Medical marijuana has become a booming industry exceeding $9Billion in annual sales across the US. Patients are looking for more natural therapies, while at the same time cannabis has been proven to help improve symptoms related to HIV/AIDS, cancer, glaucoma, and multiple sclerosis such as pain relief, nausea and vomiting, convulsions, appetite suppression.
However just like the research development and production of any medical substance, cannabis too, in its many forms, can encounter risks along the way that jeopardizes the quality of the product, and safety for the patient.
Any company that is involved in the cultivation, harvest, processing, analytical testing, storage, packaging, distribution, wholesale or selling of Cannabis is subject to regulatory inspections (depending on which country you operate in or distribute to), and like the rest of the pharmaceutical community adhering to GLP, GCP, GMP and GDP practices. Even if national regulations aren’t in place in the US, there are US state requirements, and strict regulations in some European states.
From a business standpoint, ensuring quality control of temperature sensitive cannabis products will decrease risks such as product quarantine, invalid test results, patient side effects and ensuing legal issues. Put bluntly – your cannabis business won’t stand the test of time in this exploding industry if your practices are not GxP compliant – from lab to clinical to distribution.
Regulations – USA
As of March 2019, 33 US states have laws allowing medical use of cannabis, in additional 9 states also allow recreational use. For a comprehensive state by state overview on legalized medical Cannabis use, go to http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
Each state has their own governing bodies that define GxP regulations in that state.
Source of Image: National Conference of State Legislatures, March 2019
Regulations – Canada
Documentation is key. As per section 231 of the Cannabis Regulations, license holders (other than cannabis drug license holders) must maintain records demonstrating their adherence to the GPP. License holders must be able to demonstrate, using records available at the licensed site, that the activities conducted are compliant.
Regulations – Europe
There is no harmonized EU law on cannabis use. The criminal or administrative response to drug use offences is the responsibility of EU Member States, not of the European Union. For example, in Germany in 2017, the national German legislature expanded the options for prescribing medical cannabis products by passing a law amending provisions under the Narcotics Law and other regulations. These products, however, must comply with the relevant requirements laid down under Medicinal and Narcotics Law, including GMP and GDP. Therefore, the BfArM (the Federal Institute for Drugs and Medical Devices) has taken over new responsibilities by establishing the Cannabis Agency. This agency is meant to help in ensuring supplies for medical-quality cannabis.
Since medical cannabis is considered a pharmaceutical product in all of Europe, all products must fully GMP and ISO certified both in the country in which it is products, AND as well from a European Union authority.
Eudralex Vol 4 – Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Storage areas should be designed or adapted to ensure good storage conditions. It states:
In particular, they should be clean and dry and maintained within acceptable temperature limits. Where special storage conditions are required (e.g. temperature, humidity) these should be provided, checked and monitored.
Can I get audited?
In Canada, yes 100%. They started in 2017 following three recalls of cannabis for medical use related to the unauthorized use of PCPs. Health Canada began a series of unannounced inspections and targeted testing of cannabis products from licenses producers under the Access to Cannabis for Medical Purposes Regulations to ensure that only authorized PCPs were used during the production of cannabis. Later that year, Health Canada announced it would require mandatory testing for the presence of pesticide active ingredients in all cannabis products, before the products could be sold or provided to individuals.
So, what is GxP?
GxP is the broader umbrella for GLP, GCP, GMP and GDP. That is…
GLP (Good Laboratory Practices)
GCP (Good Clinical Practices)
GMP (Good Manufacturing Practices)
GDP (Good Distribution Practices).
These are sets of standards are designed by regulatory agencies to control the quality and licensing for the development, manufacture and distribution of food and drug products. Each country has their own set of GxP guidances, but overarching global agencies such as WHO (World Health Organization), PICs (Pharmaceutical Inspection Convention) and others strive to harmonize national regulations.
GxPs and a company’s Quality Management System go hand in hand. A QMS is the backbone of a company to ensure all processes, policies, are focused on consistently meeting customer requirements. In the market of human medicines, customer requirements equate to the safety, efficacy and quality of the medicinal products. A scientifically sound and well validated QMS helps a company meet GxP guidelines.
So, what do each of these mean in the Cannabis industry?
GLPs for Cannabis Analytical Laboratories
Good Laboratory Practices ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical that is created or modified in any laboratory intended for human use.
Before cannabis is packed, labelled and sold, legal producers have to prove that pesticide limits are within acceptable limits. Independent laboratories use extraction techniques to make sure that the cannabis does not go over the allowed limits of pesticides set by state or regulatory standards. The list of pesticides and the chemicals to be tested is huge, often over 100, and acceptable limits are usually very low. Combine that with the fact that plants are grown in the earth and as a result, will have some residual levels of pesticides.
What does that mean? Very expensive part of the Cannabis business! Tests can be on average $1000 per test. For hundreds of pesticides against the set standards, that adds up quickly.
As an example, here is a list of pesticides and standards set out by Health Canada.
Thus, proper storage in refrigerators is imperative to protect the financial value of the stock and products. In addition, GxP requires documentation that proves temperature control while in the refrigerator, in process at the labs and through distribution to the consumers.
Old technology that so many labs still use for monitoring refrigerators or other lab equipment, such as chart recorders, can put GLP, and Cannabis products, at risk. Manual processes for checking temperature graphs, storing paper and writing deviation reports is subject to human handling errors. Read more about why Chart Recorders are not the right choice to protect your financial investment in this paper.
GMPs for Cannabis Manufacturing and Processing Facilities
Good Manufacturing Practices are a system of procedures and documentation for the proper design, monitoring and control of manufacturing processes and facilities to ensure product has the identity, strength, quality and purity which it is represented to possess.
GMPs covers all aspects of production processes, personnel and facilities:
How Complaints Are Handled
GMPs state all facilities must be environmentally controlled including temperature, humidity, and light for the storage and use of materials and products. You need to ensure products won’t freeze in winter, or bake in the attic in the summer. This means you need to temperature map that facility to learn where the hot and cold spots are, then create your monitoring program around that. To learn more about GxP Mapping of facilities, read this paper.
According to GMPs, new facilities must always undergo a mapping exercise, but there are instances that lend to a re-mapping of facilities, and these include: HVAC modifications, significant warehouse layout changes, extensions to facilities and sometimes even new product lines will warrant a mapping exercise. Keith Konya, Sr. Manager of Facilities Express Scripts / CuraScript, learned a few good lessons by going through the mapping exercise.
"We identified three hot spots which were caused by heaters blowing directly on pallet locations. The heaters have been repositioned as well as pallet locations removed from service." Keith Konya(Sr. Manager of Facilities Express Scripts / CuraScript)
GDPs for Cannabis Supply and Distribution
Good Distribution Practices (GDPs) entail quality procedures and SOPs that ensure consistent storage, transport and handling of temperature sensitive products throughout the supply chain. That means even when it leaves your possession as a legal producer, your transport partners must be in compliance as well with your product quality control requirements.
Qualification and Validation of facilities, systems and partners
Deviations and Changes
Documentation and records
Warehouses – mapping and monitoring
Counterfeit and recalls
In the GMPs section above, we discussed mapping and qualification of facilities. What about while the product is in-transit? How are you monitoring temperature control along the fragmented way? Cold chain monitoring solutions such a USB data loggers, temperature indicators and other technology can give you peace of mind that the quality of your products is monitored after manufacture and through the supply chain.
Where to start
Each environment is going to be slightly different. In labs, you will need to evaluate your refrigerators, freezers (if any), cool rooms. For your distribution operations (GDP), you will evaluate your current warehouses facilities, transport vehicles and boxes used for shipping.
Let’s use the example of GMP – for manufacturing and processing. First you will set up a business case to implement GMPs. First:
Assess your current infrastructure and equipment
Involve your different departments (Quality, IT, Finance)
Quantify financial loss if something went wrong
Once you have a business case for why GMPs are important for your business, then develop:
URS (User Requirement Specifications)
Layout (with your equipment and a measuring scale)
Project manager in contact with several departments.
Contact your equipment distributor (VWR)
Contact providers directly
To monitor the environmental conditions of your products in refrigerators or using a Central Monitoring System, there are many different types of monitoring solutions that could it. Such as:
Wired or wireless?
Dedicated network or Wi Fi?
Cloud or local hosting?
Local or remote alarms?
What kind of alarms?
Centralization for several sites/buildings (worldwide)?
Other specific needs: Write down your “Must have”, “Should have” "Mustn’t have”. Leave place to comment each requirement.
ALL systems are user friendly! What does it mean for you?
If you need help setting up a QMS and start evaluating your facilities, operations and processes, contact ELPRO’s GxP team of validation engineers to get started.
Sounds like a lot of work, headache and resources!?
It is. The companies that take the time to implement GxPs from the beginning of their business will have a significant advantage over those that try to retool their processes and Standard Operating Procedures (SOPs) later. As state and one day national requirements get stricter, your business will be set to avoid product recalls, negligent product quality policies and possible legal action.
GxPs also help build your company’s reputation and quality brand in this massively growing and competitive industry.
GMP Cannabis is the future of the industry. The early adopters of the practices employed by the pharmaceutical company will be ahead of the regulatory curve and be best positioned for success in the market.
To learn more about this topic, watch our free webinar on-demand 5 Blunt Reasons to Implement GMPs for Cannabis today.
About the author
Benoît (Ben) Chedhomme has been helping for the past 13 years, mostly life science companies to protect their temperature sensitive products from cold chain failure. His main expertise is on validation of facilities or equipment, and temperature monitoring for storage and transportation. Benoît also performs many compliance assessment projects for pharmaceutical companies to evaluate the different options that could be implemented to reach regulatory compliance. At last, Benoît has been working around the packaging market for years and has been assisting many customers into their qualification process. Benoît is currently the Canadian Territory Manager at ELPRO, who provides monitoring for small laboratories with stand-alone equipment, to multi-national projects requiring cold chain monitoring, thermal mapping, and facility monitoring systems.