TGA Medicinal Cannabis
I’m often asked to clarify the difference between TGA Medicinal Cannabis and EU GMP Medicinal Cannabis, i.e. who is that has the highest “Gold Standard” for Medicinal Cannabis? I suspect this has come about because many are trying to claim that their cannabis is cultivated, harvested and processed in accordance with the strictest pharmaceutical standards (therefore is the best quality).
This is a meaty topic and I am going to try and keep it as simple as possible.
1. GMP Basics
There are many dodgy people out there selling snake oil and to mitigate this, governments around the world have established:
- agencies to regulate medicines and ensure the safety and efficacy of those products, (as expected by the community) and
- quality standards that a manufacturing facility must meet in order to be granted a licence and legally manufacture medicines (Good Manufacturing Practices, or GMP)
These GMP principles are essentially standards that pharmaceutical facilities need to meet in order to be considered compliant by regulators – medicinal cannabis facilities are no different. These GMP principles have been developed over many years largely in response to common mistakes made by manufacturing facilities around the world. I often refer to the acronym GMP, as “Gross Mistake Prevention” – you can either follow the GMP guidelines, or you can make all the mistakes that everyone else did and learn the hard way.
These GMP principles have also been formalised internationally via a secondary collaboration model between governments called the Pharmaceutical Inspection Co-operation Scheme (PIC/S), of which many countries are members.
PIC/S is also charged with developing and publishing the world-renowned GMP bible: PIC/S Guide to Good Manufacturing Practice for Medicinal Products. Note this is not to be confused with the WHO Guide to GMPs, and we have explained why in a blog here.
PIC/S membership is a voluntary collaboration between regulatory agencies of all member countries and is very different from a mutual recognition agreement (MRA) between countries (more on that later). PIC/S has a rigorous accession process to ensure that only the most competent GMP inspectorates join, and it can take over 3 years to become a full member. However, once an agency has achieved PIC/S membership, they can be proud of this achievement and say that they are manufacturing under the GMP “Gold Standard” guidelines – the patients in their countries can be assured of high-quality medicines!
Whilst being a PIC/S member is a coveted and exclusive club, I know first-hand of many other respectable government agencies who are not yet PIC/S members. Though there is a great value in becoming a part of PIC/S, the legislative changes that are required can often stymie a government’s appetite.
PIC/S is a broad topic all unto itself so if you would like to read more about the wonderful work of PIC/S, why not read this blog by one of my former colleagues Bob Tribe.
Unfortunately, the prescriptive regulatory GMP standards required for medicinal cannabis products often clashes with the common ‘suck it and see” approach by many in the cannabis industry. Many companies, in a rush to be the first to market, have either:
- not familiarized themselves with regulatory differences between markets, meaning their timelines are drawn out due to all the extra compliance hurdles, or
- not fleshed out their business plan sufficiently (so they do not have the required resources with appropriate experience in place, or their plan is a poor fit for the locality).
By following simple GMP principles many mistakes can be prevented. As a GMP practitioner with over 20 years industry experience, I believe it’s easier to simply follow the GMPs, rather than risking your business or the life of your patients!
2. What are the differences?
2.1. Differences between regulators
The belief that there are differing GMP standards around the world, I suspect originates from Canada as they initially chose not to regulate the domestic medicinal cannabis production under GMP. However, when the manufacturers later wished to enter the European market, they needed to get European GMP certification.
I’m going to discuss briefly, the difference between the GMP required for TGA medicinal cannabis and the GMP required for EU medicinal cannabis:
There is no difference.
99.9% of the time the two GMP codes are the same word for word. Someone arguing that they are better because they make in product to “EU GMP” or “TGA GMP” or even “NZ Medsafe GMP” just does not make sense because they are all PIC/S signatories and use the same GMP code!
I have to concede however, that whilst the GMP regulations are comparable in PIC/S member countries, the application of the PIC/S code can differ slightly between countries. This variation can be influenced by:
- the education, training, and experience of the regulating body (and their focus)
- each regulator’s administrative classifications and divisions of labour
- what “version” of the PIC/S GMP Guide each country is using.
However, these differences are usually corrected when identifying a target market, ensuring you use the right consultants, and designing your Quality system to address any extra compliance items that are required.
This brings me back to MRAs. The governments of Australia, Canada, New Zealand and Singapore and many European countries have MRAs that recognise that the GMP standards in the various countries are equivalent to their own. Therefore, a manufacturer in one of these countries is accepted by another MRA partner country as equivalent or comparable and there is no need for a re-inspection.
In short, any medicinal cannabis manufacturer that has a GMP manufacturing licence issued by a participating PIC/S regulatory authority meets the GMP gold standard. For a quick summary, see our blog on 10 Golden Rules of GMP.
2.2. Differences between Pharmacopoeias
While the same GMP code is used by different countries, there can be differences in testing, stability, and impurity requirements for different pharmaceutical products. The limits will depend on the intended use of the product (e.g. topical or inhaled) as well as specific manufacturing requirements for different product forms (e.g. sterile vs non-sterile).
However, these limits are well characterised and can be found in chemistry pharmacopoeias. By my last count there 24 unique pharmacopoeias around the world. The ones we mostly adhere to are from the larger economies, like the United States Pharmacopoeia (USP), the European Pharmacopoeia (EP or Ph. Eur). There are also other pharmacopoeias issued by China, Japan, etc.
In Australia, the testing standards for medicinal cannabis are outlined in TGO93, in New Zealand it is outlined in the Medicinal Cannabis Agency – Minimum quality standard. Both standards state that they comply with GMP testing requirements in the European Pharmacopoeia.
The general rule of thumb is that if you intend to supply a certain market, your product needs to comply with the testing requirements for that country. The difference lies less in WHAT product qualities are is tested (these tend to be the same with maybe some slight variations in compliance thresholds) and more HOW a product is tested – i.e. which proven validated test methods are used to assure a result?
If there is a preference for the test methods in one pharmacopoeia over another, this doesn’t mean that the tests conducted aren’t as valid as the tests stipulated by the other pharmacopoeia.
Bottom line? Conduct the testing required by the target country according to the specified pharmacopoeia and monographs.
2.3. Differences in the GMP starting point
Most regulators have an expectation that herbal products are grown in accordance with Good Agricultural and Collection Practices (GACP). Again, these guidelines have been harmonised around the world. Two guidelines of particular note are issued by the World Health Organisation (WHO) and the European Medicines Agency (EMA). There are slight differences in the expectations of both; the former is based on principles while the latter is more specific. I have provided links to both these guidelines so you can make the comparison yourself.
At PharmOut’s medicinal cannabis conference at the end of 2020, the Portuguese Inspector, Luis Meirinhos-Soares from Infarmed, reaffirmed that there was an expectation that this GACP certification was performed by a competent authority, i.e. a government agency to EU GACP standards. Heavy metals for example, most likely come from soils and this will impact the heavy metal residues in final products.
However, it does beg the question, is this a GMP risk or an agricultural one? Why would any decent farmer grow products on heavy-metal contaminated soil? GACP principles also specify the careful selection of the site to ensure that there are no toxic residues prior to commencing cultivation. Differences between GMP and GACP are covered extensively in a different blog here.
Practically, PharmOut likes to consider the GMP line as starting somewhere between harvesting and drying. There are some caveats to consider though:
- The GMP line is highly dependent on the final product.
- In the Australian market the GMP line also depends on whether GACP materials are cultivated on the same site as manufacturing activities, or an independent one.
- In the Australian market there are different types of extraction allowed under GACP vs GMP.
3. In conclusion
Hopefully this blog goes some way to explaining that no country really holds a “Gold Standard” for Medicinal Cannabis as they all use the same GMP code. There is just medicinal cannabis that has been manufactured in compliance within the framework of a country’s GMP standards and pharmacopoeial requirements.
The common questions is: “Who is making the best medicinal cannabis?”
The better question is: “What quality standards does my medicinal cannabis product have to meet for my target market?”
If you want to have a chat, or find out more information, why not get in contact with one of our experienced consultants and have a chat?
If you found this blog useful, you may also be interested in the ones below:
- Can Australia be a global leader in Medicinal Cannabis?
- Exporting Medicinal Cannabis from Australia to Germany
- Medicinal Cannabis Stability
- What is the difference between GACP and GMP?
Many thanks to ECS Botanics for allowing us to share some of their site photos – the first outdoor cultivation in Australia. Data from ECS site and our other outdoor sites, confirm now confirm at least a 55x lower electricity use per gram with almost a carbon negative footprint! Does this matter? Pause for a moment, the North American cannabis industry consumes more electricity that the whole of Portugal!