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CBD Safety in Edibles: What Regulators are Thinking

By Steven Gendel, Ph.D.
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Despite the popularity of cannabidiol (CBD) infused edibles among consumers there are storm clouds on the horizon for this market. The potential threat stems from continuing uncertainty about the regulatory status of CBD in the United States (US) and the European Union (EU). Recent statements by government agencies in both areas are reminders that regulators could make decisions or take actions that would suddenly end the viability of this market. Any company that sells, or is planning to sell, CBD infused edibles such as bakery items, candy and beverages needs to understand what the regulators are thinking now and what might happen in the future.

in the US, the 2018 Farm Bill created a category of products called hemp that are derived from the Cannabis sativaplant and contain less than 0.3% tetrahydrocannabinol (THC). This law also explicitly confirmed the authority of the US Food and Drug Administration (FDA) to regulate the safety of hemp-derived infused edibles. This means CBD needs to navigate the New Dietary Ingredient pathway for dietary supplements, and either the food additive petition process or the Generally Recognized as Safe (GRAS) pathway for foods before it can be used as an ingredient in a food. All three of these processes require that someone (an individual, a company or a group) acting as a petitioner or notifier must submit safety data to the agency or arrange for a safety evaluation by independent experts.

Just some of the many hemp-derived CBD products on the market today

In the EU, CBD is regulated as a Novel Food in a process that is triggered by a submission to the European Commission. The submission must include safety data that is evaluated by the European Food Safety Authority (EFSA). In England and Scotland, CBD products are also novel foods and are evaluated using a process like that in the EU. As in the US, it is the responsibility of an applicant to provide the safety data.

The standard used by the FDA to judge the safety of new food substances in all three pathways is that there should be a “reasonable certainty in the minds of competent scientists that the substance is not harmful under the conditions of its intended use.” The standard used by EFSA for novel foods is, “the food does not, on the basis of the scientific evidence available, pose a safety risk to human health.”

It is important to realize that both in the US and the EU the safety standard for evaluating new food substances only considers the safety of that substance. The laws or regulations that define agency authority do not allow for consideration of any potential benefits. Approval (or rejection) must be based solely on the safety of the substance. Further, safety is evaluated in the context of the intended use of the substance, the planned level of use and the resulting consumer exposure to that substance.

What do we know about FDA’s and EFSA’s current thinking about CBD safety? 

Unfortunately, both the FDA and EFSA have made it abundantly clear that they believe the available scientific data does not meet the required safety standards. FDA has issued multiple warning letters to companies that sell CBD products and has rejected two NDI notifications for CBD. Although these actions were primarily based on non-safety issues (illegal health claims and the drug exclusion provision in the FD&C Act, respectively), in each case the FDA also raised safety concerns. This was done by saying that the agency is not aware of any data that would support a GRAS determination or that the products raise “concerns about the adequacy of the safety evidence.” This doubt echoes statements from the agency in public meetings and advisories. These doubts were expressed as recently as June 2022 during a meeting of the FDA Science Advisory Board.

Similarly, EFSA has stated that they feel that there are critical gaps in the existing CBD safety data. In April 2022, they published a statement with a detailed analysis of the relevant scientific literature and explicitly identified critical data gaps. EFSA said that these data gaps prevented them from evaluating CBD as a novel food.

What do the regulators see as data gaps?

Although the details of each of the data gaps are technically complex, for both the FDA and EFSA they fall into few broad categories.

FDAlogoThe first is that the agencies feel that they need better information on how CBD behaves in the human body. This is described as understanding the absorption, distribution, metabolism and excretion (ADMA) of CBD. The agencies also would like to see data on whether repeated use of CBD might cause damage to specific organs that does not occur from single exposures.

The second need is for more data related to the negative effects that have been observed in some previous work. This includes effects on the liver and reproductive system.  In particular, the agencies would like to know whether it is possible to identify a level of exposure that is low enough to not cause any negative effects. This is termed the No Observed Adverse Effect Level (NOAEL). In an ingredient safety assessment, the NOAEL is used to establish a safe intake level, called the Acceptable Daily Intake (ADI). Comparing the ADI to the expected exposure for the intended use allows the regulators to assess overall safety for a substance.  If the expected exposure is below the ADI, the substance is considered safe. Both agencies feel that the existing data do not allow them to identify a NOAEL for CBD.

The third data need relates to the composition of the CBD products used in safety studies. Food safety determinations are based on the total composition of an ingredient that is produced using a fully defined process. Even if the potential ingredient is 95% or 99% pure, a safety evaluation needs to know what is in that other 5% or 1%, and that this is the same from batch to batch. For example, the presence or absence of residual processing chemicals (such as extraction solvents) and the nature and concentration of substances such as other cannabinoids and terpenes will differ between manufacturers and processes. These differences could affect the overall safety profile for each CBD product. Therefore, it is considered important that studies supporting a safety determination for a new substance be carried out with the actual article of commerce.

Unfortunately, many different CBD preparations have been used in past studies, and in most cases these preparations were poorly characterized. This makes it difficult or impossible to combine the safety data obtained using one product with data obtained with a different product. For example, data obtained using CBD isolates from two different sources cannot be combined unless it can be shown that they were made using the same process and have the same overall composition.

What does this mean for the future?

Neither the FDA nor EFSA is likely to take any positive action on CBD until they receive safety data that fill the gaps that they have identified.

Given these data problems, it is likely that there will be little or no movement on regulatory approvals for CBD in edibles (or dietary supplements in the US) for at least several years. In the US, these products will remain in legal limbo, with state regulations playing the leading role in determining what is allowed on the market. Products with health claims will continue to be particularly vulnerable to FDA action.  The situation in the EU will be at least as confusing because, in the absence of action from EFSA, the regulatory and market status of CBD edibles will be determined by each member country independently.

In view of this uncertainty and business confusion, that are three ways that companies making CBD and CBD edibles can respond. First, in the short term, they can develop and implement manufacturing processes that ensure that their products are consistent from batch to batch and that they have the intended dose of CBD per serving or per product unit. This includes working with the analytical community and organizations such as AOAC and ASTM to ensure that there are validated testing methods available for the CBD and for the final edible products.

In the medium term, business risk management plans for companies that make CBD and CBD infused edibles should consider the possibility that new scientific data will push food safety authorities to actively conclude the CBD does not meet the current regulatory safety standards. In that case, the regulators might start to act against all CBD-containing products.

The structure of cannabidiol (CBD), one of 400 active compounds found in cannabis.

Businesses should also be aware that the agencies could make a positive safety determination but that they would use the available data to establish a low maximum allowed dose per serving or set very low limits on the presence of specific contaminants such as other cannabinoids.

In the longer term, the CBD industry as a whole might consider advocating for legislative changes. The best statutory fix is likely to be one that that regulates all cannabis-derived products in a system or agency that is separate from the food safety system. This approach is being used in Canada under the Cannabis Act. It is also similar to the way that alcoholic beverages are regulated in the US. This approach, if appropriately designed, could avoid the need for safety determinations but might also limit market access. While this approach could bring clarity and certainty to the market, it is important to remember that it will take time and effort to create a functionally system under this scenario.

There are many market reports that forecast on-going high rates of growth for the CBD market.  However, the regulatory and scientific developments that are likely to occur of the next couple of years will determine whether those projections can become reality.

Companies making these products need to monitor changes and prepare to respond to either positive or negative events.

These companies should also remember that edible products are mostly made from food ingredients using standard food product processes. It is critical that these products be made under a system that prevents food-borne hazards.

Leaders in Cannabis Formulations: Part 5

By Aaron Green
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Natural cannabinoid distillates and isolates are hydrophobic oils and solids, meaning that they do not mix well with water and are poorly absorbed in the human body after consumption. Cannabinoid oils can be formulated into emulsions to form a fine suspension in water to modulate bioavailability, stability and flavor.

Happy Chance is a cannabis infused products company offering better-for-you products to their customers. Happy Chance recently launched a low-glycemic index fruit bite line made from fresh ingredients, distinguishing them from traditional gummies. Splash Nano is a cannabis infused products ingredients company specializing in nano emulsions. Happy Chance utilizes Splash Nano technology in their fruit bites formulations.

We spoke with Katherine Knowlton, founder of Happy Chance, and Kalon Baird, co-founder and CTO of Splash Nano to learn more about their products and how they came to do business together. Prior to Happy Chance, Knowlton worked as a chef. Prior to Splash Nano, Baird was a consultant to the cannabis industry.

Aaron Green: Katherine, how did you get involved in the cannabis industry?

Katherine Knowlton, Founder of Happy Chance

Katherine Knowlton: I am a chef by trade. I went to culinary school in 2015. My partner also got into the cannabis space in 2017, which was right around the time when adult use cannabis became legal in California. As a chef, I am very passionate about cooking for optimal health and well-being. I noticed right away the abundance of candy- and sugar-laden products on the market. I set out to create a wellness driven product blending healthy, whole foods with a better value proposition, better-for-you and better-for-the-planet.

Green: Okay, great. Kalon, same question: how did you get involved in the cannabis industry?

Kalon Baird: I left a corporate job in 2011 and started cultivating in Southern California. I started to develop techniques for horticulture and developed a connection with the plant. I was a consultant for many years, and then decided to take a different path when legalization happened and got into the regulated manufacturing space. My goal was to bring new products to market to help satiate the demand for the infused category, the non-smokeable categories and to pursue niche product development.

Green: Tell me about your recent product development interests?

Kalon Baird, Co-Founder and CTO of Splash Nano

Baird: We’re interested in the research that comes out regarding cannabis minor constituents. We work with other research labs doing two-dimensional chromatography. We’re trying to figure out what compounds exist in the plant that aren’t just the major cannabinoids, and how to work with them in a pharmacological context so that they can be standardized and replicated at scale.

So, it’s not just about making a sugary THC gummy, it’s about seeing what minor cannabinoids, what minor terpenoids and what other unknown compounds can we explore, and then put back into products.

Green: That’s 2D GC-mass spec?

Baird: Yeah, it’s GC-by-GC and tandem mass spec. There are only a couple people that make that piece of equipment. The lab that we work with on that project is called Veda scientific. They’re one of the only people in the cannabis space that uses that machine. And they’re right in our backyard. The tech enables us to further quantify terpene profiles and helps to differentiate our products.

Green: I’d like to focus first on the Splash Nano technology and then we’ll dig into how you got to know each other, and then we’ll finish off with learning more about Happy Chance. So Kalon, tell me more about Splash Nano.

Baird: We employ nano emulsion technology. It’s essentially the science of making oil and water compatible and suspended in a way that reduces droplet size. With nano emulsions, you create an interfacial layer that enhances absorption and solves technical problems like being able to make cannabis oil compatible in water-based matrices, and sometimes in non-water-based matrices. The idea is that as we spread out the particles and as we change attributes of how they’re coated, they’re more bioavailable, and you get a more consistent and faster onset experience like you would in the pharmaceutical or alcohol industry. It’s bringing the industry standard up to the consumer package level and the pharmaceutical level, so that people aren’t waiting the typical hour-long timeframe to absorb that first dose.

Green: Tell me about your business model.

Baird: When we started out in 2018, we were going for a manufacturing license. In the meantime, we saw the drink category evolving and we wanted to be a part of that conversation in that ecosystem. We started developing our own nano emulsions that we knew would be useful when we got our license. We knew that we would sell the base material to co-packers who would put them into beverages. We didn’t want to co-pack the beverages ourselves. So, we developed a drink additive that was our proof of concept that had legs for the technology so that we could show people how to use it. That proof of concept spun off and became its own product and now it’s in the market under the brand name Splash Nano and comes in four distinct product SKUS using minor cannabinoids as differentiators.

The Splash Nano drink additive

Meanwhile, our bread-and-butter business was working with smaller brands, like Happy Chance that needed a path to market but couldn’t get the license or couldn’t go through that whole rigmarole of a two-year waiting period and a half a million dollars and all the other stuff. So, we started taking on all these smaller brands effectively licensing their brand IP and their ideas. In the process, we ended up learning a ton about product development and it became kind of a passion.

We have three core revenue streams. One of them is contract manufacturing, or private labeling. The other one is our own product Splash Nano which is a drink additive. And then the last is we open sourced the technology and sell that as a business-to-business platform so that people can infuse their own products with our fast-acting emulsions. We’re working on a licensing model that will allow other states to create that same consistency, where we send a black box model out to them, and then they infuse the cannabis and then turn that into a product.

Green: Moving on to Katherine here. Tell me about Happy Chance, and how you came up with the brand concept and the product idea.

Knowlton: Going back to what I touched on earlier, many traditional edibles in the space are brownies, cookies and candy type of products that do not contribute to wellness. I wanted to give the wellness driven consumer an option in cannabis. I wanted to create a powerhouse edible that was not only functional and complete but that elevated the consumer’s experience as a whole because of the ingredients we choose and the whole cannabis we source.

Some of the Happy Chance fruit bites

I’m someone who values better-for-you products that contribute to optimal health and well-being. So, I set out to make something. I didn’t really know what I wanted to make in the beginning. I bought a dehydrator and a food processor, and I started messing around with different applications in my kitchen. Over 100 variations later, the fruit bite was born.

The fruit bite is made with dates – a natural sugar that delivers nutritional power: a low glycemic index and high in vitamins, minerals and antioxidants. A sweet you can feel great about. And we use pumpkin seeds which have a lot of great protein. We are working with a company in California that takes imperfect fruits and vegetables and upcycles that back into the food supply chain. We utilize the whole fruits and vegetables as a dried intermediate, capturing all the flavor of nutrients. No added natural flavors and nothing from concentrate.

Green: How does the consistency differ from a gummy?

Knowlton: The consistency is similar to a Lara bar or an Rx bar. Essentially, it’s that same consistency in a bite form and so it’s very different than a gummy. It’s a low dose, low sugar alternative to the modern-day gummy.

Green: So, you’ve got this healthy concept for the fruit bite. You’re looking at suppliers and technologies to infuse the product. How did you finally decide on Splash Nano?

Knowlton: I watched my partner lose his company a few years ago to a larger vertically integrated company. The MSO promised the moon and the stars, and they got lost in the weeds of their eco-system, ultimately losing their company. That said, I was very sensitive when I first started on this journey. I even took on my own partners who didn’t work out either. I spoke with a lot of manufacturers in the selection process. Splash Nano was the tenth manufacturer I spoke with.

It was a very organic way of meeting. I am also based in Santa Barbara where Splash Nano is located. My partner’s brother shared an office space with Kalon, so we met through that connection. I learned right away that Splash was founded on wellness, much like Happy Chance. It was important to source clean cannabis, an aspect that Kalon and his team take pride in. We quickly discovered that Kalon’s Splash Nano technology was going to work in my product. Happy Chance immediately found a home, and it has been an organic evolution of realistic business and friendship.

Green: Kalon, I’d love to get your perspective as well. How do you think about partnering with brands?

Baird: Because of our contract manufacturing experience, we’ve been able to touch approximately 50 brands over our three-year tenure in this space. We’ve seen kind of everything from the multi-state operator to the owner-operator and everything in between. I developed a passion for working with these smaller brands for a lot of different reasons. This industry is built on the success of small mom and pops. Yes, the multi-state operators do have a place and they absolutely add a lot of value. But at the same time, they have their own natural challenges. You have essentially a culture of employees versus a business owner that’s making a lot of their own decisions.

There are advantages to somebody like Katherine, who’s in the trenches of business, and understands the ebbs and flows and ups and downs of this industry and be able to get through some of those challenges a lot more organically and a lot more sustainably. Katherine has such a deep pulse on her business and on her customer and on her own money. She tends to make a lot more calculated decisions, and I really appreciate that.

There’s a lot of waste that gets accumulated in this industry through packaging, through bad decisions, and over extensions of capital. It’s sad to watch and you see these people that have great potential, but it’s kind of lost in this sort of the framework of a large organization. Again, I like multi-state operators, they’re great. There’s nothing wrong with them, but it’s just a different flavor. I’m trying to highlight the fact that working with somebody that has a pulse on her business, and the passion for what she’s doing is wonderful. It’s not just about making money; it’s about adding value.

Green: Katherine, talk to me about sustainability and how you’ve woven that into your product.

Knowlton: We’re dedicated to supporting Product, People and Planet. That’s the whole mission and ethos of Happy Chance. As a chef, I wanted to be intentional about where our ingredients come from. We only source organic and upcycled ingredients – an essential recipe in sustaining a healthy, eco-friendly plant. Intention and integrity are always at the forefront of our products. We prioritize partnering with more transparent supply chains. We want to show the world how cannabis can promote positive lifestyle changes that support living more actively and consciously.

To reiterate, we are also not using anything from concentrate. We are using the entire strawberry, the entire blueberry and so it encapsulates all the flavor and all the nutrition that you would have from a fresh fruit into our products.

Green: How do you think about sustainability in product packaging?

Knowlton: As far as packaging goes in this industry, we’re very limited in what we can do. Compostable packaging isn’t really available, but we have partnered with a packaging company that definitely has mindfulness at the core of their mission. They have established their entire supply chain to ensure they are focusing on green practices and reducing waste each step of the way. Their energy efficient machinery creates a zero-waste manufacturing process to reduce their carbon footprint and they utilize soy and vegan inks to help reduce air pollution by minimizing toxic emissions in the air. My hope for the industry is that as it continues to evolve, we can become less wasteful as far as packaging goes.

Green: Rapid fire questions for both of you: What trends are you following in the industry right now?

Knowlton: As a chef and coming from the CPG world, I’m passionate about health and wellness. I think that it’s important to stay on trend with what we’re seeing in CPG. There’s definitely a market as far as people wanting these better-for-you products. I want to bring that into the cannabis space.

Baird: We’re seeing the inclusion of minor cannabinoids, terpenoids, standardized recipes and faster- or slower-acting delivery systems. So, I’m following trends in advanced drug delivery systems paired with minor cannabinoids.

Green: What are you most interested in learning about?

Knowlton: I’m most interested in how I can take what I’ve learned in the food space and help bring that into the world of cannabis through Happy Chance. Ultimately cannabis is plant medicine. So, how can we educate people that the ingredients we choose to make products should be good for us too. I think that there’s a lot that can be done with it from a from a health and wellness standpoint.

Baird: I’m interested in learning more about the analytical overlay between quantifying and standardizing entheogens and plant medicines like cannabis into the product development process in CPG. I’m thinking of ways to blend the two worlds of traditional science and New Age medicine.

Green: Awesome, that concludes the interview. Thank you both, Katherine and Kalon.