Tag Archives: Testing

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How Do You Know You’re Right? qPCR vs. Plating

By Dr. Sherman Hom
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Cannabis testing to detect microbial contamination is complicated. It may not be rocket science, but it is life science, which means it’s a moving target, or at least, it should be, as we acquire more and more information about how the world we live in works. We are lucky to be able to carry out that examination in ever increasing detail. For instance, the science of genomics1 was born over 80 years ago, and just twenty years ago, genetics was still a black box. We’ve made tremendous progress since those early days, but we still have a long way to go, to be sure.

Much of that progress is due to our ability to build more accurate tools, a technological ladder, if you will, that raises our awareness, expertise, and knowledge to new levels. When a new process or technology appears, we compare it against accepted practice to create a new paradigm and make the necessary adjustments. But people have to be willing to change. In the cannabis industry, rapid change is a constant, first because that is the nature of a nascent industry, and second because in the absence of some universal and unimpeachable standard, it’s difficult to know who’s right. Especially when the old, reliable reference method (i.e. plating, which is basically growing microorganisms on the surface of a nutritional medium) is deeply flawed in its application to cannabis testing vs. molecular methods (i.e., quantitative polymerase chain reaction, or qPCR for short).

Dr. Sherman Hom, Director of Regulatory Affairs at Medicinal Genomics

Plating systems have been used faithfully for close to 130 years in the food industry, and has performed reasonably well.2 But cannabis isn’t food and can’t be tested as if it were. In fact, plating methods have a host of major disadvantages that only show up when they’re used to detect cannabis pathogens. They are, in no particular order:

  1. A single plating system can’t enumerate a group of microorganisms and/or detect specific bacterial and fungal pathogens. This is further complicated by the fact that better than 98% of the microbes in the world do not form colonies.3 And there is no ONE UNIVERSAL bacterial or fungal SELECTIVE agar plate that will allow the growth of all bacteria or all fungal strains. For example, the 5 genus species of fungal strains implicated in powderly mildew DO NOT plate at all.
  2. Cannabinoids, which can represent 10-30% of a cannabis flower’s weight, have been shown to have antibacterial activity.4 Antibiotics inhibit the growth of bacteria and in some cases kill it altogether. Salmonella species & shiga toxin producing coli (STEC) bacteria, in particular, are very sensitive to antibiotics, which leads to either a false negative result or lower total counts on plates vs. qPCR methods.
  3. Plating methods cannot detect bacterial and fungal endophytes that live a part or all of their life cycle inside a cannabis plant.5,6 Examples of endophytes are the Aspergillus pathogens (A. flavus, A. fumigatus, A. niger, and A. terreus). Methods to break open the plant cells to access these endophytes to prepare them for plating methods also lyse these microbial cells, thereby killing endophytic cells in the process. That’s why these endophytes will never form colonies, which leads to either false negative results or lower total counts on plates vs. qPCR methods.
  4. Selective plating media for molds, such as Dichloran Rose-Bengal Chloramphenicol (DRBC) actually reduces mold growth—especially Aspergillus—by as much as 5-fold.This delivers false negative results for this dangerous human pathogen. In other words, although the DRBC medium is typically used to reduce bacteria; it comes at the cost of missing 5-fold more yeast and molds than Potato Dextrose Agar (PDA) + Chloramphenicol or molecular methods. These observations were derived from study results of the AOAC emergency response validation.7
  5. Finally, we’ve recently identified four bacterial species, which are human pathogens associated with cannabis that do not grow at the plating system incubation temperature typically used.8 They are Aeromonas hydrophila, Pantoea agglomerans, Yersinia enterocolitica, and Rahnella aquatilis. This lowers total counts on plates qPCR methods.

So why is plating still so popular? Better yet, why is it still the recommended method for many state regulators? Beats me. But I can hazard a couple of guesses.

A yeast and mold plate test

First, research on cannabis has been restricted for the better part of the last 70 years, and it’s impossible to construct a body of scientific knowledge by keeping everyone in the dark. Ten years ago, as one of the first government-employed scientists to study cannabis, I was tapped to start the first cannabis testing lab at the New Jersey Dept. of Health and we had to build it from ground zero. Nobody knew anything about cannabis then.

Second, because of a shortage of cannabis-trained experts, members of many regulatory bodies come from the food industry—where they’ve used plating almost exclusively. So, when it comes time to draft cannabis microbial testing regulations, plating is the default method. After all, it worked for them before and they’re comfortable with recommending it for their state’s cannabis regulations.

Finally, there’s a certain amount of discomfort in not being right. Going into this completely new area—remember, the legal cannabis industry didn’t even exist 10 years ago—we human beings like to have a little certainty to fall back on. The trouble is, falling back on what we did before stifles badly needed progress. This is a case where, if you’re comfortable with your old methods and you’re sure of your results, you’re probably wrong.

So let’s accept the fact that we’re all in this uncharted territory together. We don’t yet know everything about cannabis we need to know, but we do know some things, and we already have some pretty good tools, based on real science, that happen to work really well. Let’s use them to help light our way.

References

  1. J. Weissenbach. The rise of genomics. Comptes Rendu Biologies, 339 (7-8), 231-239 (2016).
  2. R. Koch. 1882. Die Aetiologie der Tuberculose.  Berliner Klinische Wochenschrift, 19, 221-230 (1882). 
  3. W. Wade. Unculturable bacteria—the uncharacterized organisms that cause oral infections. Journal of the Royal Society of Medicine, 95(2), 91-93 (2002).
  4. J.A. Karas, L.J.M. Wong, O.K.A. Paulin, A. C. Mazeh, M.H. Hussein, J. Li, and T. Vekov. Antibiotics, 9(7), 406 (2020).
  5. M. Taghinasab and S. Jabaji, Cannabis microbiome and the role of endophytes in modulating the production of secondary metabolites: an overview. Microorganisms 2020, 8, 355, 1-16 (2020).
  6. P. Kusari, S. Kusari, M. Spiteller and O. Kayser, Endophytic fungi harbored in Cannabis sativa L.: diversity and potential as biocontrol agents against host plant-specific phytopathogens. Fungal Diversity 60, 137–151 (2013).
  7. K. McKernan, Y. Helbert, L. Kane, N. Houde, L. Zhang, S. McLaughlin, Whole genome sequencing of colonies derived from cannabis flowers & the impact of media selection on benchmarking total yeast & mold detection tools,  https://f1000research.com/articles/10-624 (2021).
  8. K. McKernan, Y. Helbert, L. Kane, L. Zhang, N. Houde, A. Bennett, J. Silva, H. Ebling, and S. McLaughlin, Pathogenic Enterobacteriaceae require multiple culture temperatures for detection in Cannabis sativa L. OSF Preprints, https://osf.io/j3msk/, (2022)

AOAC Launches Cannabis Proficiency Testing Program

By Cannabis Industry Journal Staff
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In a press release published this week, AOAC International announced it has partnered with Signature Science, LLC as the test material provider for the new AOAC Cannabis/Hemp Proficiency Testing program. What makes this proficiency testing (PT) program so unique is that AOAC will be the only PT provider to offer actual cannabis flower as the matrix.

This month, the pilot round with twenty cannabis testing labs begins with hemp-only samples being shipped in early May. The first live round of the PT program is scheduled for November of this year and will offer participating labs the choice of cannabis flower samples or hemp samples.

The program will include one sample for cannabinoid and terpene profiles, moisture and heavy metals, as well as a second sample for pesticide residue testing. According to the press release, mycotoxins will be added to the mix soon.

The new PT program was developed by stakeholders involved with the AOAC Cannabis Analytical Science Program (CASP), including state regulatory labs, industry labs, state and federal agencies and accreditation bodies. Shane Flynn, senior director of AOAC’s PT program, says the program is a result of scientists coming to them with concerns about testing in the cannabis space. “AOAC has a long history of bringing scientists together to address emerging topics, so when stakeholders came to AOAC with their concerns and need for quality proficiency testing in the cannabis industry, AOAC acted,” says Flynn. “Stakeholders noted the analytical differences in testing cannabis versus hemp and had specific concerns around it and asked for a program that would provide actual cannabis samples in addition to hemp. This is truly a program that was created by the stakeholders, for the stakeholders.”

AOAC says they plan on introducing microbiology to the PT program, with microbial contamination tests in both cannabis and hemp samples. They are also considering adding additional matrices, like chocolate and gummies.

Signature Science is an ISO 17043 accredited proficiency test provider that also has a DEA-licensed controlled substances lab, making them an ideal candidate to partner with AOAC for the PT Program. They entered into a 3-year MoU with AOAC for the program. Their team developed and validated methods used to create the samples for the PT program at their DEA-licensed lab in Austin, Texas.

Steep Hill Expands to Vermont

By Cannabis Industry Journal Staff
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Steep Hill, the company that started the first cannabis testing laboratory in the United States, today announced their expansion into Vermont. Their licensee, Steep Hill Vermont, is the first lab in the state to receive pre-approval from the state, according to a press release.

The leadership team is made up of CEO Kos Parulekar, Dr. Mark Scialdone, chief scientist and Callie Chapman, who will be the lab director. Parulekar previously held management roles at General Electric and The World Bank.

Dr. Scialdone will be speaking at the Cannabis Quality Conference & Expo. Click here to learn more. Dr. Scialdone worked at DuPont for eighteen years before joining the cannabis industry and becoming an expert in plant oil extraction, analysis and natural product chemistry. Dr. Scialdone is a member of the ASTM D37 cannabis committee, the NCIA testing policy working group and is a founding member of the cannabis chemistry subdivision at ACS. “We chose to partner with Steep Hill because of their breadth of experience from opening multiple cannabis testing labs across the country that are considered the gold standard for quality results, rapid turnaround time, and impeccable customer service,” says Dr. Scialdone. “Vermont has long had the status of the Humboldt County of the East having a long tradition in cannabis, so opening a testing lab here makes sense on many levels.”

Chapman is a chemical engineer who previously worked for Autumn Harp as their head of cannabis product development. “Working with the State of Vermont, our laboratory plans to expand cannabis testing services, while offering quick turnaround times and educational resources for cultivators, manufacturers, and other industry participants,” says Chapman. “Our goal is to be a key partner in the success of the Green Mountain State’s adult use market and continue to grow our industry.”

Just a few months ago, in December of 2021, Steep Hill announced their expansion into Illinois. In March of 2019, the company expanded into New Jersey through their partnership with Green Analytics East.

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FDA Issues First Warning Letters for Delta-8 THC

By Cannabis Industry Journal Staff
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In an unprecedented move, the U.S. Food & Drug Administration (FDA) has issued warning letters today to companies selling products containing delta-8 THC. In total, the FDA sent out five warning letters to companies for violating the Federal Food, Drug, and Cosmetic Act (FD&C Act).

Image from the FDA’s consumer update on Delta-8 THC

The violations include illegal marketing of unapproved delta-8 THC products as treatment for medical conditions, misbranding and adding delta-8 THC to food products. Back in September of last year, the FDA published a consumer update on their website, seeking to educate the public and offer a public health warning on delta-8 tetrahydrocannabinol, otherwise known as delta-8 THC.

Delta-8 THC is a cannabinoid that can be synthesized from cannabidiol (CBD) derived from hemp. It is an isomer of delta-9 THC, the more commonly known psychoactive cannabinoid found in cannabis. Delta-8 THC does produce psychoactive effects, though not quite as much as its better-known cousin, delta-9 THC. Many regulators and industry stakeholders are increasingly concerned about the rise in popularity of delta-8 products, namely because of the processing involved to produce it. Delta-8 THC is often synthesized using potentially harmful chemicals.

The FDA has a history of sending a lot of warning letters to companies marketing CBD products inaccurately and making drug claims. Earlier this year, they sent a number of letters to companies claiming that CBD can cure or prevent Covid-19.

FDAlogoAccording to Janet Woodcock, M.D., principal deputy commissioner at the FDA, they are getting more and more concerned about the popularity of delta-8 THC products sold online. “These products often include claims that they treat or alleviate the side effects related to a wide variety of diseases or medical disorders, such as cancer, multiple sclerosis, chronic pain, nausea and anxiety,” says Woodcock. “It is extremely troubling that some of the food products are packaged and labeled in ways that may appeal to children. We will continue to safeguard Americans’ health and safety by monitoring the marketplace and taking action when companies illegally sell products that pose a risk to public health.”

The FDA sent warning letters to the following companies selling delta-8 THC products:

  • ATLRx Inc.
  • BioMD Plus LLC
  • Delta 8 Hemp
  • Kingdom Harvest LLC
  • M Six Labs Inc.

Perfecting Your Packaging for Cannabis Beverages

By Julie Saltzman
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Some consumers participating in the legal cannabis market want to avoid inhalable products. They are concerned about the effects of the smoke or they want their usage to be discreet — without the pungent aroma emanating from burning cannabis flower. For those consumers, edibles are the preferred option and a growing product category.

Within the edibles space, the beverage segment — with limited product options in some states — may offer significant potential for growth. In 2021, cannabis-infused beverages accounted for only 1% of total legal cannabis product sales and about 5% of the edibles segment in the United States, reports market researcher BDSA. But cannabis beverage sales are growing around the U.S.

In California, cannabis drinks grew their market share in the edibles category from 4% in 2018 to 7% in 2021. Nevada saw beverages increase their share of edibles revenues from 7% to 10% in the same time frame. And cannabis beverages’ share of edibles sales in Massachusetts went from less than 1% in 2019 to 8% in 2021.

Pegged at $180 million in revenue last year, the cannabis beverage market is projected to reach nearly $500 million by 2026, predicts BDSA.

Today, gummies and chocolate products dominate the edibles category. Although beverages are currently a small segment of edible sales, they may have some inherent advantages — familiarity, faster-acting products from improved bioavailability, and taste and flavor innovations — over other cannabis products. Since beverages can incorporate many different flavors from fruity, cola and sweet to coffee, tea, sour and bitter, these myriad flavor variations can mask or minimize any off-tastes associated with THC.

Viewed as part of their everyday regimen, consumers drink beverages for hydration, nourishment, refreshment and enjoyment. Cannabis beverages are well-suited for consumers’ lifestyles, while gummies and chocolates may be perceived as sugary treats and special occasion items.

Cruise Beverage B Happy Nitro-Infused CBD Drinks.

Brand owners are beginning to recognize the limited availability of products and growth potential of cannabis-infused beverages and are looking to enter the category. Packaging plays a key role in cannabis beverages, with sustainability, regulatory compliance (e.g., child-resistant), labeling compliance (e.g., warning symbols and text), convenience and branding all contributing to the success of the expanding product category.

Sustainable Packaging

Consumers, especially younger generations, are concerned about the environment and support brands that align with their values. According to the 2020 Sustainable Market Share Index from the NYU Stern Center for Sustainable Business, sustainability-marketed products delivered about 55% of the market growth in consumer packaged goods (CPG) from 2015 to 2019 in the U.S. despite being only 16% of the market. Sustainability-marketed goods grew seven times faster than products not marketed as sustainable and nearly four times faster than the overall CPG market.

As a primary consumer touchpoint, packaging is a good way for cannabis beverage brands to show their commitment to the environment. But finding the most sustainable packaging option for a particular application may not always be as straightforward as it seems. Many considerations are involved — material choice (e.g., plastic, glass, or aluminum), recyclability of the material, the weight of the material, recycled content of the final package, package design (minimalist vs. excessive), transportation costs and other factors like reusability.

To help facilitate the process, Berlin Packaging uses life cycle analysis to determine a product’s environmental impact or carbon footprint over its entire life cycle, including sourcing & raw materials extraction (minerals resource use), manufacturing (energy and water usage), distribution (freight miles, fuel usage) and end-of-life (recovery, recycling, reprocessing).

We have the know-how to improve the sustainability of any packaging material — whether it be lightweighting, use of post-consumer recycled (PCR) content, greater recycling rates and more.

Regulatory Compliance

Because legal cannabis products are regulated by individual states and not at the federal or national level, the regulations for cannabis packaging requirements can vary widely from one state to another. However, there are some common rules that all states follow.

Child-resistant capable cap fits snugly over the top of a can.

All cannabis products — including beverages — require child-resistant packaging to meet the standards of the Consumer Product Safety Commission. For aluminum cans, Berlin Packaging offers a child-resistant capable mechanism that fits snugly over the top of a can. Available in polypropylene or a bio-based resin, the single-use device can be custom developed to fit the exact specifications of the customer’s cans. In-stock products are available for standard 202 can ends.

Along with child-resistant capable packaging, states also require some type of warning symbol and statement on the label to indicate the product contains cannabis. Depending on the state, the symbol may be a triangular or diamond shaped in a bright or contrasting color to call attention to it on the label. The symbol typically houses a cannabis leaf image or “THC”.

Convenience

Like any packaged drink, cannabis beverages need to check all the boxes for consumer convenience — easy to drink, portability, cupholder friendly and resealable.

Users can easily reseal PET and glass bottles with continuous thread or lug finish closures, but cans present a challenge. Berlin Packaging offers a solution with a resealable can that opens like a traditional stay-on-tab. Here’s how it works. Lifting the pull tab breaks the tamper-evident band and unlocks the slider mechanism. Pulling the slider opens the can and makes the familiar venting sound — even after reopening.

The configuration of the opening creates a smooth laminar flow to improve the drinking experience. Moving the slider back to its original position and pushing down the pull tab, which produces a clicking sound, reseal the closure. The tamper-evident band remains on the can underneath the pull tab.

Branding

Cannabis beverages come in drops, shots, syrups, carbonated, iced tea, lemonade, fruity, water, sports & energy, mocktails, tea, coffee and hot cocoa.

Because cannabis has been associated with medicinal uses, many consumers use cannabis products to manage their wellbeing and health. Thus, some cannabis products have been positioned to relieve stress, promote relaxation and sleep, reduce pain and inflammation, improve mental focus, enhance mood or simply for indulgence and enjoyment.

Product positioning and the experience the brand owner wants to create for the consumer can help inform the brand design, personality, and narrative or storytelling. It’s also important that the brand design and messaging resonate with the product’s target audience.

Studio One Eleven, Berlin Packaging’s in-house innovation division, can help cannabis beverage marketers with their product branding from concept to commercialization. We offer market research and consumer insights, brand strategy and visual branding design, brand name development, structural package design, and more. Our services are available at no additional charge in exchange for a customer’s packaging business.

Cruise Beverage distributes nitrogen-infused CBD drinks with all-natural ingredients in 12-oz aluminum cans under the B Happy brand. The team at Studio One Eleven helped Cruise Beverage and its B Happy brand tell their story of free-spirited enjoyment with updated branding, expressive flavor names (i.e., Loosen Up Lemon, Peaceful Pear, Mellow Mango, and Blissful Blood Orange), and unique packaging graphics.

Uplifting illustrations speak to the brand’s sense of freedom and relaxation, and the hand-drawn style reflects the craftsmanship of the CBD beverage product. A white background with flavorful pops of color says clean and fresh, while tiny bubble imagery communicates the delightful effervescence of the fizzy drinks.

The Rise of a New Market… And a New Consumer

By Christiane Campbell
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The adult beverage industry, like any other category of consumer branded products, is driven by trends. If you’re old enough to remember Bartles & Jaymes wine coolers, you probably also remember Zima and Smirnoff Ice, and more recently “healthy” options like Skinny Girl and Michelob Ultra. The sensation that was craft beer saw many brands being acquired by Big Alcohol so that while the brands remain, ownership and production have changed significantly. Gin, tequila and vodka have had their moments in the sun and the current market is undeniably saturated with what is probably the largest current trend – hard seltzers. However, with the seltzer craze waning, many are wondering what’s next. And with the growing sober/California sober trends, some are betting it is cannabis-infused beverages.

Cannabis-infused beverages offer both an alternative method of consumption of cannabis and are also an attractive alternative to alcohol. Infused beverages are more appealing to the new demographic of casually curious cannabis consumers. i.e., consumers that may not be interested in smoking a joint or vaping, but are comfortable micro-dosing from a can or bottle, as they would a seltzer or beer. The same type of consumer may be moving away from alcohol consumption to eliminate hangovers or other negative health effects.

The emerging market and curious consumer group present an enormous opportunity right now for cannabis-infused beverage brands. Of course, with opportunity and growth come challenges. And while cannabis-infused beverages face a host of legal and regulatory challenges relative to sourcing, manufacturing, packaging, labeling, shipping, marketing, distribution and sale, one of the most critically important business assets to address at inception is the brand.

Lines are Blurring, Gaps are Being Bridged

The U.S. cannabis market is currently a geographic hamburger. Hear me out: Geographically, you have a relatively mature market out west and a relatively new and growing market along the east coast. These are the buns. You have a mixed bag in between, with some states coming online and allowing medical or adult use cannabis use and others that have not yet embraced any form of legalization. The landscape has lent itself to the development of regional brands, such that brands that are so similar they might otherwise confuse consumers, have been able to co-exist in different regions without issue, or because there is little to no trade channel or market overlap. Similarly, adult beverages and cannabis have historically been separate verticals, with an arguably low likelihood that a consumer would assume a particular cannabis product and adult beverage product emanate from the same source.

A drink additive, made by Splash Nano, that uses nano emulsion technology

However, lines are blurring and gaps are being bridged. Walls are breaking down. The increasing number of states coming online with legalized cannabis, and the proliferation of multi-state operators (MSOs), means that cannabis brands can grow to be more than siloed regional brands. This will inevitably lead to brands that previously co-existed bumping into one another and there’s bound to be some pushing and shoving. The advent of infused beverages likewise bridges the gap between cannabis products and alcoholic beverages. While the respective industries were not historically per se related, competing, or overlapping, now you’ve got infused beverages that bridge the gap between the two, and traditional alcohol brands (e.g., Boston Beer Company, Molson Coors, Lagunitas, Pabst.) entering the market (albeit under different brands). This makes a strong argument that cannabis and alcohol (or, more generally, adult beverages) are within each other’s logical zones of expansion, for purposes of a likelihood of confusion analysis.

The growing pains infused beverage brands will experience are analogous to those craft beers saw in the 2000 – 2010s. Many craft brewers had catchy, cheeky names and brands that contributed to their ability to engage consumers and develop a following, but failure to clear and protect the brands prior to launch detracted from the brands’ market values. Localized use prior to expansion also led to many brands bumping into one another and stepping on each other’s trademark toes. This was significant as the brands sought investment dollars or an exit strategy, making clear that the brand itself contributed heavily to valuation.

Mitigating Risks and Overcoming Challenges: Search and Protect 

The risks and challenges can be significantly mitigated and/or overcome with proper preliminary clearance searching and assessments, and by seeking and obtaining state or federal protection for the brand or brands, to the extent possible.

Quatreau CBD infused sparkling water

Of course, clearance searches and assessments come with their own challenges, as does federal protection. With respect to clearance searches, these typically look at U.S. federal and state trademark databases. These resources are not sufficient for purposes of clearing a proposed cannabis brand. Many brands are not recorded at the federal or state level and indeed may not even show up in a basic search engine. An appropriate search looks at social media resources like Instagram, Twitter, Facebook and known cannabis resources like Leafly and Weedmaps. Additionally, the scope of the search should exceed cannabis products and services and at least look at alcohol and merchandise. Adoption and use of a brand for a cannabis-infused beverage is high risk if that brand is similar to a prior existing alcohol brand. A current example is Cointreau’s taking aim at Canopy’s adoption and use of QUATREAU for an infused beverage.

A U.S. federal trademark registration presents its own unique challenges, but is incredibly valuable and beneficial to a brand since it provides the owner with a nationwide presumption of ownership and validity in a trademark, and can also secure priority for the owner with a constructive first use in commerce date that is years before actual use of a mark begins. The U.S. Trademark Office categorically denies protection of brands that violate its “lawful use” rule, and will treat as per se unlawful any applied for mark that covers marijuana, or that covers foods, beverages or pharmaceuticals that contain CBD. With respect to brands that cover products containing THC, since it is federally scheduled, use of the brand would violate the Controlled Substances Act (CSA). With respect to brands that cover CBD or products containing CBD, these may be lawful pursuant to the Farm Bill and the U.S. Trademark Office’s subsequent allowance of marks that claim CBD “solely derived from hemp with a delta-9 tetrahydrocannabinol (THC) concentration of not more than 0.3 percent on a dry weight basis,” however under the Food Drug Cosmetics Act (FDCA) it is currently federally unlawful to introduce CBD – even if it fits the definition above – into foods or beverages.

Even if cannabis is not specifically claimed in a trademark application, cannabis brands have a natural gravitation toward names and logos that can do some of their marketing for them, and announce to the world they cover cannabis. This increases the chances that a trademark application for the brand will get push-back from the U.S. Trademark Office, and if not at the initial review stage, then at the point in time when the brand must submit to the U.S. Trademark Office a sample of (lawful) use of the applied-for mark. While this all sounds like bad news for cannabis-infused beverages, all is not lost.

There are typically ancillary and federally lawful products and services cannabis companies offer under their brands that can be covered in a U.S. federal trademark application, and arguments to be made that registered protection of a brand for the ancillary items should be sufficient to enforce against third parties using the same or confusingly similar brands in their space. Some cannabis brands’ lawful ancillary products are actually product lines (e.g., beverages) offered under the same brand that contain no cannabis. Others may be more causally related, like online forums and blogs. The former is closer to the actual product, and the latter would be more beneficial to a brand that is inherently stronger and more distinctive. One note of caution: A trademark application and eventual registration that expressly disclaim cannabis (THC or CBD) may be difficult to enforce against a third party using the same or a similar mark on and in connection with cannabis. So, while there is a natural inclination to follow a U.S. Trademark Office request to disclaim coverage of cannabis, there may be enforcement consequences down the road.

The cannabis-infused beverage market is poised for explosive growth. The brands that survive – and succeed – will be those that position themselves for growth by clearing and buttoning up their brands as early as possible. The market leaders will be those that select strong and distinctive brands, with geographic and market space around them for growth and expansion; and those that protect and enforce their brands, to the extent possible, at the federal and/or state levels.

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FDA Warning Letters: Stop Claiming CBD Prevents COVID

By Cannabis Industry Journal Staff
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Once again, the U.S. Food and Drug Administration (FDA) has issued a number of warning letters to companies selling hemp-derived cannabidiol (CBD) products. This time around, the FDA sent these warning letters to companies that had statements on their website claiming CBD is an effective treatment or prevention of Covid-19.

In this latest round, the FDA sent a total of seven warning letters to:

Just some of the many hemp-derived CBD products on the market today
  • Greenway Herbal Products LLC
  • UPSY LLC
  • Functional Remedies, LLC dba Synchronicity Hemp Oil
  • Nature’s Highway
  • Heaven’s Organic LLC
  • Cureganics
  • CBD Social

Earlier this year, a slew of preliminary research studies went viral for shedding light on promising signs that certain cannabis compounds could help treat or prevent Covid-19. The conclusions from most of that research is: It is still too early to tell if any of these studies will show evidence of cannabis treating Covid-19, let alone if they mean cannabis products can be used as a treatment or preventative for Covid-19. However, the research is significant and we should keep an eye on any developments that come from those studies.

The hemp-derived CBD market has a history of clashes with the FDA over health claims. Since the Farm Bill legalized cannabis with less than 0.3% THC back in 2018, the hemp-derived CBD market has proliferated, with all sorts of companies seizing the opportunity. Jumping on the health and wellness trend, companies incorporated this messaging into their marketing campaigns. Over the past four years, the FDA has issued dozens and dozens of warning letters and threatened enforcement actions to companies making unsubstantiated health claims about CBD.

While CBD definitely does have medical benefits, such as being used as an anti-inflammatory or anticonvulsant, preliminary research alone is not enough to say it does. Products need to be approved by the FDA with a new drug application (NDA) in order to make those claims. Therefore when companies make unsubstantiated health claims about their CBD products, like claiming it can prevent Covid-19, they are violating the FD&C Act by marketing “unapproved new drugs” or “misbranded drugs.”

The bottom line is companies that are marketing CBD products need to ensure that their marketing materials and labeling comply with FDA requirements and avoid making unapproved drug claims.

An Evaluation of Sample Preparation Techniques for Cannabis Potency Analysis

By Kelsey Cagle, Frank L. Dorman, Jessica Westland
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Sample preparation is an essential part of method development and is critical to successful analytical determinations. With cannabis and cannabis products, the analyst is faced with a very challenging matrix and targets that may range from trace level through percent level thus placing considerable demands on the sample preparation techniques.1 The optimal sample preparation, or “extraction”, method for potency analysis of cannabis flower was determined using a methanol extraction coupled with filtration using regenerated cellulose filters. 

In the United States (US), Canada, and other countries where medicinal and/or adult recreational cannabis has been legalized, regulatory entities require a panel of chemical tests to ensure quality and safety of the products prior to retail sales2. Cannabis testing can be divided into two different categories: Quality and Safety. Quality testing, which includes potency analysis (also known as cannabinoid testing or cannabinoid content), is performed to analyze the product in accordance with the producer/grower expectations and government regulations. Safety testing is conducted under regulatory guidelines to ensure that consumers are not exposed to toxicants such as pesticides, mycotoxins, heavy metals, residual solvents and microbial contaminates.

Potency testing evaluates the total amount of cannabinoid content, specifically focusing on tetrahydrocannabinol (THC) and cannabidiol (CBD). In the US, the biggest push for accurate total THC is to differentiate between hemp (legally grown for industrial or medicinal use), which is defined as cannabis sativa with a THC limit ≤ 0.3 %, and cannabis (Cannabis spp.), which is any cannabis plant with THC measured above 0.3 %3. Potency testing is typically performed by liquid chromatography (LC) with UV detection to determine the quantity of major cannabinoids.

In addition to reporting THC and CBD, their respective precursors are also important for reporting total potency. Tetrahydrocannabinolic acid (THCA) is the inactive precursor to THC while cannabidiolic acid (CBDA) is the precursor to CBD.4,5

Methods and Materials

Sample Preparation

All samples were homogenized using an immersion blender with a dry material grinder. The nominal sample amounts were 200 mg of flower, 500 mg of edibles, and 250 mg of candy samples.

Potency Extraction Method (1)

Twenty milliliters (mL) of methanol (MeOH) was added to each sample. The samples were mechanically shaken for 10 minutes and centrifuged for 5 minutes.

Potency Extraction Method (2)

Ten mL of water was added to each sample. The samples were mechanically shaken for 10 minutes. 20 mL of acetonitrile (ACN) was then added to each sample and vortexed. An EN QuEChERS extraction salt packet was added to the sample. The samples were placed on a mechanical shaker for 2 minutes and then centrifuged for 5 minutes.

Each extract was split and evaluated with two filtration/cleanup steps: (1) a regenerated cellulose (RC) syringe filter (Agilent Technologies, 4 mm, 0.45 µm); (2) a PFTE syringe filter (Agilent Technologies, 4 mm, 0.45 µm). The final filtered extracts were injected into the ultra-performance liquid chromatograph coupled with a photodiode array detector (UPLC-PDA) for analysis.

Figure 1: Calibration curve for THC potency

Calibration

Standards were obtained for the following cannabinoids at a concentration of 1 mg/mL: cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabinol (CBN), tetrahydrocannabinol (9-THC), cannabichromene (CBC), tetrahydrocannabinol acid (THCA). Equal volumes of each standard were mixed with MeOH to make a standard stock solution of 10 ug/mL. Serial dilutions were made from the stock to make concentrations of 5, 1, and 0.5 ug/mL for the calibration curve (Figure 1).

Instrumental Method

All instrument parameters were followed from Agilent Application Note 5991-9285EN.8 A UPLC with a PDA (Waters Corp, Milford, MA) detector was employed for potency analysis. An InfinityLab Poroshell 120 EC-C18, 3.0 x 50 mm, 2.7 um column (Agilent Technologies, Wilmington, DE) was utilized for compound separation. The organic mobile phase composition was 0.05 % (v/v) formic acid in HPLC grade MeOH and the aqueous mobile phase composition was 0.1 % (v/v) formic acid in HPLC grade water. The mobile phase gradient is shown in Table 1. The flow rate was 1 mL/min (9.5 minute total program), injection volume was 5 uL, and column temperature was 50 °C.

Table 1: LC mobile phase gradient for potency samples6

Discussion and Results

Table 2 summarizes the relative standard deviations (% RSD) were found for the THC calibrator (at 1 ug/mL) and one extract of a homogeneous sample (utilizing 7 replicates).

Table 2- %RSD values for the instrument response precision for THC in both the calibrations and the homogeneous extract.

The cannabinoid potency of various cannabis plant and cannabis product samples were determined for the various extraction techniques In the chromatograms THC was observed ~8.08 minutes and CBD was observed ~4.61 minutes (Figure 2).

Figure 2: Chromatogram of the 10ug/mL calibrator for potency/cannabinoid analysis

Total potency for THC & CBD were calculated for each sample using the equations below. Equation 1 was used because it accounts for the presence of THCA as well as the specific weight difference between THC and THCA (since THCA will eventually convert to THC, this needs to be accounted for in the calculations).

Table 3 shows the % THC and the total THC potency values calculated for the same flower samples that went through all four various potency sample preparation techniques as described earlier. Figure 3 also provides LC chromatograms for flower sample 03281913A-2 and edible sample 03281912-1.

Table 3-THC and Total THC potency values for the same cannabis flower sample processed through the combination of extractions and cleanups.
Figure 3: Potency/Cannabinoid analysis chromatogram for flower sample 03281913A-2 (red trace) and edible sample 03281912-1 (green trace).

The results indicated that with the “Potency Extraction Method 2” (ACN/QuEChERS extraction) coupled with the RC filter provided a bias of 7.29 % greater for total THC % over the other extraction techniques. Since the other 3 techniques provided total THC values within 2% of each other, the total THC of the sample is more likely ~14%.

Since the sample dilution for the above data set reduced the CBD content, an undiluted sample was run and analyzed. This data is reported in Table 4.

Table 4- CBD and Total CBD potency values for the same cannabis flower sample processed through different sample preparation techniques.

The CBD results indicated that with the “Potency Extraction Method 1” (methanol extraction) coupled with RC filter, allowed for a greater CBD recovery. This may indicate the loss of CBD with an ACN/QuEChERS extraction.

With an average ~14% total THC and 0.06% total CBD for a homogenous cannabis flower sample, the optimal sample preparation extraction was determined to be a methanol extraction coupled with filtration using a regenerated cellulose filter. Since potency continues to remain at the forefront of cannabis regulatory testing it is important to utilize the right sample prep for your cannabis samples.

References

  1. Wang M, Wang YH, Avula B, Radwan MM, Wanas AS, Mehmedic Z, et al. Quantitative Determination of Cannabinoids in Cannabis and Cannabis Products Using Ultra-High-Performance Supercritical Fluid Chromatography and Diode Array/Mass Spectrometric Detection. Journal of Forensic Sciences 2016;62(3):602-11.
  2. Matthew Curtis, Eric Fausett, Wendi A. Hale, Ron Honnold, Jessica Westland, Peter J. Stone, Jeffery S. Hollis, Anthony Macherone. Cannabis Science and Technology, September/October 2019, Volume 2, Issue 5.
  3. Sian Ferguson. https://www.healthline.com/health/hemp-vs-marijuana. August 27, 2020.
  4. Taschwer M, Schmid MG. Determination of the relative percentage distribution of THCA and 9-THC in herbal cannabis seized in Austria- Impact of different storage temperatures on stability. Forensic Science International 2015; 254:167-71.
  5. Beadle A. CBDA Vs CBD: What are the differences? [Internet]. Analytical Cannabis. 2019 [cited 2020 Apr 22]; https://www.analyticalcannabis.com/articles/cbda-vs-cbd-what-are-the-differences-312019.
  6. Storm C, Zumwalt M, Macherone A. Dedicated Cannabinoid Potency Testing Using the Agilent 1220 Infinity II LC System. Agilent Technologies, Inc. Application Note 5991-9285EN
Milan Patel, PathogenDx
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The Need for More Stringent Testing in Cannabis

By Milan Patel
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Milan Patel, PathogenDx

As the demand for legal cannabis continues to rise and more states come online, it is imperative to enact more rigorous and comprehensive testing solutions to protect the health of consumers. People use cannabis products for wellness and to find relief; they should not be susceptible to consuming pathogens and falling ill. Especially for immunocompromised consumers, the consequences of consuming contaminated cannabis or hemp are dire. Of course, there should be federal standards for pathogen testing requirements like we have for the food industry. But right now, as cannabis is not yet federally legal, testing regulations vary between states and in many states, testing requirements are too loose and enforcement is minimal. It is up to state legislators, regulators and cannabis operators to protect the health of consumers through implementing more stringent testing.

From the outset, the environmental elements needed to grow cannabis – heat, light, humidity, soil – make cannabis ripe for pathogens to proliferate. Even when growers follow strict sanitation procedures through the supply chain from seed to sale, contaminations can still occur. Cannabis companies need to be hypervigilant and proactive about testing, not just reactive. The lack of regulations in some states is alarming, and as the cannabis industry is highly competitive and so many companies have emerged in a short time, there are unfortunately unscrupulous actors that have skated by in a loose regulatory landscape, just in the game to make a quick buck, even at the expense of consumer health. And there are notable instances where states do not have enforcement in place to deter harmful manufacturing practices. For instance, there are some states that don’t mandate moisture control and there have been incidents of companies watering down flower so it has more weight and thus can be sold at a higher cost – all the while that added moisture leads to mold, harming the consumer. This vicious circle driven by selfish human behavior needs to be broken by stricter regulations and enforcement.

While in the short term, looser testing regulations may save companies some money, in the long run these regulatory environments carry significant economic repercussions and damage the industry at large, most importantly injury or death to customers and patients. Recalls can tarnish a company’s brand and reputation and cause sales and stock prices to tank, and since cannabis legalization is such a hotly contested issue, the media gloms onto these recalls, which opponents to legalization then leverage to justify their stance. In order to win the hearts and minds of opponents and bring about federal legalization sooner, we need safer products so cannabis won’t be cast in such a dangerous, risky light.

Certainly, there’s a bit of irony at play here – the lack of federal regulations heightens the risk of contaminated cannabis reaching consumers, and on the flip side recalls are used by opponents to justify stigmatizing the plant and keeping it illegal. Nevertheless, someday in the not-too-distant future, cannabis will be legalized at the federal level. And when that day happens, federal agents will aggressively test and regulate cannabis; they’ll swab every area in facilities and demand thorough records of testing up and down the supply chain; current good manufacturing practices (cGMP) will be mandated. No longer will violations result just in a slap on the wrist – businesses will be shut down. To avoid a massive shock to the system, it makes sense for cannabis companies to pivot and adopt rigorous and wide-sweeping testing procedures today. Wait for federal legalization, and you’ll sink.

Frankly, the current landscape of cannabis regulation is scary and the consequences are largely yet to be seen. Just a few months ago, a Michigan state judge reversed part of a recall issued by the state’s Marijuana Regulatory Agency (MRA) on cannabis that exceeded legal limits of yeast, mold and aspergillus, bringing contaminated cannabis back to shelves without even slapping a warning label on the packaging to inform consumers of the potential contamination. This is a classic case of the power of the dollar prevailing over consumer safety and health. Even in well-established markets, the lack of regulations is jarring. For example, before this year in Colorado, testing for aspergillus wasn’t even required. (Aspergillus inhalation, which can cause Aspergillosis, can be deadly, especially for people who are immunocompromised). Many states still allow trace amounts of aspergillus and other pathogens to be present in cannabis samples. While traces may seem inconsequential in the short term, what will happen to frequent consumers who have been pinging their lungs with traces of pathogens for 30 years? Consistently inhaling trace amounts of pathogens can lead to lung issues and pulmonary disease down the road. Look what happened to people with breathing and lung issues during the last two years with COVID. What’s going to happen to these people when the next pandemic hits?

We need state regulators and MSOs to step up and implement more aggressive testing procedures. These regulators and companies can create a sea of change in the industry to better protect the health and well-being of consumers. Just complying with loose regulations isn’t good enough. We need to bring shortcomings around testing into the limelight and demand better and more efficient regulatory frameworks. And we should adopt the same standards for medical and adult use markets. Right now, several states follow cGMP for medical but not adult use – that’s ridiculous. Potentially harming consumers goes against what activists seeking legalization have been fighting for. Cannabis, untainted, provides therapeutic and clinical value not just to medical patients but to all consumers; cannabis companies should promote consumer health through their products, not jeopardize it.

For best practices, companies should conduct tests at every step in the supply chain, not just test end products. And testing solutions should be comprehensive. Most of the common tests used today are based on petri dishes, an archaic and inefficient technology dating back over a century, which require a separate dish to test for each pathogen of interest. If you’re waiting three to five days to see testing results against fifteen pathogens and a pathogen happens to be present, by the time you see results, the pathogen could have spread and destroyed half of your crops. So, not only do petri dishes overburden state-run labs, but due to their inherent inefficiencies, relying on these tests can significantly eat into cannabis companies’ revenues. At PathogenDx, we’ve created multiplexing solutions that can identify and detect up to 50 pathogens in a single test and yield accurate results in six hours. To save cannabis companies money in the long run and to make sure pathogens don’t slip through the cracks, more multiplexing tests like the ones we’ve created should be implemented in state labs.

Right now, while the regulatory landscape is falling short in terms of protecting consumer health, better solutions already exist. I urge state regulators and cannabis companies to take testing very seriously, be proactive and invest in creating better testing infrastructure today. Together, we can protect the health of consumers and create a stronger, more trustworthy and prosperous cannabis industry.

Beyond Compliance: Understanding and Combating Contamination

By Jill Ellsworth MS, RDN, Tess Eidem, Ph.D.
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As an emerging field in cannabis, contaminant testing remains a gray area for many businesses. The vast differences in state-by-state regulations, along with the frequent changes of previously established rules make testing a difficult, time-consuming process. But at its core, the science and reasoning behind why we test cannabis is very clear – consumer safety and quality assurance are key factors in any legal, consumer market. The implications of federal legalization make cannabis testing even more important to the future of the cannabis supply chain. Understanding the types of contaminants, their sources and how to prevent them is essential to avoiding failures, recalls and risking consumer safety.

When talking about cannabis contaminant testing there are four groups of contaminants: pesticides, heavy metals, foreign materials and microbes. The microbes found on cannabis include plant pathogens, post-harvest spoiling microbes, allergens, toxin release and human pathogens. While all of these can be lurking on the surface of cannabis, the specific types that are tested for in each state vary widely. Understanding the full scope of contaminants and looking beyond state-specific compliance requirements, cultivators will be able to prevent these detrimental risks and prepare their business for the future.

Environmental controls are essential to monitor and regulate temperature and humidity

Beyond just the health of the plant, both medical patients and adult use consumers can be adversely affected by microbial contaminants. To immunocompromised patients, Aspergillus can be life-threatening and both adult use and medical consumers are susceptible to allergic reactions to moldy flower. But Aspergillus is just one of the many contaminants that are invisible to the human eye and can live on the plant’s surface. Several states have intensive testing regulations when it comes to the full breadth of possible harmful contaminants. Nevada, for example, has strict microbial testing requirements and, in addition to Aspergillus, the state tests for Salmonella, STEC, Enterobacteriaceae, coliforms and total yeast and mold. Over 15 states test for total yeast and mold and the thresholds vary from allowing less than 100,000 colony forming units to allowing less than 1,000 colony forming units. These microbes are not uncommon appearances on cannabis – in fact, they are ever-present – so understanding them as a whole, beyond regulatory standards is a certain way to future-proof a business. With such vast differences in accepted levels of contamination per state, the best preparation for the future and regulations coming down the pipeline is understanding contamination, addressing it at its source and harvesting disease-free cannabis.

The risk of contamination is present at every stage of the cultivation process and encompasses agricultural practices, manufacturing processes and their intersection. From cultivation to manufacturing, there are factors that can introduce contamination throughout the supply chain. A quality control infrastructure should be employed in a facility and checkpoints within the process to ensure aseptic operations.

Microbial monitoring methods can include frequent/consistent testing

Cultivators should test their raw materials, including growing substrates and nutrient water to ensure it is free of microbial contamination. Air quality plays an important role in the cultivation and post-harvest processes, especially with mold contamination. Environmental controls are essential to monitor and regulate temperature and humidity and ensure unwanted microbes cannot thrive and decrease the value of the product or make it unsafe for worker handling or consumers. Developing SOPs to validate contact surfaces are clean, using proper PPE and optimizing worker flow can all help to prevent cross-contamination and are part of larger quality assurance measures to prevent microbes from spreading across cultivars and harvests.

Methods of microbial examination include air quality surveillance, ATP surface and water monitoring, raw materials testing, and species identification. Keeping control of the environment that product is coming into contact with and employing best practices throughout will minimize the amount of contamination that is present before testing. The solution to avoiding worst case scenarios following an aseptic, quality controlled process is utilizing a safe, post-harvest kill-step, much like the methods used in the food and beverage industries with the oversight of the FDA.

The goal of the grower should be to grow clean and stay clean throughout the shelf life of the product. In order to do this, it is essential to understand the critical control points within the cultivation and post-harvest processes and implement proper kill-steps. However, if a product is heavily bio-burdened, there are methods to recover contaminated product including decontamination, remediation and destroying the product. These measures come with their own strengths and weaknesses and cannot replace the quality assurance programs developed by the manufacturer.