Over the past few weeks the withdrawal of cannabis products from the German market has been a topic which generated a lot of publicity. Therefore, we want to share some tips on how to safely launch your medical cannabis products in the German market.
One of the biggest issues recently covered was the topic of irradiation. Cannabis flowers originating from Canada or the Netherlands are routinely irradiated in order to reduce the microbiological burden of the flowers. German law generally forbids the distribution of irradiated products; however, exceptions to this regulation have been granted. The provision of such exceptions is regulated by AMRadV (Irradiation Decree), which outlines the specifications with which a medicinal product must comply. Failure to comply with regulation may result in discontinuation of the distribution and marketing of a product, but this situation can be avoided as you will see in the following.
Looking at Irradiation
Why is irradiation required in the first place? First of all, it is important to bear in mind that the cultivation of plants is a non-sterile process. In fact, basic regulatory principles require high and consistent quality of a product, which in the case of medical cannabis refers among other aspects to a low level of microbiological contamination. This is published in the general texts of the European Pharmacopea for herbal medicines (PhEur 5.1.8 and 5.1.4). Herbal medicines such as dried cannabis flowers and extracts have to comply with official limits for microbiological contamination in oral or inhalation formulations. To assure that the therapeutic activity is not affected, limits or absence for different microorganisms have to be met, for example for aerobic bacteria, yeast or mold or particular strains of E.coli and Salmonella.
In some cases the manufacturing process can lead to high level of bioburden, thus an additional method for decontamination such as gamma-irradiation is used to limit microbiological contamination (PhEur 5.1.1). If this is the method of choice for your products, you will need to illustrate as part of your AmRadV submission that irradiation is the appropriate method for the reduction of such bioburden.
In the course of submission for a license, the required documentation may be elaborate and may range from the manufacturing process and its validation to equipment to risk evaluation to stability data of the irradiated product, all of which results in the compilation of an entire dossier.
Access to the German Market
One of the first steps to enter the German market is the founding of a German company. This company has to be established in Germany with a Managing Director in place. The German system is a federal system with different local authorities, thus the location of the company offices defines the authority responsible for the processing of applications. It should be considered that the local interpretation of the legal situation for medical cannabis may differ among the various federal states.
The Managing Director has to be supported by committed roles within the company, all of which are described in your internal Quality Management System (QMS). QMS provides clarity by defining roles, responsibilities and processes, thereby ensuring that your product is manufactured, imported, released and distributed according to the underlying principles of Good Manufacturing Practice (GMP) requirements as outlined in the GMP guide of Eudralex, volume 4.
Setting up a Quality Management System
If you do not have just one company involved in the supply chain, the setup of the supply chain is crucial for your launch readiness and interactions among the various parties in the supply chain. There are several service providers that you may want or need to involve in your business. The responsibilities of these providers have to be agreed upon and described in the QMS, and once completed, communicated to the authorities.
For example, you may involve a manufacturer for cannabis flowers or extracts, a final packager for your product, a storage company for your product, a test lab for performing testing and a wholesaler for distributing the product on your behalf. However, the final responsibility for the quality of the product lies with the Managing Director of your German company.
Once you set up business, and quality agreements with all the third parties are in place, consider that the most detailed stipulations are required for the manufacturer. It is important to keep in mind that the location of the manufacturer will impact your local regulatory activities. In case the manufacturer is located outside the EU, your company has the role of an importer into Germany/Europe and needs to hold an import license [acc. to section 72 Medicinal Products Act (Arzneimittelgesetz (AMG)]. In case the manufacturer is located in Germany or the EU, this license application is not required. Nonetheless, all manufacturers are required to hold a GMP authorization, and we advise you to review the existing one relevant for the submission to the authority. Obtaining the GMP authorization anew will require some extra time in order to conduct additional inspections.
Finally, your product cannot be sold in the German or any European market, unless a Qualified Person has released the product based on specifications and testing results. This person has to live in the EU and can either be employed in your company or act on your behalf.
The above mentioned details are relevant for the following four licenses, as they play an important role in the ability to launch a product in the German Market:
1) The narcotic license is required for every party handling the product if you are distributing and marketing medical cannabis with a THC-content above 0.2% [acc. to section 3 Narcotics Act (BtMG)].
2) The pharmaceutical company registration is required if your marketing plans foresee including your company’s name on the product label. From a liability point of view, this means that the company is responsible for placing the product on the German market and has to be registered as a pharmaceutical company (acc. to section 67 Medical Products Act).
3) The Import License is required (acc. to section 72 Medical Product Act) in case you import medical cannabis from countries outside the EU.
4) The wholesaler distribution authorization may become relevant for companies bringing medical cannabis to the German market (acc. to section 52 Medical Product Act).
Once you have had a chance to take a closer look at the above mentioned topics, you will be able to navigate through the main challenges confronting you when distributing and marketing medical cannabis in the German market. Should you have additional questions about this topic please feel free to contact us.