The Practical Chemist

Instrumentation for Heavy Metals Analysis in Cannabis

By Chris English
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Determination of Toxic Metals in Cannabis

Heavy metals are common environmental contaminants often resulting from mining operations, industrial waste, automotive emissions, coal fired power plants, amount other sources. Several remediation strategies exist that are common for the reduction/elimination of metals in the environment. Phytoremediation is one method for removing metals from soil, utilizing plants to uptake metals which then bioaccumulate in the plant matter. In one study, cesium concentrations were found to be 8,000 times greater in the plant roots compared to the surrounding water in the soil. In 1998, cannabis was specifically tested at the Chernobyl nuclear disaster site for its ability to remediate the contaminated soil. These examples demonstrate that cannabis must be carefully cultivated to avoid the uptake of toxic metals. Possible sources would not only include the growing environment, but also materials such as fertilizers. Many states publish metal content in fertilizer products allowing growers to select the cleanest product for their plants. For cannabis plant material and concentrates several states have specific limits for cadmium (Cd), Lead (Pb), Arsenic (As) and Mercury (Hg), based on absolute limits in product or daily dosage by body weight.

Analytical Approaches to Metals Determination

Inductively Coupled Plasma, Ionized Argon gas stream. Photo Courtesy: Sigma via Wikimedia Commons

Flame Atomic Absorption Spectroscopy (Flame AA) and Graphite Furnace Atomic Absorption Spectroscopy (GFAA) are both techniques that determine both the identity and quantity of specific elements. For both of these techniques, the absorption in intensity of a specific light source is measured following the atomization of the sample digestate using either a flame or an electrically heated graphite tube. Reference standards are analyzed prior to the samples in order to develop a calibration that relates the concentration of each element relative to its absorbance. For these two techniques, each element is often determined individually, and the light source, most commonly a hollow cathode lamp (HLC) or electrodeless discharge lamp (EDL) are specific for each element. The two most common types of Atomic Emission Spectroscopy (AES) are; Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and ICP-Mass Spectrometry (ICP-MS). Both of these techniques use an argon plasma for atomization of the sample digestates. This argon plasma is maintained using a radio frequency generator that is capable of atomization and excitation of the majority of the elements on the periodic table. Due to the considerably higher energy of the plasma-based instruments, they are more capable than the flame or furnace based systems for measurement of a wide range of elements. Additionally, they are based on optical emission, or mass spectrometric detection, and are capable of analysis of all elements at essentially the same time.

Technique Selection

Flame AA is easy to use, inexpensive and can provide reasonable throughput for a limited number of elements. However, changes to light sources and optical method parameters are necessary when determining different metals. GFAA is also limited by similar needs to change the light sources, though it is capable of greater sensitivity for most elements as compared to flame AA. Runtimes are on the order of three minutes per element for each sample, which can result in lower laboratory throughput and greater sample digestate consumption. While the sensitivity of the absorption techniques is reasonable, the dynamic range can be more limited requiring re-analyses and dilutions to get the sample within the calibration range. ICP-OES allows the simultaneous analysis of over 70 elements in approximately a minute per sample with a much greater linear dynamic range. ICP-OES instruments cost about 2-5 times more than AA instruments. ICP-MS generally has the greatest sensitivity (sub-parts-per-trillion, for some elements) with the ability to determine over 70 elements per minute. Operator complexity, instrument expense and MS stability, as well as cost are some of the disadvantages. The US FDA has a single laboratory validated method for ICP-MS for elements in food using microwave assisted digestion, and New York State recently released a method for the analysis of metals in medical cannabis products by ICP-MS (NYS DOH LINC-250).

The use of fertilizers, and other materials, with low metal content is one step necessary to providing a safe product and maintaining customer confidence. The state-by-state cannabis regulations will continue to evolve which will require instrumentation that is flexible enough to quickly accommodate added metals to the regulatory lists, lower detection limits while adding a high level of confidence in the data.

Cannabis M&A: Practice Pointers and Pitfalls When Buying or Selling a Cannabis Business

By Soren Lindstrom
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The Stage is Set

According to the Marijuana Policy Group, the U.S. cannabis industry is expected to reach more than $13 billion in sales by 2020 and create more jobs than the U.S. manufacturing industry. According to Viridian Capital’s Cannabis Deal Tracker, there were close to 100 M&A transactions in the U.S. cannabis industry in 2016 and approximately $1.2 billion was raised in equity and debt. As the cannabis industry has grown more mature and businesses begin to have more capital available, the M&A activity within the industry is poised to grow significantly over the next years to assist businesses gain necessary scale and take advantage of synergies and diversification.

The Obvious Wrinkle

U.S federal law has prohibited the manufacture and distribution of cannabis since 1935. The U.S. regulates drugs through the Controlled Substances Act, which classifies cannabis as a Schedule I drug (i.e., drugs determined to have a high potential for abuse with no currently accepted medical use and a lack of accepted safety regarding their use). Yet, more than 25 states have by now legalized cannabis for medical and/or recreational purposes and, as a result, there is a clear conflict between such state laws and existing federal law. To possibly help bridge that conflict, the U.S. Attorney General’s office in 2013 issued guidance directing the federal government not to intervene with state cannabis laws except in specific, limited circumstances, but, contrarily, the DEA has shown no desire to re-classify cannabis. To add to the confusion, President Trump and the new U.S. Attorney General have provided mixed statements and signals about their positions.

All of this means that it continues to be risky to acquire cannabis businesses. The requirements to legally grow, distribute, prescribe, and use cannabis for either medical or recreational purposes vary widely by country, state, and local jurisdiction, making it tricky to determine whether such businesses can be legally combined, in particular, across state lines.

Pick the Right Team of Advisors

When preparing to sell or buy a cannabis business, it is important to pick the right team of advisors. Your regular legal counsel, accounting firm or CPA may not be the right advisors for a cannabis M&A transaction. Choose a legal counsel that not only has experience with cannabis laws and regulations, but also has cannabis M&A experience and can offer expert advice on areas like IP, employment, tax matters, etc. Similarly, verify that your accounting firm or CPA has real experience with financial and quality of earnings analysis and due diligence.

Conduct Gating Due Diligence Up Front

In any contemplated M&A transaction, it is wise to prioritize your due diligence investigations. There will always be some more prominent risks and business objectives in a particular industry or with respect to a specific target business. It will be more cost and time effective if those specific risks and business objectives are prioritized early in the due diligence process. These can dictate whether you even want to pursue the target further before you dig into a deeper and broader due diligence investigation. Conducting gating due diligence up front is even more important in an industry like cannabis that contain complex and thorny regulatory hurdles.

So, before you spend money and time on a broader legal, business and financial due diligence investigation, have your legal counsel analyze and confirm that the potential transaction is feasible from a regulatory perspective. This will include whether it is possible to obtain or transfer necessary local and/or state licenses and whether a combination or sale can occur across state lines if necessary. Early on in the process, It is also advisable to request that the target business complete a legal compliance questionnaire or discuss with the target its regulatory compliance program, policies and training. Such up front due diligence will either clear a path to negotiations and broader confirmatory due diligence or flush out “red flags” that may kill a possible deal or require the buyer to investigate further before proceeding.

Important Terms and Pitfalls in the M&A Agreement

Generally, a sale or purchase agreement for a cannabis business does not appear to vary much from a similar agreement in any other industry. However, the complex environment and the premature nature of the industry impacts certain deal terms and processes in different ways from most other developed industries.

Here are few examples to keep in mind when preparing and negotiating a sale or purchase agreement:

  • Third Party and Governmental Consents: Buyer’s legal due diligence must focus on the consents that may be required from seller’s suppliers, customers, landlords, licensors or other third parties under relevant contracts. Additionally, the due diligence should focus on consents and approvals required by local and state regulators as a result of the sale. The M&A agreement should contain solid seller representations and warranties about all such consents and approvals and any such material consents and approvals should, from a buyer’s perspective, be a condition precedent to closing of the transaction.
  • Legal Compliance: A buyer should not agree to a boilerplate seller representation about the target’s compliance with laws. Be specific and tailor seller’s legal compliance representation to relevant state and local cannabis laws, regulations and ordinances. From a seller perspective, be careful and thoughtful about any appropriate exceptions (including the federal prohibition) to be disclosed to buyer in the disclosure schedules underlying the sale or purchase agreement.
  • Financial statements: The cannabis industry is very fragmented and consists of many small businesses. Many of these small businesses do not have financial statements prepared in accordance with GAAP and may consist of only management prepared financials. In that scenario, a buyer should have its financial advisor do an analysis of the financials available and ask seller to provide a representation and warranty about the accuracy and good faith preparation of the provided financials.
  • Escrow: Typically, a buyer will request some part of the purchase price be placed with an independent financial institution for a period of time post-closing as a source of recovery for losses as a result of breaches by seller of any of the representations and warranties in the definitive sale or purchase agreement. Due to the federal cannabis and banking regulations, many of the larger commercial banks will not provide financial services to cannabis businesses, in particular if the business touches the plant. The parties must therefore consider alternatives, including local financial institutions with more relaxed compliance requirements or perhaps place the escrow in a trust account of a law firm or other independent party.
  • Working Capital Dispute Procedures: Similar to the escrow, larger accounting firms generally do not provide services to cannabis businesses. Due to the rapid evolution of cannabis related regulations, if the terms of the transaction include provisions for a post-closing working capital/purchase price adjustment and related dispute procedures, it is advisable to not name an arbiter in the agreement. Instead, parties should agree to mutually select the arbiter if and when a dispute should arise.
  • Indemnification: Because of the tricky legal environment of the cannabis industry, it may be prudent for a buyer to request, at the very least, that certain parts of seller’s legal compliance representation and warranty not be subject to the “regular” caps, deductibles and other indemnification limitations. Also, if a buyer has unearthed a significant issue in its due diligence investigation, it should consider asking seller for a special indemnity for such issue that would be indemnifiable regardless of buyer’s knowledge of the issue and not be subject to the general indemnification limitations.
  • R&W Insurance: If there’s a lot of competition for the purchase of a target, particularly in a bidding process, it is now common for buyer to offer to purchase a representation and warranty insurance policy (“R&W Insurance”) to possibly gain an advantage by limiting the seller’s post-closing indemnification exposure. The good news is that many of the R&W Insurance carriers do offer such insurance in connection with the sale and purchase of cannabis businesses. However, typically, R&W Insurance cannot be obtained for insured amounts of less than $5 million. Experienced M&A counsel can advise of the advantages and disadvantages of R&W Insurance and assist in the negotiation of the related terms.

The above are just some examples of what to expect in a cannabis M&A transaction. Every M&A transaction will have its unique issues that will need to be appropriately reflected in the sale or purchase agreements and good M&A practices will continue to evolve with the industry. If you are an owner of a successful cannabis business, buckle your seat belt and be prepared for an exciting ride as the industry gets closer to significant consolidation.

Biros' Blog

Washington Changes Course, Selects MJ Freeway as New ASV

By Aaron G. Biros
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Two weeks ago, we reported on the State of Washington choosing Franwell as their apparent successful vendor (ASV) for their seed-to-sale traceability system contract. Late last week, the Washington State Liquor and Cannabis Board (WSLCB) sent out an email explaining that they are no longer going with Franwell and the new ASV is MJ Freeway.

The email (left) consisted of a letter sent by Peter Antolin, Deputy Director of the WSLCB, to licensees “who had written to the Board and staff regarding the marijuana traceability Apparent Successful Vendor and RFID tags.” Apparently, the reason behind switching the ASV to MJ Freeway is because Franwell’s system requires only one method for tagging plants- RFID tags. According to the letter, Deputy Director Antolin says the initial request for proposal (RFP) stated that the traceability system needs to support a variety of tagging methods, including bar codes and RFID. “The RFP requirements did not allow a vendor to make any assumptions regarding use of a single tagging methodology or allow vendors to include any such costs affecting the state or our licensees in their proposal,” says Antolin. As they made clear in the previous press release, the ASV is not the official contract winner until they complete negotiations and sign the contract.

On June 7th, Franwell withdrew their proposal for the state’s traceability system, thus Washington went with the second highest scoring vendor, MJ Freeway. Deputy Director Antolin says they submitted a strong bid, but there are still many questions left unanswered. How could such a glaring mistake be overlooked when the state named Franwell the highest scoring bidder? Is MJ Freeway’s system robust enough and capable of handling the state’s cannabis licensees’ traceability requirements even though they were not the highest scoring bidder? The deadline for the new system to be in place is October 31, 2017, which is quickly approaching for such a massive systems overhaul.

The WSLCB’s oversight highlights a few inadequacies with the state’s regulatory agency, particularly their indecision and lack of foresight. So much of the concept behind seed-to-sale traceability rests on Cole Memo compliance. A big reason why some states seek to implement a robust tracking system is to remain compliant with the Cole Memo; preventing diversion to crime organizations with regulatory oversight is a key tool that states use to tell the federal government they are complying with their directive and intend to protect their state’s legal cannabis operations from federal prosecution. Without a proper system in place, the state runs the risk of exposing their entire cannabis market to threats of federal enforcement, a scenario that seems unlikely but could be disastrous to cannabis businesses and the local economy.

The WSLCB needs to get their act together fast.

Dr. Allison Justice

What Does it Really Mean To Be Organic in Cannabis?

By Dr. Allison Justice
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Dr. Allison Justice

If you ask an organic chemist, it’s any molecule with a carbon attached. If you ask a consumer of USDA Certified Organic vegetables, they might say it is food produced without chemicals pesticides, that it is safer and cleaner and even more nutritious. Possibly another consumer will say it’s just a hoax to pay more for food, but what does the USDA Certified Organic Farmer say?

Most will agree it is a very rigorous process of record keeping, fees, rules and oversight. The farmers have limited choices for pesticides and fertilizers; they incur higher labor costs, suffer potentially lower yields and generally have higher input costs. However, at the end of the day the farmer does get a higher price point.

With so many misconceptions about organic food, it is difficult to know what is actually organic by definition. First let’s think about what the word pesticide means. A pesticide is “a substance used for destroying insects or other organisms harmful to cultivated plants or to animals.” By definition, a vacuum used to suck off spidermites is a pesticide, so instead we should say that no synthetic pesticides are used. These are pesticides that enter and reside for long periods of time within the plant, which are potentially harmful to the end consumer. Though organic food does not contain synthetic pesticides, the perception of the food being healthier is also not always accurate. Growers often use foliar applied teas or manures, which increase the chance of the product containing E. coli or other harmful microbes. In addition, certain sanitizing agents or gamma irradiation is not allowed, so the post-harvest cleaning is not always as thorough as for conventional foods. When cannabis is sold as a dried product, the consumer cannot wash the flower as they might do before eating an apple. As growers, we should make sure we are disinfecting the flower before harvest and keeping the plant/processes clean throughout curing.

I often hear cannabis growers saying they are producing an organic product, but this simply cannot be true. The term “organic” is a labeling term for agricultural products (food, fiber or feed) that have been produced in accordance to the federal government’s USDA organic regulations. Due to our (cannabis growers) ongoing disagreements with the federal government, this is not a term we can put on our product. However, we can still grow to the same standards as USDA-certified farmers. How can we do this? By using OMRI (Organic Materials Review Institute) approved products. OMRI is a third-party, nonprofit organization that lets growers know if a product can be used in certified Organic production. You can find this seal on many fertilizers or pesticides.

Next, if it is a pesticide product that is not OMRI approved, check to see if it is registered by the EPA (Environmental Protection Agency). The EPA will provide ingredients and crops that are approved, amounts which can be used safely and storage/disposal practices on the label. Products that are put through the EPA registration are evaluated for their environmental, human and residual risks. Companies pay a hefty fee for this process, and much research goes into providing this information – ALWAYS READ THE LABEL!

A couple of exceptions to an EPA registration are pesticides that are 25B-exempt and biological control. 25B-exempt pesticides are pesticides that pose minimal or no risk to humans. A complete list of these products can be found here. Examples of these pesticides include rosemary, garlic, spearmint, etc.

Biological control is a method for controlling pests by the use of natural enemies. Biological control agents are allowed in organic production. If you are still wondering which pesticides or fertilizer are OK to use in cannabis and you do not live in a state with already enforced regulation, check out allowed lists in states that do.

So we know we cannot be considered a USDA organic cannabis farmer, but we CAN strive to meet the same standards:

  • Follow your state’s regulations; they are there for a reason!
  • Use OMRI products, 25B-exempt products and BCAs.
  • Keep an eye out for upcoming third-party certification companies, such as Clean Green or MPS (beware of the ones that want you to only use their products), because we need more than the state to regulate what we put onto our crop.
  • Finally, always think about the microbial load you’ve put on your plants. Although many can be very beneficial and help to produce high quality crops, many species can be harmful to the end user.
Soapbox

When the Company’s Revenue Drops, Who’s to Blame?

By Dr. Ginette M. Collazo
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The ultimate goal of any business is to produce and generate revenue. Now, when the company’s revenues drop, who’s fault is it? This question, though silent, is in the minds of everyone in an organization, especially when things start to become difficult.

Working as a consultant in productivity with different industries around the world, I have come to realize that question is not openly discussed, but everyone wants to know the answer. To answer it, we will explore the most common areas of opportunity related to this problem.

When we talk about productivity, we are talking about final tangible results, because of the production process and the effort made by each one; when speaking of income, we are talking about the difference between the purchase price and the cost of entering the market. Seeing these definitions, we might conclude that the increase in income is directly related to the increase in productivity.

On the other hand, we must not lose perspective that the increase in productivity is also directly related to the decrease of losses.

First, we have to put into perspective the goals and objectives that a business or organization may have. Many companies go on believing that everyone is clear about the goals and organizational objectives and what is expected in each one of those roles that compose the organization. The reality is that, if we do not know where we are going, the chances of reaching the goal decrease.

When organization’s objectives are properly communicated, and documented, in such a way that the evaluation of the performance is directly linked to the expected results, the chances of success increase substantially.

On many occasions, I have heard phrases such as: “we work hard, we spend many hours, all sacrifice ourselves… we should be more successful”. The question then is: what are we encouraging, efforts or results?

It is hard for organizations to translate or differentiate between organizational goals and individual objectives (expected results) for each of those roles in the company. We all agree that we want to be the first in sales, the best in service and produce the highest quality, but how is that done?

To be the first in sales, what do I have to do as a seller? Get three customers in a three-month period? As secretary, process the orders in the first three days of receiving them? As a carrier, suggest three ideas be more useful in daily deliveries? How does that translate into individual performance?

We focus too much on telling people what they must do, but we forget to be clear on what we expect them to achieve. Hence, the effort versus result dissonance. The success of an organization is the collective behavior that arises from the conduct of individuals. If we align people, we align the organization.

Other elements that we must ponder, and that are directly related to productivity, are: how much of what we do holds value? How much of what we do does not have value? Moreover, how much of what we do, though it has great value, shall be performed by the requirements of law or regulation?

An analysis of productivity is critical, particularly in a time when we want to do more with less. Lately, an area of great success for many organizations is to streamline processes to make them more simple, efficient and with less risk of error. Human errors generated many losses. Defects, the re-process, the handling of complaints and lawsuits are costing companies money equivalent to the salary of 7,200 employees every day (according to statistics in the United States).

Human errors can be avoided. The idea that to err is human has led us to ignore this problem. We think that we can do nothing and lose an infinite number of opportunities for improvement that can help us to increase our income, reducing losses.

Only 16% of organizations measure the cost of human error. The remaining 84% do not measure it and are paying a high price without knowing it. In Puerto Rico, there are no statistics that could shed light on how many local companies lose because of human error, but it is very likely that the numbers are alarming. Human error can be reduced by 60% in less than a year when an intervention is done on systems. Approximately 95% of human errors are due to the design of the company’s systems, and they can be the simplest errors even in the most complex processes.

Today, we have more information, and we know that errors are symptoms of deeper problems in the processes created by the organizations. People play a crucial role regarding how robust methods are, but, we must not lose perspective that human beings operate according to the policies, procedures, and instructions which the same organization designs. Then, if people work according to the designs of the organization, is it not easier to modify designs than eliminating people?

So, who’s fault? Organizations are responsible for providing clear guidance to individuals in the right direction, and individuals have the responsibility of translating their efforts into results. Both have to work with the same objective in mind, and both employers and employees should communicate openly about these objectives. Only by working in partnership will achieve success. Forget who is to blame and focus on the processes and goals that help us be successful.

Soapbox

Budtenders: Providing Education and Customer Service

By Rachel Stires
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Budtenders represent the front line of any cannabis dispensary, and as such they are responsible for fostering a valuable customer service experience that will have clients returning in the future. However, the role of budtender goes much deeper than simply providing customer service. If you want to develop a profitable business with deeply embedded customer loyalty, you can do no better than to hire an exceptional team of budtenders to provide your patrons with useful information and a memorable customer service experience that will keep them coming back for repeat sales.

Offering Education for All Customers

Perhaps the most important role the budtender plays in any dispensary is providing the customer with useful knowledge that will help them make an informed purchase. For many people, legal cannabis is still a very new concept, and there are a good deal of customers who have never tried cannabis products during prohibition. For these customers, it will be essential that an experienced budtender walk them through everything they need to know and help them choose a strain that will be best suited to their needs. In addition to dosing and strain advice, budtenders can help explain how various paraphernalia works, as pipes and bongs will likely be foreign to them.

For less seasoned smokers, information on dosing can be the difference between a positive and negative experience. This is primarily a concern with edibles due to the long lasting nature of their effects, but can benefit other methods of delivery as well. The effects and potency of different strains can vary widely, so it can be difficult to judge how much to ingest. Though it is impossible to overdose on cannabis, using too much can have a negative impact on the experience. By offering experienced insight into the product they are selling, budtenders can ensure that the customer will have a more positive experience with cannabis, leading to lasting relationships with your company.

Budtenders can provide plenty of value for more experienced consumers as well. The fact of the matter is, there is an endless sea of different types of cannabis products on the market, and learning all of them requires more research than many cannabis consumers are willing to invest. Whether a customer uses cannabis for medicinal or recreational purposes, they will likely have developed preferences when it comes to what they like to smoke. It is important that budtenders be knowledgeable enough to direct the customer to a product that will live up to their expectations.

A client suffering from anxiety shouldn’t be recommended towards an energetic sativa, for example, as this will likely give them a bad case of paranoia, resulting in a negative experience that could send their business elsewhere. Likewise, a daytime smoker probably won’t be happy with a relaxing Indica that will put them to sleep. Budtenders need to keep up with the various strains that are in stock at all times and be able to direct their customers to the right product.

Budtender Presentation and Service

Of course, being knowledgeable about cannabis is a necessity, but a good budtender must also be able to convey this information in a manner that educates the customer. The best budtenders will be approachable and prepared to answer any question thrown their way. They should be able to present the information like a teacher, a quality that will put customers at ease and leave them confident they are in good hands.

Dispensaries can set themselves apart from the competition by choosing their budtenders wisely. It is important to hire budtenders who present themselves in a highly professional manner including down to their manners and clothing. When a customer buys cannabis from a store, they may have preconceived notions about the budtenders working there. By hiring knowledgeable, personable and professional budtenders, businesses can tackle negative stereotypes surrounding the newly emerging cannabis industry and improve customer satisfaction.

If you’ve been to a lot of cannabis dispensaries, you’ll know that some of them might feel like a drug dealer just leased a building and set up shop, business as usual. With legalization comes the opportunity to legitimize cannabis consumption to a degree not possible before, and many dispensaries are helping to change the perception of the industry by catering to more refined crowds with attractive shops and a professional atmosphere. A good team of budtenders can go a long way towards establishing a dispensary as an upscale business.

Overall, A great budtender is an invaluable asset to any dispensary, and staffing your business with them is your best bet at building lasting relationships with your customers. Budtenders with expansive knowledge of cannabis strains, effects, and dosage, as well as a professional and personable demeanor are essential to the success of a dispensary, and without them a business might suffer.

Soapbox

Quality Controls and Medical Cannabis: What We Can Learn from Pharma

By Dr. Ginette M. Collazo
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When we discuss growing and producing medical cannabis, we must think of it as a medicine. By definition, it is a substance intended to assist you with a medical condition, to help you feel better and not harm you. Drugs produced in the pharmaceutical industry go through extensive quality controls to ensure a level of safety for the consumer or patient. Yet when we talk process and quality controls in medical cannabis production, there is still a lot to learn.

Are we waiting for the wake-up call? Well, ring! Recently Health Canada, the regulatory body overseeing Canada’s medical cannabis market, decided that “It will begin random testing of medical marijuana products to check for the presence of banned pesticides after product recalls affecting nearly 25,000 customers led to reports of illnesses and the possibility of a class action lawsuit.”

Proper quality controls help protect businesses from unforeseen issues like those massive recalls in Canada. These can assure that the product is safe (won’t harm you), has integrity (free of contamination), and that the product is what it says it is (identity). To achieve this important goal, we must have robust systems that will guarantee product quality. Why is this important? Quality controls can ensure a safer and more consistent product, helping build patient and consumer trust and brand loyalty, preventing a public relations nightmare like a recall due to pesticide contamination.

Food processing and sanitation
Product recalls due to manufacturing errors in sanitation cause mistrust among consumers.

The FDA, among other regulatory bodies, has established excellent guidelines to implement these controls. So there is a lot we can learn from the pharmaceutical industry and that FDA guidance regarding quality controls and assurance. After all, we are all interested in the same thing: a safe and effective product.

So, let’s take a look at some of the controls included in the CFR (Code of Federal Regulation), Part 211 , which include Good Manufacturing Practices (GMPs) for finished products, and how you can implement them in the growing business of growing cannabis.

  1. Personnel selection and training: The GMPs establish that “Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training… to enable that person to perform the assigned functions.” These include the creation of specific curricula per position and the establishment of requirements for specialized tasks. We all want to be successful so training, in this case, is what we call the vaccine for mistakes.
  2. Facilities: “Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction, and location to facilitate cleaning, maintenance, and proper operations.” This requirement includes segregation of spaces to avoid cross-contamination, housekeeping, the cleaning process and detergent types, material storage conditions, humidity levels, temperature, water, and even ventilation requirements to prevent contamination with microorganisms. All with the intention of protecting the product.
  3. Pest control: “There shall be written procedures for the use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. Such written procedures shall be designed to prevent the contamination of equipment, components, drug product containers, closures, packaging, labeling materials, or drug products and shall be followed.” There have been many issues pertaining this requirement. In 2010, Johnson & Johnson received many complaints claiming that the product had a musty, moldy odor. Later, the firm identified the cause of the odor to be a chemical, called 2, 4, 6-Tribromoanisole or TBA; a pesticide used to treat wooden pallets. One of the specific requirements of this section is to avoid the use of wooden pallets, but if you decide to use them, the method of sterilization by heat treatment seems like the only safe option for sterilizing wooden pallets and wood cases.
  4. Equipment/Instrumentation: “Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and its cleaning and maintenance.” The intention is to not alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. What would happen if lubricants/coolants or any other substance, not intended to be part of the product, comes in contact with the product?
  5. Procedures and documentation: “There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall include all requirements of this subpart. These written procedures, including any changes, shall be drafted, reviewed, and approved. When we have followable, well written, clear, and specific procedures, we avoid possible errors that can get us in trouble.
  6. Defects Investigation: “Written production and process control procedures shall be followed in the execution of the various production and process control functions and shall be documented at the time of performance. Any deviation from the written procedures shall be recorded and justified.” We want to be successful, for that we need to learn from failures, understanding the root causes, correcting and preventing re-occurrence is what will keep you competitive. As you can see this requirement is essential for, quality, business and to evidence that such deviations did not adulterate the product.
  7. Process controls: Besides written procedures and deviations management, operation controls are pivotal in guaranteeing the quality as well as complete documentation of your process. These controls will vary depending on your technology and your product. If you do alcohol (ethanol) extraction, for example,  you want to keep an eye on the temperature, dissolution time, and even have color standards to be able to quickly and correctly identify possible abnormalities, while you can still correct the mistake. In-process product testing will allow you to monitor “performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the final product.”

Regardless of federal regulatory guidance, quality controls can be that one factor which can make or break your business. Why re-invent the wheel?

The Practical Chemist

Instrumentation Used for Terpene Analysis

By Tim Herring
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Terpenes are a group of volatile, unsaturated hydrocarbons found in the essential oils of plants. They are responsible for the characteristic smells and flavors of most plants, such as conifers, citrus, as well as cannabis. Over 140 terpenes have been identified to date and these unique compounds may have medicinal properties. Caryophyllene, for example, emits a sweet, woody, clove taste and is believed to relieve inflammation and produce a neuroprotective effect through CB2 receptor activation. Limonene has a citrus scent and may possess anti-cancer, anti-bacterial, anti-fungal and anti-depression effects. Pinene is responsible for the pine aroma and acts as a bronchodilator. One theory involving terpenes is the Entourage Effect, a synergistic benefit from the combination of cannabinoids and terpenes.

Many customers ask technical service which instrumentation is best, GC or HPLC, for analysis of terpenes. Terpenes are most amenable to GC, due to their inherent volatility. HPLC is generally not recommended; since terpenes have very low UV or MS sensitivity; the cannabinoids (which are present in percent levels) will often interfere or coelute with many of the terpenes.

Figure 1: Terpene profile via headspace, courtesy of ProVerde Laboratories.

Headspace (HS), Solid Phase Microextraction of Headspace (HS-SPME) or Split/Splitless Injection (SSI) are viable techniques and have advantages and disadvantages. While SPME can be performed by either direct immersion with the sample or headspace sampling, HS-SPME is considered the most effective technique since this approach eliminates the complex oil matrix. Likewise, conventional HS also targets volatiles that include the terpenes, leaving the high molecular weight oils and cannabinoids behind (Figure 1). SSI eliminates the complexity of a HS or SPME concentrator/autosampler, however, sensitivity and column lifetime become limiting factors to high throughput, since the entire sample is introduced to the inlet and ultimately the column.

The GC capillary columns range from thicker film, mid-polarity (Rxi-624sil MS for instance) to thinner film, non-polar 100% polysiloxane-based phases, such as an Rxi-1ms. A thicker film provides the best resolution among the highly volatile, early eluting compounds, such as pinene. Heavier molecular weight compounds, such as the cannabinoids, are difficult to bake off of the mid-polarity phases. A thinner, non-polar film enables the heavier terpenes and cannabinoids to elute efficiently and produces sharp peaks. Conversely the early eluting terpenes will often coelute using a thin film column. Columns that do not contain cyano-functional groups (Rxi-624Sil MS), are more robust and have higher temperature limits and lower bleed.

For the GC detector, a Mass Spectrometer (MS) can be used, however, many of the terpenes are isobars, sharing the same ions used for identification and quantification. Selectivity is the best solution, regardless of the detector. The Flame Ionization Detector (FID) is less expensive to purchase and operate and has a greater dynamic range, though it is not as sensitive, nor selective for coeluting impurities.

By accurately and reproducibly quantifying terpenes, cannabis medicines can be better characterized and controlled. Strains, which may exhibit specific medical and psychological traits, can be identified and utilized to their potential. The lab objectives, customer expectations, state regulations, available instrumentation, and qualified lab personnel will ultimately determine how the terpenes will be analyzed.

Biros' Blog

Regulate Marijuana Like Alcohol? Not So Fast

By Aaron G. Biros
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You’ve heard it in a lot of campaigns to legalize cannabis on a state level and even as the name of a bill in Congress for legalization on the federal level. The Marijuana Policy Project through their campaigns in several states, along with activists, politicians and lobbyists, have used the phrase “Regulate Marijuana Like Alcohol” as a rallying cry to pass legislation reforming cannabis laws. This isn’t an attack on them; those campaign names serve the cause well, moreover it was the name of successful campaigns in Massachusetts, Maine, California, Alaska and Colorado among others. It is a relatable and fair comparison, helping to normalize the concept of adults using cannabis in a legal environment.

But that feeling of validation is short-lived after lawmakers write the actual regulations. In reality, I don’t think a single state can confidently say they actually regulate cannabis like alcohol. Most states do not allow public or social consumption of cannabis; many people that would like to enjoy cannabis in a social setting are restricted to the confines of their home.

420 Rally at Civic Center Park, Denver, CO.
Photo: Cannabis Destiny

Voters in Colorado passed Amendment 64 in 2012 with this language in the very beginning of the bill: “In the interest of the health and public safety of our citizenry, the people of the State of Colorado further find and declare that marijuana should be regulated in a manner similar to alcohol.” If you look closely, you can see how important phrasing is when it comes to the specific regulations. The key words here are “a manner similar to alcohol,” not exactly like alcohol. That language is critical to understanding how regulators address the double standard.

The most obvious way lawmakers regulate cannabis like alcohol is through a tiered system of license holders: manufacturers, distributors or wholesalers and retailers. Many states might set a limit on potency, just like they do with alcohol, according to Pamela S. Erickson, former executive director of the Oregon Liquor Control Commission. Both of the drugs are taxed and there are usually regulations for both governing the advertising of products, such as preventing targeting youth or encouraging high consumption. Regulators might limit the store hours or locations for both cannabis and alcohol. Beyond those similarities, there are a number of areas where cannabis is over-regulated and alcohol is seemingly under-regulated. It is very possible that much of this has to do with the power of the alcohol lobby. In 2016, the alcohol industry spent over $26 million on lobbying efforts, according to the Center for Responsive Politics, a non-profit, nonpartisan group that tracks lobbying efforts. During election season, the alcohol industry spent more than $11 million on campaign contributions. There are several examples of the alcohol industry actively fighting legalization efforts, including paying for anti-cannabis ads in a Politico newsletter and even funding opposition campaigns. While this doesn’t exactly pertain to the regulation of cannabis versus alcohol, it gives you a glimpse of how deep their coffers go and the amount of influence they have on politics.

Last year, the city of Denver passed a ballot measure, Initiative 300, which will legalize the social consumption of cannabis in permitted venues. The Denver Social Consumption Advisory Committee met for the final time last week. That committee designed two styles of permits: one for events and one for established businesses, which would receive a designated consumption area permit (DCA). Those permitted venues must be 1,000 feet from schools, child-care centers or drug rehabilitation centers. They need a waste plan, compliance with the Indoor Air Quality Act and they cannot sell cannabis products. Rachel Gillette, attorney in the cannabis law group and shareholder at Greenspoon Marder, says the legal implications of the initiative are still up in the air. “This was a step in the right direction,” says Gillette. “You can’t pass a law to regulate marijuana like alcohol and then say people can only use it in their home. You are going to run into problems like people smoking on the street. This is why this initiative was introduced.”

Rachel K. Gillette, Esq., practicing at the cannabis law group in Greenspoon Marder

The general idea here is B.Y.O.P.- bring your own pot. They cannot have a liquor license, the location cannot be accessible to the general public, they have to submit a detailed security plan and patrons have to sign a waiver to get in, according to Westword. Signing a waiver to get into a bar should seem asinine to anyone, but I have been to some dive bars where a waiver could’ve definitely been useful. The point is that cannabis doesn’t lead to violence or destructive behavior, alcohol is the drug that does that. There is plenty of evidence to support that, including a comparative risk assessment of the drugs, which found alcohol’s danger to be strongly underestimated previously.

Senate Bill 63 in the Colorado State legislature would have been very similar, issuing licenses for “marijuana consumption clubs.” However that bill was voted down last Thursday, largely due to the uncertainty of federal policy, according to ABC News.

Amendment 64 also has specific language saying you cannot consume cannabis in a public space, but that is not exactly the case with liquor, even when you consider open container and public intoxication laws. “In my previous interactions with the state and particularly the liquor licensing authority, they consider liquor-licensed premises to be de facto public spaces but you can’t consume cannabis there, which is why hotels, bars and restaurants explicitly prohibit cannabis consumption, they have a liquor license,” says Gillette. “There is a bit of conflict in the law here.”

Yet other rules, such as mandatory childproof containers for cannabis retailers, seem a bit draconian compared with buying a bottle of twist-off wine from the grocery store. “Childproof packaging isn’t required in liquor stores anywhere,” says Gillette. “Why cant responsible adults be trusted to keep it out of a child’s reach? Unfortunately there is a lot of trepidation to allow responsible adults to be responsible when it comes to cannabis.” In some ways, we are seeing states begin to regulate cannabis very closely to how they would alcohol, yet there is a long way to go. “There is still this nanny state mentality where we run the risk of regulating it to the point of absurdity,” says Gillette. For now at least, we need to be cognizant of the age-old stigma and work to normalize social cannabis use in a legal sense. Until that time comes, we will have to tolerate lawmakers regulating cannabis in a manner similar to alcohol, not exactly like alcohol.

Chris English
The Practical Chemist

Accurate Detection of Residual Solvents in Cannabis Concentrates

By Chris English
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Chris English

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.

Headspace Analysis

Figure 1: Shatter can be melted and dissolved in a high molecular weight solvent for headspace analysis (HS). Photo Courtesy of Cal-Green Solutions.

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).

Figure 2: Resolution of early eluting compounds by headspace – flame ionization detection (HS-FID). Chromatogram Courtesy of Trace Analytics.

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.