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.
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.
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.”
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.
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.
Edibles and vape pens are rapidly becoming a sizable portion of the cannabis industry as various methods of consumption popularize beyond just smoking dried flower. These products are produced using cannabis concentrates, which come in the form of oils, waxes or shatter (figure 1). Once the cannabinoids and terpenes are removed from the plant material using solvents, the solvent is evaporated leaving behind the product. Extraction solvents are difficult to remove in the low percent range so the final product is tested to ensure leftover solvents are at safe levels. While carbon dioxide and butane are most commonly used, consumer concern over other more toxic residual solvents has led to regulation of acceptable limits. For instance, in Colorado the Department of Public Health and Environment (CDPHE) updated the state’s acceptable limits of residual solvents on January 1st, 2017.
Since the most suitable solvents are volatile, these compounds are not amenable to HPLC methods and are best suited to gas chromatography (GC) using a thick stationary phase capable of adequate retention and resolution of butanes from other target compounds. Headspace (HS) is the most common analytical technique for efficiently removing the residual solvents from the complex cannabis extract matrix. Concentrates are weighed out into a headspace vial and are dissolved in a high molecular weight solvent such as dimethylformamide (DMF) or 1,3-dimethyl-3-imidazolidinone (DMI). The sealed headspace vial is heated until a stable equilibrium between the gas phase and the liquid phase occurs inside the vial. One milliliter of gas is transferred from the vial to the gas chromatograph for analysis. Another approach is full evaporation technique (FET), which involves a small amount of sample sealed in a headspace vial creating a single-phase gas system. More work is required to validate this technique as a quantitative method.
Gas Chromatographic Detectors
The flame ionization detector (FID) is selective because it only responds to materials that ionize in an air/hydrogen flame, however, this condition covers a broad range of compounds. When an organic compound enters the flame; the large increase in ions produced is measured as a positive signal. Since the response is proportional to the number of carbon atoms introduced into the flame, an FID is considered a quantitative counter of carbon atoms burned. There are a variety of advantages to using this detector such as, ease of use, stability, and the largest linear dynamic range of the commonly available GC detectors. The FID covers a calibration of nearly 5 orders of magnitude. FIDs are inexpensive to purchase and to operate. Maintenance is generally no more complex than changing jets and ensuring proper gas flows to the detector. Because of the stability of this detector internal standards are not required and sensitivity is adequate for meeting the acceptable reporting limits. However, FID is unable to confirm compounds and identification is only based on retention time. Early eluting analytes have a higher probability of interferences from matrix (Figure 2).
Mass Spectrometry (MS) provides unique spectral information for accurately identifying components eluting from the capillary column. As a compound exits the column it collides with high-energy electrons destabilizing the valence shell electrons of the analyte and it is broken into structurally significant charged fragments. These fragments are separated by their mass-to-charge ratios in the analyzer to produce a spectral pattern unique to the compound. To confirm the identity of the compound the spectral fingerprint is matched to a library of known spectra. Using the spectral patterns the appropriate masses for quantification can be chosen. Compounds with higher molecular weight fragments are easier to detect and identify for instance benzene (m/z 78), toluene (m/z 91) and the xylenes (m/z 106), whereas low mass fragments such as propane (m/z 29), methanol (m/z 31) and butane (m/z 43) are more difficult and may elute with matrix that matches these ions. Several disadvantages of mass spectrometers are the cost of equipment, cost to operate and complexity. In addition, these detectors are less stable and require an internal standard and have a limited dynamic range, which can lead to compound saturation.
Regardless of your method of detection, optimized HS and GC conditions are essential to properly resolve your target analytes and achieve the required detection limits. While MS may differentiate overlapping peaks the chances of interference of low molecular weight fragments necessitates resolution of target analytes chromatographically. FID requires excellent resolution for accurate identification and quantification.
Formed in 2015, Outco is a vertically integrated, licensed producer of medical cannabis in Southern California. Outco manages Outliers Collective, the first licensed dispensary continually operating in San Diego County. They operate the first licensed cultivation on Native American land in Southern California, the first cultivation building permit in Southern California and the first licensed extraction facility in San Diego County. Outco is on track to be the largest licensed producer of medical cannabis in Southern California.
The company prides themselves on attention to detail; the well versed team implements real science in their cultivation and extraction processes. Lincoln Fish, co-founder and chief executive officer of Outco, has more than 30 years of experience as an entrepreneur. Before entering the cannabis industry, Linc started and sold companies in the healthcare technology and nutraceutical spaces.
Fish’s experience with FDA regulations in nutraceuticals prepared him for running a business in such a tumultuous, highly regulated environment like cannabis. “One thing I took from the nutraceutical industry is how to present products to consumers and letting them know it is safe, effective and consistent,” says Fish. He says he noticed a serious lack of consistency in products. They tested 25 different vape cartridges, with their own oil, to find a consistent product they can use and know that consumers will safely and consistently get the same results. “There is a lot of room for more professionals and a lot of room for more science,” says Fish. “We try to position ourselves in a way that is consistent with where we think policy will go so we are very careful with recommendations from a scientific standpoint, patient information and product safety.”
According to Fish, they currently distribute cannabis products to about 75 licensed dispensaries in Orange County, San Diego and Los Angeles. With construction underway at their cultivation facility on Native American land, Fish says they plan to generate roughly 2600 pounds of cannabis each month. Gearing up for that in addition to the expanding recreational market requires some planning in advance, says Fish. Part of that plan is making sure quality controls are in place to keep consistency in the product quality and dosage. They are also actively seeking to open their distribution channels further.
“We are building out a full lab of our own in addition to third party testing to perform internal quality controls,” says Fish. Equipped with their own laboratory instrumentation like HPLC and GC, they hope to establish proper in-house quality controls as well as provide that resource to younger startup companies. As one of the founding partners of Canopy San Diego, an ancillary startup accelerator, Fish sees great potential in working with younger companies to get them off the ground. Fish met Outco’s vice president of extraction, Dr. Markus Roggen, at a Canopy San Diego event. It was there that they had the idea to build a startup accelerator for companies that actually touch the plant- extractors, cultivators and infused-product manufacturers, as opposed to a startup accelerator that would only help ancillary businesses.
Dr. Roggen, who is an organic chemist by training, heads up Outco’s supercritical CO2 extraction operation. “I came to the ‘art’ of cannabis extraction with an open, yet scientifically focused mind,” says Dr. Roggen. “My approach was to look past the myths and stories about extraction methods and focus on finding data, as there really wasn’t much available. I therefore, from the beginning, started to study the capabilities of our extraction equipment by chemometric methods.” Chemometrics is the science of relating measurements made on a chemical system or process to the state of the system via applications of mathematical methods. “Already the first sets of experiments showed that long-held beliefs in the cannabis community were inaccurate,” says Dr. Roggen. “For example the particle size of extracted material matters. Or that it is possible to preserve and even isolate terpenes by CO2 extraction methods.” With plans to have a full plant and analytical chemistry laboratory on site, they hope to perform more research that focuses on optimizing extraction processes.
Dr. Allison Justice leads their cultivation team with a background in greenhouse management and commercial horticulture. Dr. Justice says plants are grown, starting at a young age (seed or vegetative cutting), with the protection of biological control agents. “Biological control is a management strategy that entails the release of beneficial insects or fungi, such as parasitoids and predators, in order to suppress or regulate insect populations in greenhouses and grow rooms,” says Dr. Justice.
When implemented properly, this eliminates the need to use synthetic pesticides. “Biological control agents are not put in place to eradicate pest populations yet are applied as preventives to minimize plant damage and maintain their own populations.” They are constantly evaluating light types, spectrum and intensity to determine optimal ranges, according to Dr. Justice. They don’t use any pre-mixed “cannabis” nutrient supplements for their plants, instead they design an experiment to determine the desired levels and ratios of essential plant nutrients. “We have found it crucial to determine what ratios of nutrients the plant actually needs and by knowing this, we know how to manipulate the recipe determined by the plant’s given nutritional symptoms,” says Dr. Justice. Every type of adjustment in cultivation and extraction is based on results from experimentation rooted in legitimate science. Instead of guessing when it might be time to harvest, they use a water activity meter, logging and recording all the data to determine the appropriate time to trim and cure plants. Performing analytical testing at every step is key, says Fish.
Looking toward the recreational market, Fish sees an obvious opportunity to expand their wholesale operations substantially, with several larger new cultivation projects planned. “The key though is to produce flower and concentrate offerings with the same standards we employ for medical cannabis,” says Fish.
Sample preparation experts and analytical chemists are quick to suggest QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) to cannabis laboratories that are analyzing both flower and edible material for pesticides, mycotoxins and cannabinoid content. Besides having a quirky name, just what makes QuEChERS a good extraction technique for the complicated matrices of cannabis products? By understanding the chemistry behind the extraction and the methodology’s history, cannabis laboratories can better implement the technology and educate their workforce.
In 2003, a time when only eight states had legalized the use of medical cannabis, a group of four researchers published an article in the Journal of AOAC International that made quite the impact in the residue monitoring industry. Titled Fast and Easy Multiresidue Method Employing Acetonitrile Extraction/Partitioning and “Dispersive Solid-Phase Extraction” for the Determination of Pesticide Residues in Produce, Drs. Michael Anastassiades, Steven Lehotay, Darinka Štajnbaher and Frank Schenck demonstrate how hundreds of pesticides could be extracted from a variety of produce samples through the use of two sequential steps: an initial phase partitioning followed by an additional matrix clean up. In the paper’s conclusion, the term QuEChERS was officially coined. In the fourteen years that have followed, this article has been cited over 2800 times. Subsequent research publications have demonstrated its use in matrices beyond food products such as biological fluids, soil and dietary supplements for a plethora of analytes including phthalates, pharmaceutical compounds and most recently cannabis.
The original QuEChERS extraction method utilized a salt blend of 4 g of magnesium sulfate and 1 g of sodium chloride. A starting sample volume of 10 g and 10 mL of acetonitrile (ACN) were combined with the above-mentioned salt blend in a centrifuge tube. The second step, dispersive solid phase extraction (dSPE) cleanup, included 150 mg of magnesium sulfate and 25 mg of primary secondary amine (PSA). Subsequent extraction techniques, now known as AOAC and European QuEChERS, suggested the use of buffered salts in order to protect any base sensitive analytes that may be critical to one’s analysis. Though the pH of the extraction solvent may differ, all three methods agree that ACN should be used as the starting organic phase. ACN is capable of extracting the broadest range of analytes and is compatible with both LC-MS/MS and GC-MS systems. While ethyl acetate has also been suggested as a starting solvent, it is incompatible with LC-MS/MS and extracts a larger amount of undesirable matrix components in the final aliquot.
All laboratories, including cannabis and food safety settings, are constantly looking for ways to decrease their overhead costs, batch out the most samples possible per day, and keep their employees trained and safe. It is not a stretch to say that QuEChERS revolutionized the analytical industry and made the above goals tangible achievements. In the original publication, Anastassiades et al. established that recoveries of over 85% for pesticides residues were possible at a cost as low as $1 per ten grams of sample. Within forty minutes, up to twelve samples were fully extracted and ready to be analyzed by GC-MS, without the purchase of any specialized equipment. Most importantly, no halogenated solvents were necessary, making this an environmentally conscious concept. Due to the nature of the cannabis industry, laboratories in this field are able to decrease overall solvent usage by a greater amount than what was demonstrated in 2003. The recommended starting sample for cannabis laboratories is only one gram of flower, or a tenth of the starting volume that is commonly utilized in the food safety industry. This reduction in sample volume then leads to a reduction in acetonitrile usage and thus QuEChERS is a very green extraction methodology.
As with any analytical method, QuEChERS is not perfect or ideal for every laboratory setting. Challenges remain in the cannabis industry where the polarity of individual pesticides monitored in some states precludes them from being amenable to the QuEChERS approach. For cannabis laboratories looking to improve their pesticide recoveries, decrease their solvent usage and not invest their resources into additional bench top equipment, QuEChERS is an excellent technique to adopt. The commercialization of salt blends specific for cannabis flowers and edibles takes the guesswork out of which products to use. The growth of cannabis technical groups within established analytical organizations has allowed for better communication among scientists when it comes to best practices for this complicated matrix. Overall, it is definitely worth implementing the QuEChERS technique in one’s cannabis laboratory in order to streamline productivity without sacrificing your results.
The AOCS Annual Meeting is an international science and business forum on fats, oils, surfactants, lipids and related materials. The American Oil Chemist’s Society (AOCS) is holding their meeting in Orlando, Florida from April 30 to May 3, 2017. Last year’s meeting included discussions on best practices and the pros and cons of different extraction techniques, sample preparation, proficiency testing and method development, among other topic areas.
Posters on display for the duration of the Annual Meeting will discuss innovative solutions to test, preparing samples, discovering new compounds and provide novel information about the compounds found in cannabis. David Egerton, vice president of technical operations at CW Analytical (a cannabis testing laboratory in Oakland, CA), is preparing a poster titled Endogenous Solvents in Cannabis Extracts. His abstract discusses testing regulations focusing on the detection of the presence of solvents, despite the fact that endogenous solvents, like acetone and lower alcohols, can be found in all plant material. His study will demonstrate the prevalence of those compounds in both the plant material and the concentrated oil without those compounds being used in production.
The conference features more than 650 oral and poster presentations within 12 interest areas. This year’s technical program includes two sessions specifically designed to address cannabinoid analytics:
Lab Proficiency Programs and Reference Samples
How do you run a lab proficiency program when you cannot send your samples across state lines? What constituents do you test for when state requirements are all different? Are all pesticides illegal to use on cannabis? What pesticides should be tested for when they are mostly illegal to use? How do you analyze proficiency results when there are no standard methods? Learn about these and other challenges facing the cannabis industry. This session encourages open and active discussion, as the cannabis experts want to hear from you and learn about your experiences.
The need for high-quality and safe products has spurred a new interest in cannabinoid analytics, including sample preparation, pesticide, and other constituent testing. In this session, a diverse group of scientists will discuss developing analytical methods to investigate cannabis. Learn the latest in finding and identifying terpenes, cannabinoids, matrix effects, and even the best practice for dissolving a gummy bear.
Cynthia Ludwig, director of technical services at AOCS, says they are making great progress in assembling analytical methods for the production of the book AOCS Collection of Cannabis Analytical Methods. “We are the leading organization supporting the development of analytical methods in the cannabis industry,” says Ludwig. “Many of the contributors in that collection will be presenting at the AOCS Annual Meeting, highlighting some of the latest advances in analyzing cannabis.” The organization hopes to foster more collaboration among those in the cannabis testing industry.
In addition to oral and poster sessions, the 2017 Annual Meeting will feature daily networking activities, more than 70 international exhibitors, two special sessions, and a Hot Topics Symposia which will address how current, critical issues impact the future of the fats and oils industry.
Lezli Engelking founded the Foundation of Cannabis Unified Standards (FOCUS) in 2014 to protect public health, consumer safety, and safeguard the environment by promoting integrity in the cannabis industry through the use of standards. Standards are an agreed upon way of doing things and specify guidelines or requirements for producing goods or providing services, according to FOCUS.
Standards can take the form of a “reference document, which may include specifications, guidelines, conditions or requirements for products, operations, services, methods, personnel and systems on how to design, operate, manufacture or manage something.” Peter Maguire, VP of System Applications for Lighthouse Worldwide Solutions and committee chair of the FOCUS Cultivation standard, joined the organization wanting to make a positive impact on the industry that is in line with protecting people and medical patients. He sees so much variability in the industry and the need to homogenize standard operating procedures (SOPs). “I have worked with multiple cultivation facilities and a few of them have operating procedures in place but having them in place is only half the solution- it’s critical to have the right ones in place,” says Maguire. He has twenty years of experience in contamination control in manufacturing, before entering the cannabis industry.
The FOCUS cultivation standard was created by experts who have years of experience in both cannabis cultivation, good agricultural practices and in the tightly regulated pharmaceutical industry. “FOCUS created these guidelines as a sort of roadmap for success in business; You need to keep your employees healthy and your products safe to survive in the long term,” says Maguire. We sit down with Lezli Engelking to find out how the standards are created, what makes them significant and what businesses can gain by working with them.
CannabisIndustryJournal: Why are standards important?
Lezli: Standards are the international language for trade – they exist in every industry. “The U.S. Department of Commerce estimates that standards and conformity assessment impact more than 80% of global commodity trade.” FOCUS is not reinventing the wheel with what we are doing. We are simply adapting a business model the federal government already uses. In the 80s, when the heroin epidemic swept across the US, methadone clinics popped up in every state in the country within two years. The clinics were all operating under different state, city and county regulations – much like the cannabis industry is today. The federal government took a look at the situation and decided they needed a way to regulate these clinics in order to protect public health and safety. They released a Request For Proposal (RFP) looking for an organization to create voluntary-consensus standards and a third-party certification system for the methadone clinics. Commission on Accreditation of Rehabilitation Facilities (CARF) is the organization that answered and won that RFP. CARF continues to work with Health and Human Services to maintain the standards and provide third-party certification to the clinics today. FOCUS develops international, voluntary consensus standards and a third party certification program for the global cannabis industry based on the CARF model. This is extremely important, because of the National Technology Transfer and Advancement Act, (Public Law 104-115), signed into law March 7, 1996 by President Clinton. The act requires that all federal agencies use standards developed by voluntary-consensus standards bodies, instead of government-unique standards wherever possible. Perhaps even more importantly, the Act includes provisions that encourage federal agencies to partner with the private sector in the development of standards that not only help improve the efficiency and effectiveness of government, but also strengthen the U.S. position in the global marketplace.
CIJ: What exactly goes into developing a voluntary-consensus standard?
Lezli: Voluntary-Consensus refers to the type of standard and how it is developed. Everyone who participates in the development of voluntary-consensus standards does so on a voluntary basis. Committee members must come to a consensus on every point within the standard- down to every comma or semicolon. Once the development process is complete, the standards must undergo a 30-day public review period. The process for developing voluntary-consensus standards is designated by International Organization for Standardization (ISO). ISO has member agencies in 163 countries that participate in the development of standards. The American National Standards Institute (ANSI) is the American body for ISO. FOCUS follows all ISO/ANSI guidelines in the standards development process. This is extremely important because it means FOCUS standards are suitable for accreditation and adoption into regulations according to the National Technology Transfer and Advancement Act. All voluntary-consensus standards are developed under the principles of:
Openness| Participation in the standard development process is open to individuals with a stake in the standard who bring useful expertise along with the spirit and willingness to participate.
Balance| Focus stakeholder groups involve all stakeholder groups: industry, regulatory, quality assurance, medical, law enforcement, business, research, consumers, patients and the general public.
Voluntary-Consensus| Individual subcommittees of volunteers develop each area of the standard, offering their unique expertise to form a consensus. They are not paid for their participation.
Lack of Dominance| No party has dominant representation, or influence to the exclusion of fair and equitable consideration of other viewpoints.
CIJ: More specifically, how are the FOCUS standards developed?
Lezli: To create a baseline standard, FOCUS utilized World Health Organization (WHO) guidelines for Good Manufacturing Practices (GMP), Good Agricultural Practices (GAP), Good Laboratory Practices (GLP), Code of Federal Regulations (CFR) for pharmaceutical GMPs, nutraceutical GMPs, food safety standards, OSHA and HACCP. From there, applicable cannabis regulations from around the world were added. All of this information was compiled into auditor-style checklists. Each committee member was provided time to go edit, remove or add to items in the checklist on their own. Over the next two years, each of the eight committees had monthly meetings, going through and coming to a consensus on each line item of the standard. Once the committees completed development, the standards were open for a 30-day Public Review to collect comments and feedback. The first eight FOCUS standards, completed and ready for use, cover Cultivation, Retail, Extraction, Infused Products, Laboratory, Security, Sustainability and Packaging & Labeling.
FOCUS is currently recruiting committee members to begin development of five new cannabis standards later this year: Advertising/Marketing, Insurance, Banking/Finance, Patient Care and Research. Committees will receive a list of proposed suggestions for what should be considered in developing the standards. Each committee member will develop a list to select criteria they think should be included into the standard. FOCUS will compile the lists, then committees will go through the monthly standards development/vetting process for each line item in the standard.
CIJ: So what does a business have to gain by adopting a FOCUS standard?
Lezli: Compliance becomes easily manageable with the FOCUS software platform, integrating standards, training and SOPs into the everyday operations of the business. FOCUS certified clients could expect to reduce costs, reduce risk and reduce liability by assuring they are producing safe, quality and consistent products. FOCUS certification allows a business to differentiate themselves from their competitors, and prove to their patients and customers they can trust their products. Certification also allows businesses to access reasonable insurance rates and drives interest from investors.
FOCUS is here to partner with cannabis businesses. We are there to hold their hand, by providing guidance and assistance along every step of the way. Unlike state mandated audits that delineate what a business is doing right or wrong, FOCUS is an on-going compliance management system. We are here to make sure a business runs as efficiently as possible and take the guesswork out of compliance. Under FOCUS certification, a business receives ongoing consulting, customized SOPs, employee training and a documentation management software system to track and prove compliance.
CIJ: Can you give us an update on FOCUS’ progress in 2016?
Lezli: A large milestone for FOCUS this year, aside from completing version one of the standards, is choosing an appropriate software platform, (Power DMS) to house the standards and provide an ongoing compliance management system for our clients. Power DMS also houses regulatory standards for law enforcement; health care, federal aviation and fire departments, so most agencies in public health are already familiar with it. The familiarity and access to this platform is a huge benefit on the regulatory side. It allows first responders to access the schematics of a FOCUS certified client in the event of an emergency. This is crucial in the event of an explosion from extraction equipment, or a fire in a cultivation facility, as without first identifying where the hazards are, they will not access the facility. The FOCUS software platform allows first responders access to all pertinent information through computers in police cars, ambulances, or fire trucks.
For the industry, the FOCUS software platform is equally as impressive. Not only does the platform house the standards and all SOPs, it is also complete compliance management system. FOCUS certified clients have a simple management tool that houses all training and documentation, assuring all required compliance documentation can be easily accessed at any time. The platform also allows FOCUS certified clients to provide access to governing bodies in advance of state audits –streamlining the process and minimizing time and interruption caused by state audits. The FOCUS platform tracks all changes to required documents, provides real time updates on employee training, creates appropriate traceability logs, and provides updates on regulatory changes, including which SOPs need to be changed to maintain compliance. The platform allows FOCUS to be way more than an auditing company. FOCUS is a partnership in compliance for cannabis companies wanting to maintain good business practices and stay compliant with regulations.
We have about 140 new committee members that will assist existing committees with standards updates and participate in the development of the next set of FOCUS standards for advertising/marketing, banking/finance, research, patient care and insurance. All committees will convene before 2017.
Sample volume remains to be the primary influence on whether an automated solution is a logical investment for a cannabis testing facility. Due to both the complexity of the material being tested and the extraction approach at hand, it may be difficult to find an automated platform that can fully accommodate your laboratory’s needs. Hamilton Robotics in collaboration with United Chemical Technologies (UCT) has developed a solution that allows for automation of specific sample clean up steps commonly utilized in cannabis pesticide testing schemes. The MPE2 Positive Pressure Extraction/Evaporation Module is a standalone manifold that can also be incorporated into a number of automated liquid handling decks. Used in tandem with dispersive solid phase extraction (dSPE) salts/sorbents packed into a 96 well plate, this combination provides laboratories with high throughput extraction convenience with comparable results to traditional dSPE for the analysis of over forty pesticides.
As states continue to expand testing requirements for pesticides, it is vital that your laboratory is equipped with a method that allows versatility for the addition of new compounds without burdening your extraction team. There are a variety of dSPE salt and sorbent blends readily available that have been optimized for cannabis extractions. This allows for the use of a reliable extraction technique that can be adapted for the automation age. Hamilton is widely recognized throughout both clinical and forensic laboratory settings and the MPE2 platform is an excellent first system for laboratories beginning to automate/semi-automate their processes.
Following an initial QuEChERS extraction, additional cleanup is typically recommended for extracts that are being analyzed for pesticide content due to the low detection limits often required. dSPE provides the necessary sample clean up to obtain those thresholds, but often burdens a laboratory staff with additional time consuming preparation steps. Traditionally, dSPE salts are packed into 2 mL centrifugation tubes that require a cumbersome supernatant pipetting step followed by additional vortex, spin and transfer steps. By packing the dSPE sorbents into a well plate format, the user is able to completely automate this above described clean up ultimately saving time and adding convenience without jeopardizing any recovery data.
For most compounds, the recovery was greater than 65% for both methods of dSPE. The mean recoveries for traditional dSPE were 98.0%, 99.2% and 97.9% at pesticide concentrations of 50 ng/mL, 100 ng/mL and 200 ng/mL, respectively. For comparison, the mean recoveries at the same concentrations for well plate dSPE were 85.0%, 88.9% and 89.1%. Therefore, there was typically about a 10-11% absolute difference in recovery between the two methods, which can be corrected for by implementing the use of internal standards. When comparing the recovery differences between the two methods, there are six compounds with noticeably larger discrepancies across all three concentrations, namely: chlorpyrifos, cyprodinil, diazinon, spinetoram, spiromesifen 278 and trifloxystrobin. If these data sets are excluded, then the average absolute differences in recovery between the two methods decrease to 8.8%, 6.4% and 5.8% for concentrations of 50 ng/mL, 100 ng/mL and 200 ng/mL, respectively.
Overall, laboratories can estimate on saving 40-60 minutes per 96 samples processed using the Hamilton MPE2 in conjunction with a UCT dSPE plate. When a liquid handling robot is also available, this time saving estimation is potentially doubled. Time spent per sample, including the training of laboratory scientists, is an important factor to consider when setting up your laboratory. Automation is in an investment that can greatly reduce a laboratory’s overall labor costs in the long run.
Hemp-derived cannabidiol (CBD) products are quickly becoming a burgeoning industry. Consumers can purchase the products in all fifty states and can receive the therapeutic effects of certain cannabinoids without any psychoactivity. Commonly used to help treat inflammation, pain, seizures and anxiety, CBD comprises a sizable portion of the cannabis market that patients and consumers are flocking to.
Founded by Paul Benhaim in 2013, Colorado-based Elixinol is reaching this market with a line of hemp-derived CBD oils and capsules. The company has grown rapidly and now has agreements with exclusive distributors in Japan, Puerto Rico, The United Kingdom and South Africa.
According to Chris Husong, sales and marketing director at Elixinol, achieving superior quality is central to the company’s growth strategy. “We are thinking about the long-term play here,” says Husong. Achieving the highest quality possible starts with sourcing from industrial hemp farms in Northern Europe, according to Husong. Through good manufacturing practices (GMPs), the company pays close attention to every detail involved in producing the hemp-derived CBD oil.
Safety and transparency are two core tenants in the company’s goal to strive for quality products. “We use third-party independent labs for our testing including one in Northern Europe where we source from in addition to Proverde Labs when it reaches us in Colorado,” says Husong. They test their products for over 300 chemicals (including pesticides, residual solvents and heavy metals) as well as for microbiological contamination and a unique terpene profile using GC-MS/GC-FID.
In addition to stringent manufacturing safety procedures and testing, tracking is a huge part of meeting quality standards. Each product batch also has a lot number. While batch numbers are a requirement in GMPs, lot numbers mean that they are well equipped in the event of a product recall. After the product is packaged, they perform additional spot-checks periodically.
Contract manufacturing and white-labeling products is a large part of their business, so the company needs to meet rigorous quality standards for their partners as well. “We provide our oil to a variety of associates, but we are always looking for new partners on the cutting edge, innovating with new products that we can help with,” says Husong. Very often, this means doing a full plant extraction for different uses. Utilizing a full-spectrum plant extraction helps maintain a well-balanced cannabinoid profile with many of the original terpenes found in the plant.
What makes their product so appealing to consumers is not just the quality, but also the method of delivery into the bloodstream and very precise dosing. “Our liposome products have a relatively new technology that allows the oil to be absorbed into your system via fatty acids, which lets you absorb the compounds much faster, requiring less of it and more consistency,” adds Husong. In addition to their fast-acting delivery mechanism, they produce capsules dosed to precisely fifteen milligrams and a delivery system they call ‘Xpen,’ which draws the oil in an oral applicator to a precise dose of fifteen milligrams every time.
After the manufacturing process, the company pays close attention to detail in their packaging and distribution. “The packaging is built to maintain that quality in the manufacturing process and to extend the shelf life of our products,” says Husong. The technology that goes into their packaging involves using Miron Violet glass, which is anti-fungal and prevents external light from deteriorating the oil inside.
This growing sector in the cannabis market is representative of a greater trend: the commodification of hemp and cannabis. When businesses like Elixinol scale up production of goods such as CBD oil, a lens focused on consistency and quality can not only improve business operations but also raise the standard across the entire industry.
Based in Santa Monica, California, Sagely Naturals was founded in the summer of 2015, with the goal to produce a sustainably sourced, topical CBD cream with no psychoactive effects to treat daily aches and pains. The co-founders, Kerrigan Hanna and Kaley Nichol, have extensive backgrounds in the food service industry, and as a result they pride themselves in quality controls and proper safety procedures. Since the launch of Sagely Naturals, they have been selling their Relief & Recovery Cream online and in a wide variety of retail outlets beyond just cannabis dispensaries. Their ability to distribute outside of dispensaries is due to the fact that the product’s active ingredient, Cannabidiol (CBD), is derived from hemp, instead of cannabis with higher levels of Tetrahydrocannabinol (THC).
Their attention to detail in consistency and quality makes them stand out as cannabis processors, using a contract manufacturer with good manufacturing practices (GMPs) along with the proper standard operating procedures (SOPs) in place. “All of our contract manufacturer’s corrective and preventative actions (CAPAs) are outlined in the company’s SOPs, which are in place for everything including specific manufacturing processes, receiving and shipping materials and testing batches,” says Hanna. “The contract manufacturer also provides certificates of analysis (COAs) for every product they make.” According to Hanna, they exclusively use current GMP-certified facilities. One such SOP lays out the responsibilities for the quality control department in order to release and approve ingredients of their products.
There are some SOPs that could pertain specifically to the processing of hemp or cannabis products, according to Hanna. “Receiving and handling raw materials like hemp, batch coding, the actual formulation and manufacturing process, quality controls and cleaning and sanitation [could be tailored to pertain to cannabis],” says Hanna. Proper SOPs laid out in the manufacturing process include the cleaning and sanitation of machines, as well as adjusting settings, formula ratios and initialing and dating product labels on every batch, among more specific operating procedures.
According to the co-founders, they spent a large amount of time vetting their hemp supplier, making sure they are using cutting-edge technology, growing it sustainably, and adhering to strict SOPs. “The team includes a Ph.D. chemist, who also is a founding member of our supplier and extractor,” says Hanna. “We work with CO2 extraction because we wanted the most control over the compounds that end up in our product. We are able to purposefully choose which cannabinoids end up in our product.” Through supercritical carbon dioxide extraction and post-extraction processing, the team is able to eliminate any trace of THC, guaranteeing the consumers will receive no psychoactive effects.
In looking toward long-term growth, the co-founders emphasize the importance of environmental sustainability. “Having honest ingredients is one of our company missions along with having honest practices,” says Hanna. “None of our ingredients are tested on animals so we are an animal cruelty-free organization.” Their hemp is grown using organic and environmentally friendly practices. “We prioritize using plant-based ingredients, so the formulation of our Relief & Recovery Cream relies on using organic and raw materials—such as essential peppermint and safflower oil.” Companies like Sagely Naturals using contract manufacturers to process hemp could represent the future of the cannabis industry. When safety, sustainability and quality issues come into the spotlight more, so will the need for outlined SOPs, proper documentation and extensive lab testing.
In states where cannabis is legalized, some analytical laboratories are tasked with identifying and quantifying pesticide content in plant material. This is a relatively new concept in the study of cannabis as most forensic laboratories that work with seized plant material are only concerned with positively identifying the sample as cannabis. Laboratories of this nature, often associated with police departments, the office of the chief medical examiner or the local department of public health are not required to identify the amount of THC and other cannabinoids in the plant. While data is abundant that compares the average THC content in today’s recreational cannabis to that commonly consumed in the 1960s and 1970s, limited scientific studies can be found that discuss the pesticide content in street-grade cannabis.
Using the QuEChERS approach, which is the industry gold-standard in food analysis for pesticides, a comparison study was carried out to analyze the pesticide and cannabinoid content in street-grade cannabis versus medicinal cannabis. For all samples, one gram of plant material was ground into a fine powder prior to hydration with methanol. The sample was then ready to be placed into an extraction tube, along with 10 mL of acetonitrile and one pouch of QuEChERS salts. After a quick vortex, all samples were then shaken for 1 minute using a SPEX Geno/Grinder prior to centrifugation.
For pesticide analysis, a one mL aliquot of the top organic layer was then subjected to additional dispersive solid phase extraction (dSPE) clean-up. The blend of dSPE salts was selected to optimize the removal of chlorophyll and other interfering compounds from the plant material without compromising the recovery of any planar pesticides. Shaken and centrifuged under the same conditions as described above, an aliquot of the organic layer was then transferred to an auto-sampler vial and diluted with deionized water. Cannabinoid analysis required serial dilutions between 200 to 2000 times, depending on the individual sample. Both pesticide and cannabinoid separation was carried out on a UCT Selectra® Aqueous C18 HPLC column and guard column coupled to a Thermo Scientific Dionex UltiMate 3000 LC System/ TSQ VantageTM tandem MS.
Due to inconsistent regulations among states that have legalized medicinal or recreational cannabis, a wide panel of commonly encountered pesticides was selected for this application. DEET, recognized by the EPA as not evoking health concerns to the general public when applied topically, was found on all medical cannabis samples tested. An average of 28 ng/g of DEET was found on medicinal samples analyzed. Limited research as to possible side effects, if any, of having this pesticide present within volatilized medical-grade product is available. Street-grade cannabis was found to have a variety of pesticides at concentrations higher than what was observed in the medical-grade product.
Tetrahydrocannabinolic acid A (THCA-A) is the non-psychoactive precursor to THC. Within fresh plant material, up to 90% of available THC is found in this form. Under intense heating such as when cannabis is smoked, THCA-A is progressively decarboxylated to the psychoactive THC form. Due to possible therapeutic qualities of this compound, medical cannabis samples specifically were tested for this analyte in addition to other cannabinoids. On average, 17% of the total weight in each medical cannabis sample came from the presence of THCA-A. In both medical and recreational samples, the percentage of THC contribution ranged from 0.9-1.7.
A fast and effective method was developed for the determination of pesticide residues and cannabis potency in recreational and medical cannabis samples. Pesticide residues and cannabinoids were extracted using the UCT QuEChERS approach, followed by either additional cleanup using a blend of dSPE sorbents for pesticide analysis, or serial dilutions for cannabinoid potency testing.