This article was first published on Practical Law (Thomson Reuters).
A Q&A guide to distribution and marketing of drugs law in Italy. The Q&A gives a high level overview of distribution and marketing of drugs law, including pre-conditions for distribution; licensing; wholesale distribution; marketing to consumers; marketing to professionals and engagement with patient organisations. To compare answers across multiple jurisdictions, vist the Distribution and Marketing of Drugs Country Q&A Tool.
This Q&A is part of the global guide to Distribution and Marketing of Drugs. For a full list of jurisdictional Q&As visit global.practicallaw.com/drugsdistributionguide.
Drugs cannot be placed on the Italian market without marketing authorisation from the Italian Medicines Agency (Agenzia Italiana del Farmaco) (AIFA) or the European Medicines Agency (EMA) under Legislative Decree No. 219/2006 (Drugs Code) or Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency (EMA Regulation).
Before they are placed on the market, all drugs must be classified for price and reimbursement purposes (that is, whether the product is reimbursed by the National Health Service (NHS) and its cost). In the case of national, decentralised or mutual recognition procedures, the class and price of the drug are directly included in the marketing authorisation issued by the Medicines Agency. Conversely, when the marketing authorisation is issued by the EMA following a centralised procedure, the Medicines Agency then issues a decree that:
The decree is published in the Official Gazette and after publication, a drug authorised by the EMA can be made commercially available in Italy.
Additionally, if the marketing authorisation holder intends to sell (directly or indirectly) the medicinal products to hospitals and other public health facilities, it must request inclusion of the drug in the list of reimbursable medicinal products prepared and held by each region in Italy.
Import of drugs is subject to particular rules (see Question 4).
Early access to drugs (before marketing authorisation is granted) is allowed in the following cases:
The Ministry of Health issued a ministerial decree regulating requirements and particulars of the compassionate use of drugs on 7 September 2017, replacing the previous ministerial decree of 8 May 2003. The new decree broadens the scope of compassionate use with regard to both the drugs that can be supplied under a CUP and the patients who can benefit from a CUP.
CUPs can apply to:
From the perspective of the patients, under the new decree, patients already treated with clinical benefit in a closed clinical trial can now access CPUs to ensure therapeutic continuity. Patients who cannot be included in a clinical trial can also participate in CPUs.
A drug that is not authorised in Italy can still be provided to patients and fully reimbursed by the NHS if, on the basis of an assessment carried out by the Medicines Agency:
As an alternative, the supply of non-authorised medicines can be done on a named-patient basis (Article 5, Drugs Code). In this situation, an unauthorised drug can be supplied to a particular patient on written request from a physician.
The Drugs Code regulates the procedures for issuing marketing authorisations by the Medicines Agency. There are three types of procedure:
In exceptional circumstances and after consultation with the applicant, marketing authorisation can be granted subject to the fulfilment of certain obligations, mainly relating to the safety of the medicine. The maintenance of the authorisation is subject to the annual assessment of compliance with these conditions.
The relevant regulatory authority is the Italian Medicines Agency.
Under the Drugs Code, if a drug has already been authorised by another EU member state, the mutual recognition procedure applies (see Question 4). In particular, the Medicines Agency will be the local entity entitled to recognise any marketing authorisation issued by another member state. It will look at the evaluation report drawn up by the member state within 90 days from receipt of the summary of product characteristics, labelling and package leaflet prepared by the member state.
Additionally, there are simplified procedures for the following categories of products:
Under the Drugs Code, “brokerage of drugs” means any activities aimed at facilitating the sale and purchase of drugs where the broker does not hold any drugs.
Brokers must meet certain requirements and have obligations, including (Article 112-ter, Drugs Code):
Decisions issued by public authorities such as the Medicines Agency and the Ministry of Health can be challenged before the administrative courts. The claimant must prove that it has an actual interest that is affected by the decision issued by the authority and must file the claim within 60 days from notification of the decision.
The competent courts are the Regional Administrative Court (Tribunale Amministrativo Regionale) (TAR) in first instance and the Consiglio di Stato in the second and last instance. With regard to decisions from the Medicines Agency and the Ministry of Health, the competent regional court is the TAR of the Lazio Region, located in Rome.
The costs depend on the authorisation procedure to be followed, the completeness of the supporting dossier (for example, in the case of generic drugs, the dossier does not include all results of clinical trials), as well as on the number of different pharmaceutical forms and dosages that the applicant intends to authorise.
The fees for obtaining a new marketing authorisation are up to EUR80,693.31 (for a decentralised procedure where the Medicines Agency acts as reference member state) and EUR67,244.41 (for other procedures). These figures are up to date as of 29 March 2019.
For each supplemental pharmaceutical form and dosage requested together with the application for the new authorisation, the fees will be EUR6,991.09 (for decentralised procedure) and EUR6,666.47 (for other procedures). If the addition of supplemental pharmaceutical form and dosage is requested at a later stage, the fees are higher.
With regard to distribution/supply, drugs are classified into two main categories:
Prescription drugs include any drug subject to:
Non-prescription drugs include:
The main difference between OTC and other non-prescription drugs is that OTC medicines can be placed so they are directly available to patients when they enter into a pharmacy, while the others are kept by pharmacists behind the counter.
Drugs are classified into three main classes for price and reimbursement:
Drugs in Classes A and H are reimbursed by the NHS, so their price is agreed following negotiations between the marketing authorisation holder and the Medicines Agency. Conversely, Class C drugs are paid for by consumers and the authorisation holder is free to fix their price (but it must be communicated to the Medicines Agency).
Prescription drugs can be distributed only by pharmacies, which are the authorised stores for the sale of all categories of drugs. The authorisation to sell drugs is granted by the competent local health authority on condition that a number of requirements (set out in Law No. 362/1991) and implementing regulations are met.
Non-prescription drugs can be distributed not only by pharmacies but also by para-pharmacies, which are not authorised as pharmacies but are nevertheless subject to the fulfilment of structural, organisational and technological requirements set out in the Decree of the Ministry of Health of 9 March 2012.
In Italy, attending physicians (for example, those in private individual practice) are prevented from selling or distributing drugs to patients.
Prescription drugs can only be prescribed to consumers by physicians, but not all physicians can prescribe all categories of drugs. For example, drugs subject to a restricted medical prescription can be prescribed only by certain medical specialists.
Italian legislation does not allow the online sale of prescription drugs because they can only be sold in pharmacies. Therefore, only non-prescription-drugs can be legally sold online, under the following conditions provided for by Article 112-quater of the Drugs Code:
Import into Italy of drugs that are authorised in other countries is regulated by the Ministerial Decree of 11 February 1997. Import is allowed if the drugs:
Depending on the specific activity concerned, several authorities supervise the distribution of drugs, including the:
All decisions issued by public authorities can be appealed before the Regional Administrative Court. The competent court will depend on the location of the relevant authority. For example, if the decision is issued by a local health authority, the competent court will be in the region where the local health authority is located.
Breach of regulations on the distribution and sale of drugs can result in criminal and administrative sanctions, depending on how serious the infringement is. For example, manufacturing or distributing drugs without authorisation are subject to criminal sanctions.
Additionally, any marketing authorisation can be either suspended and/or revoked by the Medicines Agency if it determines that the requirements that formed the basis of the granted authorisation are no longer met.
Revocation of marketing authorisation is ordered when the drug:
In lieu of revocation, the Medicines Agency can suspend the marketing authorisation if it needs to conduct further inquiries into any of the scenarios listed above. Suspension is also ordered for minor irregularities that can be cured within a reasonable period of time.
In the same situations, the Medicines Agency can, in place of revocation or suspension, amend the authorisation, specifying the period within which the unmodified packaging must be removed from the market.
The wholesale distribution of drugs is governed by Articles 100 to 106 of the Drugs Code. Wholesalers must be authorised by the competent regional authority and the authorisation must list the specific drugs they are authorised to distribute. Authorisation is not required if the distributor has been already licensed to manufacture the same drugs.
To obtain the authorisation, the wholesale distributor must meet the following requirements:
Authorisation is granted within 90 days from receipt of the application, unless the applicant is requested to provide additional documents or information. The competent authority must notify the authorisation to the applicant and to the Ministry of Health.
Typically, wholesalers purchase drugs directly from marketing authorisation holders and sell them to pharmacies. Wholesalers are responsible for ensuring the availability of a wide range of drugs, to grant their prompt supply to pharmacies and other authorised entities to provide drugs located in a given area (Article 105, Drugs Code).
The regulatory authorities responsible for wholesale distribution are the Ministry of Health, the Medicines Agency and the Italian Regions. In particular, the competent regional authority is that located in the area where the wholesale activity is carried out. If more regions are covered by the distribution, wholesalers must be authorised by each region individually.
The competent region, the Ministry of Health and the Medicines Agency can carry out inspections at any premises belonging to wholesalers to control their compliance with the applicable regulations.
Wholesale distribution without authorisation (or after authorisation has been revoked or suspended) is punished with imprisonment from six months to one year and a fine ranging from EUR10,000 to EUR100,000. Same sanctions apply to a wholesaler that has not appointed the qualified person responsible for distribution activity.
In addition, wholesalers who (without reason) apply different conditions from the ones previously indicated as general contractual conditions on retailers are subject to a fine ranging from EUR30,000 to EUR100,000.
Drugs can be advertised only if they have been authorised for distribution by the Italian Medicines Agency or the European Medicines Agency (see Question 1).
Advertising of drugs is governed by Articles 113 to 128 of the Drugs Code. Article 113 sets out a broad definition of advertising activity which focuses on the purpose of the information supplied (the promotion of drugs). According to a recent judgment of the Court of Milan (No. 8240/2017), information about drugs published in a newspaper or on the internet is intended as “marketing activity” if:
The following are the fundamental principles on the advertising of drugs:
By the 30th of April each year, pharmaceutical companies must:
Advertising to consumers is mainly governed under the Drugs Code and the guidelines issued by the Ministry of Health about specific communication channels, including the internet and social networks. The main restriction concerns the prohibition on advertising prescription drugs to consumers and the need to obtain prior authorisation from the Ministry of Health to advertise non-prescription drugs.
Advertising to HCPs is regulated by Articles 119 to 121 of the Drugs Code, which covers methods and limits on advertising, both in relation to the activity of pharmaceutical sales representatives and the content and requirements of the advertising material, as well as the limits on sponsorship of seminars and similar events.
Marketing activities are also regulated by the guidelines issued by the Conferenza Stato-Regioni (a committee of the representatives of the Italian Government and regions) in 2006 and by regulations issued by each region with regard to the details of the activities that can be performed by pharmaceutical sales representatives. A draft of new guidelines issued by the Medicines Agency on the advertising of drugs addressed to HCPs is currently under discussion.
Marketing of drugs is also governed by codes of conduct, for example, by the Farmindustria Code (applied by the pharmaceutical companies joining the association “Farmindustria”) and the Assogenerici Code (issued by the association of companies dealing with generic drugs). Companies that are not members of these associations can consider the codes as reference guidelines.
The Farmindustria and Assogenerici Codes mainly govern the relationships between companies and healthcare professionals and patient organisations, and focus on the:
Italian companies also apply the European Federation of Pharmaceutical Industries and Associations (EFPIA) Code.
In addition to the legal regime described in Question 19, the Drugs Code provides further specific limitations on the advertising of drugs relating, in particular, to the content of the message addressed to patients. For example, the advertising message:
Advertising to consumers is not allowed for:
Other categories of drugs can be advertised to the public subject to prior authorisation from the Ministry of Health. Authorisation is considered granted if the Ministry does not object to the request after 45 days from its submission by the applicant. The authorisation is valid for two years but the Ministry can suggest a shorter term depending on certain characteristics of the advertisement.
Subject to the limits and restrictions listed in Question 21, advertising to consumers is allowed through several channels, from television to journals and online (for example, through dedicated websites or on certain social networks). With regard to social networks, see Question 24.
According to Article 115 of the Drugs Code, the distribution of medicines to the public for promotional purposes is prohibited.
Physicians are free to decide how to supply the free samples to their patients. However, there are severe restrictions on the provision of free samples by pharmaceutical sales representatives to healthcare professionals (see Question 31).
Under Law Decree no. 223 of 4 July 2006 (implemented, with amendments, into Law no. 248 of 4 August 2006), pharmacists are prohibited from launching special offers such as competitions, prize-winning, and operations of underselling of medicines.
In July 2017, the Ministry of Health issued guidelines on advertising over-the-counter (OTC) drugs through internet and social networks. The guidelines distinguish between the institutional websites of pharmaceutical companies, other websites owned by pharmaceutical companies and third parties’ websites. On institutional pharmaceutical websites, companies can publish the (mere) list of drugs distributed without any authorisation from the Ministry of Health. On the other two types, authorisation from the Ministry of Health is required (for example, on product websites or banners appearing on third parties’ websites).
With specific reference to social networks, advertising of OTC drugs is allowed on Facebook, YouTube and Instagram (subject to authorisation from the Ministry of Health). The main principle is that the advertising message must have “static character”. This means that it cannot be changed either by the concerned company or by other subjects, for example, by allowing comments or reactions from users.
However, with regard to the publication of messages on a Facebook wall, even if the company disables the functions that allow the insertion of messages and reactions, it is not technically possible to limit the sharing by users of the posted messages and this can be followed by further inclusion of comments or reactions. For this reason, the guidelines provide that the company must insert the disclaimer “The Ministry of Health only authorises the content of the advertising message. Any comments are the sole responsibility of the user, the company dissociates itself from the comments of the users”.
Further, in relation to advertising of OTC drugs on Facebook, on 25 July 2018, the Ministry of Health issued an update to the guidelines of 2017, providing for, among others, the possibility to submit to the Ministry of Health an editorial plan for each drug (consisting of up to ten posts) with an indication of the Facebook page on which the posts will be published.
The Ministry of Health is the main authority responsible for supervising advertising activities to consumers.
The Ministry of Health monitors and supervises promotional materials for consumers to ensure that their contents comply with regulatory requirements and with the relevant technical and scientific conditions set out in marketing authorisations.
In addition to the Ministry of Health, the Italian Competition Authority can monitor advertising to consumers to prevent any unfair commercial practices, including misleading and unlawful advertising.
Any decision of the competent authorities, including decisions rejecting advertising authorisations or decisions applying sanctions, can be challenged before the competent Regional Administrative Court (see Question 6).
For breach of compliance with advertising provisions of the Drugs Code, the Ministry of Health can order the advertiser to terminate its marketing activities immediately and to circulate a press release containing a correction or a specification of the unlawful advertisement. The Ministry of Health can impose fines ranging from EUR2,600 to EUR15,600 for infringement of the above provisions. Fines are higher (from EUR10,000 to EUR60,000) if drugs are shown in movies or television shows in breach of Article 115 of the Drugs Code.
Additionally, if the Italian Competition Authority discovers the existence of an unfair commercial practice, it can also impose an administrative fine ranging from EUR5,000 to EUR5,000,000 depending on the materiality and the duration of the infringement.
The Drugs Code clarifies that advertising drugs to healthcare professionals (HCPs) can be carried out only to HCPs authorised to prescribe or distribute the relevant drugs.
Advertising to HCPs can be carried out through the following main channels (all subject to specific restrictions highlighted below):
The implementation of advertising addressed to HCPs can be carried out by the marketing authorisation holder or by a third party, or together by the marketing authority holder and a third party (co-promotion), under specific agreements. However, the obligations and responsibilities for the information activity remain with the marketing authorisation holder.
All advertising activities to HCPs are subject to specific restrictions under the law and national and regional regulation, as well as the codes of conduct for the pharmaceutical sector associations.
With regard to scientific information activity, the frequency of visits to HCPs by pharmaceutical sales representatives is provided for under the guidelines for regional regulation of scientific information on drugs, issued by the Conferenza Stato-Regioni in 2006, and implemented by laws and regulations enacted by each Italian region.
In particular, according to the guidelines, each representative is allowed to make a limited number of annual visits to doctors (approximately between three and five for each physician authorised to prescribe the drug as implemented by each region). If a representative is responsible for the scientific information service of several products, the maximum number of visits is set from three to five per year, per doctor on a regional basis, provided that the limited number of visits does not include visits aimed at providing new relevant information on appropriate use of drugs (for example, new therapeutic indications, or new safety information, or warnings, adverse events, contraindications and side effects).
Rules on hospitality are provided by Article 124 of the Drugs Code and also in the codes of conduct for pharmaceutical company associations. Under Article 124 of the Drugs Code:
The provisions above also apply also to conferences, workshops and meetings of pharmacists on topics that are relevant to drugs.
An advertisement to healthcare professionals must always include a summary of the product characteristics, supply regime, classification of the drug for reimbursement purposes and its price.
Articles, tables and other illustrations taken from medical journals or scientific works must be reproduced in full and faithfully, with the exact indication of the source.
Advertising materials must be filed with the Medicines Agency at least ten days before the relevant campaign starts.
Advertising messages to patients cannot induce them to think that some drugs have the same or a higher efficacy than other drugs (Article 117, Drugs Code). Nothing more specific is provided under the current legal framework. Under the Farmindustria Code, non-demonstrable comparisons without an objective basis are not allowed.
Expected new guidelines from the Medicines Agency on advertising of drugs to healthcare professionals may also include a more complete regulation of the comparative advertising.
No discounts are allowed to healthcare professionals.
Free samples can be supplied only by pharmaceutical sales representatives to healthcare professionals authorised to prescribe the relevant drug, after a written and dated request (Article 125, Drugs Code). The main provisions on the supply of free samples include:
Pharmaceutical companies can enter into consultancy agreements with healthcare professionals for the performance of activities (such as speakers at conferences) or for their participation in observational studies or training and education services. These activities are not expressly governed under the Drugs Code, but are regulated by the codes of conduct of the main associations of the pharmaceutical sector.
For example, under the Farmindustria Code, the following conditions must be met:
It is forbidden to grant, offer or promise to healthcare professionals any prizes, pecuniary or in-kind benefits, unless they are of negligible value and related to their job (Article 123, Drugs Code).
Scientific material for consultation (not specifically related to the relevant advertised drug) can be given free of charge, in compliance with the requirements established by the Ministry’s decree of 14 April 2008. Under this decree, material can consist of:
Scientific material for consultation or work can be assigned free of charge to public health facilities and healthcare professionals.
The main authority responsible for supervising marketing activities to healthcare professionals is the Medicines Agency. Scientific information activity is also regulated by the Italian regions.
The Medicines Agency supervises scientific information activities both in the context of the assessment of the advertising material to be deposited before distribution to healthcare professionals and with regard to the conduct of conferences, workshops and the like.
Every January, each pharmaceutical company must communicate to the Medicines Agency the number of healthcare professionals visited by their pharmaceutical sales representatives in the previous year, specifying the average number of visits that have been made. By the end of January each year, each pharmaceutical company must notify the Medicines Agency of the list of sales representatives used during the previous year, indicating their qualifications and type of employment contract with the pharmaceutical company.
Decisions of public authorities can be challenged before the Regional Administrative Courts (see Question 16).
For breach or non-compliance with the Drugs Code relating to advertising to healthcare professionals, the Ministry of Health can order the advertiser to immediately stop the activities and to circulate a press release containing the correction or specification of the unlawful advertisement. Additionally, the Ministry can impose fines from EUR2,600 to EUR15,600. Higher amounts are imposed if free samples are supplied without the indication “free sample, not for sale” (from EUR5,000 to EUR30,000).
If the advertising concerns drugs reimbursed by the National Health Service, breach of the advertising regulations can trigger the drugs to be suspended from reimbursement for a period of between ten days and two years based on the seriousness of the breach.
Relationships with healthcare providers that do not meet the requirements provided for by applicable law and regulations can expose the company to criminal sanctions (for corruption or comparaggio, which is a similar crime applied exclusively in the context of relationships with healthcare providers).
Relationships between pharmaceutical companies and patient associations are governed under ethical codes issued by both pharmaceutical associations and patient associations. In particular, the Farmindustria Code and the Assogenerici Code address the relationships between pharmaceutical companies and patient organisations. Additionally, single companies often adopt codes of conduct, which generally include some provisions on the relationships between pharmaceutical companies and patient organisations.
The Farmindustria Code and the Assogenerici Code provide that:
Additionally, the Farmindustria Code establishes that the same limits and restrictions provided on payments/reimbursement of travel/accommodation expenses to healthcare professionals also apply to patient organisation representatives when they provide services to or receive hospitality from pharmaceutical companies. In particular, these restrictions mostly concern hotel categories, travel seats, number of events per year and locations.
Certain codes of ethics/conduct issued by patient organisations contain provisions on the relationships between their members and pharmaceutical companies. These codes typically include only general provisions on the need to maintain independence and autonomy from pharmaceutical companies.
The Farmindustria Code has been recently updated to include regulation of Patient Support Programs (PSPs) carried out by pharmaceutical companies for patients undergoing treatment with an authorised medicine (for example, telephone and home therapy support services, and distance monitoring of the therapy).
The main recent significant legislative changes in the field of distribution and marketing of drugs address:
Other issues are being debated for the purpose of their regulation in the next budgetary law, currently in preparation. They include the automatic replaceability of biologic drugs and correspondent biosimilars, and the marketing of homeopathic drugs after the expiration of the deadline for the granting of a marketing authorisation, established at 31 December 2019.