Tag Archives: heavy metals

From The Lab

What Cannabis Manufacturers Can Learn from the Pharmaceutical Industry About Trace Metal Impurities in Plastic Materials

By Robert (Rob) Thomas
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Plastics and polymers are widely used materials in the manufacture of cannabis and hemp consumer products, including vessels, containers, bottles, bags, transfer lines, carts, pods, and other components. However, they are not typically associated with metal contamination of the cannabinoids being produced. By far the most common source of trace-element contamination is heavy metals in the soil, growing medium, or fertilizer. These metals can be taken up through the plant’s root system and ultimately find their way into leaves, shoots and flowers and, finally, into extracted cannabinoids.

A secondary source of metal contamination has also been shown to be from stainless steel vessels, containers and equipment used in the production process. In addition, metal components such as coils, atomizers, tanks, and electrical/battery connections used in vaping cartridges are of particular concern nowadays, as they can leach metal particles into vaping liquids due to manufacturing defects and/or long-term storage of the devices. Some of the metals used include stainless steel, nichrome, brass, solder, and other alloys.

However, it is well documented in the pharmaceutical industry that plastic materials used in manufacturing equipment can potentially contribute to elemental contamination of drug products. The United States Pharmacopeia (USP) has devoted several chapters to this issue.

So, if metal impurities in plastic materials are something the pharmaceutical industry takes seriously, why isn’t this receiving the same attention in the manufacture of cannabis consumer products?

To investigate this question, it is useful to first look at how the pharmaceutical industry approaches the problem—and then examine what evidence exists in the public domain indicating that it could also be an issue for cannabis manufacturers.

 

What Can the Pharmaceutical Industry Teach Cannabis Manufacturers?

Drug products can chemically interact with their associated packaging systems and with the plastic materials and components used during manufacturing, storage, and administration. It is therefore logical that these interactions should not adversely affect either the suitability of the drug product or the packaging system. While suitability for use encompasses many quality attributes, the impact of plastic materials on patient and consumer safety is particularly important.

To address these issues, the United States Pharmacopeia (USP) has developed general chapters covering the quality and suitability of plastic materials used in pharmaceutical applications, including:

  • USP Chapter <661> — Plastic Packaging Systems and Their Materials of Construction Used in Pharmaceutical Manufacturing. [3]
  • USP Chapter <1661> — Evaluation of Plastic Packaging and Manufacturing Systems and Their Materials of Construction With Respect to Their Impact on User Safety.

 

The Potential for Contamination

Pharmaceutical manufacturing involves numerous steps required to convert raw materials into an active pharmaceutical ingredient (API) and ultimately into a drug product. Many of these steps use components that are wholly or partly constructed from plastics or polymers.

These materials can also contain additives such as:

  • antioxidants
  • stabilizers
  • lubricants
  • plasticizers
  • colorants

All of these materials have the potential to contain elemental impurities. It is therefore possible for raw materials, process streams, production intermediates, APIs, and finished drug products to come into contact with plastic components during manufacturing. These interactions can potentially introduce process-related impurities and alter the quality of the pharmaceutical product.

The issue becomes particularly important when plastic vessels are used in liquid storage systems, because the opportunity for interaction between the plastic and the liquid increases.

 

Manufacturers Have a Responsibility

The pharmaceutical industry places the responsibility on manufacturers to establish that plastic components and systems are suitable for their intended use.

This is accomplished through a comprehensive risk-assessment approach in which the materials are appropriately characterized, tested, and evaluated.

Among the criteria considered are:

  • The components should be constructed from well-characterized materials intentionally selected for their intended use.
  • Their general physicochemical properties should be established.
  • Their biological reactivity should be appropriately evaluated.
  • Their safety should be established through appropriate chemical testing, including extractables and leachables profiling, together with toxicological assessment of the results.

The question isn’t simply, “What plastic are we using?” The more important question is: “What can potentially come out of that plastic and enter the product?”

 

How Are Plastic Materials Tested?

Because pharmaceutical manufacturing uses a wide variety of plastic materials and exposes them to many different conditions, there is no single extraction procedure that perfectly represents every manufacturing situation. At the same time, it would be impractical to impose a substantial number of extraction conditions on every manufacturer. The pharmaceutical approach therefore uses a standardized set of extraction conditions designed to assess both organic and inorganic impurities.

USP Chapter <661.3> describes five model extraction methods shown in Table 1.

Table 1: Chemical extraction conditions used to evaluate the suitability of plastic components for the manufacture of drug products or substances.

 

For the assessment of extractable metals, the plastic component is either filled with the test solution, or an appropriate amount of plastic is placed into a high-purity borosilicate flask containing the test solution.

The material is then heated to approximately 55 °C for 96 hours, cooled, and analyzed for relevant metals using ICP-OES or ICP-MS in accordance with USP Chapter <233>.

 

What Metals Are Important?

A well-characterized plastic or polymer should be tested for relevant metals that are known components of the material.

These metals can originate from:

  • starting materials used to manufacture the plastic
  • catalysts and other reagents
  • stabilizers
  • colorants
  • plasticizers
  • other additives

Relevant metals have been identified in compendial and regulatory documents, such as USP Chapter <232> [6] and ICH Q3D guidelines [7], which lists 24 elemental impurities and permitted daily exposure (PDE) limits in micrograms (µg) according to the route of administration and the toxicity of the element as shown in Table 2.

Table 2: USP Chapter 232 and ICH Q3D guidelines permitted daily exposure (PDE) limits for elemental impurities [6,7]. Note: These values are typically based on 10g maximum of the drug product per day, so they should be divided by 10 to calculate the allowable limit in µg/g in the drug product.

The potential significance of a metal depends not only on its concentration but also on how the final product is consumed. For example, the limits for some elements are considerably more restrictive for inhalation products than for orally administered products. [6,7] That distinction is highly relevant to cannabis products, particularly vaping products, where inhalation is the route of exposure.

It’s also important to emphasize that most state-based cannabis regulations in the US only require the monitoring of the  Class 1 “big four” heavy metals (Pb, Cd, As, Hg) to be compliant. This means that if any other metals were present in the cannabis products due to equipment contamination, they would escape scrutiny because there is no requirement to measure them. So, there is clearly a need to expand the elemental panel beyond the  “big four” to ensure consumer safety.

 

What Metal Impurities Are Actually Found in Plastics?

So what metals are actually present in plastics and polymers?

There have been numerous studies investigating toxic metals in plastic materials, although much of this work has focused on laboratory plastics such as flasks, beakers, and tubing. One landmark study was published in Analytical Chemistry in 1977 by John R. Moody and Richard M. Lindstrom.

The researchers evaluated common laboratory container materials and demonstrated that many were unsuitable for trace-metal analysis. For experienced ICP-MS practitioners working at the ultra-trace level, this is hardly surprising. Low-quality plastic laboratory ware can contribute significant contamination, which is why high-purity materials are routinely used when the lowest possible limits of quantitation are required.

Some polymers, including polypropylene and polyethylene, can contain significant concentrations of alkali metals, alkaline-earth elements, transition metals, and other elements, as exemplified in Table 3, which is taken from a study that provides an excellent illustration of the problem. In addition, additives, plasticizers, coloring agents and mold-release agents can introduce additional metals.

Table 3: Trace metals found in common plastic and polymer materials

Other Evidence in the Public Domain

Other studies have investigated toxic-metal concentrations in plastic materials used for food packaging.

Although the results do not necessarily establish that the metals actually leach into food, they provide compelling evidence that a broad range of metallic impurities can be present in plastic and polymer materials.

One particularly relevant study investigated heavy metals and metalloids in various types of plastic bags. The researchers examined polyethylene, HDPE, LDPE, and PVC materials and used closed-vessel microwave digestion followed by ICP-OES analysis.

The results demonstrated that many elemental impurities were present at concentrations in the tens of parts per million, while some elements—including copper, zinc and barium—were present at concentrations exceeding 100 ppm. A subset of this data is shown in Table 4.

The results were not isolated to a single material, as similar findings were obtained from other types of plastic bags.

Table 4: A panel of elemental impurities found in polythene bags (results in mg/kg)

These concentration levels are quite significant. But again, there is an important distinction. The presence of metals in a plastic material does not automatically mean that those metals will migrate into a cannabis product. Without an appropriate extractables study, we do not know the answer to that question.

 

What Does This Mean for the Cannabis and Hemp Industry?

This brings us to the key question. What are the implications for cannabis producers?

The pharmaceutical industry has spent decades developing a comprehensive approach to elemental impurities. The ICH Q3D risk-assessment framework considers potential sources throughout the manufacturing process, including:

  • raw materials
  • manufacturing equipment
  • water
  • container-closure systems
  • drug substances
  • excipients
  • packaging
  • processing steps

Plastic materials therefore become one component of a much larger risk-assessment strategy.

A classic way to visualize this is with a fishbone—or Ishikawa—diagram, designed to identify potential root causes of elemental contamination, as shown in Figure 1.

Figure 1: Classic fishbone diagram of the pharmaceutical manufacturing process to identify the root cause of a problem to better understand elemental impurities in drug products.

 

A Cannabis Elemental-Impurity Risk Assessment

So, the question is, could this approach be adopted by the cannabis industry?  Every stage of the cannabis production process, including cultivation, extraction processing, manufacturing, packaging, and delivery, could potentially contribute elemental contaminants.  And in particular, what plastic components and materials are most likely to be leaching metals when in contact with the multitude of chemicals and solvents used in the extraction process, as well as cannabinoids, terpenes, and diluents used in the formulation of the cannabis consumer products? A proposed fishbone diagram for the cannabis manufacturing process is represented in Figure 2.

Figure 2: Proposed classic risk assessment fishbone diagram for cannabis consumer products

The objective would be to determine which metals could enter the final product at each stage. This approach was proposed in a recent Journal of Testing and Evaluation (JTE) publication that examined the use of a risk-assessment strategy to identify sources of heavy metals in cannabis and hemp products.

The key question is:

Where can the metals come from—and can we demonstrate that each potential source is under control? We know from the published studies that plastic materials can contain measurable concentrations of metals. But what would happen if those same plastic materials were subjected to an extractable metals procedure similar to that used by pharmaceutical manufacturers?

Would the metals actually be released?

 

What Should Cannabis Manufacturers Do?

In today’s disjointed regulatory environment, there is no clear guidance for cannabis producers. However, if a similar situation occurred in a pharmaceutical manufacturing plant, the plant would be expected to investigate the potential source of elemental contamination due to the industry’s regulatory framework and FDA oversight. For cannabis manufacturers, however, there is currently no comparable requirement to conduct such a systematic evaluation.

As a result, a potentially important source of contamination could be escaping scrutiny.

The pharmaceutical approach provides a useful model. Cannabis manufacturers could develop their own risk-based extractables and leachables testing program for plastic components that come into contact with cannabis extracts and finished products.

For example, instead of using extraction conditions developed for pharmaceutical manufacturing, cannabis-specific studies could investigate commonly used cannabis formulations, diluents, solvents, and carriers, including:

  • MCT (medium-chain triglycerides) oil
  • glycerin
  • propylene glycol
  • ethanol
  • terpenes
  • hemp seed oil
  • vegetable oil

Plastic components could be exposed to these materials under controlled conditions and subsequently analyzed for relevant elemental impurities using ICP-MS or ICP-OES. The results could then be incorporated into a broader elemental-impurity risk assessment.

This would allow manufacturers to move from simply asking: “Is this plastic food grade?”….to asking a much more scientifically meaningful question: “Have we demonstrated that this plastic is suitable for its intended use with our cannabis product?”

 

Final Thoughts

With the current state-driven regulatory system, there is very little incentive to fully understand the sources of heavy metals throughout the cannabis production process—or in the final consumer products. And in particular, there is no reason to look beyond the “big four” if state regulators don’t require it. However, there is compelling evidence in the public domain that additional metals could be leaching from plastic materials, particularly when cannabinoid extracts and oils are stored in them for extended periods.

But there has not yet been enough testing to definitively establish the extent of the problem. A suitable leaching procedure could be developed based on approaches already used by pharmaceutical manufacturers. But instead of extraction protocols described in USP Chapter <661>, cannabis-specific protocols could use common diluents used in cannabis formulations to investigate extractable metals from plastic components.

At present, there are no comprehensive state regulations requiring cannabis producers to address this issue. So, until the industry adopts a meaningful risk-assessment approach, we simply don’t know whether plastic materials are a significant source of elemental contamination in cannabis products.

We can only hope that when the industry eventually comes under the scrutiny of federal regulators, we might find out the answer. But until then, we can only keep on asking the questions….and maybe someone is listening!

Safety & Compliance in the Absence of Regulatory Clarity & Consistency

By Joel Chappelle
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As the legal landscape surrounding cannabis continues to evolve, the creation of robust, sensible and consistent safety regulations remains stalled. A patchwork of broadly inconsistent state rules and regulations, along with years of federal inaction and policy stagnation have the potential to create significant risks for consumers. Given the industry’s explosive, multi-billion-dollar growth, consumers have access to an ever-increasing number of products produced by an increasing number of actors, pursuant to widely divergent standards and rules. Given this, the industry would be well-served to take on the responsibility of promulgating a coherent regulatory framework with robust (but sensible) safety regulations. The importance of collaboration among cannabis industry stakeholders cannot be overstated if we are to develop and adopt consistent standards that guarantee product safety at every step of the supply chain.

Joel Chappelle, along with several renowned experts, will lead the Seed to Sale Safety Workshop at the Cannabis Quality Conference this October 16 in New Jersey. Click here to learn more. Inconsistencies in safety standards and regulations open the door to a range of potential hazards, including contaminant risk, labeling accuracy, potency quantification and many others. Absent a clear understanding of seed-to-sale risks, many of which are not even mentioned in state regulations, cannabis companies face significant exposure, often without even knowing it.

To mitigate these risks, it is vitally important for the cannabis industry to collaborate in the ongoing development of safety standards. This means understanding and implementing safety measures starting with the cultivation process. Careful consideration should be given to factors such as the use of pesticides and herbicides, soil quality and irrigation methods. Standardized safety testing to ensure uniformity between products for potency, contaminants, heavy metals and microbial organisms is crucial to consumer safety. Accurate and comprehensive labeling is likewise necessary for consumers to be adequately informed.

For as long as consistent state and federal guidelines governing cannabis safety remain elusive, the need for industry self-regulation will be paramount. Cannabis companies must work together to share best practices, establish standard operating procedures and adopt stringent safety measures. By promoting transparency and collaboration, stakeholders can build credibility and consumer trust while fostering a safer and more reputable industry.

As the industry continues to grow, it is incumbent upon all stakeholders to continue prioritizing consumer safety through, among other things, a focus on education and inter-industry collaboration, if we are to continue cultivating a trustworthy and sustainable cannabis market for the future. The path forward will require stakeholders to pursue continuous education, improvement, and collaboration in the development of a holistic safety framework capable of ensuring consumer safety.

Colorado to Bolster Hemp Testing Rules, Rollout Delayed

By Aaron G. Biros
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Earlier this year, the Colorado Department of Public Health and Environment (CDPHE) announced a plan to introduce new testing rules for the state’s growing hemp industry. Under the new regulations, hemp products must be tested for residual solvents, heavy metals and pesticides, in addition to making sure they contain less than 0.3% THC.

The CDPHE are planning on a gradual rollout to prevent any supply chain issues or a lab testing bottleneck, similar to what we’ve seen in other states launching new testing requirements in years past, such as Arizona or California. Well, the Colorado rollout appears to be hitting similar snags and because of supply chain issues related to instruments and consumables in laboratories, the implementation of those testing rules is somewhat delayed. What was originally supposed to be implemented over the summer was pushed back to an October 1 deadline, and that deadline has now been pushed back to 2022.

The pesticide testing list to be implemented January 1, 2022

As a result of supply chain shortages and the learning curve to test for such a wide range of pesticides, Colorado is opening hemp testing to out-of-state labs in an effort to stay on schedule with the rollout. Dillon Burns, lab manager at InfiniteCAL, a cannabis testing company with locations in California and Michigan, just completed an audit with the CDPHE in their work to get certified and start conducting hemp testing for businesses in Colorado.

Burns says they’re well-acquainted with the list of pesticides because of how similar the list is to California’s requirements. “For the pesticide testing rules that were supposed to go into effect on August 1st, it’s basically the same list as California just with slightly different action levels,” says Burns. “I would say these action limits are generally stricter – they have much lower LOQs [limits of quantification].”

The pesticide testing list (continued) to be implemented January 1, 2022

Come January 1, 2022, they are expecting an additional 40 pesticides to be required under the new rules. “But currently, it’s still unclear when these regulations will actually go into effect,” says Burns. The full pesticide testing list is currently slated to be implemented on April 1, 2022.

The supply chain issues referenced above have a lot to do with what the state is asking labs to test for. Previously, most of the pesticides tested for under Colorado’s adult use and medical cannabis programs could be analyzed with an LC/MS. A handful of pesticides on the new list do require GC/MS, says Burns. It’s entirely possible that a lot of labs in Colorado just don’t have a GC/MS or are in the process of training staff and developing methods for using the new instrument. “Cleanliness of these instruments is such a priority that it takes time to acquire the right skill set for it,” says Burns.

Dillon Burns, Lab Manager at InfiniteCAL

The new testing rollout isn’t just another compliance hurdle for the cannabis industry; these rules are about protecting public health. Dillon Burns said he’s seen hiccups in California with the amount of new hemp farmers getting into the space. “The hemp products we’ve tested in California often fail for pesticides,” says Burns. It’s a lot easier in most states to get a license for growing hemp than it would be for growing adult use cannabis. “You’ll see a lot more novice growers getting into hemp farming without a background in it. They’ll fail for things they just haven’t considered, like environmental drift. We see a lot of fails in CA. Hemp is bioaccumulating so it presents a lot of problems. If they’re not required to look for it, they weren’t monitoring it.”

When asked how the market might react to the new rules, Burns was confident that Colorado knows what they’re doing. “I don’t anticipate that [a testing bottleneck] happening here. The regulators are reasonable, supportive of the industry and opening it up to out-of-state labs should help in preventing that.”

Kaycha Labs Joins NIST’s CannaQAP

By Cannabis Industry Journal Staff
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Kaycha Labs, a cannabis lab testing company headquartered in Fort Lauderdale, Florida, has announced their participation in the National Institute of Standards and Technology’s (NIST) Cannabis Quality Assurance Program (CannaQAP).

The NIST is an organization under the U.S. Department of Commerce that promotes innovation through standards, technology and advancing science. The NIST’s CannaQAP platform works with cannabis labs to help improve competence in analytical science and standardization.

The program requires participating labs to conduct exercises that help inform the NIST about current industry standards and capabilities for hemp and cannabis testing. One of the goals of the program is aiding in the design and characterization of cannabis reference materials.

Kaycha Labs took part in two exercises for the CannaQAP study. Exercise 1 included testing for potency with 17 cannabinoids in hemp oil and Exercise 2 included potency, heavy metals and moisture content testing in plant materials.

Chris Martinez, president of Kaycha Labs, says the program can benefit the entire industry when it comes to regulatory compliance testing. “As a leading cannabis lab company with a network of labs in multiple states, it is imperative we demonstrate that our labs apply compliant and consistent testing methodologies,” says Martinez. “Assuring all industry participants, including State and Federal government regulators, that precise and consistent testing data is the norm will benefit the entire industry.”

Kaycha Labs, while based in Fort Lauderdale, actually has cannabis testing labs in California, Colorado, Florida, Massachusetts, Nevada, Oklahoma, Oregon and Tennessee, making them an ideal candidate for CannaQAP.

Exercise 1 has been completed in its entirety and published here. Exercise 2 has completed the participation and data submission legs of the study and NIST is preparing it for publication. On their website, it says that announcements about their upcoming Exercise 3 are coming soon.

4 Trends Propelling the U.S. Cannabis Testing Market: 2021-2027

By Priya Deshmukh
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As the legalization of cannabis in the U.S. continues to grow, stringent regulatory requirements around the country are being adopted to ensure that only safe and high-quality cannabis is sold. The U.S. cannabis testing market is estimated to see tremendous growth over the coming years. Further, the FDA has made several resources available for addressing cannabis products like CBD to ensure that consumers and stakeholders are getting safe products.

According to Global Market Insights, Inc., U.S. Cannabis testing market size is projected to surpass USD 4.1 billion at a CAGR of 10.4% through 2027, in light of below mentioned trends:

Strategic initiatives by major industry players

HPLC (high pressure liquid chromatography) instrument.

Prominent players operating in the U.S. cannabis testing market such as CannaSafe, Anresco, Collective Wellness of California, EVIO Inc., Digipath Inc., PSI Labs, SC Labs, Inc., Steep Hill, Inc. etc. are focusing on developing enhanced cannabis testing solutions and accreditation for gaining strong market presence. For example, earlier this year SC Labs developed a comprehensive hemp testing panel that is purported to meet testing standards in every state with a hemp program.

Citing another instance, in 2019, a leading cannabis resource Leafly, introduced the Leafly Certified Labs Program, under which a network of labs is independently assessed by Leafly for quality and accuracy. This program has been designed to address inconsistency in cannabis testing by ensuring that lab data comes from labs that have been confirmed to provide accurate results.

Rising adoption of high-pressure liquid chromatography (HPLC) technique

A lot of cannabis testing procedures are carried out using liquid chromatography. It is estimated to witness higher preference over the coming years. In 2020, the liquid chromatography segment recorded a valuation of USD 662.4 million. Further, liquid chromatography is a valuable alternative to gas chromatography when it comes to analysis of cannabinoids, pesticides and THC which is why this technology is often preferred for potency testing as it offers more precise analysis. Moreover, purification standards are highly controlled in liquid chromatography which helps in obtaining accurate results, which is complementing the segment growth.

Growing popularity of heavy metals testing for cannabis

Cannabis samples are liquified in strong acid in a pressurized microwave prior to evaluation for heavy metal content. Image courtesy of Digipath, Inc.

Heavy metals are known to be one of the major contaminants found in cannabis and its products apart from residual solvents, microbial organisms and pesticides. In addition, heavy metals are highly toxic in nature and on exposure can lead to poisoning and other complications. As a result, heavy metal testing for cannabis and its products is increasingly becoming popular. Several government organizations have made heavy metal testing mandatory for cannabis products. Moreover, increasing legalization of cannabis across several countries for adult use and medical purposes is likely to instigate the demand for heavy metal testing of cannabis products, thereby fostering the growth of heavy metals testing segment over the coming years. For the record, in 2020, the segment had recorded a market revenue of USD 352.5 million.

Increasing support from government bodies in the Mountain West

With increasing legalization for medical and adult use, the cannabis testing market in the Mountain West zone of the U.S. is likely to observe a tremendous growth over time. Moreover, growing support from various government bodies is playing a key role in enhancing the business space. For example, Montana’s Department of Revenue helps labs get licensed along with the state’s environmental laboratory that oversees inspections and licensing. Further, presence of a large number of cultivators of cannabis and manufacturers of cannabis-based products are also positively influencing the regional market growth. Considering the significance of these growth factors, the U.S. cannabis testing market in the Mountain West is estimated to register a substantial CAGR of 9.6% through 2027.

SC Labs Develops Comprehensive Hemp Testing Panel

By Cannabis Industry Journal Staff
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SC Labs, a cannabis testing company with roots in Santa Cruz, California, announced this week that they have developed a comprehensive hemp testing panel that covers a number of contaminants on a national regulatory level. In the press release, the company says they aim to fill the void of national hemp testing requirements.

The hemp testing panel they have developed purportedly meets testing standards in states that require contaminant levels below a certain action limit. The SC Labs hemp testing panel could theoretically be used for regulatory compliance testing across the country, reaching action limits and analyte levels that meet the strictest state requirements.

The panel tests for pesticides, heavy metals, microbiology, mycotoxins, residual solvents and water activity.

The panel is one sign of progress on the long road to nationally harmonized testing standards. “As an industry, we’ve been advocating for national, standardized, and transparent testing regulations for years now,” says Jeff Gray, CEO of SC Labs. “The government has been slow to respond so we decided it was time to act. As an industry, we’ve been advocating for national, standardized, and transparent testing regulations for years now. The government has been slow to respond so we decided it was time to act.”

SC Labs is headquartered in Santa Cruz, but has licenses in California, Oregon, Texas and Colorado (pending). Their California and Oregon locations are both ISO 17025-accredited and conducting THC-containing cannabis testing, as well as hemp testing.

Cannabis Compliance Testing: Safety vs. Quality

By Vanessa Clarke, Melody Lin
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Dr. Markus Roggen is a chemist, professor, cannabis researcher and founder & CEO of Complex Biotech Discovery Ventures (CBDV). Founder & CEO of Ascension Sciences (ASI), Tomas Skrinskas has been at the leading edge of transformative healthcare technologies, including computer assisted surgery, surgical robotics and genetic nanomedicines, for over 15 years.

Leading researchers from the cannabis industry – Dr. Markus Roggen (Complex Biotech Discovery Ventures) and Tomas Skrinskas (Ascension Sciences) – highlight the challenges facing the industry’s current compliance testing standards and the opportunities emerging from the latest developments in nanotechnology and advanced analytical testing. Here are the key insights from the discussion. 

What are the current compliance testing requirements for cannabis products? Are they sufficient in ensuring safety and quality?

In the current landscape, Canada’s compliance testing requirements are clearly laid out in the form of guidance documents. Specifically, for pesticide testing, cannabinoid concentration content in products, heavy metals, etc. Compliance testing can be roughly divided into two categories: 1) establishing the concentrations of wanted compounds, and 2) ensuring that unwanted compounds do not exceed safety limits.

In the first category, cannabinoids and terpenes are quantified. Their presence or absence is not generally forbidden but must stay within limits. For example, for material to be classified as hemp, the THC concentration cannot exceed 0.3 %wt., or a serving of cannabis edible should contain below 5 mg of THC. The second category of compliance testing focuses on pesticides, mold and heavy metals. The regulators have provided a list of substances to test for and set limits on those.

Are those rules sufficient to ensure safety and quality? Safety can only be ensured if all dangerous compounds are known and tested for. Take for example Vitamin E acetate, the substance linked to lung damage in some THC vape consumers and the EVALI outbreak. Prior to the caseload in the Fall of 2019, there were no requirements to test for it. It’s not only additives that are of concern. THC distillates often show THC concentrations of 90% plus 5% other cannabinoids. What are the last 5% of this mixture? Currently, those substances have not been identified. Are they safe? There is no concrete way to determine that.

The aforementioned guidelines have the best intentions, but do not adequately address two key obstacles the industry is currently facing: 1) what happens in practice, and 2) what can easily be audited? Making sure people follow the requirements is the challenge, and it comes down to variability of the tests. Testing has to happen on the final form of the product as well as every “batch,” but there is little guidance on how that is defined. With so much growth happening in the industry, how are these records even tracked and scrutinized?

And finally, there’s the question of quality. How do you define quality? Before establishing quantifiable quality attributes, it can’t be tested.

If compliance testing is insufficient, then why aren’t more cannabis companies testing beyond Health Canada’s requirements?

Compliance testing has always been focused on the end product, THC and CBD levels, and consumer safety. As long as cannabis companies are testing to determine this, doing further testing means added costs to the producer. There is a rush to get cannabis products to the new market because many consumers are eager to buy adult use products such as extracts or edibles, and quality is not the biggest selling point at this very moment.

However, there are unrealized advantages to advanced analytical testing that go beyond Health Canada’s requirements and that offer greater benefits to cannabis producers and product developers. Producers often see testing as an added cost to their production that is forced upon them by the regulators and will only test once the product is near completion. For cannabinoid therapeutics and nutraceuticals, advanced analytical testing is critical for determining the chemical makeup and overall quality of the formulation. This is where contract researchers, such as Ascension Sciences, come in to offer tests for nanoparticle characterization, cannabinoid concentration, dissolution profiles and encapsulation efficiency.

HPLC (high pressure liquid chromatography) instrument.

A lack of budget and awareness have prevented cannabis companies from advanced analytical testing. However, testing that goes beyond lawful requirements is an opportunity to save money and resources in the long term. This is where companies, like Complex Biotech Discovery Ventures (CBDV), offer in-process testing that provides a deep characterization and analysis of cannabis samples during every stage of product development. If tests are conducted during production, inefficiencies in the process are revealed and mistakes are spotted early on. For example, testing the spent cannabis plant material after extraction can verify if the extraction actually went through to completion. In another case, testing vape oil before it goes into the vape cartridges and packaging allows producers to detect an unacceptable THC concentration before they incur additional production costs.

Which methods are the most successful for cannabis testing?

The most effective method is the one that best determines the specific data needed to meet the desired product goal. For example, NMR Spectroscopy is paramount in assessing the quality of a cannabis sample and identifying its precise chemical composition.

HPLC (liquid/gas chromatography) is the most precise method for quantifying THC, CBD and other known cannabinoids. However, if a cannabis extractor wants to quickly verify that their oil has fully decarboxylated, then an HPLC test will likely take too long and be too expensive. In this case, IR (Infrared Spectroscopy) offers a faster and more cost-effective means of obtaining the needed data. Therefore, it ultimately depends on the needs of the producer and how well the testing instruments are maintained and operated.

What’s next in analytical testing technology? What are you working on or excited about?

In terms of compliance, regulations to standardize the testing is the hot topic at the moment. For nanotechnology and nanoparticles, the big question now is what is known as the “matrix” of the sample. In other words, what are the cannabinoids, and what else is in the sample that’s changing your results? The R&D team at Ascension Sciences is in the process of developing a standardized method for this to combat the issues mentioned earlier in the interview.

The smoke analyzer in CBDV’s lab

Ascension Sciences is also excited about characterizing nanoparticles over time to determine how cannabinoids are released and how that data can be transferred or made equivalent to consumer experiences. For example, if a formulation with quicker release, faster onset and better bioavailability is found in the lab, product development would be more efficient and effective when compared to other, more anecdotal methods.

At CBDV, the team is working on in-process analytical tools, such as decarboxylation monitoring via IR Spectroscopy and NMR Spectroscopy. CBDV is also looking at quantifying cannabis product quality. The first project currently in motion is to identify and quantify cannabinoids, terpenes, and other compounds present when vaping or smoking a joint using a smoke analyzer. 

A lack of budget and awareness have prevented cannabis companies from testing beyond what’s required by Health Canada. Compliance testing is designed to ensure safety, and for good reason, but it is currently insufficient at determining the quality, consistency and process improvements. As the above factors are necessary for the advancement of cannabis products, this is where further methods, such as advanced analytical testing, should be considered.

Product Safety Hazards: Looking Beyond Food Safety in Cannabis

By Radojka Barycki
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I think that we need to start changing the terminology around the hazards associated with cannabis from food safety hazards to product safety hazards. These hazards have not only been associated with harmful effects for those that ingest cannabis infused products, but also for those that consume the cannabis products in other ways such as inhalation (vaping or smoking). So, when we refer to these hazards as food safety hazards, the immediate thought is edibles, which misleads cultivators, manufacturers and consumers to have a false sense of security around the safety of products that are consumed in other ways.

Food processing and sanitation
By standardizing and documenting safety procedures, manufacturers mitigate the risk of cannabis-specific concerns

There are several product safety hazards that have been associated with cannabis. These hazards can become a public health problem if not controlled as they could harm the consumer, regardless of the method of consumption.

Let’s take a look at the different types of hazards associated cannabis:

Biological Hazards refer to those microorganisms that can cause illness to the consumer of a product that contain them. They are not visible to the naked eye and are very dangerous when their metabolic by-products (toxins) are ingested or their spores are inhaled. The symptoms for illnesses caused by these microorganisms will vary. Consumers may experience gastrointestinal discomfort (vomiting, diarrhea), headaches, fever and other symptoms. The ingestion of these pathogens, allergens or their by-products may lead to death, if the illness is not treated on time or if the consumer of the product is immunocompromised. In addition, the inhalation of mold spores when smoking cannabis products, can lead to lung disease and death. Some of the biological hazards associated with cannabis are: Salmonella sp., E. coli, Clostridium botulinum, Aspergillus sp. and Penicillium sp.

Chemical Hazards refer to those chemicals that can be present in the plant or finished product due to human applications (pesticides), operational processes (extraction solvents and cleaning chemicals), soil properties (heavy metals), environmental contamination (radiological chemicals) or as a result of occurring naturally (mycotoxins and allergens). Consuming high concentrations of cleaning chemicals in a product can lead to a wide range of symptoms from mild rash, burning sensation in the oral-respiratory system, gastrointestinal discomfort or death. In addition, long term exposure to chemicals such as pesticides, heavy metals, radiological contaminants and mycotoxins may lead to the development of cancers.

Physical Hazards refer to those foreign materials that may be present in the plant or finished product. Foreign materials such as rocks, plastics or metals can cause harm to the consumer by chipping teeth or laceration of the mouth membranes (lips, inner cheeks, tong, esophagus, etc.) In the worst-case scenario, physical hazards may lead to choking, which can cause death due to asphyxiation.

These hazards can be prevented, eliminated or reduced to an acceptable level when foundational programs (Good Agricultural/Cultivation Practices, Good Manufacturing Practices, Allergen Management Program, Pest Control, etc.) are combined with a Food [Product] Safety Plan. These lead to a Food [Product] Safety Management System that is designed to keep consumers safe, regardless of the method of consumption.

PharmLabs Accredited to ISO 17025

By Cannabis Industry Journal Staff
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According to a press release emailed today, Perry Johnson Laboratory Accreditation Inc. (PJLA) announced the accreditation of PharmLabs LLC to ISO/IEC 17025. Based in San Diego, California, PharmLabs has four locations, with three in the Southern California region and one in Maui.

PharmLabs offers a very wide variety of services including: California Compliance testing, a specialized Hemp Testing Program, Hemp Biomass Verification testing, and THC-free testing for the state of California. In addition, they offer the testing of cannabinoids, pesticides, residual solvents, microbiological contaminants, mycotoxins, heavy metals, terpenes, water activity, moisture content, and filth/foreign material testing.

“Our experience with [Perry Johnson Laboratory Accreditation] has been incredible over the years. Since we have multiple locations, we have had many visits with PJLA and their knowledge and quick response time has helped us get where we need to be,” says Greg Magdoff, founder of PharmLabs.

According to the press release, PharmLabs has plans to expand throughout the state of California and the rest of the United States in both hemp and cannabis testing in legal states.

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Hemp in the United States: An Opinion

By Dr. Anthony Macherone
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The Agriculture Improvement Act, also known as the Farm Bill, was signed into law in December 2018. A major provision in the law legalizes hemp as an industrial crop. In August of 2016, USDA, DEA, and FDA published a Statement of Principles in the Federal Register (FR 53365) that defined industrial hemp as any part or derivative (including seeds) of the plant Cannabis sativa L. with a dry weight concentration of tetrahydrocannabinols not greater than 0.3% (wt/wt).

USDA LogoGlobally, the hemp market was estimated at $3.9 billion in 2017 and the hemp seed segment is predicted to grow “at a CAGR of 17.1%” through 2025. Some of the markets affected by hemp production include nutraceuticals, food, textiles, construction materials, and personal care products. It is also anticipated that cannabidiol (a non-psychoactive cannabinoid extracted from hemp) production will grow to support the burgeoning recreational and medicinal cannabis markets in the U.S., Canada and other countries around the world.

In U.S. states and Canada where recreational or medicinal marijuana programs have been legalized, regulations have been defined to assure the safety and quality of the products sold to consumers. These regulations include analytical chemistry and biological assays to identify and quantify pesticides, mycotoxins, heavy metals, residual manufacturing solvents, terpenes, and microbial contaminates. With regards to hemp, the USDA recently released guidelines for testing of hemp. To date, the only required test from the Federal perspective is total ∆9-tetrahydrocannabinol (THC) content < 0.3% by weight. Total THC is essentially the sum of tetrahydrocannabinolic acid (THCA) and THC (Total THC = 0.877(THCA) + THC) but this may be eventually expanded to include all salts and isomers of cannabinols as noted above. Another complication: what constitutes “dry”? The CFR does not answer this.

Agilent Technologies has invested in the development and implementation of the analytical protocol, the services needed to support these assays, the required consumables, reagents, and supplies, and the training of sales and support personnel to comprehensively ensure compliance of hemp with USDA regulations.