Virtual—“COVID is not going to stop our attempt to spread truthful science and information,” said Raqiyyah Pippins, Partner at Arnold & Porter Kaye Scholer LLP, as she opened the session “Examining New Trends in Claims Substantiation: A Study of Innovative Claims, Ever Increasing Use of Influencers to Promote Products, and Risk” at the 8th Annual Legal, Regulatory & Compliance Forum on Dietary Supplements, put together by the Council for Responsible Nutrition (CRN) and the American Conference Institute (ACI). In that one statement, Pippins summed up not only this event, but the vast number of virtual events spawned by the industry as COVID shut down in-person events. She also summed up the tenacity of the industry—not just in creating events whole-cloth, but in moving in-person events online.
And truthful science and information were had in spades at this event.
Steve Mister, President and CEO at CRN, noted in his State of the Industry Address that sales of vitamins are up—he cited data from IRI which found that in the 12 weeks ended May 17, 2020, vitamin sales were up 62% online and 30% in-store, compared to the same 12 weeks in 2019. This, of course, is due to COVID—which has had plenty of other effects on the industry: “Our member companies had to figure out what to do to protect the safety of their line workers, enforce social distancing, and prevent the spread of the virus. They also had to ensure that the products themselves were not transmitting the virus—which, FDA said, no, they’re not, but there was a fear that if an employee tested positive, they would have to destroy the products the employee was working on. And then there’s the work-from-home order—how do you ensure a safe workplace if your employees aren’t in a workplace?”
Mister also summed up the questions Industry members have now, looking towards the future: “Our member companies are trying to develop return-to-work policies, which means establishing long-term workplace changes—what are you doing about break rooms, what are you doing about face coverings, what are you doing about travel policies? How do you make sure your employees can safely get to and from work? And lots of companies are negotiating new supplier contracts, and trying to establish multiple sources for ingredients, because it’s not good enough to rely on a single source from China—what if there’s a second wave? And manufacturers are trying to get priority status for limited-source contracts—if there’s only so much of a product, and the supply runs out, who gets the last of the product and who gets left empty-handed? These are not unique to the natural products industry, but these are the issues we are facing. This is a year interrupted.”
But while the year was interrupted, the flow of information was not. The day featured a lengthy discussion regarding NDIs versus GRAS and self-GRAS. Andrew Shao, Ph.D., SVP of Global Scientific & Regulatory Affairs at Chromadex, explained that there is a negative reinforcement cycle regarding NDIs: “There’s confusion regarding the regulatory framework—it’s been Draft Guidance since 2011. And there’s a lack of enforcement, which means that there’s poor compliance—there’s no incentive to actually put together an NDI, which means that consumers are at risk, because companies aren’t investing in the science needed to ensure product safety. This also places responsible companies at a competitive disadvantage, because we put in the time and money needed to get the science and submit an NDI, and then other companies can piggyback off our work—it’s happened to Chromadex before, where our flagship ingredient, Niagen, a form of nicotinamide riboside, has all the safety data, but other companies can put nicotinamide riboside in their products on the strength of our data—even if it’s a different form of the ingredient. This puts consumers at risk.”
On the other hand, Shao said, GRAS isn’t necessarily any better—it’s a lengthy process and not mandatory, so there’s little incentive there. He also raised some issues with GRAS self-determination, noting a lack of transparency, particularly surrounding safety standards. In sum, he said, there’s no market exclusivity or data protection, there’s no incentive to invest in science or transparency or to participate in the notification process at all, and there’s no consequences for piggy backing off of other companies’ data or for failing to notify FDA of an ingredient.
Regardless, those who choose to do NDI can use these tips from Shao: “Regulators want to know how the ingredient is measured and how is it made, with manufacturing process information. They want analytical methods for how it’s measured. They want product specifications, including all potential degradants. They also want to know what it does, the intended technical effect. And build a relationship with regulators—go through the front door, don’t try to get around regulations. Respond quickly and completely when a request is made. Maintain an open dialogue. And request a meeting early in the process, before you submit the NDI notification.”
This advice was backed up by Steven Tave, Director of the Office of Dietary Supplements—“We are open to meetings. We don’t want to reject an NDI on a technicality—of course you can submit again, but we’d rather help you get it done right on the first try. Our doors are open to you.”
Ashish R. Talati, Partner at Amin Talati and Wasserman, on the other hand, said that we shouldn’t be so quick to dismiss GRAS or self-GRAS. “While NDIs have to meet a reasonable expectation of safety, GRAS has to meet a reasonable certainty of no harm, which is actually a higher standard,” he explained. And when done right, Talati noted, there’s nothing wrong with it. “There is this perception that self-GRAS is an easy process. It is not. In my years of working with this, I have seen companies spend thousands upon thousands of dollars on this and lots of time. It requires a panel of experts to look at the information—in my experience, companies go out of their way to find panelists who are credible, who are experts in the area. And these experts make $3-5 thousand—they’re not going to put their reputation on the line for that kind of money. And FDA doesn’t mind. They don’t want people submitting notifications if people can self-GRAS. There’s this perception that self-GRAS is a loophole, or cheating, but it’s not—it’s not a lower standard of safety than a GRAS notification, and that is not a lower safety standard than a food additive petition. When it’s done right, it’s perfectly legal and correct. The focus really ought to be on companies that don’t do anything—no NDI, no GRAS, no Food Supply Exemption, but still they go to market. GRAS should not be looked down upon.”
There was also a discussion on CBD. First, in a panel on defining dietary supplements, Stan Soper, Outside General Counsel at Nutraceutical Corporation, discussed the usual comparison for CBD: red yeast rice. “Red yeast rice contains lovastatin, which, in its purified form, is a drug. But the industry argued that we weren’t selling lovastatin, we were selling red yeast rice, which contains naturally occurring lovastatin—and red yeast rice had been in the food supply. So it was determined that as long as the lovastatin levels in a red yeast rice product were naturally occurring, it was fine to sell, and FDA tests these products regularly. The problem is that, whereas we weren’t looking to sell lovastatin, people are looking to sell CBD, not always hemp extract.”
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In a panel discussion focused on hemp, Kelly Shea, SVP of Government Affairs & Corporate Communications at Charlotte’s Web, noted that hemp was expected to be the crop that would save American farmers—“Tobacco is struggling, soy is struggling, hemp was supposed to be what farmers could turn to in order to save themselves, but the price of hemp biomass has fallen about 80% since July 2019. Significant inventories of biomass and extracted oil remain unsold. Lack of action by FDA has hurt farmers who doubled down on what they hoped would be a good crop.”
Martin Hahn, Partner at Hogan Lovells US LLP, is of the opinion that there’s no real reason for this. “Hemp itself has been consumed as an ancient grain for 10,000 years. It hasn’t been consumed for quite some time in America—because in 1970, the Controlled Substances Act was passed, and hemp was banned. FDA should be considering that. The FDCA says it’s the article approved by FDA that can be marketed—but what is the article, in this case? What is the definition of article under the exclusionary clause? I think there’s a real legal issue here—is the article the highly purified form of CBD, or is it something else? I think there’s an argument to be made that broad- or full-spectrum oil could be a different article from the 99.9% pure CBD approved by FDA as a drug.”
When it comes to safety, too, Hahn noted that there’s no reason for delay. “CRN has done a safety assessment finding that up to 40mg of CBD are safe, and the U.K. has set an upper limit of 70mg, so anywhere in there is safe. Or companies could submit NDIs showing the safety of their specific extract.”
Melody Harwood, Head of Scientific & Regulatory Affairs, Neptune Wellness Solutions, agreed. “If you look at Canada and Europe, there has been a significant hemp industry, which is great for creating a framework for the industry. There is no indication that there are safety issues related to the products being sold in Canada.”
When it comes to warning letters, there was general agreement: They’re necessary—but not the action the industry needs. “We love the warning letters,” Shea said. “We’ve gone from 250 companies making these products a couple years ago to about 3,600 today. We really want to be regulated, so that the products are trusted, so that there’s transparency. We want to be treated like every other well-regulated product out there. I’m waiting with baited breath for the sampling study of the current CBD marketplace that’s supposed to be coming out from FDA any day now.”
That said, Hahn noted that FDA’s warning letters aren’t necessarily bringing any clarity to the industry. “The warning letters aren’t just targeting the 99.9% pure products, they seem to be having problems with full- and broad-spectrum problems. It’s reinforcing the industry’s confusion.”
And regardless, these letters are not enough: “FDA inaction allows bad actors to remain on the market,” said Harwood. “There are those who will get on the market and make a bunch of bucks, and then if the FDA gets on them they’ll get out, but FDA inaction allows them to get in in the first place. It’s stagnating farmers’ access to this market, too. They’re allowed to grow it, and maybe to bring it to cosmetics, but they’re finding that there is an oversupply for this product.”
Shea added, “Every time FDA says something about how these products should be illegal, stocks take a dive. Publicly traded companies tank. The retailers run away. It’s been hard on the whole supply chain.”
Not to mention, Hahn pointed out, the opportunities for class action lawsuits. “They can say that this product should not be on the market. And it’s hard, across state lines—the Farm Bill did not preempt state laws when it took hemp off the controlled substances list, so there are states that consider hemp a schedule 1 controlled substance, which is a felony.”
Harwood offered some suggestions for responsible companies looking to continue in this marketplace: “Companies that make egregious claims on their products are subject to enforcement. Develop good manufacturing controls, don’t make egregious claims, and label your products appropriately.”
Other highlights: Amanda Darlington, Director of Government Relations at CRN, noted that there are important laws to keep an eye on. “Five years ago or so, some people out of Harvard pushed a bill in Massachusetts that would restrict access to weight loss supplements and OTC diet pills, because they said it was connected to the development of eating disorders. The bill didn’t go anywhere, and they’ve introduced it in several other states, targeting energy drinks as well. And the thing is, victims of eating disorders have testified repeatedly that their disorders often started through teas and such pushed by influencers—not weight loss supplements sold by natural products retailers. So there’s no studies backing these bills, and the bills aren’t even touching on the actual problem.”
There was also an in-depth discussion of claims. Ryan Bradley, ND, MPH, with the National University of Natural Medicine, broke it down: “Is the product essential for ‘normal’ human in vivo immune response? You can use ‘Supports immune function,’ and that’s fine. Is human in vivo immune response ‘supported’ by the product? Again, you can make that claim—there’s a fine line there, though, in the case of a vitamin deficiency—is deficiency a ‘disease,’ or is correcting that deficiency ‘mitigation’? You shouldn’t use ‘strengthened’—it’s unclear, and also, there’s a lot there with inflammation that you don’t want to touch. Don’t use ‘in response to’—that implies ‘disease fighting.’ Prevention and treatment are also clearly claims in violation of FDA/FTC guidance.”
Bradley also noted that a structure/function claim requires evidence—and that there’s not a lot of guidance there. “It’s defined as ‘competent and reliable scientific evidence,’ which is tests or research based on the expertise of professionals—not specified who—that has been conducted in an objective manner by persons qualified to do so—again, who?—using procedures generally accepted in the profession—which ones?—to yield accurate and reliable results—does that imply reproduced studies? There are no universal standards for professional backgrounds, outcomes, or the level of evidence necessary.”
Richard Cleland, Assistant Director of Advertising Practices, Bureau of Consumer Protection, FTC, spoke on claims as well. An important takeaway: Keep an eye on influencers. For instance, one company, Teami, has received a warning letter—and what first brought the company to the FTC’s attention was claims made by an influencer. Part of the warning letter FTC sent the company was a warning to remove the claims made by Teami’s influencers. “Advertisers are responsible for the conduct of their influencers,” Cleland emphasized. “You can reduce the risk by establishing clear guidelines up front and by monitoring your influencer’s posts. The latest guidance requires influencers to disclose when they have any financial, employment, personal, or family relationship with a brand—and that’s not limited to money, influencers have to disclose if they received any products or anything of value to mention its product. Influencers should disclose if they received free or discounted products, even if they weren’t asked to mention the product.” He noted that FTC offers guidance on their site, which may be a good tool to share with influencers.