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The current fragmented regulatory approach to cannabis medicines across Europe is challenging to harmonize.
Editor’s Note:This article was published in Pharmaceutical Technology Europe’s June 2019 print issue.
After a radical shift in public, medical, and scientific opinion about the effectiveness of cannabis-based medicines in the treatment of certain conditions, most European countries have legalized the use of these drugs. But European states, particularly in the European Union, have adopted a range of different regulatory policies for dealing with the medicines, particularly with regard to the quality standards in the cultivation of the cannabis crops and the manufacture and distribution of their medicinal products.
The vast majority of countries have approved cannabis medicines after they have gone through the standardized authorization process based on good manufacturing practice (GMP) and positive clinical trials. Also, many have stipulated that they should only be available by prescription.
A growing number of countries, however, have begun to allow access to the medicines through unconventional regulatory schemes with less quality controls on cultivation and manufacture and less importance given to evidence from clinical trials. The result has been a fragmented regulatory approach across the region to cannabis medicines, which will be a challenge for regulators to harmonize.
Although the Cannabis sativa plant has a long history as a source of medicines, its use as a means of treatment of illnesses had declined by the past century. In 1961, the United Nations’ Single Convention on Narcotics Drugs (CND) categorized it as a drug with no medical use, effectively ending its availability as a legal medicine in the many European and other countries that signed the treaty (1).
Its revival as a medical treatment over the past 20 years followed mounting scientific evidence that cannabinoids-substances found in the cannabis plant that act on specific receptors in the human brain and body-could effectively treat conditions like chronic pain and neurological disorders such a multiple sclerosis and epilepsy. Scientists also discovered that the human body has its own cannabinoids-endocannabinoids-and that synthetic cannabinoids could be made in the laboratory.
In certain countries, there has been a sharp rise in consumption of cannabis medicines after they were allowed to be prescribed or even made available without prescription. In the Netherlands, the medical use of cannabis-mainly for the treatment of chronic pain prescribed by pharmacists-went up from 6.9 per 100,000 patients in 2010 to 24.6 per 100,000 patients in 2016 (2).
Even countries with a relatively relaxed policy on the use of cannabis as a medicine broadly followed a regulatory framework laid down by an amended version of the 1961 CND.
Compliance with the treaty’s requirements on medical use of cannabis is monitored by the Vienna-based International Narcotics Control Board (INCB), which is responsible for the implementation of the UN drug control conventions, including the CND. The CND requires that governments establish a national cannabis agency to control the production and regulation of the supply of cannabis for medical use, according to the INCB’s latest annual report (3).
“The national agency is required to license producers, purchase and take possession of stocks, and maintain a monopoly on wholesale trading and stocks,” says the INCB (3). “All programmes for the medical use of cannabinoids must be developed and implemented under the full authority of the state concerned.”
The INCB is critical of what it regards as “poorly regulated” medical cannabis programmes. These programmes include allowing the use of cannabis for a wide variety of medical conditions in the absence of evidence of efficacy and safety from controlled clinical trials, the provision of nonâstandardized cannabis products under minimal medical supervision, and the cultivation of cannabis by patients themselves or the purchase of it from commercial outlets that produce cannabis illicitly.
The Netherlands, the first European country to relax rules restricting use of medical cannabis, introduced a law in 2003 allowing doctors to prescribe it for a wide range of conditions, leaving the doctor to judge whether it would be an effective treatment (1).
In compliance with the 1961 CND but also to ensure quality control, a single, private Dutch company, Bedrocan, has been granted a monopoly to produce cannabis, with its products mainly comprising the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), the compound that gives cannabis a euphoric effect. Bedrocan’s products are not only sold in the Netherlands but exported to several other European countries.
After Germany changed its legislation two years ago to allow doctors to officially prescribe medicinal cannabis products, the country’s Federal Institute for Drugs and Medical Devices (BfArM), its medicines licensing as well narcotics control body, set up a German Cannabis Agency.
“The functions of the Cannabis Agency are based on the requirements set out by the (amended 1961) Convention,” explained Prof. Dr. Werner Knoess, head of the new agency, in an interview in BfArM’s latest annual report (4). “We monitor the cultivation, harvest, quality assurance, storage, packaging, and distribution of cannabis to wholesalers and chemists or manufacturers.”
The agency has been selecting suitable companies to cultivate cannabis, which will then be purchased by the agency for distribution through third parties to medicine producers and pharmacists. The BfArM had to draw up its own pharmacopoeia monograph to ensure that the cannabis meets pharmaceutical-grade standards.
Because of what it regards as limited knowledge of the effectiveness and safety of cannabis medicines, the BfArM’s narcotics control branch is conducting a five-year survey on their application, due to be completed in 2022.
An increasing number of European states are now permitting access to unlicensed cannabis-based medicines through individualized schemes like named-patient systems and compassionate or exceptional use.
Under a law in Italy allowing any doctor to prescribe plant extracts, cannabis preparations for medical use can be provided by any pharmacy as long as it complies with the specifications on the prescriptions.
After a review by its Home Office (interior ministry) concluded that there was ‘conclusive’ or ‘reasonable’ evidence of the therapeutic benefits of cannabis-based medicines in the treatment of certain medical conditions, the UK government announced in October 2018 plans to change its Misuse of Drugs Regulations to allow doctors to prescribe unlicensed cannabis medicines (5). The doctors would have to be specialist physicians with knowledge of cannabis medicines and the conditions for which they have therapeutic value. They would be able to specify the formulation of the medicines to the manufacturer, which will have to meet GMP standards.
The United Kingdom is the home base of GW Pharmaceuticals, which over the past 20 years has been pioneering the development of cannabis-based medicines through the standard authorization procedure for pharmaceuticals including GMP quality assurance and controlled clinical trials.
The company’s lead product is Epidiolex, a CBD treatment for two childhood-onset drug-resistant epilepsy syndromes, Lennox-Gastaut and Draver. The drug was approved by the US Food and Drug Administration (FDA) in June 2018 and was due to complete the European Medicines Agency’s authorization process for marketing in the EU in the second quarter of 2019.
GW’s first cannabis medicinal product-Sativex, a mouth spray comprising 50/50 CBD and THC for relief of multiple sclerosis symptoms-was approved in the UK in 2010 and is now available in numerous countries across the world under marketing agreements with international pharma companies such as Bayer and Almirall.
The strategy being followed by GW is to maintain a world-leading position in cannabinoid medicines through its proprietary cannabinoid product platform. This includes the building-up of a library of internally generated novel cannabis types, development of in-house extraction, processing and analytical techniques, and in-house formulation and manufacturing capabilities.
Despite following the standardized route to the development and authorization of its products, GW is still subject in the UK and elsewhere to national regulations on controlled substances like cannabis. The company’s cultivation, manufacture, distribution, exporting, and importing of cannabis and its medical derivatives has to be regularly licensed by national narcotics agencies.
However, international monitoring organizations such as INCB are complaining that changes to national regulations to lift restrictions on medicinal cannabis are undermining controls on the recreational use of the plant’s extracts, particularly THCs.
The long-established system, backed by international treaties, of strict curbs on cannabis consumption is also being weakened by the spread of applications of cannabis-based substances to skin-care cosmetics and toiletries. CBD oils are even being made available as a food in Europe, although they have to be given approval as a novel food product to be marketed.
In November 2018, the expert committee on drug dependence at the UN’s World Health Organization (WHO) in Geneva recommended a relaxation of restrictions on cannabis and cannabis-related substances. The deregulation of the cannabis market may work against pharmaceutical companies focused on the development of high-quality but highly regulated cannabis-derived medicines.
CBD and THC are the only cannabinoids that have been researched in depth for their possible medical properties, but there are at least 70 others that may be effective medical treatments.
“We are at the forefront of [a] new area of science,” says GW (6). But the potential of that science may be more difficult to achieve with a decriminalized cannabis market in which the divide between recreational and medical use will become blurred.
1. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), “Medical Use of Cannabis and Cannabinoids,” Rapid Communication (Lisbon, December 2018).
2. B. de Hoop, E.R. Heerdink, and A. Hazekamp, Cannabis Cannabinoid Res., 2018 3(1) 54–55.
3. INCB, “Chapter I: Cannabis and Cannabinoids for Medical, Scientific, and ‘Recreational’ Use: Risks and Benefits,” 2018 Annual Report (Vienna, 5 March 2019).
4. BfArM, 2017–2018 Annual Report (Bonn, June 2018).
5. MHRA, “The Supply, Manufacture, Importation, and Distribution of Unlicensed Cannabis-Based Products for Medicinal Use in Human ‘Specials’,” Guidance Document (London, November 2018).
6. GW Pharmaceuticals, Annual Report and Accounts 2018 (Cambridge, 2019).
Pharmaceutical Technology Europe
Vol. 31, No. 6
When referring to this article, please cite it as S. Milmo, “Regulating Cannabis-Based Medicines in Europe,” Pharmaceutical Technology Europe 31 (6) 2019.