The Pharmaceutical Intellectual Property and Competition Law Review: Italy
The Italian pharmaceutical business registered the highest growth rate from 2008 to 2018 and represents the third sector in terms of research and development investments in Italy. Moreover, according to data recently published by a local industry association, Italy is the biggest manufacturer of medicines in the EU.2 This trend has not been significantly affected by the covid-19 crisis.
In a universal healthcare system where essential healthcare treatments are guaranteed free of charge to all the population, the pharmaceutical sector is, on the one hand, driven by control of public expenditure and, on the other, by innovation and quality. As explained in more detail in this chapter, Italy is the country where managed entry agreements with payers (i.e., agreements under which the payment is somehow connected with the benefit that the medicine is able to guarantee to patients) are most developed. This legal instrument enables both pharma companies and payers to share financial risk due to uncertainty surrounding the introduction of new technologies.
In this search for balance, originators and generics whose relationship is often affected by anticompetitive behaviours ultimately aimed at hindering the market entry of generic drugs have found their place. In this respect, over the past few years the Italian Antitrust Authority has been one of the most active authorities at the EU level, also in terms of enforcements.
Legislative and regulatory framework
In the pharmaceutical sector, the applicable Italian legislative and regulatory framework mainly consists of:
- Regulation (EC) No. 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency;
- Regulation (EC) No. 1394/2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No. 726/2004;
- Legislative Decree No. 219/2006 implementing Directive 2001/83/EC;
- Legislative Decree No. 50/2016 on Code of Public Contracts;
- Legislative Decree No. 30/2005 on Code of Industrial Property;
- Law No. 287/1990 on rules for protecting competition and the market;
- Article 48 of Decree Law No. 269/2003, converted, with amendments, into Law No. 326/2003, which establishes the procedure for fixing the price of medicinal products reimbursed by the National Health System; and
- Resolution No. 3/2001 of the Inter-ministerial Committee for Economic Planning setting forth criteria for the negotiation of prices of medicinal products.
The expression 'patent linkage' generally refers to the practice of subordinating the marketing of generic drugs to the assessment, by the competent regulatory authority, that the product for which a marketing authorisation is sought does not infringe the intellectual property rights of any third party (patent or supplementary protection certificate).
Linkage mechanisms tend to be supported by those countries (mainly developing countries) where there are not early resolution mechanisms and an efficient judicial system. However, while patent linkage may be useful to prevent litigation between originators and generic drugs manufacturers, it is often used by the former as a defensive tool to delay the market entry of the latter and keep prices for their patented drugs higher for longer.
The EU does not support patent linkage mechanisms, mainly on the grounds that they are in contrast with the EU regulatory system and, in particular, with the scope of the EU Bolar exemption (European Directive 2001/83/EC, Article 10) according to which clinical trials for generics and biosimilar are exempt from infringement.
Italy does not recognise the patent linkage concept, although until 2012, the Italian Code of Industrial Property (CIP) included a specific provision preventing generic drugs manufacturers from starting the registration process for the relevant products before the last year of validity of the patent or supplementary protection.18
This provision was repealed by Law No. 27/2012, following the start by the European Commission, on 14 March 2011, of an infringement procedure for violation of the EU legislation on medicinal products. Since then, Italian legislation no longer prevents the manufacturer of a generic drug from starting the approval process and obtaining a marketing authorisation for the relevant drug pending the patent or SPC for the originator's product or active ingredient. On the contrary, Article 68 of the CIP expressly exempts from infringement studies and experiments (e.g., preclinical studies and clinical trials) and the subsequent practical activities, aimed at obtaining, also abroad, a drug marketing authorisation, whenever the relevant activity takes place.
In other words, as long as the generic or biosimilar drug manufacturer does not offer for sale or put on the market the generic product, or both, it is allowed to conduct any type of activity in preparation of the future commercialisation of the same, once the patent or SPC expires (the above-mentioned Bolar exemption).19
The rights of generics and biosimilar manufacturers have been further broadened by Regulation (EU) 2019/93320 (in force since 1 July 2019), which has introduced new exemptions to the exclusive right of an SPC holder (the SPC manufacturing waiver). Pharma companies established in the EU are now allowed to manufacture a generic or biosimilar version of a medicinal product protected by an SPC, provided that it is exclusively intended for export to a non-EU market where the patent protection has been expired or never existed, or storing medicinal products for a period of six months preceding the SPC expiry (including any related act that is strictly necessary for said making or storing), or both.
These new rules represent a significant revolution in the market for generic and biosimilar medicinal products as they offer a real opportunity for their manufacturers to increase the volume of their exports to third countries and be ready to enter the European market immediately after the certificate expires.
At the same time, Regulation (EU) 2019/933 provides also for clear safeguards to ensure transparency and avoid the possible illicit diversion onto the EU market of generics and biosimilars produced for export, including:
- notification requirement: companies intending to start manufacturing SPC-protected medicines for export shall notify the competent national patent authorities and SPC holders no later than three months before the start of the making in the Member State or no later than three months before the first related act, prior to that making;
- due diligence requirement: manufacturers shall inform their supply chain that the products in question are only for exporting or storing, or both, with a view to EU day-one entry on the market of a Member State upon expiry of the corresponding certificate; and
- labelling obligation: any export of SPC-protected products outside the EU will be subject to compliance with specific labelling requirements.
Finally, the SPC manufacturing waiver does not apply to those certificates that have already taken effect at the time the Regulation has entered into force, whereas it applies to those SPCs that were already applied for before the entry into force of the Regulation, but have not yet taken effect before that date, for which a transitional regime is provided.21
In conclusion, while makers of generics and biosimilars can still be sued by originators under Article 66 of the CIP22 if they offer for sale or undertake any preparatory sale act outside the scope of the Regulation (EU) 933/2019, the measure of the SPC manufacturing waiver should be energetically applauded by all the European generic and biosimilar industries for all the positive effects it is expected to generate, potentially increasing their competitiveness with manufacturers established in non-EU countries, not to mention the fact that it may also facilitate a faster availability of a wider choice of medicines at lower prices within the EU borders as soon as the relevant patent or supplementary protection expires.
The Italian Antitrust Authority (IAA), which was established by Law No. 287/1990, is the competent authority to ensure the protection of competition and the market, through the supervision and repression of abuses of dominant position and agreements restricting fair competition. The IAA is endowed with powers to conduct specific investigations of alleged violations of competition law and general investigations also in the pharmaceutical sector. In the case of detected violations, the IAA can order interim measures to warn against the elimination of the violation and can impose fines of up to 10 per cent of the turnover of the sanctioned company. In addition, the IAA controls concentration operations, which for their relevance are subject to reporting obligations to the IAA, and may order their suspension or require specific conditions for their authorisation. Finally, the IAA may take legal action against public administration measures that infringe competition law.
Among the enforcement priorities in the pharmaceutical sector, the IAA focuses on co-marketing agreements, which are common to promote the sale and marketing of medicines. According to such agreements, two pharmaceutical companies agree to sell, concurrently and autonomously, the same product with different trademarks. However, said agreements may generate antitrust concerns if their effective use is a means of exchanging commercially sensitive information, fixing prices or achieving market sharing.
Furthermore, the IAA control focuses on the abuse of dominant position risk, which might occur if a company holding the patent unlawfully seeks to expand the scope of the right by preventing competitors from entering the market. To ensure the potentially pro-competitive function of the patent protection, the IAA intervenes against abusive uses of patents; for instance, if there is a misuse of the patent right with respect to the function for which it was granted to the detriment of competition.
The interplay between innovative companies and manufacturers of generic drugs constitutes another issue of greater interest for competition law in the pharmaceutical sector, also because of its implications on public expenditure. To mediate between the protection of industrial property rights and the competitive and efficient guarantee of right to health, the IAA must ensure that the transition from patent protection to the generic drugs' market entry is carried out in accordance with competitive principles. The first priority in this respect for the IAA is to ensure that there are no private agreements between originators and manufacturers of generics aimed at delaying full competition in the market and at gaining market share from the patent holder when the patent expires.23
Under this approach, according to the report of the European Commission on competition enforcement in the pharma sector published on 28 January 2019, the IAA resulted the most active authority within the EU in the period 2009–2017, having issued pecuniary sanctions to pharma companies totalling €198.5 million.24
The IAA is the competent authority to merger control assessing whether the concentrations, which for their relevance must be notified to the IAA itself pursuant to Article 16 of Law No. 287/90, lead to the constitution or strengthening of a dominant position endangering in a substantial and durable way competition in the national market.
In the Italian economical context, the IAA must balance the need, on the one hand, to avoid the operations of concentration leading to a structure in which high market shares concentrate in the hands of a few operators, and, on the other hand, the interest to promote growth of the many small and micro-sized enterprises. In light of this, the IAA tends to limit as much as possible its own interventions with regard to concentrations by imposing conditions or prohibiting operations only in cases where it is essential to protect competition in the relevant market.25
In the period 2007–2017, the IAA authorised with remedies 24 concentrations out of a total number of transactions requiring further investigation amounting to 46,100. In total, the IAA ordered the adoption of 147 measures in the 24 operations covered by its ex post assessment, with an average of about six measures per decision. Taking into consideration the relevant industries, the IAA imposed the higher number of remedies for concentrations in the retail distribution, insurance and banking sectors. Conversely, there were no relevant decisions concerning the pharmaceutical sector, whose merger operations normally have a transnational dimension and involve the European Commission.26
The two main drivers of competition in the pharmaceutical sector are product innovation through R&D and price. For this reason, the most important competitive dynamics entail the relationship between originators and manufacturers of generic drugs, which is often affected by anticompetitive behaviours ultimately aimed at hindering the market entry of generic drugs. In this respect, with the most recent landmark decisions, the IAA focused on abusive conducts and anticompetitive agreements.
In January 2012, the IAA sanctioned with a €10.6 million fine for abuse of dominant position holding that the dominant company (Pfizer) had abused patent protection for a certain medicine to achieve an undue extension of the exclusivity regime, delaying the entry into the market of generic medicines, which cost significantly less than the originators.27
In 2014, in the Lucentis Avastin case,28 the IAA sanctioned Hoffmann-La Roche and Novartis with a pecuniary fine amounting respectively to €90.6 million and €92 million, as they entered into an anticompetitive agreement aimed at discouraging and limit off-label use of Hoffmann-La Roche's oncology medicine for treatment of age-related macular degeneration. According to the IAA, the arrangement was intended to disseminate information raising concerns about the safety of Avastin used in ophthalmology to shift demand towards the more expensive Lucentis. The decision of the IAA was confirmed by the Council of State with its decision No. 4990 dated 15 July 2019.29
In the same year, the IAA investigated on the alleged conclusion of an anticompetitive agreement by Novartis and Italfarmaco that had been coordinating their activities for a three-year period in relation to tender procedures for the supply of a drug with a long-acting octreotide active ingredient. Although the IAA closed the case finding no infringement, the same had suspected that the two competitor companies had implemented bid-rigging practices to influence the outcome of tender procedures, in particular to fix prices and share the market between them. During the investigations, the IAA had focused on the effects of the co-marketing arrangement Novartis and Italfarmaco had entered into with the suspect it was a mean for a pervasive exchange of sensitive information between the two companies.30
In the Aspen case in September 2016,31 the IAA imposed a €5.2 million fine on Aspen for abusing its dominant position by setting unfair prices for important off-patent medicines used to treat cancer. The IAA found that Aspen abused its dominant position in Italy by threatening to initiate supply termination, imposing price increases of between 300 and 1,500 per cent and by applying particularly aggressive tactics towards the AIFA in negotiating these prices. The IAA decision was upheld by the Administrative Court of the Lazio Region.32 An appeal against this judgment is pending before the Italian Council of State.
Recently, in the covid-19 emergency, the IAA has intervened several times in relation to anticompetitive conducts of pharmaceutical companies. Specifically, on 17 March 2020, the IAA suspended the marketing of an antiviral drug sold for more than €600 and ordered the blackout of the related website.33
Outlook and conclusions
In its search for balance between innovation and quality, on the one hand, and control on public expenditure, on the other, the Italian legislator has put in place a complex legislative and regulatory framework that, while still protecting patent and exclusivity rights of developers of new drugs with the purposes of prompting investments in research and development, is also characterised by universal access to medicines and expenditure savings, connected with the availability of biosimilar and generic drugs. In this respect, the pharma business short and medium-term outlook seems encouraging, notwithstanding the impact of the covid-19 contingencies.
To make sure that all marketing opportunities offered by the Italian pharmaceutical sector are properly exploited and that patents and exclusivity rights are duly protected, both developers of originators and generics should take into account the IAA's incisive supervisory and enforcement activity aimed at detecting and repressing anticompetitive behaviours in this sector.
1 Roberto Cursano is a partner, Lorenza Mosna and Riccardo Ovidi are associates, and Irene Carlet is a legal trainee at Studio Professionale Associato a Baker & McKenzie.
2 Italian Association of Pharmaceutical Companies, Report on the pharmaceutical industry in Italy, 2019, www.farmindustria.it/documenticategory/i-numeri-dellindustria-farmaceutica-in-italia/.
3 The centralised procedure is compulsory, among others, for: (1) human medicines containing a new active substance to treat HIV, AIDS, cancer, diabetes, neurodegenerative diseases, auto-immune and other immune dysfunctions, and viral diseases; (2) medicines derived from biotechnology processes, such as genetic engineering; (3) advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines; and (4) orphan drugs (medicines for rare diseases). It is optional for other medicinal products: (1) containing new active substances for indications other than those stated above; (2) that are a significant therapeutic, scientific or technical innovation; and (3) whose authorisation would be in the interest of public health at EU level.
4 Pursuant to the centralised procedure, the EMA's Committee for Medicinal products for Human Use carries out a scientific assessment of the application and gives a recommendation on whether the medicine should be marketed. However, the EMA has no authority to actually authorise marketing in the different EU countries since, under EU law, the authorising body for all centrally authorised product is the European Commission, which takes a legally binding decision based on the EMA's recommendation. Once granted by the European Commission, the centralised marketing authorisation is valid in all EU Member States as well as in the European Economic Area countries Iceland, Liechtenstein and Norway. Commission decisions are published in the Community Register of medicinal products for human use.
5 The mutual recognition procedure, which is applicable to the majority of conventional medicinal products, is based on the recognition of a pre-existing national marketing authorisation by one or more EU countries. To be eligible for the mutual recognition procedure, a medicinal product must have already received a marketing authorisation in one EU country. An application for mutual recognition may be addressed to one or more EU countries. The applications submitted must be identical, and all EU countries notified. The country charged with evaluating the application or reference Member State notifies the other concerned Member States. The reference Member State is then charged with deciding on the product. This evaluation process may take up to 210 days, and ends with the granting of a marketing authorisation in that EU country. The concerned Member States then have 90 days to recognise the decision of the reference Member State, and the summary of product characteristics (SPCs), labelling and packaging. National marketing authorisations are granted within 30 days.
6 The decentralised procedure applies to situations where the application for marketing authorisation is submitted simultaneously in several EU countries and allows its common assessment. It can be used for medicinal products that do not need to be authorised via the centralised procedure and have not already been authorised in any Member State. Pursuant to this procedure, one of the Member States takes the lead in evaluating the application as reference Member State. Within 120 days of the receipt of a valid application, the latter develops a draft assessment report, SPCs, labelling and package leaflet and forwards the same to the other (concerned) Member States who then have 90 days to express their approval. At the end of the procedure, each Member State who approved the documentation developed by the reference Member State shall issue a marketing authorisation. The advantage of this procedure is that the applicant may obtain the requested marketing authorisation simultaneously in several Member States without having to hold a prior marketing authorisation granted by another Member State.
9 Conditional marketing authorisations are valid for one year and can be renewed annually. The marketing authorisation holder is required to fulfil specific obligations (ongoing or new studies, and in some cases additional activities) with a view to providing comprehensive data confirming that the benefit-risk balance is positive. Once comprehensive data on the product have been obtained, the marketing authorisation may be converted into a 'standard marketing authorisation', which is initially valid for five years and can be renewed for unlimited validity. Medicines for human use are eligible if they are aimed at treating, preventing or diagnosing seriously debilitating or life-threatening diseases.
10 The medicine must be undergoing clinical trials or have entered the marketing-authorisation application process and while early studies will generally have been completed, its safety profile and dosage guidelines may not be fully established.
11 Pursuant to the Decree of the Ministry of Health dated 7 September 2017, a request for compassionate use can be filed by the responsible physician provided that: a phase III clinical trial on the investigational medicine is undergoing (in exceptional cases it is allowed to provide medicines for which a phase II or phase I trial has been completed); the requested medicine is already authorised for indications other than those required by the patient (off-label use); and the medicine, although duly licensed, is not yet available in Italy. Compassionate use programmes must be notified to the AIFA and expire as soon as the medicine is placed on the market. The Italian Council of State, with its Opinion No. 2356/2016, stated that, even though the relevant medicine has already been placed on the market, patients can benefit from free-of-charge compassionate use until the reimbursement agreement has been approved.
12 Giuseppe Franci Ferrari, Fausto Massimino 'Diritto del Farmaco. Medicinali, diritto alla salute, politiche sanitarie', Cacucci Editore.
13 Giuseppe Franci Ferrari, Fausto Massimino 'Diritto del Farmaco. Medicinali, diritto alla salute, politiche sanitarie', Cacucci Editore.
18 Article 68.1 bis CIP: 'companies intending to manufacture medicinal products outside patent protection may start the registration procedure for the product containing the active ingredient one year prior to the date of expiration of the supplementary protection or, in the absence, of the patent protection of the active ingredient, having regard to any possible extension'.
19 Italian case law dealing with cases where originators tried to enforce their rights at the stage of obtaining marketing authorisations by generic companies (mostly issued before the repealing of Article 68.1 bis CIP) is quite well-developed. Since the famous Roche Products Inc v. Bolar Pharmaceutical Co decision, Italian courts (with few exceptions) have agreed that preclinical tests and clinical trials aimed at obtaining the marketing authorisation for generic drugs are permitted under the Bolar clause, regardless of the prohibition set forth by (the now repealed) Article 68 Paragraph 1 bis CIP. In particular, the Court of Milan, on 11 June 2009 in Eli Lilly and Company Ltd and Eli Lilly Italia Spa v. Sandoz International and others, following the interpretation of Article 68 CIP adopted in other decisions by the same court, stated that the mere filing of a request for marketing authorisation for a generic drug, lacking any actual proof of the commercial exploitation of the same, is not sufficient per se to ground a patent infringement claim. In fact, the filing of a request for (and even the subsequent obtainment of) the marketing authorisation does not necessarily indicate a certain time for market entry. According to the court, the principle set forth by Article 68.1 CPI (the Bolar exemption) overcomes the (one-year) limit imposed by Article 68.1 bis CIP. In this respect, the court clarified that only the actual undertaking of specific preparatory activities for the manufacturing and commercialisation of a generic product – such as the purchasing or production of the active ingredient, the storage of the product, the set up of an actual distribution network on the territory or the launch of a promotional campaign – may amount to patent infringement. In the Sanofi v. Teva Pharma case, the same Court of Milan uphold the originator's request for a preliminary injunction against a generic product that had already obtained market approval. The decision was issued after the repealing of Article 68.1 bis CPI. The Court of Milan found that the activities carried out by the defendant in addition to the registration process for the generic product – namely the publication on the Official Gazette of the price of the generic drugs, the communication to the database service provider ADF Service of the intention to start selling the generic drugs, for the purpose of including the product into the Pharma database, and the inclusion of the drug into the transparency list held by the Italian Medicine Agency – clearly represented infringing preparatory activities suitable to cause a prejudice to the originator, both in terms of customers distraction and economic damages due to the reduction of the reimbursement allowed by the NHS.
20 Regulation (EU) 2019/933 of the European Parliament and of the Council of 20 May 2019, amending Regulation (EC) No 469/2009 concerning the supplementary protection certificate for medicinal products.
21 According to the Whereas (26) of the Regulation 'it is justified that this Regulation also cover, over a certain period of time, a certificate that was applied for before the date of entry into force of this Regulation, but has not yet taken effect before that date, irrespective of whether or not that certificate was granted before that date. The exception should apply, therefore, from 2 July 2022 to a certificate that takes effect from the date of entry into force of this Regulation. The concept of 'certain period of time' for each individual certificate that takes effect after the date of entry into force of this Regulation should ensure that the exception is applied, on a progressive basis, to such a certificate, depending on the date on which it takes effect and on its duration. Such application of the exception would allow the holder of a certificate that has been granted, but that has not yet taken effect by the date of the entry into force of this Regulation, a reasonable period of transition to adapt to the changed legal context, while at the same time ensuring that makers of generics and biosimilars can benefit effectively, without excessive delay, from the exception'.
22 According to Article 66 CPI, the acts of producing, using, placing on the market, selling the product that is the subject matter of a patent or importing such a product for the aforementioned purposes; and using a process that is the subject-matter of the patent or offering, placing on the market, selling a product that is produced directly by a process that is the subject-matter of the patent, or importing such a product for the aforementioned purposes, are reserved to the right holder.
23 F. Massimino, G. F. Ferrari, Diritto del Farmaco. Medicinali, Diritto alla Salute, Politiche Sanitarie, Cacucci ed., Bari, 2015, 347-354; C. Rabitti Bedogni in the Minutes of the I Italian Antitrust Association Convention, I principali sviluppi nel diritto della concorrenza comunitario e nazionale, Sorrento, 20-21 May 2011; Commission Communication, of 8 July 2008, Executive Summary of the Pharmaceutical Sector Inquiry Report, available at http://ec.europa.eu/competition/sectors/pharmaceuticals/inquiry/communication_en.pdf.
24 EU Commission, Report on Competition Enforcement in the Pharmaceutical Sector (2009-2017), available at https://ec.europa.eu/competition/sectors/pharmaceuticals/report2019/report_en.pdf.
25 IAA, Annual Report, published on 31 March 31 2019, p. 45, available at https://www.agcm.it/dotcmsdoc/relazioni-annuali/relazioneannuale2018/Relazione_annuale_2019.pdf.
26 IAA, Annual Report, published on 31 March 31 2019, p. 45, available at www.agcm.it/dotcmsdoc/relazioni-annuali/relazioneannuale2018/Relazione_annuale_2019.pdf.
27 The IAA Decision of 11 January 2012; www.agcm.it/media/comunicati-stampa/2012/1/alias-5857.
28 The IAA Decision of 27 February 2014; the relevant press release of the IAA is available at www.agcm.it/media/comunicati-stampa/2014/3/alias-6801.
29 Judgment No. 4990 of the Council of State of 15 July 2019.
30 The relevant press release of the IAA is available at www.agcm.it/media/comunicati-stampa/2014/2/alias-6744.
31 The IAA Decision of 29 September 2016; the EU Commission Report on Competition Enforcement in the Pharmaceutical Sector (2009-2017) makes reference to this case as well, available at https://ec.europa.eu/competition/sectors/pharmaceuticals/report2019/report_en.pdf.
32 Judgment of the Regional Administrative Court of the Lazio Region of 26 July 2017.
33 The relevant press release of the IAA is available at https://en.agcm.it/en/media/press-releases/2020/3/PS11723.