Questions and answers about the production of cannabis primary products and cannabis intermediate products

The company must maintain a system to ensure that security risks are dealt with. A security risk assessment must be performed and documented. If security situations arise, the company must consider if there is cause for taking further security measures. This risk assessment must consider the risks associated with the company’s production, including site access, staff, camera surveillance, alarm system, keys/codes, etc.

The company must ensure that access is restricted. Unauthorised persons are only permitted to enter the premises where production or handling of cannabis takes place if duly escorted. See further information in our Recommendations for security of companies that manufacture medicinal cannabis (PDF) (in Danish only).

The person responsible for security is a key figure, and the company must ensure that this person has the needed resources to complete their tasks adequately. This person must have thorough knowledge of the company’s security procedures. To be authorised by the Danish Medicines Agency as a person responsible for security, you must pass the assessment of good conduct by the Danish National Police.

You are generally not allowed to advertise for any cannabis primary products, intermediate products or end-products. Please see the thorough description given in the advertising provisions of the Act on a Medicinal Cannabis Pilot Programme and on a Scheme for Cultivation, Production, etc. of Medicinal Cannabis, Part IX.

When products are admitted to the Danish Medicines Agency's list of cannabis primary products for treatment of Danish patients, a product sheet is prepared with specifics about the product. This product sheet will be available on our website together with any instructions on how to prepare the product once the cannabis intermediate product has been admitted to the list. Find more information on the website of the Danish Medicines Agency (in Danish only).

The requirement for a competent person is very much like the qualified person (QP) that pharmaceutical companies are required to employ pursuant to the rules of good manufacturing practice for medicinal products (GMP). The competent person must be present to safeguard patient safety by vouching for the quality of the products and ensure that all requirements and rules have been complied with for every batch released to the market.

The competent person should be separated organisationally from the company's management and sales division as it will ensure that the competent person releases only products fulfilling the qualitative requirements. The requirement for a competent person is essential to ensure patient safety and quality, which is why this person's qualifications and independence are of utmost importance.

The competent person must be at the company regularly, and not only when products are to be released. The company determines the hours needed based on the activities of the company, but the Danish Medicines Agency considers that at least 10 hours are needed to justify that the person is at the company regularly.

A competent person cannot be approved before a new application or an application to vary an existing authorisation is submitted. Thus, the approval of a competent person takes place in connection with the review of applications. If the person fulfils the competent person requirements in the executive order and the guide ‘Requirements for and expectations of the competent person in a company authorised to produce cannabis products’ (in Danish only), approval of this person should not be a problem.

A competent person who does not fulfil these requirements will generally not be approved as a competent person by the Danish Medicines Agency.

It is only possible to export cannabis bulk and cannabis primary products – and thus not finished cannabis intermediate products for patient use.

Also note that imported cannabis primary products cannot be exported, neither as cannabis primary products nor as cannabis intermediate products.

A site is a geographical location. The manufacturing authorisation is site specific, which means that all geographical locations must appear on the authorisation with addresses and with a description of the activities carried out at each individual site.

Yes, manufacturers are permitted to subcontract activities, including storage and distribution, in Denmark. The requirements appear from the executive order on cannabis intermediate products (Danish title: Bekendtgørelse om cannabismellemprodukter).

A manufacturer of cannabis intermediate products can distribute their own registered cannabis intermediate products to wholesale distributors, pharmacies and hospital pharmacies, if relevant also by means of a carrier. If the manufacturer intends to use a carrier, they must enter into a contract with that carrier. Transportation of cannabis intermediate products is governed by the executive order on distribution of medicinal products (Danish title: Bekendtgørelse om distribution af lægemidler) and the executive order on euphoriant substances (Danish title: Bekendtgørelse om euforiserende stoffer).

The manufacturer of cannabis intermediate products can sell cannabis intermediate products to companies holding an authorisation for wholesale distribution of medicinal products and a relevant authorisation for handling euphoriant substances and to pharmacies and hospital pharmacies.

The pharmacy owns the cannabis intermediate product once it has received the product.

Thus, the pharmacy must arrange for the return of the product to the manufacturer usually by means of a carrier. Transportation of cannabis intermediate products is governed by the executive order on distribution of medicinal products (Danish title: Bekendtgørelse om distribution af lægemidler) and the executive order on euphoriant substances (Danish title: Bekendtgørelse om euforiserende stoffer). Transport is expected to take place without undue delay.

Yes, the activities of production, storage and/or delivery can be subcontracted, whereas this is not possible for the release of products.

A pesticide is also called a plant protection product or a herbicide. Pesticides are used to protect plants or plant products from pests such as fungi or insects or to prevent infestation from such pests. It can also be used to control weeds or prevent the growth of unwanted plants.

Pesticides can be both chemical substances and microorganisms. So, whether a substance is a pesticide depends on what it is going to be used for. It is not a question of whether the substance is chemical or of natural origin – or if it can otherwise be used in food products.

The use of natural predators is not considered as pesticide use.

The Pesticide Regulation 1107/2009 belongs under the Ministry of Environment and Food of Denmark. If the company is not sure whether a substance is a pesticide, the Ministry of Environment and Food of Denmark can help clarify the matter. If the ministry assesses it not to be a pesticide, the substance is not subject to the ban on pesticides of the Act on a Medicinal Cannabis Pilot Programme (Danish title: lov om forsøgsordning med medicinsk cannabis).

Read more about pesticides on the website of the Danish Environmental Protection Agency.

You can import cannabis that has been cultivated using certain permitted pesticides.

First of all, pesticides are only permitted in the cultivation of cannabis primary products for oral use (i.e. cannabis products taken by mouth and absorbed by the body through the gastrointestinal system in the same way as food products).

In addition, all the active substances (the exterminating/controlling substances) contained in the pesticide used must meet the following three conditions:

1. All active substances must be approved in the EU pursuant to Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market (the Pesticide Regulation); and
2. All active substances must appear from Annex IV of Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin, and
3. All active substances must appear from Annex 2 of the Danish Agricultural Agency's Guide on organic agricultural production (which is to say, permitted active substances for organic agricultural production).

The importer (manufacturer of cannabis intermediate products) must be able to document that the active substances contained in the pesticides used meet the three conditions for each single batch of cannabis to be imported.

The importer (the manufacturer of cannabis intermediate products) must go through the following steps:

1. The importer must obtain the exact chemical name, (ISO) common name or CAS number of the active substances contained in the pesticides used in the cultivation of the imported cannabis.
2. The importer must ensure that every active substance has been approved for use in the EU in the European Commission's database of approved active substances. To carry out an accurate search, the importer must know the exact chemical name, ISO common name or CAS number.

EU Pesticides Database: https://ec.europa.eu/food/plants/pesticides/eu-pesticides-database_en

1. The importer must check if every active substance also appears from Annex IV of the MRL regulation (Regulation (EC) no 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin). This check can also be run in the European Commission's database of approved active substances.
2. The importer must check that every active substance appears on the list in the Danish Agricultural Agency's Guide on organic agricultural production, Annex 2 – the list of products that may be used for plant protection in special cases.
   
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All the checks run by the company must be documented by a print-out from the database and references to the exact number in the MRL Regulation, Annex IV as well as the Guide on organic agricultural production.

When cannabis intermediate product manufacturers apply for admission of a cannabis intermediate product and its related primary product, they must submit documentation, including, inter alia, batch analysis results and analyses pursuant to the European Pharmacopoeia, Ph.Eur. 2.8.13, documenting that there are no pesticide residues in the cannabis primary product. This analysis is to establish that the product contains no other pesticides than those allowed.

The Danish Medicines Agency administers the rules on the import of cannabis to Denmark, including the rules on permitted pesticides. The agency also administers the rules on cultivation, production and distribution of cannabis bulk and production of cannabis primary products.

The Danish Environmental Protection Agency assesses if a substance classifies as a pesticide under the Pesticide Regulation as this falls under the agency’s remit.

The Danish Agricultural Agency publishes the Guide on organic agricultural production.

Two companies may enter into detailed quality agreements describing the division of responsibilities in relation to batch release. These are not the same as the QP-QP agreements appearing from annex 16 of EU-GMP, but the principles from annex 16 can be applied.

This means that it is acceptable for a competent person to base the release on partial deliveries from a competent person from another company as long as the standard EU-GMP requirements, e.g. for conclusion of a formal quality agreement and audits are, fulfilled.