For the second year in a row, FDA acknowledged without objection nearly half of new dietary ingredient notifications (NDINs). The pre-market notifications are a fundamental requirement in the Dietary Supplement Health and Education Act of 1994 (DSHEA) aimed to ensure new ingredients are reasonably expected to be safe.
Current and former FDA officials were wary to suggest the data foreshadows a long-term trend in an industry that has grown tremendously over the last quarter century. But the acknowledgement rate in recent years marks an improvement over the historical average.
In FY19, FDA’s Office of Dietary Supplement Programs (ODSP) acknowledged 19 of 40 NDINs, or about 48% of notifications, Natural Products Insider learned through a Freedom of Information Act request.
FDA will object to an ingredient notification due to safety concerns, because the submission is incomplete, or because the substance either does not qualify as a dietary ingredient or it is excluded from being marketed in a supplement since it was first studied as a drug. CBD, the hemp-based compound that has flourished in the U.S., falls under the latter category, according to FDA.
Five years ago, people felt “filing an NDI was turning yourself in to FDA,” said Kevin Bell, a partner and practice leader of the patent and dietary supplement practices with Arnall Golden Gregory LLP (AGG), a law firm with nearly 200 attorneys in Atlanta and the nation’s capital.
Bell cited concerns from industry that a rejection letter from FDA would jeopardize a company’s ability to sell a product or ingredient.
Asked about recent trends in the acknowledgement rate, ODSP Director Steven Tave cautioned the sample size is fairly small. FDA has received about 1,200 NDINs since DSHEA was signed into law, Tave said.
FDA has estimated the market contains between 50,000 and 80,000 dietary supplements, leaving some industry insiders and outsiders to question whether more NDINs should have been filed with the agency.
FDA’s goal is neither to acknowledge nor object to as many notifications as possible, Tave said. Rather, the agency wants to “conduct a meaningful, substantive review of as many notifications as we get,” he said.
Tave explained FDA would like to reduce the number of notifications that are incomplete or don’t qualify as a dietary ingredient so the agency can focus on a safety evaluation as the law intended.
A collaborative process
ODSP has emphasized to notifiers in recent years that the process is collaborative rather than adversarial, current and former FDA officials said in interviews. Pre-notification meetings have played an integral role in that process, they said.
“This is not meant to be a mystery,” Tave said. FDA wants to ensure “there’s transparency and expectations about what we’re looking for and what they should be submitting.”
The onus is on the notifier to present FDA the safety documentation, Tave said, but he emphasized the process is not an “adversarial” one “in any sense.”
“We’re not out looking to use technicalities as a weapon,” he stated. “We are here to engage in a collaborative process with responsible industry to help ensure that we all pursue the goal of consumer safety.”
“Hopefully, we’re in a constant state of improvement,” Tave added.
Following the 2016 publication of FDA’s second draft NDI guidance, the agency “made a concerted effort to be more available and open to communications with stakeholders about the NDIN process,” said Robert Durkin, ODSP’s former deputy director who is of counsel in the FDA and health care practices with AGG. “We started to have a lot more pre-NDI meetings.”
Added Durkin, who was responsible for signing FDA’s NDIN response letters: “If we got 50 days into a review, and realized there was something missing or something that wasn’t quite right, we had established relationships with the notifiers where we could reach out and have a conversation with them, share with them what we found and give them a chance to make an amendment to the notification if it was something that could be saved.”
FDA’s NDI review team simply “wants to protect the public health,” the lawyer said. “They don’t want to prevent someone from bringing a safe, legitimate product to commerce.”
FY19 FDA responses to NDI notifications
Acknowledgement letters without objections (AKL) 19 (47.5%)
Not dietary ingredient/dietary supplement (NDL) 9 (22.5%)
Inadequate safety/identity (IAL) 4 (10%)
Incomplete (ICL) 8 (20%)
Source: FDA via Natural Products Insider Freedom of Information Act request
Tave said ODSP will meet with a company throughout the NDIN process, including after they have submitted a notification and received an objection.
“The thing that we can’t control is the safety data,” the FDA official remarked. “An ingredient is going to inherently have a reasonable expectation of safety or not. And if there’s an ingredient that can safety be marketed … to consumers, we don’t want to stand in the way of that. But at the same time, there’s no amount of dialogue that’s going to get an unsafe product to a place where we’re not going to object.”
Some companies will resubmit their notification and may ultimately receive an acknowledgment following a second or third attempt, Tave said. Other firms that have received an objection “come back in without any real meaningful changes,” he added.
Since the NDIN requirement is a notification rather than an approval process, it’s possible some firms that receive an objection letter from FDA still go to market with their new ingredient.
If FDA objects to an NDIN, a company certainly has a right to reach out to the agency for further dialogue, said Daniel Fabricant, Ph.D., previously director of FDA’s then-Division of Dietary Supplement Programs.
“Once somebody doesn’t do that, I think it kind of speaks volumes,” said Fabricant, president and CEO of the Natural Products Association (NPA). “Doing [toxicology] on a new ingredient is going to you cost between $350,000 and $500,000.”
Fabricant questioned why a company that has invested a hefty sum on such safety work and received an objection wouldn’t go back to the agency and provide additional documentation.
Not ‘hall pass’
While an acknowledgement or so-called good day letter is the best outcome for a supplement company, it doesn’t mean FDA considers the NDI or supplement “safe,” or that FDA is barred from acting against a supplement if it’s found to be unsafe.
As FDA states in its response letters, the agency could take action against a supplement containing an NDI if it’s found to be adulterated, unsafe or misbranded, Tave said. FDA’s response letters also describe acceptance of a notification as a “procedural matter.”
“An acknowledgement is not a hall pass for all future behavior,” Tave explained.