By Brad Douglass, Ph.D., EAS Independent Consultant
FDA has not received and accepted any generally-recognized as safe for food-use (GRAS) notifications for purified cannabinoids (a.k.a. cannabinoid isolates) to date. Zero. Said another way, if the title of this article were a punny crossword puzzle clue, the only possible answer would be black squares.
Puzzles aside, the Agricultural Improvement Act of 2018 (the “2018 Farm Bill”) further defined the pathway by which “hemp-derived” ingredients can be legally incorporated into food. Hemp-ingredient companies have materialized selling purified cannabinoids that are naturally-occurring in hemp. Despite the young market, these companies are facing difficult times as the buyers for these ingredients are few and manufacturers mostly compete on price. The GRAS path offers a route out of this conundrum.
What is GRAS?
The GRAS for food-use pathway was established by the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act). It delineated how substances that are GRAS for their defined conditions of use in food are different from food additives.
Past EAS Issues of the Month columns by EAS Senior Consultant James Hoadley, Ph.D. have delved into why firms might consider pursuing GRAS notifications and/or New Dietary Ingredient Notifications (NDIN) so I will refrain from wholesale repetition. Two key points on specificity are nonetheless worth repeating: 1) a substance is deemed GRAS for a specific use under specific conditions and 2) a GRAS notification is specific to the company filing the notification.
There are a number of practical reasons why firms that produce cannabinoids would seek to pursue the GRAS pathway. Here are four:
1. Market Expansion
Currently, firms that produce purified hemp cannabinoids are mostly selling their wares to businesses operating in state-regulated delta-9 tetrahydrocannabinol (THC) markets or to operations that may not be in full-compliance with dietary supplement regulations. Almost all firms that produce food products, including beverages, and most dietary supplement manufacturers, will not use ingredients that do not have a history of use in food or that cannot be legally marketed.
For ingredients such as purified hemp cannabinoids that do not have a history of use as articles used for food, the only way to open-up the food, beverage, and dietary supplement markets is via the GRAS/NDIN pathways.
2. Safety Demonstration
An integral part of any GRAS dossier is the basic demonstration of acceptable risk (cf. safety) for the named substance and impurities. This includes any byproducts that may be introduced by the manufacturing process. Whether one is interested in pursuing a GRAS Notification for submission to FDA or for a self-affirmed GRAS conclusion, the process involves an evaluation of safety for the conditions of use (e.g. serving size, no-observed adverse event level, etc.).
Beyond the ethical necessity of understanding the hazards of a product meant for human consumption, pursuing GRAS helps protect a firm from product liability in the event that harm is created. But more importantly, GRAS helps guard against product liability by seeking to prevent the potential hazard in the first place. That is always good for business.
3. Avoiding Drug Preemption
FDA has described in numerous forums, including the Administration’s own website, why it has concluded that cannabidiol (CBD) cannot be used as an ingredient in food or dietary supplements. The key is section 201(ff)(3)(B) of the FD&C Act. This section disqualifies an ingredient from use in food or dietary supplement products if the ingredient is 1) an active ingredient in an approved drug or 2) if substantial clinically-investigation of the substance as a drug has been conducted AND made public.
While the situation remains unclear for CBD, the only way to avoid a similar murky situation for other cannabinoids (e.g. cannabigerol, CBG) is for those ingredients to be marketed as a food or dietary supplement prior to the public disclosure of clinical trials directed at the development of that substance as a drug.
It is FDA’s position that “legal” marketing entails more than simple inclusion of the substance in marketed products—the substance must have been the subject of GRAS or NDIN pathways, if required, to be legally marketed. To that point, FDA is highly unlikely to conclude that legal marketing includes the marketing of products in state-regulated cannabis systems while THC remains federally illegal.
4. Side-Stepping Price Wars
The nascent hemp-derived ingredients market is experiencing significant downward price pressure. The reasons are simple. There is currently more supply than demand (see #1 above) and all commercial offerings are essentially generic.
The GRAS pathway is a mechanism out of this me-too trap. A GRAS cannabinoid would be a premium ingredient by virtue of GRAS status alone. Premium ingredients command premium prices. And the types of sophisticated customers that firms like to do business with do not mind paying premium prices for compliance.
EAS Consulting Group can help. We have assisted many firms step through the intricacies of GRAS, NDIN, and other similar filings. Part of the insight we offer comes from experience as regulatory insiders having former FDA officials within our ranks. More about EAS offerings in this area can be found here.
Bottom-line, if you represent a firm that creates hemp-derived cannabinoids, are a regulator that has responsibility over products that incorporate non-THC cannabinoids, or are just an interested reader that has been left puzzled by this Issue of the Month, do not hesitate to reach out to us at EAS.