Back in 2020, the European Commission formally classified edible cannabidiol (CBD) products like gummies, drinks, oils and even bread as novel foods (NFs). Today, all submitted applications remain on hold, with no CBD products receiving NF authorisation in the UK or Europe.
Here Libby Clarke, managing consultant for Toxicology at Broughton, explores how companies can optimise their testing strategies.
Both European and UK law defines NFs as food, drink or ingredients that were not consumed to a significant degree by people in the European Union before May 1997. This includes food products new to the EU market that were already consumed elsewhere, as well as foods produced using new technologies or from newly discovered sources. The CBD market is included in this — CBD products began to establish around 2016, and the popularity of gummies, chocolates and drinks available has been on the rise ever since.
NF applications for edible CBD products must be approved by the European Food Safety Authority (EFSA). In January 2019, the European Commission updated the Novel Food Catalogue to include extracts of Cannabis sativa. By March 2022, it had reportedly received over 150 NF applications, and EFSA was conducting scientific assessments for 19 at that time.
In June 2022, during these assessments, EFSA concluded that there were significant knowledge gaps in submitted applications, which needed to be addressed before the safety of CBD products could be established and approval granted. Consequently, all applications were placed on hold.
This action was taken because EFSA felt that the submitted applications lacked critical information, particularly the effects on absorption, distribution, metabolism and excretion (ADME), as well as the liver, gastrointestinal tract, endocrine system, nervous system and psychological function. EFSA also reported that manufacturers had not adequately clarified the potential impact of lower doses.
Therefore, the existing evidence must be further substantiated by long-term studies that focus on a low dose range. Endocrine and reproductive studies were another example of where human trials have been lacking, and where manufacturers have been unable to evidence low-dose effects.
The trouble with tiering
EFSA proposed using a tiered framework to assess the risk of novel foods, additives and pesticides. This framework acts as a guide for businesses who are designing their toxicological testing strategy as part of their NF application. The approach is based on a hierarchy of tests, beginning with simple absorption, in vitro genotoxicity and extended in vivo 90-day toxicity tests. Should further testing be deemed necessary, more in-depth studies should be carried out. If tier two studies, which may include prenatal developmental toxicity and single dose ADME analyses, raise further concerns, then more specialised tier three tests would be required. Tier three tests aim to investigate specific concerns such as reproductive and developmental toxicity, or a particular mode of action behind an observed effect.
While the tiered system is a robust approach for most NFs, it is unlikely to be viewed as sufficient for addressing the CBD data gaps highlighted by EFSA.
Although recent publications investigating liver toxicity and reproductive effects enable the calculation of a derived no-effect level for CBD, the identification of the sensitive endpoint is still unclear. Most of the data we have comes from clinical trials, including data from GW Pharmaceuticals’ Epidolex, used in the treatment of seizures, and Savitex, used to treat symptoms of multiple sclerosis. However, the reported adverse side effects reported in patients taking clinical doses may not be helpful for assessing NF safety, as the general population is likely to be taking much lower doses in comparison.
Specific studies are needed that can establish drug interactions, accumulation and potential low dose effects. A three-month rat study might be appropriate to determine the general toxicity of a CBD product, but it’s likely that human studies will also be required, especially when considering potential psychological effects of taking CBD at a low dose for extended periods of time. Consequently, manufacturers may benefit from an alternative, more specialised approach to testing CBD-containing NFs than offered by the tiering system.
Strategic study design
A targeted approach to testing is needed, one that is designed to answer the specific concerns flagged by EFSA. To reduce costs and increase efficiency, manufacturers must carefully consider which tests are conducted and when, and establish which must be run first, and if any studies can run concurrently.
While there may be some tests that can cover multiple bases, others will be highly specific to individual products. For example, gummies and other solid food products will take much longer than a drink will to be absorbed by the body, and an oil-based product may also be absorbed quickly due to CBD’s solubility in fats. Consequently, any absorption data submitted as part of one application will most likely only be relevant to the named product.
The data-gathering stage could take a year or longer, depending on the testing strategy, with additional time for initial study planning, data processing and incorporation of findings in an application. For smaller manufacturers, the cost of gathering the necessary data will be significant, and perhaps even prohibitive.
However, joining a consortium to collaborate and share the cost of more general studies could help these smaller firms mitigate the effects of fewer resources. Collaborating with CBD specialists like Broughton, can also help manufacturers can close any gaps in their applications and accelerate the route to regulatory approval.
The post Broughton: How to design a robust CBD testing strategy appeared first on Cannabis Health News.
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Author: Opinion editor
