GMP Training for Cannabis Manufacturing and Testing

GMP training is an important part of manufacturing and testing pharmaceutical products. It is the means of ensuring employees can properly perform their job to specified standards. Those standards ensure products are manufactured consistently, in a controlled manner, and to defined quality specifications. Training employees on a regular schedule, with job specific instruction, and thorough documentation help companies meet their standards of manufacturing and testing of their pharmaceutical products.

The first component to a quality training program is that training occurs on a recurring basis. When a new employee joins a company, it is necessary for them to learn, understand, and be tested on their job specific duties. After initial training they are qualified to do their job. They will then be required to perform refresher training that makes sure they are still up to date with any changes to the processes used for their job. For example, if a process is changed, the employee needs to have documented training on the change, proving they understand the change and can employ the process properly.

The second component to a quality training program is that the training covers the scope of an employee’s job. Each employee has their own specialized tasks in a manufacturing or testing facility, and they are responsible for knowing their job as it’s defined by the company. For example, a quality control chemist does not need to know the intricacies of a process chemist’s job, and vice versa. Each respective chemist needs to fully understand their own job so they can perform it up to the standards set in training.

Recurring training is a standard element of any quality process in the pharmaceutical industry. The proof of that training is in documentation. Documentation consumes a large amount of time in a quality manufacturing and testing environment. It is not fun and few people like it. It can take more time than the work itself. Still, without documentation, there is no proof of what has been done. It is important that companies have a documented training program that outlines each job in the company. Each job will have specific duties associated with it, and each duty requires training.

This article isn’t meant to touch on the qualifications of individuals bring to a job, but it grazes an interesting point. People who may not be qualified to start in a job can become qualified. An employee may not know how to operate a Gas Chromatography (GC) instrument when they start the job, but if they know how to operate an HPLC, there’s little reason why they can’t be trained to run a GC. On the job training (OJT) is a viable way to build up your employees’ capabilities and careers. When OJT is well documented, it’s the proof of a person’s education. It’s not only important to prove that your process is being executed by properly trained employees, but it’s also important to your employees’ careers.

If you have more questions, check out and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.

GMP Cannabis, THC, and CBD are on their way to the market. This is a fact. In order for labs to stay on top of the market, they must adapt to the practices of the pharmaceutical industry. This is a basic list of 10 things cannabis testing labs should already be doing.

  1. Thou shalt not perform analysis without proper training and understanding of the equipment. Qualifying a properly trained technician is dependent on the job they are doing. Have they been trained on the instrument? Have they taken sufficient analytical chemistry courses to understand how to interpret results? An analyst must know how to interpret the results, or figure out why the results they are get are inconsistent. If the results do not make sense, the analyst must troubleshoot the instrument based on what the data is telling them and then find out what went wrong. This type of critical and analytical thinking requires a thorough training program for all analysts.
  2. Thou shalt not perform laboratory analysis without Standard Operating Procedures (SOPs) that are followed exactly as they are written. This assumes that a laboratory has done a good job of writing their SOPs in the first place. SOPs define exactly how a test will be performed; this reduces any variation in process that could affect the results. SOPs also define the technique that an analyst should use – for example, are all analysts in the lab using the same mass or volume measurement techniques? If there is variance in the process, there will be variance in the results.
  3. Thou shalt not perform laboratory analysis using SOPs that have not been validated. In order to reduce variations in results, a method (e.g. the way you analyze your sample by HPLC) must produce the same results reliably. A validation is a set of experiments that is used to prove that the method does in fact produce the same results that are within the specifications of the desired method.
  4. Thou shalt not perform laboratory analysis without accurately weighing and measuring the samples. This also falls under the category of training, but is perhaps the most important factor in accurately and reliably analyzing samples. This is also the most difficult technique to master, because there are so many variables. The best way to accurately weigh and measure samples is to perform any weighing and measuring the same way every time it is done. Exactly the same way – no excuses. Everyone in the lab should also weigh and measure samples with the exact same technique. This reduces the amount of variability in results throughout the lab.
  5. Thou shalt not perform laboratory analysis without accurately documenting the results from weighing and measuring. This is self explanatory, but it may not be done this way in every lab. I have had the misfortune of seeing an analyst simply weigh out a sample, pour in ethanol up to an arbitrary line, shake it up, and inject the sample into an HPLC. He never recorded the weight of the sample or the volume of liquid that was added, and didn’t account for either of them… This kind of sloppiness is what makes labs untrustworthy.
  6. Thou shalt only use analytical reference standards (ARSs) that have been produced by an ISO accredited lab. Creating in-house reference standards is possible, but it is highly unlikely that your lab has the capabilities of qualifying them. An accredited ISO lab synthesizes THC/CBD/etc and has exact ways of measuring the quantities that are in their ARSs. If you have variability, or uncertainty, in the amounts of THC/CBD/etc in your ARSs, your analysis will not be accurate. Reliable ARSs are the backbone of good analysis.
  7. Thou shalt inject your ARS’s at a minimum of 5 times for any number of samples. This is how to determine if your instrument is working within its specifications/calibration, and includes the chromatography column and the instrument in general. If there is a poor Relative Standard Deviation (RSD), i.e. the 5 injections of the ARS are not within a specified percentage (think precision), the analysis of the samples is disregarded.
  8. Thou shalt calculate the Relative Standard Deviation of the 5 ARS injections. This is done by taking the average of the response factors for a given peak (e.g. THC), dividing it by the standard deviation, and multiplying by 100%. For a very tight group of data, an analyst with good preparation technique and a well calibrated instrument will pull 2% RSD. RSD is the means of showing just how precise your techniques and instruments are running, and is a very important tool for tracking the performance of your work.
  9. Thou shalt establish correction factors for different cannabinoids being analyzed. Not all cannabinoids will have the same response factor in the same chromatography instrument. This is particularly true for spectrophotometry (e.g. HPLC), that uses light to detect the presence of molecule. Since different molecules will absorb different amounts of light, the apparent amounts/concentrations will be thrown off if they are not corrected for.
  10. Thou shalt document everything. All analysis must be documented with the weight or measures of the samples that are used, and contain all data collected from each test. The records must contain the calculations used to draw conclusions, and must make a statement of the results. The test results must be compared to qualified reference standards that clearly show identity, strength/potency, quality, and purity of the drug product.

If you have any comments or questions, please post them in the comments section or email

The quality control practices your Cannabis Testing Laboratory doesn’t want you to ask about…

Running a pharmaceutical manufacturing operation requires planning, standardization, and structure. This article explains the basic operating parameters quality control (QC) lab in compliance with Good Manufacturing Practices as described in the 21 CFR 211 – i.e. the Code of Federal Regulations that govern the production of pharmaceutical products.

This article aims to describe the basic controls for running a quality control facility. The planning and standardization required is dependent on individual situations – types of samples, the source of the samples, and whether the is independent or part of manufacturing. This is a overview of the guidelines, not an executable process. An executable process can be developed with the help of a consultant. If you need an experienced GMP consultant, you’ve come to the right place. Without one, you will very likely waste a significant amount of time and money trying to implement GMPs.

Quality Assurance (QA) and Quality Control (QC)

Any pharmaceutical manufacturing operation is centered around QA and QC. QA is the department responsible for reviewing the testing process after it is completed. They are to review the all records associated testing, and store them. QA coordinates all maintenance and calibration activities of equipment, and ensures that all QC systems are in accordance with GMPs as defined by the company’s SOPs.

The QC unit is responsible for approving or rejecting any pharmaceutical product. QC reviews production records to ensure that no mistakes were made during manufacturing, and if errors were made, that they were properly investigated and corrected. All procedures pertaining to the QC unit are to be in writing and followed as written. All QC personnel are to be trained in current GMP regulations (cGMP’s) as applicable to the employee’s job. QC personnel training must be administered by qualified individuals on an on-going basis.

Laboratory controls and general requirements

Step 1 is having a quality control manager (QCM). The QCM is the person who manages the operations of a testing laboratory. They are the person who establishes all specifications, standards, and testing procedures. They ensure all standards are followed and documented. If there is a deviation from the standards, they are required to document and justify why the deviation occurred and determine if the deviation affects the quality of the product.

All the specifications, standards, and testing procedures must be scientifically sound. They must be based on experiments that prove the tests accurately determine the identity, strength, quality, and purity of the product. All the tests must be fully documented and executed according to procedure.

The tests must show that samples conform to the defined written specifications of identity, strength, quality, and purity. During testing, all samples need to be properly labeled and describe the sampling and testing procedures used to determine conformity to the standards. If the samples do not pass testing standards, they must be rejected for use. Samples may be retested, but they must pass all testing standards.

All equipment must be calibrated at suitable intervals and a service history must be maintained for each instrument. A written program for equipment calibration will be maintained and executed that contains specific instructions for maintenance schedules, limits for instrument accuracy and precision, and directions for action if specifications are not met. Any instrument that does not meet established written specifications will not be used for testing.

Testing and releasing samples as safe for consumption

Each set of samples that arrives in the laboratory should be assigned a batch number. If the QC unit is in the same company as manufacturing, the batch number should be known from the point the seeds or clones are first planted, and traced all the way through final testing, packaging, and distribution. Traceability is very important in quality control, and everything must be documented along the way.

For each batch of drug product, the specification criteria must be met to determine that batch conforms the product specifications – i.e. that testing proves the proper identity, strength, quality, and purity of each active ingredient. All testing performed for identity, strength, quality, and purity will be described in written procedures (test plans). All test plans must be established, validated, and documented to prove accuracy, sensitivity, specificity, and reproducibility.

The testing will define how many samples need to be taken in proportion to the size of the batch. The testing must be sufficient to prove appropriate specifications for approval and release from testing. In addition to the standard testing, all batches must pass sterility testing that proves it to be free of microbiological contamination. Any batches that fail to meet the specifications and criteria must be rejected as not safe for consumption. Retesting may be performed, but the samples of the drug product must meet all specifications and criteria.

Stability testing and establishing shelf life

Stability testing is used to determine the expected shelf life of a drug product. This is a tricky subject for the marijuana industry at the moment. Over time, THC degrades to CBN. This means that one of the active ingredients is no longer working at full efficacy for a given product. This changes from strain to strain, and the type of product – e.g. flowers or extracts. That said, this will be a challenge for many companies to implement, but is in fact the direction the industry must go towards to move up to the standards of the FDA.

Stability testing is similar to the testing used to release a drug product as safe for consumption. The difference is that stability testing uses stored samples of approved batches, and tests them periodically to find the rate of degradation.

Stability testing is a separate written program from testing. In addition to regular testing, it defines the sample size and testing intervals, storage conditions, validated test plans, and testing the sample in the same containers used as received by consumers. The testing must be performed on multiple batches (of the same strain) in order to determine an appropriate expiration date. Accelerated degradation studies (e.g. higher temperature and humidity conditions) can be performed in order to extend the expiration dates.

Testing and approval (or rejection) of drug products

This pertains to the process of testing. It is the control of the samples during testing, and is used to make sure there are no mix-ups in samples or results. The samples must be placed in an appropriate container that is labeled and has associated test plans that follow along with it through the process.

The identity and quantity of each sample will be placed on a label of the container for each batch that is being tested. The label should include the name of the supplier, batch number, and the location of manufacturing. Records must be kept that show the results of each test and be maintained for a period of time after the expiration.

When a sample or set of samples pass testing, they may be released for consumption. If any of the tests do not pass, the batch is rejected. If a batch is rejected, an investigation is performed to determine the root cause of the failure. The approval process is completed when the QCM signs off on all test plans and the specification summary sheet for a particular batch.

Laboratory records and reports

Laboratory records are exceptionally important to QC testing. It is the documentation that proves a product is safe for human consumption. The QA and QC divisions are the the checks and balances of the pharmaceutical industry. The QA division gives all final approvals for releasing drug products after reviewing completed testing from an entire batch, and maintains all documentation of records and completed testing.

There are several requirements for laboratory records. The must describe the sample, its source, the quantity, batch number, date of sampling, and date of testing. A statement of results for each test plan must be tabulated in a specification summary sheet; it should indicate the location of testing and all the methods. The methods, as mentioned before must meet the standards of accuracy and reliability established by the QC division.

The test plans must document the weight or measures of the samples that are used, and will contain all data collected from each test. The records must contain the calculations used to draw conclusions, and must make a statement of the results. The test results must be compared to qualified reference standards that clearly show identity, strength/potency, quality, and purity of the drug product.

Each step of the test plan must be initialed and dated by the QC analyst (QCA) to ensure that each step of the test plan was performed without deviation. All test plans must be checked for accuracy by a second QCA or QCM. Any changes to a test plan must include a reason for the change, and be approved by the QCM.

Current Good Manufacturing Practices (cGMPs) is the pharmaceutical industry’s term for summarizing all the practices involved in manufacturing drugs that are safe for human consumption. The sum of the practices are called “quality systems.” It’s not just the pharmaceutical industry that uses cGMPs – the food industry does as well. cGMPs is a new concept to the marijuana industry, but there are a few companies that have already embraced it. The most prominent one that comes to mind is APHRIA, hailing from the breadbasket of Canada, in Southern Ontario.

Early adaptation to cGMPs are important to the industry. When medical and recreational cannabis become federally regulated and legalized, cGMPs will be required to ensure product and consumer safety. The evolution of GMP had good reason behind it – people were dying as a result of bad manufacturing practices. On average, the industry has more people hurting themselves while attempting to manufacture drug products, rather than consuming them. This, however, does not mean that the products are all safe for human consumption. The companies that take the time to implement cGMPs from the beginning of their business will have a drastic advantage over those that try to retool their process and standard operating procedures (SOPs). The benefits of GMP go beyond the minimum requirement of having a safe to consume product – it also builds the reputation of your company’s brand and its image.

GMP and ISO are both quality systems that are used to manufacture goods under specifications that either ensure consumer safety, or exact specifications guaranteed to be true. The difference is that GMP is a federal requirement for a drug product, whereas ISO is a voluntary certification. For example, a company manufacturing marijuana and concentrates will need to be a GMP facility in the future, whereas a marijuana testing facility would only need to be a ISO certified lab since they are only testing marijuana.

GMP Cannabis is the future of the industry. The early adopters of the practices employed by the pharmaceutical industry will be ahead of the regulatory curve and be best positioned for success in the market.

If you have more questions, check out and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.


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The quality control practices your Cannabis Testing Laboratory doesn’t want you to ask about…

This question was asked in the comments section in cannabis extracts in Reddit – how do you produce pure Δ9 THC that’s appearing in dispensaries??? A fellow named Adam Mueller answered this question, and figured out the sub/supercritical conditions to produce pure Δ9 THC and was issued a patent for it last year.

It is also possible to extract and purify THC to a high concentration using other methods. However, they mostly use solvents that are known to be carcinogenic. CO2, on the other hand, defines a “Green Solvent” – no carcinogenicity, and no waste products that pollute the environment.

Patent: US 2014/0248379 – Process for producing an extract containing THC and CBD from cannabis plant material, and cannabis extracts.

Adam Mueller has several patents describing the extraction of cannabinoids from hemp and drug varieties of cannabis. He represents Delta-9-Pharma GmbH, a company out of Germany. While this information may not be novel to people who are already performing extracts, it is of interest to people who would like to learn about the conditions.

This patent explains the steps from taken from grinding up plant matter, subjecting it to subcritical or supercritical conditions and producing a pure CBD and THC product. An interesting point is that CBD can be converted to THC with the right conditions. Past that, the product is dewaxed and ready for delivery in the activated decarboxylated form.

There are some aspects of the patent that are very useful, but there are downsides to running supercritical CO2, given what we know about the “entourage effect” described by Ethan Russo (1). Cannabinoids alone do not have the highest medicinal benefits as a mixture terpenes and cannabinoids. While this patent describes a way to obtain highly purified CBD and THC, the terpenes end up in a separate fraction. Recombining THC, CBD, and terpenes is not unheard of, but it does require a bit more work.

Raw materials

Mueller’s primary source of raw materials is hemp. This is a logical starting material for countries where it is illegal to cultivate marijuana. For the validation of the patent, he used five different strains that are from French, Hungarian, and Finnish origins. In general, these are industrial hemp varieties that are used for fiber production. The legal requirements for such strains are that they contain no more than 0.3% THC by dried weight of the starting materials.

Sub/Supercritical conditions

Mueller provides a range of conditions that can be used to extract cannabinoids with supercritical CO2. Supercritical conditions range from 31-80℃ and 75-500 bar. Subcritical conditions range from 20-30℃ and 100-350 bar.

Subcritical and supercritical extracts do not come out with the same consistencies. Subcritical extractions preserve more terpenes, while supercritical extractions lose terpenes and increase the waxes. Subcritical extracts have an oil like consistency, have less plant lipids (waxes), and may not need dewaxing, depending on the application and what customers want – it is nearly ready for use in vape pens or to be dabbed. Supercritical extracts have a more solid “crumble” consistency, have more plant lipids, and most certainly require dewaxing in order to be used in vape pens or dabs. Both can be used for edibles.

A follow up point is that both subcritical and supercritical runs can be done on the same starting material. First perform a subcritical run and collect the extract – the extract will still have some terpenes present without being overwhelmed with waxes. Then, the same starting material can be run a second time under supercritical conditions. Running subcritical conditions produces relatively low yields, so to maximize yield (i.e. profitability) one really needs to run supercritical conditions. You may find the extra work of doing two runs is not worthwhile, considering you have to have to do twice the work. There’s always a trade-off somewhere in a process, and this one is for you to decide. For maximum yield, Mueller suggests performing two runs on the same material.

Mueller increases yields by using “entraining agents.” Butane, propane, and ethanol are used in concentrations of 1-10%.

Entraining agents have different properties than supercritical CO2. The critical point (CP) of CO2 is 73.8 bar and 31.5℃; butane has a CP of 38.0 bar and 152 (2); propane’s CP is 42.5 bar and 96.7C (3); ethanol’s CP is 63 bar and 241. A mathematical description requires computational chemistry to show how the entraining agents interact with the CO2. Suffice it to say, CO2 will be in the supercritical phase and the entraining agents will be in the liquid phase (3), (4). This changes the solvent characteristics of the CO2 and improves extraction yields.

His optimal supercritical conditions range from 45-65, 100-350 bar, with his best conditions being 60C and 250 bar. His preferred subcritical conditions range from 20-30 and 100-350 bar.

Mueller illustrates the system in figures 1-3. It’s a complicated system that is appropriately named a “CO2 extraction plant.” This system was designed for process scale. The system has three components: the extraction system (figure 1), the CBD cyclization system (figure 2), and the CBD/THC separation system (figure 3).

How CO2  supercritical work – solubility

Figure 1

The extraction starts in the extraction vessel (F1: 1-4). The column(s) is packed with plant material, and the sub/supercritical CO2 begins to strip the plant material of cannabinoids. The cannabinoids are called the solute, and the CO2 is called the solvent. A solvent becomes saturated when it has no more “room” for more solutes to be carried by the solvent.

The cannabinoid saturated solvent then passes into the separating vessels (F1: 5a-5b) in a continuous process. Fresh solvent enters the extraction vessel, dissolves cannabinoids and other phytochemicals, and carries them into the separating vessels. The cannabinoids are the first solutes to pass through the separating vessels, followed by terpenes, and then the undesirable phytochemicals.

The order of the solutes entering the separating vessel (packed with adsorbents) is dependent on how strong of an interaction each molecule has with the adsorbent media. Cannabinoids have the weakest interaction (first out) and the undesirable phytochemicals have the strongest (last out).

The solubility of the different solutes in the solvent depends on both pressure (P) and temperature (T). The general scheme of the system is to go from high P to low P, and high T to low T, in graduated steps. At high P and T have the highest solubility.

As the P and T are reduced, the solubility of certain components is reduced. For example, the extraction vessels and separating vessels run at 60℃ and 250 bar. The terpene/cannabinoid rich solvent is then pumped over to the first collection vessel (10), at 45℃ and 60-75 bar. That reduction in P and T causes the terpenes to fall out of solution. Meanwhile, the cannabinoids are still in solution.

The cannabinoids are then pumped to the next collection vessel (14). T and P are reduced to 20℃ and 50 bar. Under these conditions, the cannabinoids fall out of solution, and are ready for collection.

Dewaxing and decarboxylation

Dewaxing is pretty standard in the industry these days. Unless you run very cold conditions, you’re going to pick up wax in both hydrocarbon and CO2 extractions. To put it simply, cold ethanol is used to dissolve the extract, followed by freezing and filtration. The extract can then be moved on to decarboxylation, which is a well documented process in the industry.

Converting CBD to THC

Figure 2

The second admirable part of this patent is the cyclization reaction of CBD to THC. Molecular/zeolytic sieves and zinc chloride are employed as a catalyst to aid the reaction. The molecular sieves act as a water binding agent, and the zinc chloride acts as a catalyst to reduce the activation energy required for the cyclization reaction.

The conditions are 300 bar and 70℃, and the reaction takes place over a 2 hour time period. The apparatus in figure 2 shows a simple reaction vessel containing the catalysts and extract that are plumbed to a separate collection vessel. The extract is pumped out to the collection vessel by precipitation with 55 bar and 25℃.

CBD THC reaction


Figure 3

The final step described in the patent is the separation of CBD, ΔTHC, and ΔTHC. This is achieved by using a purification material/media commonly used in separation science – silica. As is described below in the chromatography, silica has a charge to it, that reacts with the molecules that are to be separated/purified from one another. Some molecules have a stronger interaction than others and therefore travel slower through the silica packed column. In this case, Mueller ends up with pure fractions of the three cannabinoids.

The silica used in the patent has an average size of 0.1mm, and is commonly used in separation science. Looking at figure 3, you will see that the CBD/THC mixture starts at the bottom of the column. When the supercritical CO2 is pumped into the system, the mixture travels up the column and begins to separate the mixture.

After the separation column, there are three collection vessels. As with the initial extraction, CBD, ΔTHC, and ΔTHC are separated out by precipitation. The precipitation occurs from dropping the P and T in steps from high to low. CBD is precipitated at 70 bar and 50℃. ΔTHC is precipitated at 60 bar and 30℃, and ΔTHC is precipitated at 55 bar and 25℃.

Separation of plant phytochemicals, terpenes, and cannabinoids

The  first step in this patent produces pure THC/CBD while removing the plant alkaloids, flavonoids, and chlorophyll. It also removes terpenes.

Without good separation/purification, the terpene fraction can be contaminated with plant alkaloids, flavonoids, and chlorophyll. This is one of the inherent downsides to CO2 extractions compared to butane extractions; phytochemical contamination can be reduced in butane extractions by keeping conditions at sub-zero temperatures. In CO2 extractions, it can be reduced by not cranking the extractor into “hyperdrive” conditions.

Although the loss of terpenes is an inherent problem with supercritical CO2, it’s easiest to preserve terpenes by performing a subcritical run followed by supercritical run. This maximizes the yields, but is not explicitly described as the method used in this patent – it only suggests that the materials are extracted a second time.


The use of adsorbents is illustrated by way of a packed column in figure 1. An adsorbent is a substance that attracts molecules, and the molecules subsequently adhere to the surface. Note that this is not the same as absorbing, where a molecule is taken into the structure of the substance. An adsorbant has a transient interaction with the molecules it attracts, where the molecules stay on the surface. An absorbant actually soaks up a molecule into its pores, rather than just staying on the surface.

Adsorbents are used in this patent to remove undesirable molecules, such as alkaloids, flavonoids, and chlorophyll. The adsorbents attract undesirable molecules. They adhere to the surface under sub and supercritical conditions, temporarily falling out of the supercritical solution, while the terpenes and cannabinoids stay in solution and pass on to the next section of the system. It is a clever way to remove the undesirables, but is relatively common in separations science.

The adsorbents are silica gel, diatomaceous earth, bentonite, bleaching earth, activated carbon, and mixtures of magnesium oxide and alumina zeolitic. Although it’s not explicitly said, there are two ways that the adsorbents can be used. First, you can pack the plant matter on top of a bed of adsorbents. The second method is to have secondary column in-line, downstream of the extraction chamber, that pulls out all undesirables. The second is much more clean and efficient, but requires additional equipment, and at these kinds of pressure ratings, stainless steel is not cheap.


A more subtle point, that may not be immediately apparent, is the application of chromatography. Chromatography is loosely defined as the separation of mixtures. In this case, the mixture to be separated is the undesirable plant phytochemicals and the desirable terpenes/cannabinoids. The main function of chromatography media (i.e. adsorbents and silica) is to allow some molecules to travel through the media faster than others.

When a molecule has a strong interaction with the chromatography/purification media, it travels slower. When a molecule has a weak interaction, or is repelled by the media, it travels faster. Imagine each phytochemical being a molecular magnet. For example THC and CBD are very weak magnets compared to alkaloids, flavonoids, and chlorophyll. In fact, the undesirable molecules are like strong magnets.

The way this works, is that the adsorbents are also like strong magnets, but have the opposite charge of the undesirable phytochemicals. Opposites attract, and the undesirable phytochemicals are strongly attracted to the adsorbent, while the desireable terpenes and cannabinoids have a weak attraction to the adsorbent. The weaker the interaction, the faster the molecules can travel through the media, and vice versa.

Extraction, purification, and resolution in supercritical extractions

Extraction is the first step in any purification scheme. The industry is currently focusing on whole plant extracts, without much purification beyond dewaxing. This patent utilizes purification in the process – this is how CBD, ΔTHC, and ΔTHC are separated from each other.

As described above, chromatography is the mechanism of separating molecules. This can be done by columns packed with silica, and other packing materials. In chemistry, the packing materials are called purification media. Whatever packing material is used, the purpose is to slow down some of the molecules in order to separate the ones you want from the ones you don’t want.

You can’t talk about chromatography without talking about resolution. Resolution can be simply defined as the amount of separation of two molecules in a purification process. Depending on what kind of packing materials used, you can separate groups of molecules from one another. Some packing materials work better for some types of molecules, and is a chore to find the right media when starting a new purification scheme.

When you put together the extraction step and follow it with purification steps, you can separate groups of molecules. The choice of using purification is one that is dependent on whether one wants a pure product.

The end product

One really needs to ask themselves how important purity is. The more pure of a product desired, the more effort that is required. Do you really want pure crystalline THC and CBD? If yes, this process may be right for you. If you just want an extract, you may want to consider these steps, but take what information is useful to you.

Again, a process is only useful if it is economically viable. The extra effort spent in making pure products is significant, but is a daily reality in the pharmaceutical industry. A point to consider is that the closer you get to a pure product, the higher the chance of losing your product due to mistakes.

Having spent years in chemical purifications, plenty of solvent and product have been lost to simple, avoidable mistakes. To avoid mistakes, clearly define your process before you begin. Always have a plan and think about what you’re going to do before you execute the plan. Be careful, take your time, take good notes, and always keep the safety of the consumer as your top priority.


In 2007, a patent was filed for delta-9 THC processing. It covered a range of organic solvents with boiling points preferably below 0C – ie “low boiling point solvents.” This fits the description of several hydrocarbons – the author preferred isobutylene, propane, butane, and cyclobutane.

This patent was validated with very pure THC – from 95-99% – nearly reagent grade. So while it validates the situation in under perfect laboratory conditions, it does not reflect the true extraction conditions that happen every day for medical and recreational extractions.

The important points of this patent are the temperatures. The desired solvent exists as a gas at room temperature, but can be in the liquid phase when put under pressure and temperature constraints. Controlled temperatures not only dictate the phase of the hydrocarbons (i.e. gas or liquid), but also prevent degradation of cannabinoids, preserve terpenes, and reduce solubility of plant lipids.

Some side notes on the choice of solvents were low toxicity, low environmental impact, and generally recognized as safe for use in pharmaceutical applications. These factors combined are some of the reason for using propane and butane as the industry standard for cannabis extractions.

That covers the theory behind the process. Below you’ll find a few points on the methods that make this a very good process.

Assuming one has an understanding of the standard closed loop extraction process, you can imagine how this process goes. You’ve passed your butane/propane through the extraction column and the extract is sitting in the collection vessel.

It does not specifically say in the patent, but there are two ways this could go. The first option is that the butane is boiled off (reclaimed) to a certain percentage, and then transferred to a secondary container. The second is that the butane is allowed to boil off without care for reclaiming. I find the second option less likely, but it is a possibility.

Assuming the first option, the partially purged extract is transferred to a second collection chamber while it is still of high enough viscosity. This process is called a cannula transfer. The second collection vessel is where there are inert conditions, and the butane/propane is evaporated off.

Solvent is evaporated by increasing the temperature of the second collection vessel and passing inert gas over the surface of the extract – in this case, I’m almost sure the author used a side-arm round bottom flask. I’ve covered the value of inert gasses in a few of my posts at Hemphacker, but it is definitely a standard operating procedure in a chemistry laboratory. In this case, they use argon gas to assist the removal of butane from the extract.

Using inert gas helps remove the solvent by changing the dynamics of partial pressures at the surface of the solution – this is a long topic and out of the scope of this article. However, the change in partial pressure increases the rate of evaporation for butane and allows one to to reduce the temperature to 4C, from what would normally be done at much higher purging temperatures. Now we’re in terpene preservation territory.

The low temperatures are beneficial because it reduces the degradation of the cannabinoids, and also keeps the terpenes in a low-volatility condition. In addition, the author claims that these temperatures make it easier to handle the extract.

As a result of evaporating off propane/butane at a lower temperature, the author claims that the invention induces a more crystalline form of the extract rather than the formation of a homogenous solid. I would hypothesize that the slow cool temperatures allow crystal formation, in what is a more gentle process that does not disrupt the nucleation of seed crystals. They claim to have shown this by x-ray diffraction, but no data is given to supplement the claim. Still, the extract is not 100% crystalline, as claimed by the author; as an analogy, think of how some parts of an extract will auto-butter before others.

One point to keep in mind is that this is a pure starting material, for the sake of explaining the invention of the process. By experience, a chemist performing extractions knows that the results vary by strain to strain, because of the different distribution of cannabinoids and terpenes.

This is a fundamental patent to understand the origins of live resin extractions. This author has several more patents on the subject, but I chose to write about this one because it was the “first mover.” The cannabis community owes much thanks to pioneers in science, who laid the way for us to preserve the ultimate essence of the plant.
I hope that you all find this interesting. Please share your thoughts and comments!

When the extractor has been properly shut down, it’s time to disassemble it and reveal the cannabinoid alchemy you’ve performed, turning solid green plant matter into a concentrated liquid gold $)

Final image - Shut down

Step 7 – Extractor Disassembly – remove stainless steel hose (D) from extractor column valve (1)
Component #Component NameAbbreviationOpen/OnClosed/Off
1Extraction Column ValveECVx
2Low Pressure Recovery ManifoldRM2x
3High Pressure Recovery ManifoldRM3x
4Purge PortPPx
5Recovery CylinderRCx
6Vacuum PumpVPx
7Recovery PumpRPx
Step 7.1 – Extractor Disassembly – open extractor column valve (1) to allow air to enter extractor
Component #Component NameAbbreviationOpen/OnClosed/Off
1Extraction Column ValveECVx
2Low Pressure Recovery ManifoldRM2x
3High Pressure Recovery ManifoldRM3x
4Purge PortPPx
5Recovery CylinderRCx
6Vacuum PumpVPx
7Recovery PumpRPx
Step 7.2 – Extractor Disassembly – remove extraction column (11)
Component #Component NameAbbreviationOpen/OnClosed/Off
1Extraction Column ValveECVx
2Low Pressure Recovery ManifoldRM2x
3High Pressure Recovery ManifoldRM3x
4Purge PortPPx
5Recovery CylinderRCx
6Vacuum PumpVPx
7Recovery PumpRPx
Step 7.3 – Extractor Disassembly – remove extractor base from extractor collection vessel (12)
Component #Component NameAbbreviationOpen/OnClosed/Off
1Extraction Column ValveECVx
2Low Pressure Recovery ManifoldRM2x
3High Pressure Recovery ManifoldRM3x
4Purge PortPPx
5Recovery CylinderRCx
6Vacuum PumpVPx
7Recovery PumpRPx


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