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Important legal notice

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**Opinion of the European Economic and Social Committee on the Proposal for a Directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use COM(2008) 665 final — 2008/0260 (COD) **

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Official Journal C 306 , 16/12/2009 P. 0028 - 0032 *

Opinion of the European Economic and Social Committee on the Proposal for a Directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use

COM(2008) 665 final — 2008/0260 (COD)

2009/C 306/06

On 23 January 2009 the Council decided to consult the European Economic and Social Committee, under Article 95 of the Treaty establishing the European Community, on the

"Proposal for a Directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use"

The Section for the Single Market, Production and Consumption, which was responsible for preparing the Committee's work on the subject, adopted its opinion on 19 May 2009. The rapporteur was Mr CEDRONE.

At its 454th plenary session, held on 10 and 11 June 2009 (meeting of 10 June), the European Economic and Social Committee adopted the following opinion by 93 votes in favour and three abstentions.

1. Conclusions and recommendations

1.1 The EESC welcomes the Commission initiative, which aims to improve the pharmacovigilance system and its harmonisation at the EU level, and gives priority to patients and their health needs.

1.2 The EESC emphasises that it is important to base the gradual strengthening of the pharmacovigilance instrument primarily on transparency and the simplification of procedures in an increasingly concrete framework of greater harmonisation between Member States’ procedures in order develop a common methodology, since the EESC is convinced of the need to work towards the goal of free movement of medicinal products and the completion of the single market in this sector.

1.3 The EESC is therefore in favour of the improvement to the legislative framework in force, which amends and substantially enhances Directive 2001/83/EC, discussed herein, and Regulation No 726/2004 (on which a specific opinion (CESE 1023/2009) has been drawn up — rapporteur: Sylvia Gauci). These measures take account of limitations encountered during the application of the current provisions and aim to replace existing national rules, which are liable to present — often unnecessary — barriers to the free movement of medicines in the EU and hinder a practical risk reduction process.

1.4 The EESC emphatically endorses the objective whereby all stakeholders are directly involved in the pharmacovigilance process, including not just professionals in the sector and the relevant public sector bodies but also patients themselves, who thus become active partners in the risk reduction process and play an increasingly active part in therapeutic choices that are more in tune with their health needs. The EESC believes that the new elements introduced by the proposals must neither call into question, nor weaken existing structures and procedures at local level, especially those that involve the patient and health professionals, provided that common parameters for comparable data are assured in transparent and rapid procedure.

1.5 The EESC points out that this initiative is fully in line with the renewed Lisbon Strategy, which, in addition to simplifying procedures, seeks to foster continuous development of the pharmaceutical sector in order to create a sector founded on knowledge-based economic growth that can contribute significantly to high-skill employment and fully respond to the healthcare demands put forward with increasing insistence by civil society.

1.6 It considers the establishment of an EMEA committee with pharmacovigilance as its specific and sole task, and the availability of a continuously updated EU database on potential risks (Eudravigilance) that is easily accessible to all citizens to be the strong points of the legislative measure, which follows a request for increasingly simple and more practical instruments for the preparation of the information leaflets that accompany all pharmaceutical products.

1.7 As a result, the EESC's assessment is positive since the initiative will reduce administrative burdens and simplify procedures for reporting adverse reactions, not least by cutting back on the current paper-based procedure for reporting between Member States.

1.8 Given the importance of pharmacovigilance for public safety in ensuring the citizens’ right to safe and effective pharmaceutical products, the EESC calls for pharmacovigilance to be included in its own right in EU research programmes, starting with those set up under the Seventh Framework Programme, via programmes directly involving the EU, its Member States, industries, universities and public and private research centres.

1.9 The EESC believes that once the key issue of pharmacovigilance has been dealt with, a number of issues affecting this sector will remain unresolved such as, for instance, the price of pharmaceutical products, the varying availability of medicinal products within the Member States themselves, issues relating to the use of generic medicines and their harmonised distribution, protection against counterfeit medicines and illegal supply chains, the safe importing of active ingredients and excipients, etc. These problems have to be addressed in order to achieve the intended freedom of movement of medicinal products in the European Union and the completion of the single market.

2. Introduction

2.1 Civil society's consistent calls for "good health" and a better quality of life place the need to provide an adequate response to healthcare issues at the top of the agenda, starting with prevention and the proper use and monitoring of medicinal products.

2.2 As one of the key tools for protecting public heath, pharmaceuticals are a valuable resource and their discovery and adequate availability are a key aspect of public heath protection. Their proper use is a key contributor to the steady rise in life expectancy while, at the same time, it helps to cut down on healthcare expenditure insofar as it reduces the cost of hospital or specialist care.

2.3 The need to review pharmacovigilance legislation was revealed by a close analysis of experience acquired and an independent study carried out in 2004 by the Commission. This report revealed several shortcomings and the need to better define the rules governing this field. As a result, the Commission decided to review existing pharmacovigilance legislation in order to bring it into line with gradual advances in general legislation on the free movement of medicinal products and making use of medicinal products safer for EU citizens.

2.3.1 Since EU pharmacovigilance legislation was first introduced in 1965, only piecemeal and limited action has been taken. In view of the limitations encountered on a day-to-day basis, we are now faced with the need for a qualitative leap in the definition of pharmacovigilance legislation, not least in order to prevent this issue from creating barriers, which are often unnecessary, to the free movement of medicinal products in the EU, which is absolutely unacceptable.

2.4 The rules currently in force are Regulation (EC) No 726/2004 of 31 March 2004 and Directive 2001/83/EC. The Directive under consideration seeks to amend the latter. Both legislative instruments have made a useful contribution to monitoring the side effects of pharmaceutical products, but the study carried out and a subsequent consultation involving all stakeholders have shown that there is room for improvement through more precise definition of these rules.

2.5 The proposed amendments fall within a strategic framework for marketing authorisations for medicinal products, and subsequent supervision and surveillance to ensure a high level of public health protection and progress towards the completion of the internal market for the pharmaceutical sector, bearing in mind the social dimension of pharmaceutical products, whose purpose should always be to benefit patients and their interests.

3. Context

3.1 In its earlier opinions, the EESC has systematically stressed the importance of Europe's competitive and highly innovative pharmaceutical industry, which over the last 50 years has been among the most high-tech, high-innovation and high-skill employment sectors, with a corresponding added value and growth rate for the modern industrial framework.

3.2 However, the positive effects of medicinal products are also accompanied by unintended, noxious side effects resulting from their use and from medication errors, including the misuse and/or abuse of the product. Misuse of medicinal products accounts for 5 % of all hospital admissions.

3.3 The responsibilities inherent in such a role are fundamental and warrant considerable attention in order to safeguard public health properly, especially since we are confronted with a marketing process in which the adverse effects of new molecules are only detected after authorisation has been granted and the new medicinal product is therefore already on the market.

4. Definitions

4.1 The term pharmacovigilance is used to define the pharmacological process dedicated to the detection, assessment, understanding and prevention of the adverse effects of medicinal products, and in particular, of short and long-term side effects.

4.2 Risk assessment during the development of medicinal products should be thorough and rigorous, even if it is impossible to identify all safety risks during clinical trials. Once a medicinal product enters the market, there is generally a substantial increase in the patients exposed to it, including patients who suffer from more than one condition at the same time or who are being prescribed a number of different types of medication.

4.3 Adverse drug reaction (ADR) is an expression that describes the unwanted, negative consequences associated with the use of given medication. An ADR could be identified as any unexpected or dangerous reaction to a drug. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial. An ADR is a "response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function".

5. Gist of the Commission proposal

5.1 The Directive aims to strengthen and rationalise the pharmacovigilance system, especially with respect to clarifying roles and responsibilities, by amending Directive 2001/83/EC, which has served so far as the legal reference framework for medicinal products for human use.

5.2 This is why the Commission has decided to amend the existing EU legislation. The objectives pursued are as follows:

- setting out clear roles and responsibilities for the parties;

- rationalising EU decision-making on drug safety issues;

- strengthening safety transparency and communication to increase the understanding and trust of patients and professionals as regards safety;

- strengthening companies’ pharmacovigilance systems;

- ensuring the proactive and proportionate collection of high-quality data relevant to safety and post-authorisation risk management;

- involving stakeholders in pharmacovigilance by enabling patients to report suspected adverse reactions and including them in decision-making;

- simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators.

5.3 The Commission explains that the proposals are consistent with the overall objective of the free movement of medicinal products, which is to remove disparities which still exist between national provisions by reconciling a high level of public health protection with the proper functioning of the internal market for medicinal products.

5.4 All interested parties, i.e. patients, healthcare professionals, the competent authorities of the Member States and the industry, were widely consulted on the proposals. The impact assessment suggested increasing the clarity, efficiency and quality of the current EU system of pharmacovigilance with a view to public health improvements and overall cost savings to the EU pharmaceutical sector.

5.5 In order to establish clearer roles and responsibilities, the new provisions clarify and codify the tasks and responsibilities of the interested parties. Although the pharmacovigilance system will remain the province of the individual Member States, marketing authorisation holders will have to report all available data exclusively to the Community's Eudravigilance database, thereby automatically ensuring an EU-level assessment of any related issues.

5.6 These strengthened safety measures for medicinal products should increase the trust of patients and healthcare professionals by including a new "key information" section in the summary of product characteristics and the package leaflet which accompany every medicinal product.

5.7 The responsibilities of the agency will be bolstered by the establishment of a new scientific committee responsible for pharmacovigilance, as set out in Article 27 of the new provisions, with the additional role of assessing risk, providing support both to the Committee for Medicinal Products for Human Use within the Agency and the coordination group of Member States.

5.8 Under the new provisions, marketing authorisation holders will have to keep a "pharmacovigilance system master file" and to provide a risk management system for each new medicinal product authorised, which should be proportionate to both the identified and the potential risks.

5.9 The new proposal makes an additional improvement to pharmacovigilance by strengthening the electronic infrastructure for reporting adverse events connected with medicines (Article 24). The scope of periodic safety update reports sent to the Eudravigilance database will be amended so that they serve to analyse the risk-benefit balance. Provision has also been made for the regulatory follow-up of periodic safety update reports. Thus, Eudravigilance will provide a clear link between pharmacovigilance evaluations and the review and updating of marketing authorisations, while at the same time giving real-time access to all information on the database.

5.10 The new legislative proposal sets out to simplify the reporting of adverse drug reactions, making periodic safety update report submission proportionate to risks. This will facilitate the reporting of adverse and unintended reactions to medicinal products taken in normal doses as well as from overdose or medication errors by both healthcare professionals and patients. It combines rules for reporting adverse reactions, applying the same provisions to medicines authorised under the centralised procedures and those authorised by individual Member States.

5.11 Section 1 of Chapter 3 concerns the recording and reporting of unintended effects. Subsequent sections provide a detailed description of the other procedures for reporting and evaluating pharmacovigilance information and more detailed technical information. The second section covers "Periodic safety update reports" the third "Community procedure", setting out in Article 107 the procedure each Member State must follow in order to suspend or revoke marketing authorisation because serious deficiencies have been found, and the fourth section "Publication of assessments"; this is an important section since it concerns the supervision of post-authorisation safety studies for medicinal products.

6. Legal basis

6.1 The proposal is based on Article 95 of the EC Treaty, which prescribes the codecision procedure and is the legal basis for achieving the free movement of goods for medicinal products for human use. Moreover, since the Amsterdam Treaty came into force, Article 95 has been intended to remove barriers to intra-Community trade and therefore justifies EU-level action in the area of medicinal products.

7. Subsidiarity and proportionality principles

7.1 EU pharmacovigilance measures guarantee the best protection of public health through the application of the same standards across the Community. They are also in line with the proportionality principle insofar as they seek to safeguard public health without imposing unnecessary administrative burdens by building on existing structures, procedures, resources and practices. The proposal envisages that the efficiency of the EU pharmacovigilance system will be increased and costs reduced due to the resulting simplification.

7.2 The objective of improving the safety of medicines placed on the Community market can be best achieved by applying the subsidiarity principle as set out in Article 5 of the Treaty. Under this article, the best way to achieve these objectives is at EU level, as the requirements for accreditation and market surveillance relating to the marketing of pharmaceutical products fall within the scope of Article 15(2) of Regulation (EC) No 765/2008 of the European Parliament and of the Council of 9 July 2008.

7.3 Furthermore, since the proposal provides for the simplification of the Community pharmacovigilance system, it falls under Annex 1 of the Commission Legislative and Work Programme for 2008.

8. General comments

8.1 Recognising the major, positive contribution that medicinal products make to the citizens’ quality of life, the EESC has always supported any initiatives liable to increase safety in the use of medicinal products, which is a fundamental aspect of public health protection.

8.2 The EESC's initial assessment of the decision to overhaul existing legislation in the light of previous experience is positive insofar as the objective of such a strategy for improving safety through the proposed amendments has been a key element of earlier EESC opinions on the various aspects of pharmaceutical policy.

Moreover, the EESC takes a positive view of the Commission's efforts towards simplification in the interests of individual patients as well as companies. It also endorses efforts being made to complete the single market in a sector as complex and important as the pharmaceutical sector.

8.3 The EESC endorses the amendments that clarify and improve the definition of terminology previously used in Directive 2001/83/EC. The new wording will help solve problems relating to previous interpretations, which sometimes gave rise to doubt and inconsistencies in application. In particular, with regard to Article 1, the EESC welcomes improvements in defining the meaning of "adverse reaction", as used in point 11, and the way in which it has been distinguished from the use of "suspected adverse reaction" in point 14 referred to in the same article. Its definition should take account of the risk of confusion with the International Conference on Harmonisation (ICH) definition.

9. Specific comments

9.1 In the same vein, the EESC takes a positive view of clarifications set out in the new point 15 with respect to the definition of "post-authorisation safety study", and the new definition in point 28 regarding the "risk management system", followed by a detailed description of the required documentation in the new Article 8(iaa) and point 28c) on the "pharmacovigilance system" and point 28d) on the proposed master file, which is defined in greater detail in Article 8(3).

9.2 The EESC draws particular attention to Article 21(a) since the new definition contributes to safety by making the marketing authorisation of the new pharmaceutical product subject to the provision of substantial documentation to establish compliance with the key safety measures set out in Article 22, subject to certain conditions established by the competent authorities regarding the safety of pharmaceutical products.

9.3 Article 22(a) requires the national competent authority to require a marketing authorisation holder to conduct post-authorisation safety studies if there are concerns about risks. On the basis of documents submitted by the marketing authorisation holder, the national competent authority may withdraw or confirm authorisation. The EESC welcomes the provisions of Article 23, which, based on the findings of the study, oblige the authorisation holder to immediately inform the national competent authority of any prohibition or restriction imposed by the competent authorities of any other country.

9.4 Article 101 clearly sets out the role of Member States in the direct management of a pharmacovigilance system, making them responsible for the collection of information on the risks of medicinal products as regards patients’ or public health in a single database, i.e. Eudravigilance, in accordance with detailed procedures set out in Article 24. A competent authority is to be appointed in each Member State with responsibility for collecting data on adverse reactions relating to medicinal products on the basis of conditions for authorisation and other uses including overdose, misuse, abuse and medication errors.

9.5 The EESC believes that Article 102 contributes to improving patient safety in the use of medicinal products since it enables Member States to impose requirements on doctors, pharmacists and other healthcare professionals in respect of the reporting of suspected or identified adverse reactions.

Brussels, 10 June 2009.

The President

of the European Economic and Social Committee

Mario Sepi

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