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Protecting Your Innovative Cannabis Strains With a Strong Intellectual Property Strategy: Part 2 – Patents for New Cannabis Strains

By Dr. Travis Bliss
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In the first installment of this three-part series we explored the reasons why cannabis breeders should adopt a strong IP strategy sooner rather than later and looked briefly at the types of IP that those breeders and growers should be considering. In this second installment, we will examine in more detail patent protection for innovative new varieties of cannabis and how one can use that patent protection to further their business objectives.

What is a patent and what do I do with one?

A patent is a right granted by the government to protect a new and useful invention. Importantly, a patent gives its owner an exclusionary right as opposed to a right to do something – the patent owner has the right to exclude others from making, using, selling, offering to sell, or importing the invention (or, for a plant, any of its plant parts) for the term of the patent, which is 20 years for the types of patents that can be used to protect new cannabis varieties.

Because it is an exclusionary right, there are essentially two things that a patent owner can use a patent to do: 1) disallow anyone else from producing and selling that variety (or any of its parts) so that the patent owner is able to capture all of the sales for that variety, or 2) use license contracts to allow other growers to grow the variety while paying royalties back to the patent holder. The latter option can often be beneficial because it can greatly expand production of the variety by licensing to multiple growers. However, this does require some oversight on the part of the patent holder to make sure that the product those growers are producing is high quality –growers who produce poor quality product can hurt the existing brand. Cannabis breeders should consider these options up front when formulating their IP strategy.

Which type of patent should I use to protect my new variety?

As a further consideration, there are two different types of patents that can be used to protect new plant varieties and there are multiple factors to consider when determining which one to pursue.

U.S. Plant Patents are a special type of intellectual property that is used solely for the protection of asexually/vegetatively reproduced plant varieties. Traditionally, plant patents have been used to protect new varieties of ornamental and fruit trees and shrubs, such as a new variety of rose bush or a new variety of apple tree, such as the ‘Honeycrisp’ apple tree, patented in 1990. This type of patent has recently been used to protect a new cannabis variety called ‘Ecuadorian sativa’, while several other cannabis varieties, ‘Midnight’, ‘Erez’, and ‘Avidekel’ varieties are awaiting plant patent approval.

On the other hand, a “utility patent” can be used for new “compositions” (e.g., a new type of grow light) or new types of “methods” (e.g., a new method of extracting compounds from cannabis or a new method of growing cannabis to produce higher THC content). This type of patent can also be used to protect a new plant variety so long as the applicant can demonstrate that the variety is novel and not obvious over what was already known in the art. To date, two utility patents have been issued to protect cannabis varieties that exhibit certain cannabinoid and terpene profiles (U.S. Patent Nos. 9,095,554 and 9,370,164), and other similar utility patent applications are also pending (e.g., U.S. Patent Pub. No. 2014/0298511).

One of the main determining factors in deciding which type of patent to pursue is the nature of the invention. Growers and breeders will likely want to seek a plant patent if they have developed a new variety of cannabis plant: 1) which was made using simple breeding techniques, 2) which can be stably reproduced in an asexual manner (such as by cuttings and cloning), and 3) which is different from its parents and certain other strains on the market, but not completely distinct from everything that already exists. On the other hand, growers and breeders may want to consider a utility patent if they have developed a new variety of cannabis plant: 1) which has unique features in comparison to everything else that exists today (such as a unique disease resistance or chemical makeup), 2) which has unique features that can be demonstrated by some sort of biological or chemical test, and 3) that can be reproduced either asexually or by seed. It is also important to keep in mind that these two routes are not mutually exclusive – one could apply for both types of patent if the variety satisfies the criteria for both.

Though there are numerous similarities between the processes for obtaining both types of patents, there are also clear differences that should be taken into consideration when making the decision about which type of patent to seek. For instance, the grant rate for plant patents is much higher, meaning there is a higher likelihood that the plant patent application will eventually be granted compared to a utility patent application. Further, plant patent applications typically move quicker through the Patent Office, frequently being granted in approximately 18 months, while utility patent applications typically take two to four years (or more) to issue.

Another factor that should be considered is cost. Because a plant patent application is much simpler to prepare and typically moves through the Patent Office more swiftly, the cost for obtaining a plant patent is generally significantly lower than for a utility patent.

Determining which type of patent to pursue requires consideration of numerous factors. However, it is important to keep in mind that, regardless of which type of patent a grower or breeder seeks, there are certain time limitations that can impact the right to obtain a patent. For example, patent protection can only be sought if the variety to be patented has not been sold, offered for sale, or otherwise made publicly available more than one year before the patent application is filed. After that time, the invention becomes part of the “public domain.” So if a breeder chooses to wait to seek patent protection for a new variety, they risk losing the ability to ever get that protection.

Clearly, growers and breeders have to weigh several options when formulating a patent strategy, including what type of patent to pursue and what to do with the patent once they obtain it. Thinking through these issues early on allows the cannabis breeder an opportunity to formulate a strategy that is most beneficial in furthering their business objectives. Additionally, regardless of the type of patent strategy used, it is often helpful to combine it with trademark and branding strategy, which allows the business to utilize a more comprehensive approach to IP for their innovative strains. The third installment of this series will focus on trademarks for cannabis products and some unique issues that facing the cannabis industry today.

Legal disclaimer: The material provided in this article is for informational purposes only and not for the purpose of providing legal advice. The opinions expressed herein are the opinions of the individual author and may not reflect the opinions of the firm or any individual attorney. The provision of this information and your receipt and/or use of it (1) is not provided in the course of and does not create or constitute an attorney-client relationship, (2) is not intended as a solicitation, (3) is not intended to convey or constitute legal advice, and (4) is not a substitute for obtaining legal advice from a qualified attorney. You should not act upon any such information without first seeking qualified professional counsel on your specific matter.

Israeli Cannabis Brand Tikun Olam Expands to US

By Aaron G. Biros
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Tikun Olam is a Jewish concept that addresses social policy, promoting acts of kindness to better society. In Hebrew, it literally means, “repair of the world.” The company by the same name, Tikun Olam Ltd, and now in the United States as T.O. Global LLC, was the first medical cannabis provider in Israel back in 2007. Working with patients, doctors and nurses in clinical trials, they developed 16 strains over the last decade that target alleviating symptoms of specific ailments.

Tel Aviv, Israel, where Tikun Olam has a dispensary

In November 2016, they launched their United States brand, Tikun, in the Delaware medical cannabis program with their partner, First State Compassion Center, a vertically integrated business of cultivation, extraction and retail in Wilmington. After the success of their pilot program, Tikun announced their expansion into the Nevada market with their licensed partner, CW Nevada LLC. Tikun is leveraging its experience with clinical trials and medical research to launch a line of cannabis products focused on health and wellness in the United States. According to Stephan Gardner, chief marketing officer at Tikun Olam, they have the largest collection of medical cannabis data in the world. “Tikun Olam started out as a non-profit, working to bring medication to patients in Israel,” says Gardner. “Opening nursing clinics gave us a tremendous amount of knowledge and data to work on the efficacy of strains developed specifically for targeting symptoms associated with certain conditions.” For example, their strain, Avidekel, was developed years ago as the first high-CBD strain ever created.

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The strain Avidekel being grown in Israel.

In a single-strain extraction, Avidekel has been used to successfully mitigate the symptoms associated with neurological conditions, like epilepsy in children, and they have the data to demonstrate that efficacy. “The American market needs some sort of guidance on how these cannabinoid and terpene profiles in certain strains can truly assist patients,” says Gardner. “We have been tracking and monitoring our patients with clinical and observational data in one, six month and annual follow ups, which are data we can use to guide the needs in the US.”

Their expansion strategy focuses heavily on the health benefits of their strains, not necessarily targeting the recreational market. “As a wellness brand in Nevada, we are positioned to work first and foremost in the medical market,” says Gardner. “Our wellness brand can cater to people looking for homeopathic remedies for things like inflammation issues, sleep disorders or pain relief for example,” says Gardner. “You will not see us going out there catering to the truly recreational market; the benefits of what our strains can do is marketed from a wellness perspective.” A cannabis product with high-THC percentages is not unique, says Gardner, but their approach using the entourage effect and proven delivery mechanisms is. “While higher THC might appeal to the rec market, that is not exactly how we will promote and position ourselves,” says Gardner. “We want to be a dominant force in the wellness market.”

Best practices include quality control protocols

That effort requires working within the US regulatory framework, which can be quite complicated compared to their experience in Israel. “We have to understand the Israeli market and American market are completely different due to the regulatory regimes each country has in place,” says Gardner. “We understand the efficacy of these products and want to educate customers on how they might benefit. We don’t want to make claims looking to cure anything, but we found in our data that a lot of symptoms in different ailments, like cancer, PTSD, Crohn’s disease, colitis and IBS, can be alleviated by strains we developed.” In addition to the medical research, they are bringing their intellectual property, cultivation methodologies, evidence-based scientific collaboration and best practices to their partners in the US.

So for Tikun’s expansion in the US, they want to get a medical dialogue going. “We will launch a fully accredited AMA [American Medical Association] program, educating medical practitioners, giving the doctors the understanding of the capabilities of cannabis and what our strains can do,” says Gardner. “We will also share our observational data with doctors so they can work to better guide their patients.” Right now, they are working on the education platform in their pilot program in Delaware. “We plan on using that as a platform to expand into other markets like Nevada,” says Gardner. “And we will be launching the Tikun brand in the Washington market this summer.” Based on the high demand they saw in the Delaware market, Gardner says they plan to launch six unique strains in the American market, with delivery mechanisms like vape products, tinctures, lozenges and topicals in addition to dried flower.

dry cannabis plants
Rows of cannabis plants drying and curing before processing.

While Tikun expands throughout the United States, their sights are set on global expansion, living up to the true meaning of the concept Tikun Olam. They entered a strategic partnership with a licensed producer based in Toronto, bringing their strains, including Avidekel, to the Canadian market. The company they are partnering with, MedReleaf, recently filed for an initial public offering (IPO) on the Toronto stock exchange. Tikun Olam is actively seeking to expand in other parts of the world as well.

Shimadzu Launches Cannabis Analyzer for Potency

By Aaron G. Biros
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On Monday, March 6th, Shimadzu Scientific Instruments, a leading laboratory analytical instrumentation manufacturer, announced the launch of a new product focused on cannabis, according to a press release. Their Cannabis Analyzer for Potency is essentially a high-performance liquid chromatograph (HPLC) packaged with integrated hardware, software, workflows and all the supplies. The supplies include an analytical column, guard columns, mobile phase and a CRM standard mixture.canAnalyzerImg1

The instrument is designed to test for 11 cannabinoids in less time and with greater ease than traditional HPLC instruments. In the press release, they claim “operators are now able to produce accurate results with ease, regardless of cannabis testing knowledge or chromatography experience.” One very unique aspect of the instrument is the lack of experience required to run it, according to Bob Clifford, general manager of marketing at Shimadzu. “We have our typical chromatography software [LabSolutions] with an overlay that allows the user to analyze a sample in three simple steps,” says Clifford. Those in the cannabis industry that have a background in plant science, but not analytical chemistry, could run potency analyses on the instrument with minimal training. “This overlay allows ease of use for those not familiar with chromatography software,” says Clifford.

An overlay of a flower sample with the standards supplied in the High-Sensitivity Method package.
An overlay of a flower sample with the standards supplied in the High-Sensitivity Method package.

The instrument can determine cannabinoid percentages per dry weight in flower concentrates and edibles. “Once you open the software, it will get the flow rate started, heat the column up and automatically begin to prep for analysis,” says Clifford. Before the analysis begins, information like the sample ID number, sample name, sample weight, extraction volume and dilution volume are entered. After the analysis is complete all the test results are reported for each sample.

Because laboratories wouldn’t have to develop quantitative testing methodology, they argue this instrument would save a lot of time in the lab. “After one day of installation and testing, users are equipped with everything they need to obtain cannabis potency results,” states the press release. According to Clifford, method development for potency analysis in-house can take some labs up to three months. “We can bring this instrument to the lab and have it ready for testing almost immediately,” says Clifford. “The methods for this instrument were developed by a team of twenty scientists working on different platforms at our Innovation Center and was tested for ruggedness, repeatability and quantitative accuracy.”

Screenshots from the software on the instrument
Screenshots from the software on the instrument

The instrument’s workflow is designed to meet three methods of analysis depending on testing needs. The High Throughput method package can determine quantities of ten cannabinoids with less than eight minutes per sample. The method was developed in collaboration with commercial testing laboratories. The High Sensitivity method package adds THCV to that target analyte list with ten minutes per analysis. The method provides the sharpest chromatographic peaks and best sensitivity. The High Resolution method package offers full baseline resolution for those 11 cannabinoids in less than 30 minutes per analysis and the ability to add cannabinoids to that target list if regulations change.

The press release states the interface should allow users to reduce the number of steps needed in the analysis and simplify the workflow. The instrument comes with a three-year warranty, preventative maintenance plan and lifetime technical support.

Hoban Law Group Files Lawsuit Against DEA

By Aaron G. Biros
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The Hoban Law Group filed a petition on behalf of three clients against the DEA in the U.S. Court of Appeals for the Ninth District on January 13th, according to a press release. The clients represented by Hoban Law Group in the suit are Hemp Industries Association, RMH Holdings, LLC and Centuria Natural Foods, Inc. The companies are based in California, Colorado and Nevada respectively and are all active in the legal hemp trade. The press release says RMH Holdings “sources its products from industrial hemp lawfully cultivated pursuant to the Agricultural Act of 2014 (also known as the Farm Bill).”

San Francisco's United States Court of Appeals for the Ninth Circuit Photo: Ken Lund, Flickr
San Francisco’s United States Court of Appeals for the Ninth Circuit
Photo: Ken Lund, Flickr

In December, the DEA published a ‘Final Rule’ that classifies cannabis-derived extracts, such as CBD oil, in their own category with a code number to “better track these materials and comply with treaty provisions.” The announcement by the DEA ultimately serves to make any cannabis extract a Schedule 1 narcotic. “Extracts of marihuana will continue to be treated as Schedule I controlled substances,” says the document.

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Bob Hoban, managing partner

Bob Hoban, managing partner of Hoban Law Group says the action is clearly beyond the DEA’s authority. “This Final Rule serves to threaten hundreds, if not thousands, of growing businesses, with massive economic and industry expansion opportunities, all of which conduct lawful business compliant with existing policy as it is understood and in reliance upon the Federal Government,” says Hoban.

The lawsuit states that they want a judicial review of the DEA’s actions “on the grounds that the Final Rule is (1) arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law, e.g. the CSA, the Farm Bill, and the DEA’s regulations; (2) contrary to constitutional right, power, privilege, or immunity; (3) in excess of statutory jurisdiction, authority, or limitations; and, (4) without observance of procedure required by law.” The suit also claims that the ‘Final Rule’ conflicts with other federal laws like the Data Quality Act, Regulatory Flexibility Act and Congressional Review Act.

According to Garrett Graff, associate attorney at Hoban Law Group, the entire Cannabis genus is not unlawful and the DEA is overstepping its authority. “As the Ninth Circuit found in 2003 and 2004 there are certain parts of the plant like the stalk and seed that are congressionally exempted from the Controlled Substances Act and thus the DEA’s rulemaking authority,” says Graff. “By creating a drug code for ‘marihuana extract’, the DEA is saying that they are a controlled substance, but that goes against a number of existing laws.”

Garrett Graff, associate partner at Hoban Law Group
Garrett Graff, associate partner at Hoban Law Group

The definition of ‘marihuana extract’ under the ‘Final Rule’ also references extracts containing one or more cannabinoids, which goes beyond the realm of cannabis altogether, according to Graff. “The DEA and many other sources have acknowledged and confirmed that cannabinoids can be derived from other varieties of flowers, cacao and other sources, making it virtually impossible to distinguish which cannabinoids would be subject to this drug code,” says Graff. “The DEA’s rule effectively makes the presence of cannabinoids a determinative factor of a controlled substance, which is inconsistent with what Congress has said.”

The petition filed is essentially the initiation or commencing of a lawsuit. Graff says their case is rooted in statute. “We hope to accomplish a striking of the rule, permanent injunction of the rule and for the DEA to engage in the appropriate processes and procedures when making rules in the future,” says Graff. “Alternatively, an amendment to the rule to make the definition of ‘marihuana extract’ consistent with existing law and reflect those portions and varieties of the plant which are in fact lawful could be considered.” It may still be roughly 30 days before the DEA responds with briefing and possibly an oral argument to follow on the various issues surrounding the petition, says Graff. The Ninth Circuit petition, including briefings and hearings, is likely to take at least several months.

The Practical Chemist

Potency Analysis of Cannabis and Derivative Products: Part 2

By Rebecca Stevens
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As mentioned in Part 1, the physiological effects of cannabis are mediated by a group of structurally related organic compounds known as cannabinoids. The cannabinoids are biosynthetically produced by a growing cannabis plant and Figure 1 details the biosynthetic pathways leading to some of the most important cannabinoids in plant material.

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Figure 1: The biosynthetic pathway of phytocannabinoid production in cannabis has been deeply studied through isotopic labeling experiments

The analytical measurement of cannabinoids is important to ensure the safety and quality of cannabis as well as its extracts and edible formulations. Total cannabinoid levels can vary significantly between different cultivars and batches, from about 5% up to 20% or more by dry weight. Information on cannabinoid profiles can be used to tailor cultivars for specific effects and allows end users to select an appropriate dose.

Routine Analysis vs. Cannabinomics 

Several structurally analogous groups of cannabinoids exist. In total, structures have been assigned for more than 70 unique phytocannabinoids as of 2005 and the burgeoning field of cannabinomics seeks to comprehensively measure these compounds.¹

Considering practical potency analysis, the vast majority of cannabinoid content is accounted for by 10-12 compounds. These include Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabivarian (THCV), cannabidivarin (CBDV) and their respective carboxylic acid forms. The cannabinoids occur primarily as carboxylic acids in plant material. Decarboxylation occurs when heat is applied through smoking, vaporization or cooking thereby producing neutral cannabinoids which are more physiologically active.

Potency Analysis by HPLC and GC

Currently, HPLC and GC are the two most commonly used techniques for potency analysis. In the case of GC, the heat used to vaporize the injected sample causes decarboxylation of the native cannabinoid acids. Derivatization of the acids may help reduce decarboxylation but overall this adds another layer of complexity to the analysis² ³. HPLC is the method of choice for direct analysis of cannabinoid profiles and this technique will be discussed further.

A sample preparation method consisting of grinding/homogenization and alcohol extraction is commonly used for cannabis flower and extracts. It has been shown to provide good recovery and precision² ³. An aliquot of the resulting extract can then be diluted with an HPLC compatible solvent such as 25% water / 75% acetonitrile with 0.1% formic acid. The cannabinoids are not particularly water soluble and can precipitate if the aqueous percentage is too high.

To avoid peak distortion and shifting retention times the diluent and initial mobile phase composition should be reasonably well matched. Another approach is to make a smaller injection (1-2 µL) of a more dissimilar solvent. The addition of formic acid or ammonium formate buffer acidifies the mobile phase and keeps the cannabinoid acids protonated.

The protonated acids are neutral and thus well retained on a C18 type column, even at higher (~50% or greater) concentrations of organic solvent² ³.

Detection is most often done using UV absorbance. Two main types of UV detectors are available for HPLC, single wavelength and diode array. A diode array detector (DAD) measures absorbance across a range of wavelengths producing a spectrum at each point in a chromatogram while single wavelength detectors only monitor absorbance at a single user selected wavelength. The DAD is more expensive, but very useful for detecting coelutions and interferences.

References

  1. Chemical Constituents of Marijuana: The Complex Mixture of Natural Cannabinoids. Life Sciences, 78, (2005), pp. 539
  2. Development and Validation of a Reliable and Robust Method for the Analysis of Cannabinoids and Terpenes in Cannabis. Journal of AOAC International, 98, (2015), pp. 1503
  3. Innovative Development and Validation of an HPLC/DAD Method for the Qualitative and Quantitative Determination of Major Cannabinoids in Cannabis Plant Material. Journal of Chromatography B, 877, (2009), pp. 4115

Rebecca is an Applications Scientist at Restek Corporation and is eager to field any questions or comments on cannabis analysis, she can be reached by e-mail, rebecca.stevens@restek.com or by phone at 814-353-1300 (ext. 2154)

OHA Addresses Oregon Growing Pains, Changes Testing Rules

By Aaron G. Biros
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Last week, the Oregon Health Authority (OHA) published a bulletin, outlining new temporary testing requirements effective immediately until May 30th of next year. The changes to the rules come in the wake of product shortages, higher prices and even some claims of cultivators reverting back to the black market to stay afloat.img_6245

According to the bulletin, these temporary regulations are meant to still protect public health and safety, but are “aimed at lowering the testing burden for producers and processors based on concerns and input from the marijuana industry.” The temporary rules, applying to both medical and retail products, are a Band-Aid fix while the OHA works on a permanent solution to the testing backlog.

Here are some key takeaways from the rule changes:

Labeling

  • THC and CBD amounts on the label must be the value calculated by a laboratory, plus or minus 5%.

Batch testing

  • A harvest lot can include more than one strain.
  • Cannabis harvested within a 48-hour period, using the same growing and curing processes can be included in one harvest lot.
  • Edibles processors can include up to 1000 units of product in a batch for testing.
  • The size of a process lot submitted for testing for concentrates, extracts or other non-edible products will be the maximum size for future sampling and testing.

    Oregon Marijuana Universal Symbol for Printing
    Oregon Marijuana Universal Symbol for Printing

Sampling

  • Different batches of the same strain can be combined for testing potency.
  • Samples can be combined from a number of batches in a harvest lot for pesticide testing if the weight of all the batches doesn’t exceed ten pounds. This also means that if that combined sample fails a pesticide test, all of the batches fail the test and need to be disposed.

Solvent testing

  • Butanol, Propanol and Ethanol are no longer on the solvent list.

Potency testing

  • The maximum concentration limit for THC and CBD testing can have up to a 5% variance.

Control Study

  • Process validation is replaced by one control study.
  • After OHA has certified a control study, it is valid for a year unless there is an SOP or ingredient change.
  • During the control study, sample increments are tested separately for homogeneity across batches, but when the control study is certified, sample increments can be combined.

Failing a test

  • Test reports must clearly show if a test fails or passes.
  • Producers can request a reanalysis after a failed test no later than a week after receiving failed test results and that reanalysis must happen within 30 days.
Gov. Kate Brown Photo: Oregon Dept. of Transportation
Gov. Kate Brown
Photo: Oregon Dept. of Transportation

The office of Gov. Kate Brown along with the OHA, Oregon Department of Agriculture (ODA) and Oregon Liquor Control Commission (OLCC) issued a letter in late November, serving as a reminder of the regulations regarding pesticide use and testing. It says in bold that it is illegal to use any pesticide not on the ODA’s cannabis and pesticide guide list. The letter states that failed pesticide tests are referred to ODA for investigation, which means producers that fail those tests could face punitive measures such as fines.

Photo: Michelle Tribe, Flickr
Photo: Michelle Tribe, Flickr

The letter also clarifies a major part of the pesticide rules involving the action level, or the measured amount of pesticides in a product that the OHA deems potentially dangerous. “Despite cannabis producers receiving test results below OHA pesticide action levels for cannabis (set in OHA rule), producers may still be in violation of the Oregon Pesticide Control Act if any levels of illegal pesticides are detected.” This is crucial information for producers who might have phased out use of pesticides in the past or might have began operations in a facility where pesticides were used previously. A laboratory detecting even a trace amount in the parts-per-billion range of banned pesticides, like Myclobutanil, would mean the producer is in violation of the Pesticide Control Act and could face thousands of dollars in fines. The approved pesticides on the list are generally intended for food products, exempt from a tolerance and are considered low risk.

As regulators work to accredit more laboratories and flesh out issues with the industry, Oregon’s cannabis market enters a period of marked uncertainty.

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Quality From Canada

Near Infrared, GC and HPLC Applications in Cannabis Testing

By Tegan Adams, Michael Bertone
5 Comments
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When a cannabis sample is submitted to a lab for testing there is a four-step process that occurs before it is tested in the instrumentation on site:

  1. It is ground at a low temperature into a fine powder;
  2. A solution is added to the ground powder;
  3. An extraction is repeated 6 times to ensure all cannabinoids are transferred into a common solution to be used in testing instrumentation.
  4. Once the cannabinoid solution is extracted from the plant matter, it is analyzed using High Pressure Liquid Chromatograph (HPLC). HPLC is the key piece of instrumentation in cannabis potency testing procedures.

While there are many ways to test cannabis potency, HPLC is the most widely accepted and recognized testing instrumentation. Other instrument techniques include gas chromatography (GC) and thin layer chromatography (TLC). HPLC is preferred over GC because it does not apply heat in the testing process and cannabinoids can then be measured in their naturally occurring forms. Using a GC, heat is applied as part of the testing process and cannabinoids such as THCA or CBDA can change form, depending on the level of heat applied. CBDA and THCA have been observed to change form at as low as 40-50C. GC uses anywhere between 150-200C for its processes, and if using a GC, a change of compound form can occur. Using HPLC free of any high-heat environments, acidic (CBDA & THCA) and neutral cannabinoids (CBD, THC, CBG, CBN and others) can be differentiated in a sample for quantification purposes.

Near Infrared

Near infrared (NIR) has been used with cannabis for rapid identification of active pharmaceutical ingredients by measuring how much light different substances reflect. Cannabis is typically composed of 5-30% cannabinoids (mainly THC and CBD) and 5-15% water. Cannabinoid content can vary by over 5% (e.g. 13-18%) on a single plant, and even more if grown indoors. Multiple NIR measurements can be cost effective for R&D purposes. NIR does not use solvents and has a speed advantage of at least 50 times over traditional methods.

The main downfall of NIR techniques is that they are generally less accurate than HPLC or GC for potency analyses. NIR can be programmed to detect different compounds. To obtain accuracy in its detection methods, samples must be tested by HPLC on ongoing basis. 100 samples or more will provide enough information to improve an NIR software’s accuracy if it is programmed by the manufacturer or user using chemometrics. Chemometrics sorts through the often complex and broad overlapping NIR absorption.

Bands from the chemical, physical, and structural properties of all species present in a sample that influences the measured spectra. Any variation however of a strain tested or water quantity observed can affect the received results. Consistency is the key to obtaining precision with NIR equipment programming. The downfall of the NIR technique is that it must constantly be compared to HPLC data to ensure accuracy.

At Eurofins Experchem , our company works with bothHPLC and NIR equipment simultaneously for different cannabis testing purposes. Running both equipment simultaneously means we are able to continually monitor the accuracy of our NIR equipment as compared to our HPLC. If a company is using NIR alone however, it can be more difficult to maintain the equipment’s accuracy without on-going monitoring.

What about Terpenes?

Terpenes are the primary aromatic constituents of cannabis resin and essential oils. Terpene compounds vary in type and concentration among different genetic lineages of cannabis and have been shown to modulate and modify the therapeutic and psychoactive effects of cannabinoids. Terpenes can be analyzed using different methods including separation by GC or HPLC and identification by Mass Spectrometry. The high-heat environment for GC analysis can again cause problems in accuracy and interpretation of results for terpenes; high-heat environments can degrade terpenes and make them difficult to find in accurate form. We find HPLC is the best instrument to test for terpenes and can now test for six of the key terpene profiles including a-Pinene, Caryophyllene, Limonene, Myrcene, B-Pinene and Terpineol.

Quality Systems

Quality systems between different labs are never one and the same. Some labs are testing cannabis under good manufacturing practices (GMP), others follow ISO accreditation and some labs have no accreditation at all.

From a quality systems’ perspective some labs have zero or only one quality system employee(s). In a GMP lab, to meet the requirements of Health Canada and the FDA, our operations are staffed in a 1:4 quality assurance to analyst ratio. GMP labs have stringent quality standards that set them apart from other labs testing cannabis. Quality standards we work with include, but are not limited to: monthly internal blind audits, extensive GMP training, yearly exams and ongoing tests demonstrating competencies.

Maintaining and adhering to strict quality standards necessary for a Drug Establishment License for pharmaceutical testing ensures accuracy of results in cannabis testing otherwise difficult to find in the testing marketplace.

Important things to know about testing

  1. HPLC is the most recommended instrument used for product release in a regulated environment.
  2. NIR is the best instrument to use for monitoring growth and curing processes for R&D purposes, only if validated with an HPLC on an ongoing basis.
  3. Quality Systems between labs are different. Regardless of instrumentation used, if quality systems are not in place and maintained, integrity of results may be compromised.
  4. GMPs comprise 25% of our labour costs to our quality department. Quality systems necessary for a GMP environment include internal audits, out of specification investigations, qualification and maintenance of instruments, systems controls and stringent data integrity standards.
Soapbox

Labeling Cannabis Products is a Booming Market

By Marsha Frydrychowski
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Legal marijuana sales are expected to hit $6.7 billion in 2016, with the market expected to climb to $21.8 billion in sales by 2020. As legal cannabis sales rise, cannabis labels are quickly becoming one of the fastest growing markets for label manufacturers.

An Industry Gaining Legitimacy

Since California first legalized medical cannabis in 1996, the cannabis industry has grown considerably. Voters in four states legalized recreational cannabis last week on Election Day, including California, which is currently the world’s 6th largest economy. Voters in another four states legalized medical cannabis as well, bringing the total to 28 states with some form of legalization measure.

The market is moving ahead and will not be limited to small businesses and dispensaries either. Already, more than 50 publicly traded companies have blitzed the market, including pharmaceuticals, medical growers and even major tech companies.

An example of a cannabis flower label in Oregon with all of the required information.
An example of a cannabis flower label in Oregon with all of the required information.

What’s more, public support for full cannabis legalization is at an all-time high 61 percent, according to a recent survey from the AP-NORC Center for Public Affairs Research. The market is here to stay.

Cannabis flower labels

Legal cannabis has primarily consisted of dispensaries selling cannabis flower or leaves (ready-to-smoke marijuana) in pouches or childproof containers. Regulations have essentially required two cannabis labels for the pouches: a branded label on the front and a regulatory label on the back. Many dispensaries also use pre-printed pouches.

Similar to the way alcohol labels must contain information for alcohol content, the informational labels that sit on the backs of pouches are legally required to provide certain accurate information, including:

The universal symbol required on all cannabis products in Colorado
The universal symbol required on all cannabis products in Colorado
  • THC %
  • CBD %
  • Net weight in grams
  • Lab name and test number confirmation
  • Batch number
  • Date tested
  • Strain name
  • Warning Label

And cannabis flower labels are just the beginning. Many smoke-free product categories are emerging with similar labeling requirements. These often allow for increased branding opportunities that will afford better profit margins for label suppliers. Some of the many products in this young category include:

  • Edibles — such as dark chocolates, baked goods, snack crackers and teas infused with cannabis.
  • Topicals — such as pain-relieving lotions and creams.
  • Tinctures — cannabis-infused oils that are applied in drops to the tongue.

Bottom line: For label and packaging suppliers, cannabis represents one of the fastest growing market opportunities today and the opportunities extend way beyond labeling for the flower itself.

Managing Compliance

As more and more states move toward legalization and regulation, uneven laws in different states are increasingly governing the market. Businesses must respond to ever-changing requirements, including labeling standards. While many dispensaries have gotten away with minimalist labels, states are increasingly demanding dispensaries meet more stringent legal requirements. For example, Oregon passed new labeling requirements this year and products that failed to meet them by October 1, 2016 were not allowed on store shelves.

Label suppliers entering the market must keep abreast of the changing regulations and be able to help brands navigate them. They need to work to understand the intricacies of this new market, rather than simply looking to redirect the capabilities they already possess. See the original post here.

 

The C4 Cannabinomics Collaborative: Q&A with Dr. Zacariah Hildenbrand

By Aaron G. Biros
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Dr. Zacariah Hildenbrand, chief scientific officer and partner at C4 Laboratories, is currently researching some of the lesser-known molecules in cannabis, and he’s on to something. His research focuses on discovering new molecules, determining their therapeutic effects and expanding our understanding of the constituents of cannabis.

Dr. Zacariah Hildenbrand, chief scientific officer and partner at C4 Laboratories.
Dr. Zacariah Hildenbrand, chief scientific officer and partner at C4 Laboratories.

Dr. Hildenbrand received his Ph.D. from the University of Texas at El Paso where he researched the molecular architecture involved in hormone-dependent cancers. At the University of Texas Southwestern Medical Center in Dallas, his post-doctoral research contributed to the development of a novel therapy for the treatment of chronic myeloid leukemia, a blood-borne cancer that afflicts small children. He has published over 25 peer-reviewed scientific journal articles and hopes to do the same with his research in cannabis.

After a career of scientific consulting, Dr. Hildenbrand met Ryan Treacy, founder and chief executive officer of C4 Laboratories, in 2015 when Treacy launched the company. In June of 2015, the laboratory began operations, providing Dr. Hildenbrand the opportunity to embark on a new and exciting field of research- cannabis.

Ryan Tracy, founder and chief executive officer at C4 Labs.
Ryan Treacy, founder and chief executive officer at C4 Laboratories.

They currently collaborate with Dr. Kevin Schug of the Shimadzu Center for Advanced Analytical Chemistry (SCAAC) at the University of Texas, Arlington and together Drs. Schug and Hildenbrand are pursuing a DEA license to expand their current cannabis research. The SCAAC is a $10.0+ million analytical laboratory with instrumentation that only a handful of people in the world has access to.

C4 Laboratories, based in Mesa, Arizona, currently offers a range of services for cannabis analysis including terpene and cannabinoid analytics, microbial, pesticide, fungicide and insecticide testing. In addition to the standard gamut of tests, they also specialize in cultivation analytics like mold and mildew culture testing, viral detection with sentinel plants and comprehensive analysis of environmental conditions.

What makes their company unique is their multidisciplinary effort to characterize the therapeutic compounds found in cannabis, the C4 Cannabinomics Collaborative. We sit down with Dr. Zac Hildenbrand to talk cannabis science, his research and what they hope to accomplish with the C4 Cannabinomics Collaborative.

CannabisIndustryJournal: What is the C4 Cannabinomics Collaborative?

Dr. Zacariah Hildenbrand: The C4 Cannabinomics Collaborative is an open collaboration between growers and scientists to discover new molecules in cannabis and to have a better characterization of individual cannabis strains based on the active constituents found in each sample. We are facilitating the collaboration of some of the world’s best cannabis growers with world-class scientists to find new information about the plant.

What we want to accomplish in this work is identifying novel molecules. Because of the [federal government’s] restrictions in researching cannabis, there is very little peer-reviewed literature on many of the compounds found in cannabis. We want to secondarily find out what those molecules do in the human body and thus make recommendations for strains targeting specific conditions.c4 logo

We also want to understand the strains currently out there by determining the most established cannabinoids and terpenes via chemotyping. You hear a lot of people talking about the effects of an Indica or Sativa and making recommendations based on that. We want to find chemical signatures based on cannabinoids and terpenes and make recommendations based on that. There are a lot of problems at hand when discussing strain names scientifically. There are nomenclature issues- people calling the same strain different names, people giving multiple names to the same strain to make it appear that their strain portfolios are more diverse.

We can identify the chemical signatures in strains based on the major cannabinoids and terpenes. Based on the terpenes and chemical profile we can determine more accurate recommendations for patients as well as in recreational applications. All of this, again, discovering the new molecules, identifying the current strains, is so we can make more informed decisions regarding cannabis use. It is not a panacea but it is a very robust plant. There are a lot of terpenes with anti-inflammatory responses. Other molecules help with blood flow, sleep, regulating blood glucose, and we all know the cases of CBD helping children with convulsions and epilepsy. We want people to make sure they have the most up-to-date information.

CIJ: How is your collaboration with the SCAAC at UT Arlington contributing to this work?

Dr. Hildenbrand: One of the instruments we use there is a supercritical-fluid-extraction supercritical-fluid-chromatography mass-spectrometer (SFE-SFC-MS). With that instrument, we can do the extraction on the machine with an extreme level of sensitivity. It is ideal for drug discovery and identifying molecules in the parts-per-quadrillion range. This particular instrument allows us to detect molecules with an extreme level of sensitivity without volatizing them during the sample extraction process.

The Shimadzu Center for Advanced Analytical Chemistry
The Shimadzu Center for Advanced Analytical Chemistry

We want to acquire samples of unique cannabis from growers that will work with us to discover new cannabis constituents. We are in the process of getting a DEA license so that we can send products across state lines to the center at UT Arlington to perform the advanced characterization. They have instrumentation that only a handful of people in the world have access to, which gives us the best opportunity to explore the unknown. When we discover new molecules, find out what they do on the molecular level, we can then isolate these compounds and ultimately use this newfound knowledge for the development of effective nutraceuticals.

CIJ: What molecules are you researching right now?

Dr. Hildenbrand: Some of the low-hanging fruit in our research looks at identifying compounds similar to the better-studied compounds such as THC and CBD. THCV has a very similar structure to THC, but has a shorter acyl carbon chain (3 carbons vs. 5).

Tetrahydrocannabivarin (THCV)
Tetrahydrocannabivarin (THCV)

THCV doesn’t induce a psychoactive response (like THC), but it does improve fat utilization, so it has remarkable potential for medicine. We are looking at what conditions are required for it to occur naturally. Cannabis doesn’t produce THCV in a high amount. 0.7% by weight is the most we have seen in Arizona. In Oregon, where craft cannabis has been refined to a much higher degree, we have heard rumblings of some strains containing up to 3% THCV. We want to find out if this is a possible weight loss tool. Our research in CBDV is very much the same.Cannabinoid Biogenesis

CBL is the breakdown product of CBC when it is treated with ultraviolet light. We know absolutely nothing about what CBL does. If we find a strain that produces high amounts of CBC, we can then treat it with UV light and force the conversion to CBL, and then ultimately determine what it does. This is a good example of low-hanging fruit and the versatility of cannabis. Based on the biogenesis of the cannabinoids, we can alter the profile of cannabis products using a series of biochemical reactions.

Cannabicyclol (CBL)
Cannabicyclol (CBL)

For example, we have been helping clients in Arizona look for a quality sleep aid in cannabis. Certainly, Indica strains will help, but the molecule CBN helps specifically with sleep abnormalities. As CBN is formed as a byproduct when CBD or THC are oxidized, we see some producers using liquid nitrogen to oxidize CBD, leading to higher CBN levels. I would like to think we are in the age of understanding CBD, THC and the major terpenes,but there are a whole milieu of compounds that require our attention and THCV, CBDV and CBL are just a few that we want to devote our efforts to right away.

CIJ: What are your plans in the immediate future?

Dr. Hildenbrand: We are in the process of finalizing the documents to bring a C4 laboratory into Oregon where we can do quite a bit of research and where we’ll have access to some very unique cannabis. We will offer full compliance testing per ORELAP and OLCC regulations, but we also want to acquire samples (free of charge) from growers that want to collaborate with us to discover new molecules. We’ve been lucky enough to start working with growers like Adam Jacques and Chris West in Eugene, but we also want to be available to other growers who want to contribute to this research.

CIJ: What are your long-term goals with this project?

Dr. Hildenbrand: At a basic level, we hope to expand the current understanding of the cannabis plant. There is a lot of “bro science” and anecdotal claims out there. There is so much that we don’t know about cannabis that we cannot simply rely on anecdotal claims for each strain. We want to bring cannabis into the same light as any pharmaceutical-grade or biomedical research.

We need to be characterizing this plant with the same level of detail as other pertinent molecular therapies. In doing so there are a lot of potential discoveries to be made and we might be able to unlock the future of medicine. A drug like Marinol, for example, has been met with mixed reviews because its only one dimensional. Furthermore, we find that the terpene molecules are tremendously beneficial and this interplay between cannabinoids and terpenes is something that we want to explore further. All and all we wish to further illustrate the therapeutic capacities of cannabis within the contexts of specific ailments and medical conditions, while discovering the medicine of the future.

Steep Hill Labs Expands to Pennsylvania, Washington, D.C.

By Aaron G. Biros
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Last week, Steep Hill Labs, Inc. announced plans to expand on the East Coast, including licensing for laboratories in Washington, D.C. and Pennsylvania. The cannabis testing company now is operating or developing in seven states, the District of Columbia along with an official arrangement with a research university in Jamaica, according to Cathie Bennett Warner, director of public relations at Steep Hill.

The same team of physicians that oversees the Steep Hill laboratory in Maryland will operate the Pennsylvania and D.C. labs. Heading that team is chief executive officer Dr. Andrew Rosenstein, chief of the division of Gastroenterology at University of Maryland Saint Joseph Medical Center and assistant clinical professor of Gastroenterology and Hepatology at the University of Maryland Medical Center. Dr. Rosenstein has been recognized by Baltimore Magazine as a top doctor in the Baltimore area, according to a press release.

Dr. Andrew Rosenstein, CEO of Steep Hill Maryland, PA and D.C.
Dr. Andrew Rosenstein, CEO of Steep Hill Maryland, PA and D.C.

According to Dr. Rosenstein, they want to provide accurate clinical results for trials with patients using cannabis. “All clinical trials will require a competent, credible and reliable lab partner and that is what we are bringing to the field- and that is why we are working with Steep Hill,” says Dr. Rosenstein. With team members having backgrounds in pathology, molecular diagnostics, clinical chemistry, microbiology and genetics, it should come as no surprise that they plan to participate in clinical research.

Dr. Rosenstein’s vested interest in cannabis safety stems from prior experience with his patients using cannabis. “Over the past five years, we have seen an increased number of patients using cannabis, particularly for managing the side effects of Crohn’s disease and cancer treatment,” says Dr. Rosenstein. “They would bring it up to us and at the time I didn’t know much about it, but anecdotally it’s really clear that a lot of patients have great responses to it.” Not knowing much about the preparation or safety of cannabis at the time led Dr. Rosenstein to advise patients to be very careful if they are immunocompromised.

Examination of cannabis prior to testing- credit Steep Hill Labs, Inc.
Examination of cannabis prior to testing- credit: Steep Hill Labs, Inc.

“When a patient is immunocompromised, a bacterial or fungal infection can be lethal, so because we had patients using cannabis, we wanted to make sure it was safe,” says Dr. Rosenstein. So when Maryland legalized medical cannabis, Dr. Rosenstein and his team saw the need to protect patient safety and Steep Hill was a perfect fit. “We really didn’t want to reinvent the wheel so we looked for someone to partner with,” says Dr. Rosenstein. “Steep Hill has the best technology and the best credibility and we didn’t want to compromise on quality and safety issues. They felt the same way so we partnered with them and culturally it has been a great fit.”

Steep Hill Express in Berkeley, CA- MD,PA and D.C. will have a similar offering of instant potency analysis
Steep Hill Express in Berkeley, CA- MD,PA and D.C. will have a similar offering of instant potency analysis

The new laboratories plan to offer a similar range of services that are offered at other Steep Hill labs, such as rapid potency testing for THC-A, ∆-9-THC, CBD, CBD-A and moisture. But Dr. Rosenstein sees clinical opportunities in the East Coast medical hubs. “We want to provide the testing component for studies, providing clinical reproducibility and consistency, and those are the things as a top-notch lab that we are interested in doing.”

A petri dish of mold growth from tested cannabis- Photo credit: Steep Hill-
A petri dish of mold growth from tested cannabis- Photo credit: Steep Hill Labs, Inc.

With a physician-led group that has experience in molecular diagnostics, partnering with Steep Hill is about being medically focused, according to Dr. Rosenstein. “First and foremost, this is about patient safety.” Because of that, he emphasizes the need for required microbiological contaminant testing, particularly because of his experience with patients. “If you’re a cancer patient and you get a toxic dose of salmonella or E. coli, that can kill you, so testing for microbiologic  contamination is of the highest priority.”

According to Warner, bridging the medical cannabis science gap with Steep Hill’s professionalism and experienced doctors practicing medicine is a big deal. “We are working very closely with their medical team to make sure these standards are medically superior,” says Warner. “To have these doctors with such a high level of knowledge in medicine working with us in cannabis analytics is a breakthrough.”