Last fiscal year, FDA acknowledged nearly half of all notifications for new dietary ingredients (NDIs) in supplements without objecting to the paperwork.
FDA data, which covers the 12-month period that ended on Sept. 30, 2018, demonstrated an improvement in the success rate of notifications to establish the safety of NDIs. Of the agency’s 38 responses to NDI notifications (NDINs) in the fiscal year, FDA acknowledged 17—or 44.7 percent—without an objection, INSIDER discovered through a Freedom of Information Act (FOIA) request.
In the first nine months of the previous fiscal year, FDA objected to 88 percent of NDINs. But as INSIDER reported in 2017, many submissions were made by individuals selling products on Amazon who didn’t have a sophisticated understanding of FDA’s notification requirements—including what qualifies as a dietary ingredient or supplement.
The law generally requires manufacturers and distributors to notify FDA 75 days in advance before marketing an NDI in a supplement. The notices must provide evidence “that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe.”
Industry leaders were pleased to observe an increase in the acknowledgement rate of NDINs without an objection.
“The improvement in the acceptance rate is significant, marked [and] appreciated,” said Michael McGuffin, president of the American Herbal Products Association (AHPA).
FY18 data regarding NDI notifications (NDINs)
NDINs submitted: 45
FDA responses to NDINs 38
Acknowledgement letters w/out objections (AKL) 17 (44.7 percent)
Not dietary ingredient/dietary supplement (NDL) 4 (10.5 percent)
Inadequate safety/identity (IAL) 11 (29 percent)
Incomplete (ICL) 6 (15.8 percent)
Source: FDA via FOIA request
AHPA has tracked NDINs since the first one was submitted in 1997—three years after the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Historically, FDA has objected to the vast majority of notifications due to safety concerns or for other reasons, including failure to submit complete information.
The improvement in FY18 “probably reflects better preparation by submitters because it certainly doesn’t reflect any change in FDA’s view of what constitutes an acceptable notification,” McGuffin said in a phone interview.
FDA officials remain open to meeting with supplement firms before they submit an NDIN. These pre-notification meetings, industry leaders said, improve the odds of getting an acknowledgement letter without an objection, or so-called AKL letter.
“We are very open to the idea of pre-notification meetings when somebody is thinking about whether to submit an NDI notification, or if they’re already planning to submit” one, said Steven Tave, director of FDA’s Office of Dietary Supplement Programs (ODSP), in a phone interview. “It’s a great opportunity to talk with our staff and make sure there’s a common understanding of what we’re expecting in a submission or what we’re looking for, and for us to hear what’s feasible and what’s not necessarily feasible.”
Among the companies that have met with FDA to discuss a new ingredient: Natural Alternatives International Inc. (NAI, NASDAQ: NAII), a formulator, marketer and manufacturer of nutritional supplements.
NAI chief executive officer Mark LeDoux said his company invested more than US$1 million in an NDIN for its patented CarnoSyn beta-alanine ingredient. In February 2019, the company announced receiving an AKL letter from FDA. The AKL letter covered a total daily intake level of up to 6.4 grams per day of its ingredient.
The company developed a “very sophisticated submission that answered all the presumed questions [from FDA] and some we hadn’t even thought of,” said LeDoux, who also is chairman of the boards of directors of NAI and the Natural Products Association (NPA).
Prior to its submission, Carlsbad, California-based NAI had several meetings with FDA and answered questions, although LeDoux reflected the agency had few inquiries since “the documents were so replete with data points.”
NAI’s investment in the notification process “gives all of our customers a great deal of comfort and credibility that we’ve gone the extra mile to make sure that the product we have in commerce is in fact safe,” LeDoux said. FDA essentially recognized the ingredient’s safety, he added, by issuing the AKL letter.
FDA officials and others observed the notification system for NDIs is distinguishable from an approval process, such as when FDA approves a pharmaceutical drug to be marketed for the treatment of certain medical conditions based on evidence establishing its effectiveness and safety.
“Please note that acceptance of this notification for filing is a procedural matter, and thus, does not constitute a finding by FDA that the new dietary ingredient or supplement that contains the new dietary ingredient is safe or is not adulterated under” the law, Robert Durkin, deputy director of ODSP, wrote in the 2019 acknowledgement letter to attorney Kevin Bell of Porzio, Bromberg & Newman P.C., NAI’s outside counsel. “FDA is not precluded from taking action in the future against any dietary supplement containing your new dietary ingredient if it is found to be unsafe, adulterated or misbranded.”
Nonetheless, under DSHEA and FDA regulations, an AKL letter is the best outcome for a company like NAI that invests in the notification process to demonstrate the safety of a new dietary ingredient.
“Not everybody’s got $1 million or more to spend on this process,” acknowledged LeDoux, whose company reported FY18 net income of $5.1 million on net sales of $132.4 million and ended the calendar year with cash of $30.3 million and working capital of $56.5 million. “It’s really up to the companies that are doing the actual work to make a decision as to the sufficiency of their dossier. In our case, we believe more is better than less.”