GxP-Blog

Cannabis can be prescribed in various forms in Germany:¹

• dried cannabis flowers “marijuana”
• isolated main active ingredient tetrahydrocannabinol (THC) “Dronabinol” for production of prescription medication (drops, capsules);
• standardized cannabis extracts as prescription medication;
• finished medicinal product, e.g. Canemes 1 mg capsules contain the substances nabilone, a fully synthetic THC analogue.

As early as 2018, pharmacies in Germany were already filling around 95,000 prescriptions² just at the expense of the statutory health insurance companies for about 145,000 dispensing units of cannabis-containing preparations, including unprocessed cannabis flowers.

While in Austria the medications dronabinol are approved in various preparations from pharmacies (capsules, drops, alcoholic solutions), along with nabiximols (THC and CBD) and nabilone (a purely chemical substance related to THC), the sale of cannabis flowers containing more than 0.3 % THC is not permitted. The Narcotic Substances Act also forbids the prescription of what is known as “medical cannabis”.³

In Switzerland, cannabis is classified as a prohibited narcotic substance. However, prescription of forbidden medicinal substances based on cannabis for medicinal purposes is allowed in certain circumstances. A cannabis medication is a narcotic substance based on cannabis with a standardized active ingredient content, which must meet safety and quality criteria in accordance with the therapeutic products legislation. In Switzerland, a doctor can prescribe a cannabis-containing medication (e.g. known as “magistral formula prescriptions”, i.e. therapeutic substances manufactured by a pharmacy on doctor's prescription).⁴

The non-medical use of cannabis should be mentioned here for information purposes only, since in addition to the cannabis preparations prescribed as medicines, there are also legal uses of CBD-containing products such as cosmetics, teas, aromatic oils, smoking products or dietary supplements. The regulations on non-medical cannabis use also vary from country to country. This opens many possibilities, along with doctor’s prescription, to offer consumers CBD in various forms. It is for this purpose that an increased demand for cannabis plants as the necessary raw material should be expected.

To meet the increasing demand for cannabis flowers for medical use, a government agency known as the Cannabis Agency was set up in Germany within the Federal Opium Agency at the Federal Institute for Drugs and Medical Devices (BfArM).

The Cannabis Agency grants growing rights, for “lots”, and oversees the growing of medical cannabis in Germany.

To receive such a public contract, the bidder, i.e. the company that would like to grow cannabis, has to submit a bid. Legal, scientific, financial, and technical information has to be provided with the bid documentation.

In April 2019, four-year contracts were awarded for the first time for growing and harvesting a total of 7200 kg of medical cannabis.

Growing and harvesting will now take place in operations that have the right to grow.

For this purpose, the Cannabis Agency and the grower sign a contract with commercial provisions and delimiting the pharmaceutical responsibilities. The content of this contract resembles the manufacturing of bulk and finished product drugs. References are made in different parts of the contract to the EU GMP Guidelines Part I. This makes it clear that this manufacturing goes beyond that of an herbal raw material. The specifications of the Cannabis Agency require the filling and packing of the processed cannabis flowers as bulk goods in bundles.

Thus, the flowers intended for supply to wholesalers, pharmacies, and extract manufacturers would be considered a bulk drug. Finally, they have to go through additional processes after harvesting such as drying, treatment to reduce germs, if applicable, and packaging—but not final packaging.

The Cannabis Agency then takes over the sale of the cannabis itself.

As with other medicinal plants, the growing, harvesting, and controls must meet all the requirements of the monograph of the German Pharmacopoeia (DAB), “Cannabis Flos” in this case, and the “Herbal Drugs” monograph of the European Pharmacopoeia. All guidelines on the quality of herbal drugs must be followed.

The entire process from growing to packing and handing over the cannabis flowers must be carried out under a quality management system.

While herbal drugs for the manufacture of medicinal products are usually grown and collected in the wild or grown in open fields, it is mandatory in Germany for cannabis plants used for medical purposes or processing to be cultivated indoors.

The controlled growing conditions allow for prevention of quality fluctuations, which are inherent in open field cultivation.

The quantity of light, its quality and duration is controlled by artificial lighting. This way, the cannabis plants are exposed to a regulated photoperiod.

Other environmental factors that can be used to standardize plant growth are CO₂ concentrations in the air, temperature and humidity, as well as water and nutrient supply.

Furthermore, cannabis flowers for medical use fall under the Narcotic Drugs Act. This alone is a reason to ensure the highest security requirements for buildings where the plants are grown. This includes, among others, the installation of an alarm system connected directly to the police.

The DAB monograph on cannabis flowers describes three product groups with different composition of the substances THC and cannabidiol (CBD). The Cannabis Agency makes much more detailed demands on the content that the cannabis to be supplied must have, depending on the lot.

The cannabis flowers must meet the pesticide residue requirements and heavy metals, aflatoxin content, and microbial impurities limits.

The enterprise that received the contract to grow cannabis must analyze the cannabis flowers after harvest, i.e. have them tested either in its own lab or externally, and issue an analysis certificate. The growing farm is also responsible for batch release in accordance with Annex 16 of the EU GMP Guidelines.

Last, but not least, the Cannabis Agency sets requirements for the packaging and labeling of cannabis flowers.

A stability test on the harvested plants is binding.

• GACP (Guideline on Good Agricultural and Collection Practice for Starting Materials of Herbal Origin)
• GMP
• Annex 7: Manufacturing of herbal drugs
• Regulations on storage in accordance with the Narcotic Drugs Act, Safety Guideline

Legally required approvals for enterprises that grow and/or process cannabis

• Permit in accordance with Section 3 BtMG 
• Manufacturing permit in accordance with Section 13 AMG

Do you need support with establishing these highly demanding conditions or meeting the legal requirements? We are here for you.

1   https://www.gelbe-liste.de/wirkstoffe/Cannabis_53341
2   Prescription medication, finished medicinal products are added to that, see ABDA, 2 Years of the ‘Cannabis Law’ – Clearly More Prescriptions, Berlin, March 4, 2019
3  https://www.abda.de/pressemitteilung/2-jahre-cannabis-gesetz-deutlich-mehr-verordnungen/
4  https://www.netdoktor.ch/therapie/cannabinoide-rechtliche-lage-7262509
5  https://www.bag.admin.ch/bag/de/home/medizin-und-forschung/heilmittel/med-anwend-cannabis.html

Literature:

Tender Procedure for Cultivation, Processing, Storage, Packaging and Supply of Medical Cannabis, Specifications, date: July 18, 2018

CONTRACT FOR CULTIVATION, PROCESSING, STORAGE, PACKAGING AND SUPPLY OF MEDICAL CANNABIS, date: August 27, 2018

ABDA, 2 Years of the ‘Cannabis Law’ – Clearly More Prescriptions, Berlin, March 4, 2019

ABDA Fact Sheet: Prescription Drugs with Cannabis, July 4, 2019

www.deutsche-apotheker-zeitung.de/daz-az/2018/daz-21-2018/high-tech-anbau-von-cannabis