Last fiscal year, FDA dietary supplement officials objected to nearly 70 percent of pre-market notifications for new dietary ingredients (NDIs) because the submissions were either incomplete or did not qualify as a dietary ingredient.
Of its 101 responses to new dietary ingredient notifications (NDINs), FDA’s Office of Dietary Supplement Programs (ODSP) acknowledged just 13 percent without an objection.
FDA officials have emphasized the ingredient notification requirement reflects its only premarket opportunity to examine the safety of dietary supplements before they reach consumers.
Often, the agency finds a notice includes inadequate information for it to conduct its safety assessment. FDA determined 40 percent of notices were incomplete. It also objected to 28 percent of NDINs because the subject of the notification didn’t qualify as a dietary ingredient/supplement.
“That tells me FDA is not being clear enough with the industry as to what needs to be in that notification and even more basic, [explain] what’s a dietary ingredient,” said Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), in a phone interview.
One of the reasons CRN is pushing FDA to finalize its NDI guidance, Mister said, is so companies understand such fundamental issues as what meets the definition of a dietary supplement. Mister added FDA should more clearly outline what it expects in a notification, which he said could be resolved quicker than more divisive issues, like the development of an authoritative list of old, exempt dietary ingredients from a NDIN.
Several regulatory experts pointed out an FDA regulation, 21 C.F.R. 190.6, describes what information should be included in a NDIN, putting the onus on distributors and manufacturers to submit a complete notice.
“It isn’t a surprise when you submit an incomplete form to anyone that it’s bounced,” said Marc Ullman, of counsel to the law firm Rivkin Radler LLP.
FDA might find a notification incomplete because the safety data provided is not unique to the product, or submitters entirely omitted details required under the NDIN regulation, observed Daniel Fabricant, Ph.D., a former FDA supplement official who leads the Natural Products Association (NPA).
A company submitting a NDIN should follow the requirements in the regulation and reach out to FDA for feedback if it still has questions, said Robert McQuate, Ph.D., a former FDA official who co-founded GRAS Associates LLC, a regulatory consulting firm.
“If you’re going to spend any money putting together a new dietary ingredient notification, invest enough so that it’s successful,” McQuate said in a phone interview. “Don’t throw a little bit of money at it only to have it fail, and then you’re winding up with no advancement from the process.”
Ashish Talati, a partner in Chicago with the law firm Amin Talati Upadhye LLP, agreed meeting with FDA is a good idea before submitting a NDIN.
“Companies should [view] it as more of a collaborative process,” the regulatory lawyer said in a phone interview. “You contact FDA. You say, ‘Look, this is the ingredient we have. This is the data that we have. What do you think?’”
FDA, he added, is “pretty good at giving you feedback.”
“In our experience, submissions are more likely to receive a positive outcome when potential notifiers take advantage of the opportunity to meet with us before they have prepared a submission,” FDA said in an emailed statement, commenting on the FY17 data, “and we will continue to work with notifiers during and after the submission to answer unresolved questions.”
Fabricant said companies that meet with FDA after receiving an objection letter also have a better chance of success in a subsequent NDIN.
A second notice for the same ingredient might include more robust data to meet the safety standard in the law—“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.”
In FY17, FDA objected to 20 percent of submissions based on concerns with the identity or safety of the new ingredient.
“I would expect that out of 100 submissions, there might be a number of them where FDA and the companies … disagree about the adequacy of the science that’s been presented,” Mister said. “Does the company have enough science to reasonably expect that this is a safe product?”
Many of FDA’s objections in FY17 may reflect a phenomenon distinct from rigorous, scientific debates over toxicology studies and other evidence needed to establish the safety of a dietary ingredient—the power and reach of Amazon.
As INSIDER previously reported, several NDINs submitted by people selling products on Amazon were incomplete and/or for products that clearly don’t qualify as a dietary ingredient, such as a body cream.
Cecilia Fan, an Amazon spokeswoman, declined to comment for this article.
Amazon’s policies require products sold on its platform to comply with all applicable local, state and federal laws, including the Federal Food, Drug & Cosmetic Act (FDCA).
Fabricant suggested distributors and retailers are functioning as the “gatekeeper,” seeking answers from FDA on the status of certain new ingredients before they are placed on the U.S. market.
“Market forces are saying, ‘Hey, we’re not so sure about this ingredient,’” he said in a phone interview. “It’s not an alphabet vitamin. It’s not a botanical we’re familiar with. It’s not an ingredient we’re familiar with. We want the agency to render an opinion.”
Responses to such notifications could help distributors and retailers distinguish lawful dietary ingredients from substances that don’t belong in supplements.
FDA did not grant requests for a phone interview to discuss the FY17 data. In an emailed statement, the agency maintained “the large number of unnecessarily submitted or incomplete notifications” in FY17 skewed the data. FDA took steps last year to address the problems, including implementing a preliminary review process to screen out NDINs that appear to have been submitted based on a misunderstanding of the notification requirements.
Asked if the system is broken, considering FDA only acknowledged 13 percent of submissions without an objection in FY17, Ullman responded, “If you don’t know what you are doing, you’re guaranteed not to get through. That’s all I would take from it.”
Regulatory experts also noted FDA’s rate of acknowledgements—or so-called good day letters—is much higher when excluding incomplete NDINs or for products that don’t qualify as dietary ingredients.
FDA, nonetheless, said, “[T]he percentage of letters that received acknowledgements [in FY17] without objection is still lower than we hope to see.”
Added the agency: “The NDI notification system is intended to help ensure the safety of dietary supplements containing new ingredients and ODSP remains committed to working with industry to navigate the NDI notification requirements."
Total NDINs (new dietary ingredient notifications) submitted to FDA: 102
Total NDINs FDA responded to: 101
Total response letters that were acknowledgements (AKL): 13 (13%)
Total response letters that were acknowledgements with objections based on inadequate safety and/or identity (IAL): 20 (20%)
Total response letters that were objections because the notification was incomplete (ICL): 40 (40%)
Total response letters that were objections because it wasn’t a dietary ingredient/dietary supplement (NDL): 28 (28%)