Commercialisation of healthcare in Italy: overview
A Q&A guide to the commercialisation of healthcare in Italy.
This Q&A provides an overview of the regulatory framework for the commercialisation of medical products in Italy. It covers the key requirements for manufacturing, advertising and selling drugs, medical devices, biological products and natural health products.
To compare answers across multiple jurisdictions, visit the commercialisation of healthcare Country Q&A tool.
This Q&A is part of the Commercialisation of Healthcare Global Guide. For a full list of jurisdictional Q&As visit www.practicallaw.com/healthcare-guide.
The regulatory framework for medical products includes the following legislative acts:
Royal Decree No. 1265 of 27 July 1934, as amended, consolidating the Law on Public Health (Testo Unico delle Leggi Sanitarie).
Legislative Decree No. 502 of 30 December 1992.
Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency (EMA Regulation).
Legislative Decree No. 219 of 24 April 2006.
Law Decree No. 158 of 13 September 2012.
Law No. 189 of 8 November 2012.
Ministerial Decree of 4 April 2013.
Directive 2001/83/EC on the Community code relating to medicinal products for human use (Code for Human Medicines Directive).
Presidential Decree No. 309/1990.
Legislative Decree No. 46 of 24 February 1997.
Legislative Decree No. 507 of 14 December 1992.
Legislative Decree No. 332 of 8 September 2000.
Directive 92/73/EEC relating to medicinal products and laying down additional provisions on homeopathic medicinal products.
Legislative Decree No. 185 of 17 March 1995.
Law No. 388 of 23 December 2000.
Law No. 158 of 13 September 2012.
Ministerial Decree of 28 February 2006.
Legislative Decree No. 169 of 21 May 2004.
Legislative Decree No. 111 of 27 January 1992.
Law Decree No. 223 of 4 July 2006.
Legislative Decree No. 17 of 19 February 2014.
Several regulatory bodies, both at the national and local levels, are responsible for regulating medical products in Italy. At the national level, the most important institutions are:
The Ministry of Health, which sets out the general policies regarding prevention, diagnosis and treatment of human diseases.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA), which is the national authority responsible for the regulation of drugs in Italy.
The National Health Institute (Istituto Superiore di Sanità), which is mandated by the Minister of Health or by the regions to:
carry out certifications of the chemical and biological purity of drugs and vaccines; and
conduct inspections and quality control of medical and diagnostic devices and equipment, food products and packaging.
At the local level, the main regulatory authorities are the:
Self-governing provinces of Trento and Bolzano.
Local health units (Azienda Sanitaria Locale) (ASLs).
Hospitals and universities.
For more information on the regulatory authorities see box: The regulatory authorities.
Private parties have a minor role in the Italian regulatory system. However, they play an important role regarding medical devices, as notified bodies must assess whether a medical device meets the requirements set out in the relevant legislation and issue a CE marking compliance certificate. Notified bodies operating in the EU must be authorised by one of the member states. In Italy, authorisation is granted by the Ministry of Health after assessing whether the requirements set out in the law are met.
Medical or clinical services can be provided to the public by private hospitals, medical centres and practices, which are active throughout the national territory, subject to the authorisation and supervision of the competent authority (Article 193, Royal Decree No. 1265 of 27 July 1934; Article 8ter, Legislative Decree No. 502 of 30 December 1992 revising the laws on public health). These private medical institutions can also be authorised to provide healthcare assistance in the framework of the National Health System (NHS) on accreditation by the competent regional authority and according to the terms and conditions laid down in agreements to be entered into between the private institution and the NHS. In this context, the exercise of the medical profession and the performance of medical acts can be carried out on a private basis by licensed professionals, subject to legal requirements and conditions.
In addition, the distribution of medicinal products in Italy is mainly carried out by private legal entities. In particular, pharmacies are usually privately owned (with important exceptions, such as municipally owned pharmacies), although they are subject to strict regulations, including public duties.
Italy regulates all types of healthcare products, such as drugs, medical devices, biologics and natural health products. However, certain natural health products are regarded as mere dietary supplements and are subject to food regulations (see Questions 19 to 24).
Medicinal products. The manufacture of pharmaceutical products in Italy requires a manufacturing licence (Articles 50 et seq, Law on Medicaments). "Manufacture" means all operations relating to the purchase of materials and products, production, quality control, release, storage, distribution of medicinal products and related controls.
Manufacturing authorisation is also required for the manufacture of products that are intended for export and for importation in Italy from non-EU states. The manufacturing authorisation is granted by the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) on inspection of the plant. The manufacturing authorisation holder must comply with good manufacturing practice (GMP), as set forth by EU law, and must appoint a qualified person, who is responsible, in particular, for GMP compliance and the release of the products' batches.
The scope of the manufacturing authorisation is defined in accordance with EU law (see Compilation of Community Procedures on Inspections and Exchange of Information, issued by the European Commission on 3 October 2014, which is referred to by AIFA). In particular, the manufacturing authorisation is granted for operations and products in relation to a manufacturing site. The manufacturing authorisation can extend to any of the following operations:
Processing operations. This includes any or all processing steps in the manufacture of a dosage form.
Primary packing. This refers to the placing and sealing of the medicinal product in the finished product packaging material that is in direct contact with the product.
Secondary packing. This refers to placing the medicinal product, which is already sealed within its primary packaging material, within an outer packaging material. This also includes labelling operations or the assembly of other components that are specified in the marketing authorisation as forming the finished product pack.
Batch certification. This refers to the certification of a finished product batch by a qualified person before its release on the market place or before it is exported.
Quality controls. This refers to the types of laboratory testing that the manufacturing authorisation holder is authorised to perform.
Manufacturing authorisations are granted for classes of products, including:
Biological medicinal products.
Within the classification above, there are sub-classes according to the activity subject to authorisation. For example, there is a sub-category of aseptically prepared products for which terminal sterilisation is not carried out on site by the manufacturing authorisation holder, but is contracted out to another site. Among aseptically prepared products, a further distinction is drawn between:
Large volume liquids.
Small volume liquids.
Solids and implants.
Other aseptically prepared products.
The holder of a manufacturing authorisation is also entitled to store and distribute the medicinal products. Therefore, a depositary or wholesale licence is not required for such products.
Active pharmaceutical ingredients (APIs). Different rules apply to the manufacturing of APIs. Manufacturers and importers of active substances established in Italy must register their activity with AIFA (Article 52 bis (2), Law on Medicaments). Sterile and biological substances must be authorised in accordance with the same rules as those applying to medicinal products (see above). Manufacturing of an API includes both the (Article 52 bis (1), Law on Medicaments):
Total and partial manufacture or importation of an active substance used as a starting material.
Various processes of dividing up, packaging or presentation prior to incorporation into a medicinal product, including repackaging or re-labelling, as carried out by a distributor of starting materials.
In summary, active substances can be imported or manufactured in Italy on the basis of one of the following:
Manufacturing authorisation by AIFA, for sterile and/or biological substances.
Registration followed by an inspection of AIFA and the grant of a GMP certificate.
Registration not followed by inspection and without the grant of a GMP certificate.
Information concerning producers and importers of APIs are uploaded by AIFA on the EU database. AIFA also makes available a list of manufacturers and importers established in Italy which are registered with the authority.
Traceability. Prescription medicinal products must bear the safety features required by the Law on Medicaments (Article 73 bis, Law on Medicaments). This includes the apposition of bollini stickers on the outer packaging of the medicinal product, which are mandatory for all medicinal products that are reimbursed by the Italian National Health System (NHS).
Provisions on bollini stickers have been implemented by Ministerial Decree of 15 July 2004, which establishes a central database for monitoring and tracing medicinal products, as well as guidelines issued by the Ministry of Health in October 2012. The apposition, removal or cancellation of bollini stickers on the packaging of a medicinal product are regarded as manufacturing steps that require a manufacturing authorisation and must be performed under the supervision of the qualified person. There are further rules governing the supply of bollini stickers to manufacturers, and on information to be entered in the central database to ensure traceability of medicinal products. These activities can also be performed by a manufacturer established abroad. In such a case, the marketing authorisation holder is responsible for complying with the obligations set forth by the law.
In addition, from 1 January 2003, an identification code consisting of a barcode and the marketing authorisation number must also be affixed on non-prescription medicinal products. The sticker is a unique identifier of the medicinal product that enables the authenticity of medicinal products to be verified and individual packs to be identified by distributors and retailers.
See Question 8.
Drugs can only be placed on the Italian market if they are granted a national marketing authorisation by AIFA, except for drugs that have been either:
Granted a centralised authorisation under Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency (EMA Regulation).
Authorised in Italy under the mutual recognition procedure or the decentralised procedure.
The marketing authorisation can only be granted to applicants that are established in the EU. The relevant application must be submitted to AIFA together with all information required by Article 8 of the Legislative Decree No. 219 of 24 April 2006 (Law on Medicaments), including (among others) the:
Identification of the applicant and the manufacturer (if different).
Name of the drug.
Composition (qualitative and quantitative) of all the drug's ingredients, expressed in standard terminology.
Therapeutic indications, contra-indications and side effects.
Posology, pharmaceutical form and method of administration.
Results of clinical trials.
The application must be made on the relevant forms made available by AIFA and accompanied by particulars and documents in accordance with Annex I to the Law on Medicaments.
The decision granting a marketing authorisation must be issued within 210 days from the receipt of a valid application.
Generic drugs placed on the Italian market must hold a market authorisation issued by the competent regulatory authorities (that is, the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) or the European Medicines Agency (EMA)).
However, generic drugs are subject to an abridged procedure under Article 10 of the Law on Medicaments if the generic application is based on a reference medicinal product that has been authorised for not less than eight years and the application is filed with AIFA not less than ten years after the authorisation of the reference medicinal product. When applying under the abridged procedure, the applicant must submit a dossier demonstrating the:
Bioequivalence of the product.
Suitability of the manufacturing process.
Measures taken to ensure quality control.
A simplified procedure is also laid down under Article 11 of the Law on Medicaments for medicinal products that have been in well-established use in Italy or in the EU for at least ten years, and whose efficacy and safety can be proved based on medical and scientific literature (bibliographic applications).
A further important distinction between generic drugs and patented medicinal products relates to the procedure for pricing and reimbursement. As a general rule, the procedure for pricing and reimbursement can only be initiated once the marketing authorisation is granted (Article 12(2), Law Decree No. 158 of 13 September 2012, confirmed with amendments by Law No. 189 of 8 November 2012 (Law 158/2012)).
Medicinal products authorised by EMA are classified by AIFA as "C-nn" (where "nn" stands for non-negotiated) within 60 days from the grant of a centralised marketing authorisation (Article 12(5), Law 158/2012). This classification is valid while awaiting the submission from the relevant pharmaceutical company of an application for a different classification. If the product is approved under the national procedure, the mutual recognition procedure or the decentralised procedure, a decision to classify the product as C-nn is taken by AIFA at the time of grant of the national marketing authorisation.
However, there is an exception under Article 12 (3) of Law 158/2012 in respect of:
Medicinal products of exceptional social and therapeutic importance, as indicated in a specific decision of the technical committee.
Medicinal products that can be used only in hospitals or other similar structures.
If the medicinal product falls within one of the exceptions above, the marketing authorisation holder must file an application for pricing and reimbursement within 30 days from the C-nn classification. Otherwise, the C-nn classification is revoked.
There is a fast-track procedure for the pricing and reimbursement of generic medicinal products and biosimilars under Article 12(6) of Law 158/2012. Under this provision, generic medicinal products and biosimilars are automatically assigned to the reimbursement classification of the reference medicinal product, without the need of a negotiation, if the marketing authorisation holder proposes a price that is clearly convenient for the National Health System. This price must reflect a discount that must be at least equal to the discount determined by Ministerial Decree on proposal of AIFA, and on account of expected volumes of sales.
The minimum discount is determined as follows (Appendix A, Ministerial Decree of 4 April 2013 on Criteria for the identification of the classes of prices for the automatic negotiation of generic medicinal products and biosimilars):
For pharmaceutical expenditure up to EUR19.99 million:
Class A products: 45% of the public price of the reference medicinal product;
Class H products: 30% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR20 million and EUR39.99 million:
Class A products: 47.5% of the public price of the reference medicinal product;
Class H products: 31.7% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR40 million and EUR59.99 million:
Class A products: 50% of the public price of the reference medicinal product;
Class H products: 33.3% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR60 million and EUR79.99 million:
Class A products: 55% of the public price of the reference medicinal product;
Class H products: 36.7% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR80 million and EUR99.99 million:
Class A products: 60% of the public price of the reference medicinal product;
Class H products: 40% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR100 million and EUR139.99 million:
Class A products: 65% of the public price of the reference medicinal product;
Class H products: 43.3% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure between EUR140 million and EUR179.99 million:
Class A products: 70% of the public price of the reference medicinal product;
Class H products: 46.7% of the manufacturer's price of the reference medicinal product.
For pharmaceutical expenditure of EUR180 million or more:
Class A products: 75% of the public price of the reference medicinal product;
Class H products: 50% of the manufacturer's price of the reference medicinal product.
Class A products are products that are reimbursed and available on the market (that is, products that can be purchased by patients in pharmacies on medical prescription). Class H are medicinal products that are reimbursed to hospitals only.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) is responsible for regulating the manufacture, advertising and sale of medicinal products.
The Ministry of Health is responsible is responsible for granting the relevant authorisation for the advertising of medicinal products to the public.
For more information on the Ministry of Health and AIFA see box: The regulatory authorities.
Medicinal products that have been licensed in other jurisdictions can be marketed in Italy following the mutual recognition procedure or the decentralised procedure, in accordance with Article 41 of the Law on Medicaments (implementing Articles 28 et seq of Directive 2001/83/EC on the Community code relating to medicinal products for human use, as amended).
Imports of medicines from non-EU countries require the importer to have a manufacturing licence, except for countries with which the EU has entered into agreements aimed at ensuring compliance with good manufacturing practices, and provided that quality controls are carried out in the country of origin.
An authorisation from the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) is also required for imports of medicinal products from other EU countries (parallel import authorisation). Such authorisation is intended, in particular, to ensure the traceability of medicinal products. Other rules on parallel imports are set out for the protection of the intellectual property rights, in particular trade mark rights (as repackaging is often required due to the use of a different language on the packaging and leaflet).
For medicinal products that have not obtained a marketing authorisation in Italy and are intended to be exported abroad, the manufacturer can apply for a certificate of medicinal product in the form laid down by the World Health Organization (WHO) and relevant guidelines, for the purpose of attesting compliance with good manufacturing practices.
Under Presidential Decree No. 309/1990, special requirements apply to imports/exports, and the commercialisation and distribution of narcotics and psychotropic substances.
Only over-the-counter medicines can be advertised to the public, subject to prior authorisation of the Ministry of Health. It is not permitted to advertise prescription medicines. The authorisation is valid for 24 months, unless granted for a shorter period. Advertisements of medicinal products can only relate to products holding a marketing authorisation and which have a published price and reimbursement decree. Any advertising material must strictly comply with the summary of product characteristics (SPC).
Advertising material intended for health operators (that is, physicians and pharmacists) must be submitted to the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) at least ten days before publication, except for materials consisting of an already approved SPC.
Samples of medicinal products and illustrative material cannot be shown or distributed during congresses or meetings, except for the SPC, documents related to the congress or scientific documents, provided that both :
A full version of the documents is provided.
The documents have been previously filed with AIFA.
The marketing authorisation holder and/or its Italy-based representative and/or importers and distributors must have a scientific service that is responsible for the information and advertising of medicinal products placed on the market. The scientific service must ensure that any promotion and advertising activity complies with the laws.
In addition to the rules above, the Italian association of pharmaceutical companies (Farmindustria) has laid out specific procedures and guidelines aimed at the regulation of advertising activities carried out by the associated companies. The implementation of those procedures is subject to annual certification by a third party accredited body.
Unlawful advertising is subject to administrative sanctions imposed by the Ministry of Health and AIFA, in addition to the publication of corrective statements, as applicable. Suspension from reimbursement can also be imposed. The Italian Competition Authority can also punish unlawful or misleading advertising as unfair commercial practices and apply fines of up to EUR500 million.
For companies associated to Farmindustria, unlawful advertising can also constitute a breach of the Code of Professional Conduct, which may result in temporary suspension and/or exclusion from the association.
Criminal sanctions apply for violation of the provisions on gifts or advantages given to healthcare professionals.
Medical devices placed on the Italian market must bear the CE marking and follow related certification procedures. Rules on medical devices are set out in Legislative Decree No. 46 of 24 February 1997. Specific rules on implantable medical devices and in vitro diagnostic medical devices are set out in Legislative Decree No. 507 of 14 December 1992 and Legislative Decree No. 332 of 8 September 2000, respectively.
Medical devices are divided into three classes, ranging from low risk to high risk: classes I, II and III (class II includes sub-classes IIa and IIb). Different certification procedures are established for each class. The procedures involve a notified body that will issue a CE marking compliance certificate and provide a copy and relevant information to the Ministry of Health.
The information requirement is met if the medical device is registered in the online database of the Ministry of Health (Repertorio dei dispositive medici). Except for this information requirement, a medical device properly registered and notified under the law of an EU member state can be placed on the Italian market without any additional registration or regulatory approval requirements.
For borderline products, the following can serve as guidelines for solving classification issues:
Manual on Borderline and Classification in the Community Regulatory Framework for medical devices (Version 1.15 (6-2013)) of the European Experts Group in charge for Borderline and Classification issues relating to medical devices.
In addition, special working groups, which include industry representatives, have been set up within the Ministry of Health to deal with borderline classification issues.
The Ministry of Health regulates the manufacture, advertising and sale of medical devices.
The Ministry of Health also intervenes in post-market surveillance. Both private and public healthcare professionals, manufacturers and their agents must communicate to the Ministry of Health all data relating to incidents that involve a medical device. In addition, if a medical device compromises patients' health and safety (even if correctly installed and used), the Ministry of Health can impose appropriate measures to prohibit or limit the commercialisation of the product, at the expenses of the manufacturer or its agent.
For more information on the Ministry of Health see box: The regulatory authorities.
Medical devices can freely circulate in the EU if they bear the CE mark. However, they must comply with the specific provisions applicable in each member state. In Italy, instructions to end-users or patients must be provided in Italian (Legislative Decree No. 46 of 24 February 1997).
In addition, a manufacturer that places in its name on the market a device classified as III, II-b and II-a must provide to the Ministry of Health all the data needed to identify that device, along with a copy of the proposed labels and instructions for use, when the device is put into use in Italy (Article 13(3-bis), Legislative Decree No. 46 of 24 February 1997).
Italian manufacturers willing to export their medical devices outside the EU can request a certificate from the Ministry of Health (certificato di libera vendita). These certificates attest CE marking for medical devices and declare that the product is compliant with Italian law. The certificate is requested by the company if such declaration is required or useful for selling the product in the country where the product is to be exported.
For imports of medical devices from non-EU countries, a special clearance must be obtained from the competent custom offices (Ufficio di sanità, marittima, aerea e di frontiera) (USMAF). Clearance is mandatory for all medical devices. In addition, to sell medical devices in Italy, manufacturers that are not established in the EU must appoint a representative in the EU. If this representative is based in Italy, it will communicate all required information concerning its address and the medical device to the Ministry of Health.
Medical devices classified as III, II-b and II-a put into use in Italy must be notified to the Ministry of Health (Article 13(3-bis), Legislative Decree No. 46 of 24 February 1997) (see Question 11).
Only CE-marked devices can be advertised to the general public, with some exceptions. The promotion of devices subject to medical prescription or which can only be applied by, or with the assistance of, healthcare professionals is prohibited (Article 21, Legislative Decree No. 46 of 24 February 1997). Detailed rules are set out in the Ministerial Decree of 23 February 2006.
Advertisements to health operators are regulated by the ethical codes of the associations of medical devices companies (such as the Eucomed and Assobiomedica codes) and are not subject to prior authorisation/approval by the Ministry of Health.
On 23 March 2013, the Ministry of Health issued guidelines on the advertising of medical devices, which set additional guidance regarding advertising in new media (that is, toll free numbers, internet, social networks, sms, e-mails, and so on).
Biological medicinal products listed in the Annex to Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency (EMA Regulation), as amended, can be placed on the Italian market on central authorisation of the EMA.
Biological medicinal products that are similar to a reference biological medicinal product already approved by the EMA (biosimilars), and for which the period of data exclusivity has elapsed, are also centrally authorised under the EMA Regulation.
The Law on Medicaments applies to biological medicinal products other than those listed in the Annex to the EMA Regulation. In this respect, the Italian law is fully in line with the provisions of Directive 2001/83/EC on the Community code relating to medicinal products for human use.
Interchangeability of biosimilars and biological reference products for the purpose of pricing and reimbursement is determined according to national law. In a paper issued on 13 May 2013, the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) took the view that biosimilars cannot be regarded as identical to the reference biological medicinal products. Therefore, biosimilars cannot be included in the "transparency lists", which allow the automatic substitution of equivalent products.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) is responsible for authorising and supervising the manufacture, advertising and sale of biological products. Pharmacovigilance on biological medicinal products placed on the Italian market is carried out by AIFA in co-operation with the European Medicines Agency (EMA). Biological products are subject to additional monitoring.
The advertising of biological products is regulated by the Law on Medicaments in the same way as for conventional medicinal products.
For more information on AIFA see box: The regulatory authorities.
Biological medicinal products listed in the Annex to Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency (EMA Regulation) are authorised centrally by the European Medicines Agency (EMA). The Biologics Working Party (BWP), established within the EMA, plays a key role in the authorisation process. The BWP, which is made up of independent experts particularly experienced in the biotechnological field, provides the Committee for Medicinal Products for Human Use with advice and recommendations on the safety and quality of biological medicinal products. Standards accepted by other regulatory agencies may be not acceptable for the EMA, which carries out an independent assessment.
The provisions on chemically synthesised drugs in the Law on Medicaments and Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products and establishing a European Medicines Agency also apply to biological products. Therefore, the position is the same as for medicinal products (see Question 7).
The provisions on chemically synthesised drugs of the Law on Medicaments apply to biological products. Therefore, the position is the same as for medicinal products (see Question 8).
Natural health products
There is no single category of natural health products under Italian law. Those products are divided into three categories:
Homeopathic and anthroposophic medicinal products.
Herbal medicinal products, including traditional herbal medicinal products, which are subject to specific rules.
Other herbal products and dietary supplements.
Homeopathic medicinal products
In accordance with Directive 92/73/EEC on medicinal products and homeopathic medicinal products, the Law on Medicaments defines homeopathic medicinal products as any medicinal product prepared from products, substances or compositions called homeopathic stocks according to a homeopathic manufacturing procedure described by the European Pharmacopoeia or pharmacopoeias officially used in EU member states.
Herbal medicinal products
Herbal medicinal products are medicinal products exclusively containing as active ingredients one or more herbal substances or preparations, or one or more herbal substances in combination with one or more herbal preparations (Article 1(ll), Law on Medicaments).
Traditional herbal medicinal products are a sub-category of herbal medicinal products. A traditional herbal medicinal product is an herbal medicament to be used for specified indications at a given strength and dosage, exclusively based on long-standing use (Article 21, Law on Medicaments). The requirement of long-standing use is satisfied if a medicament has been in use for no less than 30 years, with at least 15 years in the EU. The Herbal Medicinal Product Committee, established within the European Medicines Agency, maintains a Community list of herbal medicinal products that must be regarded as traditional herbal medicinal products by national authorities. In this respect, Italian law is fully harmonised with relevant EU legislation.
Other herbal products and dietary supplements
Herbal products are often placed on the market as foodstuffs or dietary supplements. The distinction between dietary supplements and medicinal products essentially rests on the presentation and function of the product. A medicinal product is a product that either:
Is presented as suitable for treating, preventing or making possible the diagnosis of a disease.
Actually exerts, once administered to a patient, a pharmacological, immunological or metabolic action in the human body to prevent, treat or diagnose a disease.
A dietary supplement is any product intended to support, maintain and optimise physiological functions.
Since it may be very difficult to draw a clear distinction between herbal medicinal products and dietary supplements, the Ministry of Health has published a list of herbal substances that can be used in dietary supplements. The list contains a description of the conditions of use and the physiological activity associated to each herbal substance which are consistent with a classification of the product as foodstuff or dietary supplement. Another list prohibits the use of certain herbal substances in dietary supplements and foodstuffs. However, the use of those substances is allowed if the conditions for the grant of a marketing authorisation (or a simplified registration) are satisfied (see Question 20).
Homeopathic medicinal products
The general requirements for placing homeopathic medicinal products on the market are set out in the provisional regime laid down by the Legislative Decree 17 March 1995, No. 185, which first implemented in Italy Directive 92/73/EEC on medicinal products and homeopathic medicinal products.
Homeopathic medicinal products can be subject to either the simplified registration procedure or the authorisation procedure.
Under the provisional regime, homeopathic medicinal products manufactured in a country of the European Community and available on the Italian market as of 6 June 1995 could be further marketed with the same presentation until 6 June 2000, subject to specific notification to the Ministry of Health. This deadline has been extended for the first time by Article 85(33) of the Law of 23 December 2000, No. 388. The provisional regime has been further prolonged by Article 10(10) of the Law on Medicaments. The deadline for the validity of provisional registrations was 31 December 2015. From that date, provisional registrations are subject to the simplified registration procedure set out in Article 16 of the Law on Medicaments.
The simplified registration of homeopathic products that are currently subject to the provisional regime has been further facilitated, as the information to be provided for completing module 4 of the application can be replaced by a declaration of the applicant (Law of 13 September 2012, No. 158, amending Article 20 of the Law on medicaments).
To improve the management of provisional registrations, a database was set up in 2003. This database has been available online since 2012 and is known as the "homeopathic system" (sistema omeopatici).
Homeopathic medicinal products that do not qualify for the simplified procedure must be authorised in accordance with Article 18 of the Law on Medicaments, which implements Article 16 of Directive 2001/83/EC on the Community code relating to medicinal products for human use (Code for Human Medicines Directive), as amended.
Herbal medicinal products
There is a simplified procedure for the registration of traditional herbal medicinal products, which is set out in Article 21 of the Law on Medicaments, in line with Article 16a of the Code for Human Medicines Directive, as amended by Directive 2004/724. To date, only few traditional herbal medicinal products have been registered under the simplified procedure with the Italian authority.
Herbal medicinal products that are not "traditional" must be authorised according to the general rules. However, it may be difficult to provide pre-clinical studies and clinical trials. In that case, the bibliographic authorisation procedure under Article 11 of the Law on Medicaments can be particularly useful, as it allows for the safety and efficacy of the use of an herbal medicinal product to be attested by clinical and scientific literature.
More specific provisions on the manufacturing authorisation for each category of herbal medicinal products are laid down by administrative regulations. In particular, a simplified authorisation procedure applying to herbal products that consist of herbal substances only is set out in the Ministerial Decree of 28 February 2006, replacing the provisional regime set out by the Ministerial Circular No. 3 of 18 July 2002.
Other herbal products
Herbal products that are not medicinal products according to the definition set out in the Law on Medicaments (see Question 19) can be placed on the market as foodstuffs or dietary supplements. The regulatory provisions on the manufacturing and placing on the market of those products will apply. In particular, the packaging and manufacturing of dietary supplements must be carried out in plants duly authorised by the Ministry of Health (Article 9, Legislative Decree No. 169 of 21 May 2004; Article 10, Legislative Decree No. 111 of 27 January 1992).
A person placing dietary supplements on the Italian market must notify the Ministry of Health of such placing by submitting a model of the label used for the product (Article 10, Legislative Decree No. 169, of 21 May 2004). The product can be put on the market if the Ministry of Health does not make observations within 90 days from the date of notification.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) is responsible for supervising the manufacture, advertising and sale of homeopathic medicinal products, herbal medicinal products and traditional herbal medicinal products. Therefore, the AIFA can:
Carry out inspections at manufacturing sites.
Order the withdrawal or recall of medicinal products.
Order the immediate cessation of any advertising in breach of the provisions of the Law on Medicaments.
Reports on adverse reactions caused by herbal products or dietary supplements that are not medicinal products can be submitted to the Italian National Health Institute within the framework of the project on non-conventional therapies.
For more information on AIFA and the National Health Institute see box: The regulatory authorities.
Traditional herbal medicinal products can be registered in Italy based on a national registration in an EU country under the mutual recognition procedure (MRP). The decentralised procedure (DCP) can also be used for applications in multiple EU jurisdictions. Conditions for MRP and DCP applications are set out in Article 24 of the Law on Medicaments, which implements Article 16 of Directive 2001/83/EC on the Community code relating to medicinal products for human use, as amended.
The MRP and DCP can also be used for the registration of homeopathic medicinal products, except for homeopathic medicinal products registered under the provisional regime (see Question 20, Homeopathic medicinal products).
The import and export of natural health products that are classified as medicinal products under the Law on Medicaments (that is, homeopathic medicinal products and herbal medicinal products, whether traditional or otherwise) are governed by Title IV of the Law on Medicaments.
The provisions of the Law on Medicaments which regulate the distribution and the sale to the public of medicinal products apply to any herbal product registered or authorised as a medicinal product. Therefore, the sale of those products is restricted to authorised pharmacies, for prescription products, while non-prescription products can be sold by dedicated retailers (parapharmacies) under the conditions provided by the law (in particular, see Article 5 of Law Decree No. 223 of 4 July 2006, as confirmed with amendments by Law No. 248 of 4 August 2006 on professional qualification of retailers and required notifications to the Ministry of Health).
The online sale of non-prescription medicinal products is allowed, subject to certain requirements relating to the potential online seller and the content of the website offering the medicinal products (Article 112-quarter, as amended by Article 1(1), Legislative Decree No. 17 of 19 February 2014). Online sales can only be conducted by pharmacies authorised under the current legal framework to sell medicinal products in the Italian territory, as well as parapharmacies. Pharmacies and parapharmacies operating on the Italian territory can be allowed to carry out their current activity online, provided that they make an application to the competent (regional) authority.
The advertising of prescription-only products outside the approved distribution channels is prohibited and sanctioned by the law. As a result, online sales of natural health products that are medicinal products are not allowed under Italian law.
The online commerce of dietary supplements is possible under Italian law, provided that the seller or importer complies with the relevant provisions on labelling and advertising (see Question 20, Other herbal products).
Article 128(2) of the Law on Medicaments explicitly prohibits the advertising of homeopathic medicinal products to the public. Advertising to healthcare professionals is allowed with restrictions. In particular, only information specified in Article 85 of the Law on Medicaments can be provided.
Provisions on the labelling and advertising of traditional herbal products are set out in Article 27 of the Law on Medicaments, in line with Directive 2001/83/EC on the Community code relating to medicinal products for human use, as amended.
Herbal products that are placed on the market as dietary supplements or foodstuff can be advertised to the public without specific restrictions. The relevant regulations regarding dietary supplements are applicable. In particular, labels of nutritional products must be notified to the Ministry of Health, and advertising must not lead consumers into believing that any products put on the market as a foodstuff or dietary supplement can be suitable for treating or preventing a disease (Legislative Decree of 27 January 1992, No. 111, implementing Directive 89/398/EEC). These provisions also apply to products consisting of herbal ingredients (Ministerial Circular No. 3 of 18 July 2002). Provisions on the advertising of vitamin and mineral supplements are set out in the Ministerial Circular No. 8 of 16 April 1996.
More detailed rules on product claims that can be used in the advertising of dietary supplements (for example, the use of the term "natural") are set out in the Ministerial Circular No. 4 of 25 July 2002.
Ministerial Decree No. 519 of 7 October 1998 specifically regulates dietary supplements intended for use in energy-restricted diets for weight reduction. Ministerial Circular No. 8 of 7 June 1999 sets out a detailed legal framework on supplements used for enhancing sport performance.
The administrative provisions above, in particular those related to vitamin and mineral supplements, have been confirmed and further detailed by Legislative Decree No. 169 of 21 May 2004, implementing Directive 2002/46/EC on food supplements.
There have been no significant legislative developments relating to the healthcare sector since the introduction of Law 158/2012 (Balduzzi Decree), which represented an unprecedented "revolution" for the provision of healthcare services. The Balduzzi Decree, which was enacted into law in November 2012, aims to:
Increase the transparency, efficacy and organisation of health authorities and operators.
Simplify administrative procedures, to ensure faster availability of new products.
In line with those developments, the Italian Government recently introduced a Bill for the budgetary plan of 2017 that contains provisions intended to facilitate market access for innovative and oncological medicinal products. To that purpose, the budget for innovative, orphan and oncological medicinal products has been increased. Further, the designation of a medicinal product as innovative, which is currently very difficult to obtain, would be facilitated under a new regulation to be enacted by the Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA) by 31 March 2017.
In 2017, the Italian Parliament is also expected to pass a delegation law that will authorise the Italian Government to enact legislative decrees to consolidate the existing regulations on clinical trials and to set new provisions for the implementation in Italy of Regulation (EU) 536/2014 on clinical trials on medicinal products for human use. In particular, according to the Bill currently under discussion, the process for the authorisation of clinical trials (in particular multicentre clinical trials) will be facilitated and accelerated. The Bill also contains innovative provisions on the:
Collection and use of biological samples obtained in the course of trials for use in different research projects or for scientific purposes.
Use of digital technologies in the context of clinical trials.
Italy is an important player in clinical trial research and there is a strong commitment of all stakeholders to improve the attractiveness of Italian trial sites for the development of new drugs.
Future developments on the Italian life sciences and healthcare market may be influenced by the growing role of digital health services, and by the trend in non-EU markets (particularly North America) to view Europe as the first market for obtaining regulatory approval of new products.
The regulatory authorities
The Ministry of Health
Principal responsibilities. The Ministry of Health sets the general policies regarding the prevention, diagnosis and treatment of human diseases. The Ministry of Health is responsible for co-ordinating and monitoring healthcare services provided by local bodies.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA)
Principal responsibilities. AIFA is the national authority responsible for the regulation of drugs in Italy. It is a public body operating autonomously, transparently and according to cost-effectiveness criteria, under the direction and vigilance of the Ministry of Health and in co-ordination with the Ministry of Economy. It co-operates with the regions, the National Institute of Health, research institutes, patients' associations, health professionals, scientific associations, the pharmaceutical industry and distributors. AIFA is also the Italian competent authority for issuing authorisations and conducting vigilance on clinical trials relating to medicinal products (except for those relating to first use on humans and phase I clinical trials, which are provisionally subject to the authorisation and vigilance of the National Health Institute).
The National Health Institute (Istituto Superiore di Sanità)
Principal responsibilities. The National Health Institute is mandated by the Minister of Health or by the regions to carry out certifications of the chemical and biological purity of drugs and vaccines, and to conduct inspections and quality control of medical and diagnostic devices and equipment, food products and packaging.
The Italian Agency of Pharmaceutical Products (Agenzia Italiana del Farmaco) (AIFA)
Description. This website provides a general overview of the tasks and the organisation of AIFA.
Francesca Rolla, Partner
Professional qualifications. Italy, Avvocato
Areas of practice. Class actions; commercial litigation; international arbitration; product liability; litigation and arbitration; life sciences; enforcement, bribery, corruption and Foreign Corrupt Practices Act investigations; real estate litigation; investigations, white collar and fraud; anti-trust/competition litigation.
Languages. English, French, Italian
Professional associations/memberships. International Association of Defence Counsel (IADC); International Bar Association (IBA).
Christian Di Mauro, Partner
Professional qualifications. Italy, Avvocato; France, Avocat à la Cour
Areas of practice. Life sciences; enforcement; product liability; litigation and arbitration; commercial litigation; investigations, white collar and fraud.
Languages. English, French, Italian
Riccardo Fruscalzo, Senior Associate
Professional qualifications. Italy, Avvocato
Areas of practice. Health; government regulatory; intellectual property; patents.
Languages. English, German, Italian
Professional associations/memberships. Italian Life Sciences Group, Italian office of the American Chamber of Commerce.