FDA Sends CBD Enforcement Policy to OMB, Issues Cannabis Clinical Research Draft Guidance, and Submits CBD Testing Report to Congress
This summer has been a busy one in the cannabis and cannabis-derived products spaces.
On Wednesday, July 22, 2020, the U.S. Food and Drug Administration (FDA or the Agency) sent to the White House Office of Management and Budget (OMB) for review a draft guidance, “Cannabidiol Enforcement Policy.” As the draft guidance has not yet been released, we can only speculate as to its contents. The enforcement policy could be claims based, serving-size based, product standards based, some combination of the three, or something else. Also on July 22nd, FDA announced the availability of a draft guidance for industry, “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research.” While this draft guidance focuses on cannabis and cannabis-derived drug development, it may nevertheless provide some insight into how the Agency will regulate CBD products in the future. Finally, on July 8th, FDA’s report to Congress, “Sampling Study of the Current Cannabidiol Marketplace to Determine the Extent That Products are Mislabeled or Adulterated,” was made public. The Agency was required to issue this report by June 20, 2020 per the Further Consolidated Appropriations Act, 2020, although it was a few weeks late in doing so (as was the case with FDA’s March report on its progress toward establishing a CBD enforcement discretion policy and potential regulatory pathways for ingestible CBD products).
CBD Enforcement Policy to OMB
On July 22nd, FDA sent to OMB for review a draft guidance, “Cannabidiol Enforcement Policy.” As noted above, because the draft guidance is not yet publicly available, we can only speculate about its contents. However, it seems that clarity could finally be coming to the CBD space, presuming OMB clears the guidance and FDA issues it thereafter. It is hard to believe that the Agency will back off completely from its “ingestibles are not permitted” stance. Perhaps the enforcement policy will be claims focused (e.g., outlining further what would constitute impermissible disease claims). This seems somewhat unlikely, as industry already has a good sense of what FDA will tolerate and what it will not as all enforcement action against CBD products, to date, has centered on very aggressive disease claims (e.g., cancer, COVID-19, AIDS, neuropathy, PTSD, etc.), as discussed previously (here, here, here, here, and here). However, if the Agency outlines the same in a formal enforcement discretion policy, it could give more certainty to marketers offering ingestible products bearing anything other than disease claims. Less likely is that FDA will lay out specific serving size limits (e.g., unless and until the Agency issues a CBD ingestibles rule, any supplement with 50 mg CBD per serving or less will be subject to enforcement discretion). This also seems unlikely, given the data gaps FDA perceives to exist and thus the lack of support for establishing consumption limits. While some stakeholders think that 50 mg CBD or less per serving might be an appropriate limit, we do not believe the Agency will be that proscriptive in an area that it seems to still be wading its way through. On the product standards front, it is possible that FDA could start to hold ingestible CBD marketers to the Agency’s dietary supplement regulations (e.g., good manufacturing practice (GMP) requirements). This is certainly what the supplement industry/trade associations have been pushing for, as it would raise the bar for the industry, push out unsavory firms who are producing unsafe products, and allow marketers to say that they comply with FDA requirements (which would hopefully smooth out the true patchwork of state requirements), among other benefits. However, it is not clear that FDA is prepared to go that far.
OMB review time is difficult to predict, in that some guidance documents get reviewed quickly (e.g., less than two months in the case of FDA’s cannabis clinical research guidance), whereas others take several months or longer. The oldest pending FDA guidance at OMB is from early March 2020. Generally, we might expect to see a decision from OMB on the enforcement policy somewhere between September and January 2021 (or longer).
Cannabis Clinical Research Draft Guidance
Also on July 22, FDA announced the availability of its draft guidance for industry, “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research,” which outlines several key thoughts regarding research and development of cannabis and cannabis-derived drug products. Importantly, the draft guidance provides a new method for drug sponsors, investigators, and applicants (developers) to calculate the percent of delta-9 tetrahydrocannabinol (THC) present in botanical raw materials, extracts, and finished products, which is relevant to assess the controlled substance status of the tested material.
The Agriculture Improvement Act of 2018 (2018 Farm Bill) legalized the production of hemp, which is defined as cannabis and derivatives or extracts of cannabis with no more than 0.3 percent THC by dry weight. Any cannabis or cannabis derivative with more than 0.3 percent THC is considered a Schedule I controlled substance (“marihuana”) under the Controlled Substances Act (CSA) and subject to the Drug Enforcement Administration’s (DEA) authority. In the draft guidance, FDA recommends that developers base the calculation of THC percentage “on the composition of the formulation with the amount of water removed, including any water that may be contained in excipients.” This new method of testing, while targeted at drug development, could provide insight into how the Agency may calculate the THC content of consumer CBD products in the future, although that remains to be seen.
Testing is crucial early in the development process, according to the Agency, so that developers may “gain insight into the potential control status of their product” from the start. FDA recommends that sponsors and developers consult with DEA regarding the control status of their cannabis materials or products that are under development, should such materials exceed 0.3 percent THC. The draft guidance also addresses source material for cannabis drug products, explaining that, while any cannabis meeting the definition of “hemp” under the 2018 Farm Bill is legal, currently, only cannabis above 0.3 percent THC sourced from the National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP) is permitted for clinical research (i.e., even cannabis grown in compliance with the laws and regulations of a state medical cannabis program would not be permitted to support development of a drug product for which FDA approval is sought).
While the Agency’s statements regarding the importance of research and development of cannabis-derived therapeutics are encouraging, until DEA expands sourcing availability for “marihuana” research, there will be little progress in domestic research and development. DEA is reportedly in the process of allowing additional growers and bulk manufacturers to register with DEA to produce and distribute cannabis for research purposes, but this process has been extremely protracted.
Sampling Report to Congress
The Agency’s July 8 report to Congress focuses almost entirely on its CBD product sampling efforts. It provides little in terms of policy or overall conclusions regarding the extent to which currently-marketed CBD products are mislabeled or adulterated, which was supposed to be the purpose of the report, per Congress’s direction in the Further Consolidated Appropriations Act. For the first time in the report, FDA details its testing efforts prior to the passage of the 2018 Farm Bill. In selecting a total of 78 products to test from 2014-2018, the Agency considered several factors, including products that:
- Made “serious disease claims.”
- Were produced or sold in several states to reflect interstate variation.
- Were readily accessible to consumers and available for online purchase.
- Were the basis for consumer complaints or adverse event reports.
Notably, FDA selected and tested only those CBD products that met these particular risk factors (i.e., those produced by bad actors), meaning such testing was not necessarily representative of the overall market at that time.
Of the products tested, cannabinoids were detected in 69 (88 percent) of them, and 67 (86 percent) of them were found to contain CBD. Two products were referred to DEA because they contained controlled substances – a CBD oil capsule with an average of 16 mg/g THC and a CBD gummy found to contain the synthetic cannabinoid MMB-FUBINACA,9, at 1.9 mg/gummy. Interestingly, the Agency not only tested for CBD and THC, but also for lesser-known “minor” cannabinoids, including cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and MMB-FUBINACA.
In 2019, FDA identified 34 CBD products for the testing of certain characteristics, including cannabinoid content and certain elements, by reviewing consumer and industry complaints submitted to the Agency and by conducting online surveillance. Products identified for testing included products marketed with “disease claims” and products intended for vulnerable populations, and were marketed as tinctures/oils, capsules/powders, edibles, beverages, and products marketed for pets.
Interestingly, FDA focused on testing CBD products that made “disease claims” in the 2019 set as opposed to those with “serious disease claims” in the 2014-2018 set. This distinction could signal that FDA intends to broaden its scrutiny of the CBD market, although, historically, as discussed above, the Agency has focused its CBD enforcement on marketers making aggressive therapeutic claims. It is also possible that FDA used the terms “serious disease claims” and “disease claims” interchangeably in the report.
All 2019 tested products were analyzed for elements such as arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb,), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), antimony (Sb), barium (Ba), cobalt (Co), lithium (Li), tin (Sn), and vanadium (V). The levels found in these 34 products “did not raise significant public health concerns,” which is a bit surprising, as FDA has recently rearticulated its concerns about the prominence of dangerous contaminants in some CBD products (previously discussed here).
Of the 21 products that specified how much CBD was present per serving, seven (33 percent) contained CBD within 20 percent of the amount indicated. Of the 10 products that did not indicate the amount of CBD included in the product, six contained CBD and four did not. In addition, 15 of the 31 products (48 percent) contained THC.
FDA went on to indicate that it has been working with the University of Mississippi to develop a method to detect and quantify hemp ingredients in cosmetic products. As part of this process, it selected a total of 109 hemp and/or CBD-containing cosmetic products for testing the presence and levels of CBD, THC, and five other “marker cannabinoids” (cannabidiolic acid (CBDA), CBG, cannabigerolic acid (CBGA), CBN, and tetrahydrocannabinolic acid (THCA)). Of these 109 cosmetic products, 41 of them (38 percent) indicated the product contained CBD, and the remaining 68 of them (62 percent) claimed to contain hemp ingredients, but did not specifically claim to contain CBD. Here are the results from that product testing:
- 41 products that indicated CBD was present in the cosmetic were found to contain CBD.
- Of those 41 products, 12 also contained THC, although the products did not indicate the presence of THC. In addition, of the 41 products that indicated CBD was present, 14 indicated a specific amount of CBD on the label.
- Of those 14 products, eight products contained less than 80 percent of the CBD amount indicated, four products contained within 20 percent of the CBD amount indicated, and two products contained greater than 120 percent of the CBD amount indicated.
- The 68 cosmetic products tested claiming to contain hemp ingredients, but not specifically claiming to contain CBD, did not contain any measurable cannabinoids.
Given what FDA calls “extensive data gaps regarding the current CBD marketplace,” and in light of the results from previous product testing and the directive from Congress, the Agency is undertaking a more extensive sampling effort. FDA announced that it has developed a sampling plan that is divided into two phases: near- and long-term, with near-term results informing the long-term sampling plan.
For the near-term sampling plan, FDA generated a list of 500 marketed CBD and hemp products. Only products sold online were captured in this initial phase of testing. Firms selling CBD and hemp products were identified from several public sources, including from:
- Internet searches (using terms such as “CBD,” “cannabidiol,” “hemp,” “hemp extract,” “Best CBD”);
- searching on-line distributors;
- firms that had previously been issued warning letters;
- industry event participants; and
- advertisers in trade journals.
200 products were randomly selected for testing proportionally from each category based on the total number of products in that category. Tincture/oils/gel caps represent approximately half of the products selected (n = 83).
Interestingly, all products were analyzed for 11 cannabinoids (CBC, CBD, CBDA, cannabidivarin (CBDV), CBG, CBGA, CBN, THC, delta 8-tetrahydrocannabinol (delta 8-THC), THC, THCA, tetrahydrocannabivarin (THCV)), including a quantitative determination of total CBD and total THC. This shows FDA is interested in more than just CBD and THC, although, to date, FDA’s discussions regarding other cannabinoids have been limited.
FDA also performed a quantitative analysis for the elements As, Cd, Hg, and Pb. A subset of products, based on the product type, will be analyzed for pesticides, residual solvents and microbial contaminants (Salmonella and Listeria monocytogenes). Here are the testing results:
- Of the 200 products purchased, testing for cannabinoids was completed on 147 of them. Of the 147 products tested, 138 products (94 percent) contained CBD.
- Of the samples that did not contain CBD (n = 9), seven either did not indicate CBD or clearly indicated “zero CBD” on the label.
- Two products that listed CBD on the label were not found to contain CBD.
- For products that indicated a specific amount of CBD, those amounts were compared to the testing results. Of the 102 products that indicated a specific amount of CBD:
- 18 products (18 percent) contained less than 80 percent of the amount of CBD indicated
- 46 products (45 percent) contained CBD within 20 percent of the amount indicated
- 38 products (37 percent) contained more than 120 percent of the amount of CBD indicated.
- THC levels in the products tested ranged from below the LOQ to 3.1 mg/serving, with 72 products (49 percent) found to contain THC or THCA at concentrations above the LOQ.
- Of the 147 products analyzed for cannabinoids, 133 products were also analyzed for the elements As, Cd, Hg and Pb.
- 132 of them did not contain As, Cd, Hg, or Pb at levels that represent a health concern.
- One product, a tincture, had a Pb concentration that requires additional evaluation, which is currently ongoing.
Finally, FDA plans to conduct long-term sampling, and has developed a sampling methodology to create a representative, random sample of the current CBD product marketplace. The Agency will favor products with a higher market share.
FDA expects the sampling protocol to include most, if not all, of the following product categories:
- Tinctures, oils, and extracts
- Capsules and powders
- Water and other beverages
- Other conventional foods
- Leave-on cosmetic products, like face and body lotions
- Device and combination products, like personal lubricants, tampons, and suppositories
- Vape cartridges
- Products sold for consumption by pets
As was done in the 2020 study, all products will be analyzed for 11 cannabinoids, including a quantitative determination of total CBD, total THC, and the elements As, Cd, Hg, and Pb. Additional analyses, including pesticides, residual solvents, and microbial testing will be performed on a subset of products.
This sampling and testing will be conducted by a third party. The study will start this year with no announced estimated completion date.
The Agency did not provide much useful information in the report conclusion, other than to say that the preliminary data reported from 2014 through present “cannot be used to draw conclusions about the marketplace and supports the need for the long-term study, which will capture multiple retail sources (on-line and brick and mortar) and a greater number of products.” The fact that the Agency does not know the extent to which the body of its testing work is representative of the overall market suggests that we are a long way away from any concrete regulatory framework for CBD. It is clear, however, that FDA remains concerned about potential contaminants in CBD products, and is on the lookout CBD products containing less or more CBD than advertised.
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We will continue to closely monitor this space as FDA’s regulatory approach to CBD consumer products and cannabis and cannabis-derived drug products evolves. In the meantime, if you have questions regarding an issue raised in this alert, please contact the authors or the attorney at the Firm with whom you are regularly in contact.