Articles

Click to view the March digital edition of Cannabis Science and Technology.

March 2020 Digital Edition - Cannabis Science and Technology Vol. 3. No. 2

As health concerns and social distancing plans mount because of the coronavirus (COVID-19) pandemic, major events and conferences are rescheduling or cancelling planned events throughout the U.S. to ensure public safety.

The second annual Cannabis Science Conference (CSC) East announced plans to postpone their Baltimore, Maryland event from early April to June 29–July 1, 2020. According to the conference’s announcement letter, all vendors, attendees, and sponsor commitments will be honored for the rescheduled event. “Out of respect for the concern surrounding the current public health crisis, Cannabis Science Conference has arrived at the conclusion to postpone 2020 CSC East,” said Joshua Crossney, President, CEO and Founder of CSC Events, LLC. “The CSC Events, LLC, team is committed to being good stewards of people’s health.”

In a recent interview with Crossney, he explained the difficult decision to postpone his event. “We were following the developments related to COVID-19 very closely and it just got to the point where with us being a science-based, medical, health and wellness-focused conference we just felt the only smart decision to make was to postpone because the safety of all our attendees, sponsors, and exhibitors is our number one priority,” he said.

In addition, Crossney explained that a lot of CSC East attendees, speakers, and vendors are scientists and medical professionals. “A lot of those medical professionals are working with immuno-comprised individuals on a daily basis. We also have speakers whose children and loved ones are suffering from cancer,” said Crossney. “So obviously we are taking this health crisis very seriously and we wanted to show people that we really care about them and our community. Everyone’s safety and well-being are the most important factors in what we are doing.”

The decision to postpone rather than cancel the event was another matter that Crossney did not take lightly, factoring in both the timing for people to adjust their travel and business plans as well as his commitment to the Baltimore area. “We’re really excited that there was a need for us to expand the conference with an East Coast show last year because the need for education is just so great here in the U.S. and other countries where we get attendees from. We feel that we owe it to this community in Maryland-Baltimore specifically and the East Coast in general-not to cancel,” said Crossney. “We said we were coming here to provide education and a platform for these researchers, scientists, medical professionals, and cultivation experts to come together to network and learn with patients and attendees and we meant it. We are excited to be coming back to do that in June!”

The current agenda that is listed on the CSC 

 will remain the planned agenda for the rescheduled show in June. “There might be some changes here or there, but we’re planning for the content to stay pretty well intact moving forward,” said Crossney. “We have a talk planned from the National Institute of Standards and Technology (NIST) on the need for standardization and what they are working on there as well as a similar talk from the U.S. Pharmacopeia and what they are working on. We’re also really excited about the expansion of academic cannabis all over the U.S. and we’ll have two talks dedicated to that. (See Crossney’s latest 

Crossney’s flagship event-CSC West-will take place as planned on August 31–September 2 in Portland, Oregon.

Following suit, other cannabis conferences across the U.S. have announced plans to postpone or cancel their events. Due to a recent COVID-19 outbreak in Boston, New England Cannabis Convention (NECANN) has also chosen to postpone their conference which was scheduled for March 20–22, 2020. They are currently working with their venue partners and other city officials to settle on a new date this year. In their announcement, cofounders Marc Shepard and Jeff Lawrence stated, “If anyone has any questions, please understand that we are still actively working with our partners to secure the new date and address this change, and ask that you wait before contacting us until we know exactly the new details and dates.” NECANN further commented on the conferences’ postponement by adding that, “all vendor registrations and pre-sale tickets will be honored for the new date.”

Editor's note: NECANN announced their conference is rescheduled for June 27-29, 2020 in Boston. 

The American Chemical Society (ACS) decided to terminate their Spring 2020 National Meeting & Expo that was originally meant to be held between March 22–26, 2020. The Cannabis Chemistry (CANN) subdivision of ACS had a two-day sub-meeting planned at the event. “Safety is a core value of the American Chemical Society, and it permeates all of our actions, activities and events," Thomas Connelly Jr., PhD, the ACS CEO said in a statement. “With the Pennsylvania governor’s Proclamation of Disaster Emergency last Friday, we do not feel we can guarantee the safety of the 15,000 attendees expected for the Philadelphia meeting or of the city residents themselves.” 

The ACS Fall 2020 meeting is still planned for August 16-20 in San Franciso, California.

If you do have to travel this conference season, be sure to wash your hands or use hand sanitizer when soap and water are not available. As Crossney stated, “We’re looking forward to working together with the community to get through this and we wish for everyone out there to be safe and take the extra precautions that were recommended by the 

The second annual Cannabis Science Conference (CSC) East announced plans to postpone their Baltimore, Maryland event from early April to June 29–July 1, 2020.

CSC East Postponed Amid COVID-19 Safety Precautions 

Strikingly similar results have been reported from a wide range of studies on the ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD) concentrations in strains of cannabis. Whether the source has been legalized markets in the west, medical markets in the U.S. and Canada, or collections from law enforcement and researchers, three easily distinguishable types of plant have consistently been found: THC-dominant strains (with less than 1% CBD); CBD-dominant strains (less than 1% THC); and balanced strains with comparable concentrations of both substances. Another consistent finding of these studies, carried out in a variety of laboratory settings, is a positive correlation between THC and CBD levels in those plants that can make substantial quantities (>1%) of each. The correlation between THC and CBD quantities in these varied populations suggests that there is a fundamental property of the plant that makes some combinations impossible, for instance, >15% THC and also >5% CBD. Such results have never shown up in published data sets of carefully, consistently tested samples, but those were all relatively small collections. A much larger data set has been released by the state of Washington (140,000 flower samples), and this has been scrutinized for evidence of consistently propagated strains with higher than a 2-to-1 ratio.

As cannabis emerges from the shadows of the prohibition era into the mainstream wellness market, two corresponding forces are changing the way the product is discussed and evaluated: health-conscious consumers are looking for specific benefits from the product, not simply a “high;” and the simple classifications of products that have been traditionally provided to consumers are being replaced by sophisticated biochemical and genetic evaluations.

Cannabis products today are generally sold under colorful strain names, often with combination names that refer to the predecessor strains from which the new strain was bred. In addition, cannabis products are frequently categorized as being of indica or sativa origin, or more likely as being a blend with a certain percentage of indica and sativa.

For consumers who are looking for specific health effects from cannabis, it is important that they are confident that repurchasing a product with the same, or related, strain name will give them the same positive experience they are seeking (and, conversely, that by avoiding other strain names they will not repeat a negative experience). As more and more sophisticated data is collected on the contents of cannabis products and careful investigation made of the reliability of names and classifications, it is becoming increasingly clear that our current naming systems for cannabis products is inadequate to reliably guide purchasers who are seeking reproducible experiences.

Indica and Sativa Do Not Give Meaningful Guidance on Cannabinoid Content

The terms indica and sativa date back more than 200 years. Originally they described the differences in plant shape and leaf pattern, but more recently they have been used as shorthand terms for cannabis varieties that were considered more sedating or more stimulating. After generations of cross-breeding, and with abundant opportunity for misidentification and mislabeling, the validity of these terms as a means of distinguishing expected effects has been called into question. Over the past few years, a number of rigorous studies of the biochemical properties of plants have reached the conclusion that the traditional indica and sativa terminology are not reliable indicators of the property that is of greatest interest to consumers: the cannabinoid profile.

Molecular genetics techniques, not unlike those used to trace human ancestry, are now being used to investigate plants at the level of their DNA to determine how closely related they are. One study published this year in the 

 (1)  from the University of Northern Colorado examined the relatedness of 120 samples of cannabis from three legal Western markets, covering 30 named strains. Each strain studied was categorized according to its rating on the indica-sativa continuum as recorded by Leafly.com. Analysis of the strains’ genetic properties revealed poor alignment to the traditional labeling, leading the authors to conclude that “…there is no consistent genetic differentiation between the widely-held perceptions of Sativa and Indica Cannabis types” (1). Their conclusion corresponds with earlier work, notably a study from Sawler and colleagues (2), as well as another study from the University of British Colombia (3) and a study of the strains available in the Nevada medical market (4) that found much greater homogeneity in the genetic and cannabinoid profile than would be suggested by the profusion of strain names.

The accumulating evidence of the unreliability of the indica and sativa terminology has been a factor in the decision by Leafly to no longer categorize cannabis strains by those terms (5). Instead, that organization has recognized that the cannabinoid profile of cannabis plants is better described by one of three terms: tetrahydrocannabinol (THC)-dominant, cannabidiol (CBD)-dominant, or balanced. The evidence that supports this fundamental distinction among all cannabis plants is detailed in the next section.

Converging Evidence for Three Categories of Cannabis

A range of studies during the past 15 years have established that the relative quantities of THC and CBD in cannabis plants occurs in only one of three patterns. An assortment of investigations has produced this insight: studies of genetic crosses; studies of the DNA sequences of cannabinoid synthesizing enzymes; and numerous studies of the cannabinoid profile of strain collections from medical and recreational markets. A wide range of such potency studies, using very different collections of strains, has produced strikingly similar results.

The great similarity in the results of studies of cannabinoid ratios in collections of strains from a wide range of sources points to a fundamental property of cannabis plants that is found no matter where they are cultivated. Across these many strain sources and testing laboratories, the consistent finding is that the relative quantities of THC and CBD can only be in one of three patterns: either there are equivalent concentrations of both substances; or one compound is dominant, with only trace levels of the other. Evidence supporting this three-part classification is presented here from five studies. Each of these studies used a scatter plot to display the relative amounts of THC and CBD in individual strains, and in each of these charts the data points separate neatly into three clusters.

The earliest study in this group was a 2003 cross-breeding experiment by de Meijer and colleagues that examined the offspring of high THC plants crossed with high CBD plants, and their progeny (6). The scatter plots (Figure 1) of the THC (

-axis) show three distinct clusters. High THC plants (with little CBD) are clustered on the 

-axis, the high CBD (and low THC) plants are clustered on the 

-axis, and the cluster that sloped up the middle of the chart had comparable quantities of each. The 1:2:1 ratio of the three types in the progeny of the crosses was interpreted by the authors as evidence for one genetic locus, with two codominant alleles, that control the relative quantities of THC and CBD.

A study from the University of Indiana (7) examined 157 strains of cannabis that were collected from breeders, researchers, gene banks, and law enforcement. The cannabinoid profile in that disparate collection of strains conforms very closely to the three cluster result of the cross-breeding study (Figure 2). Similarly, a 2015 study of 210 strains from the Canadian medical program’s License Providers demonstrated the same clustering of three types in scatter plots (Figure 3) of THC and CBD concentrations (with the 

-axes reversed from the earlier figures). A comparable study of 245 strains tested in New Jersey’s medical marijuana program (8) revealed the same pattern of three clusters: THC-dominant, balanced, and CBD-dominant strains, though the vast majority of the strains tested in the New Jersey medical program were the THC-dominant type (Figure 4). (See upper right for Figures 1-4, click to enlarge.)

The largest collection of strain testing results came from the state of Washington’s recreational program (9). In this study, published by Jikomes and Zoorob, more than 160,000 test results from 23 independent laboratories were reviewed. This effort produced a wealth of data on consistency and variation in strain identity, as well as on laboratory-to-laboratory consistency. A scatter plot of THC versus CBD concentrations resulted in the three-cluster arrangement that mirrors the results of other studies (Figure 5). These authors used the relative concentrations to classify each strain as being of Chemovar Type I (high THC), Type II (balanced), or Type III (high CBD). (See upper right for Figure 5, click to enlarge.)

The common pattern of three distinct clusters on these scatter plots provides strong evidence that this is a fundamental property of cannabis plants. The commonality of the result is all the more striking when the range of sources, both in material and methods, is considered.  The laboratories that conducted the cited studies were: a single state-run laboratory; a single academic laboratory; commercial laboratories serving a single medical market; and numerous commercial laboratories serving a fast-growing recreational market. The material tested came from highly controlled medical markets, a recreational market that responds to varied market demand, and strain collections that pre-date the current liberalized legal environment.  For all of these studies to produce such similar results strongly suggests that there are very few patterns possible in the ratio of cannabinoids.

THC and CBD Are Present Proportionally in Blended Strains

The clarity of the three distinct clusters in these studies is in part because of the very striking distribution of the data points in the middle of the scatter plots. In each of the scatter plots, the middle cluster, from strains that contain appreciable quantities of both THC and CBD, is tightly bunched and appears centered on an upward-sloping line.

The upward slope of the center cluster might be casually overlooked, or thought of as expected and “normal,” but such a consistent finding, especially across such varied studies, merits some scrutiny. As THC and CBD (more specifically, their acidic forms tetrahydrocannabinolic acid [THCA] and cannabidiolic acid [CBDA]) are synthesized from the same precursor molecule cannabigerol acid (CBGA), a naive assumption might be that as the plant makes more THCA it would make less CBDA, and vice versa. If that were so, the points in the middle of the scatter plots would have a downward slope, a reverse correlation. But the clear result, and one that appears to be common to all cannabis strains, is that in balanced-type plants that can accumulate significant (>1%) concentrations of both THC and CBD, the two substances are present in proportional quantities. Balanced plants with high THC also have high CBD (toward the top right of the scatter plot), and those with lower THC have lower CBD (toward the bottom left of the center cluster).

The clarity of the clustering in the scatter plots also calls attention to the white spaces, and raises the question of whether there are certain combinations of cannabinoids that are impossible to find in a single plant. Note the sectors in these plots do not contain any data points: above a certain concentration of THC, it appears that the CBD level must be miniscule, so that a strain with 15% THC and 5% CBD is not found on these plots. This is most clear in the plots with fewer data points, and less clear in the plot of thousands of data points from the state of Washington. A principal finding, though, of that study on the state of Washington data, was evidence for reporting inflated THC levels. The question remains, then, whether certain combinations of cannabinoids simply have not been reported, or are actually not possible. A closer examination of the Washington data may reveal whether it contains good evidence for some combinations of cannabinoid concentrations that have not been reported elsewhere, in smaller collections, or whether they represent “noise” in a very large and poorly controlled testing environment.

Are Strains with >15% THC and >5% CBD Possible?

To search for cannabis strains that posses a rare combination of THC and CBD, that have not been reported in small collections, a thorough re-examination has been made of the full database of test results made available by the Washington State Liquor and Cannabis Board. This collection was produced for the study by Jikomes and Zoorob (9) and they have made it available for others to query. The in-between data points, those that are not easily assigned to the three identified clusters, were investigated to look for reliable evidence for certain cannabinoid profiles that have not been documented in small collections. It may be that if enough plants are tested, any combination of THC and CBD concentrations might be found. An alternative view is that such results are simply “noise” in a very large data set, one that has been generated by many different laboratories and protocols.

Searching for results that do not fit the mold, which may either be exceptions to the rule or noise, must be done while bearing in mind important caveats. One of the conclusions of the Jikomes and Zoorob study of this collection is that there was evidence of “cannabinoid inflation” by some laboratories. Their finding of “systematic differences in the cannabinoid content reported by different laboratories” has to be considered as one possible source of unexpected results. Identifying anomalies and getting a handle on the scope of unreliable results, though, should not ruin the credibility and usefulness of the data set as a whole. 

The goal of the investigation of the state of Washington data collection was to get an indication whether the test results that lie between the typical clusters are:

simply anomalous test results (noise in the testing and reporting system);

anomalous plants (test results are accurate but the phenotype is not reliably cultivated); or

reliable results (a consistent property of a strain or grower).

The Washington test results were generated between June 2014 and May 2017, and the full data set totals 215,286 entries (10). Each entry, with a unique identification number, includes strain name, the name of the grower and the testing laboratory, the test date, and reported values for total THC and total CBD concentrations. Each entry is also identified by the type of product tested (flower, extract, wax, edible); thus the data set can be culled to just flower product, and the number of entries is reduced to 146,768. That quantity of entries still presents a challenge for common data analysis methods; in preparing their scatter plots of cannabinoid concentrations, Jikomes and Zoorob subsampled the data to allow visualization. 

To further reduce the data set, and to focus on the strains that fall between the clusters on plots of THC and CBD, the set of all flower results was cut-off to only those entries that have a CBD value greater than 1%. With that restriction, the data set reduced to 6818 entries, and the scatter plot shown in Figure 6 can be generated with standard plotting tools.  The three expected clusters are evident, as they are in scatter plots of smaller collections, but many more entries lie between the most concentrated clusters, leaving some uncertainty about  which cluster they belong to. (See upper right for Figure 6, click to enlarge.)

The conspicuousness of the points between clusters can be misleading in a plot with so many points. Just as a single star is more noticeable in a dark part of a sky than if it were in the midst of a dense galaxy, so the isolation of the points between clusters can appear more prominent when there are so many data points and the clusters are especially dense. In addition, the deletion of the entries with CBD >1% has substantially thinned the THC-dominant cluster at the bottom of the chart.

To isolate those in-between data points, a new measure was calculated: the percentage of the sum of THC and CBD that is from CBD. A plot of the percent of cannabinoid from CBD shows a very interesting pattern (Figure 7). This bar chart of 6818 items is so dense that it appears to be a curve, with an interesting shape that provides a new way to identify clusters: beginning at lower left, there is a long flat area with low CBD percentage that are the THC-dominant strains; a steep upward slope, then a rising plateau are the balanced strains; and a smaller plateau with the highest CBD percentage are the CBD-dominant strains. (See upper right for Figure 7, click to enlarge.)

The in-between strains are at the slope of values between 11% and 45% for CBD as a percentage of the combined cannabinoids. This subgroup was further reduced by calculating the ratio of THC to CBD, and selecting those entries with ratios between 2 and 8; too many of the entries with a ratio of 1–2 were of very low CBD concentration and are not in the set we are seeking. A scatter plot of just the resulting 465 “slope” entries (Figure 8) show that this data reduction has captured the very points we wish to investigate: do these represent plants that are exceptions to the defined clusters, or do they simply represent testing noise? (See upper right for Figure 8, click to enlarge.)

With the data set reduced to this manageable size by selecting the “slope” entries, a closer scrutiny of each entry is feasible. For many entries, this examination revealed duplicate samples: unique identification numbers for the same strain name from the same grower tested on the same day by the same laboratory. Duplicate samples with equivalent cannabinoid profile do not add to our understanding of the validity of the slope entries, so duplicates were removed.

Removing samples with identical profiles, though, raises another topic that was a focus area of the Jikomes and Zoorob study, in addition to variation between laboratories, and that is strain consistency. Close examination of the data set reduced by removal of duplicate samples turned up a number of anomalous results. For 19 sets of entries, covering 49 entries in total, different tests of the same strain from the same grower, conducted on the same day by the same laboratory (usually recorded within an hour of each other) had such discrepancies in the reported values as to call them into question. An extreme example of this is shown in Figure 9a: five samples of the same strain tested on the same day show THC values from 3.9% to 11.7% and CBD values from 2.5% to 8.5%. There is no way now to go back and determine which of these is the most accurate number. These 19 sets of entries also raise questions about other results that are outliers, but for which there is no comparator value that would allow us to identify an anomalous result. This sort of data adds to the concern that testing noise is a contributor to the subset of results that fall between clusters. (See upper right for Figure 9, click to enlarge.)

A different sort of anomalous result in shown in Figure 9b: rather than individual results showing too much discrepancy, these results show more uniformity than should be expected. In this case, 10 different strains from one grower were tested on the same day by one laboratory, and the results are curiously consistent. While the THC values range from 5.7% to 11.8%, the CBD values are in a very tight range, from 1.1–1.2% with only one as high as 1.5%. Such a result is not impossible of course, and might be plausible if each of these strains was proprietary to the grower (leaving aside the business logic of growing 10 strains with the same profile). A check on the strains in question, though, show several strain names that are very common in this data set (Dutch Treat and Snoop’s Dream). The values in this suspect set are unlike the results of hundreds of other entries that have the same strain name, but are from other growers. This is another set of points between the clusters that we would conclude is not reliable evidence for plants with unique properties.

A different type of anomalous result, the flip side to the curious consistency in the CBD values of entries with different names, is illustrated in Figure 9c: a set of 12 tests of a single strain name, done over 3 months for one grower, with striking consistency in the THC values (10 results between 15.1 and 15.9), but with CBD values that increase from 1.08 to 4.2. The increase in the reported CBD values occurs sequentially over the 3 months of testing with only minor deviation. For one strain from one grower to shift, steadily and smoothly, from a THC–CBD ratio of 14.7 to 3.7 in 3 months, without a change in the THC value, is a remarkable result.

Putting aside those results where there is a clear question about reliability, we are left with a set of 354 “slope” entries that fall between the clusters, and now we can investigate if there are consistent results in them or whether they are better regarded as noise. The next path to look for a reliable finding was to investigate strain names that are over-represented in this set. Several of the most common strain names in the full data set are also the most common in this “slope” subset, for example Harlequin and Cannatonic. As pointed out by Jikomes and Zoorob in their study, there is considerable evidence that common strain names have been applied to plants with very dissimilar characteristics. This is evident in a scatter plot of cannabinoid concentrations for all of the 287 entries (in the set of 6818) with the strain name “Harlequin” (Figure 9d). The majority of entries are in the blended cluster at the center of the plot, but there is wide divergence, making this plot appear as a microcosm of the population as a whole (compare Figure 6).

Looking for consistent representation of certain strains or growers in the “slope” subset produces something of a mixed bag of results. Considerable dispersion exists in both strain names and growers: the final set of 354 entries contains 271 different strain names and come from 179 separate growers. Of the different strain names, only eight represent more than 1% of the total population, and several of these names are just as common in the population as a whole as in this select subset. 

The 354 entries being investigated for reliable evidence of plants that fall between the clusters are just 0.24% of the total number of flower test results in the full database. Of these, only 43 are reported as having >15% THC and >5% CBD. In this most select subset, there are a few entries with repeated strain names, but each of these has its own data issues. In one case, there are four entries with the same strain name from the same grower, but these four samples, tested over 2 weeks in 2015, were entirely unlike the other 110 samples from that grower tested over the subsequent 3 years, all of which had conventional blended (1:1) THC and CBD values. It is possible that strain spuriously produced plants high in both THC and CBD in one instance, but that strain name does not provide a reliable guide to finding it again.

Similar problems are encountered when looking at results from individual growers who had more than one entry with >15% THC and >5% CBD.  One strain name from a grower with two entries in this subset had a strain with a THC value of 16.8% and CBD of 5.5%, but all of the other data about this strain makes this appear to be a simple clerical error: 23 other tests of this strain name, from three growers, were reported as CBD-dominant. This is particularly made clear when we see that on the same day of the results in question, another laboratory tested the same strain from the same grower and reported reverse values: 5.5% THC and 14.4% CBD. Another grower had two entries in this set, but one strain had samples tested by different laboratories two weeks apart, one with 19.1% THC and 1.5% CBD and the other with 24.2% THC and 5.9% CBD. The second test was done by the laboratory flagged by Jikomes and Zoorob for reporting THC results “significantly higher (p < 0.001; Wald test) than all other labs,” suggesting this could be a case of a spurious laboratory result.

A search for reliable strain names or growers in the set of entries with >15% THC and >5% CBD did not prove fruitful, casting doubt on the idea that such strains can be consistently produced, if they exist at all. There are some promising hints, however, that there are reliable plant characteristics in the range of >15% THC and >2% CBD. There are a few strain names that are over-represented in this subset, though they are not exclusive to it: Lavender and Green Crack have enough entries in this sub-set, without obvious data problems, that they are promising leads to continue a search for strains that fall between the clusters.

The lack of reliable evidence for strains with cannabinoid concentrations that fall outside of the three clusters (THC-dominant, CBD-dominant, and balanced) does not necessarily mean that such strains cannot exist; after all, absence of evidence is not the same as evidence of absence. It may be the case that growers have  concluded that there is not a market for strains with 15% THC and 5% CBD, and so have not attempted to initiate or propagate any plants with that combination. However, with all of the incentive for innovation in competitive markets and the interest in new experiences, it seems that someone would try to address this niche. The evidence from the very large Washington data set is that if such a strain is possible, it is a spontaneous occurrence which has not been reliably propagated.

https://doi.org/10.1186/s42238-019-0001-1

J. Sawler, J. Stout, K. Gardner, D. Hudson, J. Vidmar, L. Butler, J. Page, and S. Myles, 

https://doi.org/10.1371/journal.pone.0133292

E.M. Mudge, S.J. Murch, and P.N. Brown, 

https://doi.org/10.1038/s41598-018-31120-2

U. Reimann-Philipp, M. Speck, C. Orser, S. Johnson, A. Hilyard, H. Turner, A. Stokes, and A. Small-Howard, 

https://www.leafly.com/info/cannabis-guide

E. de Meijer, M. Bagatta, A. Carboni,  P. Crucitti, V. Moliterni, P. Ranalli, and G. Mandolin,

https://doi.org/10.1186/s42238-019-0011-z

https://doi.org/10.1038/s41598-018-22755-2

, is an Academic and Research Liaison with the New Jersey Cannabis Industry Association. Direct correspondence to: 

A large data set from Washington (140,000 flower samples) is scrutinized here for evidence of consistently propagated strains with higher than a 2-to-1 ratio.

Are There Limits to the Range of Possible Cannabinoid Ratios in Plants?

North American cannabis consumption continues to rise at a torrid pace and, according to Arcview Analytic Research, the markets for total annual legal cannabis spending in 13 states are expected to pass the $1 billion mark by the end of 2024 (1). Such high demand for legal cannabis products bodes well for the market for analytical tools used to test legal cannabis and ensure its consistency, high quality, and, most importantly, safety.

Cannabis products are frequently tested for potency, pesticides and fungicides, solvent residues, heavy metals, microbes, foreign organic matter, and moisture. The most common technologies used for these tests are high performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS), gas chromatography (GC) and GC–MS, inductively coupled plasma mass spectrometry (ICP-MS), and polymerase chain reaction (PCR).

Thousands of licenses have been issued by states to prospective laboratories looking to test cannabis products. However, only a small fraction of those licensed laboratories are actually capable of performing cannabis tests. Compliance is among the major issues many laboratories face (for example, achieving ISO 17025 accreditation). While regulatory uncertainties and understanding the state requirements continue to be key challenges, for many laboratories, just obtaining the right equipment and fine tuning methods was cited in a recent survey as the biggest hurdle.

Survey participants were asked to rate the level of importance of eight performance parameters of testing instruments on a five-point scale, where a rating of five indicates high importance. As shown in Figure 1, on average, sensitivity and accuracy was deemed the most important by survey participants, followed by reliability and durability. Service and support from the vendor also rated high.

Survey participants were asked to indicate their level of satisfaction for these same performance parameters. The parameters that averaged the lowest scores were affordability, up-to-date technology, and user friendliness.

The responses to these questions reflect the challenges in the laboratory and the cannabis testing industry as a whole. For example, the parameter with the largest difference between importance and satisfaction averages was reliability and durability. Laboratories often experience inconsistencies in their results when obtaining tetrahydrocannabinol (THC) and cannabidiol (CBD) content levels.

The gap between importance and satisfaction for sensitivity and accuracy was also notable, suggesting users are experiencing difficulty obtaining accurate measurements for THC, CBD, pesticides, heavy metals, and other analytes. Laboratories seem to also be concerned about the sensitivity of instruments, particularly when measuring pesticides and heavy metals to meet regulatory mandates.

Overall, the market for laboratory testing is still in its infancy as laboratories struggle to obtain instruments and achieve compliance, while also keeping up with the evolving regulatory mandates.

This article also refers to data from the 2020 market report focused on the North American cannabis market for laboratory instrumentation from independent market research firm TDA. The report features industry benchmarks (such as market size and growth estimates) for cannabis testing laboratories in North America, including a survey of end users. For more information about this report, contact Glenn Cudiamat, president & CEO, at (310) 871-3768 or 

Our first market profile of 2020 reviews the cannabis laboratory testing market in the U.S. and Canada.

Cannabis Laboratory Testing Market in North America

The challenges of scale-up are not insurmountable. Resources are available for start-ups and small businesses to overcome and develop plans to scale-up. This support needs to be a holistic approach. Learning from others and planning can help entrepreneurs avoid common pitfalls of scale-up.
	Here, we outline a holistic approach to scaling up.

Now is a time of great opportunity for cannabis and hemp entrepreneurs. Consumers are demanding more choices, and e-commerce is connecting buyers and sellers worldwide. Startups can grow in new ways and more rapidly than was previously possible, but when success maxes out production capacity, the entrepreneur faces a new challenge-scaling up hemp and cannabis production to keep up with demand.

Scale-up is an exciting time with much hope and promise, however, it is also a vulnerable time for new businesses. Innovators who do not plan ahead can make tragic mistakes and suffer losses too great to survive. The challenges of scale-up are not insurmountable. Plenty of entrepreneurs have succeeded, and you can too.

Resources are available for start-ups and small businesses to overcome and develop plans to scale-up. This support needs to be a holistic approach. Learning from others and planning can certainly help entrepreneurs avoid the common pitfalls of scale-up.

This article outlines a holistic approach to scaling up including:

• Understanding and controlling feedstocks
	• Navigating regulatory and compliance requirements as it relates to manufacturing
	• The importance of the strategic facility methodology for your design with the end products in mind
	• Determination of your manufacturing plant’s capabilities, purification levels, and processes
	• Utilization of cannabis and hemp-based
	scoping strategies

Let’s take a closer look at each of these strategies. Note that some supplementary information related to each of these topics can be found within reference 1.

Not to get too elementary, but as in all cases of farming, understanding and controlling the quality of feedstock is absolutely essential to delivering a consistent product. In this market, we are growing our feedstock. It is not synthetically derived; it is developed through a series of genetic mutations. We create clones from a mother plant to arrive at optimum characteristics: larger buds, more oil, and stronger, more tolerant stocks.

This is not earth-shattering information. But once you arrive at the feedstock that offers you the best oil or the best isolate (or whatever attributes you require on the backend of the processing), you must be able to control and nurture it, and prevent it from being adulterated.
	That’s not always so easy. If a third party is providing the feedstock, you are trusting them to nurture the feedstock, so that when it is introduced to the plant facility for processing, it yields the intended product.

For now, the cannabis market is largely self-regulated and therefore not strong in terms of quality assurance. That can be dangerous in terms of consistent quality of product. It demands that you do all you can to control your feedstock and understand the supply chain for the downstream piece, and to have confidence in the consistency of your final product.

If you are not controlling the feedstock on your own, audit the provider from whom you will get product. Understand how they grow and what their cycles are. Are they able to scale with demand? It’s advisable not to put all your eggs in one basket, but instead to have a group of suppliers that can provide you the same quality of material.

On the other hand, if you’re controlling your own feedstocks, make sure that your mother clone environment is well managed internally. You don’t want to adulterate anything you have in your current facility. Maintain an adequate level of documentation to ensure consistency in growth quality. After all, consistency in your feedstock equals consistency in your product.

Navigating Regulatory and Compliance Requirements Related to Manufacturing

If you were to eliminate every other consideration from effectively managing your facility, this would remain the lynchpin to becoming a successful long term manufacturer. This is the level barrier to entry.

From a risk standpoint, federal requirements are lacking in terms of testing procedures, compliance organizations, and so on.

In general, therefore, the industry is actually asking the government essentially to be regulated under some aspect of the Food Drug and Cosmetic Act or a similar regulation. This is to prevent unscrupulous aspects of the industry from shirking good manufacturing practices (GMP) as a shortcut to making money, even at the expense of releasing good quality materials to the market that people will ingest.

The fact that the industry is not really required to do anything in terms of regulation is obviously very dangerous. One tainted gel tab, gummy, or sucker could potentially destroy the industry. (Our firm in particular is working with a variety of other groups to encourage the federal government to apply some regulatory oversight as pre-emptive legislation to undermine a convoluted system where every state has its own guidelines, and no two may match completely.)

One aspect of federal legislation that might be applicable here would be the U.S. Food and Drug Administration’s (FDA) Code of Federal Regulations Title 21, pertaining to food and drugs (2). Part 111 of this code applies specifically to “current Good Manufacturing Practice in manufacturing, packaging, labeling or holding operations for dietary supplements.” We routinely encourage our clients to apply some of these guidelines for constructing and designing facilities for clean room environments, at a minimum.

Because regulatory information isn’t codified in the cannabis industry yet, manufacturers have an obligation to at least prepare their facilities to a level appropriate to what their output will be in general. The cannabis industry does not have the same level of granularity in compliance guidelines as the pharmaceutical industry has. It is still incumbent on companies to create products in an environment that suggests a level of cleanliness or control within that space appropriate to the product being created (for example, raw oil as opposed to a highly purified product).

There might be some pushback in the ranks within the industry to federal regulation, but it is no different to what is being done with the Food Safety and Modernization Act (FSMA), for example. From a business standpoint, FSMA asks food producers to prove that standards are being met for cleanliness and that operating procedures exist for food preparation and handling. To the extent that the end product is being ingested, some level of regulation and compliance is essential for the responsible growth of the industry.

The Importance of the Strategic Facility Methodology: Design with End Products in Mind

Before we get into the details here, let’s consider some strategic facility questions your organization must be prepared to answer:

• How well do our proposed facilities support our five-year business plan?
	• How much additional space do we need to meet our growth projections? When do we need it?
	• What deep-dives are needed to make key decisions?
	• What is our roadmap for implementing our strategy?

That may be a lot to absorb, so let’s break it down a bit further. When planning for a scalable facility, the best strategy has two parts. The first is to begin with the end in mind. What is it you want your facility to produce? Whether you plan to be the leading manufacturer of cannabidiol (CBD) gummies, pet food treats, or something else, you’re trying to understand the inter-relationship of all the building blocks that go into the creation of a particular type of facility-from warehousing to production to purification and so forth.

The second aspect of strategic methodology is to understand the time frame in which a master plan for your business growth is to be implemented. That plan has milestones along the way-so in a five or 10 year plan, for example, there are things to be accomplished that can be extrapolated from your current capabilities.

Developing a strategic master plan starts with an understanding of what’s possible today (that is, the products that you are building from today), and where you know you want to go-and where you do not know yet whether you want to go or not.

Planning for the unknown can be daunting, of course. If you don’t plan for some variability, however, you may find yourself stuck at some point down the road, especially once government regulations become more detailed. You need to be prepared at some level to make adjustments or upgrades to your facilities as your business develops and for regulatory compliance issues yet to come.

Beyond variability, it is important to model your projected growth. For example, what production levels are you trying ultimately to attain? That understanding is essential to setting budgets for your current plan and for successive years’ planning. No organization has an unlimited budget, and no organization has unlimited space to build. By understanding your projected growth, you can begin to optimize the usefulness of what you have now.

A responsible growth strategy, therefore, must adopt a “modular” approach. In this type of approach you determine the scalability of your existing equipment and create points in your strategic plan in which additional components can be added to that equipment, to accommodate your expansion. 

Obviously, you don’t want to buy equipment now only to discard it later, so the idea of modularity gets down to a granular level of whether you can turn up or turn down equipment to match your current and projected output levels. For example, might it make sense to buy a piece of equipment capable of processing a thousand pounds per hour, even if your current capability is 500? Can it still be efficient to use the same piece of equipment?

This is why you and your engineering and production partners must thoroughly understand your business model. You really have to understand where you’re going and where you want to go. And take to heart the advice that comes from your partners. It may be difficult to hear that you may not have enough feedstock to run your plant for a week at a particular production rate. But with that information, you can match your capability to acquire feedstock to the operational needs of your plant. From there, you can begin to understand how to build the next layer on top of that. 

Your strategic plan is developed by understanding both the inputs and the outputs of your business operations-beginning with the end in mind and working backwards from there.

Determination of Your Manufacturing Plant’s Capabilities, Purification Levels, and Processes

Here we’re moving our thinking from the strategic level to the component level. You’re still determining what your plant is going to do, and in that determination you will come up against code compliance issues at the state or municipal level. These issues will play a huge role in the capabilities and likely locations for your operations.

The components that drive the front end piece of what your business will be are subject to a variety of codes. Take extraction, for example. Each type of extraction methodology produces a different extract, from CO

 to solvent extraction with ethanol or methylene chloride or heptane and hexane. Once the oil has been extracted and the solvents have been removed, what will you do with it? Crystallize it, further distill it, create isolates, or just sell the raw material? Those are all considerations that factor not only into your strategic plan, but to the very nature of what your plan does and how it is to be designed.

As you go through this methodology, you will find that it is likely to change what your facility is, and what you need to do to ensure code compliance.

This is critically important because besides regulation at the federal level, code compliance at the state or municipal level is the most important aspect of scaling your business. You are creating an environment inside your facility that requires a wide range of code compliances-electrical classifications, hazardous occupancy building classification, storage of solvents, and more.

If you are determined to establish a CBD facility in a small office park to extract material, you are more than likely to run into code compliance issues. Not to be too glib, but if you have large tanks of solvents outside your facility, your neighbors will take note, and you will attract the attention of inspectors who might take a dim view of those tanks in that environment. Consequently, you have to make a decision up front. For example, will you be purifying product on site or have someone else handle that level of processing?

So, what’s your plan? When you’re choosing your location, you must understand the codes in that area, which in turn helps determine your facility design. Code compliance issues and regulatory requirements are the key factors in defining what your facility will be and where it will be located.

Utilization of Cannabis and Hemp-Based Scoping Strategies

Whether you classify your feedstock as hemp or cannabis, your scoping strategy ties into the regulatory environment, your locational environment, and what the municipality will allow, among other factors. The U.S. Farm Bill set a level of below 0.3% tetrahydrocannabinol (THC) to be considered industrial hemp, but ultimately it’s all cannabis, and you can’t lose sight of that very basic fact as you build your business.

Let’s consider feedstock strategy. Different plants can be cloned to provide different levels of THC, levels of oil, sizes of buds, and so forth. You have to understand what your state will allow. If you can’t have any cannabis in your state at this point, or you don’t see it happening in the future, it’s not advisable to design a facility that’s capable of providing or processing cannabis at the moment. It would make more sense to design for that capability once you understand how the regulatory environment will change. In the meantime, you may need to focus your efforts on finding other feedstocks.

If you are planning to use both low THC hemp feedstocks and cannabis, you have to plan for a separation of the two. It is essential to have good controls over the feedstock for medical marijuana manufacturing, including whatever waste is coming out of your plant. Even as states deregulate, there will still be a need for that level of control. It’s analogous to the GMP implemented in the production or processing of alcohol or tobacco.

Scoping strategies, therefore, boil down to how industrial hemp and cannabis will be handled in your facility because the two are handled differently and they are going to remain that way. If you plan to have both in your plant, you will have to accommodate both, with rules for separating them at the warehouse to guidelines for processing psychotropic from nonpsychotropic products. Those considerations will be vital to your plans for scoping your facility as your business expands.

As we’ve seen, it’s an exciting time to be in the business of cannabis processing. Scaling up your facilities requires considerable upfront planning, taking into account not only your business goals and priorities, but how specifically you expect your organization to grow over the span of five or 10 years or more. By creating a strategic plan that takes into account state and municipal codes and the federal regulatory environment to come, you can be well on your way to developing a facility design that will scale to accommodate your needs as your business grows.

https://www.crbusa.com/cannabis-hemp-production

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=111

 is a senior project manager with CRB in Kansas City, Missouri. Direct correspondece to: 

This tutorial article outlines a holistic approach to scaling up.

Scaling Up Facilities for Hemp  and Cannabis Production:  An Engineering Primer

As the global hemp industry continues to mature, the rules and regulations that encompass the space are constantly evolving. Hemp businesses preparing for success and scaling for future growth have a variety of best practices to consider, but one set of regulations becoming increasingly important in the early stages is current good manufacturing practices (cGMPs or GMPs). GMPs are the rules and regulations that ensure the quality, safety, and efficacy of food or pharmaceutical products by addressing all aspects of the production process. GMP certification is becoming paramount for hemp extraction facilities looking to remain competitive and align with international industry standards. This column discusses some of the most important considerations involved in the GMP certification process.

With the passing of the 2018 U.S. Farm Bill, which allowed for the federal legalization of hemp production and interstate transport, consumer products containing hemp-derived compounds such as cannabidiol (CBD) have continued to expand in number and scope. CBD health, nutrition, and food products are readily accessible through a number of retail and online outlets and the variety and number of these products is continuing to increase (1,2). The use of hemp-derived compounds such as CBD will likely continue to expand into other markets. For instance, CBD usage is currently being evaluated for pharmaceutical applications (3–5), which will likely serve to increase the rigor at which producers of hemp and hemp-derived compounds manufacture their products. 

Manufacturers of hemp-derived products are evaluating quality certification programs such as current good manufacturing process (cGMP) manufacturing strategies to differentiate their products from competitors, enable the use of hemp raw materials in high quality or high margin products, and to access highly regulated industries like pharmaceutics. The use of cGMP manufacturing and subsequent certification programs such as the ISO 9000 and ISO 9001 series of standards allow raw materials and finished goods to be used in quality defined and controlled consumer and pharmaceutical products. 

As the boutique and industrial hemp production and extraction industries mature and expand into other applications, there has been a growing interest in cGMP certification for food grade processes. For example, cGMP principles have been applied to a number of hemp processes and products including:

A quick side note on good agricultural practices (GAP) versus GMP: GAP are the precursor to GMP. This will ensure the safe, hygienic, and quality production of the agricultural product (that is, propagation and cultivation) prior to manufacturing (6).

Messaging from the U.S. Food and Drug Administration (FDA) describes cGMP practices as, “providing for systems that assure the proper design, monitoring, and control of manufacturing processes and facilities” (7,8). To summarize statements made in the Code of Federal Regulations (CFR) 21 Parts 110 and 117, the FDA describes the content of a cGMP system in food grade manufacturing to include the following principles:

A review and qualifications of a cGMP system

The definition and applicability of a hazard analysis and risk-based evaluation strategies of manufacturing and production processes

Supply chain considerations from raw materials through finished goods and after-market monitoring

The establishment of defined and followed practices that lead to the production of a consistent product

Considerations in process and finished goods qualification and validation strategies, supported by rational characterization strategies

21 Part 117 may be concisely described as knowing what comprises your product, understanding your process and product, and knowing what process attributes define your product. Collectively, these concepts help owners and operators understand and control important aspects (often defined as key or critical process parameters) of product manufacturing and enable a quality evaluation and control strategy to minimize defects and variability in finished goods. The principles presented in the FDA and other expert documents on the topic of cGMP principles can best be described as general guidelines and typically include aspects of a cGMP system that are required for cGMP qualification, but do not explicitly lay out a cGMP plan for the hemp industry because every process is product-specific. 

The importance of defining roles, responsibilities, and lines of communications, as well as anticipated cGMP and certification milestones during initiation of facility development, cannot be overstated. A GMP consultant can be critical to success in obtaining cGMP certification for your facility. A list of activities critical to the successful build and launch of a cGMP manufacturing facility may look something like the following:

Identify manufacturing process flow, unit operation functionality, and product and human safety attributes

Conceptualize brick and mortar functionality, flow and governing cGMP requirements

Utilize risk-based tools including process hazards analyses (PHA), risk assessments (RA), design qualifications (DQ), and validation master planning (VMP) to pre-establish critical processes and facilities influencing design, construction, and qualification criteria

Integrate process, product, personnel, material, waste, and airflows predicated on identified risks corresponding to cGMP requirements and good industry practice

Initiate cGMP conforming design and installation for architectural, mechanical, electrical, and plumbing (MEP) systems directed at mitigation of product contamination and assurance of operational safety

Conduct qualification and validation demonstrating the concepts, criteria, and RA stated outcomes defined in master-planning

Build a structured quality management system (QMS) with the appropriate depth and scope required for anticipated certifications and TPP

Create protocols and standard operating procedures (SOPs) to support product manufacture and QMS needs using prequalified raw material vendors, build bill of materials (BOM)

Integrate analytical equipment required to support raw material testing, in process checks and finished product release testing

Establish an acceptable certificate of analysis that is supported by finished product critical quality attributes (CQAs) and anticipated market requirements

Staff with trained and qualified personnel, by function, capable of demonstrating operational proficiency within the prescribed regulated environment

Ultimately, the responsibility of understanding and integrating the above list of topics into a comprehensive manufacturing, quality management, and cGMP certification scheme (supported by a hemp-centric business model) is the responsibility of the facility owner or senior management. To facilitate this, process owners and senior management should enlist the help of a qualified support team to help lead facility design. This support team will likely involve the owner and their team of staff that will be overseeing or operating the facility, a GMP consultant to guide the owner through the cGMP requirements and certifications, and a design team consisting of an architect, qualification and validation engineers, and mechanical, electrical, and plumbing (MEP) engineers. It is incredibly important that this complete team of experts is engaged early and often-proper coordination is key to success.

The Architect’s Role in the Design of a cGMP Facility

Architects are professionally licensed and specialize in designing the architectural components of a facility. While there are architects with more cGMP experience than others, it is ultimately the owner’s responsibility to be sure that the architect is aware of the cGMP requirements that will fall under the architect’s scope. While the architect will not direct the cGMP requirements, it is important to collaborate with an architect with design expertise in cGMP facilities. Note that oftentimes, the architect may hold the contract for the entire engineering team as well, so it will be important to define all requirements for the entire design team. Though they will vary from project to project, a few simple examples of items that the GMP consultant and owner may need to define for the architecture team are discussed in more detail below.

Product Quality Attributes and Critical Process and Facility Parameters

In the design of a GMP facility, all attributes of design and installation are focused on the mitigation of product contamination, the conduct of robust and routine product manufacture, and the safety and efficiency of operations. The conduct of risk analyses drive key considerations, which must be outlined for the architect upfront, driving fundamental aspects of facility design to include airflows and pressurization schemes, materials of construction, and equipment requirements (explored further below). During validation master-planning, a predefined set of criteria will be established to demonstrate conformance with the cGMPs, many of which influence the basis of design and installation of equipment critical to the architect and MEP engineers, with the goal of ultimately establishing cGMP conformance.

Requirements for Easily Cleanable Walls, Floors, and Ceilings

This may include fiberglass reinforced plastic (FRP), stainless steel, or polyvinyl chloride (PVC) walls and ceilings; epoxied floors, and coved bases between the wall and floor to create an impervious seal between the intersection of these two surfaces, making them easier to clean and maintain. Note: pay special attention to static charge that may build on these surfaces in classified areas containing flammable or explosive materials and operations, and work with your architect to select the best materials to meet your needs. 

The owner will need to explain the personnel flow and gowning requirements of the facility so that the architect can take this into consideration when space planning.

Airlock or Vestibule Requirements Between Corridors and Process Rooms

These spaces are explained in more detail under the heating, ventilation, and air conditioning (HVAC) section below. The architect will need to know where airlocks are required so that they can factor them into space planning.

The Engineer’s Role in the Design of a cGMP Facility

MEP engineers are professionally licensed with expertise in designing a facility’s mechanical (HVAC), electrical, and plumbing systems. MEP systems are not the manufacturing process, they are the support systems that breathe life into the manufacturing process. As a very simple definition, these systems provide energy, create the environment within which the process lives, and remove waste. It’s important to recognize that while these engineers have deep expertise in their fields, the focus of their roles and expertise is not necessarily to direct the cGMP specifications, but to create systems that meet the requirements of your cGMP specifications. As mentioned previously, the owner is responsible for determining what standards the engineers should design to. A GMP consultant can assist with this process and communication. As is true for the architecture team, while the engineering team will not direct the cGMP requirements, it is important to work with an engineering team with design expertise in cGMP facilities. Though they will vary from project to project, a few simple examples of items that the GMP consultant and owner may need to define for the engineering team include the following items described below.

ISO classes of cleanroom vary from ISO 1 (extremely clean) to ISO 9 (clean) (see Table I). There are many requirements for each clean room class including air change rates, filter types, and filter coverage that will impact costs associated with each class. ISO 7 classification is often observed in hemp facilities, but it is the owner’s responsibility to determine the appropriate cleanroom class and convey the cleanroom class to their designers, based on information they have received from their GMP consultant. Designers can then meet the design requirements for the cleanroom class expected.

You will have specific equipment that you have selected for your process. It is important that your engineers receive this information prior to beginning their design, and that the information is complete and accurate. Inaccuracies will result in extra design time and money spent.

While the HVAC system can ensure that the temperature and humidity requirements are met, the engineering team expects that the owner will provide these requirements.

There may be other requirements specific to your process or facility. As an example, many facilities will opt to keep conduit and piping behind walls to make it easier to clean the wall surfaces in the facility. However, some clients need access to piping for experimental changes. In this case, you may direct your designer to design the piping and conduit so that it is exposed within the room, yet held off the wall so that you can easily clean behind and around the piping and conduit to maintain your cGMP facility requirements.

Your HVAC designer will be critical to the success of your cGMP facility. It is important to consider and keep in mind what your HVAC system can and cannot do (9).   

HVAC cannot clean the surfaces of a contaminated room or equipment. The SOPs defined by the owner should specifically cover cleaning protocols. HVAC cannot compensate for workers who do not follow procedures. Ensuring that staff is trained and following SOPs is critical to the success of your cGMP facility and is the owner’s responsibility. HVAC cannot be left unmaintained. If not maintained, the HVAC systems may not adequately meet your cGMP requirements.

HVAC can control airborne contaminants through proper air filtration. There are numerous levels of air filtration, generally stated on the minimum efficiency reporting value (MERV) measurement scale. In commercial applications, filtration will generally range from a typical MERV 8-such as what would normally be utilized in a basic residence-through MERV 20, which will meet the requirements of a cleanroom. High efficiency particulate air (HEPA) filters, which will remove 99.97% of particles whose diameter is greater than .3 Î¼m, fall into the range of MERV 17 through MERV 20. HEPA filters are generally utilized in cleanrooms, among other applications. The air filtration level needs to be considered when selecting the HVAC systems, as the higher the MERV rating, the more air restriction there will be, so the fans need to be sized to overcome this static pressure, both with an unloaded and loaded filter. Prefilters are generally utilized prior to the HEPA filters to capture the larger particles, so as to not unnecessarily load the HEPA filter. This allows the owner to change the prefilter often (which are generally a lower cost item than the HEPA filters), and the HEPA filter less often. Pressure gauges and simple alarms can be helpful in alerting the facility’s maintenance crew that the filters need to be changed. Changing the filters at regular intervals is critical in meeting cGMP because an overly loaded filter will affect particulate capture rates and air change rates within the room, potentially causing the facility to fall out of spec. 

HVAC can maintain room pressure differential requirements (delta P or ΔP). Proper air cascades are critical in ensuring that air flows from clean to dirty spaces, and not the other way around. Areas that must remain cleaner than surrounding areas must be kept under positive pressurization with respect to the surrounding area. This can be done in various ways. Oftentimes an airlock, sometimes referred to as a vestibule, is utilized in the entrance to the cleanroom. This is a separate room with one door opening into the main corridor and another into the cleanroom. The doors are controlled so that they cannot be opened at the same time (either by interlocks or simply by SOP). Fan filter units can be a low cost way to ensure that the pressure cascades between the main corridor, airlock, and clean room are appropriately maintained, and with the proper filtration to protect the cleanroom.

HVAC can maintain room temperature and humidity. Temperature and humidity are controlled via air handlers with cooling coils and reheat coils. There are other methods to control temperature and humidity, and your mechanical engineer can determine the best type of equipment for your application. Note that while your engineer can design and select the proper equipment to meet your temperature and humidity needs, it is the owner’s responsibility to determine the target temperature and humidity levels, as well as the acceptable range. This will vary depending on what the process needs are. Facility owners will often set a very tight temperature and humidity range. Be cautious: more stringent than required temperature and humidity requirements can result in your engineer selecting an expensive HVAC system to meet the requirements, oversizing your HVAC system, and resulting in higher than necessary utility costs to run the equipment. Be sure to select a reasonable temperature and humidity range for what your process requires.

For any project-but especially a cGMP facility­-it is incredibly important that the owner engage their internal team that will run the facility, a GMP consultant, architect, and engineering team early and often. Proper coordination is key to success. All team members must know their roles and responsibilities within the facility design process, and ultimately it is the owner’s responsibility to be sure that everything is covered in order to obtain and maintain the desired cGMP certifications.

https://www.wsj.com/articles/cloudy-regulation-slows-cbds-seep-into-food-and-drinks-11578574807

https://www.healthmj.com/cbd/hemp-cbd-bubble-prices-market-growth/.

https://www.europeanpharmaceuticalreview.com/article/96609/cannabinoids-in-pharma-series-cannabinoids-on-the-market-today

https://www.gwpharm.com/healthcare-professionals/research/cannabinoid-compounds

https://www.rhizosciences.com/gxp-good-cannabis-practices/gap-good-agricultural-practice/

U.S. Food and Drug Administration, Current Good Manufacturing Practices (CGMPs) for Food and Dietary Supplements, 

https://www.fda.gov/food/current-good-manufacturing-practices-cgmps-food-and-dietary-supplements

https://www.ecfr.gov/cgi-bin/text-idx?SID=3f7125891958b3eb9380856f26065b5c&mc=true&node=pt21.2.117&rgn=div5

HVAC Design for Pharmaceutical Facilities (Continuing Education and Development, Inc.

https://www.cedengineering.com/userfiles/HVAC%20Design%20for%20Pharmaceutical%20Facilities.pdf

https://www.mecart-cleanrooms.com/learning-center/cleanroom-classifications-iso-8-iso-7-iso-6-iso-5/

, is the founder and owner of Oregon-based firms Root Engineers and Cole-Breit Engineering. She is a professional mechanical engineer specializing in the design of HVAC, plumbing, and process systems for the cannabis industry. Since legalization in her home state of Oregon in 2014, Laura has led her team of mechanical and electrical engineers and designers on more than 100 cannabis-related projects across the country.

This column discusses some of the most important considerations involved in the GMP certification process.

Engineering Considerations for the cGMP Manufacture of Hemp and Hemp Products

An interview with Todd Bell about the experiments and findings his group is working on with controlled atmospheres in cannabis cultivation.

With the cannabis industry continuously expanding, new technologies and methods are coming forth to increase yields and production in cannabis cultivation. One such method involves using controlled atmospheres and low oxygen with the cannabis plant to increase yields and terpene levels. Here Todd Bell, Research & Development at Grow Controlled, LLC, goes into further detail regarding the experiments and findings his group is working on with controlled atmospheres.

March 2020 Digital Edition - Cannabis Science and Technology Vol. 3. No. 2

CSC East Postponed Amid COVID-19 Safety Precautions

Are There Limits to the Range of Possible Cannabinoid Ratios in Plants?

Cannabis Laboratory Testing Market in North America

Scaling Up Facilities for Hemp and Cannabis Production: An Engineering Primer

Engineering Considerations for the cGMP Manufacture of Hemp and Hemp Products

Low Oxygen: A New Method for Cannabis Cultivation

U.S. Cannabis Academic Programs: A Conversation with Two Universities Leading the Way

Back to the Root-The Role of Botany and Plant Physiology in Cannabis Testing, Part I: Understanding Mechanisms of Heavy Metal Uptake in Plants

How Standardized Sample Preparation Can Solve the Inter-Laboratory Variation Problem