GMP & CBD: Why the EU’s Good Manufacturing Practices for the cannabis industry are so important
Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.
- Firstly, what does GMP mean?
- GMP & the cannabis industry
- Country-specific GMP (EU, Canada, USA)
- What is the difference between cannabis GMP and GPP?
- GMP certification process
- How did COVID-19 affect GMP certification?
- The bottom line
Every industry is expected to have its own unique set of rules and laws. The cannabis industry is no exception. If you’ve ever spotted a product that boasts its compliance with GMP, you should know that the product you’re looking at is one of quality, safety and effectiveness. Indeed, cannabis companies who are eager to earn their spotlight in the cannabis world often have their facilities GMP-certified.
In this article, we'll consider what challenges and opportunities may occur on the path to receiving GMP certification.
Firstly, what does GMP mean?
Good Manufacturing Practices (GMP) are the minimum requirements that a manufacturer must meet in order to ensure that their products are consistent, high-quality and safe for their intended use.
GMP certifications may also apply
to a single stage or the entire production process. These practices are implemented in various markets: they can apply to food and beverages, cosmetics, pharmaceutical products, dietary supplements and medical devices.
The basic principle of GMP is that quality control should be channelled into each batch of a product at all stages of the manufacturing process. These practices are the basis of regulation for industries. Specifically, consistency is important for:
- Physicians and patients – to validate the product composition and dosage.
- Researchers – to compare results from clinical trials and studies.
- The cannabis industry – to obtain GMP-certified active pharmaceutical ingredients (API) and provide seamless GMP manufacturing that speeds up the production timeline and diminishes risks from manufacturing activities.
It is important to note that the GMPs are guidelines, not laws. Furthermore, all international and national standards include a few basic principles that are similar to that of GMP:
- Manufacturing processes are clean, controlled, auditable and repeatable. Any changes must be documented;
- Products are manufactured in a suitable facility, with the use of appropriate and regularly maintained equipment;
- Hygiene processes are in effect to prevent contamination;
- Employees are healthy and are certified and trained to perform their tasks;
- Accurate record-keeping, documentation and accounting are carried out, including batch history from manufacturing to the distribution to the end-user;
- Repeatable audits and inspection of production stations by certified bodies are performed;
- Recall and withdrawal procedures must be in effect, and complaints on the products must be checked.
In general, GMP-certified products must:
- Suit the intended use;
- Come from the licensed supply chain;
- Be of consistently high quality, including consistency in storage, transportation and handling;
- Comply with the requirements of the marketing authorisation or product specification.
GMP & the cannabis industry
As more countries loosen their laws surrounding cannabis, global regulations on cannabis are changing. Many countries, such as the United Kingdom, Germany, Canada, the USA, Greece, Australia and many more have legalised cannabis for medical purposes. Europe is expected to become the world's largest legal cannabis market and is estimated to be worth up to €123b by 2028.
Fewer countries have legalised cannabis for recreational use. Those include Canada, Uruguay, South Africa, 11 US states, two territories, and the District of Columbia in the USA and the Australian Capital Territory in Australia. Some other countries have begun to decriminalise or de-penalise cannabis use. Countries such as the Netherlands and Spain have loosened their controls and penalties related to cannabis. This represents great progression and advancement in the cannabis world, as decriminalisation and depenalisation are the first steps towards a more tolerant attitude to cannabis legalisation.
Now let’s take a look at some of the variations on GMP espoused by different countries.
The European Union (EU)
EU authorities classify medical cannabis as a medical product, and therefore apply an established standard known as EudraLex Volume 4 of "the rules governing medicinal products in the European Union" ("EU-GMP"). European pharmaceutical companies follow this standard, and medicinal products are sold in Europe under EU-GMP.
The EU-GMP guidelines include key requirements for:
- The quality system and quality control
- Facility and equipment
- Documentation (including records keeping and data integrity)
- Validation of manufacturing, computer systems, etc
- Qualified person batch release
- Outsourced activities, including audits
- Complaints and product recall
- In-house inspection
Before entering the market, all medical cannabis sold in Europe needs to be manufactured and tested under European GMP, along with Good Distribution Practices (GDP) certification for distribution and warehousing. All European cosmetics and medications that contain CBD should be GMP-certified and listed in the Eudra Database. That is the Union database, maintained and operated by the EMA (European Medicines Agency), that lists products with GMP certificates and import authorisations. Other authorisations mean compliance withDirective 2001/83/EC, which approves cannabis production as an active pharmaceutical ingredient (API) and Directive 2003/94/EC, which outlines principles and guidelines of GMP related to medicinal products and investigational medicinal products for human use. EU-GMP certification evaluates the quality system and quality control, personnel, facility, equipment, documentation, manufacturing, complaint and recall processes.
Prior to Brexit, the UK followed EU regulations. As we all know, the UK left the EU on 31st January 2020, meaning beyond the transition period, EU laws no longer apply to the UK.
GMP certification is necessary for cannabis-based medications. Owing to the fact that CBD products are largely grouped as “novel foods” or as “food supplements” instead of medication, CBD products undergo fewer production controls when compared to medicines. Nonetheless, it is still highly likely that GMP standards will still apply.
In Canada, cannabis is legal both for medicinal and recreational purposes. Medical cannabis is regulated under the conditions of the Access to Cannabis for Medical Purposes Regulations, whereas recreational cannabis is regulated under the Cannabis Act.
Canada created unique standards known as GPP (Good Production Practices) for medicinal cannabis, which outline the requirements for cannabis cultivation and processing facilities. GPP standards evaluate facilities and equipment, quality assurance and quality control, sanitation, documentation, and security.
What’s unique about GPP is that it represents a combination of principles from both medical and consumer product regulation. It should be noted that there are significant differences between the GMP and GPP. The EU-GMP guidelines are more detailed and have established specific requirements and principles on what must be included in the quality control measures. By contrast, the GPP standards are much less detailed and are more open to interpretation. These differences make it difficult to compare the two sets of standards. A key thing to note is that GPP-compliant Canadian companies must apply for the EU-Good Manufacturing Practices (EU-GMP) certification if they intend to export their cannabis products to European markets.
In the United States, the Food and Drug Administration (FDA) sets out the guidelines for food, dietary supplements, drugs and cosmetics manufacturers. These are current Good Manufacturing Practice (cGMP), where the "c" indicates the company’s responsibility to ensure compliance with the FDA's most current guidelines, which often change.
However, because cannabis remains illegal at a federal level, there are no uniform Good Manufacturing Practice guidelines for the cannabis industry. The FDA sets out cGMP guidelines in the Code of Federal Regulations. However, the FDA has yet to establish regulations on CBD, and it remains the responsibility of the manufacturer to follow GMP guidelines and undergo inspection voluntarily.
Mutual Recognition Agreement (MRA)
The EU, United States and Canada all regulate drugs independently, which leads to different regulations and information from regulatory bodies, thereby creating trade barriers. As a result, the major markets created a Mutual Recognition Agreement (MRA) for GMP across different markets.
Since 2003, the MRA has been set between Canada and the EU, which has helped to reduce many barriers and paved the way for a more homogeneous market for its players. Unfortunately, those agreements may not cover medical cannabis, which is why many Canadian companies joined the EU-GMP certification race. For example, MRA agreements between some EU countries and Australia include medical cannabis, if it is regulated as a medication in the other country. Therefore, an Australian medical cannabis company with GMP certification from the Australian Therapeutic Goods Administration has the right to export medicinal cannabis to the EU without having a separate EU-GMP certification. Did you follow that?
What is the difference between cannabis GMP and GPP?
Receiving the Good Production Practices (GPP) certification is a less detailed and lengthy process than that of GMP. The GPP covers information on a cannabis product label, including its cannabinoid content, though its regulations do not require a batch-to-batch consistency. On the other hand, the GMP covers many additional quality aspects, such as the manufacturing process, raw material control, in-process testing, storage, distribution, validation and final product quality, including the accuracy of cannabinoid content and batch-to-batch consistency.
If a manufacturer produces a million CBD products, they might test just a fraction of them. If GMP standards are not followed, and there is no consistency in the safety of production, some of these products may be safe for consumption, while others may not. This may lead to product recalls or withdrawals, damage to brand reputation, and sometimes, lawsuits.
Why apply for GMP certification in the cannabis industry?
Here are the main ways in which GMP compliance may benefit cannabis companies:
- GMP certification helps to align international market participants to a well-known and accepted standard. However, the implementation of GMP guidelines alone will not remove the need for international inspections until cannabis is properly regulated and considered in mutual agreements
- GMP manufacturing ensures that the production and products comply with the highest quality standards
- Having a GMP certification means that cannabis products are safe, which gives companies a reputational advantage
- A GMP certification allows companies to expand to international markets
GMP compliance and certification are not widely required. However, it may become the standard as the industry matures and overlaps with more established ones such as food and pharmaceuticals. By complying with GMP standards, businesses gain access to wider international opportunities and reduce further business risks due to the stringent practices of manufacturing processes, quality testing, product stability and distribution.
The GMP certification process
The EU-GMP certification process may include the following steps:
Setting a target
There may be different reasons why a company may wish to apply for an EU-GMP certification; for instance, it may hope to enter overseas markets. Establishing a clear objective helps inform the kind of GMP certification that the company should obtain. There may be other GMP certifications, such as cGMP in the US, EU-GMP in EU and Guide-104 GMP in Canada. These certifications are similar, though they are generally more applicable to companies under the jurisdictions where they are certified. For example, if a Canadian company plans to produce cannabis-based medications or active pharmaceutical ingredients in Canada, it will have to apply for Guide-104 GMP. However, if the company plans to sell these medications in the European Union, it requires the EU-GMP certification.
At this stage of the process, the company evaluates its infrastructure and its compliance with GMP requirements. EU-GMP requirements differ from GPP as they cover wider areas, such as production and storage. This evaluation detects the gaps in infrastructure requirements and measures a company’s ability to fix them, as well as calculating the potential costs. If the company accepts the EU-GMP infrastructure requirements, it must implement and minimise these gaps in a way that is acceptable under GMP guidelines.
Quality management systems assessment
This stage is a gap analysis between the existing quality management system and the one that complies with EU-GMP. A good example is a gap assessment between GPP and EU-GMP quality management systems. Things are complicated as there are no specific requirements in GPP, and GPP compliance does not provide a shortcut to a GMP certification. On the other hand, some GPP requirements may be similar to GMP. Therefore, a GPP-compliant company is likely to meet some Quality Management System (QMS) requirements. If necessary, the QMS of a GPP compliant company can be audited and updated to conform with GMP.
Many businesses don't have high-level documentation, such as a master validation plan or a quality manual. These documents describe how the company operates. At this stage, the company needs to create these documents for further submission to the relevant authorities, including the Federal Institute for Drugs and Medical Devices in Germany.
Standard operating procedures update
A standard operating procedure (SOP) includes a company's instructions, which help employees to carry out complex routine tasks. Manufacturers can have up to several hundred SOPs. These instructions need to be updated for GMP compliance, including the update of the regulatory references within operating procedures.
If the company reaches this stage, it goes through a validation and stability programme.
The validation stage helps to update documentation, standardised operating procedures, and add missing programmes. Validation can show that the facility can manufacture products of consistently high quality and in compliance with standards. However, many cannabis processes don't require full validation, just validation for separate processes. Validation is a long process that can take up to a year.
The stability stage is necessary as it helps to establish a shelf life for the product. Stability isn't required under GPP regulations. Therefore, GPP-compliant companies are likely to undergo GMP compliance from the very beginning due to their lack of data. This is a time-consuming process. For example, if a company performs a stability program and plans to establish a one-year expiry, they would need to test the products every few months within a year. Stability stages should be designed according to international standards, such as ICH Q1 or BfArM.
After GMP implementation, it is time to run with new systems for a number of months to show that the company is functioning under the GMP standards.
This stage is not strictly necessary but highly recommended. A mock inspection is performed by a third party and helps to identify any potential issues regarding EU-GMP compliance. A mock inspection is conducted in the same way that a real inspection would be, and may include reviewing records, interviewing employees, discussing the logistics of the inspection and touring the facility. This stage helps the company prepare for future inspection and feel more confident that it will pass.
An audit is an outer, outsourced procedure. It is performed by the importer's Qualified Person (QP) for an audit or a third-party auditor. For example, the auditor of supply chain logistics ensures that the quality and integrity of products during transportation, warehousing, handling, testing and distribution is maintained through the journey from supplier to customer.
In Europe, GMP standards compliance is verified by the European Medicines Agency (EMA). It conducts inspections to examine the quality of products and their relevance to the intended use. Once the EMA, FDA, or another certifying body has received an application for GMP certification, they will arrange the inspections and confirm the company's compliance with their standards.
EU-GMP applications are submitted via EudraGMDP. This is long and costly, which is why smaller producers may lack the means to become officially GMP-certified, despite fully complying with GMP standards. The EU-GMP inspectors will issue EU-GMP certificates or manufacturing and import licences. The applicant will have to complete a GMP compliance report before an inspection. The inspection team will interview relevant personnel, review documentation and visit the facility. During the site visits, the inspectors may check manufacturing areas, quality control laboratories, stock and storage areas, temperature control, returns areas, purchasing and sales functions, and transportation arrangements. Overseas manufacturing sites will also be inspected. Further periodical inspections are also performed based on risk assessments. During the COVID-19 pandemic, licences and certificates have been issued as an electronic PDF copy.
The importance of GMP in the cannabis industry
Why is GMP so important for CBD products?
In recent years, CBD has become an internationally adopted wellness trend, sparking buzz across the globe due to its potential benefits to our wellbeing. With CBD gaining such wide-scale popularity so rapidly, many companies have seen this as a lucrative opportunity and have jumped on the trend, some of them cutting corners in the process. In addition, try as they might, authorities can't always keep up with the speed at which the CBD industry continues to grow. The CBD hype has thus exposed many consumers to fake products and dubious companies that do not follow quality standards, such as GMP regulations.
According to a 2019 investigative report by Ellipse Analytics and CBS Austin, up to 70% of the 240 bestselling hemp CBD products available online or from non-dispensary retailers might contain heavy metals, chemical pesticides, toxic mould and other harmful contaminants. The results of independent lab tests emphasise why it's important to make sure that CBD products are GMP-certified and have certificates to testify to their quality.
Is GMP for cannabis products necessary?
GMP certification is necessary for cannabis-based medications. As for CBD products, however, it remains at the manufacturer's discretion. Unfortunately, this means that not all CBD products are GMP-certified. Therefore, the lack of a GMP certification makes it difficult for consumers to know if what they're buying is a safe and unadulterated product.
Most reputable CBD companies undergo GMP certification to ensure that their CBD products are genuine and do not have harmful ingredients. Considering the lack of regulations and excess of unregulated products, obtaining GMP certification is a chance for companies to give their products the stamp of safety and legitimacy. As the cannabis industry grows and matures and demand increases, GMP certification is likely to become a requirement in the future, despite the high costs of compliance and certification.
GMP certification is applicable at a jurisdiction level, which means that to work as a GMP-compliant company in the EU, a CBD manufacturer in the US or Canada will need to apply for GMP-EU certification.
Why is GMP certification a must in the cannabis industry?
Both local cannabis products and those exported out of the country should be of a certain and consistent quality. To reach this desired quality and safety, the manufacturers should adopt quality standards and employ the best practices in all processes from cultivation and production to distribution and documentation. The main goal of the GMP certification in the cannabis industry is to create "pharma-grade" cannabis products.
As for the consumers, GMP certification helps them to make more informed decisions and is a mark of reassurance that the cannabis products they (may) buy are effective, do not contain contaminants and do not pose a risk to their health. People using cannabis products generally do so to feel relief from symptoms and improve their wellbeing. The last thing a consumer wants or needs is to end up suffering from adverse side effects due to the poor quality of their cannabis products. Therefore, GMP certification attached to a company and their products, along with a clean certificate of analysis, is the best way to ensure the safety of a CBD product. A GMP-certified CBD product demonstrates that the product has been processed, extracted, packaged and distributed in fiercely sterile conditions under the strict requirements of GMP.
By purchasing from a company whose products are tested by third-party labs, whose Certificates of Analysis are published and accessible, and who are GMP-compliant, the customer can have full confidence that their product(s) is uncontaminated and of high quality.
What may happen without GMP certification in the cannabis industry?
Although GMP standards are not commonly applied nor required in the cannabis industry, cannabis regulations are expected to become more necessary in the near future, which is great news for those who worry about purchasing unregulated products.
The failure to conform with GMP standards in the cultivation, production, packaging and distribution of cannabis products can lead to them becoming restricted goods. Such products may lack the declared active material content and contain heavy metals, toxins and other contaminants. As a result, manufacturers may lose sales opportunities in international markets due to their lack of GMP certification.
How did COVID-19 affect GMP certification?
During the Coronavirus pandemic, many cannabis facilities looking to gain their EU-GMP certifications had to be delayed due to the travel restrictions.
For some companies, this suspension posed a challenge to the receipt of GMP certification and exports to the EU market. The companies that didn't undergo an audit before the COVID-19 pandemic have had to wait until EU inspectors can travel overseas. The Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK has decided to limit the inspections only to the essential businesses for an unknown period. Nonetheless, audits remain necessary for the EU-GMP certification and exports to EU markets.
The good thing is that some local producers in the EU, such as Denmark, can be certified by domestic health agencies. In this case, EU companies can sell medical cannabis throughout the European Union, replacing more expensive foreign products.
Best GMP-certified CBD oils out there
Before we conclude this post, we thought we would remind you of three of our favourite GMP-certified CBD oils available to purchase on our website.
CBD Brothers Purple Edition Oil is made from Cannabis Hybrid Whole-Plant Extract. By this, we mean it was made from 70% cannabis Indica and 30% cannabis Sativa strains. This 10ml bottle contains 320mg of full-spectrum CBD extract with a THC content of less than 0.2%, so you’ve no need to worry about being intoxicated. What’s more, 320mg is a great concentration if you’re a novice to the CBD world. All the ingredients and components of this oil were ethically sourced from organically cultivated plants in Holland. And, you guessed it, CBD Brothers are GMP-certified!
The GMP-certified company Naturecan brings you its extra potent 40% CBD oil for a fully transformative experience. With 4000mg of CBD per 10ml bottle, this rich broad-spectrum CBD and organic MCT oil promises a higher absorption rate. Furthermore, this oil is infused with a natural spearmint flavour for a minty twist that will not only freshen your mouth, but your mind too. In every drop of this liquid gold, there is a whopping 16mg of CBD, which may be more than enough for your daily dose.
Another great CBD oil on the market - which, naturally, complies with Good Manufacturing Practices - is Kenaco’s broad-spectrum 1000mg CBD Oral Tincture. The oil is created with all-natural, vegan and vegetarian-friendly components, is sweetened with stevia and enriched with active cannabidiol. This oil has an aromatic flavour profile and is loaded with natural terpenes. The peppermint undertones and grapeseed oils will refresh and awaken your senses. And if that wasn't enough, Kanaco will also plant a tree for every product purchased!
The bottom line
The main goal of GMP certification, whatever type of GMP certification, is always to provide markets with safe products and prevent customers from potential harm. EU-GMP certification is a costly, time-consuming, and data-driven process. Sometimes, it requires the insight of consultants experienced in GMP certifications or additional mock inspections.
Even with all these challenges, GMP has many potential advantages:
- GMP certification creates an even playing field for all market participants and helps to bring their operational processes and products to an established and accepted standard
- The practices themselves ensure that cannabis and CBD products are produced under the highest quality standards
- The GMP stamp on a label translates to safe and effective cannabis and CBD products
- GMP certification contributes to the company's reputational advantage
- GMP allows companies to export products to international markets
In any case, GMP certification helps companies to reach the gold standard for international quality compliance and ensure the safety, quality, and efficacy of cannabis. However, the certification process requires funds, time, and a thorough and well-designed strategy.
What does GMP mean?
GMP stands for Good Manufacturing Practices. Good Manufacturing Practices are a set of standards and are the minimum requirements that a manufacturer must meet in order to ensure that their products are consistent, high-quality and safe for their intended use. GMP certifications may apply to a single stage of the production process or to the entire production process. GMPs are implemented in various markets: they can apply to food and beverages, cosmetics, pharmaceutical products, dietary supplements and medical devices.
What is a GMP-certified manufacturer?
A GMP-certified manufacturer is any company/manufacturer that has obtained GMP certification. This means they follow the strict practices required to possess GMP status and have undergone the necessary inspections before being confirmed as GMP-certified.
How long is GMP certification?
This depends on the extent to which the company follows GMP practices in the first place. If a company needs to fully transform the way it runs in order to align itself with GMP requirements, it could take a longer time than a company that is already partially compliant. In any case, there are multiple stages to the process of becoming GMP-certified. Validation can be a long, time-consuming process that may take up to a year in some cases.