldy to manage and enforce— and cost our industry in terms of resources (people, time and money) and eventually consumers in terms of higher supplement prices and less innovation.”

Burdock agreed that innovation is indeed at stake, and his observations reinforce the repercussions if the industry allows itself to be hamstringed.

“Work on dietary supplement ingredients has not become totally static, but a slow-down is palpable,” he said, noting that the companies he works with are focusing on long-term strategies for product development in the U.S. and E. U. rather than the hands-on work of testing products. “Responsible companies are sitting out this inning to see what happens, but they will eventually have to re-enter the market and will do what they have to do to stay in compliance.
In the meantime, the bottom feeders, who never pay much attention to the regulations anyway, will have the market for new products all to themselves.
The market will be flooded with dangerous snake oil that, at best, will defraud the public and, at worst, endanger the public with unsafe products. History will show that the [FDA’s] effort to ‘clean up’ the market will have backfired with tragic proportions.” 

CRN has been promoting that its member companies proceed responsibly while not allowing innovation to wither, according to Mister.

“We’ve encouraged companies to innovate, but to also continue to notify the agency. FDA can enforce the law with or without a guidance document, and the requirements for NDIs are clear from reading DSHEA,” he said. “We have also met with FDA to try to build a dialogue with the agency and to share with FDA our point of view so that creativity is not stifled while we wait for a response.”

Research Leads the Way 

Embria successfully completed its EpiCor NDIN less than four months before the draft guidance was issued.As such, the company understood that the actual notification process was thorough and fair, which isn’t obvious from reading only the draft guidance, according to Boot. But he expressed confidence that the outcome would have been the same regardless of the timing because of Embria’s focus.

“If the draft guidance had come out before the EpiCor notification was received, we don’t believe it would have affected the application because safety and related information went above and beyond the FDA’s needs and, therefore, nothing in the notification Would have changed,” said Boot.

“The successful NDIN for EpiCor put Embria’s flagship product in a very good position for supplement manufacturers.They understand that formulating with EpiCor is safe and free of the regulatory uncertainties facing a lot of other ingredients. And our clinical work provides the same trust and confidence that EpiCor is efficacious.”

Even though Nutratech’s AdvantraZ ingredient did not require an NDIN, concedes the value for companies in attaining one, but argues the draft guidance’s true necessity.

“A successful NDIN should be an assurance of quality, safety and efficacy.But here’s the rub: most reputable companies in our industry already cover these bases,” he said. “With AdvantraZ, we have always have been transparent in sharing supporting research, as well as quality and safety protocols. That’s why this ingredient has endured and grown over the past 15 years.

“But for manufacturers (and ultimately end-consumers), the NDI guidance— as currently drafted—will mean a loss of innovation and higher supplement costs,” Green added. “The time and money to bring new products to market—or simply to reformulate and improve existing supplements—will be prohibitive for many companies.Innovation is the lifeblood of any industry, especially ours. So there’s a significant potential downside.”

What’s Next?

The consensus is that a finalized version of the NDI guidance is not in the industry’s near future, but that action is indeed required—whether it’s pushing to innovate the products and ingredients that will drive the industry forward, or continuing to work with the FDA to ensure an end is in sight.

“Assuming a ‘wait-and-see’ posture is not a viable option and, in fact, invites disaster,” said Burdock. “If the industry is not proactive, the temptation by FDA to do nothing (and let the guidelines stand) will be very strong … [The industry] needs to keep up the pressure to get guidelines that more reasonable, realistic and reflective of the spirit of the law.”

“We’ll continue to educate the industry about the implications of the NDI guidance and, at the same time, we will keep advocating on [its] behalf to ask the Agency to make appropriate revisions,” said CRN’s Mister. “We are keeping members of Congress apprised of the situation with the goal of keeping Congressional attention and pressure on FDA to resolve this matter, and we also are working internally to develop constructive suggestions for the Agency as to what the guidance should look like.

“Industry needs to understand that the NDI requirement is part of the statute, which was not created by FDA,” he added. “We are encouraging companies to act accordingly and to continue to submit notifications for any legitimate NDIs, and to stand behind the safety of their products.”

Visit www.niemagazine.com to learn about a bill put forth by the National Health Federation in defense of the industry and consumers’ rights to innovative health products.