By Mike Montemarano, Associate Editor08.13.21
The U.S. Food and Drug Administration rejected two New Dietary Ingredient Notifications (NDINs) for full-spectrum hemp extracts containing cannabidiol (CBD) submitted by manufacturers Charlotte’s Web and Irwin Naturals. According to industry stakeholders, the decision signifies that FDA does not intend to approve of the use of CBD as a dietary ingredient, and by default, doesn’t intend to regulate it as such.
Notably, these were the first NDI notifications to receive a response from the FDA, making this a new development over the course of deliberations on where the ingredient stands.
“Based on how FDA engaged these companies over the course of months—having meeting after meeting, request after request for more safety data—and then an invitation to submit NDI notifications, we’re certainly disappointed and surprised that FDA rejected the two NDI notifications,” Steve Mister, president and CEO of the Council for Responsible Nutrition, told Nutraceuticals World. “CRN handed FDA a playbook for creating a regulatory framework for CBD, and FDA punted the ball.”
In each of the agency’s NDI responses, Cara Welch, PhD, acting director of the FDA’s Office of Dietary Supplement Programs stated that because CBD is an active ingredient in Epidiolex, an approved drug, hemp extracts that contain CBD cannot achieve regulatory status as a dietary supplement ingredient. Additionally, Welch mentioned in both letters to the respective CBD manufacturers that the studies they provided didn’t provide adequate data regarding certain endpoints, including hepatotoxicity and reproductive toxicity.
“For these reasons, the information in your submission indicates that, even if your NDI 1202 were not excluded from the definition of a dietary supplement, your notification does not provide an adequate basis to conclude that a dietary supplement containing the ingredient, when used under the proposed conditions of use, would reasonably be expected to be safe,” Welch wrote in response to Charlotte’s Web.
Mister said that he and stakeholders overwhelmingly disagree with hemp extracts’ characterization as the same “article” as Epidiolex. “FDA has wrongly mischaracterized these products as the same article as a prescription drug and has ignored, dismissed, and downplayed the ample evidence that these full-spectrum hemp products can be marketed in a manner that is reasonably expected to be safe.”
“Epidiolex, manufactured by GW Pharma, is a highly-concentrated CBD isolate that contains 10-times more CBD than either of the full-spectrum hemp ingredients and plainly is not the same article supplement companies are producing,” Mister continued.
He also voiced objection to FDA’s characterization of the safety data provided by the two companies as “insufficient.”
Mister added that, because the FDA rejects CBD’s use as a legal dietary supplement ingredient, thus not considering it to be within its inspectional jurisdiction, the current marketplace for CBD products has no government oversight, leaving companies to self-regulate for the quality and safety of their own products.
Daily Consumption Levels Not Mentioned
Daniel Fabricant, president and CEO of the Natural Products Association, said that setting a safe level of daily consumption for CBD products remains the best pathway for regulating the CBD marketplace.
"Future NDI guidance without real clarity on cannabinoids, including CBD doesn’t help the millions of Americans who already believe FDA regulates the space," Fabricant said. The response to this NDI indicates that there is confusion and misunderstanding on all sides of the issue and it must be addressed by the forthcoming guidance. There have to be clear safety rules and thinking on these matters."
A bipartisan bill introduced in the Senate could clarify the NDI process and set a safe level of consumption for CBD products, as part of a larger cannabis reform effort.
NPA has been advocating for establishment of a safe level of daily CBD consumption in supplements since 2017. The trade organization drafted a bill which was passed, which provided resources for FDA to conduct a Health Hazard Evaluation on CBD in order to be able to set a safe level of daily consumption.
This process for CBD in full-spectrum hemp extracts could follow a similar pathway to market as red yeast rice, an ingredient which was originally subject to drug preclusion by FDA during the NDI process. Once a safe level of daily consumption for red yeast rice's constituents was established for dietary supplements, the agency no longer considered red yeast rice, in supplement-level quantities, to be precluded from the NDI process.
Calling on Congress
CBD proponents argue that legal access to CBD as a dietary supplement ingredient, under the inspectional authority of FDA, was the intent of Congress when it passed the 2018 Farm Bill, which legalized the production of industrial hemp. Since then, industry stakeholders have called upon FDA to regulate CBD as a dietary ingredient.
“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,” Mister said.
This far after the passage of the 2018 Farm Bill, as uncertainty still looms, Mister said it seems likely that the only way CBD will progress toward a dietary ingredient status is through lobbying Congress members to pass a bill that would require FDA to set aside its drug preclusion concerns for full-spectrum hemp extract, and to recognize CBD as a dietary ingredient for supplements. Certainly, trade groups will be lobbying for a bipartisan bill to do just that, while assuring FDA applies the same requirements for manufacturing, labeling, and marketing of other dietary supplements.
“Today’s rejection letters disregard clear safety evidence and a distinction between the two forms and concentrations of CBD. So yes, it’s clear that Congress needs to step in to exclude CBD from the drug preclusion language,” Mister said. “FDA chose to disregard volumes of safety data presented by each submitter. FDA’s refusal to make distinctions between Epidiolex’s CBD isolate and the submitters’ full-spectrum hemp extract—different forms, different dosages, different indications, and the submitters not making any drug-like claims—makes it very clear that Congress must step in to resolve FDA’s unwillingness to act logically.”
Mister noted that since CRN first urged the agency to act two years ago, consumer interest in CBD has grown, sales have multiplied, and product innovation has expanded. “Individual states have grown impatient and begun devising their own inconsistent patchwork of regulations. Meanwhile, FDA has turned its back on the safety of millions of Americans by refusing to take action on a legal pathway to marketing CBD. While most supplement companies follow good manufacturing practices (GMPs), bad actors do exist. FDA’s refusal to regulate the CBD marketplace opens the door to CBD products that may be poorly manufactured or illegally marketed.”
Notably, these were the first NDI notifications to receive a response from the FDA, making this a new development over the course of deliberations on where the ingredient stands.
“Based on how FDA engaged these companies over the course of months—having meeting after meeting, request after request for more safety data—and then an invitation to submit NDI notifications, we’re certainly disappointed and surprised that FDA rejected the two NDI notifications,” Steve Mister, president and CEO of the Council for Responsible Nutrition, told Nutraceuticals World. “CRN handed FDA a playbook for creating a regulatory framework for CBD, and FDA punted the ball.”
In each of the agency’s NDI responses, Cara Welch, PhD, acting director of the FDA’s Office of Dietary Supplement Programs stated that because CBD is an active ingredient in Epidiolex, an approved drug, hemp extracts that contain CBD cannot achieve regulatory status as a dietary supplement ingredient. Additionally, Welch mentioned in both letters to the respective CBD manufacturers that the studies they provided didn’t provide adequate data regarding certain endpoints, including hepatotoxicity and reproductive toxicity.
“For these reasons, the information in your submission indicates that, even if your NDI 1202 were not excluded from the definition of a dietary supplement, your notification does not provide an adequate basis to conclude that a dietary supplement containing the ingredient, when used under the proposed conditions of use, would reasonably be expected to be safe,” Welch wrote in response to Charlotte’s Web.
Mister said that he and stakeholders overwhelmingly disagree with hemp extracts’ characterization as the same “article” as Epidiolex. “FDA has wrongly mischaracterized these products as the same article as a prescription drug and has ignored, dismissed, and downplayed the ample evidence that these full-spectrum hemp products can be marketed in a manner that is reasonably expected to be safe.”
“Epidiolex, manufactured by GW Pharma, is a highly-concentrated CBD isolate that contains 10-times more CBD than either of the full-spectrum hemp ingredients and plainly is not the same article supplement companies are producing,” Mister continued.
He also voiced objection to FDA’s characterization of the safety data provided by the two companies as “insufficient.”
Mister added that, because the FDA rejects CBD’s use as a legal dietary supplement ingredient, thus not considering it to be within its inspectional jurisdiction, the current marketplace for CBD products has no government oversight, leaving companies to self-regulate for the quality and safety of their own products.
Daily Consumption Levels Not Mentioned
Daniel Fabricant, president and CEO of the Natural Products Association, said that setting a safe level of daily consumption for CBD products remains the best pathway for regulating the CBD marketplace.
"Future NDI guidance without real clarity on cannabinoids, including CBD doesn’t help the millions of Americans who already believe FDA regulates the space," Fabricant said. The response to this NDI indicates that there is confusion and misunderstanding on all sides of the issue and it must be addressed by the forthcoming guidance. There have to be clear safety rules and thinking on these matters."
A bipartisan bill introduced in the Senate could clarify the NDI process and set a safe level of consumption for CBD products, as part of a larger cannabis reform effort.
NPA has been advocating for establishment of a safe level of daily CBD consumption in supplements since 2017. The trade organization drafted a bill which was passed, which provided resources for FDA to conduct a Health Hazard Evaluation on CBD in order to be able to set a safe level of daily consumption.
This process for CBD in full-spectrum hemp extracts could follow a similar pathway to market as red yeast rice, an ingredient which was originally subject to drug preclusion by FDA during the NDI process. Once a safe level of daily consumption for red yeast rice's constituents was established for dietary supplements, the agency no longer considered red yeast rice, in supplement-level quantities, to be precluded from the NDI process.
Calling on Congress
CBD proponents argue that legal access to CBD as a dietary supplement ingredient, under the inspectional authority of FDA, was the intent of Congress when it passed the 2018 Farm Bill, which legalized the production of industrial hemp. Since then, industry stakeholders have called upon FDA to regulate CBD as a dietary ingredient.
“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,” Mister said.
This far after the passage of the 2018 Farm Bill, as uncertainty still looms, Mister said it seems likely that the only way CBD will progress toward a dietary ingredient status is through lobbying Congress members to pass a bill that would require FDA to set aside its drug preclusion concerns for full-spectrum hemp extract, and to recognize CBD as a dietary ingredient for supplements. Certainly, trade groups will be lobbying for a bipartisan bill to do just that, while assuring FDA applies the same requirements for manufacturing, labeling, and marketing of other dietary supplements.
“Today’s rejection letters disregard clear safety evidence and a distinction between the two forms and concentrations of CBD. So yes, it’s clear that Congress needs to step in to exclude CBD from the drug preclusion language,” Mister said. “FDA chose to disregard volumes of safety data presented by each submitter. FDA’s refusal to make distinctions between Epidiolex’s CBD isolate and the submitters’ full-spectrum hemp extract—different forms, different dosages, different indications, and the submitters not making any drug-like claims—makes it very clear that Congress must step in to resolve FDA’s unwillingness to act logically.”
Mister noted that since CRN first urged the agency to act two years ago, consumer interest in CBD has grown, sales have multiplied, and product innovation has expanded. “Individual states have grown impatient and begun devising their own inconsistent patchwork of regulations. Meanwhile, FDA has turned its back on the safety of millions of Americans by refusing to take action on a legal pathway to marketing CBD. While most supplement companies follow good manufacturing practices (GMPs), bad actors do exist. FDA’s refusal to regulate the CBD marketplace opens the door to CBD products that may be poorly manufactured or illegally marketed.”
