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NDIs and Warning Letters

FDA Data on Pre-NDI Meetings Suggest Pathway to Success for Supplement Industry

Over a period of recent months, FDA has acknowledged half of new dietary ingredient notifications without an objection. But the number of acknowledgement letters from FDA is relatively small and may not be indicative of results for the entire fiscal year, which ends in September.

Since the 1994 passage of the Dietary Supplement Health and Education Act (DSHEA), FDA has objected to the majority of new dietary ingredient notifications (NDINs) for various reasons. This has fueled industry criticism of a notification system intended to ensure supplements containing new ingredients are reasonably expected to be safe.

Over a period of recent months, though, FDA acknowledged half of NDINs without an objection, the best-case scenario for a company notifying FDA. From October 2017 to mid-February 2018—the first five months of FY18—FDA acknowledged 48 percent of NDINs (10 of 21 notifications) without an objection.

By contrast, the acknowledgement rate over the most recent five-year period has ranged from a high of 29 percent (FY15) to a low of 13 percent (FY17). Despite the consistently low acknowledgement rates, sources familiar with the notification process—and agency data—suggest companies have a high chance of success with a NDIN if they meet with FDA officials prior to making a submission.

FDA tracked 21 pre-NDIN meetings from 2009 to 2016. The acknowledgement rate to subsequent submissions (filed between 2010 and 2017) was 71 percent.

“I think what we see here is that engagement with the agency on your notification, on your ingredient, can certainly put a notifier in a good position to get a ‘good day’ letter,” said Cara Welch, Ph.D., senior advisor to FDA’s Office of Dietary Supplement Programs (ODSP).

Welch made the comment, and shared the FDA figures above, during a conference last month spearheaded by the American Herbal Products Association (AHPA) and hosted by five trade associations, including AHPA.

Welch cautioned the FY18 data may not be indicative of results for the entire year. Furthermore, FDA couldn’t confirm for this article the total number of pre-NDI meetings held between 2009 and 2016, or overall acknowledgement rate of subsequent submissions tied to the abovementioned pre-NDI meetings.

Still, regulatory attorney Ashish Talati recommended companies embrace ODSP officials’ willingness to meet with them.

“Companies should definitely be looking to work with the agency, asking them before they do a formal submission,” said Talati, a partner in Chicago with Amin Talati Upadhye LLP, in a phone interview. “That process looks much different for companies that go through that because they have a higher chance of getting it through” without an objection from FDA.

Robert Durkin is deputy director of ODSP. He encouraged dietary supplement companies to meet with him and his colleagues before submitting a NDIN.

“We want to work with you,” he said during an event (The Big Natural) in May in Las Vegas hosted by the Natural Products Association (NPA). “We want to know you. Before you make a NDIN submission, call us. Set up a pre-NDI meeting. Let’s exchange some emails [and] have a conversation about your ingredient, about what you’re trying to do with it.”

In response to a comment from NPA’s leader—former FDA official Daniel Fabricant, Ph.D.—Durkin confirmed FDA doesn’t serve a consulting role and must speak in broad terms when discussing NDINs.

“We can’t tell you how to do it,” he said, commenting on crafting a notification and explaining, for example, FDA wouldn’t specify a notifier must conduct a 90-day safety study on an ingredient. “It’s not prescriptive. Just show us your basis [for a reasonable expectation of safety] and if we agree with it, if it’s there, you get your ‘good day’ letter.”

Relatively few companies that have gone through the NDIN process have received good day letters. Of the 977 NDINs that FDA provided a substantive response to since passage of DSHEA, only 25 percent were acknowledged without an objection, according to data Welch shared.

Talati wondered why more companies don’t take advantage of the opportunity to meet with FDA officials.

“You have an agency that’s willing to talk to you, and it’s not just saying, ‘Hey, just file it and we’ll let you know,’” he said. “They’re saying, ‘Yah, come talk to us,’ so companies should do that and they’ll learn from it. They’ll amend if needed, and they’ll get good, valuable feedback.”

In FY17, it’s probable few notifiers corresponded with FDA before submitting a NDIN; the acknowledgement rate was abysmal: just 13 percent.

In many respects, FY17 was atypical. A relatively large number (103) of NDINs were submitted to FDA, compared to previous years. (In fiscal years 2014, 2015 and 2016, FDA received 41, 35 and 58 NDINs, respectively).

Several notices in FY17 were incomplete, failing to provide even basic information required under FDA’s NDIN regulation (21 C.F.R. 190.6). Many submissions also covered products that were clearly not dietary supplements.

Following an investigation, FDA determined an increase in notices beginning in late FY16 “was related to a sales requirement imposed by a large retailer,” FDA told Natural Products INSIDER in 2017.

“[A] number of firms that wanted to sell products (cosmetics or dietary supplements) through this retailer were under the impression that they could satisfy this requirement simply by obtaining an FDA-issued ‘NDIN number’, while putting little to no effort into meeting” FDA’s notification requirements, the agency said via email.

Several rejected NDINs, it turns out, were traced to merchants wanting to sell their products on Amazon. (Amazon declined INSIDER’s 2017 requests for comment).

FDA last year revealed implementation of a process in which screens out notices that don’t meet basic requirements, so they are not assigned a NDIN number.

In FY18, through mid-February, FDA received 21 NDINs.

“Ideally, what we will see for FY18 is a return to the numbers that we would normally see, at least of legitimate notifications,” Welch observed during the Dietary Supplements Regulatory Summit on May 16 in Washington.

FDA, she said, is looking for “comprehensive, substantive notifications … that really give us a picture of the product and the ingredient that’s going to be going onto the market.”

Welch’s colleague, Durkin, suggested he would rather be focusing on substantive issues, like assessing the safety of an ingredient, rather than writing a letter that a NDIN doesn’t meet all the requirements in FDA’s NDI regulation or fails to qualify as a dietary ingredient under federal law.

“Those letters do have to happen, but I hate them,” Durkin said. “I hate them because we’re not protecting the public health, and we’re not serving the regulated industry.”

Finally, Durkin suggested his agency is committed to a thoughtful analysis and response letter when reviewing comprehensive NDINs covering a legitimate dietary ingredient.

Response letters to NDINs from FDA, he remarked at NPA’s event, must be “meaningful.”

“They have to give an indication of why we don’t think your product is reasonably expected to be safe,” Durkin said, “or if we do a good review, and you get a ‘good day’ letter, we have to have confidence in that.”

 

 

TAGS: Ingredients
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