Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs
Marval, O’Farrell & Mairal / Italy
The key facts about regulatory reforms in Italy. Prepared in association with Baker Mckenzie, a leading law firm in Italy, this is an extract from The Pharma Legal Handbook: Italy, available to purchase here for GB 119.
Cannabinoid Drugs
1. Are Cannabinoid Drugs authorized in your country?
In Italy, the use of recreational cannabis is prohibited under Presidential Decree no. 309/1990 (the “Presidential Decree”).
However, it is possible to use cannabis for medical purposes.
Indeed, the Decree of the Ministry of Health no. 98 of 28 April 2007 (the “2007 Decree”) officially recognized and acknowledged the therapeutic properties of cannabis and updated the tables annexed to the Presidential Decree listing active principles and their medicinal compositions (in particular, Delta-9-tetrahydrocannabinol (THC), Trans-delta-9-tetrahydrocannabinol (Dronabinol), and Nabilone were added to the table II-B of the Presidential Decree and admitted to importation).
The 2007 Decree also authorized physicians in Italy to prescribe extemporaneous preparations (preparazioni magistrali) made by pharmacists using either Dronabinol or a plant-based active substance based on Cannabis for medical use.
The Decree of the Ministry of Health of 23 January 2013 (the “2013 Decree”) has subsequently inserted additional active compounds of cannabis origin in the table II-B of Presidential Decree.
In addition to the national legislation, there are also a number of regional laws allowing the administration and, in some cases, the production of medicine and extemporaneous preparations based on cannabinoids for therapeutic purposes. These regional laws provide for easier and cheaper access to cannabinoid-based drugs or have authorized new clinical trials or production of these drugs.
2. What are the regulatory authorities with jurisdiction over Cannabinoid Drugs?
According to art. 2.1, letter d) of the Presidential Decree, the Regulatory authority with jurisdiction over cannabinoid drugs is the Ministry of Health (“MoH”) which also represents the State Cannabis Body (Organismo statale per la cannabis), as provided under the Convention on Narcotic Drugs adopted in New York on 30 March 1961.
3. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Cannabinoid Drugs?
Cannabinoid drugs are subject to the general provisions set out by the Presidential Decree for the authorization, use, import, export and market of narcotic drugs and psychotropic substances.
In particular, pursuant to art. 17 of Presidential Decree, anyone who intends to carry out any of the aforementioned activities shall obtain the prior authorization from the MoH, and another, additional, permit is requested to import or export such products. The authorizations issued by the MoH have a two-years duration and are subject to the payment of a government concession fee. However, the obligation to obtain the aforementioned authorizations does not apply to pharmacies with reference to the purchase, sale and administration of narcotic drugs and psychotropic substances.
As for the pricing and reimbursement, there is not a specific legal framework for cannabinoid drugs. Indeed, the general framework provided for by the Decree of the Ministry of Health of 2 August 2019 (the “2019 Decree”) applies to cannabinoid drugs as well.
4. Which are the cannabinoid drugs that have received market approval to date?
As of today, to our knowledge, only one medicinal product based on extracts of cannabis sativa has been authorised for marketing (i.e., SativexR), which is generally prescribed to alleviate the symptoms in adult patients suffering from moderate to severe spasticity due to multiple sclerosis, who have not shown an adequate response to other, different, antispasmodic drugs and have shown a clinically significant improvement with reference to spasticity symptoms during an initial test period of therapy.
5. Who can prescribe Cannabinoid Drugs?
Since 2007 Decree came into force, any physician is eligible to prescribe cannabis products and synthetic cannabinoids for therapeutic use; subsequently, the 2013 Decree also authorized physicians to prescribe cannabis-based drugs of vegetable origins.
6. Is there a list of doctors authorized to prescribe Cannabinoid Drugs?
There is no list of physicians authorized to prescribe cannabinoid drugs.
7. What approvals or notifications are required to prescribe Cannabinoid Drugs?
No specific approval or notification is required to prescribe cannabinoid drugs.
There are, however, some general procedural obligations set forth by articles 38 to 45 of the Presidential Decree to be followed.
In addition, art. 61 of Presidential Decree requires pharmacists to keep a specific register to record the quantities and qualities of drugs included in the first four tables of the Presidential Decree that have been sold or used during the year.
8. Which organizations are authorized to sell/distribute Cannabinoid Drugs available?
According to art. 17 of the Presidential Decree, anyone who intends to produce, employ, import, export, receive for transit, trade in any capacity or otherwise possess for trade narcotic and psychotropic substances referred to in art. 14 of the Presidential Decree (which includes THC and its derivatives) has to obtain the prior authorization from the Ministry.
The market authorization for SativexR is held by GW Pharma. However, since SativexR is considered a “class H” drug, it is not dispensable in pharmacy, but it can be distributed by the Local Health Companies, A.S.L and Hospital Health Companies, A.S.O..
9. Is there a list of retailers/ distributors authorized to sell Cannabinoid Drugs?
Yes, according to art. 16 of the Presidential Decree, the list of all companies and entities authorized to grow, produce, use and market narcotic and psychotropic substances is kept by the MoH, published on the Official Gazette and annually updated through decree of the MoH.
10. Are there proposals for reform or significant change to the regulation of Cannabinoid Drugs?
N/A.
11. When are they likely to come into force?
N/A.
Medicinal Cannabis
12. Is Medicinal Cannabis authorized in the country?
Yes, medicinal Cannabis is legal in Italy since the approval and entry into force of the 2007 Decree, which officially recognized the therapeutic properties of Cannabis and updated the tables annexed to the Presidential Decree listing active principles and their medicinal compositions.
However, the Decree of the Ministry of Health of 9 November 2015 (“2015 Decree”) provides that the medical use of cannabis cannot be considered a therapy on its own, but rather a treatment supporting standard therapies, when the latter have not produced the desired benefits, or have resulted in side effects that cannot be tolerated, or require dosage increases that could lead to the appearance of side effects.
The 2015 Decree also established the uses for which medical cannabis may be prescribed.
13. What are the regulatory authorities with jurisdiction over Medicinal Cannabis?
According to art. 2.1, letter d) of the Presidential Decree, the Regulatory authority with jurisdiction over cannabinoid drugs is the Ministry, which also represents the State Cannabis Body (Organismo statale per la cannabis), as provided under the Convention on Narcotic Drugs adopted in New York on 30 March 1961.
14. What is the regulatory framework for the authorization, pricing, and reimbursement of Medicinal Cannabis?
Article 17 and 19 of the Presidential Decree provide the authorization procedure to be followed for growing, producing, importing, exporting, commercializing and deploying medical cannabis. Such authorization requirement, however, does not apply to pharmacies.
The procedure for setting the price of medical cannabis is set out in point 6 of the Technical Annex to the 2015 Decree, which states that the price of medical cannabis is to be fixed by revising the Annex A to the Ministerial Decree of 18 August 1993 every two years by means of Decree of the Ministry. The current price is set to 9 Euros/gram.
As for the reimbursement, the 2015 Decree, in point 3 of the relevant Technical Annex establishes that the rembursement of medical cannabis by the National Healthcare System (“NHS”) is subject to the indications issued by the single Regions or Autonomous Provinces. As of today, 8 Regions authorized the reimbursement for all the uses of medical Cannabis established by the aforementioned 2015 Decree and one (Apulia) even extended the uses for which medical cannabis can be prescribed and refunded.
15. How is the production and import of Medicinal Cannabis regulated and by which agencies/authorities?
According to art. 17 of the Presidential Decree, anyone who intends to grow, produce, import, export, commercialize and deploy medical cannabis shall obtain the prior authorization from the MoH. However, there is no need for such authorization in case of pharmacies, which are expressly exempted from the authorization process.
Note that if someone has already obtained the authorization from the Ministry and intends to import or export medical cannabis, an additional permit from the Ministry shall be obtained and the procedural obligations established by articles 51 to 55 of the Presidential Decree shall be complied with.
The authorization issued by the Ministry has a two-years duration and is subject to the government concession fee. Additionally, art. 3 of the 2015 Decree states that the MoH (i) has decisional power over the areas in which Cannabis plants can be cultivated (ii) establishes the imported, exported and distributed quantities on the national territory, (iii) authorises the import, export, wholesale distribution and store of Cannabis plants and plant material, and (iv) provides for the determination of the production quotas of active substance of plant origin based on Cannabis on the basis of the requests of the Regions and Autonomous Provinces.
16. What approval or notifications are necessary to produce or import Medicinal Cannabis?
According to art. 1 of the 2015 Decree, the MoH has the power to import medical cannabis and to authorise its import, according to the procedure established by articles 17 and 27 of the Presidential Decree. Such procedure prescribes the obtainment of a first, prior authorization for the production of the drugs included in the tables attached to the Presidential Decree and, in case of import, a second permit is needed from the MoH.
17. What is the regulatory framework for the marketing and distribution of Medicinal Cannabis?
The regulatory framework for the marketing and distribution of medicinal cannabis is established by articles 37 to 42 of the Presidential Decree, under which anyone who intends to market and distribute narcotic drugs and psychotropic substances has to present a formal request to the MoH, providing the information required by art. 37 of the Presidential Decree.
Subsequently, the MoH, after carrying out the necessary verification procedure, may grant the authorization and eventually set the requirements and conditions to be complied with. Additional procedural requirements are set forth by articles 38 to 42 of the Presidential Decree.
18. How can patients obtain Medicinal Cannabis?
According to the 2015 Decree, patients can be prescribed medical cannabis from physicians if they present one of the following symptoms (indicated in point 4.1 of the Technical Annex to the 2015 Decree):
• analgesia in pathologies involving spasticity, associated with pain resistant to conventional therapies;
• analgesia in chronic pain where treatment with non-steroidal anti-inflammatory drugs or with cortisone or opioid drugs has proved ineffective;
• the anticinetosic and antiemetic effect in nausea and vomiting, caused by chemotherapy, radiation therapy, HIV therapies, which cannot be achieved with traditional treatments;
• the stimulating effect of appetite in cachexia, anorexia, loss of appetite in patients with cancer or AIDS and in anorexia nervosa, which cannot be obtained by standard treatment;
• the hypotensive effect in treatment-resistant glaucoma;
reduction of involuntary body and facial movements in Gilles de la Tourette syndrome which cannot be obtained with standard treatments.
19. Who can prescribe Medicinal Cannabis?
Since the entry into force of the 2013 Decree, which amended the Presidential Decree and inserted cannabis-based active compounds of plant origin in the table II-B, physicians are authorized to prescribe medicinal cannabis.
20. Is there a list of doctors authorized to prescribe Medicinal Cannabis?
N/A.
21. What approvals or notifications are required to prescribe Medicinal Cannabis?
No specific approval or notification is required to prescribe medicinal cannabis. However, there are particular requirements that the relevant prescription sheet has to comply with in order to be valid, as established in art. 43 of the Presidential Decree. In addition, art. 61 of Presidential Decree requires pharmacists to keep a specific register to record the quantities and qualities of drugs included in the first four tables of the Presidential Decree that have been sold or used during the year.
22. Where is Medicinal Cannabis available?
Medicinal cannabis is available at pharmacies, in accordance with the Presidential Decree.
23. Is there a list of retailers authorized to sell Medicinal Cannabis?
On 4 April 2022, the MoH and the Ministry of Defence signed the Collaboration Agreement for the launch of a pilot project for selecting companies able to cultivate cannabis plants to be supplied to the Military Chemical and Pharmaceutical Plant in Florence for the manufacture of medicines and pharmaceutical raw materials (i.e., Cannabis FM2). However, pending the full availability of Cannabis FM2 produced by Florence military facility, the Ministry confirmed on its website that it will continue to authorize the import of cannabis for the preparation of extemporaneous preparations..
24. Are there proposals for reform or significant change to the regulation of Medicinal Cannabis?
N/A. It is worth noting, however, that a proposal to hold a popular referendum for the liberalization of cannabis cultivation has been recently rejected by the Constitutional Court with sentence no. 51 of 2022.
Opioid Drugs
25. Are Opioid Drugs authorized in your country?
According to the Presidential Decree, opium and opioid drugs are authorized in Italy and listed in the Table I attached to the Presidential Decree. In addition to that, Law no. 38 of 15 March 2010 has amended art. 14 of the Presidential Decree in order to simplify the access procedure for medicines used in pain therapy, by providing the possibility of also prescribing the drugs included in the Table section A of the Presidential Decree.
26. What are the regulatory authorities with jurisdiction over Opioid Drugs?
According to art. 2.1, letter d) of the Presidential Decree, the regulatory Authority for opioid drugs is the Ministry.
27. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Opioid Drugs?
Opioid drugs are subject to the same provisions as other narcotic and psychotropic substances, so there is not a specific legal framework for their authorization and the procedure provided for by article 17 of the Presidential Decree applies.
As for the pricing and reimbursement, such aspects are negotiated between the Italian Drug Agency (“AIFA”) and the pharmaceutical companies, as provided by the 2019 Decree, which establishes AIFA jurisdiction with regard to the negotiation procedures related to the price and reimbursement of medical products to be paid by the NHS.
28. Which are the Opioid drugs that have received market approval to date?
Based on the list of medicinal products that received the necessary market authorization from AIFA, the approved Opioid Drugs include, inter alia, the following active principles:
• Fentanyl;
• Paracetamol;
• Codeine;
• Naloxone.
29. Who can prescribe Opioid Drugs?
All physicians in Italy can prescribe opioid drugs.
30. Is there a list of doctors authorized to prescribe Opioid Drugs?
N/A.
31. What approvals or notifications are required to prescribe Opioid Drugs?
No specific notification or authorization is required to prescribe opioid drugs. Furthermore, Law no. 38 of 15 March 2010, concerning provisions to ensure access to palliative care and pain therapy, has amended the Presidential Decree in order to simplify the access procedure for medicines used in pain therapy, by providing the possibility of prescribing also the drugs included in the Table section A of the Presidential Decree. In addition to that, in case the opioid drugs are used within a pain therapy, there is a general obligation to keep track of the levels of pain suffered by the patient, in order to assess the suitability of the therapy deployed.
In addition, art. 61 of Presidential Decree requires pharmacists to keep a specific register to record the quantities and qualities of drugs included in the first four tables of the Presidential Decree that have been sold or used during the year.
32. Which organizations are authorized to sell/distribute Opioid Drugs available?
According to art. 17 of the Presidential Decree, anyone who intends to deliver narcotic and psychotropic substances referred to in art. 14 of the Presidential Decree has to obtain the prior authorization from the Ministry. However, such obligation does not apply to pharmacies.
33. Is there a list of retailers/ distributors authorized to sell Opioid Drugs?
Yes, according to art. 16 of the Presidential Decree, the list of all companies and entities authorized to grow, produce, use and market narcotic and psychotropic substances is kept by the MoH, published on the Official Gazette and annually updated by decree of the same MoH.
34. Are there proposals for reform or significant change to the regulation of Opioid Drugs?
N/A.
35. When are they likely to come into force?
N/A.
