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
Cannabis is listed in Schedule 1 of the Misuse of Drugs Regulations (1988), as amended. In 2019, Ireland implemented the Misuse of Drugs (prescription and control of supply of cannabis for medical use) Regulations 2019 to facilitate the import, prescription and supply of cannabis-based products that meet the requirements of the regulations under the Medical Cannabis Access Program (MACP).
The first stage of the MACP is for companies to apply for assessment of their product by the Health Products Regulatory Authority (HPRA) for suitability and inclusion — according to Schedule 1 — as a specific controlled drug.
When accepted, prescription via a registered medical consultant is possible for patients who failed to respond to standard treatments for the following medical conditions: spasticity associated with multiple sclerosis, intractable nausea and vomiting associated with chemotherapy and severe, refractory (treatment-resistant) epilepsy.
Currently, only three cannabis-based products have been accepted. As part of the MACP, the Health Service Executive (HSE) will keep a central register to record data including enrolled prescribers, anonymised patient identifiers and the products prescribed/supplied. The MACP is running on a pilot base for 5 years.
CBD as a pure substance (that is, manufactured synthetically) does not fall under the Misuse of Drugs legislation. CBD products produced from hemp (Cannabis sativa) via cold pressing are legally accepted owing to their low quantities of THC; however, health claims are not accepted when selling as food supplements. Products containing CBD extracted via CO2-extraction fall under the Novel Food Regulation (EC) 2015/2283 and require a market authorisation.
In 2001, the Office of Medical Cannabis was established as the concerned authority controlling the cultivation and delivery of cannabis for medical and scientific purposes. Cannabis is defined as soft drug (List II) and underlies the Dutch Narcotic Act.
The cultivation of cannabis started with a first licence in 2003 to Bedrocan. In 2019, the Netherlands developed plans to licence a second company for the cultivation of medical cannabis to overcome shortages of the product in Europe.
Cannabis-based products carrying a medical claim fall under the Medicinal Product Act. Products containing CBD in combination with THC fall under the Opium Act and require a prescription, whereas products containing pure CBD do not fall under the Opium Act but still need a prescription.
Dutch law is working with exceptions to the established guidelines to make CBD-based products legal for marketing, should they fulfil the following prerequisites:
Advice from the Medicines Evaluation Board or Netherlands food and consumer product safety authority regarding product categorisation is recommended.
Medical cannabis has been legal in Portugal since 2018, with law No. 33/2018 (18 July) establishing the legal framework for use, preparations and substances for medical purposes, including prescription and dispensation in pharmacies connected to a licence from the National Authority for Medicines and Health Products (Infarmed). Cultivation of cannabis is under state control and permission via a licence is needed.
An amendment of law 33/2018 in 2018 classified CBD for medical use only, leading to the availability of CBD-based products only by prescription. To import cannabis or CBD requires a licence to be issued by Infarmed.
CBD as food and/or a food supplement has been banned since 2018, owing to the Novel Food regulation. Cosmetic products are legally regulated by regulation (EC) No. 1223/2009, consultancy No. 15/CD/2013, decree-law No. 189/2008 (24 September) and prohibit the use of narcotic substances. Consultation with Infarmed is recommended for classification before marketing a product containing CBD as a non-psychogenic substance.
Here, a legal regulation on medical cannabis is still missing. The Spanish Agency for Medicines and Medical Products (AEMPS) prohibits cannabis and cannabis extracts being dispensed for medical use, although authorisation for the cultivation of cannabis plants for medical and scientific purposes are granted.
The national legal background on narcotic drugs is laid down in law 17/1967 (8 April), implementing the regulation on narcotic drugs according to the provisions of the 1961 United Nations Single Convention.
As Spain has a strong tradition of Cannabis Social Clubs (CSCs), medicinal users may have access to cannabis by joining one. Regarding quality and safety, this is still an unsatisfactory situation: relevant analysis to ensure the absence of pesticides and other residues are not done and the concentration of active ingredients is unknown.
The marketing of products containing cannabidiol was stopped almost immediately, with CBD being defined as a novel food by the Novel Food Regulation (EC) 2015/2283), which was implemented on 1 January 2018. Supervising authorities of the food market stopped the marketing of CBD products in Spain in 2018. Spain lacks a national regulation for cannabis to be used as food.
Cannabis is a Class B controlled drug in the UK, listed in Schedule 1 of the MDR (2001) and in the Misuse of Drugs Designation Order (2015). However, in 2018, so-called cannabis-based products for medicinal use in humans (CBPM) were included in Schedule 2 of MDR (2001), allowing specialised physicians to legally prescribe them to patients with unmet clinical needs without requiring a Home Office licence.
Nevertheless, companies wishing to supply or manufacture these products still need a Home Office Controlled Drug licence.
A CBPM is defined as a medicinal product or substance used in the preparation of a medicinal product, which contains cannabis, cannabis resin, cannabinol or a cannabinol derivative and are unlicenced products prescribed on a “named patient” basis.
Cannabidiol (CBD) in its pure form does not fall under the control of the MDR (2001). A CBD product with a medical claim needs marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA).
Following the MDR (2001) update and the resultant mix of licenced and unlicenced status of such medicines in the UK, the National Institute of Health and Care Excellence (NICE) published a guideline on 11 November 2019 that covers the prescription of cannabis-based medicinal products for specific conditions.
The NICE committee determined that the initial prescription of such a product must be made by a specialist medical practitioner who should also have a special interest in the condition being treated.
Products covered by the guideline include CBMPs (as set out by the UK government in the 2018 regulations), licenced products, THC with CBD (Sativex) and nabilone, plant-derived cannabinoids such as pure CBD and synthetic compounds that are identical in structure to naturally occurring cannabinoids (such as dronabinol).
Regulation 2 of the MDR (2001) allows that some products may be considered to be exempt from control in limited circumstances. To market a CBD product containing cannabinoids (such as. THC), it must meet all three requirements of the exemption definition.
These specify that the controlled drug should not be designed for use as a narcotic, the controlled drug cannot be recovered by readily applicable means and limits the maximal amount of each component of controlled drug to one milligram per product or preparation.
Concerning food products, the Food Standards Agency (FSA) clearly stated: “Businesses need to submit and have fully validated, novel food authorisation applications by 31 March 2021. After this date, only products for which the EFSA has a valid application will be allowed to remain on the market.”
Manufacturers of cannabis-based products should obtain legal advice regarding product classification with their respective national authorities to reduce time-to-market and ensure that their products are compliant with the relevant national legislations.