INSIDER Law
FDA 2019

CBD industry faces safety-related catch-22

FDA isn’t willing to review safety information for CBD through a traditional regulatory pathway for dietary supplements.

U.S. regulators want assurances CBD is safe before deciding whether to allow the hemp-based compound to be lawfully marketed in dietary supplements.

But the agency isn’t willing to review safety information through a traditional regulatory pathway to market because it has determined CBD is excluded from the definition of a dietary supplement.

“The agency’s priority, as it states over and over, is protecting public health,” said Michael McGuffin, president of the American Herbal Products Association (AHPA), in an interview. “How do we square the agency’s commitment to that priority—protecting public health—with refusal to review safety information on an ingredient that is broadly marketed in the United States?”

CBD has proliferated in “dietary supplements” despite FDA’s position that the compound was first studied as a drug by GW Pharmaceuticals plc and cannot be lawfully marketed in a supplement or traditional food.

FDA has received a handful of new dietary ingredient notifications (NDINs) possibly related to CBD, including three submissions in 2019.

However, an FDA official confirmed the agency will not conduct a safety analysis of the products subject to NDINs due to its determination that CBD is excluded from being marketed in a supplement. 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.

When evaluating the above notifications, FDA first determines whether the submission is complete and contains the required information under FDA’s applicable regulation, 21 C.F.R. 190.6, said Steven Tave, director of FDA’s Office of Dietary Supplement Programs (ODSP), in an interview. If the notification is complete, FDA next determines whether the ingredient qualifies as a dietary supplement and whether or not it’s excluded from being marketed in a supplement, he explained.

“With all the CBD-containing notifications we’ve received to date, our determination has been, consistent with the agency’s position, that the product is excluded,” Tave said. “And when we have CBD or not, whenever we determine that a product is not a dietary ingredient or can’t be in a dietary supplement, we stop the review there. We do not continue to do a substantive review of chemistry or toxicology or safety because we don’t have the resources to do advisory reviews of excluded ingredients.”

FDA’s unwillingness to evaluate the safety data in CBD-related NDINs, McGuffin said, “seems to be incongruous with the agency’s first priority—protecting public health.”

It also is providing a “disincentive” for “industry to do the right thing,” noted a senior executive with a hemp company, who agreed to be interviewed on background to speak frankly.

Responsible companies who “would invest the resources to submit an NDIN are being punished, and the people who don’t care are being rewarded,” the executive said.

“It forces you to use the GRAS back door,” added the hemp executive, describing a process known as GRAS (generally recognized as safe) self-determination in which a panel of experts reach a consensus about the safety of an ingredient but do not share the data with FDA for the agency’s review.

“It’s unfortunate because the new dietary ingredient notification process was developed for dietary supplements, and it’s underutilized,” the source said. “And this situation that FDA has created is forcing people to circumvent the very route to market that’s designed for a botanical extract and use the GRAS process.”

FDA has raised concerns about potential harm from CBD, including the potential for liver injury, drug interactions and male reproductive toxicity. But the agency is “discouraging companies from” submitting safety data the agency has requested, said Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN).

While, through an NDIN, a company can obtain confidential protection for its data, sharing the same data on the public docket would allow “the whole world to see” it, he pointed out.

If FDA eventually allows CBD to be marketed in a supplement, “every company is going to use that data and submit it as part of their NDI to show that [their products are] safe,” Mister said. “I have absolutely no compensation for the work that I’ve done because everybody will get to use it.”

Three NDINs possibly related to CBD were submitted to FDA in the summer of 2019, the agency disclosed in an email. The notifications have not yet been posted on FDA’s NDIN webpage, and Natural Products Insider was unable to immediately obtain a copy of them from FDA or confirm the names of the companies who submitted them.

In its responses to two NDINs submitted in 2017 for hemp products, FDA mentioned CBD could not be marketed in a supplement. Several sources with expertise in regulatory matters suggested the notifications were very rudimentary ones that would not have met safety requirements in the law.

One of the notifications submitted in 2017 was for a product called “Superior Hemp Oil.” In its response letter, FDA stated its long-held position that CBD products are excluded from the definition of a dietary supplement.

“This is because CBD has been authorized for investigations as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public,” the agency explained. “Prior to such authorization, it [CBD] was not marketed as a dietary supplement or as a food.”

Elizabeth Moriarty, a formulator and custom manufacturer of HoneyColony’s Superior Hemp Oil, described HoneyColony’s NDIN, which was submitted by a former HoneyColony employee, as “a rather stunning choice … based upon a profound lack of awareness combined with youthful enthusiasm.”

“Neither HoneyColony nor my company, Luminary Medicine Company, are financially or logistically prepared to challenge the FDA position that CBD and/or THC are ineligible for supplement status,” she wrote to Natural Products Insider in a 2018 email.

John Venardos is CEO of the recently formed CBD Association in Washington, D.C. and an expert on regulatory matters who previously worked at Bodybuilding.com and Herbalife. He said leading providers of clinical research services have been conducting dozens of safety studies on CBD-containing commercial products under development for the market. Law firms in Washington, D.C. also have divulged several CBD-related safety studies are ongoing.

“Responsible companies” would want to consult with FDA’s dietary supplement office to discuss their concept of a new product and share the underlying safety data with FDA, Venardos said in an interview.

“We as an organization, together with other stakeholders, have a responsibility to work with FDA, as well as members of Congress, and the [Trump] administration, to try to find a way to move this forward in the interest of public safety, innovation and the use of a helpful dietary ingredient that CBD can become,” he said.

Some large companies that would like to enter the CBD market may be unwilling to invest in the safety data until FDA or Congress establishes a legal path to market.

“You can’t have the safety data unless you give companies a pathway,” Mister stated. “First of all, give them an incentive to do the work. As a dietary supplement company, why would I invest in safety studies for CBD when the agency is telling me it will never be a legitimate ingredient? So you’ve got to create the financial incentives for companies to do the work by saying, ‘Yes, if you prove it’s safe, we will let it be a dietary ingredient.’ And then, secondly, you need to give them some protection for the data.”

Jonathan Miller is general counsel to the U.S. Hemp Roundtable, a coalition of hemp companies. He said it is urgent FDA move to actively regulate the market.

“We have tons of unregulated products, and some of them are misleading consumers in terms of what’s on their label,” he said in an interview. “Others might have heavy metals or other toxins in them. Until the FDA acts, that’s going to continue.”

Miller added, “This regulatory gray area is bad for health and safety.”

Amid the regulatory uncertainty, what should “responsible companies” in the hemp-based CBD industry do?

AHPA lets its members know they have “an affirmative responsibility” to ensure their products are safe, McGuffin said. “We don’t advise, but we encourage companies to take that responsibility seriously. We encourage them to at least initiate the safety review that they would submit at a time at which FDA opens up that door.”

TAGS: Ingredients
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