Tag Archives: laboratories

June 18, 2018

Designing the Perfect Cannabis Edible in California

By Celia Schebella

Are you a product designer in the edible cannabis market? Well, you live at the intersection of the food and pharmaceutical industries and need to know both worlds, utilizing best-practice product development principles, regardless of which industry you are working in. In the cannabis industry, this means knowing your chemistry principles, food science, food safety, Good Manufacturing Practices (GMPs, applicable to the food industry) along with the more intense records and documentation requirements of the pharmaceutical industry.

California is the most recent state to implement legal recreational cannabis. It is estimated to deliver $7.7B in sales by 2021, including a reduction of medical use cannabis and an uptake of adult recreational use. How often do you live at the inception of such a potentially enormous market? Not often, so product developers, here is an opportunity. However, with that opportunity comes the responsibility. A recent emergency legislation adopted by the California Cannabis Safety Branch states:

Operational Requirements Licensees must have written procedures for inventory control, quality control, transportation, security and cannabis waste disposal. Descriptions of these procedures or Standard Operating Procedures (SOPs) must be submitted with the annual license application. Cannabis waste cannot be sold, must be placed in a secured area and be disposed of according to applicable waste management laws. Good manufacturing practices must be followed to ensure production occurs in a sanitary and hazard-free environment, cannabis products are contaminant free and THC levels are consistent throughout the product and within required limits. Extractions using CO2 or a volatile solvent must be conducted using a closed-loop system, certified by a California-licensed engineer. Volatile, hydrocarbon-based solvents must have at least 99% purity. Finally, volatile solvent, CO2 and ethanol extractions must be certified by the local fire code official.

Part of this emergency legislation for all California cannabis product manufacturers is the newly published GMP requirements, which appear to be a combination of food, supplements and HACCP requirements. Helpful resources to learn more about this new California emergency legislation impacting cannabis product manufacturers can be found at the California Manufactured Cannabis Safety Branch with the details of the emergency cannabis regulations.

Once developers have decided on a product, research and education to develop a good understanding of the regulatory environment is a must. For example, in order to develop compliant cannabis edibles, compliance with state, and in some cases local regulations, for food and cannabis must be met. Proactive compliance is a big part of designing a successful product in the most efficient manner.The attention to detail here will create a safe and satisfying experience for consumers as they receive a consistent product every time.

As a product developer you must first know the incoming cannabis plant characteristics to determine what type of cannabinoids they contain to determine what types you wish to source. This requires a strong and well documented supplier program that can identify reliable suppliers of high purity and consistent cannabis raw materials, the same principles that are typically required of food manufacturers. When looking for examples of credible ingredient supplier programs, looking at those used by the food industry is a good start. Make sure supplier management programs apply to all the raw materials and direct-contact packaging that you plan to use in your new product.

Once reliable sources of raw material have been secured, the next challenge is to conduct periodic tests of cannaboids levels found in your incoming cannabis. With this information, you need to adjust blending amounts to reflect the correct cannaboid dose in the finished ready-to-eat (RTE) product. Like any other medicinal product, the active ingredient dosage will directly impact the effect on the consumer, thus it is important that you, the manufacturer, are completely aware of the exact cannaboid levels in your incoming ingredients, your blending amounts and your final product levels. This will require a robust either in-plant or commercial laboratory testing program. There is a great deal of technology and chemical analyses available to help dose the product accurately. This must also include robust testing and verification steps. If a consumer of your product were to over-consume from “normal” consumption rates of your cannabis-based food product, the liability, both financial, civil, ethical and criminal would fall on your company. The attention to detail here will create a safe and satisfying experience for consumers as they receive a consistent product every time.

design your products with commercial manufacturing viability in mindOnce regulatory responsibilities for manufacturing and marketing a cannabis-based food product have been met, so that you may sell a compliant and consistent product, it is time to add some creative juices and make the product interesting and enjoyable to consumers. With cannabis edibles, for example, explore what sort of food is appealing to consumers. Consider when, where and with whom your potential customers would be eating that food. Evaluate the best packaging design and size to suit the occasion. Ensure the packaging is child resistant yet practical for adult consumers. And above all manufacture a food that is delicious. Curiosity will attract your customers for the first time but quality and consistency will keep them coming back.

Product developers are usually fantastic at developing great lab scale products, but part of a developer’s job is to ensure that the design and manufacturing process is scalable for consistent and compliant commercial manufacturing. So design your products with commercial manufacturing viability in mind. Try to minimize the number of ingredients whilst still making a consumer-desirable product. Finally, rationalize your ingredients across your portfolio to avoid overcrowding the warehouse and risking expired ingredients.

If successful, your consumers will desire your product, your compliance team will be satisfied, your manufacturing partners will be thankful, the State of California will determine that you are fully compliant and your sales team’s job will have great business and professional success. In the end, you will have developed and launched a successful legacy product!

June 12, 2018

From The Lab

Quality Plans for Lab Services: Managing Risks as a Grower, Processor or Dispensary

By Dr. Edward F. Askew

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Editor’s Note: The views expressed in this article are the author’s opinions based on his experience working in the laboratory industry. This is an opinion piece in a series of articles designed to highlight the potential problems that clients may run into with labs.

This article is the first in a series that will look into the risks any user of laboratory services (growers, processors or dispensary owners) will face from the quality systems in place in the laboratory. I will discuss specific risk areas in clear and understandable language so as to not obscure the substance of the article series with abbreviations and nomenclature that is not familiar with the reader. Subjects of the articles that follow will focus on the specific laboratory certification or accreditation requirements and how the user may find out if their risks are addressed. As these articles are meant to be interactive with the reader, users are encouraged to send questions or suggested topics to the author.

This article will be an introduction to the typical laboratory process that generates the “paperwork wall” and how it might impact the user.My experience with laboratory certification or accreditation (difference between the two discussed later in this article) comes from over 30+ years in the environmental chemistry field. My experiences include working under the Clean Water Act, Safe Drinking Water Act, FIFRA (pesticides) and ISO 17025 laboratory analyses and laboratory management. I have also received training to perform ISO 17025 and EPA Drinking Water audits. During this time I have been audited as a laboratory analyst/laboratory manager and have performed audits.

As such, I can open up the laboratory structure beyond the sterile “paperwork wall” that has been constructed to allow the user to see the quality of data that is used in final reports that can wreak havoc. This article will be an introduction to the typical laboratory process that generates the “paperwork wall” and how it might impact the user.

One of the common misconceptions that a user has with a “certified or accredited” laboratory is that procession of a certificate indicates that ALL laboratory analyses produced are accurate and precise. I liken this to the “paperwork wall” that laboratories produce when the user questions any results reported to them. The laboratory management assumes that they have answered the user complaint (i.e. a certified/accredited laboratory cannot make a mistake) and the user will not pursue further questions once the certificate is produced.Accreditation does not guarantee that the laboratory personnel can perform the analyses the user is paying for; just that the laboratory’s paperwork has been audited.

First off, let’s look at what the difference between the terms certified laboratory vs. accredited laboratory. These simple words mean specifically different types of laboratories. According to the NIST National Voluntary Laboratory Accreditation Program (NVLAP):

Certification is used for verifying that personnel have adequate credentials to practice certain disciplines, as well as for verifying that products meet certain requirements.
Accreditation is used to verify that laboratories have an appropriate quality management system and can properly perform certain test methods (e.g., ANSI, ASTM, and ISO test methods) and calibration parameters according to their scopes of accreditation.

So, how does that impact the user?

If your state or 3rd party certificate only accredits a laboratory, then the accreditation agency only inspects the laboratory’s quality program as it applies to written documents and static equipment. (e.g. The quality manual is written and the standard operating procedures (SOPs) are in place).
Accreditation does not guarantee that the laboratory personnel can perform the analyses the user is paying for; just that the laboratory’s paperwork has been audited.
Certification on the other hand says that the laboratory personnel are qualified to perform the laboratory analyses and that the final laboratory results meet specific (certain) requirements. In other words, the laboratory’s quality plan and SOPs are met.

There are three different paths that are utilized by state cannabis control agencies to accredit or certify a cannabis laboratory.

ISO 17025: The ISO laboratory quality standard for laboratory accreditation is the most broadly used. ISO 17025 is an international standard and its implementation in the United States is regulated by ILAC. There are three 3rd party companies that audit for and award ISO 17025 accreditation certificates. They are Perry Johnson Laboratory Accreditation Inc., ANAB and A2LA.
TNI: The NELAC Institute standards are utilized by one state to handle their cannabis laboratory accreditation.
States: Some states have tried to blend an ISO 17025 requirement with their own state’s certification requirements to produce a mixed accreditation-certification program. But, this type of program may rely on two or more agencies (e.g. ISO 17025 3rd party auditors communicating with state auditors) to cover all specific laboratory areas.

In two of the paths above, the final result is that the laboratory receives accreditation. That means that only the quality management system and the scope (e.g. SOPS, laboratory instruments, etc.) have been audited, not the laboratory personnel or their capabilities. The third pathway may produce a certified laboratory or may not.

To provide an example of where an accredited laboratory followed their paperwork but produced inadequate results:

I received a laboratory report for organic chemical analyses of a client’s process.
- The laboratory results placed the user in noncompliance with the state and federal regulatory limits.
- But, the laboratory result contained data flags (e.g. additional information that explains why the laboratory result failed the laboratory’s quality requirements).
- The laboratory still received payment from the user as the laboratory performed the analyses.
I had to explain to the regulatory agency that some of the data flags when investigated showed:
- The laboratory failed to use the approved analytical method.
- The detection level for the regulatory chemical was so low that the laboratory had no instrument capable to see those chemicals at the concentrations reported by the laboratory.
The state regulators accepted the explanation I provided and the user was no longer under a regulatory administrative order.
But, when I presented this information to the accreditation agency that accredited this laboratory I was informed:
- The laboratory flagged the data so it can be reported to the user.
- If the user wanted more from the laboratory, then the user will have to outline their specific requirement in a quality contract with the laboratory. (i.e. If the laboratory identifies the problems then they can report the data no matter what happens to the user).

So now, what is being done behind the “paperwork wall”? Areas such as those listed below can impact the results received by the user.

Laboratory quality culture: What does the laboratory staff think about quality in their normal daily work?
Laboratory staff competence: What is the level of training and real world competence of the staff that actually works on the analyses?
Laboratory capabilities: Does the laboratory actually have the laboratory instruments and equipment that can perform the analyses the user needs?
Laboratory quality control parameters: What is in the quality manual and does it make sense?
Laboratory analytical method validation: Are the analytical methods used by the laboratory validated by approved statistical procedures?

What should the user have in place to limit their risks from laboratory analyses?

Failsafe sampling preparation plans: Make sure the user samples for the laboratory are collected correctly.
Failsafe’s on laboratory sample reports: Protect the user from bad laboratory reports.
User auditing of the laboratory: Go to the laboratory and see if the laboratory can pass muster.

What’s Next: The next article will go behind the laboratory “paperwork wall” to detail the culture that impacts the user results negatively and how that can be recognized. Follow-up articles will help users developing quality plans that identify risks and how to limit them.

June 11, 2018

The Four Pillars of Cannabis Processing

By Christian Sweeney

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Cannabis extraction has been used as a broad term for what can best be described as cannabis processing. A well-thought-out cannabis process goes far beyond just extraction, largely overlapping with cultivation on the front-end and product development on the back-end¹. With this in mind, four pillars emerge as crucial capabilities for developing a cannabis process: Cultivation, Extraction, Analytics and Biochemistry.

The purpose and value of each pillar on their own is clear, but it is only when combined that each pillar can be optimized to provide their full capacities in a well-designed process. As such, it is best to define the goals of each pillar alone, and then explain how they synergize with each other.

At the intersection of each pillar, specific technology platforms exist that can effectively drive an innovation and discovery cycle towards the development of ideal products.Cultivation is the foundation of any horticultural process, including cannabis production. Whether the goal be to convert pigments, flavors or bioactive compounds into a usable form, a natural process should only utilize what is provided by the raw material, in this case cannabis flower. That means cultivation offers a molecular feedstock for our process, and depending on our end goals there are many requirements we may consider. These requirements start as simply as mass yield. Various metrics that can be used here include mass yield per square foot or per light. Taken further, this yield may be expressed based not only on mass, but the cannabinoid content of the plants grown. This could give rise to a metric like CBD or THC yield per square foot and may be more representative of a successful grow. Furthermore, as scientists work to learn more about how individual cannabinoids and their combinations interact with the human body, cultivators will prioritize identifying cultivars that provide unique ratios of cannabinoids and other bioactive compounds consistently. Research into the synergistic effect of terpenes with cannabinoids suggests that terpene content should be another goal of cultivation². Finally, and most importantly, it is crucial that cultivation provide clean and safe materials downstream. This means cannabis flower free of pesticides, microbial growth, heavy metals and other contaminants.

Extraction is best described as the conversion of target molecules in cannabis raw material to a usable form. Which molecules those are depends on the goals of your product. This ranges from an extract containing only a pure, isolated cannabinoid like CBD, to an extract containing more than 100 cannabinoids and terpenes in a predictable ratio. There are countless approaches to take in terms of equipment and process optimization in this space so it is paramount to identify which is the best fit for the end-product¹. While each extraction process has unique pros and cons, the tunability of supercritical carbon dioxide provides a flexibility in extraction capabilities unlike any other method. This allows the operator to use a single extractor to create extracts that meet the needs of various product applications.

Analytics provide a feedback loop at every stage of cannabis production. Analytics may include gas chromatography methods for terpene content³ or liquid chromatography methods for cannabinoids^{3, 4, 5}. Analytical methods should be specific, precise and accurate. In an ideal world, they can identify the compounds and their concentrations in a cannabis product. Analytics are a pillar of their own due simply to the efforts required to ensure the quality and reliability of results provided as well as ongoing optimization of methods to provide more sensitive and useful results. That said, analytics are only truly harnessed when paired with the other three pillars.

Biochemistry can be split into two primary focuses. Plant biochemistry focuses back towards cultivation and enables a cannabis scientist to understand the complicated pathways that give rise to unique ratios of bioactive molecules in the plant. Human biochemistry centers on how those bioactive molecules interact with the human endocannabinoid system, as well as how different routes of administration may affect the pharmacokinetic delivery of those active molecules.

Each of the pillars require technical expertise and resources to build, but once established they can be a source of constant innovation. Fig. 1 above shows how each of these pillars are connected. At the intersection of each pillar, specific technology platforms exist that can effectively drive an innovation and discovery cycle towards the development of ideal products.

For example, at the intersection of analytics and cultivation I can develop raw material specifications. This sorely needed quality measure could ensure consistencies in things like cannabinoid content and terpene profiles, more critically they can ensure that the raw material to be processed is free of contamination. Additionally, analytics can provide feedback as I adjust variables in my extraction process resulting in optimized methods. Without analytics I am forced to use very rudimentary methods, such as mass yield, to monitor my process. Mass alone tells me how much crude oil is extracted, but says nothing about the purity or efficiency of my extraction process. By applying plant biochemistry to my cultivation through the use of analytics I could start hunting for specific phenotypes within cultivars that provide elevated levels of specific cannabinoids like CBC or THCV. Taken further, technologies like tissue culturing could rapidly iterate this hunting process⁶. Certainly, one of the most compelling aspects of cannabinoid therapeutics is the ability to harness the unique polypharmacology of various cannabis cultivars where multiple bioactive compounds are acting on multiple targets⁷. To eschew the more traditional “silver bullet” pharmaceutical approach a firm understanding of both human and plant biochemistry tied directly to well characterized and consistently processed extracts is required. When all of these pillars are joined effectively we can fully characterize our unique cannabis raw material with targeted cannabinoid and terpene ratios, optimize an extraction process to ensure no loss of desirable bioactive compounds, compare our extracted product back to its source and ensure we are delivering a safe, consistent, “nature identical” extract to use in products with predictable efficacies.

Using these tools, we can confidently set about the task of processing safe, reliable and well characterized cannabis extracts for the development of world class products.

[1] Sweeney, C. “Goal-Oriented Extraction Processes.” Cannabis Science and Technology, vol 1, 2018, pp 54-57.

[2] Russo, E. B. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.” British Journal of Pharmacology, vol. 163, no. 7, 2011, pp. 1344–1364.

[3] Giese, Matthew W., et al. “Method for the Analysis of Cannabinoids and Terpenes in Cannabis.” Journal of AOAC International, vol. 98, no. 6, 2015, pp. 1503–1522.

[4] Gul W., et al. “Determination of 11 Cannabinoids in Biomass and Extracts of Different Varieties of Cannabis Using high-Performance Liquid Chromatography.” Journal of AOAC International, vol. 98, 2015, pp. 1523-1528.

[5] Mudge, E. M., et al. “Leaner and Greener Analysis of Cannabinoids.” Analytical and Bioanalytical Chemistry, vol. 409, 2017, pp. 3153-3163.

[6] Biros, A. G., Jones, H. “Applications for Tissue Culture in Cannabis Growing: Part 1.” Cannabis Industry Journal, 13 Apr. 2017, www.cannabisindustryjournal.com/feature_article/applications-for-tissue-culture-in-cannabis-growing-part-1/.

[7] Brodie, James S., et al. “Polypharmacology Shakes Hands with Complex Aetiopathology.” Trends in Pharmacological Sciences, vol. 36, no. 12, 2015, pp. 802–821.

June 6, 2018

EVIO Labs Expands Ahead of California Testing Deadline

By Aaron G. Biros

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In a few short weeks, the regulations in California’s cannabis market will expand to include more laboratory testing. The previous exemption for selling untested product will be eliminated come July 1^st, meaning that every product on dispensary shelves will have to be tested for a number of contaminants.

EVIO labs photo — Pesticide testing, expanded residual solvent testing and foreign materials testing will be added come July 1st.

According to William Waldrop, chief executive officer and co-founder of EVIO Labs, the state is currently finalizing a revision to the existing emergency rules, which is designed to target the potential supply bottleneck situation. “To help alleviate the bottleneck, the state is eliminating the field duplicate test on every batch of cannabis or cannabis products,” says Waldrop. “This will give the labs additional bandwidth to process more batches for testing.” So one test per batch is the rule now and batch sizes will remain the same. This, of course, is contingent on the state finalizing that revision to the emergency regulations.

William Waldrop, chief executive officer and co-founder of EVIO Labs

In addition to that change, the state will expand the types of testing requirements come July 1^st. New mandatory pesticide testing, expanded residual solvent testing and foreign materials testing are added in addition to the other tests already required.

With July 1^stquickly approaching, many in California fear the rules could lead to a major market disruption, such as the previously mentioned bottleneck. Waldrop sees the elimination of duplicate testing as a preventative measure by the state. “It is a good move for the industry because it allows labs to test more batches, hopefully reducing the bottleneck come July,” says Waldrop. Still though, with only 26 licensed laboratories in the state as of March, testing facilities will have to meet higher demand, performing more tests and working with more clients.

EVIO Labs is preparing for this in a number of ways. They already have a lab in Berkeley and are working to expand their capacity for more analyses. In addition to their lab in Berkeley, the company is working to get three more locations operational as quickly as possible. “Right now, EVIO Labs is expanding through the identification of new market locations,” says Waldrop. “We have announced the acquisition of a facility in Humboldt and we are outfitting it for state-mandated testing. We have secured a location in LA, and licensing for LA just began as of June 1^stso we are going through the local licensing process at this time. We are still moving through the licensing process for our facility in Costa Mesa as well.”

“In the meantime, we have expanded capacity of personnel in our Berkeley facility to support our client base until these other locations come online,” says Waldrop. “We are refining our business, bringing on additional equipment and more resources.” While the rules haven’t been implemented yet, Waldrop says he’s seen an uptick in business with licensed operators requesting more testing for the new July 1^ststandards.

While some might feel a bit panicky about how the new standards could disrupt the market, Waldrop says his clients are looking forward to it. “Our clients are very happy with the proposed new rules, because it reduces the cost of testing per batch, which will inherently reduce wholesale costs, making cannabis more affordable for patients and recreational users.”

May 31, 2018

Hazard Analysis and Critical Control Points (HACCP) for the Cannabis Industry: Part 4

By Kathy Knutson, Ph.D.

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In Part 3 of this series on HACCP, Critical Control Points (CCPs), validation of CCPs and monitoring of CCPs were defined. When a HACCP plan identifies the correct CCP, validates the CCP as controlling the hazard and monitors the CCP, a potential hazard is controlled in the manufacturing and packaging of cannabis-infused edibles. The food industry is big on documentation. If it’s not documented, it did not happen. The written hazard analysis, validation study and monitoring of CCPs create necessary records. It is these records that will prove to a customer, auditor or inspector that the edible is safe. Here in Part 4, more recordkeeping is added on for deviation from a CCP, verification and a recall plan.

Take Corrective Action When There Is a Deviation from a Critical Control Point

Your food safety team conducts a hazard analysis, identifies CCPs and decides on monitoring devices, frequency and who is responsible for monitoring. You create an electronic or paper record of the monitoring for every batch of edible to document critical limits were met. Despite all your good efforts, something goes wrong. Maybe you lose power. Maybe the equipment jams. Nothing is perfect when dealing with ingredients, equipment and personnel. Poop happens. Because you are prepared before the deviation, your employees know what to do. With proper training, the line worker knows what to do with the equipment, the in-process product and who to inform. In most cases the product is put on hold for evaluation, and the equipment is fixed to keep running. The choices for the product include release, rework or destroy. Every action taken needs to be recorded on a corrective action form and documents attached to demonstrate the fate of the product on hold. All the product from the batch must be accounted for through documentation. If the batch size is 100 lb, then the fate of 100 lb must be documented.

Verify Critical Control Points Are Monitored and Effective

First, verification and validation are frequently confused by the best of food safety managers. Validation was discussed as part of determining CCPs in Part 3. Validation proves that following a CCP is the right method for safety. I call validation, “one and done.” Validation is done once for a CCP; while verification is ongoing at a CCP. For example, the time and temperature for effective milk pasteurization is very well known and dairies refer to the FDA Pasteurized Milk Ordinance. Dairies do not have to prove over and over that a combination of time and temperature is effective (validation), because that has been proven.

I encourage you to do as much as you can to prepare for a recall.A CCP is monitored to prove the safety parameters are met. Pasteurization is an example of the most commonly monitored parameters of time and temperature. At a kill step like pasteurization, the employee at that station is responsible for accurate monitoring of time and temperature. The company managers and owners should feel confident that CCPs have been identified and data are being recorded to prove safety. Verification is not done by the employee at the station but by a supervisor or manager. The employee at the station is probably not a member of the food safety team that wrote the HACCP plan, but the supervisor or manager that performs verification may be. Verification is proving that what was decided by the food safety team is actually implemented and consistently done.

Verification is abundant and can be very simple. First, every record associated with a CCP is reviewed by a supervisor or manager, i.e. someone who did not create the record. This can be a simple initial and date at the bottom of the record. Every corrective action form with its associated evaluation is verified in the same way. When HACCP plans are reviewed, that is verification. Verification activities include 1) testing the concentration of a sanitizer, 2) reviewing Certificates of Analysis from suppliers, 3) a review of the packaging label and 4) all chemical and microbiological testing of ingredients and product. The HACCP plan identifies CCPs. Verification confirms that implementation is running according to the plan.

Verification is like a parent who tells their child to clean their room. The child walks to their room and later emerges to state that the room is clean. The parent can believe the word of the child, if the child has been properly trained and has a history of successfully cleaning their room. At some frequency determined by the parent, the room will get a parental visual check. This is verification. In the food industry, CCP monitoring records and corrective action must be reviewed within seven days after the record is created and preferably before the food leaves the facility. Other verification activities are done in a timely manner as determined by the company.

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

Write a Recall Plan

In the food industry, auditors and FDA inspectors require a written recall plan. Mock recalls are recommended and always provide learning and improvement to systems. Imagine your edible product contains sugar, and your sugar supplier notifies you that the sugar is recalled due to glass pieces. Since you are starting with the supplier, that is one step back. Your documentation of ingredients includes lot numbers, dates and quantity of sugar.You keep good records and they show you exactly how much of the recalled lot was received. Next you gather your batch records. Batches with the recalled sugar are identified, and the total amount of recalled sugar is reconciled. You label every batch of your edible with a lot code, and you identify the amount of each affected lot and the customer. You have a press release template in which you add the specific information about the recall and affected lots. You notify every customer where the affected edible was shipped with a plan to return or destroy the edible. When you notify your customers, you go one step forward.

How would your company do in this situation? I have witnessed the difficulties a company faces in a recall when I was brought in to investigate the source of a pathogen. Food safety people in my workshops who have worked through a recall tell me that it was the worst time of their life. I encourage you to do as much as you can to prepare for a recall. Here are two good resources:

Chapter 15 in the Participant Manual of the Preventive Controls for Human Food rule Warning! The manual is over 500 pages, so be careful what you print. It can be purchased for only $30 by following the link to the bookstore.

The Food Recall Manual of the University of Florida Extension Another warning! The manual is 134 pages.

Please comment on this blog post below. I love feedback!

May 15, 2018

A2LA Accredits First Rec Alaska Cannabis Lab

By Aaron G. Biros

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The American Association for Laboratory Accreditation (A2LA) announced recently the accreditation of The New Frontier Research (TNFR) laboratory to ISO/IEC 17025:2005. TNFR, based in Wasilla, Alaska, was previously evaluated by A2LA for competence and proficiency to perform the minimum tests required by Alaska.

TFNR is now the first recreational cannabis-testing laboratory in Alaska accredited to ISO/IEC 17025 standard. According to Roger Brauninger, A2LA biosafety program manager, this accreditation is a sign of attention to thorough science. “Cannabis testing laboratories that have gained ISO/IEC 17025 accreditation have demonstrated their competence and commitment to rigorous science,” says Brauninger. “In the greatly scrutinized recreational cannabis industry, we are pleased to have granted the first accreditation of its kind in Alaska.”

Roger Brauninger, A2LA biosafety program manager

According to the press release, the ISO/IEC 17025 accreditation is the most significant third-party lab accreditation an organization can receive. The standard confirms labs have management, quality and technical systems designed for accurate and repeatable analyses, in addition to proper administrative processes for testing.

Jessica Alexander, technical director of the TNFR laboratory, says this is the first step in many to researching the medical properties of cannabis. “By achieving ISO/IEC 17025 accreditation, The New Frontier Research believes that it advances the cannabis industry as a whole so that we can conduct legitimate research to unlock the amazing potential that this plant has for development of more effective medicines to address problems like opioid dependence and pediatric seizures,” says Alexander.

May 1, 2018

Steep Hill Announces Major International Expansion

By Aaron G. Biros

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According to a press release, the Steep Hill team announced they are expanding internationally in a big way on Monday. Steep Hill, a well-known cannabis lab-testing and research company with roots in California, announced plans for licensing agreements in Mexico, Germany, Spain, France, Italy, Switzerland and the United Kingdom.

Photo credit: Steep Hill- a petri dish of mold growth from tested cannabis

The Canadian branch of the company, Steep Hill Canada, will lead the expansion efforts into Mexico and the six European Union countries. According to Martin Shefsky, chief executive officer of Steep Hill Worldwide, they are actively looking for other operating partners in new areas as well. “I’m extremely pleased at the opportunity to partner with Steep Hill to bring safe cannabis and scientific integrity to emerging international markets,” says Shefsky. “I anticipate that before long, full legalization will be implemented throughout the European Union and our presence will enable growers, producers, processors, and retailers – to offer standardized tested cannabis for patients and consumers across the European Union, while also enabling us to create a platform to share scientific and technology developments throughout the global cannabis market.”

In 2016, Steep Hill announced new licensing agreements to expand into Washington D.C. and Pennsylvania. In August of 2017, they expanded to Hawaii and several months later announced their expansion into Oregon. “It is an exciting time for us and our investors, as we pursue this first-mover advantage in anticipation of new global cannabis import-export markets,” says Jmîchaeĺe Keller, chief executive officer and chairman of the board of Steep Hill, Inc.

“In unregulated markets, we want to be on the ground supporting the legalization and regulatory process, helping regulators avoid making the mistakes that other jurisdictions have made in the past,” Keller says. “We believe that our role as the industry standard, allows us to leverage our world-class scientific knowledge and state of the art technology to help regulators provide confidence in the marketplace that the cannabis patients consume, is both safe and effective. We look forward to collaborating closely with Martin and his group to strive for this gold standard, across all international borders.”

April 18, 2018

From The Lab

The Other Side of Cannabis: Terpenes

By Dr. Zacariah Hildenbrand, Allegra Leghissa, Dr. Kevin A. Schug

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Have you ever wondered why all beers have that strong, characteristic smell? Or why you could tell the smell of cannabis apart from any other plant? The answer is simple – terpenes.

These 55,000 different molecules are responsible for a majority of the odors and fragrances around us, from a pine forest, to the air diffuser in your house ^1–3. They all share the same precursor, isoprene, and because of that, they are all related and have similar molecular structures. Unfortunately, it is this uncanny similarity that makes their analysis so challenging; we still lack a complete list of which terpenes expected to be found in each given plant species ^1,2.

Many different methods have been developed in an effort to provide a time-optimized and straightforward analysis. Gas chromatography (GC) is usually center stage due to the volatility of the terpenes. Therefore, there is significant concern with the type of GC detector used ².

The flame ionization detector (FID) is a good quantitative detector for GC, but qualitatively it does not provide any information, except for retention time; the differentiation between terpene species is achieved solely by use of retention indices (RI), which are based on elution times from a particular GC stationary phase. The best part of the FID is its low cost, reliability, and relatively easy interface, which make it an effective tool for quality control (QC) but less so with respect to research and discovery ².

The primary choice for a research setting is the mass spectrometer (MS) detector. It is more expensive and complicated than FID, but importantly, it provides both good quantitative capabilities, and it provides mass spectra for each species that elutes from the chromatograph. However, for terpene analysis, it may still not be the best detector choice. Since terpene class molecules share many structural and functional similarities, even their fragmentation and sub-sequential identification by MS may lead to inconsistent results, which need to be confirmed by use of RI. Still, MS is a better qualitative analysis tool than the FID, especially for distinguishing non-isobaric terpenes ².

Recently, new technology based on vacuum ultraviolet spectroscopy (VUV) has been developed as a new GC detector. The VUV detector enables analysis of virtually all molecules; virtually all chemical compounds absorb light in the range in the 125-240 nm wavelength range probed by the detector, making it an essentially universal detector ^4–11. Previously, spectroscopic absorption detectors for GC have lacked sufficient energy to measure absorption of most GC-amenable species. The VUV detector fills a niche, which is complementary to MS detection in terms of the qualitative information it provides.

With the VUV detector, each compound exhibits its own unique absorbance spectrum. Even isomers and isobars, which are prevalent in terpene mixtures and can be difficult to distinguish different species by their electron ionization mass spectra, can be well differentiated based on their VUV spectra ^6,9,10. Nevertheless, because analytes exhibit different spectra, it is not required to achieve a perfect chromatographic separation of the mixture components. Co-eluting peaks can be separated post-run through the use of library spectra and software inherent to the instrument ^4,10. This ability is called “deconvolution”, and it is based on the fact that two co-eluting terpenes will give a peak with an absorbance spectrum equal to the sum of the two single absorbance spectra ⁴. Figure 1 shows the deconvolution process for two co-eluting terpenes, camphor and (-)-isopulegol. Due to their different absorbance spectra (Figure 1C), it is possible to fully separate the two peaks in post-run, obtaining sharp peaks for both analytes ⁶.

The deconvolution process has been shown to yield precise and accurate results. Thus, chromatographic resolution can be sacrificed in favor of spectroscopic resolution; this enables the development of methods with faster run times. With the ability to deconvolve unresolved peaks, a long temperature ramp to chromatographically separate all isomeric terpenes is not required ⁶. Additionally, the presence of coeluting components, which might normally go undetected with some GC detectors, can be easily judged based on comparison of the measured spectra with pure reference spectra contained in the VUV spectral library.

The other issue in terpenes analysis is the extraction process. Terpenes can be extracted with the use of solvents (e.g., methanol, ethanol, hexane, and cyclohexane, among others), but the process is usually time-consuming, costly and not so environmentally-friendly ². The plant needs to be manually crushed and then aliquots of solvent are used to extract components from the plant, ideally at least 3 times and combined to achieve acceptable results. The problem is that some terpenes may respond better to a certain solvent, making their extraction easier and more optimized than for others ². The choice of solvent can cause discrimination against the extraction some terpenes, which limits the comprehensiveness of analysis.

Headspace is another technique that can be used for the sample preparation of terpenes. Headspace sampling is based on heating the solid or liquid sample inside a sealed vial, and then analyzing the air above it after sufficient equilibration. In this way, only volatile analytes are extracted from the solid/liquid sample into the gas phase; this allows relatively interference-free sampling ^12–14.

How do we know whether our extraction analysis methods are correct and comprehensive for a certain plant sample? Unfortunately, there is not a complete list of available molecules for each plant species, and even if two specimens may smell really similar to our nose, their terpenes profiles may be notably different. When working with a new plant material, it is difficult to predict the extraction efficiency for the vast array of terpenes that may be present. We can only perform it with different extraction and detection methods, and compare the results.

The route for a comprehensive and fast analysis of terpenes is therefore still long; however, their intoxicating aromas and inherent medicinal value has provided a growing impetus for researchers around the world. Considering the evolving importance of Cannabis and the growing body of evidence on the synergistic effects between terpenes and cannabinoids, it is likely that newly improved extraction and analysis methods will be developed, paving the way for a more complete list of terpene species that can be found in different cultivars. The use of new analytical technologies, such as the VUV detector for GC, should aid considerably in this endeavor.

References:

[1] Breitmaier E., Terpenes: Flavors, Fragrances, Pharmaca, Pheromones. John Wiley & Sons 2006.

[2] Leghissa A., Hildenbrand Z. L., Schug K. A., A Review of Methods for the Chemical Characterization of Cannabis Natural Products. J. Sep. Sci.2018, 41, 398–415 .

[3] Benvenuto E., Misra B. B., Stehle F., Andre C. M., Hausman J.-F., Guerriero G., Cannabis sativa: The Plant of the Thousand and One Molecules. Front. Plant Sci2016, 719, DOI: 10.3389/fpls.2016.00019.

[4] Schug K. A., Sawicki I., Carlton D. D., Fan H.,Mcnair H. M.,Nimmo J. P., Kroll P.,Smuts J.,Walsh P., Harrison D., Vacuum Ultraviolet Detector for Gas Chromatography. Anal. Chem.2014, 86, 8329–8335 .

[5] Fan H.,Smuts J., Walsh P.,Harrison D., Schug K. A., Gas chromatography-vacuum ultraviolet spectroscopy for multiclass pesticide identification. J. Chromatogr. A2015, DOI: 10.1016/j.chroma.2015.02.035.

[6] Qiu C.,Smuts J., Schug K. A., Analysis of terpenes and turpentines using gas chromatography with vacuum ultraviolet detection. J. Sep. Sci.2017, 40, 869–877 .

[7] Leghissa A., Smuts J., Qiu C., Hildenbrand Z. L., Schug K. A., Detection of cannabinoids and cannabinoid metabolites using gas chromatography-vacuum ultraviolet spectroscopy. Sep. Sci. Plus2018, 1.

[8] Bai L.,Smuts J., Walsh P., Fan H., Hildenbrand Z., Wong D., Wetz D., Schug K. A., Permanent gas analysis using gas chromatography with vacuum ultraviolet detection. J. Chromatogr. A2015,1388, 244–250 .

[9] Skultety L., Frycak P., Qiu C.,Smuts J., Shear-Laude L., Lemr K., Mao J. X., Kroll P., Schug K. A., Szewczak A., Vaught C., Lurie I., Havlicek V., Resolution of isomeric new designer stimulants using gas chromatography – Vacuum ultraviolet spectroscopy and theoretical computations. Anal. Chim. Acta2017, 971, 55–67 .

[10] Bai L., Smuts J., Walsh P., Qiu C., McNair H. M., Schug K. ., Pseudo-absolute quantitative analysis using gas chromatography–vacuum ultraviolet spectroscopy–a tutorial. Anal. Chim. Acta2017, 953, 10–22 .

[11] Schenk J., Nagy G., Pohl N. L. B., Leghissa A., Smuts J., Schug K. A., Identification and deconvolution of carbohydrates with gas chromatography-vacuum ultraviolet spectroscopy. J. Chromatogr. A2017, 1513, 210–221 .

[12] Van Opstaele F., De Causmaecker B., Aerts G., De Cooman L., Characterization of novel varietal floral hop aromas by headspace solid phase microextraction and gas chromatography-mass spectrometry/olfactometry. J. Agric. Food Chem.2012, 60, 12270−12281 .

[13] Hamm S., Bleton J., Connan J., Tchapla A., A chemical investigation by headspace SPME and GC-MS of volatile and semi-volatile terpenes in various olibanum samples. Phytochemistry2005,66, 1499–1514 .

[14] Aberl A., Coelhan M., Determination of volatile compounds in different hop Varieties by headspace-trap GC/MS-in comparison with conventional hop essential oil analysis. J. Agric. Food Chem.2012, 60, 2785−2792 .

April 17, 2018

Massachusetts Prepares for Adult-Use

By Aaron G. Biros

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Last month, the Cannabis Control Commission, the regulatory body overseeing Massachusetts’ newest industry, finalized their regulations for the market. At the beginning of this month, the state began accepting applications for business licenses. Now with the full implementation of adult-use sales on the horizon, businesses, regulators, consumers and local governments are preparing themselves for the legalization of adult-use cannabis. Sales are expected to begin June 1^st.

On March 29^th, the Cannabis Control Commission announced their finalized rules were filed, published and took effect. Leading up to the filing, the Commission reports they held 10 listening sessions, received roughly 500 public comments and conducted 7 hearings for roughly 150 policy decisions. The license categories that businesses can apply for include cultivator, craft marijuana cooperative, microbusiness, product manufacturer, independent testing laboratory, storefront retailer, third-party transporter, existing licensee transporter, and research facility, according to the press release.

What separates Massachusetts’ rules from other states’ rules are a few of the license categories as well as environmental regulations, as Kris Kane highlights in this Forbes article. Experimental policies, like the microbusiness and craft marijuana co-op licenses, Kane says, are some tactics the Commission hopes may help those affected by the drug war and those who don’t have the capital and funding required for the larger license types.This is a groundbreaking reform previously unseen in states that have legalized cannabis.

The Commission will also establish a Social Equity Program, as outlined in the final rules (section 17 of 500.105). That program is designed to help those who have been arrested of a cannabis-related crime previously or lived in a neighborhood adversely affected by the drug war. “The committee makes specific recommendations as to the use of community reinvestment funds in the areas of programming, restorative justice, jail diversion, workforce development, industry-specific technical assistance, and mentoring services, in areas of disproportionate impact,” reads one excerpt from the rules (section 500.002) identifying the need for a Citizen Review Committee, which advises on the implementation of that Social Equity Program.

This is a groundbreaking reform previously unseen in states that have legalized cannabis. Massachusetts may very well be the first state to actively help victims of the prohibition of cannabis.Some municipalities are hesitant and skeptical, while others are fully embracing the new industry with open arms.

For environmental rules, Kane notes the Commission is taking unprecedented steps to address energy usage in the cultivation process, pushing the industry to think about environmental sustainability in their bottom line and as part of their routine regulatory compliance. He says the Commission mandates a 36 watts-per-square-foot maximum for indoor cannabis cultivators.

On Monday, April 2^ndthe state began accepting applications for businesses seeking licensure. Within a few days, nearly 200 businesses have applied. That number is expected to grow significantly over the next few weeks.

While businesses continue applying for licenses, local governments are preparing in their own way. Some municipalities are hesitant and skeptical, while others are fully embracing the new industry with open arms.

A couple weeks ago, the City Council of Springfield, Massachusetts passed a six-month moratorium on cannabis sales, citing the need for more time to draft local regulations for businesses first. “I believe the moratorium is in place to make sure that we get it right the first time,” Councilor Adam Gomez, chairman of the council’s Economic Development Committee told MassLive. “We don’t have a chance to get it right the second time. The residents of Springfield supported this.” There are also talks of a potential temporary ban in Truro, MA.

Meanwhile in the city of Attleboro, ABC6 News reports Mayor Paul Heroux is “working to make his city marijuana friendly as city councilors work to draft regulation ordinances.” In Peabody, two businesses just received approval to begin operating as medical dispensaries.

April 11, 2018

Is There a Looming Supply Bottleneck in California?

By Aaron G. Biros

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California’s regulated adult use cannabis market has been up and running for around four months now and rumors of a potential supply bottleneck on the horizon are beginning to circulate. There are a number of factors that could have an impact on the cannabis supply in the market, most of which stem from changes in the distribution channels now that the state is implementing new regulations.

Those include a slow rollout in licensing cannabis businesses, new testing requirements, the supply carryover period prior to January 1^stas well as new labeling and packaging regulations. In this piece, we are going to examine some of those rumors, see if there might be some truth to them and provide some guidance for what businesses can do to prepare for this.

A Slow Start to Licensing

This one is perhaps the most obvious factor to impact the supply chain in California. Much of the delays in licensing cannabis businesses came from the issue of local control, where businesses needed to get approval from their municipality before getting a state license. In the first month of the new market, it took Los Angeles weeks longer than other counties to begin licensing dispensaries. Whereas San Diego retailers saw a massive influx of customers right away, forcing them to buy up product to meet the high demand. Smaller producers also had trouble getting licenses as quickly as some of the larger ones.

Basically it all boils down to a slow start for the new market, according to Diane Czarkowski, co-founder of Canna Advisors. “The state is requiring businesses to get their local licenses before they can get their state license and that will create a delay in operators being able to bring products to market,” says Czarkowski. She says this is pretty typical of new markets, or when a market experiences dramatic changes quickly. “It could be a brand-new market, like in Hawaii, where the operators were ready with product, but there were no labs to test the products, which caused delays.” In addition to the licensing roll out being slow to start, the temporary licenses initially awarded to businesses are set to expire soon, by the end of April.

Stricter Rules to Come

The same logic goes for the testing regulations. New testing and labeling requirements, according to the Bureau of Cannabis Control regulating the market, will be phased in throughout 2018.

CA cannabis testing chart — California’s plan for phasing in testing requirements.

The state has already phased in cannabinoids, moisture content, residual solvent, pesticide, microbial impurities and homogeneity testing to some extent. On July 1^st, the state will add additional residual solvent and pesticide testing as well as foreign material testing. At the end of 2018, they plan on requiring terpenoids, mycotoxins, heavy metals and water activity testing. All of those tests cost money and all of those tests could impact suppliers’ ability to bring product to market. “Oftentimes regulations require different types of testing to be done to products without recognizing that adequately completing those tests requires different methods, equipment, and standards,” says Czarkowski. “Most labs do not have all of the necessary components, and they are very costly. Producers could wait weeks to get test results back before they know if they can sell their products.”

Back when we spoke with Josh Drayton, deputy director of the California Cannabis Industry Association, about the upcoming changes to the California market, he voiced his concerns with the coming testing rules. “A lot of testing labs are concerned they are unable to test at the state’s threshold for some of these contaminants and pesticides; the detection limits seem very low,” says Drayton. “The testing portion will take years to work out, I am sure we will remove and add different pesticides and contaminants to the list.” California’s testing industry is, however, capable of adapting to changing rules, as they’ve done in the past on more than one occasion. It should be noted that many labs in the state are on the cutting edge of testing cannabis, working with The Bureau to implement the new rules.

roybingham — Roy Bingham, CEO of BDS Analytics

Cannabis products made prior to December 31^st, 2017, did not need to comply with the stricter testing rules that are coming in the next few months. This carryover period allowed dispensaries to have products on the shelves when the new market launched in the beginning of 2018. Retailers knew this rule meant they needed to stockpile product in the event of a supply bottleneck, and it appears much of that product is now sold and running out, according to Roy Bingham, founder and chief executive officer of BDS Analytics. “The true impact of licenses is starting to be felt since the carryover from December buying prior to the licensed market has been sold,” says Bingham. “Some of the major brands have consciously not applied for licenses. Some of that has to do with the flexibility the government has given them to wait.”

A fourth reason for a potential bottleneck could also come from packaging and labeling rules. “There will have to be many modifications to products to ensure they follow the new potency regulations, and many formulations will have to be modified in order to meet new regulations,” says Czarkowski. Distributor licenses, according to The Bureau, have a number of compliance documentation requirements, such as arranging for all product testing, quality assurance and packaging and label accuracy. Everything has to be packaged before it gets to a dispensary, which is a new rule California businesses need to comply with.

Pricing is the Indicator

There are a handful of reasons why prices could increase; some of them are more defined than others, the biggest factor being the tax burden passed on to consumers, where reports showed up to a 40% increase from last year. A price increase in the future could also come from The Bureau implementing testing regulations throughout 2018, as mentioned previously.

If prices were to surge enormously and very quickly, that might be an indicator that a shortage is fast approaching. A dramatic increase in price over this year could squeeze margins for smaller producers, forcing retailers to pass that burden on to consumers as well.“So yes, the rumors are true.”

According to Roy Bingham, there has been a significant increase in pricing in all categories at the retail level. “In January and February, we are seeing about 10% increases per month in average retail prices,” says Bingham. “If we look at concentrates in California during 2017, they averaged about $34 by the end of the year, whereas it was about $31 at the start of 2017. So in January, prices have increased up to $38, which is a bit above trend, but in fact we were seeing a trend upwards before January 1^stas well.” Comparing that with edibles pricing, Bingham says we see a clear jump at the start of 2018. “It was basically flat in 2017, averaging $14 roughly almost straight-line across, dipped in December, then in January it jumped to $17 and then to $18 in February, a big increase and significantly more than concentrates,” says Bingham. He also says flower was hovering around $9 per gram in December 2017, but surged above $10 in February 2018.

According to Cannabis Benchmarks, the California wholesale averages surged in the summer of 2017 up to $1,631 by September, then reached their lowest point in December, with their spot index at $1,368. The Cannabis Benchmarks report underlines some important reasons for the changes in pricing, but they also attribute it to the new licensing system.

“Increasing operating expenses for businesses preparing to enter California’s licensed system in 2018 were key to propping up supply side rates in the first six months of 2017. New compliance requirements were being instituted to varying degrees by local governments, while market participants warily eyed draft regulations from state officials for guidance as to how to prepare their sites and facilities to meet under-construction regulatory mandates.”

Their report highlights some very important aspects of the supply chain. “Again, it is likely that the increased costs faced by operators up and down the supply chain exert some upward pressure on wholesale rates, preventing them from steep year-over-year declines that were observed in some of the other major Western markets,” reads the Cannabis Benchmarks report.

So How Can Businesses Prepare?

Well to start, producers should make sure their operations and product are clean and safe. Making sure your product will pass a pesticide test should be top of mind. Dispensaries should also be wise in selecting their suppliers, performing supplier quality audits or some form of verification that they meet your standards is key in a consistent supply chain.

Dr. Jon Vaught, chief executive officer of Front Range Biosciences, believes tissue culture could be a viable solution for some California producers. Using tissue culture, as a form of propagation instead of mothers and clones can be cleaner, cheaper and more efficient, thus allowing growers to keep up with demand and prevent a shortage.

Dr. Jon Vaught, CEO of Front Range Biosciences

Dr. Vaught says growers could look to tissue culture as a means to “mitigate risk to their supply chain and mitigate the risk of potential loss and improve their ability to efficiently grow their plant.” Maintaining a disease-free, sterile environment is a huge advantage in the cannabis market. “The real use of tissue culture is to provide disease free, clean, certified material, that has gone through a QA program,” says Dr. Vaught. “In greenhouses, the ability to control your environment is also critical because your margin of error is high. Variations in sunlight, weather, humidity all of these things have an impact in your plants. Technology can help monitor this.”

We’ve covered the basics of tissue culture previously on CIJ, with Dr. Hope Jones chief science officer of C4 Laboratories. She echoes many of Dr. Vaught’s points, firmly believing that, having existed for decades, tissue culture is an effective propagation tool for advanced breeders or growers looking to scale up.It is a complex supply chain that requires systems thinking.

It is important to note they don’t think growers should try this at home. Work with professionals, get the necessary funding, the training and facilities required if this is a project that interest you. “There’s a pretty big barrier to entry there,” Dr. Vaught urges. “The ability to manage thousands or millions of plants in a greenhouse increases risk, whereas in the lab, you’ve got a safe, secure, sterile environment, reducing risk of disease, making things easier to manage. The producers most successful at large scale are controlling those variables to the T.”

Ultimately, one segment of the market can’t prevent a bottleneck. It is a complex supply chain that requires systems thinking. Regulators need to work with producers, manufacturers, retailers, distributors, patients, consumers and laboratories to keep an eye on the overall supply chain flow.

Diane Czarkowski says the California market should prepare for this now if they haven’t already. “We have seen supply issues in every market going through a change. Other potential bottlenecks will occur because former distribution channels will be required to change,” says Czarkowski. “So yes, the rumors are true.”