Manufacturing cannabis is difficult enough. Manufacturing Medicinal GMP Cannabis is working a whole different level. It is bringing the industry standard to the level of pharmaceutical grade cannabis. Although this press release was in June, it went largely unrecognized despite its significance.
ICH Guidelines are particularly relevant for GMP Cannabis Manufacturing, because ICH recognizes that some APIs are derived from botanical substances. This is the case for a company like MedReleaf, that is manufacturing GMP Cannabis flowers and consumable products to the specifications of Health Canada Good Production Practices (GPPs). However, MedReleaf is applying ICH principles, suggesting that they are treating all aspects of their manufacturing to the ICH GMP guidelines.
Significance of manufacturing GMP Cannabis under ICH GMP Guidelines.
This is a very important step towards the legitimization of Medicinal GMP Cannabis Manufacturing, and the ability to export into international markets. Right now, Canada is poised to be the world supplier of GMP Cannabis, that meets the strict requirements of countries like Chile, Germany, and Australia, to name a few.
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 firstname.lastname@example.org.
This short article describes the theory and basics of Cannabis Chromatography. CannaChemist has spent quite a bit of time patiently waiting for molecules to separate in chromatography columns used to purify organically synthesised columns, and shares her knowledge here to help you resolve products like THC from CBD rich tinctures.
Chromatography, or “color writing” is a reliable purification and analytical technique that has been used for over a century. In 1897, the American chemist David Talbot Day observed that crude oil turned into bands of color as it seeped upwards through clay. In 1900, the Russian-Italian chemist Mikhail Tsvete used chromatography for the separation of plant pigments such as chlorophyll (green), carotenes (orange), and xanthophylls (yellow). Chromatographic techniques continued to advance substantially, gaining widespread use and winning the 1952 Nobel Prize in Chemistry. Today, there are countless variations of chromatography and even automated instruments that are used by scientists around the world, making all kinds of research more efficient than ever.
It’s all about sand… Silicon Dioxide.
Chromatography is a way of separating and purifying all chemical compounds, not just colors, taking advantage of their differences in properties. More specifically liquid, column, or flash chromatography is a practical and straightforward way to purify a substance from a complex mixture (a natural extract or chemical reaction) by passing it through an inert solid called silica, or silicon dioxide. The different compounds in the mixture will have different degrees of attraction, or stickiness, to the silica, and will pass through it at different rates.
Silicon dioxide, a major constituent of sand, is a network of silicon oxygen bonds. The less polar, or more oily compounds will have less attraction to the polar silica, and come off of the column first. If you had a mixture of THC and CBD, the THC would elute first, since it contains only one alcohol functional group instead of the more polar CBD, which contains two. During this process, the compounds and the silica are dissolved in solvents such as pentane and ethyl acetate. The ratio of ethyl acetate to pentane is increased during the column to elute compounds of increasing polarity. However, this practice can be problematic for greasy nonpolar compounds such as terpenes, and even cannabinoids. If there is not enough attraction between the molecules and the silica, they will all travel quite quickly and elute together, not achieving a good separation.
Reversed Phase Chromatography.
Another form of chromatography, called reversed phase, can be used for these instances. A special hydrocarbon-coated silica is used, which reverses the elution order. Polar solvents such as water and acetonitrile (an organic solvent) are used. The ratio of acetonitrile to water is gradually increased during the run to draw the nonpolar compounds through the stationary phase. THC has greater attraction to the hydrophobic stationary phase, so CBD travels more quickly. If you are looking to remove lesser amounts of THC from a predominantly-CBD sample, reversed phase chromatography, although more expensive than untreated silica, is an ideal technique.
If you’re interested in learning more about chromatography and separating cannabinoids, send us an email at email@example.com.
Orion GMP Solutions and Hemp Hacker are very proud to establish a working relationship with Medicine Man Technologies. Medicine Man Technologies is a quality manufacturing consulting group that specializes in assisting its clients become legal and compliant manufacturers of GMP Cannabis.
When we don’t have an answer, we know where to send you.
“Consider the present alternative, which is, we continue ignoring the significant benefits of cannabis, and refuse to contemplate the areas where traditional medicine is ineffectively managing critical conditions. We must provide a united front in advocating for medicinal cannabis as an innovative solution and a way forward within the realms of modern medicine by challenging and dispelling the myths and attitudes associated with cannabis, and sharing what we have recognized as the beneficial attributes associated with this plant”
Our commitment is to put the focus back on patients. Leah’s motivation regarding the emerging medicinal cannabis industry is to “challenge stigmas that have been propagated by judgmental perspectives of society related to negative stereotypical views, of which do not reflect the reality of the people we care for.”
Philosophy of Empathy and Compassion:
“Those who work within the medical and caregiving communities generally enter the health profession because of a belief in the alleviation of suffering for humanity. We aim to speak with empathy and compassion from the perspective of those who deserve to live a life free of suffering. Let us advocate for more empathetic approaches that will benefit our population, alleviate suffering, and maximize dignity, value, and quality of life. It is our responsibility to benefit our people, and to provide them with answers to identified problems and conditions, even and especially when these conditions do not respond to available medicine or practices.”Bisiani’s work is in “innovative approaches, thinking outside the box, and creating change, through the courage of our convictions. Actually, what I truly believe is there is no box,” says Bisiani.
Education is crucial:
Bisiani characterizes the situation well: “It’s real, it’s positive, it’s logical, and it’s humane. All change takes time, because making dreams a reality and anything worth fighting for, requires effort. Let us continue encouraging a solid and robust duty of care, that should be, at the very least, a baseline expectation within our medical community. We are creating a framework that enables current information for prescribers, patients, and society. We can reverse the stigma, and make it clear we are advocating exclusively for medicine through clinical based research, providing data and evidence for medicinal cannabis as a therapeutic alternative to non-effective regimes. Once provided, there will be a responsibility to honor these results or else be accused of denying assistance and permitting ongoing suffering and anguish. A multidisciplinary approach is required to enable an overall treatment plan to compliment the use of medical cannabis. Considerations of age, nutrition, environmental factors, lifestyle, can all be adjusted to maximize life quality first and foremost. Balance is what we aim for.”
The current landscape of pain in aged care:
“Pain is a fundamental and universal human experience, and thus access to effective pain relief should be regarded as an essential and universal human right. With the influx of baby boomers into the aged care community and an increase in life expectancy of our population, there is a growing need for more effective pain management regimes. Opioid analgesics are widely prescribed currently, yet these agents are associated with the highest degree of drug-related harm. The frequent and significantly dangerous adverse effects associated with opioids are detrimental to living safely, as they often predominantly affect mood, conscious thought, judgement, can create hallucinations and delusions, change cognition, and affect mobility. In relation to people living with dementia, these regimens can exacerbate the symptoms of dementia and potentially place them at higher risk of complications. Another huge issue regarding people living with dementia is that they may be unable to verbally express their pain. People living with dementia feel pain just as acutely as we do, and it is our responsibility to ensure their pain is managed, to avoid catastrophic events associated with acute delirium, behavioral expression and increased debility. It has been indicated that many geriatrics prescribed opioid pain management regimes are still not having their pain effectively managed. There is an urgent need for an alternative approach.”
An available solution:
The potential benefits of medicinal cannabis in treating poorly managed intractable chronic pain has been suggested as a beneficial alternative approach to enhancing quality of life and maximizing comfort and well-being in Australia’s older population. We are the ones with the drive and ability, so that we may revolutionize modern medicine in a way that creates a sustainable future for those in need. We are moving forward, and are fighting for what is right because we care on a level that is inundated with true compassion.
There are numerous cannabis manufactures of edibles and concentrates that are bracing themselves for the State of California’s first licensing process that is slated to take effect January 1st, 2018. While the regulations, license fees, and formatting remain to be finalized, the majority of the requirements will stand. The most recent proposal has yet to be finalized but absent the final word from the regulators, it is easy to feel as if preparing your application is like trying to hit a moving target. There is certainly some truth in that, but there are some fundamental parts to the application process that are almost guaranteed not to change. By following these tips, and working with experts that understand Good Manufacturing Practices, you can put yourself at the front of the pack when application time comes around.
Tip 1: Obtain local authorization and support.
Even if your jurisdiction has not finalized their licensing process, the state has made it clear that local jurisdictions can provide a letter of authorization that will satisfy the state’s requirements to obtain a provisional license. In a future article, we will discuss the importance of gaining community support.
Tip 2: Have your business plan/pro forma prepared.
By over-preparing and having proof of the required surety bonds as well as sources of capital, the sprint to complete the application will be much less stressful, allowing you continued focus on your current operations.
Tip 3: Walk down your processes, document them, and build your Quality Management System.
How do you plan to document the solvents or oils used during the extraction? Have you verified they are of sufficient purity and unadulterated? Do you have your Calibration Plan written? What does your annual training plan look like? How about the documentation of critical control points during your manufacturing process?
Careful preparation is key.
These types of procedures can take months to prepare and vet, and it’s easy to get overwhelmed at first. Our experts with a background in manufacturing and compliance will assist you in preparing these documents so that you are prepared for a successful application submittal the first time. Don’t wait until the auditors show up, or even worse, a consumer product lawsuit is filed against you for alleging adulteration. Having the proper procedures and controls in place, and then following them will be your only form of protection if you end up in court.
At Orion GMP, we have been eating, sleeping, and breathing Good Manufacturing Practices and SOPs for longer than we’d like to admit. It’s common practice in practically every manufacturing industry in the world. But we acknowledge that it’s a learned process, and that it can seem overbearing and unnecessary without understanding the complexity of other highly regulated industries. Bridging our knowledge of Industry GMPs from both the process and auditing side with our expertise and passion for the cannabis industry allows us to strategically help you make sure you aren’t just complying with the regulations bestowed from above, but are utilizing them to safeguard product quality and also save money. It’s always harder to swim against the current, so if you are going to comply with the new regulations, why not make it profitable at the same time?
If you are interested in meeting California GMP Cannabis Guidelines, send us an email at firstname.lastname@example.org.
Not all solids are created equal. Some molecules can be “more solid” than others. What does this mean? Well, certain kinds of functional groups on the molecule, such as the alcohol, or –OH group, are like little magnets that bind the molecules to each other and make them clump up as a solid. Sucrose, or table sugar, has eight alcohol functional groups. This gives it a crystalline structure and the ability to dissolve in strongly polar solvents such as water. The more –OH groups you have, relative to the overall molecule’s size and other properties, the more solid character the molecule possesses. CBD, or cannabidiol, has two alcohol groups, that is why it is called cannabi-di-ol, meaning “two alcohols”. On the other hand, THC only has one alcohol functional group. The other oxygen is an ether, which is less polar than an alcohol because it is not a hydrogen bond donor. Other portions of the molecule including the terpenoid portion, the benzene ring, and the pentane tail contribute hydrophobic character to the molecule, so even though alcohol groups are present, neither of these cannabinoids are polar enough overall to dissolve well in water, but organic solvents, such as ethanol and methanol will dissolve them more readily.
You might be thinking, a solid is a solid, so why does this matter? It matters for recrystallization. If you added just a small amount of solvent to a mixture of CBD and THC, which would dissolve more easily? The one that is less solid, the THC. If you have a mixture of CBD and THC already dissolved, which one will precipitate more easily? The one that is more solid, the CBD.
THC and CBD are both soluble in alcohol solvents, which is very useful for extraction, but for a recrystallization procedure, a solvent that is a little more selective about what it can dissolve is necessary. A less polar solvent, such as pentane, is needed so at the end of recrystallization the final product can be filtered and collected as a solid. Pentane is just a straight chain consisting of 5 carbons, a very nonpolar solvent. At room temperature, it doesn’t dissolve the cannabinoids well. For recrystallization, temperature control is the trick. When the pentane is near its boiling point (36C), it can actually dissolve the cannabinoids just from that extra input of kinetic energy, and when the solution cools back down to room temperature, which molecule do you think will precipitate first? The CBD!
Articles by CannaChemist are focused on concepts surrounding cannabis chemistry, both regarding the 400+ molecules present in the cannabis plant, and the chemicals typically used for processing and manufacturing cannabis products. These writings are for the purpose of educating and advising those that are striving to achieve GMP standards in the cannabis industry. The intention is that by increasing the knowledge of chemistry principles, you will be able to develop safer, more efficient, reliable, and inventive procedures for your cannabis manufacturing company.
No procedures or ideas developed based on these writings should be attempted without the same safety precautions that would be employed in an industrial or academic setting.