Successful marketing of medicinal cannabis and cannabis-derived products: part I

Barbara Siebertz, Senior Manager, Regulatory Affairs and Special Projects, and Ute Hegener, Director, Regulatory Affairs at PharmaLex, discuss the current legal and marketing situation in Europe

The European Union (EU) is missing a harmonised law on the medical and, if appropriate, recreational use of cannabis. A high-level overview of the national legal requirements of some European countries on medical medicinal cannabis is provided below, thereby highlighting the differences within the EU.

Denmark

In December 2017, Denmark adopted its legislation for a 4-year medical cannabis pilot project, allowing physicians to prescribe cannabis products which, until then, were not legal in Denmark. With the implementation of the medicinal cannabis pilot programme, cannabis is legally available.

Cultivation and production for medical use started with the introduction of a special development plan, giving companies the ability to apply for a cultivation and handling license to produce cannabis for patients as well as for export. Up until now, licenses have been given to two companies.

Since 1 July 2018, the Executive Order on Euphorizing Substances was amended. Hemp (content of tetrahydrocannabinol [THC] up to 0.2%) does not fall under the definition of a euphoriant substance.

Depending on the products manufactured from hemp, rules on medicines, food and food supplements need to be followed. Denmark defines cannabidiol (CBD) as a pharmacological substance, so only products with a low concentration of CBD might be classified as a food supplement.

France

In France, cannabis is regulated by the Code of Public Health, including “narcotic substances.” Article R5132-86 lists the kind of exclusions that are effective for

  • cannabis, plant and resin, products containing it or those obtained from cannabis, plant or resin
  • tetrahydrocannabinols, except for delta 9-tetrahydrocannabinol, and its esters and ethers, salts and the salts of the afore cited derivatives and products containing them.

The Code of Public Health also lists exceptions (Article R5132-86-1) to the exclusions, such as delta 9-tetrahydrocannabinol for the production of Marinol, which is authorised as part of a Temporary Use Exemption by name.

After establishing a group of experts in September 2018, the Temporary Specialized Scientific Committee (CST) analysed the use of medical cannabis in other European countries, the results of clinical trials and medical literature.

The National Agency for Safety of Medicines and Health Products (ANSM) subsequently accepted the CST’s proposal to allow medical use for certain defined indications, including palliative situations or the painful spasticity of multiple sclerosis.

With the various government departments concerned, ANSM started to prepare the technical arrangements necessary to establish an experimental phase. According to information from Franceinfo, ANSM announced on 22 January 2020 that the medical cannabis experiment will start in September 2020 and will include approximately 3000 patients. The planned time schedule of this experimental phase is 2 years.

Another exception to the Code of Public Health is related to cannabis that’s free from narcotic properties (Article R5132-86, II Subsection 2) and describes authorisation by ministerial order for culture, importation, exportation, industrial and commercial use.

A ministerial order dated 22 August 1990 defines the conditions for cannabis-based non-narcotic requirements and allowed the manufacturing of liquids for electronic cigarettes, cosmetic products or capsules as legally acceptable. Concerning CBD products, MILDECA (Mission Interministérielle de Lutte Contre les Drogues et les Conduites Addictives) published an update of the legislation (Cannabidiol [CBD] le point sur la législation) in June 2018.

Germany

With the amendment of the German Narcotic Drug Law in March 2017, the doors were opened to market medical cannabis products in Germany. The basis of the amendment were the definitions of cannabis in Annex I and III of the Narcotic Drug Law.

Annex I of the Narcotic Drug Law lists cannabis as a non-marketable narcotic drug, but defines certain exemptions: for seeds, for specific certified varieties originating from European countries, the content of THC may not be more than 0.2%, and only for use as defined in Annex III.

Annex III defines exemptions for the marketing and prescription of narcotic drugs to which cannabis was added as follows: “Cannabis (marijuana, plants and parts of plants belonging to the species of Cannabis) based on state-controlled cultivation according to article 23 and 28 paragraph 1 of the Single Convention on Narcotic Drugs from 1961, as well as preparations approved and authorised as finished medicinal products.”

Germany’s supervising authority on medical cannabis is the “Cannabis-Agentur.” A tender on cultivation of medical cannabis in July 2018 led to signed contracts with three companies, for a total amount of 10,400 kg of cannabis, scheduled for a period of 4 years. The first harvest is expected in the last quarter of 2020.

Cannabinoids, not being psychoactive, do not fall under the Narcotic Drug Law. A careful review of the production process is considered as CBD extracts from the plant or parts of the plant might still contain psychoactive substances (such as THC) and will then fall within the remit of the Narcotic Drug Law.

In 2016, CBD was transferred to the list of prescription substances, without no restriction on strength, leading to necessary prescriptions for CBD products with a medical claim.

As CBD-containing products (or CBD itself) have not been used as foods or food ingredients before 15 May 1997, these products are defined as Novel Foods, according to the Novel Food regulation ([EC] 2015/2283), implemented on 1 January 2018.

The Higher Regional Court of Hamm, Germany, had already decided in 2016 that the precondition for marketing cannabis-based products, such as CBD oil, is the cultivation of plants with a THC content below 0.2% from certified seeds for the purpose of commercial and scientific use.

With this decision, cannabis-based products containing CBD, with a TCH content less than 0.2%, such as CBD oil, were not marketable in Germany. Two other court decisions prohibited the marketing of CBD products, as these products are either defined as Novel Foods and, as such, need a marketing authorisation, or contained THC contents that were higher than the legal limit of 0.2%.

Cannabinoids, not being psychoactive, do not fall under the remit of Germany's Narcotic Drug Law

The use of cannabis in cosmetics is regulated by entry 306 of Annex II to Regulation 1223/2008. Narcotic drug substances are excluded from use in cosmetics, thereby excluding Cannabis. This restriction is not applicable to the use of hemp seed oil or synthetically produced cannabidiol, but still excludes plant-derived cannabidiol.

Italy

Decree 309/90 is the Law on Narcotic Drugs (governing psychotropic drugs and substances, prevention, treatment and rehabilitation of the related states of drug addiction). Psychotropic substances are defined and divided in four tables according to Article 14; Cannabis is listed in Table II (Table II and Table IV provide for minor penalties).

From November 2015, the Italian Competent Authority took the responsibility of supervising all companies registered for cultivation, manufacture, use, marketing and sale of psychotropic substances. The Italian Competent Authority has the only license to grow medical cannabis in Italy.

To ensure patient demand for medical cannabis, Italy ran an additional tender in July 2019. Import licenses for medical cannabis are now issued to companies from the Netherlands and Canada.

The Italian Legislation differentiates between two different categories products:

  • products containing THC (controlled substance) are considered to be medicinal products only
  • products containing CBD without THC or THC at a very low levels are considered to be cosmetics, food supplements or medical devices; only extracts derived from Cannabis sativa seeds are allowed for this category.

Medical products are prescribed as magistral preparations (non-renewable medical prescriptions on a named patient basis) and are considered to be “off-label,” also needing authorised consent by the patient. Marketing as food or a food supplement is admitted only for products containing traces of THC below 0.2 mg/kg.

A decree dated 4 November 2019 established maximum levels of THC in food and food supplements; for the latter, the limit is 0.2 mg/kg (the sum of [–]–trans-Δ9-THC and its non-active precursor Δ9-THCA-A and Δ9-THCA-B.)

For food use, Law n. 242 dated 2 December 2016 set a maximum THC concentration in cultivated cannabis, which is 0.2% and, in any case, may not exceed 0.6%. It’s applicable to varieties listed in the Common Catalogue of varieties of agricultural plants, following Article 17 of the Directive 2002/53/EC.

Companies