When entering the medical cannabis industry, whether as a manufacturer, a provider, or a consultant, countless things need to be carefully considered. Some of these are big and some are small but all are important – and one of the most important areas of consideration is regulatory practices and compliance.
Perhaps the most notable set of regulations that any company operating in the pharmaceutical or medicines industry is GMP. But the situation can become even more confusing and complicated when it comes to medical cannabis. That’s why we have put together this article: to understand how GMP regulations are applied to medical cannabis products and why they are important.
First and foremost: what does GMP actually stand for?
I suppose there is no better place to start than at the beginning with the most obvious point. GMP stands for Good Manufacturing Practice which, in many ways is rather self-explanatory; however, it goes a lot more complex than you might first think. This simple phrase refers to the processes, procedures and documentation that all contribute to ensuring the high quality and consistency of a product – in this case, medical cannabis.
GMP and Medicines
GMP standards are applied to a variety of products, including cosmetics, foods, and pharmaceutical products. That’s right, all medicines sold in the UK and most other countries around the world, from the paracetamol in your kitchen cupboard to Epidyolex prescribed for treatment-resistant epilepsy have all been manufactured to GMP standards.
This refers to everything from the defined manufacturing process and critical manufacturing steps to the need for suitable premises, storage, and transportation of all products. GMP approval affects every step of the manufacturing process, and with good reason.
As the World Health Organisation puts it: “The guiding principle of GMP is that quality is built into a product, and not just tested into a product.”
This is particularly important when it comes to the production of medicines, as has been learnt the hard way at various points throughout recent history. The idea of GMP was born out of the realisation that end-point quality testing was insufficient to guarantee the consistency, safety, and quality of individual products. Tragic incidents like the Thalidomide scandal of the 1960s which led to an estimated 10,000 cases of infants born with serious deformities in Europe alone, triggered the introduction of further regulations on the pharmaceutical industry.
In the 21st century, more globalised efforts were made to promote the consistency and safety of pharmaceutical products regardless of the country of manufacture. The most influential examples of these efforts are the World Health Organisation and the International Conference of Harmonisation.
A Brief History of UK & EU GMP
The first UK guide to Good Manufacturing Practices was published in 1971 – it was known as ‘the Orange Guide’ due to the colour of its cover. At just over 30 pages long, the guide, titled “Guide to Good Pharmaceutical Manufacturing Practice”, was distributed as a voluntary guide to manufacturers to inform them of regulatory requirements for the production of pharmaceuticals. By 1993, the ‘guide’ was finally published as “Rules and Guidance for Pharmaceutical Manufacturers”.
Around this time, EU member nations began to remove their individual GMPs in favour of a single, uniform European guide. This was the birth of the European Union Good Manufacturing Practices (EU GMP) which remains in force in the UK today. It was created using what were considered the two leading written GMPs in Europe at that time – the British and French regulations.
EudraLex is the body that publishes the Guidelines for Good Manufacturing Practices for medicinal products intended for human and veterinary use.
GMP and Medical Cannabis
Even though cannabis has been in use for thousands of years, it was prohibited in the majority of the world during the GMP development period. Continued legislative conflicts, as seen in the USA, can sometimes mean that the regulatory bodies that enforce GMP rules for other industries do not do so for the cannabis industry. In the USA, state lawmakers and business owners are forced to navigate this new, rapidly developing industry without uniform guidance.
Luckily, in the UK and many of the countries in the EU, medical cannabis has been legalised. There is, therefore, some guidance on manufacturing standards for medical cannabis and CBD products. Nonetheless, it is worth noting that cannabis is rarely the same as the majority of other pharmaceutical products; it is a complex ‘compound drug’ which can make it difficult to regulate in the same way.
Nonetheless, there are still no universally accepted standards for the manufacture of cannabis, other than the current GMP guidelines. In some countries, the state may establish their own respective National Cannabis Agency which oversees GMP compliance. For example, in the Netherlands, the Office for Medical Cannabis operates within the Healthcare Inspectorate – the authority that ensures compliance. Similar agencies have been set up in other countries, including Canada and Germany.
So, how exactly do Good Manufacturing Practices apply to cannabis products?
Well, this is the golden question and, unfortunately, there isn’t yet a clear answer. To start with, different elements of GMP are applied at different steps in the process. For example, the cultivation of medical cannabis will be subject to Good Agricultural and Collection Practices while the distribution of the products will be assessed using Good Distribution Practices. Applying GMPs, therefore, requires communication and cooperation across every level of the supply chain in order to achieve suitable compliance.
Each country in the EU in which medical cannabis is legal will have its own National Competent Authority with a dedicated cannabis programme. It is therefore important for medical cannabis manufacturers to understand the processes and procedures of the agency in the country they are looking to operate in. Examples of these agencies were mentioned earlier (the Office of Medical Cannabis in the Netherlands). If a manufacturer does not achieve full GMP compliance as specified by these agencies, then they will not be able to distribute their products in that market or export to other markets in the EU.
Germany’s medical regulatory body, BfArM (The Federal Institute for Drugs and Medical Devices) has released additional guidelines on medical cannabis production.
These agencies carry out inspections when a manufacturer applies for licensure as well as for all elements that may be compromised in the manufacturing supply chain. Inspections involve audits on all quality-related documentation, site tours, personnel interviews, and reviews of the site master file and batch records. These inspections aim to identify potential risks and ensure the manufacturer has the resources needed to maintain consistent regulatory standards.
Applying GMP to medical cannabis can undoubtedly be a difficult road to navigate. But don’t worry, there are resources out there that can be invaluable. Nonetheless, it is always recommended that medical cannabis employers consider employing an experienced consultant to help iron out any complications and misunderstandings and generally make the process as easy as possible.