The lack of a clear regulatory pathway to market for CBD products in the US is frustrating the industry, reports CBD-Intel
The US Food and Drug Administration (FDA) continues to deny approval of a new dietary ingredient (NDI) for full-spectrum hemp extracts, which has prompted frustrated responses from industry.
The nub of the problem appears to be disagreement between the FDA and the industry over whether CBD should be classed as a drug or a dietary supplement. The term “new dietary ingredient” refers to ingredients that were not marketed in the US in a dietary supplement before 15th October 1994.
The denial came at the end of an 18-month process of back and forth on the details and included several specific reasonings that were rejected as incorrect by industry members.
The FDA letters to Irwin Naturals and to Charlotte’s Web said full-spectrum extracts cannot be used as an ingredient in dietary supplements because CBD is the active ingredient in the FDA-approved drug Epidiolex, and because it was not marketed as a supplement before it was investigated as a drug. The letters further said the studies presented failed to show the product “will reasonably be expected to be safe,” specifically citing concerns on reproductive and liver toxicity.
Charlotte’s Web and ValidCare, a research company conducting clinical trials – including on CBD liver toxicity that was used as part of the Charlotte’s Web application – objected to a number of the specific safety concerns.
Charlotte’s Web, in a reply to the FDA, said it was particularly frustrated that a number of these concerns were based on incorrect assessments and could have been dealt with if brought up in any of the numerous meetings and talks the company had with the FDA’s Center for Food Safety and Applied Nutrition throughout the process.
“We want clear FDA approval and regulation,” said Kelly Shea, the company’s senior vice president of government affairs and corporate communications. “We believe the consumer deserves access to safe and reliable hemp CBD products and we believe that it is the FDA’s job to set the regulatory environment to ensure all manufacturers are in compliance.”
ValidCare CEO Patrick McCarthy said the, as yet, unpublished trial data from the study showed no evidence of liver toxicity. The study included 839 people, about 150 more than required. McCarthy said three people showed clinically elevated enzymes examined for liver toxicity, but each of those participants was taking pharmaceutical drugs that could cause the enzyme elevation. “We’re not able to correlate it to the hemp-derived product,” he told CBD-Intel.
The FDA’s July 2020 approval of Epidiolex CBD lists “elevated liver enzymes” as one of the “most common side effects”.
McCarthy explained that the Epidiolex drug study was conducted under the specifications of treating children with rare seizure disorders. “The studies they did were mainly on children with convulsions,” he said. “For the FDA to give a blanket statement on CBD as a whole, they probably wanted to see a study on healthy adults.”
ValidCare is conducting a follow-up study to gather additional information on liver toxicity, which they hope to conclude by the end of the year. Results so far show “no inconsistency” from the previous study, McCarthy said.
The company is also aggregating results from a study on whether hemp products cause testicular changes. The FDA requested the additional data after a separate study showed hemp products used on rodents may have caused testicles to shrink generationally.
“We’re just trying to prove for the FDA whether we have a public health issue. The drug is out there, it’s not approved, and it either causes or doesn’t cause these concerns,” McCarthy said. “Our desire was really to get them the data so that they could do their job better.”
He said the FDA seems to have experienced a change in mindset regarding CBD. The ultimate goal of ValidCare as an independent research group is to gather meaningful data, he said. “We’re an unbiased party here. If we’re collecting data, we want to make sure that we’re collecting data that’s going to matter.”
He explained that there are different requirements for FDA drug approvals and for dietary supplement approvals, which are cheaper and easier for businesses to seek. For now, he said, the FDA seems to be categorising all cannabinoid products as drugs: “That’s really where the tension line is drawn between the FDA and the industry right now.”
In contrast, companies are saying CBD products should be considered as dietary supplements, not drugs, so they should not have to provide the level of safety data required for drugs.
“CBD companies are arguing that it is a natural product,” McCarthy said. “The FDA is saying that’s not their line of thinking. It’s a drug until they say it’s not a drug.”
McCarthy said that the FDA’s approach to its examination of CBD complicates industry regulations.
“They’re in a pickle, chemically,” he said of CBD companies. “At the end of the day, cannabidiol is the same in hemp as it is in marijuana. The FDA seems to be standing firm that cannabinoids will be treated as a drug.”
Charlotte’s Web responded to the FDA’s objection in August, differentiating full-spectrum hemp extracts (FSHE) from purified CBD in isolate form, the latter of which is an FDA-approved drug.
“The FDA’s position that our FSHE with naturally occurring CBD is the same as CBD isolate is inconsistent with several credible publications we provided, which evidence that the products are different pharmacologically,” the company said. “Since the passing of the 2018 Farm Bill, there has been significant reliance on the FDA to create a regulatory pathway for the hemp wellness category. However, after two and a half years, it is increasingly apparent that, in the FDA’s own words: ‘legislation might be appropriate.’ We agree with the FDA’s suggestion that Congress act by passing legislation to enable FDA oversight of FSHE as a dietary supplement, to properly regulate the hemp wellness category.”
The Council for Responsible Nutrition (CRN) also believes the FDA has got it wrong on FSHE.
“The FDA has wrongly mischaracterized these products as the same article as a prescription drug and has ignored, dismissed, and downplayed ample evidence that these full-spectrum hemp products can be marketed in a manner that is reasonably expected to be safe,” CRN president Steve Mister said. “Meanwhile, the agency has done little to protect consumers from the unregulated marketplace it has created from more than two years of inaction.
“Despite very clear direction from Congress when it removed hemp from the Controlled Substances Act in 2018, FDA seems to have made up its mind not to support CBD in supplements and is now trying to justify it. That’s the only logical conclusion to draw from FDA’s actions – and its continued inaction. These mixed messages from FDA are unacceptable, and Congress must exercise leadership by stepping in to end it.”
Shea said Charlotte’s Web was continuing to work with Congress and the FDA to push toward regulation. Two bills were introduced in Congress in 2021 that would categorise hemp products as dietary supplements. “Congress will act, because they know they need to,” she said.
She added: “We have a large, unregulated industry that does not offer consumers the quality and protection they deserve. Even with the drug preclusion issue, there is absolutely nothing stopping the agency from issuing detailed enforcement discretion and enforcing against companies that don’t comply with those standards.”
What This Means: ValidCare’s McCarthy said, based on its letters, the FDA does not seem to be considering a pathway for hemp as a dietary supplement. He described this as a “huge change” that has occurred in recent months.
He noted that the FDA previously referred to its CBD committee as the “CBD products task force” and now refers to it as the “Cannabis Product Council”. He said the name change indicated to him that the FDA was categorising CBD products in the same realm as all other cannabis products.
CBD-Intel provides impartial, independent and premium market and regulatory analysis, legal tracking, and quantitative data for the cannabidiol (CBD) sector.
We provide our clients with the tools to navigate this fast-moving sector, tailor their business strategy, optimise resources and make informed decisions. In addition, we offer customised research and consultancy support.