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Life Sciencesin 25 jurisdictions worldwideContributing editors: Alexander Ehlers and Cord Willhöft 2012

Published by Getting the Deal Through

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Introduction Alexander Ehlers and Cord Willhöft Ehlers, Ehlers & Partner 3

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Life Sciences 2012

Contributing editors Alexander Ehlers and Cord Willhöft Ehlers, Ehlers & Partner

Business development managers Alan Lee George Ingledew Robyn Hetherington Dan White

Marketing managers Ellie Notley Alice Hazard

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Publisher Richard Davey

Life Sciences 2012 Published by Law Business Research Ltd 87 Lancaster Road London, W11 1QQ, UK Tel: +44 20 7908 1188 Fax: +44 20 7229 6910 © Law Business Research Ltd 2012

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Bird & Bird LLP united kingdom

United KingdomGerry Kamstra

Bird & Bird LLP

Or�ganisation and financing of health car�e

1 How is health care in your jurisdiction organised?

Health care is provided in England through two systems, namely by the government-run National Health Service (NHS) and by private health-care arrangements. In Scotland, Wales and Northern Ireland there are equivalent service providers to the NHS. In each country the administration of the government-funded service is organised by geographical regions, in England by Strategic Health Authori-ties (SHAs) acting on behalf of the Department of Health (DoH), though certain functions such as some of the purchasing of medicines and equipment and pricing of medicines are carried out centrally (in England through Buying Solutions (the NHS purchasing agency) and the DoH respectively). Private health-care providers, although falling outside the scope of regulation by the DoH, are nevertheless regulated by legislation.

2 How is the health-care system financed in the outpatient and

in-patient sectors?

The NHS (and its equivalents under the devolved governments) is publicly funded through governmental spending allocated to the DoH (and its equivalents) and provides free-at-the-point-of-delivery outpatient and in-patient care (though fixed, lower-than-cost, fees are payable by non-exempt patients at the point of dispensing of NHS prescriptions and of delivery of NHS dental and eye care ser-vices). Private health care is provided by physicians (who may be contracted to the NHS in addition to having a private practice) and by private clinics and hospitals (though many NHS clinics and hospi-tals host private health-care services under contract) that are paid by the patient or by their health insurance scheme. Dispensing of medi-cines and home-use medical devices is carried out in the outpatient sector by privately-owned pharmacies (which include large national chains of retail pharmacies), which in the case of NHS prescriptions will seek reimbursement from the DoH; and in the in-patient sec-tor by hospital pharmacies, which in the case of NHS hospitals are reimbursed by the host hospital. Patients may choose to ‘mix-and-match’ NHS services with private health-care services, with it being commonplace for patients covered by private health-care schemes (roughly 14 per cent of the population) to rely on the NHS for acute or emergency health-care services and for prescriptions and on pri-vate health-care providers for non-emergency care and treatment.

Compliance – phar�maceutical manufactur�er�s

3 Which legislation governs advertisement of medicinal products to the

general public and health-care professionals?

The regulation of advertising relating to medicinal products in the EU is governed by what are now articles 86 to 100 of EU Directive 2001/83/EC and by implementing legislation at national level, as well as by industry codes at international and national levels. EC law is

implemented in the UK by the Medicines (Advertising) Regulations 1994 and the Medicines (Monitoring) Regulations 1994, as amended (primarily by 1999, 2004 and 2005 Regulations). Paragraph 5 of the Monitoring Regulations provides that, where a complainant and the health ministers (through the UK enforcement agency and the advertising unit of the Medicines and Healthcare Regulatory Agency (MHRA)) agree within a reasonable time, a complaint may be referred to and dealt with by a self-regulatory body, rather than by the court.

The relevant self-regulatory bodies, which operate their own codes of practice, are identified in chapter 9 of the MHRA publica-tion The Blue Guide: Advertising and Promotion of Medicines in the UK (2005 edition). These are the Prescription Medicines Code of Practice Authority (PMCPA), which administers the Association of the British Pharmaceutical Industry (ABPI) Code of Practice; the Proprietary Association of Great Britain, whose code of prac-tice regulates over-the-counter (OTC) medicines; the Health Food Manufacturers Association, whose code of practice covers specialist health products; the British Dental Trade Association; the Office of Communications, which regulates the contents of broadcasted pro-grammes and advertising; and the Advertising Standards Authority and Committee of Advertising Practice. The relationship between the MHRA, the PMCPA and the ABPI is the subject of a memorandum of understanding. There is also legislation generally applicable to promotional practices, such as the Trades Descriptions Act 1968, Consumer Protection from Unfair Trading Regulations 2008/1277 and the Business Protection from Misleading Marketing Regulations 2008/1276.

4 What are the main rules and principles applying to advertising aimed

at health-care professionals?

Advertising to health professionals is addressed by regulation 14 of The Medicines (Advertising) Regulations 1994, which provides that any advertisement must contain essential information compatible with the summary of product characteristics and must contain:• thelicencenumberofthemedicinalproduct;• thenameandaddressoftheholderoftheproductlicence;• thesupplyclassificationofthemedicinalproduct;• thenameoftheproduct,andalistoftheactiveingredients;• oneormoreoftheindicationsfortheproductconsistentwith

the terms of the licence;• asuccinctstatement(whererelevant)oftheentriesinthesum-

mary of product characteristics relating to side-effects, precau-tions and relevant contraindications;

• asuccinctstatementoftheentriesinthesummaryofproductcharacteristics relating to dosage and method of use relevant to the indications shown. The method of administration should also be shown where this is not obvious;

• anywarningrequiredbythelicensingauthorityinadvertise-ments; and

• thecostofthemedicinalproduct.

united kingdom Bird & Bird LLP

142 Getting the Deal Through – Life Sciences 2012

In the case of the above particulars marked with an asterisk they must be printed in a clear and legible manner and be placed in such a position in the advertisement that their relationship to the claims and indications for the product can readily be appreciated by the reader.

Audio-visual advertising to health professionals is addressed by regulation 15, which requires all of the above particulars to be provided (except the last one), although they may be provided in writing. regulation 16 addresses ‘abbreviated advertisements’ (an advertisement, other than a loose insert, which does not exceed an area of 420cm2, in a publication sent or delivered wholly or mainly to persons qualified to prescribe or supply relevant medicinal products) and requires the inclusion of essential information compatible with the summary of product characteristics, the second and fourth par-ticulars above and words stating that more information is available from the licence holder.

Under regulation 17 the above requirements do not apply to an advertisement that is on a promotional aid (which the MHRA considers to include pens, notepads and mugs) if the advertisement consists solely of the name of the product and the advertisement is intended solely as a reminder.


at the general public?

Regulation 7 prohibits any advertisement that is likely to lead to the use of a prescription-only product. Regulation 9 permits advertise-ments of non-prescription medicines that do not:• givetheimpressionthatamedicalconsultationorsurgicalopera-

tion is unnecessary;• suggestthattheeffectsoftakingthemedicinalproductareguar-

anteed, are unaccompanied by side effects or are better than, or equivalent to, those of another identifiable treatment or medici-nal product;

• suggest thathealthcanbeenhancedbytakingthemedicinalproduct;

• suggestthathealthcouldbeaffectedbynottakingthemedicinalproduct;

• directtheadvertisementexclusivelyorprincipallyatchildren;• refertoarecommendationbyscientists,healthprofessionalsor

persons who are neither of the foregoing but who, because of their celebrity, could encourage the consumption of medicinal products;

• suggestthatthemedicinalproductisafoodstuff,cosmeticorother consumer product;

• suggestthatthesafetyorefficacyofthemedicinalproductisdueto the fact that it is natural;

• leadtoerroneousself-diagnosis,byadescriptionordetailedrep-resentation of a case history;

• refer,inimproper,alarmingormisleadingterms,toclaimsofrecovery; or

• use,inimproper,alarmingormisleadingterms,pictorialrepre-sentations of changes in the human body caused by disease or injury, or of the action of a medicinal product on the human body or parts thereof.

6 What are the most common infringements committed by

manufacturers with regard to the advertisement rules?

According to the PCMPA, generally complaints are about printed materials or about what is said by manufacturers’ representatives. The largest proportion of complaints (about 40 per cent) are made by health professionals.

7 Under what circumstances is the provision of information regarding off-

label use to health-care professionals allowed?

Regulation 3 prohibits the promotion of products that do not have a marketing authorisation. However, it is also true that article 5.1 of Directive 2001/83/EC permits the supply of unlicensed prod-ucts to doctors who require them in cases of ‘special need’, and the UK Regulations governing such use are currently under review by the MHRA. Consistently with the existence of this derogation the MHRA does permit the provision of scientific information about off-label uses to health-care professionals who solicit this, provided always that this does not amount to promotion. In addition, clause 3 of the ABPI Code allows the promotion of uses that are not author-ised in the UK but are authorised in at least one other major indus-trialised country at any ‘truly international meeting of high scientific standing with a significant proportion of attendees from countries outside the UK’ and providing certain conditions are met in relation to such promotion.

8 Which legislation governs the collaboration of the pharmaceutical

industry with health-care professionals? Do different rules apply

regarding physicians in the in-patient and outpatient sector?

The regulation of collaboration between the pharmaceutical industry and health-care professionals is covered by legislation and codes of practice, including not only those identified in the answer to question 3 above, but also (inter alia) the Clinical Trials Regulations 2004, the Data Protection Act 1998, the Re-use of Public Sector Information Regulations 2005, the General Medical Council guidance to doc-tors, the NHS Best Practice Guidance on Joint Working Between the NHS and Pharmaceutical Industry and Other Relevant Commercial Organisations 2008 (which also apply to professionals in private practice) and the ABPI Guidance Notes on Joint Working Between Pharmaceutical Companies and the NHS and Others for the Benefit of Patients 2009. The latter two guidance notes provide a reasonably comprehensive guide to the legal and best practice principles that must be followed to achieve transparency, good clinical practice and ethical compliance. More recently, the enacting of the Bribery Act 2010 has prompted the ABPI to issue a guidance note (dated July 2011) on the application of the Act to (for example) arrangements with foreign public officials. Also a new body, the Health Research Authority (HRA), is being established in late 2011 to streamline regulation, create a unified approval process and promote propor-tionate standards for compliance and inspection within a consistent national system of health research. The legislation and guidance cited here does not differentiate between practice in the in-patient and outpatient sectors, though obviously some rules are more applicable to one sector than the other.

9 What are the main rules and principles applying to the collaboration of

the pharmaceutical industry with health-care professionals?

See the answer to question 8.


manufacturers with regard to collaboration with health-care

professionals?

From the point of view of ethical practice towards patients, lack of transparency (for example failure to indicate sponsorship by the manufacturer) is the most common infringement. From a health-care professional point of view, use of disguised methods of pro-motion (for example, the use of ‘advisory boards’ paid for by the manufacturer).




the pharmaceutical industry with patient organisations?

Clause 23 of the ABPI Code sets out the conditions under which a pharmaceutical company may interact with patient organisations or any user organisation such as disability organisations, carer or relative organisations and consumer organisations to support their work, including assistance in the provision of appropriate informa-tion to the public, patients and carers. The rules basically ensure transparency of, and accountability for, the support. In addition, the relevant patient organisation may have guidelines or be constrained by Charity Commission requirements, or both.

12 Are manufacturers’ infringements of competition law pursued by

national authorities?

Yes; by the Office of Fair Trading using its powers under the Com-petition Act 1998 and the Enterprise Act 2002.

13 Is follow-on private antitrust litigation against manufacturers possible?

Yes; either before the Competition Appeal Tribunal or in the High Court.

Compliance – medical device manufactur�er�s

14 Is the advertising of medical devices and the collaboration of

manufacturers of medical devices with health-care professionals

and patient organisations regulated as rigorously as advertising and

collaboration in the pharmaceuticals sector?

The regulation of medical devices in Europe is subject to a different legislative regime to that applicable to medicines. Regulation 12(1) of the Medical Devices Regulations 2002, as amended (which imple-ment Directive 93/42/EC, as amended) allows the display at a trade fair, exhibition, demonstration or similar gathering of a device which has not satisfied the requirements of Directive 93/42/EC or the Regu-lations; otherwise a device falling within the scope of the legislation that has not yet satisfied the requirements of the legislation may not be put onto the market or promoted. The regulation of advertising and promotion of devices that have satisfied the requirements of the legislation is governed by voluntary codes, namely the Association of British Healthcare Industries (ABHI, the trade association inter alia for medical device manufacturers) Code of Business Practice 2009 and the Eucomed (the European trade association for medical technology manufacturers) Code of Ethical Business Practice 2009 (including Guidelines on Interactions with Healthcare Professionals 2008) and Position Paper on Access to the Operating Room for Med-ical Device Company Representatives (1 October 2011). Complaints under the ABHI Code may be referred to a panel of independent individuals, chaired by an independent barrister.

Phar�maceuticals r�egulation

15 Which legislation sets out the regulatory framework for granting

marketing authorisations and placing medicines on the market?

The Medicines Act 1968, as amended (which implements Directive 2001/83/EC relating to the Community code on medicinal prod-ucts for human use (as amended by Directive 2002/98/EC, Direc-tive 2003/63/EC, Directive 2004/24/EC, Directive 2004/27/EC and Regulation (EC) No. 1901/2006)), Regulation (EC) No. 1901/2006 (relating to medicinal products for paediatric use), Regulation (EC) No. 726/2004 (relating to biological and other medicinal products and establishing the European Medicines Agency (EMA)) and Regu-lation (EC) No. 1394/2007 (relating to advanced therapy medicinal products).

16 Which authorities may grant marketing authorisation in your

jurisdiction?

The MHRA is the UK competent authority under the EC Directives and Regulations and is the executive agency of the Department of Health under UK legislation. The EMA is located in London but is a Community agency and is responsible for the grant of EU-wide (central) authorisations under the EC Regulations.

17 What are the relevant procedures?

There are four alternative routes to obtain a marketing authorisation (MA) for a medicinal product in the EU (including of course the UK):• theNationalProcedure(NP);• theNationalProcedurefollowedbytheMutualRecognition

Procedure (MRP);• theDecentralisedProcedure(DCP);and• theCentralisedProcedure(CP).

The route available to a prospective applicant for an MA depends upon various factors including the nature of the product itself (eg, whether it is a biological or not, or whether it is a new active sub-stance or not) and the diseases that the product is intended to treat.

Where an MA is required in only one member state and the medicinal product does not fall under the mandatory scope of the CP (see below), an MA application can be made to the competent regula-tory authority of that member state. This is of limited applicability as the majority of applicants will seek to market the product in more than one member state.

The MRP can be used where an MA has already been granted by one member state (the reference member state or RMS) and an MA is sought in one or more other member states (the concerned member states). Instead of needing to submit a full MA application to that other member state, the applicant simply requests that the member states ‘recognise’ the existing MA and grants an MA on that basis. The procedure involves the preparation of an Assessment Report by the RMS, which is forwarded on to the concerned member states for review and consideration. Providing the concerned member states do not disagree, the MA will be granted in the concerned member state. If the concerned member state does disagree, a dispute resolution procedure conducted by the Coordination Group for Mutual Rec-ognition and Decentralised Procedure (CMD(h)), will be followed and if the CMD(h) cannot agree, the issue will be referred to the Committee for Medicinal Products for Human Use (CHMP) for a final decision.

The DCP route was introduced by Directive 2004/27 (amending the Medicines Directive) and is used where the applicant has not yet received an MA for that product in any member state and is seeking MAs in more than one member state. The DCP route has been avail-able since November 2005. Under the DCP, the MA applications are made simultaneously in all member states in which the appli-cant wishes to obtain an MA. The applicant chooses one member state to act as a RMS, which then takes the lead in assessment and conducting the procedure. The RMS prepares a draft Assessment Report, which is forwarded on to all concerned member states for their simultaneous review and approval, whereupon a timed proce-dure is initiated resulting in the grant MAs in each of the member states (or in the case of disagreement, the matter is again referred to the CMD(h) and the CHMP). The Centralised Procedure allows for a single application to be made to the EMA for a MA cover-ing the whole Community. This application is then evaluated by the CHMP, which issue an opinion to the Commission on whether the MA should be granted, whereupon the Commission itself will make the final decision.

The CP route is governed by Regulation 726/2004 and has both a mandatory and an optional scope. The CP must be used for:• productsdevelopedbycertainbiotechnologicalprocesses;



• productscontaininganewactive ingredientfortreatmentofAIDS, cancer, neurodegenerative disorder, autoimmune diseases and other immune dysfunctions and viral diseases; and

• productsdesignatedasorphanmedicinalproductsunderRegula-tion 141/2000.

The CP may optionally be used for:• newactivesubstances,whichhavenotpreviouslybeenauthor-

ised in the Community (regardless of the indication);• productsthatareshowntoconstituteasignificanttherapeutic,

scientific or technical innovation or that the granting of a central authorisation is in the interests of patients; and

• genericproductsofareferencemedicinalproductitselfauthor-ised under the CP.

18 Will licences become invalid if medicinal products are not marketed

within a certain time? Are there any exceptions?

Under Regulation 5(7) of the Medicines for Human Use (Market-ing Authorisations Etc) Regulations 1994 (which implements article 24(4) of Directive 2001/83/EC), a UK marketing authorisation (other than a parallel import licence) shall cease to be valid if at any time after it is granted the medicinal product to which it relates is not placed on the market in the UK for a period of three consecutive years, unless an exemption is granted in accordance with article 24(6) of the 2001 Directive. An exemption under article 24(6) may be granted in exceptional circumstances and on public health grounds that are duly justified.

19 Which medicines may be marketed without authorisation?

Schedule 1 of the Medicines for Human Use (Marketing Authori-sations Etc) Regulations 1994 sets out the circumstances in which this may occur. The principal exemption is that a medicinal product may be supplied in response to a bona fide unsolicited order, formu-lated in accordance with the specification of a doctor, dentist, sup-plementary prescriber, nurse independent prescriber or pharmacist independent prescriber and for use by his individual patients under his direct personal responsibility in order to fulfil the special needs of those patients, provided that certain conditions are also fulfilled as to the non-advertisement and manufacture of the product.

20 Are any kinds of named patient (or similar expanded access)

programmes in place? If so, what are the requirements for pre-launch

access?

Under Article 5(1) of Directive 2001/83, member states are permit-ted to put in place national arrangements to allow an authorised health-care professional to commission the manufacture of an unli-censed medicinal product to meet the special needs of an individual patient under their direct personal responsibility. There are currently arrangements in place in the UK for unlicensed medicines manufac-tured in the UK and a notification scheme for medicines imported into the UK. Those national provisions are set out in the Medicines for Human Use (Marketing Authorisations Etc.) Regulations 1994, as amended and the Medicines for Human Use (manufacturing, whole-sale dealing and miscellaneous amendments) Regulations 2005. The MHRA is currently considering possible options for reform, with formal proposals to be put forward in late 2011. The proposals will also include the creation of a statutory register for practitioners sup-plying unlicensed herbal medicines, allowing the UK derogation in Article 5 (1) of Directive 2001/83/EC to apply to them also.

Pr�icing and r�eimbur�sement of medicinal pr�oducts

21 To what extent is the market price of a medicinal product governed by

law or regulation?

The statutory powers covering pharmaceutical pricing are contained in sections 260 to 266 of the National Health Service Act 2006, under which some eight sets of Regulations are in force. Under section 261 the DoH has entered into a voluntary price regulation scheme with the Association of the British Pharmaceutical Industry (ABPI) called the Pharmaceutical Price Regulation Scheme (PPRS), which is peri-odically renegotiated, the latest version being the 2009 PPRS.

The PPRS only applies to branded NHS medicines, defined as a human pharmaceutical product for which a marketing authorisation has been granted and to which the owner applies a brand name that enables the product to be identified without reference to its generic name. The PPRS applies to members of the ABPI and to non-mem-bers who inform the DoH that they will adhere to the PPRS, and such companies are thereby exempt from the statutory price regulation powers. The PPRS does not set prices for branded NHS medicines but it does set a ceiling on companies’ profits on NHS sales, while not guaranteeing them.

The 2009 PPRS sets a target of 21 per cent on a company’s return on capital employed from home sales of NHS medicines, so it regulates prices of branded medicines by regulating overall profits obtained on sales to the DoH. The price of generic medicines is not directly regulated either but under the Drug Tariff the reimburse-ment paid to pharmacies dispensing medicines prescribed by an NHS health-care professional is fixed, so there is competition to supply generic medicines at a price that gives pharmacies the greatest profit having regard to the reimbursement set by the Drug Tariff. The Drug Tariff is produced monthly by the Pharmaceutical Directorate of the NHS Business Services Authority, NHS Prescription Services for the DoH.

On the other hand the reimbursement paid to pharmacies for branded proprietary (eg, on-patent) medicines is effectively the manufacturer’s list price (by virtue of being listed in the Drug Tariff under its generic name with a price that reflects the list price, or if it is not listed by reference to its generic name the list price will apply by default) – hence the need for the PPRS to indirectly regulate list prices. In addition, the National Institute for Clinical Excellence (NICE) undertakes reviews on behalf of the DoH of the cost-benefit of products (generally a class of products or therapies at a time) resulting in guidance to the NHS about the use of such products. The role of NICE in effectively precluding the use by the NHS of certain products has been controversial (and been the subject of a number of judicial reviews, some successful) and the new coalition government that came into power in May 2010 has carried out a consultation in relation to the future role of NICE and to a ‘value-based’ control of pricing of pharmaceuticals. In its response to the consultation (18 July 2011) the government noted the wide range of opinions and conceded that further consultation would be required before aban-doning the current PPRS and the current role of NICE, commenting that in any event that a ‘value-based’ pricing system would (like the PPRS) have to be a voluntary scheme.

22 Must pharmaceutical manufacturers negotiate the prices of their

products with the public health-care providers?

See question 21.

23 In which circumstances will the national health insurance system

reimburse the cost of medicines?

As indicated in the answers to questions 2 and 21, medicines are dispensed under the NHS scheme free at the point of delivery (subject to the payment of a fixed, lower-than-cost fee – currently £7.40 per



prescription – by non-exempt patients) and reimbursement is effected via payments by the DoH to pharmacies. Exempt patients are those that are 60 or over, are under 16, are 16-18 and in full-time educa-tion, are pregnant or have had a baby in the previous 12 months and have a valid maternity exemption certificate, have a specified medi-cal condition and have a valid medical exemption certificate, have a continuing physical disability that means that they cannot go out without help from another person and have a valid medical exemp-tion certificate, hold a valid war pension exemption certificate and the prescription is for their accepted disability, are NHS in-patients or are in receipt of government income support or pension credits. A doctor can issue an NHS (reimbursable) prescription for any licensed or unlicensed medicine (including medicines for off-label use and ‘specials’) except products that are ‘blacklisted’ in Part XVIIIA of the Drug Tariff (corresponding to schedule 1 of the NHS (General Medical Services Contracts) (Prescription of Drugs etc) Regulations 2004, most of which are OTC medicines, health supplements and cosmetics that the patient must pay for).

24 If applicable, what is the competent body for decisions regarding the

pricing and reimbursability of medicinal products?

The Department of Health, as described in the answer to question 21.

25 Are manufacturers or distributors of medicinal products statutorily

obliged to give a discount?

No. However the various renegotiated versions of the PPRS over the years have required manufacturers to make price cuts on products supplied to the NHS, the latest 2009 PPRS requiring an initial price cut of 3.9 per cent in February 2009 followed by a cut of 1.9 per cent in January 2010. Also, manufacturers commonly offer discounts to purchasing pharmacies and this practice is taken into account by the DoH when calculating the reimbursement to pharmacies for medi-cines dispensed under NHS prescriptions (the ‘clawback’).

Medicine quality and access to infor�mation

26 What rules are in place to counter the counterfeiting and illegal

distribution of medicines?

The MHRA’s Enforcement and Intelligence Group has powers to bring criminal proceedings in respect of counterfeit medicines under the Medicines Act 1968 (although there is no offence of counterfeit-ing medicines it is an offence to deal in medicines without a licence under sections 8(3)(a) and 45(1)), the Trademarks Act 1994 and the Proceeds of Crime Act 2002. In addition the MHRA has information exchange agreements with the customs authorities (HMRC) to assist in the use of their enforcement powers.

The MHRA is conducting a consultative review of its powers to regulate the medicine supply chain and commented upon the paral-lel consultation by the European Commission upon a legal proposal to combat counterfeit medicines (which is one part of its three-part ‘Pharmaceutical Package’, the other two falling within the ambit of questions 27 and 28).

The MHRA’s principal intention in the light of these consulta-tions is to tighten up regulation of the wholesale supply chain start-ing from importation, by imposing (inter alia) obligations upon wholesalers to disclose their criminal records and to carry out ‘due diligence’ on the medicines that they import and supply. The MHRA also supports the Commission’s proposals that the outer packag-ing of medicines be sealed to the point of delivery (providing that this does not interfere with the legitimate parallel importation of products or the use of medicines in clinical trials), that the pedigree of a product be made traceable and accessible to all actors in the

distribution chain and that the importation of medicines into a mem-ber state require a licence even if they are to be exported again.

Private civil actions to impede trade in counterfeit medicines are also available to owners of patents, supplementary protection certifi-cates or trademarks, which are most effectively enforced by prevent-ing importation using Regulation (EC) 1383/2003. Regulation (EC) 1383/2003, as procedurally implemented in the UK under the Goods Infringing Intellectual Property Rights (Customs) Regulations 2004 (as amended by the Goods Infringing Intellectual Property Rights (Customs) (Amendment) Regulations 2010 and the Goods Infringing Intellectual Property Rights (Customs) (Amendment) (No. 2) Regula-tions 2010), enables the owner of a patent, supplementary protec-tion certificate or trademark to file an application with HMRC’s Intellectual Property Authorisation Unit requesting that goods of a certain description (ie, the suspected counterfeit goods) be detained at the border. HMRC will then review the application (including the applicant’s undertaking to pay HMRC’s costs) and if accepted it will detain the relevant products upon their arrival at the border. HMRC will then notify the applicant of the seizure and send sam-ples if requested. Upon receipt of the notification, the applicant must bring civil proceedings for infringement of the relevant right within 10 days in order to continue the detention (the maximum period of detention is 20 days).

27 What recent measures have been taken to facilitate the general

public’s access to information about prescription-only medicines?

One of the three proposals published in December 2008 by the European Commission in its ‘Pharmaceutical Package’ is a legislative proposal to liberalise the dissemination of non-promotional infor-mation on prescription medicines to patients. The UK government has responded to this proposal and in 2009 the MHRA carried out a consultation with relevant stakeholders upon the Commission’s proposals and the government’s response. The majority of UK stake-holders agreed with the Commission and the government that direct-to-consumer advertising should remain banned under Directive 2001/83/EC and that only certain communication channels for the dissemination of information should be allowed, including internet and health-related publications (but not TV and radio).

The Commission put forward various options for the regula-tion of non-promotional information and of these, the majority of UK stakeholders supported a self-regulatory approach (without pre-vetting) underpinned by national enforcement provisions. EU-wide consultation on the Commission’s proposal is still ongoing but it appears that a consensus is not clear. For example, the EU Committee of the Regions (an EU political assembly that must be consulted upon legislation that has regional or local effects) issued an opinion in March 2010, saying that it is difficult to establish which information channels can be defined as health-related publications and therefore proposes that such channels be removed from the proposal (except from information from patient organisations).

28 Outline major developments to the regime relating to safety monitoring

of medicines.

On 31 December 2010 the European Commission published Regu-lation (EC) No. 1235/2010 and Directive 2010/84/EC amending as regards pharmacovigilance Regulation (EC) No. 726/2004 concern-ing medicinal products authorised through the centralised procedure (including advanced therapy medicinal products under Regulation (EC) No. 1394/2007) and Directive 2001/83/EC concerning medici-nal products authorised through the national, decentralised and mutual recognition procedure. The Regulation entered into force on 1 January 2011 and will apply from 2 July 2012. The Directive will enter into force on 20 January 2011 and will be applicable from 21 July 2012.



This EU legislation was adopted after a number of significant weaknesses in the existing EU system of pharmacovigilance were identified through an independent Commission-sponsored study, extensive public consultation (in 2006 and again in 2007) and detailed analysis by the Commission services.

The final text of the newly adopted EU legislation, consistent with the original proposal, strengthens and rationalises the Commu-nity system of pharmacovigilance for medicinal products for human use and in particular it:• Clarifiestherolesandresponsibilitiesofthepartiesconcerned,

including the role of the supervisory authority for pharmacovigi-lance, which is the competent authority of the member state in which the pharmacovigilance system master file is located. This authority will be responsible for verifying, on behalf of the EU, that the marketing authorisation holder (MAH) for the medici-nal product satisfies the pharmacovigilance requirements laid down in Titles IX and XI of Directive 2001/83/EC and it may, if considered necessary, conduct pre-authorisation inspections to verify the accuracy and successful implementation of the phar-macovigilance system described by the applicant in support of its application for authorisation.

• IntroducesaPharmacovigilanceRiskAssessmentAdvisoryCom-mittee that will be responsible for the provision of pharmacovigi-lance assessments and of a number of recommendations on the safety of medicines at the EU level, for example: • on risk-management systems and monitoring their effective-

ness; and • on the mandatory conduct of post-authorisation efficacy

studies where concerns relating to some aspects of the efficacy of the medicinal product are identified, and can be resolved only after the medicinal product has been marketed or when the understanding of the disease or the clinical methodology indicate that previous efficacy evaluations might have to be revised significantly.

• Introduces the possibility for competent authorities to issuemarketing authorisation subject to one or more of the following conditions: to take certain measures for ensuring the safe use of the medicinal product to be included in the risk-management system; to conduct post-authorisation safety studies (PASS); to comply with obligations on the recording or reporting of sus-pected adverse reactions, which are stricter than those referred

to in Title IX of Directive 2001/83/EC; any other conditions or restrictions with regard to the safe and effective use of the medicinal product; the existence of an adequate pharmacovigi-lance system; and to conduct post-authorisation efficacy studies where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed.

• IntroducesanobligationonMAHstomaintainandmakeavail-able on request a ‘Pharmacovigilance System Master File’ in respect of one or more medicinal products. This is applicable to central marketing authorisations granted before 2 July 2012 as from either: the date on which those marketing authorisations are renewed; or the expiry of a period of three years starting from 2 July 2012, whichever is earlier; and applicable to national mar-keting authorisations (including those authorised through the mutual recognition and decentralised procedure) granted before 21 July 2011 as from either: the date on which those marketing authorisations are renewed; or the expiry of a period of three years starting from 21 July 2011, whichever is earlier.

• Removesthecurrentroutinerequirementforindustryperiodicreports (PSURs) for low risk, old and established products. In particular, periodic safety update reporting shall be linked to the risk-management system for newly authorised medicinal prod-ucts and routine reporting shall not be, in principle, required for: • generic medicinal products; • medicinal products containing an active substance for which

well-established medicinal use has been demonstrated; and • homeopathic medicinal products or for traditional-use regis-

tered herbal medicinal products. It is foreseen, however, that national competent authorities

should also require periodic safety update reports with regard to such products when concerns arise relating to pharmacovigilance data or as a result of the lack of available safety data when the use of the active substance concerned is concentrated in medicinal products for which periodic safety update reporting is not routinely required.• Introducesspecificprovisionsonthesupervisionofnon-interven-

tional post-authorisation safety studies, which are applicable as to centrally authorised medicinal products only to studies that have commenced after 2 July 2012 and as to nationally author-ised medicinal products (including those authorised through the mutual recognition and decentralised procedure) only to studies that have commenced after 21 July 2011.

• Simplifiesadversereactionreporting,andprovidesaclearlegalbasis for the reporting of suspected adverse drug reactions. In particular, a new ADR definition has been provided (‘a response to a medicinal product that is noxious and unintended’); medica-tion errors resulting in an ADR will also be reported; after a tran-sitional period, the information on suspected adverse reactions will be submitted electronically to the Eudravigilance database.

The Health and Social Care Bill 2010-11 (which is currently proceeding through the UK legislative chambers) aims, as its core principle, to facilitate commissioning of patient services by General Practitioners. The Bill, if passed, will have far-reaching effects on the way health-care services will be provided by the NHS.

Update and tr�ends

Gerry Kamstra [email protected]

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• Strengthens safety, transparency and communications relat-ing to medicines. This is, particularly due to the establishment of a European medicines safety web-portal that contains the conclusions of the scientific assessment as well as any relevant recommendations. It is also foreseen that, at a later stage, both health-care professionals and the public will have appropriate levels of access to the data contained in Eudravigilance database, but always in an aggregated format.

Based on the estimates provided by the European Medicines Agency and the national competent authorities, it seems that full implemen-tation of the new legislation may take until at least 2013.


Studio Legale Bird & Bird itaLy

ItalyMassimiliano Mostardini and Mauro Turrini

Studio Legale Bird & Bird



The first comprehensive legislation concerning public health was introduced in Italy by Law No. 2248 of 20 March 1865, and later articulated by Law No. 5849 of 21 December 1888. The first unified text concerning public health was adopted with Royal Decree No. 603 of 1 August 1907, which was subsequently replaced by Royal Decree No. 1265 of 27 July 1934, which was further amended and contains the rules concerning the organisation and competences of public health structures, health-care professionals and a number of provisions concerning public health in general.

Law No. 296 of 13 March 1958 placed the Ministry of Health in charge of all aspects concerning public health in Italy. The Ministry is assisted at national level by the Superior Council of Health – the general advisory body – and the Superior Institute of Health – a technical-scientific body; and at local level by the regional authori-ties, local health authorities (ASL) and hospitals. Presidential Decree No. 4 of 14 January 1972 transferred a number of competences from the central government to the regions. Other institutions assisting the Ministry of Health at national level include the State-Regions Con-ference, the Italian Medicines Agency (AIFA), the Superior Institute for prevention and safety at work (ISPESL) and the Regional Health Services Agency (Agenas).

The Italian National Health-Care System (NHS) was established in Italy by Law No. 833 of 23 December 1978, which almost com-pletely nationalised public health services in Italy and which – in line with article 32 of Italian Constitution enshrining protection of public health among fundamental rights of individuals – was based on the following principles: universality (ie, services for all persons regularly registered in Italy); equality (ie, services provided irrespective of sex, age, nationality, social position); and sociality (ie, not only care but also prevention).

The NHS was subsequently reorganised to rationalise resources and increase effectiveness (see, in particular, Legislative Decrees No. 502 of 30 December 1992, No. 229 of 19 June 1999 and No. 153 of 3 October 2009, and also more generally Constitutional Law No. 3 of 18 October 2001). As a result, the fundamental principles and objectives pursued by the NHS are now defined at national level by the state, which sets out harmonised essential levels of assistance (LEA), which are put into practice locally, mostly by regions, which are now responsible for the management, planning, organisation and financing of public health.


in-patient sectors?

The NHS is financed by regional taxes paid for by employees, their employers and self-employed workers directly.

In-patient treatment is free and is provided by local health authorities and hospitals.

Outpatient treatments are provided for free as long as they fall within the LEA. In particular, family doctor services, class A medici-nal products (see question 21 – a fee may apply in some regions), visits to medical specialists and diagnostic tests fall within the LEA.




Title VIII (articles 113-128) of Legislative Decree No. 219 of 24 April 2006 (Legislative Decree No. 219), which implements Directive 2001/83/EC on the Community code relating to medicinal products for human use as well as Directive 2003/94/EC concerning good manufacturing practices, regulates the advertisement of medicinal products to the general public and health-care professionals.

In particular, in relation to advertisements to the general public, the following are also relevant: Legislative Decree No. 205 of 6 Sep-tember 2006, which consolidates all existing consumer protection provisions in Italy, including advertising and dissemination of correct and not misleading information (the Consumer Code); the Guidelines of the Ministry of Health of 17 February 2010 concerning adver-tising, inter alia, of medicinal products via the internet, telephone (including MMS and SMS) (the Ministry of Health Guidelines); and the code issued by the Institute of Advertising Self-Regulation (IAP).

As to advertisement to health-care professionals, the following are also relevant: the Guidelines of the State-Regions Conference on scientific information provided by medical sales representatives of 20 April 2006 (the State-Regions Conference Guidelines), as imple-mented at the regional level; and industry associations’ codes of conduct (see, in particular, the Farmindustria Code of Professional Conduct, which includes a number of provisions concerning advert-ing to health-care professionals).

Finally, article 2598 of the Civil Code concerning unfair com-mercial practices is also relevant in case of misleading advertising and adverting contrary to fair business practises in general.

According to article 113 of Legislative Decree No. 219, ‘adver-tising of medicinal products’ shall include any form of door-to-door information, canvassing activity or inducement designed to promote the prescription, supply, sale or consumption of medicinal products. It shall include, in particular: advertising of medicinal products to the general public; advertising of medicinal products to persons qualified to prescribe or supply them; visits by medical sales representatives to persons qualified to prescribe medicinal products; the supply of samples; the provision of inducements to prescribe or supply medici-nal products by the gift, offer or promise of any benefit or bonus, whether in money or in kind, except when its intrinsic value is mini-mal; sponsorship of promotional meetings attended by persons quali-fied to prescribe or supply medicinal products; and sponsorship of scientific congresses attended by persons qualified to prescribe or supply medicinal products, and in particular payment of their travel-ling and accommodation expenses in connection therewith.

italy Studio legale Bird & Bird


The main principles concerning the advertising of medicinal products are the following: advertising of medicinal products in respect of which a marketing authorisation has not been granted in accordance with EU law is prohibited (ie, a national authorisation issued by AIFA after a purely national procedure, a mutual recog-nition procedure or a decentralised procedure, or an authorisation issued by the European Commission following the centralised proce-dure as per Regulation (EC) 726/2004 – see question 17); advertising of medicinal products shall always comply with all the particulars listed in the relevant authorised summary of product characteristics (‘SmPC’); and advertising of medicinal products shall promote an appropriate use of said products and shall not be misleading.



Advertising to health-care professionals shall be limited to those health-care professionals who may prescribe or sell medicinal prod-ucts, typically medical doctors and pharmacists. Advertising to health-care professionals during visits of sales representatives shall, in principle, always include presentation of the most recently authorised SmPC, supply classification and public price.

In case of failure to comply with its guidelines, AIFA can order termination or suspension of the advertising and dissemination of a corrective statement to be published in an AIFA medicinal products bulletin, on the relevant pharmaceutical company’s website and on national newspapers.

Advertising to medical doctors also includes visits to laboratories and centres of research aimed at improving scientific knowledge.

As to advertising to pharmacists (with the exception of those working in hospitals), the legislation provides that advertising of pre-scription medicinal products shall be limited to the sole information contained in the SmPC. Advertising of non-prescription medicinal products may include all information that may be relevant to the pharmacist for advising patients on their adequate use.

With the sole exception of authorised SmPC, promotional mate-rial disseminated to health-care professionals shall be submitted to AIFA at least 10 days prior to its dissemination. In case of no reply by AIFA, dissemination of promotional material shall be deemed authorised (the 10-day tacit consent procedure). Reference to the date of submission to AIFA shall be placed on the authorised pro-motional material.

AIFA may at any time prohibit or suspend dissemination of pro-motional material if, in its reasoned opinion, it does not comply with the rules and principles set out in the legislation.



Advertising aimed at the general public shall be limited to medicinal products that do not require the help of a medical doctor for the diagnosis, and the prescription and monitoring of their use.

Advertising of medicinal products that are available on medical prescription only, that contain substances defined as psychotropic or narcotic, that are reimbursed, even in part, by the NHS or that are intended for research and development trials as well as distribution of medicinal products to the public by the industry for promotional purposes is forbidden.

Likewise, advertising of any medicinal product prepared in a pharmacy in accordance with a medical prescription for an individ-ual patient (‘magistral formula’), or in accordance with the prescrip-tions of a pharmacopoeia and intended to be supplied directly to the patients served by the pharmacy in question (‘officinal formula’), and industrial preparation medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the speci-fications of an authorised health-care professional and for use by an individual patient under his or her care, respectively as per articles

3(a) and (b) and 5 of Legislative Decree No. 219, are also forbidden.Dissemination to the public via written publications, radio or

television images or reference to the name of a medicinal product in a context that may cause its consumption even without it being promotional is also forbidden.

Advertising aimed at the general public shall clearly be identified as such. The product shall be clearly identified as a medicinal product and shall include at least the following: the name of the medicinal product as well as the international non-proprietary name (INN) recommended by the World Health Organization (WHO), or, if one does not exist, the usual common name; information necessary to correctly use the medicinal product; and a clear indication to read product information before using the medicinal product. Advertising aimed at the general public shall not give the impression that a medi-cal consultation or surgical operation is unnecessary; suggest that the effects of taking the medicine are guaranteed, are unaccompanied by adverse reactions or are better than, or equivalent to, those of another treatment or medicinal product; suggest that the health of the subject can be enhanced by taking the medicine; suggest that the health of the subject could be affected by not taking the medicine (except in case of vaccination campaigns); be directed exclusively or principally at children; refer to a recommendation by scientists, health professionals or celebrities; suggest that the medicinal product is a foodstuff, cosmetic or other consumer product; suggest that the safety or efficacy of the medicinal product is due to the fact that it is natural; lead to erroneous self-diagnosis; refer, in improper, alarm-ing or misleading terms, to claims of recovery; or use, in improper, alarming or misleading terms, pictorial representations of changes in the human body caused by disease or injury, or of the action of a medicinal product on the human body or parts thereof.

With the sole exception of advertising in newspapers consisting of the mere reproduction of the authorised product information and a picture or graphic reproduction of the medicinal product, or of pictures or graphic reproductions of a medicinal product available without prescription placed on price labels, advertising of medicinal products aimed at the general public is subject to the competent com-mittee of the Ministry of Health’s prior authorisation. In case of no reply by the competent committee within 45 days from the receipt of a valid application, the authorisation shall be considered as granted (45-day tacit consent procedure). The authorisation is valid for 24 months, unless a shorter period is indicated in the authorisation.

In case of failure to comply with the law, the Ministry of Health orders the termination of the advertising as well as the dissemination of corrective communications.



The most common infringements committed by manufacturers include the use of medical claims for products not so classified; hav-ing recourse to non-authorised promotional materials; granting of gifts or pecuniary advantages or benefits exceeding the limit allowed by the law.

In case of failure to comply with the law, AIFA and the Ministry of Health may apply sanctions. See questions 4 and 5.



In principle, advertising of medicinal products for which a marketing authorisation has not been granted in accordance with EU law is pro-hibited and all parts of the advertising of a medicinal product shall comply with the particulars listed in the relevant SmPC (see question 4). Exceptions may apply in case of dissemination of information concerning new therapeutic indications by independent speakers at scientific meetings for the purpose of scientific discussion where no reference is made to a specific medicinal products; in case of dis-



semination of information not compliant with the SmPC authorised in Italy but with an SmPC authorised in other EU member states at international conferences, provided that the conference is attended by medical doctors from said countries and that all information material disseminated during said conferences has been previously submitted to AIFA in accordance with the 10-day tacit consent procedure (see question 4); in case of written replies to unsolicited requests of infor-mation made concerning a specific medicinal product.




Collaboration of the pharmaceutical industry with health-care pro-fessionals is not expressly regulated by the law in Italy.

There are a number of provisions, however, which are variously relevant (see question 9).



The main rules and principles applying to the collaboration of the pharmaceutical industry with health-care professionals include the following.

Article 123 of Legislative Decree No. 219 provides that in the context of the provision of scientific information before health-care professionals, the granting, offer or promise of gifts, pecuniary advantages or benefits in kind is forbidden unless they are inexpen-sive and relevant to the practice of medicine or pharmacy.

A similar provision is also contained in the State-Regions Confer-ence Guidelines as implemented regionally, which also specifies that inexpensive gifts or gadgets shall be understood as goods having an economic value of no more than €20, which shall be also considered the limit per health-care professional per year.

Moreover, article 4.1 of Farmindustria Code of Professional Conduct, which is directly binding for associated members only, provides that collaboration with health-care professionals (eg, sci-entific consultancies, speeches at conferences, studies, scholarships) shall comply with the following criteria: a written contract, clarifying the need for the service in question, must be stipulated between the physician and the pharmaceutical company specifying the nature of the service offered; the contract must include the consultant under-taking to disclose the relationship with the pharmaceutical company whenever collaboration includes presentation in public of the results of said collaboration; documentation concerning the collaboration must be kept by the relevant company for at least three years and the consideration paid by the company shall meet cost-performance criteria and reflect the market value of such services; the decision on such initiatives must be reserved to the executive top management; and, in case the collaboration includes hospitality services, they must comply with the relevant provisions of the code of conduct.

Finally, according to article 53 of Legislative Decree No. 165 of 30 March 2001, civil servants (including health-care professionals working for the NHS) may not perform any paid activities unless a prior authorisation has been obtained. This does not apply, however, in cases of certain paid activities such as collaboration with news-papers, magazines, et cetera and participation in conferences and seminars, as they are assumed not to hinder performance of civil servants’ public duties.

Failure to comply with the rules above may cause liabilities, for example, under criminal corruption provisions contained in articles 170-172 of Royal Decree 1265/1934, concerning conduct of health-care professionals favouring prescription or consumption of medici-nal products as a result of the promise or receipt of gifts, pecuniary advantages or benefits in kind. Sanctions, which also apply to those inducing the commission of the crime, range from imprisonment to fines and orders including temporary shutting down of the relevant

manufacturing site.Crimes such as corruption may also lead to liability under Leg-

islative Decree No. 231 of 8 June 2001, concerning administrative liability of legal entities.



professionals?

The most common infringements committed by manufacturers with regard to collaboration with health-care professionals include failure to obtain a prior authorisation for paid services rendered by health-care professionals (see question 9); and the granting, offer or prom-ise of gifts, pecuniary advantages or benefits in kind to health-care professionals exceeding the limit provided by the law (see questions 6 and 9).



Collaboration of the pharmaceutical industry with patient organi-sations is not expressly regulated by the law in Italy. There are a number of provisions, however, which are variously relevant, include the following.

Article 4.5 of Farmindustria Code of Professional Conduct pro-vides that: • allformsofeconomicsupport,whetherdirectorindirect,bythe

pharmaceutical company towards a patients’ association must be based on a specific and preliminary agreement aimed at regu-lating the amount of financing and the reasons for its disburse-ment and to be entered into in accordance with specific internal procedures;

• publicusebyapharmaceuticalcompanyofthelogoormaterialowned by a patients’ association must be authorised in advance by the association;

• any form of sponsorship by the pharmaceutical companiesregarding patients’ associations must be transparent and without promotional objectives;

• nocompanycanrequesttobethesolefinancierofapatients’association; and

• pharmaceuticalcompaniesmustincludeontheirowninternetsites the list of the patients’ associations that they support.



Infringement of competition law affecting the Italian market can be pursued by the Italian Antitrust Authority. This can be typically the case of anti-competitive agreements or abuse of dominant posi-tion aiming to prevent or hinder competitors entry into the market. Where the conduct above also infringes the rules concerning the mar-keting of medicinal products, AIFA can also decide to pursue them as per Legislative Decree No. 219. Decisions adopted by the Antitrust Authority and AIFA can be challenged before the Administrative Regional Tribunal of Lazio.


Unfair competition practices can be challenged in Italy under article 2598 of the Civil Code by lodging a claim before the competent civil law tribunal. Measures the tribunal may order include injunction and pecuniary sanctions.








Advertising of medical devices in Italy is regulated by Legislative Decree No. 46 of 24 February 1997, which implements Directive 93/42/EEC concerning medical devices. In particular, article 21 prohibits advertising to the general public of medical devices to be supplied under prescription only or to be used with assistance of health-care professionals only.

With the exception of medical devices identified as per Ministry Decree of 23 February 2006, advertising to the general public of medical devices not falling within the scope of article 21, may be performed following the granting of the relevant Ministry of Health authorisation (see question 5). Authorisation shall be deemed granted if the relevant competent committee has not adopted a position within 45 days from the receipt of a valid application (the 45-day tacit consent procedure).

The following provisions are also relevant as to advertising of medical devices to the general public: the Consumer Code, Ministry of Health Guidelines; and the self-regulation code issued by the IAP (see question 3).

Advertisement of medical devices to health-care professionals is not expressly regulated by law. However, advertisement of medical devices to health-care professionals must also comply with relevant product information and be disseminated via adequate and selected channels (eg, specialised magazines).

Provisions concerning advertisement of medical devices to health-care professionals are also contained in Industry asso-ciation codes of conduct (see, in particular, Assobiomedica Code of Professional Conduct) and the State-Regions Confer-ence Guidelines, which apply at regional level if and to the extent they have been implemented.

Article 2598 of the Civil Code is also relevant in case of mislead-ing advertising and advertising contrary to fair business practices (see question 3).

Collaboration between manufacturers of medical devices and health-care professionals and patient organisations is not regulated by law. However, there are a number of provisions contained in the industry association codes of conduct (see, in particular, Assobio-medica Code of Professional Conduct) and the State-Regions Confer-ence Guidelines, which may be relevant in that respect.

The medical device sector is less regulated compared to the pharmaceutical sector. This may be because the medical devices are reasonably heterogeneous, highly influenced by technological inno-vation, and mostly supplied via highly regulated public tender pro-cedures directly to NHS structures.




Title III of Legislative Decree No. 219, which implements Directive 2001/83/EC on the Community code relating to medicinal products for human use, sets out the regulatory framework for granting mar-keting authorisations and placing medicines on the market in Italy.


jurisdiction?

The authority responsible for the granting of marketing authorisa-tion for medicinal products is AIFA, which was established as per article 48 of Law No. 326 of 24 November 2003, and to which were transferred to all competences on medicinal products formerly vested

in the Ministry of Health. AIFA is an independent public authority subject to the supervision and direction of the Ministry of Health.


The administrative procedures concerning the granting of a market-ing authorisation in Italy may differ according to the registration route followed by the applicant to have a product authorised on the Italian market; or the type of product concerned.

As to the registration route, an applicant can, according to the cases, opt for: a purely national procedure; a mutual recognition procedure (MRP); or a decentralised procedure (DCP). The cen-tralised procedure, which is managed at EU level by the European Medicines Agency (EMA) and the European Commission as per Regulation (EC) 726/2004, can also enable a company to obtain an authorisation for placing a product on the Italian market. In case of a purely national procedure AIFA must issue a decision within 210 days; while in the case of a MRP or a DCP, if Italy acts as refer-ence member state, AIFA shall perform its assessment within 90 and 120 days respectively, which should be followed, within 90 days, by the recognition of concerned member states. Where no consensus is reached, a referral to the EU is triggered. Finally, in case of an MRP or DCP, where Italy acts as a concerned member state, AIFA shall recognise the assessment performed by the authority of the reference member states within 90 days from its receipt.

As to the type of product, an applicant may, as the case may be, proceed with the submission of: a full registration dossier, as per article 8 of Legislative Decree No. 219, which shall include, inter alia, the results of pharmaceutical (physico-chemical, biological or microbiological) tests, pre-clinical (toxicological and pharmacologi-cal) tests, clinical trials concerning the relevant medicinal product, typically applicable to innovative products (ie, originator products); or an abridged dossier that may exempt an applicant, totally or in part, by providing the results of pre-clinical tests and of clinical trials. In particular, applicants: • shallnotberequiredtoprovidetheresultsofpre-clinicaltests

and of clinical trials if they can demonstrate that the medicinal product is a generic of a reference medicinal product, namely a medicinal product that has the same qualitative and quanti-tative composition in active substances and the same pharma-ceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies) of a refer-ence medicinal product that is or has been authorised under a full dossier for not less than eight years in a member state or in the EU (ie, generic application); or if they can demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the EU for at least 10 years, with recognised efficacy and an acceptable level of safety provided the test and trial results are replaced by appropriate scientific literature;

• shallberequiredtoprovidetheresultsoftheappropriatepre-clinical tests or clinical trials if they cannot demonstrate that the medicinal product falls within the definition of a generic medici-nal product or where the bioequivalence cannot be demonstrated through bioavailability studies or in case of changes in the active substance or substances, therapeutic indications, strength, phar-maceutical form or route of administration, to the reference medicinal product (ie, hybrid application).



According to article 38(5) and article 35(7) respectively of Legisla-tive Decree No. 219 a marketing authorisation ceases to be valid in cases where the concerned medicinal product is not placed on the market within three years after the issuing of the authorisation or



in cases where the medicinal product initially placed on the mar-ket is subsequently no longer marketed for three consecutive years (sunset clause’). Moreover, in cases where a medicinal product is not placed on the market within 60 days after the issuing of the market-ing authorisation, the authorisation holder shall inform AIFA of the delay and of the subsequent placing on the market.

Moreover, according to Guidance on the application of the sun-set clause issued by AIFA on 31 March 2009, it has been further clarified that, for the purpose of the application of the sunset clause, the first placing on the market of a medicinal product shall be the placing of the product in the distribution chain (eg, the first sale to a wholesaler), while a product shall be considered still on the market as long as at least one authorised dosage of the product is still on the market.

AIFA can, in exceptional circumstances and for adequately justi-fied reasons concerning public health, exclude the application of the sunset clause with regard to a specific medicinal product.


In principle, no medicinal product may be placed on the market in Italy unless a marketing authorisation has been issued by AIFA or by the European Commission (see also question 17). However, there are some exceptions to this general principle. Article 3(a) and (b) of Leg-islative Decree No. 219 provides that medicinal products prepared in a pharmacy in accordance with a medical prescription for an individ-ual patient (‘magistral formula’) or in accordance with the prescrip-tions of a pharmacopoeia for the subsequent direct supply to patients served by the pharmacy (‘officinal formula’) can be marketed in Italy without having obtained a prior marketing authorisation.

Article 3(f) of Legislative Decree No. 219 provides that advanced therapy medicinal products, as defined under Regulation (EC) 1394/2007, can also be used without having obtained a prior marketing authorisation – to be issued for such products at com-munity level – in all cases where these products are prepared on a non-routine basis according to specific quality standards, and used in Italy in a hospital under the exclusive professional responsibility of a health-care professional, in order to comply with an individual medical prescription for a custom-made product for an individual patient (hospital exemption). Manufacturing of these products shall, in any case, always be authorised by AIFA.

Article 5 of Legislative Decree No. 219 provides that medici-nal products industrially manufactured in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised health-care professional and for use by an individual patient under his or her direct personal responsibility or responsibil-ity of the structure where he or she works are excluded from the obligation to obtain a prior marketing authorisation.

Finally, according to the Ministry of Health Decree of 11 Febru-ary 1997, a medicinal product not authorised in Italy but in another EU member state can be imported in Italy and used in compliance with the relevant SmPC provided that the relevant procedure is fol-lowed. In particular, in cases where a medical doctor deems it advis-able to administer a product authorised abroad but not in Italy to a specific patient he or she must provide the Office of Maritime, Air and Border Health of the Ministry of Health (USMAF) with the following information: the name and pharmaceutical form of the medicinal product, the manufacturer, the holder of market-ing authorisation, a declaration that the medicinal product is duly authorised in the exporting country, the quantity requested with the indication that said quantity covers not more than 30 days of the therapeutic need of the relevant patient; the details of the patient, the special need that justifies the request, the informed consent of the patient, and a declaration that the use of the medicinal product will be under his direct personal responsibility.

20 Are any kinds of named patient programmes in place? If so, what are

the requirements for pre-launch access?

Compassionate use of medicinal products is a treatment option for patients in the European Union suffering from a disease for which no satisfactory authorised alternative therapy exists or who cannot enter a clinical trial. Compassionate use programmes are intended to facili-tate the availability to patients – either on a named patient basis or to cohorts of patients – of new treatment options under development.

Compassionate use of medicinal products as per article 5(1) of Directive 2001/83/EC is regulated in Italy by articles 5 and 158(10) of Legislative Decree No. 219 as well as the Ministry of Health Decree of 8 May 2003.

In particular, article 5(f) of Legislative Decree No. 219, which implements article 5(1) of Directive 2001/83/EC, provides that indus-trial manufacturing and administration of medicinal products in case of bona fide unsolicited orders, formulated in accordance with the specifications of an authorised health-care professional and for use by an individual patient under his or her direct personal responsi-bility or responsibility of the structure where he or she works are allowed with no need to obtain a prior marketing authorisation by AIFA.

The Ministry of Health Decree of 8 May 2003 provides that the authorisation of the use of a medicinal product not authorised but under clinical investigation in Italy or abroad can be issued in cases where: the product is intended to be used in accordance with the therapeutic indication under investigation; a phase III study is ongo-ing or complete or, only in cases of life-threatening disease, a phase II is completed; and the data gathered are sufficient to assess the safety and efficacy of the concerned medicinal product.

Recourse to the exemption under article 5 over the years has been somewhat abused. This was recently confirmed by AIFA, which clarifies that recourse to this option should be strictly limited to cases of individual needs and patients and should not be interpreted extensively.



law or regulation?

According to article 8, paragraph 10, of Law No. 537 of 24 Decem-ber 1993, as amended, medicinal products in Italy are classified essentially in three classes.

Class A contains medicinal products that are deemed necessary to ensure to all patients the LEA set out by the President of the Coun-cil of Ministers Decree of 29 November 2001. Class A medicinal products are indicated for serious, chronic or acute illness and are freely supplied to patients (except where a fee is imposed at regional level) and fully reimbursed by the NHS (except where AIFA expressly makes reimbursement conditional on a specific indication). Prices of Class A medicinal products are negotiated with AIFA’s Price and Reimbursement Committee (CPR) according to article 48, paragraph 33, of Law No. 326 of 24 November 2003, and CIPE decision No. 3 of 1 February 2001.

Class C contains medicinal products that are deemed not neces-sary under the meaning above. Class C medicinal products are indi-cated for minor diseases and their cost, in principle, must be borne by patients and they are not reimbursed by the NHS. Price of Class C medicinal products are freely determined by manufacturers and can be decreased at any time, but may only be increased during January of odd-numbered years.

Class H contains medicinal products that can be supplied to and administered by hospitals only and whose prices are, in principle, negotiated during relevant public tender procedures organised by the NHS.



22 Must pharmaceutical manufacturers negotiate the prices of their

products with the public health-care providers?

As mentioned under question 21, prices for Class A medicines are negotiated with the CPR.

The reimbursement price negotiation procedure is regulated by CIPE decision No. 3 of 1 February 2001. Criteria to be taken into account while fixing the reimbursement price include the cost-benefit of the medicinal product in respect of existing alternative therapies; price, consumption data and supply condition already applied in other EU member states; and expected sale volumes. The procedure should last, in theory, 90 days (see also AIFA Rules of procedure of 27 September 2010); however, in practice, in most cases it lasts longer.

23 In which circumstances will the national health insurance system

reimburse the cost of medicines?

As to the outpatient sector, Class A medicinal products are, in prin-ciple, fully reimbursed by the NHS. Exceptions may apply in cases where AIFA has made full reimbursability conditional on a specific therapeutic indication (see question 21). In the in-patient sector, Class H medicinal products are fully reimbursed by the NHS (see question 21).

24 If applicable, what is the competent body for decisions regarding the

pricing and reimbursability of medicinal products?

The CPR is the competent body. It is chaired by AIFA’s executive director and is made up of 12 members selected from among major experts at national level on price of medicinal products, health econ-omy and pharmaeconomy.



According to article 9(4) and 9(5) of Law No. 386 of 17 August 1974, manufacturers selling to hospitals and public institutes of hos-pitalisation and care must apply a discount of not less than 50 per cent of the price to the public to medicinal products.

However, average discounts applied in practice are usually about 75 per cent of the price to the public and in some cases they can even reach 99 per cent. The lawfulness of very high discounts has been questioned in Italy and brought recently to the attention of the Ital-ian Tender Supervising Authority. The outcome of the investigation was essentially that the lawfulness of very high discounts should be assessed case by case (eg, cases where the continuity of the treat-ment on the territory may cause benefit in the long term could be approved).

It should be also noted that, irrespective of the mandatory dis-count system, the legislature – because of the increasing NHS deficit – has over last few years intervened with a number of additional price cuts.




A number of rules are in place in Italy to tackle counterfeiting and illegal distribution of medicines and more generally to ensure the safe monitoring of all products placed on the market. They include provi-sions on labelling and traceability as well as on monitoring of wasted medicinal products (see, in particular, Legislative Decree 540/1992, now replaced by the relevant provisions of Legislative Decree No. 219, Ministry Decree of 2 August 2001 and Ministry Decree of 15 July 2004).

In 2005 AIFA, together with the Ministry of Health, the Supe-

rior Institute of Health and the Carabinieri NAS, launched IMPACT Italy, which is a group whose mission is to tackle the counterfeiting of medicinal products. In 2006 a similar group, IMPACT International (‘the International Medical Products Anti-Counterfeiting Taskforce’) was launched by the WHO. IMPACT aims to build coordinated net-works between countries to halt the production, trading and selling of fake medicines around the globe. IMPACT is a partnership com-prised of all the major anti-counterfeiting players, including interna-tional organisations, non-governmental organisations, enforcement agencies, pharmaceutical manufacturers’ associations, and drug and regulatory authorities.

Reference should also be made to recent ratification of the Coun-cil of Europe’s MEDICRIME Convention, which constitutes, for the first time, a binding international criminal law instrument on coun-terfeiting of medical products and similar crimes involving threats to public health.

Counterfeiting and illegal distribution of medicinal products are covered by the recently adopted Directive 2011/62/EU. The Directive, which entered into force on July 2011 and which must be implemented by January 2013, aims at strengthening the protec-tion of patients and consumers by ensuring a better control of the distribution chain and, in particular, by preventing falsified medicines entering the legal supply chain and reaching patients. The Directive essentially increases the responsibilities of manufacturers of finished medicinal products. In particular, the Directive introduces harmo-nised safety and strengthened control measures across Europe pre-scribing obligatory features on the outer packaging of medicines to demonstrate that they are authentic; strengthened requirements for the inspection of the manufacturers of pharmaceutical ingredients; the obligation for manufacturers and distributors to report any sus-picion of falsified medicines; and an obligatory logo that must be placed on the websites of legally operating online pharmacies, with a link to official national registers.



According to article 31 of Legislative Decree No. 219, AIFA pub-lishes all decision concerning the marketing authorisation for medici-nal products granted in the Official Journal.

AIFA also publishes on its website the list of all medicinal prod-ucts whose commercialisation is authorised in Italy, including medici-nal products reimbursed by the NHS (class A), not reimbursed (Class C) and whose use is limited to hospitals (Class H). The list includes information on the name of the medicinal product, the active prin-ciple, the marketing authorisation holder, the supply classification and the price.

AIFA also publishes, monthly, a specific transparency list con-cerning all authorised generic medicinal products, which can be sub-stituted with reference medicinal products. It also publishes on its website additional information to inform the public about medicines and AIFA’s general activities.

Additional measures facilitating the general public’s access to information about prescription-only medicines might follow in the near future once the current Commission proposals of 2008 on infor-mation to patients will eventually enter into force. The proposals, as revised by the European Parliament, set out a clear framework whereby companies with marketing authorisation for a product may – and to some extent must – provide good-quality and objec-tive information on their prescription-only medicines to the general public.


of medicines.

Pharmacovigilance, which is pursued in Italy by AIFA in conjunction with regions and local health authorities in a National Network of



Pharmacovigilance, comprises the following key activities: collecting and managing data on the safety of medicines; looking at the data to detect ‘signals’ (any new or changing safety issue); evaluating the data and making decisions with regard to safety issues; acting to protect public health (including regulatory action); communicating with stakeholders; and auditing, both of the outcomes of action and the key processes involved. Stakeholders directly involved in phar-macovigilance include patients as the users of medicines; doctors, pharmacists, nurses and all other health-care professionals working with medicines; regulatory authorities, including the EMA and those in the member states responsible for monitoring the safety of medi-cines; and pharmaceutical companies and companies importing or distributing medicines.

On 31 December 2010 the European Commission published in the Official Journal of the European Community Regulation (EC) 1235/2010 and Directive 2010/84/EC amending, as regards phar-macovigilance, respectively Regulation (EC) 726/2004 concerning medicinal products authorised throughout the centralised procedure (including advanced therapy medicinal products under Regulation (EC) 1394/2007) and Directive 2001/83/EC concerning medicinal products authorised throughout the national, decentralised and mutual recognition procedure. Regulation (EC) 1235/2010 entered into force on 1 January 2011 and will be applicable as from 2 July 2012 while Directive 2010/84/EC entered into force on 20 January 2011 and will be applicable as from 21 July 2012.

New pharmacovigilance legislation strengthens and rational-ises the EU system of pharmacovigilance for medicinal products for human use and, in particular: • itclarifiesrolesandresponsibilitiesforthepartiesconcerned,

including the role of the supervisory authority for pharmacovigi-lance, which is the competent authority of the member state in which the pharmacovigilance system master file (see below) is located;

• it introducesaPharmacovigilanceRiskAssessmentAdvisoryCommittee, which shall be responsible for the provision of phar-macovigilance assessments and of a number of recommendations on the safety of medicines at the EU level;

• it introduces the possibility for competent authorities toissue marketing authorisation subject to one or more specific conditions;

• itintroducestheobligationformarketingauthorisationholdersto maintain and make available on request a pharmacovigilance system master file in respect of one or more medicinal products;

• itremovesthecurrentroutinerequirementforindustryperiodicreports (PSURs) for low risk, old and established products;

• it introduces specific provisions on the supervision of non-interventional post-authorisation safety studies;

• itsimplifiesadverse-reactionreportingandaclearlegalbasisforthe reporting of suspected adverse drug reactions; and

• itstrengthensmedicinesafetytransparencyandcommunication.

A number of pieces of EU legislation that may have an impact on existing obligations of stakeholders operating, in particular, in the pharmaceutical field are due to be implemented in Italy in the near future (see questions 26–28). However, to what extent new provisions will actually affect current business practices is still hard to say as it will depend essentially on the actual implementing measures adopted. An increase of duties and responsibilities upon manufacturers, either in terms of control of the supply chain and information to be provided to general public may, in any case, be expected (see Directive 2011/62/EU on counterfeiting of medicines and Commission Proposal on information to patients).

As to general trends in the health-care field (pharmaceutical as well as medical device sectors), the drastic economic conditions affecting many national health services around the world are making prevention and early detection of diseases increasingly important. In view of this, it may also be expected that ‘personalised treatments’ and ‘health technology assessment’ (HTA) will become increasingly important in the future for the purpose of reducing NHS costs.


Massimiliano Mostardini [email protected] Mauro Turrini [email protected]

Via Borgogna, 8 Tel: +39 02 3035 6000

20122 Milan Fax: +39 02 3035 6011

Italy www.twobirds.com


Bird & Bird LLP netherLands

NetherlandsColette Mulder

Bird & Bird LLP



The health-care system in the Netherlands has a private character with a public framework. The government does not directly partici-pate in providing actual health care. The government is, however, responsible for the accessibility, affordability and quality of health care. The government, for example, determines that everyone who lives or works in the Netherlands is required to purchase health-care insurance. To make this possible the government ensures that health-care is affordable and insurers are obliged to offer health-care insurance to everyone, irrespective of personal characteristics and subject to the same conditions. Private health-care providers such as individual practitioners and care institutions are responsible for providing the health-care services. The insurance system is operated by private health-care insurance companies.

Since 1 January 2006 the Netherlands has had a new insurance system for health-care costs. The Health Insurance Act provides for a standard benefit package for everyone, compensation for people with low incomes, the possibility to change insurer every year, competi-tion between insurers and the stimulation of health-care providers to provide better quality health care.

Health-care insurers are obliged to accept everyone for a stand-ard benefits package for the same price, in order to prevent discrimi-nation on the basis of risk. The standard benefits package covers the standard costs of, for example, a general practitioner, hospital or pharmacy. Health-care insurers may decide which health-care pro-viders will provide the service and how the health-care is delivered. The insurers negotiate with the health-care providers to obtain good health care at competitive prices. In addition to the standard benefits package it is also possible to purchase complementary private health insurance for care that is not covered by the standard benefits pack-age. Health insurers are, however, not obliged to accept requests for private health insurance.

In addition, everyone who lives or works in the Netherlands is insured for exceptional medical expenses under the Exceptional Medical Expenses Act (AWBZ) regarding health risks that are not covered under health-care insurance such as long-term care at home, vaccinations or patient transportation costs.

To ensure the quality of the health care, the government has drawn up legislation regarding the performance of individual health-care providers, the quality of health-care institutions, the rights of patients and the use of medical equipment and devices. The Health Care Inspectorate (IGZ) ensures compliance with the legislation, professional standards and guidelines and may impose corrective measures or in serious cases institute disciplinary or criminal pro-ceedings. The Dutch Health Care Authority supervises both health-care providers and insurers.


in-patient sectors?

Health care in the Netherlands is financed by a health-care cost sys-tem that came into effect on 1 January 2006. The health-care system is financed by a combination of fixed premiums and income-related contributions.

The insured pay a nominal premium to the health-care insurer. In addition, everyone must pay an income-related contribution, levied by the tax authority and put into a Health-Care Insurance Fund. Employers are obliged to reimburse their employees for this income-related contribution and employees pay tax over this reimbursement. The Health-Care Insurance Fund reimburses the collected money, after applying a risk equalisation, to the health-care insurers. The government implemented a risk equalisation system to compen-sate health-care insurers for predictable differences in their medical expenditures. This should ensure that insurers do not discriminate between patients with a low or high health risk.

Children under the age of 18 years are insured for free. The government finances their insurance premiums. Persons with low incomes may receive compensation from the government to help them pay for their health-care insurance.

Complimentary private health insurance in addition to the stand-ard benefit package is paid directly by the insured person themselves.




Advertisement of medicinal products is subject to various laws and rules. EU Directive 2001/83/EC, as amended, on the community code relating to medicinal products for human use is implemented in the Netherlands by the Medicines Act. The advertisement of medicinal products is laid down in chapter 9 of the Medicines Act. In addition there is a guideline regarding the further substantiation of the term ‘hospitality’ set out in the Medicines Act.

The Foundation for Advertisement of Medicinal Products (Foun-dation CGR) has set out, within the legal framework of the Medi-cines Act, detailed advertising rules in its self-regulatory Code of Conduct for Advertisement of Medicinal Products (CGR-Code). An integral part of this code is the Code on Public Advertisement of Medicinal Products (CPG-Code) drawn up by the Inspection Board for the Public Promotion of Medicines (KOAG). In addition, the Foundation CGR has also drawn up codes and guidelines on, for example, hospitality, sponsoring, grants and medicinal products on the internet.

The general Advertising Code Authority deals with the self-reg-ulating system of advertising rules with which all advertising should comply. The rules are laid down in the Dutch Advertising Code.

netherlands Bird & Bird llP


Apart from these self-regulatory codes, the Dutch Civil Code contains some general provisions with regard to misleading and com-parative advertising.

Also the laws and guidelines regarding the professional conduct of health-care professionals apply.



In general, the advertising of medicinal products, whether aimed at health-care professionals or the general public, is only permitted for products for which a marketing authorisation has been granted (unless within an international scientific context and subject to cer-tain conditions). The advertisement should encourage the rational use of the medicinal product by presenting it objectively and must comply with the particulars listed in the summary of product char-acteristics and must not be misleading.

Advertising to health-care professionals is set out in chapter 9, paragraph 3 of the Medicines Act. Advertising to health-care profes-sionals must contain information on the composition, therapeutic indications, contraindications, mode of action and adverse events in accordance with the summary of product characteristics. In addition, the advertisement shall include the classification of the medicinal product. In the Netherlands there are two categories: prescription and non-prescription (over-the-counter medicinal products). The non-prescription medicinal products are further classified into three categories: products that may only be sold in a pharmacy (UA); or only in a pharmacy and drugstore (UAD); or products which are for general sale at any location such as supermarkets (AV). Any docu-mentation containing advertising of a medicinal product shall include the date on which it was drawn up or last revised and whether it is reimbursable by health-care insurance. The broadcasting of teleshop-ping messages is prohibited.

It is prohibited to provide free samples of medicinal products, unless:• adatedandpersonallysignedrequestissubmittedbyaphysi-

cian, dentist or midwife;• thesampleisnotlargerthanthesmallestpresentationavailable

on the market;• nomorethantwosamplesofthesamemedicinalproductare

provided to a physician, dentist or midwife each year.• thesamplestatesthatitisfreeandmaynotbesold;• eachsamplecontainsthesummaryofproductcharacteristics;

and• recordsarekeptoftowhom,onwhichdateandinwhichquan-

tity the sample was provided.

Providing free samples of certain medicinal products listed in the Opium Act is prohibited.No gifts, donations, payments or hospitality may be provided to health-care professionals unless: • theofferedfunds,servicesorgoodsarereasonabletakinginto

account the performance of the professional; • itisbasedonawrittenagreementandrelevanttothepracticeof

medicine, pharmacy, dentistry or midwifery;• theofferedhospitalityislimitedtowhatisstrictlynecessaryto

be able to participate in a meeting or event; and• giftsordonations thatdonot require aperformanceof the

professional are modest in value and relevant to the practice of medicine, pharmacy, dentistry or midwifery.

The marketing authorisation holder shall keep a copy of each of its advertisements, indicating the persons to whom the advertisement is addressed, how it was distributed and the date of first distribution.

More specific rules regarding advertising to health-care profes-sionals can be found in the self regulatory codes of the Foundation for Advertisement of Medicinal Products.



Advertising of prescription-only medicines aimed at the general pub-lic is prohibited. Advertising of non-prescription medicines to the general public is permitted, provided the advertising is in accordance with the Dutch Medicines Act and the Code of Conduct Advertise-ment of Medicinal Products.

These rules and principles permit advertising of non-prescription medicines if the advertisement: • issetoutinawaythatitisclearforthepublicthatthemessageis

an advertisement and that it is clear for the public that it concerns a medicinal product;

• containsthenameofthemedicinalproduct;• containsinformationnecessaryforcorrectuse;and• containsanexplicitrequesttoreadthepatientinformationleaflet

or the text on the outer packaging.

Public advertisement is not permitted if it suggests that: • theuseofthemedicinalproductwillmakeamedicalconsulta-

tion or surgery unnecessary; • theproducthasnoadverseeventsorisbetterthanorequalto

another medicinal product or treatment; • thehealthofapersonmaybeimprovedbyusingthemedicinal

product; • the health of a personmay be affectedwhen not using the

product; or• thesafetyorefficacyoftheproductisduetothefactthatit

regards a natural substance.

Public advertising is furthermore prohibited if: • itisexclusivelyorprimarilydirectedatchildren;• itcontainsrecommendationsfromscientists,professionalsor

persons well-known to the public;• it is comparedwith foodstuff, cosmetics or other consumer

products; • itmayleadtoincorrectself-diagnosis;• itreferstoclaimsofrecoveryinamisleadingway;• itcontainsfrighteningormisleadingpictorialrepresentationsof

changes in the human body caused by a disease or injury or the functioning of the medicinal product on the human body; or

• itstatesthatthemedicinalproduct isreimbursablebysocialhealth-care insurance.

More specific rules regarding advertising aimed at the general public can be found in the self-regulatory Code on Public Advertisement of Medicinal Products.

Advertisements for the general public must be approved by the self-regulatory body KOAG prior to publication. The KOAG assesses compliance of the advertisement with the self-regulatory Code on Public Advertisement of Medicinal Products. An authorisation num-ber will be issued if the advertisement is approved and this is valid for 12 months. This number must be included in the advertisement.



In the Netherlands, most infringements are committed with regard to public advertisements. Most infringements are discovered on the internet and mainly concern websites with advertisements for pre-scription-only medicinal products. However, websites with advertise-ments for unauthorised medicinal products and off-label medicinal products also appear regularly.

Anyone (ie, consumers or health-care professionals) can report infringements of the advertisement rules to the Dutch Health-care Inspectorate, who may impose an administrative fine on infringers. The fines can amount to up to €150,000. See also question 10.





Off-label prescription of medicinal products by physicians occurs on a large scale in the Netherlands. The Dutch Medicines Act determines that off-label prescription of medicinal products is solely allowed within the scope of the protocols or standards developed by medical professional groups.

Advertising for off-label use is prohibited. However the self-reg-ulatory Code of Conduct for Advertisement of Medicinal Products makes a difference between advertising and information. Informa-tion regarding off-label use to health-care professionals is allowed as long as the information does not qualify as advertising. The Founda-tion for Advertisement of Medicinal Products has set out guidelines on the difference between advertising and information. According to these guidelines the difference should be assessed on a case-by-case basis taking the addressee, content, presentation and layout and context into account.




The collaboration of the pharmaceutical industry with health-care professionals in the in-patient as well as the out-patient sector is governed by legislation, self-regulatory codes and codes of conduct. In addition to the legislation and codes set out in question 3, the Data Protection Act, the Medical Scientific Research in Human Subjects Act (WMO) and the Decree on Research with Medicinal Products apply. Also the ICH Harmonised Tripartite Guideline for Good Clinical Practice and the World Medical Association Declaration of Helsinki are relevant. There are also many codes of conduct such as the Code regarding the Protection of Personal Data and the Codes of Conduct for Physicians or the Code of Conduct for Medical Spe-cialists, which cover the relation with the pharmaceutical industry. Furthermore, there exist pharmaceutical industry codes of conduct and sub-codes issued by the pharmaceutical industry associations such as Nefarma, Bogin or Neprofarm.



In addition to the rules and principles set out in question 4, rules with respect to clinical trials also apply to the collaboration of the phar-maceutical industry with health-care professionals. Serious adverse events and adverse reactions have to be notified by the investigator (for example a physician) performing the trial to the sponsor (for example a pharmaceutical company). Also specific rules for privacy regarding the patients apply. Companies that perform a trial via a physician are obliged to agree with the physician that he will observe the applicable privacy regulations such as managing the data on pri-vate persons with due care and informing a patient on the processing and storing of personal data. Furthermore, the guidelines and codes cover good clinical practice, transparency and ethical rules.



professionals?

Hospitality rules are regularly infringed. For reasons of transparency and in order to assess whether hospitality rules are violated, written service agreements between health-care professionals are required. Such service agreements sometimes are disproportionate with regard to the sales/promotion activities of the health-care professional and the remuneration by the manufacturer. Furthermore, hospitality rules are regularly infringed in meetings and conferences, where the hospi-tality is not subordinate to the main goal of the meeting.



The Code of Conduct for Sponsoring Patient Organisations sets out further detailed rules, in addition to the CGR-Code and CPG-Code, with regard to the relation between the pharmaceutical industry and patient organisations. The Code sets out rules on transparency and the safeguarding of the independence of the patient organisation. Financial support in the form of grants, sponsorship, support in kind and the like are allowed. The relation between the industry and the patient organisation may not be exclusive unless it regards a specific project. Direct or indirect promotion of one or more specific pre-scription medicinal products is prohibited.

The Foundation CGR enforces the Code of Conduct for Spon-soring Patient Organisations.



The Dutch Competition Authority (NMa) may pursue manufactur-ers’ infringements of competition law on the basis of the Competi-tion Act.


On the basis of article 6 of Regulation (EC) No. 1/2003, national courts have the power to apply articles 81 and 82 of the EC Treaty, now articles 101 (prohibited agreements and concerted practices) and 102 (abuse of dominant position) of the Treaty on the Function-ing of the European Union (TFEU). This means that private parties (undertakings) in the Netherlands can initiate proceedings against, for example, manufacturers of medicinal products for infringement of one or both of these articles and claim damages. In the Nether-lands, claiming damages is usually based on a wrongful act. The pri-vate proceedings can be initiated regardless of the public proceedings with the European Commission or the Dutch Competition Authority (NMa). However, it is easier to get damages awarded when it has been determined in a public proceeding with the European Commis-sion or NMa that the other party has infringed article 101 or 102 of the TFEU.






Advertising of medical devices and the collaboration of manufactur-ers with health-care professionals and patient organisations is not strongly regulated in the Netherlands. Opposed to the legislative regime applicable to medicinal products, the legislation for medical devices does not contain specific provisions with regard to advertise-ment and hospitality.

The Medical Devices Act (MDA) (which implements Directive 93/42/EC) solely contains a criminal provision regarding the promo-tion of unsuitable medical devices and the marketing of unsuitable medical devices (article 13 MDA). Furthermore, the Dutch Civil Code (DCC) contains general advertising rules with regard to mis-leading and comparative advertising, which also apply to medical devices (article 6:194-196 DCC). There is a self-regulatory Code on Public Advertising of Medical Devices 2009 of the Inspection Board for the Public Promotion of Medicines (KOAG) and the general Dutch Advertising Code of the Advertising Code Authority. Adver-tising for medical devices must comply with these codes. However, these codes do not address hospitality. In addition there is a diver-sity of codes of conduct, which regard the interactions between the industry and health-care professionals such as the code of conduct of



Diagned (Dutch code regarding in vitro diagnostics), EDMA (Euro-pean code on in vitro diagnostics), Nefemed (Dutch code regarding medical devices, which will be amended as of 1 January 2012) and Eucomed (European code regarding medical devices). These codes contain rules with regard to hospitality.

Currently there are such developments within the area of medical devices, which sometimes makes it difficult for the public to distin-guish between medical devices and (self-use) medicinal products. The gap creates room for advertising including hospitality. The Health-care Inspectorate and KOAG are of the opinion that more clarity is to be created with regard to the position of medical devices and the claims made in advertisements. The KOAG has therefore drawn up the Code on Public Advertising of Medical Devices 2009. No specific advertising rules for medical devices have however been laid down in legislation thus far.




The Dutch Medicines Act (which implements Directive 2001/83/EC as amended on the community code relating to medicinal products for human use) including the Regulation Medicines Act and the Decree Medicines Act sets out the regulatory framework for grant-ing marketing authorisations and placing medicines on the market. In addition the Dutch Medicines Evaluation Board (CBG) has drawn up several advisory documents and guidelines with the position of the CBG with regard to various aspects of the authorisation of medicinal products such as bio-equivalence, sunset clause, labelling, line exten-sions, variations, etc.

Regulation (EC) No. 726/2004 sets out the requirements for Community procedures for the authorisation of medicinal products and establishes a European Medicines Agency. Regulation (EC) No. 1394/2007 lays down specific rules concerning the authorisation of advanced therapy medicinal products.


jurisdiction?

Medicinal products in the Netherlands have to be granted a market-ing authorisation by the Medicines Evaluation Board (CBG) before they can be placed on the market. The CBG is an independent admin-istrative body of the Ministry of Health, Welfare and Sport.

The European Medicines Agency (EMA) is a decentralised agency of the European Union located in London and grants mar-keting authorisations valid in the entire EU and EEA/EFTA states (a centralised or community authorisation) under Regulation (EC) No. 726/2004.


There are four different procedures available to obtain a marketing authorisation (MA) for medicinal products in Europe: • thenationalprocedure;• themutualrecognitionprocedure(MRP);• thedecentralisedprocedure(DCP);and• thecentralisedprocedure.

Which MA procedure is to be used depends on whether the applicant wishes to market the medicinal product in one or more member states or throughout the EU and whether the medicinal product itself belongs to a certain category. In addition each MA procedure offers various advantages and disadvantages. Although the four procedures differ in the process, the requirements with regard to the quality, safety and efficacy of the medicinal product is the same.

Independent national procedures may only be used for medicinal

products, which are placed on the market in only one member state and which do not fall under the mandatory scope of the centralised procedure. For the Netherlands, applicants in a national procedure must submit an MA file to the Dutch Medicines Evaluation Board (CBG). A risk/efficacy assessment will be undertaken by the CBG. The CBG has up to 210 days to reach a final decision. This period may be suspended to allow the applicant to answer questions. When the decision is favourable, the summary of product characteristics (SmPC), the patient information leaflet and the label text (including layout) will be stipulated after which the MA is granted. The medici-nal product is thereupon added to the register of medicinal products and a marketing authorisation number (RVG number) is assigned.

The MRP and DCP are European authorisation procedures. These procedures must be applied when an applicant wishes to mar-ket a medicinal product in more than one member state with the exception of medicinal products that fall within the mandatory or optional scope of the centralised procedure. Both the MRP and the DCP are based on the principle of recognition by which one member state recognises the MA granted (in the case of an MRP) or approves the prepared assessment of the medicinal product by another mem-ber state (in the case of a DCP).

The MRP is used when one member state, the ‘reference member state’ (RMS) has already issued an MA to the applicant. The assess-ment report (including the SmPC, labelling and patient information leaflet) on the medicinal product of the RMS forms the basis for requesting the other member states, the ‘concerned member states’ (CMS), to mutually recognise the MA. Unless the CMS have objec-tions, on the grounds of a potential serious risk to public health, they shall approve the assessment report and authorise the medicinal product for their territory. When a CMS has objections against the assessment of the RMS a dispute procedure must be followed. The issues are referred to the Coordination Group for Mutual Recogni-tion and Decentralised Procedures (CMD(h)). If consensus is then not reached, the RMS refers the matter to the Committee for Medici-nal Products for Human Use (CHMP) for arbitration. If the decision of the CHMP is unfavourable for the applicant, it can appeal the decision with the European Medicines Agency (EMA). The Com-mission makes a final decision on the application.

When the applicant has not received an MA for its medicinal product in any member state, the DCP is applied. The applicant sub-mits an application in the member states where it wishes to obtain an MA and requests one member state to act as RMS in the procedure and to prepare a draft assessment report (including the draft SmPC, labelling and patient information leaflet). Subsequently, the other member states generally adopt the assessment of the RMS and grant the MA for their territory, unless they have important objections on the grounds of a potential serious risk to public health. In the event of objections the DCP has a dispute resolution procedure similar to the MRP.

Once the CMS have approved the assessment of the RMS in an MRP and DCP, for the Netherlands, Dutch translations of the SmPC, patient information leaflet and labelling texts are submitted to the CBG and a national marketing authorisation is issued by the CBG.

The centralised procedure leads to a European MA, which allows the MA holder to market its medicinal product throughout the EU. The centralised procedure laid down in Regulation (EC) No. 141/2000, is mandatory for medicinal products that:• aredevelopedbycertainbiotechnologicalprocesses;• containanewactivesubstanceforwhichthetherapeuticindi-

cation is the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune diseases and other immune dysfunctions and viral diseases; and

• aredesignatedasorphanmedicinalproductspursuanttoRegula-tion (EC) No. 141/2000.

For the following medicinal products the centralised procedure is optional:



• medicinalproductsthatcontainanewactivesubstance;• medicinalproductsthatconstituteasignificanttherapeutic,sci-

entific or technical innovation or the granting is in the interests of patients; or

• genericmedicinalproductsofa referencemedicinalproductauthorised through the centralised procedure.

The applicant will only need to submit a single application to the EMA. After the scientific evaluation by the CHMP and upon receipt of the opinion of the EMA, the European Commission will grant an MA for the entire EU.



Article 24(4-6) of Directive 2001/83/EC as amended and imple-mented in Article 47(4) of the Dutch Medicines Act determines that any authorisation that within three years of its granting is not fol-lowed by the actual placing on the market of the authorised product, in this case the Netherlands, or is no longer actually present on the market for a period of three consecutive years shall cease to be valid. The competent authority may grant exemptions on public health grounds and in exceptional circumstances if duly justified. This rule is known as the ‘sunset clause’.

The Dutch Medicines Evaluation Board has, in addition, deter-mined that the starting date for the three-year period is the date on which the product may be placed on the market, in other words, the date on which the marketing authorisation is granted, taking market exclusivity into account. Also the latest case law has determined that the sunset clause takes effect after the patent protection period has expired.


The basic principle of the medicinal product legislation is that only medicinal products that have obtained a marketing authorisation may be marketed. Only a limited number of exceptions apply to this rule. In short, these exceptions are:• anymedicinalproductpreparedinapharmacyinaccordance

with a medical prescription (magistral formula) or in accordance with the prescriptions of a pharmacopoeia (officinal formula) for an individual patient;

• medicinalproductsintendedforresearch;• medicinalproductssuppliedinresponsetoabonafideunsolic-

ited order of an authorised health-care professional and for use by an individual patient (named patient).

• unauthorisedmedicinalproductsinresponsetothesuspectedorconfirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation, any of which could cause harm;

• medicinalproductsavailableforcompassionateuse,wherebytheMedicines Evaluation Board considers the use of a new medicinal product intended for multiple patients with a chronically or seri-ously debilitating disease or whose disease is considered to be life-threatening and who cannot be treated satisfactorily by an authorised medicinal product. The concerned medicinal prod-uct must either be the subject of an application for a marketing authorisation or must be undergoing clinical trials.

20 Are any kinds of named patient (or similar expanded access)

programmes in place? If so, what are the requirements for pre-launch

access?

The Netherlands has a named patient programme in place. Named patient as laid down in article 5(1) of Directive 2001/83/EC has been implemented in article 40(3) of the Dutch Medicines Act and has been worked out in article 3.17 of the Regulation Medicines Act. The Dutch Health-Care Inspectorate (IGZ) is charged with the enforce-

ment of the named patient programme.Article 3.17 of the Regulation Medicines Act determines that

a manufacturer, wholesaler or pharmacist may supply a medicinal product, for which no marketing authorisation has been granted in the Netherlands, to a physician, if:• thephysiciandeemsitnecessarythatapatientbelongingtoits

practice is to be treated with the medicinal product;• thereisnoadequatemedicinalalternativeavailableonthemar-

ket in the Netherlands nor otherwise obtainable;• thephysicianhasrequestedinwritingtosupplythemedicinal

product to him;• thewrittenrequestofthephysicianhasbeensubmittedtothe

IGZ;• theIGZhasdeterminedthequantityofthemedicinalproduct

and the time period during which the medicinal product may be supplied to the physician; and

• themanufacturer,wholesalerorpharmacistkeepsanadministra-tion in which the quantity of the medicinal product, the name of the physician, the number of patients for whom the medicinal product is intended and the observed adverse events is recorded.

A Dutch Court has determined that the IGZ is not competent to grant permission in advance on a named patient application nor refuse such application. The IGZ may solely assess this afterwards and take enforcement measures when the stipulations in article 3.17 of the Regulation Medicines Act have not been met. The Ministry of Health will amend the law on this point to ensure that the IGZ is competent to grant permission in advance and refuse named patient applications.



law or regulation?

In the Netherlands there are two mechanisms to regulate the prices of medicinal products.

First of all, the Regulation on Maximum Prices for Medicines enacted on the basis of the Act on Medicine Pricing. The Regulation forms the basis on which the minister of public health, welfare and sport is authorised to determine the maximum price of a medicinal product. The actual pricing is carried out by the government agency Farmatec. The price is calculated by averaging the price of similar medicinal products in four reference countries: Belgium, Germany, France and the United Kingdom, using generally accepted price lists of the reference countries. The maximum prices are determined by means of a ministerial order, in principle, twice a year, in March and October. Subsequently, the maximum prices are published in the G-Standard, which is issued every month and contains information on all the products and medicines that are or may be dispensed by or used in the pharmaceutical industry.

Secondly, prices are regulated by the medicine reimbursement system/(GVS). The Health Insurance Act forms the basis for the GVS. The insured have a right to reimbursement for authorised medicines for use outside a hospital when the medicine has been included in an Annex of the Health Insurance Regulation. The GVS constitutes the following medicinal products allocated in the Health Insurance Regulation: • Annex1Amedicinalproducts.Medicinalproductsareplaced

in clusters of mutually interchangeable products. A medicinal product is interchangeable when it has a similar indication, has a similar route of administration and is intended for the same age group as a medicinal product already included in the Annex of the Health Insurance Regulation. A maximum reimbursement price is determined for each cluster. The reimbursement limit is the average of the pharmacy purchase prices of the medicinal products in the cluster on a certain reference date. In cases where



the actual price of the medicinal product exceeds the determined maximum reimbursement price, the patient will have to pay the price difference;

• Annex1Bmedicinalproducts.Medicinalproductswhichcan-not be clustered with another medicinal product. The medicinal products are non-interchangeable with other medicinal products. The therapeutic value and the cost efficiency is assessed with regard to products that have already been included in an Annex. These medicinal products are fully reimbursed, there is no reim-bursement limit; and

• Annex2medicinalproducts.Medicinalproductsthatmaybereimbursed under certain conditions laid down in the Health Insurance Regulation.

To ensure inclusion of a medicine in the Annex, a manufacturer must submit an application to the government agency Farmatec. After the application has been received, it will first of all be determined which procedure must be followed: an abridged procedure or a complete procedure. An abridged procedure is only possible for medicinal products with the same active substances, the same strength and the same pharmaceutical form as a medicinal product already included in annex 1A of the Health Insurance Regulation. For all other medic-inal products the complete procedure must be followed, whereby the advice of the Committee on Pharmaceutical Aid and the Health Insurance Board is requested before the minister of public health, welfare and sport determines whether or not the medicinal prod-uct is eligible for reimbursement. In general, for both procedures (abridged and complete), the minister shall decide within 90 days from the receipt of the application whether the medicinal product shall be reimbursed, although in practice this term is usually longer. The reimbursement prices are published every month in the Govern-ment Gazette, after which they are also included in the G-Standard.

For medicinal products used in hospitals, the performance funding takes effect as of 1 January 2012. Hospitals will no longer receive a fixed budget for the costs of all the provided health care and the medicines but will be paid for each care that they perform, separately. For this purpose DBCs have been developed. DBC stands for ‘Diagnose’ (Diagnosis) ‘Behandeling’ (Treatment) ‘Combinatie’ (Combination). The DBC-system regards all the care activities, from the first consultation and diagnosis by the medical specialist up to the discharge from the hospital, including the medicines. The hospital care is divided into a segment with fixed DBC-prices (A-segment) and a segment where prices are open for negotiation (B-segment). The DBCs in segment A, are clustered in product groups per medical specialty. A product group contains DBCs that are in the same price range and per product group an average price has been determined. Segment B contains frequent hospital care and is subject to market forces and free price-making. Expensive and orphan medicinal prod-ucts will be funded in the DBC system through add-ons. Add-ons are part of a DBC but may be charged in addition to the DBC. The Policy Guideline for Expensive Medicinal Products and the Policy Guideline for Orphan Medicinal Products of the Dutch Health Care Authority (NZa) will cease to have effect and the medicinal products listed in these policies will become an add-on as of 2012.

22 Must pharmaceutical manufacturers negotiate the prices of their products with the public health-care providers?

Pharmaceutical manufacturers negotiate the prices of their medicinal products with the (hospital) pharmacists and health insurers.

A pharmaceutical manufacturer generally offers its medicinal product to pharmacists at a sales price below the list price of their medicinal product. A list price (in the Netherlands also called the pharmacy purchase price) is the price of the medicinal product that is registered in the G-Standard (see question 21) as the official sales price to pharmacists. The actual sales price is realised by a discount on the pharmacy purchase price by the manufacturer of the medici-nal product.

A number of health insurers apply a ‘preference policy’ in which health insurers designate certain medicinal products to become eligible for reimbursement by the insurer. The insurer must on the basis of the Decree Health Insurance designate at least one medicinal product per active substance or combination of active substances. Health insurers apply the preference policy in different ways: one is that the manufacturers are given a certain time to adapt their pharmacy purchase price in for example the G-standard. After that time the health insurer determines which medicinal products will be included in the preference policy of the insurer. The other possibility is that the insurer puts out a tender. The pharmacy purchase price of the medicinal product does not change, but the insurer will receive the discount price afterwards on the basis of the medicinal products charged by the pharmacists. It remains between the parties what the eventual agreed price is. Often the health insurer selects those medicinal products as ‘pre-ferred’ on the basis of the lowest price but also other conditions may apply such as that the supplier can guarantee that it can sup-ply the entire market during the term that the medicinal product has been declared ‘preferred’ (usually one year).

23 In which circumstances will the national health insurance system reimburse the cost of medicines?

As set out in question 21, the national health insurance system will reimburse the costs of authorised medicines included in one of the annexes of the Health Insurance Regulation with regard to the medi-cine reimbursement system. Medicinal Products used in hospitals are paid by the hospitals and funded through the health-care insurance contributions.

Off-label use of medicinal products generally qualify for reim-bursement of the costs of the medicinal product. The Health Insur-ance Regulation determines in annex 2, however (see also question 22), that the right for reimbursement of a number of medicinal prod-ucts listed in this annex is linked to certain indications. In addition, for some medicinal products in annex 2 it is expressly determined that off-label use of the medicinal product is also reimbursed when the following criteria are met:• theinsuredsuffersfromadiseasethatoccurstolessthanoneout

of 150,000 residents in the Netherlands;• theefficacyofthemedicinalproductforthatindicationhasbeen

scientifically substantiated; and• thereisnoothertreatmentpossiblewithanyauthorisedmedici-

nal product for that indication in the Netherlands.

The costs of medicinal products for compassionate use may only be reimbursed when the use of the medicinal product regards rational pharmacotherapy. For unauthorised imported medicinal products the additional condition applies that the product is intended for a patient who suffers from a disease that occurs to less then one out of 150,000 residents in the Netherlands.

In addition, medicinal products prepared in a pharmacy in accordance with a medical prescription (magistral formula) are also solely reimbursable when the treatment therewith is regarded as rational pharmacotherapy.

24 If applicable, what is the competent body for decisions regarding the pricing and reimbursability of medicinal products?

The Ministry of Public Health, Welfare and Sport will determine the maximum prices for medicinal products and determine which products will be placed on the lists in the Annexes of the Health Insurance Regulation for the medicine reimbursement. Farmatec is a unit of the Ministry of Public Health, Welfare and Sport and deals with the procedures for maximum prices and reimbursement. The Dutch Healthcare Authority (NZa) is an independent administrative body that deals with the health-care budgets. See also the answer to question 21.





Manufacturers or distributors of medicinal products in the Nether-lands are statutorily not obliged to give a discount.




The Dutch Medicines Act prohibits the marketing of medicinal prod-ucts that have not obtained a marketing authorisation. The coun-terfeiting and illegal distribution of medicinal products fall under this prohibition. Breach of this rule is an economic offence and can qualify as a criminal offence when committed intentionally.

Customs together with the Health-Care Inspectorate supervise the compliance of the Medicines Act. Based on the Anti-Piracy Regu-lation (Regulation (EC) 1483/2003), it is possible for the customs authorities to detain counterfeit medicinal products that are being imported into the Netherlands. Also, owners of trademarks or pat-ents may file an application with customs requesting that certain suspected counterfeit goods are to be detained. Trademark and pat-ent owners must institute civil proceedings for infringement of their rights to maintain such detention.

In addition, the new legislation on falsified medicines (Directive 2011/62/EU of 8 June 2011, amending Directive 2001/83/EC) which is part of the legislative proposals of 2008 of the European Com-

mission, in its ‘Pharmaceutical Package’ has entered into force. The new legislation aims, among other things, to strengthen EU legisla-tion to better protect EU citizens from the serious threats posed by falsified medicinal products. Member states shall bring into force the laws, regulations and administrative provisions necessary to comply with this new Directive by 2 January 2013. For the Netherlands, this mainly means that the Medicines Act will need to be amended.



One of the legislative proposals of 2008 in the European Commis-sion’s ‘Pharmaceutical Package’ regards clear rules on information provided by pharmaceutical companies on prescription-only medi-cines. The proposal aims to ensure that the public has access to reli-able information on available medicines, the grounds on which they have been authorised and how they are monitored. Currently there are many differences between the member states with regard to the access of patients to adequate information regarding their medicinal product. The proposal aims to harmonise this situation. The original proposal of 2008 has been revised by the European Commission and will now be debated on by both the European Parliament and the Council of Ministers.

In the Netherlands the general public can find product infor-mation on prescription-only medicines in the medicines database (available online) of the Medicines Evaluation Board. In addition

The new European pharmacovigilance legislation has entered into force and will become applicable in July 2012. The new legislation is laid down in Regulation (EU) No. 1235/2010, amending Regulation (EC) No. 726/2004 and Directive 2010/84/EU, amending Directive 2001/83/EC. This legislation will improve patient safety and public health through better prevention, detection and assessment of adverse reactions to medicinal products. It will also involve the European citizen more and provide them with more information. Patients will be able to report adverse drug reactions directly to the competent authorities and the reporting of adverse reactions will be broadened. Also, there will be more attention for transparency. In the Netherlands the Dutch Medicines Act will be amended on the basis of the amendments of the European pharmacovigilance legislation.

In addition, parliament accepted on 1 November 2011 the legislative proposal regarding amendments to the Dutch Medicines Act. The most important changes in the proposal regard; the permission of reminder advertising; certain nurses who, on the instruction of a health-care professional, provide or administer patients with prescription medicinal products will qualify as health-care

professionals; and nurses who in practice prescribe or administer medicinal products to patients will be allowed to medical meetings in combination with a certain degree of hospitality. The amended Medicines Act will enter into force on a date determined by a Royal Decree.

Also, the Foundation for Advertisement of Medicinal Products (Foundation CGR) has drawn up rules of conduct regarding the publication of financial relations between health-care professionals and the pharmaceutical industry (Code Publication Financial Relations). The Code contains obligations for the pharmaceutical industry to disclose al its financial service agreements and sponsor agreements with health-care professionals in a central transparency register. Financial relations below d500 a year are excluded from the Code. The nature of the financial relation, the name and address of the pharmaceutical company, information of the health-care professional or the institution and the amount shall be made public in the register. The publication applies for three years, after which the information will be removed from the register. The Code will enter into force on 1 January 2012.


Colette Mulder [email protected]

Van Alkemadelaan 700 Tel: +31 70 353 8800

2597 AW The Hague Fax: +31 70 353 8882

The Netherlands www.twobirds.com



the Adverse Events Database of the Netherlands Pharmacovigilance Centre (Lareb) is available to the public. This database contains information on known adverse events of a medicinal product and it contains information on which adverse events have been reported to Lareb for a medicinal product.


of medicines.

Following adoption by the Council and the European Parliament and publication on 31 December 2010 in the Official Journal of the EU, the new European legislation on pharmacovigilance has entered into force and will become applicable in July 2012.

This new pharmacovigilance legislation was one of the three legislative proposals of 2008 of the European Commission, in its

‘Pharmaceutical Package’. The new legislation regards Regulation (EU) No. 1235/2010, amending Regulation (EC) No. 726/2004 and Directive 2010/84/EU, amending Directive 2001/83/EC. The legisla-tion aims to better protect public health by simplifying the current rules and procedures and strengthening the European system for the safe monitoring of medicines. The objectives in short are:• providingclearrolesandresponsibilitiesforthememberstates

and the EMA;• strengtheningtherulesonEUdecision-making,transparencyand

communication, including involving concerned parties such as patients for direct reporting of suspected adverse reactions;

• strengtheningthepharmacovigilancesystemsofthemarketingauthorisation holder; and

• ensuring theproactive andproportionate collectionofhigh- quality data.

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