Keeping track of all the biology, chemistry, and engineering used to determine how to produce safe foods, food additives, and botanically derived nutraceuticals can be a complete drain.

Here are 8 GMP Cannabis Safety Tips, that will keep a production environment cleaner, more efficient, and decrease risks of contamination:

Wash your Hands.

Washing your hands before and after handling cannabis, as well as between handling different batches of cannabis, is one of the best steps towards stopping cross contamination of finished product.  Establishing a formal hand washing policy is a great practice that shows commitment to hand hygiene in a production facility as well as protects employee health.

Monitor your Temperatures.

Cook cannabis infused cooking oils or baked goods to proper temperatures that kill bacteria, including Salmonella, Listeria, and the types of E. coli, that cause illness.  Record the temperature for each batch that is generated, then if there is a problem, there are batch records to research or investigate what went wrong and fix it.

Not only is monitoring temperature important for cannabis food products, it is essential for controlling extraction product quality.  Continuous monitoring of temperature during extraction and distillation processing will reduce the risk of the product forming undesirable impurities and cannabinoid breakdown products.

Separate Processed and Unprocessed Material.

Keep any pathogens that could be on unprocessed cannabis from spreading by establishing procedures that keep unprocessed and processed product separate.  Storage in completely different rooms is best for preventing cross contamination.

Be Proactive Against Contamination.

All employees should understand the concept of cross-contamination, it is everyone’s duty to prevent cross contamination within the working environment, and between the work floor and administrative/personnel areas.

Establish Equipment Sanitization Procedures. 

Keep product batches in different containers, and don’t use the same equipment to process them, unless the equipment is appropriately sanitized with an experimentally validated internal sanitization protocol in between processing of different batches.

Establish Work Surface Sanitization Procedures.

Countertops should be appropriately sanitized regularly in accordance with a validated procedure as well.

Say Yes to Environmental Pathogen Swab Tests.

Take proactive actions to monitor the environmental conditions of your production facility.  If a pathogen persists in the production environment, there is a much higher risk of the production area or line being contaminated with that microbial species.  In this instance, ignorance is not bliss.  There are many instances of the same strain found in an outbreak being isolated from high traffic areas within production environments.

Don’t Get Lazy With the Storage.

Store finished product in a cool and dry environment, with a stable and continuously monitored humidity level as soon as possible, post processing.  Remember, the less pathogenic cells present, the less chance they will make a consumer ill.  Proper storage conditions keep most types of bacteria from growing to numbers that can cause illness.

Product Uniformity is the Goal.

Implementing these 8 tips within your production setting will take time, but it is worth it.  Being proactive and diligent of recording important steps within the process places producers in a position of power within the entire process.  Instead of having things go wrong and having to spend precious time testing every single step of a production line, a manager can simply take a look at the batch records to gain clues that will help solve problems much faster.  This data can also assist in improving a process and finally, ensures that each batch is produced under the same conditions, resulting in product uniformity.

Contact Us.

Orion GMP Solutions is a Pharmaceutical Engineering Firm based out of Denver Colorado.  We specialize in the implementation and auditing cGMPs for GMP Cannabis Manufacturers.  If you would like to get more information, please send us an email at info@oriongmp.com.

This content was written and sponsored by Orion GMP Solutions.

Based on my lab experiences, I had an idea in mind for how I would purify CBD. Now it is time to put my ideas to the test!

Finding the Supplies

Having never done any chemistry outside of a university or industrial setting, I was completely unfamiliar with how to get supplies on my own. I was thinking of ordering solvents online, but by pure luck, I stumbled upon a vendor in downtown Ypsilanti, right off of Michigan Ave, while I was getting some takeout. Right as I was about to get in my car and drive home, I saw a storefront display with a bright blue solution in a beaker stirring. I was really curious, so I went inside to see what was going on. The store, ambiguously named Ypsilanti Oil Company, had a bunch of chemistry supplies and equiptment. Located across from the Ypsilanti Farmers Marketplace, they are an “Aromatherapy Service” company, the idea being that someone would buy herbs from the farmers market and then be able to get the supplies to go home and make their own extracts. I saw that they had hexanes, so I bought a one quart (946 mL) bottle for $42.40.

Excited about my spontaneous purchase and ready to try some things, I obtained 1 gram of a 70% CBD extract from a local “provisioning center” for $60, and ordered a 12 pack of 1 dram (3.7 mL) vials from Amazon for $7.

Step 1. Dissolve the CBD extract in hexanes

For a spatula, I used a knife from a pumpkin carving toolkit because it was narrow enough to fit into the CBD sample and also the vials.


  

I did not have a scale or syringes, but I would estimate that I dissolved approximately 200 mg of the CBD sample in 1.5-2 mL of hexanes. In other words, I filled the 1 dram vial half full with hexanes, and then added two “scoops” like the one shown above, which was about 1/5 of the 1g sample. I did not use any heat to dissolve the sample, just a bit of stirring for a few minutes with the knife, until the solution was homogenous and clear. I did notice that there were some “dirt” particles that did not dissolve, so if I were to do this again on a larger scale, I would probably add a filtration step before growing the crystals.

 

Step 2. Freeze Overnight

I put the vial, tightly capped, in my freezer overnight. 24 hours later, I found some clear crystals!

Step 3. Decant and Collect

I waited an additional 24 hours to see if I could get more crystal growth, but it looked about the same the next day. I then waited for the solution to warm up to ambient temperature and decanted off the excess solvent, leaving behind the crystal solids shown below. For the decanted liquid, or the mother liquor, I am evaporating to increase saturation and re-freezing to see if I can grow a second batch. I plan on testing the crystal samples along with the original one to determine the extent of purity improvement. Also, in the future, I will look into how to get the best yield and mass recovery.

Overall, I was able to grow some CBD crystals using only one solvent (hexanes) and without any heat.

Contact us at info@oriongmp.com to discuss how CannaChemist can help your organization refine chemistry processes.

CBDecomissioning THC

There are reported methods and patents for converting CBD into THC and for maximizing THC production, but what about the other way around? Could there be a way to convert psychoactive THC into non-psychoactive CBD?

Mechanisms for opening THC.

Looking at the structures of these cannabinoids, one can imagine a plausible mechanism to open up THC’s ether ring to the phenol of CBD. Fortunately, this kind of chemistry has been done before, and there are examples in the literature. Many molecules in nature have similar structures to THC and CBD because they are all part of a larger family of molecules called terpenoids, made from the same biochemical building blocks. So although the conversion of THC to CBD has not actually been reported, to my knowledge, there are conditions in the literature that are directly applicable to this transformation. Specifically, in 2012, the Baran synthesis group at the Scripps Research Institute in La Jolla, CA published a paper in JACS, where they synthesized diverse meroterpenoids from a boron-containing scaffold derived from sclareolide, a fragrant lactone found in sage. Their divergent and scalable synthesis allowed access to a wide variety of structures from nature, and also some synthetic analogues. Among the many reactions that they report, one of them is directly analogous to the conversion of THC to CBD: the conversion of chromazonarol to isozonarol.

Scaling up.

Usually, reactions done on a small scale (15 mg of starting material was used) are not directly applicable to an industrial scale without substantial effort. Since it was a final step, they did not need to optimize the reaction to be environmentally friendly or cost effective, as it was not a priority for the broad goals of this project. The conditions that they report (dichloromethane as solvent, -78 degree C temperature, BCl3 as a Lewis acid, 2,6-di-tert-butyl-4-methylpyridine as a bulky, more selective base), might not be directly scalable, especially for those with limited experience in synthetic chemistry.

Semisynthesis.

The field of natural product synthesis specializes in these types of transformations, to be able to convert one structure to another in order to access a natural product target either from simple commodity chemicals (total synthesis) or another natural product (semisynthesis). The conversion of THC to CBD would be classified as semisynthesis, since the starting material is another natural product – THC. Semisyntheses can have an advantage that the starting material is often similar in structure to the product, thus requiring fewer steps.  However, some molecular targets cannot easily be accessed by semisynthesis, but their unique structure can be made from scratch, essentially, using organic chemistry methods to construct the scaffolds from chemical feedstocks. Both total synthesis and semisynthesis are used industrially for different purposes, and both strategies incorporate the same organic chemistry principles when designing a route.

The thought process.

As an important and necessary part of synthesis, reaction conditions are optimized using small amounts before scaling up; hypothesis-driven trial-and-error, or in some cases, high-throughput screening can be used to develop a more robust and ideal process. All factors of this reaction have the potential to be changed: the solvent, the Lewis acid, and the base. I would recommend, first, for a chemist to do this reaction with THC, using the same scale, reagents, and conditions as those in the paper. This would require access to a fume hood, to avoid exposure to the toxic reagents. After getting a sense of this, for example find out: what is the yield of CBD? How much recovered THC? Is any of the tetra substituted olefin formed? Then, the reaction conditions can be altered (time, temperature, equivalents) to increase yield, and a different solvent, Lewis acid, or base can be swapped to reduce toxicity and cost. This reaction optimization process may sound complex, and will definitely not be an easy problem to solve, but I know from experience, from a chemistry standpoint, this problem is solvable. With careful observation, organic chemistry intuition, and perseverance, there is no reason we cannot develop a method for converting THC into CBD, essentially “de-commissioning” a Schedule I substance.

 

Contact Us. 

Orion GMP Solutions is a Pharmaceutical Process Engineering firm based out of Denver Colorado. We specialize in the implementation and auditing of GMP Cannabis Manufacturers to assist them in reaching international markets. If you would like to get more information, please send us an email at info@oriongmp.com

This content was written and supported by Orion GMP Solutions