CBD Manufacturing from Hemp
CBD Manufacturing processes include the hemp processing, extraction, isolation and manufacture or finished products containing CBD.
Before that can occur, theCBD (Cannabidiol) oil and other ingredients must be manufactured to a standardised form so they can be used in finished products.
This requires a well documented and consistent process for producing CBD oil and other high value manufacturing ingredients which can be derived from hemp, varieties of cannabis containing <0.3% THC.
The CBD Manufacturing process contains many steps from seed to sale. Because CBD is intended for use as a medicine, or a food supplement, it is essential that both hemp cultivation and CBD extraction and manufacture follow GMP CBD Manufacture (Good Manufacturing Practice) – the standards that ensure safe production of food and drugs.
CBD Manufacturing Process
To make CBD for use in food or medicine, hemp must be cultivated, harvested, dried, processed, extracted, refined and purified using specialised equipment and processes.
The steps to CBD Manufacture from cultivation to CBD Isolate and beyond include:
- Cultivar selection – High CBD Hemp Cultivars
- Cultivation – High CBD Medical Hemp Cultivation
- Processing – Hemp Post Harvest Processing
- Selecting Quality Extraction Material – CBD Processing from Hemp
- Extraction – CBD Hemp Extraction
- Refinement – CBD Manufacture from Hemp
- Isolation – CBD Isolation from Hemp
Hemp CBD Manufacturing overview
The manufacturing process for cannabis derived medicines such as CBD is multi-step and requires several different stages, each with a separate set of equipment. In total, the process takes many months from growing the plant through to extracting and refining the CBD before sale or incorporation into finished medicines.
Because CBD manufacture uses an herbal raw material – hemp, there are often inconsistencies between batches which require troubleshooting and small adjustments to the process. High quality manufacturers invest the time and resources necessary to ensure a consistent product. This includes developing a reliable supply chain to ensure that the extracted material are of high quality and consistency.
Rhizo Sciences, LLC employs chemistry, quality assurance, microbiology, and production management professionals who have a wide range of collective experience in the cannabis, botanicals and pharmaceutical manufacturing industries. These professionals bring to the table a prismatic approach to what works in cannabis manufacture to deliver the desired quality and consistency. The industry has proven that it isn’t solely the right process and equipment that brings a successful yield, but instead the experience in that process and equipment.
The following outline is representative of CBD manufacture for medicinal use.
High CBD Hemp Material Incoming and Receiving
Cultivation of high CBD, low THC hemp (Cannabis Sativa) flower is done in an separate facility (or a distinct, separated part of the same manufacturing facility) dedicated to growing, trimming, and drying the material. Once it reaches the doors of the processing and manufacturing facility it is considered a “raw material”.
High CBD Hemp is most often cultivated outdoors on speciality farms (medical hemp cultivation) to produce high CBD hemp flowers.or whole plant high CBD hemp biomass In some situations, hemp is also cultivated in greenhouses or indoors. Alternatively, industrial hemp biomass may be used which typically has lower levels of CBD and higher risks of contaminants. This material is not ideal for medicinal manufacture but may be suitable for isolate manufacture
Read more about selecting appropriate raw material and the difference between Medical Hemp vs Industrial Hemp.
Upon arriving at the facility all raw materials go through Incoming and Receiving testing and inspection to ensure they are pure and fit for use in the manufacture of medicine.
Incoming and Receiving testing is not unique to incoming hemp raw material. This type of testing and inspection is also conducted on any materials, components, or packaging which will be used in the manufacture of finished product.
Examples of materials which are tested and inspected during Incoming and Receiving testing include:
- Bottles, droppers, and caps.
- Vape pens, chargers, batteries, and tanks.
- Labels and cartons.
- Ingredients and excipients.
- Processing chemicals.
Due to the potential variability, heterogeneity or inconsistency of incoming hemp flower and related products, a standardised process for sampling for dried herbal product is followed to ensure representative sampling, inspection and testing to ensure they are suitable for use.
Grinding Hemp Flower for Extraction
Grinding is the process of taking hemp raw material and breaking it down into smaller particles. This increases the surface area of the hemp flower, making it easier and more efficient when extracting the CBD and other cannabinoids.
CBD Hemp Oil Extraction
Extraction is conducted using an extraction machine such as an ethanol or CO2 extractor. At high pressures, CO2 acts as a solvent (similar to hydrocarbon liquids) instead of an inert gas, allowing it to pass through the raw material and selectively dissolve target compounds. After extraction the CO2 sublimates at normal atmospheric pressure thus producing a clean extract which does not have residual solvents. The ground raw material is packed into CO2 extraction vessels rated to the pressures involved.
When extraction is complete, a series of fractioned cannabinoid and terpene extracts will be ready for further processing. The extracts contain all of the necessary active ingredients that will be used in the final products. At this stage the extract requires refinement before it is bioavailable as a medicine or finished product. At this stage in processing the extract is referred to as raw crude.
Hemp Oil Dewaxing
Raw crude from the extraction process contains waxes, plant pigments and other impurities which are removed in a process called dewaxing. To begin this process a food grade solvent such as ethanol is added to the raw crude which facilitates the precipitation of undesired waxes present due to the solubility selectivity determined at extraction. Removal of these waxes will increase purity and concentration of cannabinoids.
Upon chilling in a freezer, waxes begin to precipitate and dewaxing is performed via filtration.
By breaking bonds of fatty plant matter, the separation and removal of waxes from the wintered material is conducted. Dewaxing stabilizes the cannabinoid solution, preparing for successful formulation.
Dewaxing purifies the cannabinoid solution, allowing for a more potent final oil. For successful dewaxing, the polar substances within the solution must be separated from the non-polar.
The bi-product of dewaxing is a hemp wax. This wax contains little to no cannabinoids. In some applications, the wax may be saved for use in products. In most applications, the wax is destroyed.
Time, temperature, and the amount of waxes present will determine the efficiency of wax removal. The ultimate goal of dewaxing is always to eliminate all waxes from the solution. The less waxes that are present, the more stable and potent the final oil will be.
With heavy loads, this will require multiple stages of dewaxing and filtration with intervals sufficient to allow precipitation of waxes.
Hemp Oil Filtration
Once waxes have been successfully separated and the wintered material has reached the temperature target, the solution will be filtered. Filtration is the final step in dewaxing.
During dewaxing, the non-active components of the solution are separated. Cannabinoids are kept suspended in the solvent due to temperature and mixing procedures.
By filtering the wintered solution the waxes may be removed, leaving the cannabinoids dissolved within the solvent.
To perform filtration, the supernatant is transferred to a clean vessel through a food grade filtration system. The type of filtration used is dependant on the workability of the current solution, and is determined by an experienced Processing Technician.
Types of filtration include gravity filtration, vacuum filtration, pour-through filtration, and wintered filtration. The goal of filtration is for the properly chilled and prepared solution to pass through porous media to 0.2µm threshold without remaining waxes.
After sufficient intervals to stabilize the temperature, a sample will be drawn and evaluated for any remaining waxes. Dewaxing success is dependant on experience of Processing Technician and the available equipment. Filtration will continue through several cycles until testing proves the process has reached maximum success.
Use of a centrifuge will greatly increase success of filtration. Filtration can take anywhere from 48 hours to 5 days, depending on skill of Processing Technician and available equipment.
Following filtration of waxes, pure cannabinoids remain suspended in the food grade solvent added during the Dissolving phase. The solvent added to facilitate dewaxing now needs to be removed.
Removal of the solvent is performed using careful vacuum and temperature control optimized to limit any degradation of the target cannabinoid compounds. Cannabinoids are extremely sensitive to heat, and incorrect temperature control will destroy the purity and strength of the extract.
The most often used instrument for solvent removal is a rotary evaporator. The rotary evaporator must be furnished with the correct accessories to properly conduct solvent removal with cannabis. These accessories include things like a vacuum pump, a bulb specified to the proper size and material, and heating bath solvent capable of meeting necessary heat settings.
The rotary evaporator will be set to carefully chosen specifications to pull off the solvent, while protecting cannabinoids and increasing purity of the final material.
When done correctly, the solvent will be recovered at a purity of 90% or greater. In these cases, the solvent may be re-used for future processes, saving the company large amounts of money and saving storage space.
Storage and recovery of solvents is often a major part of the labor, cost and floorspace allocated to extraction and refinement processes for hemp oil, and is a common reason why companies choose CO2 extraction over ethanol extraction due to the massive volumes of ethanol which must be recovered and stored, which represent an explosion risk.
Regardless of care taken during previous steps of hemp processing to extract CBD oil, impurities are inevitable and non-preventable, even by the most skilled techican. To create the purest extract possible, a final distillation is completed which, when properly conducted, serves many important purposes including:
- Removal of impurities.
- Isolation of terpenes, a vital component to formulation of effective cannabis medicine.
- Decarboxylation of cannabinoids for oral bioavailability.
- Concentration and purification of cannabinoids – predominantly CBD but also THC and minor cannabinoids such as CBG, CBC, CBN and others.
Short Path Distillation is the single most important and yet precarious of all the purification steps. Short Path Distillation should only be conducted by an experienced Processing Technician. Conducting Short Path Distillation without proper training and experience can lead to destruction of terpenes and cannabinoids.
During Short Path Distillation, a combination of temperature, circulation, and vacuum manipulation are used to isolate and separate different cannabis component extracts.
A Short Path Distillation system is usually built piece-by-piece for optimal functionality. Rhizo Sciences is versed in these distillation systems and will source and install Short Path components which are appropriate for the projected throughput of the facility.
Proper use of Short Path Distillation can yield anywhere from 70% cannabinoids to 95%, depending on the material, the equipment, and the technician expertise. The material which results from Short Path Distillation is called “CBD distillate”.
Hemp Derived CBD Isolate is purified 99.5%+ CBD and appears as white a crystal, powder or granules. Isolation of cannabidiol is a multistep technical process requiring specialised equipment and experienced staff.
Most CBD isolate is produced using a combination of distillation and chromatography to produce a high purity liquid (80%+ to 90%). At this purity, CBD crystallises spontaneously to form crystals of almost pure CBD. To separate these from the oil they are often precipitated out of solution from a solvent such as pentane or supercritical CO2.
Because chromatography and solvent precipitation both rely on complex solvent mixtures and recovery, and may require multiple passes in order to achieve high levels of purification (99.5% to 99.9%).
Formulation is where cannabis extract (oil, distillate or isolate) is mixed into different food-grade carriers and excipients to form a final product. Final product forms include:
- Extract syringes.
- Vape cartridges.
- And many more.
Calculations are conducted to determine how much extract will be required to reach the target medicinal potency of cannabinoids per dose.
For example, an oral oil may be formulated by dissolving cannabinoid extract into olive oil. Terpenes may be added to adjust for flavor. These additions will need to be calculated, and potency tests conducted to ensure the formulation is on target.
Packaging and Labeling
Packaging and labeling is conducted so that the final formulated material may be marketed for consumer sale and/or use.
Packaging and labeling tasks include:
- Bottling or filling.
- Placing caps or droppers.
- Assembling patient use packets.
- And much more.
All packaging materials used must be of food grade materials to be considered fit for use. Labels and cartons will go through several departments for edit to ensure the company message is properly communicated and that there are no illegal drug claims made.
The packaging and labeling process is considered a production step and must be treated as any other step, with tight quality assurance controls in place.
Finished Product Testing
Prior to reaching market, all finished products must undergo testing to ensure quality standards are met.
The testing will always meet, at minimum, the requirements of local and federal government regulations for safe manufacturing of hemp products. These tests often include:
- Microbiological activity (yeast, mold, bacteria).
- Water activity.
- Pesticide residue.
- Heavy metals.
- And more.
All finished products must be held in QUARANTINE until test results are returned. Test results must pass in order for products to be released for retail sale.
Some tests will have specifications set forth by the local government, such as a plus or minus 5 percent (+/-5%) of target potency test. Other tests will have specifications set by the company which use internal specifications to ensure product uniformity.
All materials, components, in-process material, and finished products must be stored in environmentally controlled conditions. This is to protect the integrity of the materials and to promote a consistent product.
Cannabis raw material or materials which contain cannabis will be kept in controlled areas for protection from theft, either inside production spaces or in other locked areas.
Materials which require refrigeration will be kept in environmentally monitored refrigerators.
Warehouse inventory must be tracked to ensure materials are properly allocated during production. By carefully and methodically managing warehousing, all components of finished product may be traced from seed, or source, to shelf. For outdoor hemp farms this level of tracking is not presently available, but is common in indoor hemp farms – and will likely be a key part of medical cannabis quality standards for pharmaceutical or ethically produced product lines.
Final products must be held and distributed according to GDP, or Good Distribution Practices. These guidelines are designed to ensure the correct materials reach the intended final user or distributor.
First in first out (FIFO) principals will be utilized which guarantees stock is properly rotated. This keeps product fresh and ensures materials do not expire while on the warehouse shelves. FIFO practices also ease in inventory, as there is only one active lot/batch of material in use at any time.
All distribution history must be carefully documented, including what specific batch numbers of each product the customers are receiving. This information is required so that in the case of a recall, all product can be traced to the final end user and pulled from shelves.
Good Distribution Practices are the final step in achieving a full seed-to-shelf traceability system.
The production process for manufacturing cannabis medicine in a GMP environment is made up of many distinct steps. Each phase of the production lifecycle is as important as the others in bringing a clean, pure, and quality product to market.
Rhizo Sciences is dedicated to seeing each client through from facility blueprints to manufacturing to final GMP certification. It is the mission of Rhizo Sciences to bring safe cannabis medicine to the public by enabling manufacturers to create the best medicine available on the market.
Our staff is experienced in running a GMP hemp manufacturing operation, and is skilled in training client personnel to independently operate the facility. We are a chosen partner in the international market because of our dedication to quality, and the success of our throughput.
We are able to source, qualify, and install all the equipment necessary to conduct the steps mentioned throughout this document. Each facility will be designed to manage the projected throughput of flower, and the specific goals of the client.
We are ready to help your company build and operate a successful production facility using our proven GMP methods in manufacturing effective and pure cannabis medicine.