One of several firms developing platforms to biosynthesize cannabinoids via fermentation, Amyris has studied how the cannabis plant creates CBD and effectively reverse engineered the process by taking the same genes that ‘instruct’ the plant to make CBD and inserted them into a yeast. This then eats sugars in a big fermentation tank and produces CBD. (While the yeast is genetically engineered, there is no yeast in the final product.)
Speaking to FoodNavigator-USA at the recent IFT annual meeting and Expo in New Orleans, Amyris chief operating officer Eduardo Alvarez said producing CBD in this way offered significant benefits over extracting it from cannabis plants, including consistent purity and dosage; improved yield; no pesticides; no heavy metals or other contaminants from the soil; the reassurance of no THC; and lower water and land usage.
Purity, scalability, and cost
“We see three major advantages,” he said. “Purity, scalability and lowest cost.
“So on purity, we hear from consumers that they worry about the safety of the product and we really do believe our method produces the safest CBD molecules in the market.
“On scalability… using our [fermentation-derived Reb M] sweetener as an example, we are able to scale production this year 10-fold, by next year we’ll scale up six fold on top of that… so let’s compare that with a leaf-based CBD. If you look at one of the leading players, Canopy, they went up by a factor of four to five fold over the first two to three years, so you can see how scalability is going to be key especially while keeping purity and traceability.”
While Amyris is one of several companies in the emerging fermentation-derived CBD space, he added, cannabinoids are closely related to terpenes, an area in which Amyris has “substantial experience and expertise.” Because of this prior terpene work, Amyris has completed a significant portion of the development steps toward the cannabinoid pathways, he added.
“We have a history of scaling fermentation and biotech based products, specifically with terpenes, which is a family of products that really will help us accelerate and ensure the highest purity.”
Yeast and other microbes are increasingly being used as production platforms for cannabinoids, sweeteners, flavors, colors and proteins via fermentation because the approach is claimed to be more efficient - and sustainable – than raising animals or devoting vast tracts of land to growing plants in order to extract molecules that might only be found in the plant in microscopic quantities.
Isolates vs broad and full spectrum extracts
Asked whether food and supplement companies, especially in the natural products arena, wanted isolates or broad or full spectrum hemp extracts (which contain CBD, but also other cannabinoids, terpenes etc), he said:
“I think the market is really evolving… but we believe that producing isolates of high purity, high availability, repeatable, is going to be a very important first step.”
For customers looking beyond CBD, he said, “Because we have the terpene platforms, we can produce other related products [along with CBD] with equal scalability and time, so we will be able to formulate the mixes [of CBD and other cannabinoids] as a second step, once we have the clinical trials to verify which combinations work best.”
Under a deal signed in March for cannabinoid development, licensing and commercialization, LAVVAN will be responsible for the global manufacture and commercialization of the cannabinoids, while Amyris will contribute its R&D expertise.
Asked whether the regulatory uncertainty over CBD - which is not currently permitted in foods and supplements in the US - gave him pause, Alvarez said:
"We know the FDA will do the best it can to protect the public… We have a lot of history working with the FDA; specifically we’ve worked with them on our [fermentation-derived] sweeteners…and we believe they are trying to balance doing the right thing for the public and also moving fast.”
While some stakeholders at the recent FDA public hearing on CBD seemed to be pushing for a different regulatory pathway for “highly purified CBD isolates” such as those used in some drug trials, versus hemp extracts (which, they argued, should be permitted to go through the GRAS/NDI notification process), Alvarez said the important thing was to focus on the composition and safety of the products themselves, not how they were produced/sourced.
“We would love for the FDA to provide clarity [on the legal path forward for CBD] knowing that there may be multiple paths… [but] also keeping the focus on product safety and composition, and not on the underlying technologies.”
Nielsen predicts that, by 2025, the US hemp-derived CBD market could be worth $6bn, 44% of which ($2.65bn) will be from foods and beverages, with snacks representing a key area of opportunity, regulatory challenges notwithstanding.
"This suggests a sizeable opportunity for CPG snack and confectionery manufacturers within the CBD space. Today’s shoppers are increasingly seeking out snacks with added health and wellness benefits. Lockstep with this smart snacking trend, some believe that adaptogens and botanical hemp extracts that naturally contain CBD could be the next frontier in snacking.
"Some future CBD consumers may look to CBD-infused food offerings to enhance focus, relaxation and to assist in promoting their general health and wellness. For others, consumption may be geared toward targeting specific ailments such as feminine pain, digestive issues and sleep disorders. Therefore, CPG snack companies interested in reaching these consumers should start factoring various need states, use cases and snacking occasions into their R&D equation.
"For example, incorporating CBD into a snack category that fits into an existing routine may perform better than those that are more oriented around indulgence or infrequent occasions. As a result, consumption occasions like pre/post workout snacks, breakfast-on-the-go bars and bedtime snacks should be part of the consideration set."
What's the regulatory path forward for CBD?
While not everyone was on the same page about the legal path forward for hemp-derived CBD during the FDA's recent public hearing, multiple speakers made clear that the current situation is untenable, with one predicting a wave of lawsuits, and others demanding that the agency either crack down on companies marketing such products, or explicitly spell out that existing regulatory frameworks can accommodate them.