Firms receiving an “inadequate” letter but who really want the full acknowledgment letter can always choose to resubmit data to FDA. Fabricant, who previously served as Director of FDA’s Division of Dietary Supplement Programs, and Hilmas, who was Chief of the FDA Dietary Supplement Regulation Implementation Branch, both stressed that firms can benefit from maintaining open dialogue with FDA throughout the process in order to draw a clear bead on what information the agency is looking for.
Examining five years’ worth of NDI submission data, Hilmas estimated that of 61 acknowledgment letters FDA sent during that five-year period (ending in 2014), only two were achieved without the company having talked to FDA; the others were sent to companies that had communicated with the agency. Of companies that received an “inadequate letter,” Hilmas said that 27% of companies chose to resubmit and, of those, nearly half who maintained open dialogue with the agency went on to get acknowledgment letters.
“Certainly sticking with it and engaging the agency and maybe doing some additional safety studies seems to work to get to an [acknowledgment letter],” Fabricant said. And, he pointed out, if a company received an “inadequate” letter, meaning FDA only has minor questions remaining, “you do meet the regulatory burden, so at that point, it’s a lot easier to engage the agency.”
The key, Fabricant stressed, is to submit your notification in the first place if one is needed. “It’s critical. By notifying the agency, consistent with 21 CFR 190.6, the burden really is on FDA to demonstrate the product is unsafe” thereafter, he said. “If you notify the agency, and unless you receive an incomplete letter in response that your data wasn’t complete to 21 CFR 190.6 and that you didn’t in fact meet the burden for filing, you’ve effectively notified the agency.”
“Without notifying the agency,” however, Fabricant said “it’s a technical adulteration for failing to submit a NDI notification and providing appropriate safety data. I don’t think anyone who’s a responsible corporate citizen is going to want to have that as how they’re viewed out there in the sphere.”
“If your company even thinks you should file, this should push you in the right direction,” he said.
Will FDA Enforce NDIs More Heavily?
Although FDA draft guidance is not binding by law, it provides a solid map to how FDA may go about enforcing NDI provisions in the future. Now that the agency has laid forth its current thinking, will it aggressively go after companies not meeting their NDI burdens?
NPA webcast speaker Cara Welch, PhD, senior advisor at FDA’s Office of Dietary Supplements, repeated what FDA has said in the past—that the agency believes there may be a high percentage of companies in the market who have not submitted notifications when they should have.
“We believe, more anecdotally than anything, that more notifications should have been submitted over the last 20 years than actually have been submitted, and so it’s important to us to ensure that industry is aware of our expectations of when notifications should be submitted,” she said.
“Once finalized, the guidance will set the stage for future actions for those that are not complying with the requirements,” Welch added.
Fabricant said firms should also consider product categories already on FDA’s enforcement radar as areas ripe for NDI enforcement as well.
“If you look at past history, look at where the focus has been,” Fabricant said. “There’s been a lot [of attention] on sports nutrition. There’s been a lot on weight loss. Those are the areas where there tends to be kind of an interest in pushing the line somewhat with newer molecules, so I think people in those areas just need to be careful in terms of what they bring to market.”
Will FDA also have more resources to fund broad-scale enforcement now that the dietary supplements division is a full-blown office within the agency? That remains to be seen, Fabricant said, adding that NPA also plans to inquire about this.
“In terms of the agency priorities and funding, now that the agency is an Office and the strategic plan has since expired—this is 2016—when will we see a new strategic plan from the agency on dietary supplements, and what will be the plan for enforcement of NDIs and statutory authority there? I think everyone wants to see the agency enforce the NDI provisions in full and really pick those items out that shouldn’t be out on the market as dietary supplements or dietary ingredients.”
The agency seems to feel the same. “The NDI notification process is very important to the FDA. The notification process is FDA’s only premarket opportunity to review products, to review the formulation and the safety of products, and we take that seriously,” Welch said.