The US cannabis industry has come a long way in the last two decades. In 1996, California legalized medical cannabis, pioneering a dialogue on cannabis research, testing and regulation. The industry experienced its next groundbreaking development in 2012, when Washington and Colorado legalized the sale of recreational cannabis, a move that eventually gained traction in other states over the next few years. As of 2017, recreational cannabis sales are legal in DC, Oregon, Nevada, Maine, Massachusetts, Alaska and California, while many other states have legalized medical cannabis, including Montana, Arizona, New Mexico, New York, Illinois, Michigan, Louisiana and Florida. The noticeable trend of the legalization of medical and recreational cannabis across the US has opened a variety of testing opportunities for laboratory product and analytical instrument companies, as the cannabis market, though burgeoning, is slated for stellar growth.

As a growing market, the cannabis industry has thus far lacked official standards or references for testing, largely due in part to the fact that its use and research is not yet federally legal. However, cannabis industry players are slowly making their moves towards understanding and standardizing the science around cannabis testing to ensure the legitimacy of the industry.

Early last month, the Association of Official Analytical Chemists International (AOAC) announced that it will work alongside industry partners, such as instrument companies and testing labs, to develop and finalize Standard Method Performance Requirements (SMPRs) for cannabis potency. Chaired by Susan Audino, PhD., of S.A. Audino & Associates, the AOAC Working Group on Cannabis Potency is part of the AOAC Stakeholder Panel on Strategic Foods Analytical Methods (SPSFAM) and is working towards creating fit-for-purpose methods for potency testing. According to an AOAC press release, the draft SMPRs are expected to undergo review for potential approval in March.

Dr. Audino discussed with IBO how her work with the AOAC began during an AOAC meeting in 2015, when she served as the chair of a symposium regarding the scientific and analytical challenges of the cannabis industry. “My concern was that the community was ambivalent about becoming involved in the cannabis sector, thereby missing an opportunity and obligation to address scientific needs,” she explained. The symposium was extremely well-received, and Dr. Audino consequently worked with Dr. E. James Bradford, executive director of the AOAC, to secure six Organizational Affiliates (OAs) that were open to creating and funding a Cannabis Advisory Panel. OAs are “a cross-sector group representing food and beverage, dietary supplements, government agencies, technology providers, ingredient suppliers, contract research organizations, and test kit manufacturers,” according to the AOAC. In summer 2016, the first meeting with the OAs took place, with the conclusion to approach the SPSFAM with a proposal during the annual AOAC meeting that year. With the proposal also received positively, the Panel held bimonthly meetings to create SMPRs for cannabis potency, with two established in fall/winter 2016: potency in plant material and potency in concentrates.

According to Dr. Audino, as of the publication date of this IBO article, there are not yet any existing finalized standard methods on cannabis testing from any official organization. The Panel Dr. Audino helped spearhead decided to focus on developing standards for an aspect of cannabis that would carry the most weight in the industry, and chose potency. “Potency is an important methodology to develop because it has such great impact for the medicinal population, recreational population and, to some extent, in the regulatory communities,” Dr. Audino stated. “Once the team decided on potency, we identified which of the tens of phytocannabinoids we thought were most important to consider, and we developed a list of approximately 15 key phytocannabinoids.”

Of the 15 phytocannabinoids, the working group narrowed the testing focus to five: THC, THCA, CBD, CBDA and CBN. As Dr. Audino stated, these fives phytocannabinoids were chosen due to their importance in the cannabis industry and the availability of certified reference standards.

The OA instrument companies that are part of the working group are SPEX, Sigma-Aldrich, SCIEX and CEM. According to Dr. Audino, initially, the working group approached potential OAs to assess if the companies were interested in devising analytical testing methods and, if so, if they would be willing to provide financial support for the project. The aforementioned companies are part of the very first AOAC Cannabis Advisory Panel, a major development for the future of cannabis testing methods. “This panel in particular represents the different facets of the AOAC that are critical to cannabis-centric method development: instrument, ancillary equipment, certified reference materials, consumable chemicals and an analytical testing lab,” Dr. Audino explained. “Not all organizational affiliates were in a position to fund this Advisory Panel at the time it was formed, and we are hopeful they will find resources in the future.”

Also part of the OAs of the cannabis potency working group is GW Pharmaceuticals, a biopharmaceutical company focusing on cannabinoid-based medicines, and California-based cannabis testing lab, SC Labs. Josh Wurzer, co-founder and Laboratory Director of SC Labs, discussed with IBO the role that SC Labs is playing in the AOAC working group, explaining that SC Labs has been testing cannabis since the inception of the cannabis testing industry. “In the beginning, it was a big hassle that we had zero reference methods,” Mr. Wurzer said. “Here we are, eight years later, and we still have no reference methods and very little in the way of published methods that apply to what we do.” When SC Labs became aware of the AOAC’s interest in developing reference methods for cannabis and was looking for OAs, the company jumped on board.

SC Labs has received much interest from instrument companies in collaborating on method development, though the interest varies from vendor to vendor. “Most of the larger companies wouldn’t even sell equipment to the cannabis testing market just a few years ago, and some still won’t,” said Mr. Wurzer. In the last couple years, however, Mr. Wurzer notes that there has been a move towards opening up to the cannabis industry. “The companies that embraced our industry early on definitely have a head start,” he noted. “Politics has even played a part. With the uncertainty for our industry caused by the recent elections, some manufacturers have backed off of planned projects.”

According to Mr. Wurzer, SC Labs was the first lab to test for residual solvents in extracts of cannabis. The lab also had the first test for pesticides that was sensitive enough to detect pesticides in cannabis and cannabis-derived products on a regular basis. “Many labs were testing for the wrong pesticides, and our strong background in and connection to the cultivation industry helped us develop a test that was actually relevant to the plant,” Mr. Wurzer explained. “There are a handful of pests that attack cannabis, and if you don’t look for the pesticides that kill those pests, your test is not very useful.” As Mr. Wurzer noted, in the initial stages of testing, SC Labs was detecting pesticides in almost 50% of samples tested.

SC Labs then developed validated methods and attempted to convince retailers to test the cannabis they sold. “It was a lot of work early on to convince people to give us their valuable product and pay for the test with the distinct possibility that they would be told that the product was unsafe,” he said. Although the number of samples with detected pesticides has dropped, Mr. Wurzer states that a large portion of the market is still dealing with cannabis that has pesticide contamination levels that would be inadmissible in other states; this can suggest that pesticide testing is a potential growth opportunity for instrument companies.

Generally, testing labs can each have their own standards, which may or may not be adopted by other labs. “We have our own methods for potency, which are proprietary,” said Mr. Wurzer, adding that this is not unusual in the analytical testing industry. “What is different is that we don’t have a good industry mechanism for ring testing for our cannabinoid assay (or most of the other tests we perform for that matter).”

Another issue, he states, is the lack of official reference methods for the cannabinoid assays. “The advantage of having industry-accepted reference methods when most labs will develop their own anyways is that reference methods become a baseline for performance,” he explained. “If a lab is going to develop a proprietary method (and most do), it better outperform the appropriate reference method.”

Though SC Labs has its own testing methods, the lab has not published them yet, so the methods have not been adopted by other labs; however, the company plans on submitting its methods to the AOAC as an OA of the cannabis potency working group, as SC Labs is working on a more collaborative effort to progress the cannabis industry. “Over the past couple years, we have come to the conclusion that the advantages of sharing our data and methodology is beneficial to our company,” said Mr. Wurzer. “The better our competitors do, the more faith the broader industry has in testing, which is beneficial to us.”

Based on the OAs involved in the working group, it can be deduced that the SMPRs include a workflow that is to be standardized, from sample preparation to detection. Dr. Audino points out that although the instruments used for cannabis potency testing are not new by any means, the complexity of the matrices in the plant can be a challenge for most analytical labs. “The cannabis plant is highly complex and heterogeneous, particularly between hybrid plants,” Dr. Audino explained. “Challenges begin with bulk sampling, sub-sampling, then sample preparation.”

Mr. Wurzer also detailed the complicated sample preparation techniques used by SC Labs, explaining how the sample must first be properly extracted into an appropriate solvent for HPLC analysis. “We use bead beaters for tissue disruption, and then there are several dilution steps, the addition of internal standard and filtering,” he said.

Since the matrices of the cannabis plant are so complex, it is extremely important to use the appropriate instrument that is sensitive enough for potency testing. SC Labs uses HPLCs with UV detectors for cannabinoid testing. Although GC is commonly cited as a tool for cannabis analysis, as Mr. Wurzer indicated, GC was mentioned in early published methods due to the fact that initial methods were chiefly intended for forensic testing. “Since the cannabinoids are very heat sensitive, GC does not work without complicated derivatization steps,” Mr. Wurzer explained. “We use GC with either FIDs or MS for residual solvents and terpenes, and LC/MS for pesticides,” he said. “We use both qPCR and media-based assays for microbiological testing.”

Although LC/MS can be used, SC Labs does not use LC/MS for potency testing. “LC/MS is overkill for potency testing and underperforms HPLC/UV,” Mr. Wurzer said. “HPLC/UV has better accuracy, precision, a greater linear range and is more rugged than LC/MS.” He added, “Plus, if you use DAD and get a spectra of each peak, you still get a secondary confirmation on identity.”

The federal prohibition of cannabis is not helping matters, as companies and labs can be limited in their reach. “Cannabis testing labs are not able to participate in traditional proficiency test schemes and are not able to access known standard reference materials in desired matrix, thereby making suitable and appropriately characterized surrogate materials difficult to locate,” Dr. Audino said.

SC Labs is also tackling the federal prohibition of cannabis by reaching out to law enforcement, inviting officials to a tour of the lab to see the work of the testing company. “Even if they don’t support the movement, people generally agree that there should be a quality control component,” Mr. Wurzer said. “Now, we see a lot more support from mainstream industry and people like the AOAC.”

Embracing the need to develop SMPRs for cannabis testing is a major move by the AOAC, and signifies the slow but sure growth of the cannabis industry. “It is [the Panel’s] hope for the cannabis methods development to continue to gain in momentum and interest such that an independent stakeholder panel can be formed,” Dr. Audino stated.

The AOAC’s decision to create cannabis potency standards has also provided support to testing labs like SC Labs, after the lab spent many years on “the fringes of the analytical community,” as Mr. Wurzer stated. “It has been really great to see organizations like the AOAC, the American Chemical Society, the American Herbal Products Association and the American Herbal Pharmacopoeia embracing cannabis,” he said. “Anything we can do to shepherd the cannabis industry into the mainstream is a worthwhile endeavor, as far as we are concerned.”

According to Dr. Audino, the Cannabis Advisory Panel has also recently added other aspects of cannabis testing on its agenda. “The Advisory Panel recently decided to advance efforts to pesticides and some edible matrices, again anticipating the development of two SMPRs between the 2017 mid-year and 2017 annual meetings,” she said. “The canvas is quite large and the need for method development is just as large; there is a lot of work ahead of us, and we will continue to address important matrices and analytes [in cannabis testing].”