EN Official Journal of the European Union C 67/92

Opinion of the European Economic and Social Committee on the ‘Proposal for a Regulation of the European Parliament and of the Council on fees payable to the European Medicines Agency for the conduct of pharmacovigilance activities in respect of medicinal products for human use’

COM(2013) 472 final — 2013/0222 (COD)

2014/C 67/18

Rapporteur: Ms HEINISCH

On 12 July and 1 July 2013 respectively, the Council and the European Parliament decided to consult the European Economic and Social Committee, under Articles 114 and 168 of the Treaty on the Functioning of the European Union, on the:

Proposal for a Regulation of the European Parliament and of the Council on fees payable to the European Medicines Agency for the conduct of pharmacovigilance activities in respect of medicinal products for human use

COM(2013) 472 final — 2013/0222 (COD).

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 2 October 2013.

At its 493rd plenary session of 16 and 17 October 2013 (meeting of 16 October), the European Economic and Social Committee adopted the following opinion by 144 votes to one with seven abstentions:

1. Conclusions and recommendations

1.1 The European Economic and Social Committee (EESC) welcomes the Commission proposal, which makes an important contribution to the further improvement of medicinal product safety and the transparency of the assessment processes. The Committee particularly welcomes the improvements compared with the Commission's first draft, in particular special rules for SMEs.

1.2 The Committee welcomes the principle that the marketing authorisation holder will not have to pay fees twice for the same pharmacovigilance activity. It calls on the Commission to ensure that, simultaneously with the introduction of the new fees, national fees charged for the same activity are abolished.

1.3 The EESC welcomes the Commission's proposals regarding the periodic safety update reports (PSUR) and post-authorisation safety studies (PASS). The Committee calls on the Commission, however, to allow further fee reductions for medicinal products with a well-understood safety profile.

1.4 The EESC believes that the processing of EU-wide assessment procedures carried out on the basis of pharmacovigilance data (referrals) is a national responsibility, which should not be financed exclusively from fees paid by marketing authorisation holders. Such assessment procedures are a key task of the competent authorities at national and EU level and should, the Committee believes, be financed from EU funds, inter alia in order to ensure the independence of the assessment.

1.5 The EESC welcomes the proposal that the EMA will levy an annual flat-rate fee from marketing authorisation holders for pharmacovigilance activities. However, the Committee notes that the pharmacovigilance activities are only available to a limited extent, if at all. The Committee therefore suggests that the flat-rate fee be suspended pending availability of these services.

1.6 The Committee welcomes the Commission's proposal that fees should be shared as fairly as possible between all market authorisation holders affected. The EESC suggests that the proposed approach involving "chargeable units" should be reconsidered.

2. Introduction

2.1 The maintenance or restoration of good health is for most people a high priority, and for many the highest.

2.2 Medicines, together with advice and treatment from members of the medical professions, are of key importance for the maintenance or restoration of health. Patients, as citizens of the European Union, rightly expect optimum treatment with effective and safe medicines in all Member States. All regulations concerning medicines must assign the highest priority to the interests of patients.

2.3 Risks arising from the use of medicines must be excluded as far as possible or at least minimised, and safety must be paramount. This requires adequate checks before authorisation and ongoing surveillance after authorisation. This activity, known as pharmacovigilance, is the responsibility of all stakeholders, marketing authorisation holders, members of the medical professions, patients, as well as the competent authorities in the Member States and the EU as a whole.

2.4 Patients expect uniform decisions to be taken on medicines authorised in several Member States on a sound scientific basis and to be communicated in uniform and easily understandable language. The European Medicines Agency (EMA) and its specialised bodies have a key role to play in coordinating scientific assessment and in uniform communication.

2.5 If the EMA is to be able to perform these important tasks, it must be appropriately financed. At present the EMA is unable to levy fees for many pharmacovigilance activities. This possibility is created by the Commission proposal.

2.6 When introducing new fees, it must be ensured that the pharmaceutical manufacturers pay an appropriate financial contribution for the services they require.

2.7 The contribution of the pharmaceutical manufacturers must be designed in such a way that medicines continue to be available to patients in the European Union; the levying of fees must not jeopardise the marketing of products for economic reasons so that patients cannot be appropriately treated.

2.8 Patients expect EU-wide procedures for the assessment of pharmacovigilance data to be based exclusively on scientific considerations, independently of the fees of the pharmaceutical manufacturers.

3. Background

3.1 In earlier opinions the Committee has repeatedly stressed the importance of a competitive and innovative pharmaceuticals industry in Europe. In the last 50 years it has been one of the modern industrial sectors with the highest levels of technology and innovation rates. Throughout Europe this sector employs hundreds of thousands of, mostly highly qualified, specialised workers, and it achieves a high level of added value.

3.2 However, the positive effects of medicinal products can also be accompanied by undesirable side effects resulting from errors in use or medication, including the misuse and/or abuse of the product.

3.3 The use of medicinal products thus requires a high degree of responsibility and close attention should be paid to this, as public health is at stake here, particularly given that many side effects of new medicines are often identified only after authorisation and marketing.

3.4 The amendment to Directive 2001/83/EC and Regulation (EC) No 726/2004 published on 15 December 2012 widens the tasks of the EMA with regard to pharmacovigilance, including EU-wide pharmacovigilance procedures, the monitoring of literature cases, the improved use of information technology- tools and the provision of more information to the general public. Furthermore, the pharmacovigilance legislation stipulates that the Agency should be enabled to fund those activities from fees charged to marketing authorisation holders. New categories of fees should therefore be created to cover the new and specific tasks of the Agency.

3.5 To finance these activities, the revised pharmacovigilance legislation provides for fees to be charged to marketing authorisation holders. These fees should be related to pharmacovigilance activities performed at the level of the EU, notably in the context of the EU-wide assessment procedures. These procedures include scientific assessment carried out by rapporteurs from the national competent authorities of the Member States. These fees are therefore not intended to cover the pharmacovigilance activities of the national competent authorities performed at national level. Member States may accordingly continue to charge fees for the activities performed at national level, which should, however, not overlap with the fees laid down in this legal proposal.

4. Definitions

4.1 According to the definition of the World Health Organisation (WHO), the concept of pharmacovigilance means the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem, risk management, prevention of therapy errors, the provision of information on medicines and the promotion of rational therapy with medicines.

4.2 The concepts of side effects and adverse drug reactions (ADR) mean undesirable negative effects of treatment with a medicine.

4.3 Periodic safety update report (PSUR) means a compilation of comprehensive data on the uses and risks of one or more medicines over an extended period, generally more than three years, which has to be submitted by the marketing authorisation holder to the competent authorities of the countries in which the product has been authorised.

4.4 A referral, an EU-wide procedure for the assessment of pharmacovigilance data, is a regulatory procedure at European level aimed at arbitrating between different scientific positions or reservations in connection with the authorisation of medicines.

4.5 A post-authorisation safety study (PASS) is a scientific study aimed at drug safety. This may be initiated voluntarily by the marketing authorisation holder or may be carried out as a condition imposed by the competent authority following authorisation for pharmaceutical products. The main objectives of these studies are to identify the frequency of occurrence of known side effects under everyday conditions, to identify rare, hitherto unknown side effects which went undetected in clinical studies because of the small number of cases, and to investigate possible risks arising from everyday use by specific groups of patients (e.g. the very old, pregnant women, patients with impaired liver function etc.).

4.6 EudraVigilance (European Union Drug Regulating Authorities Pharmaco vigilance) means an information network and management system operated as a core service by the EMA, aimed at ensuring drug safety in the European Economic Area. EudraVigilance supports in particular the electronic communication of reports on side effects before and after the authorisation of a pharmaceutical product (including suspected cases) and their systematic collection, as well as the early identification of drug risks and appropriate measures to minimise risks.

4.7 The Extended EudraVigilance Medicinal Product Dictionary (xEVMPD) is an extended version of the EVMPD medicinal product dictionary, which was closed in July 2011. Marketing authorisation holders feed the database with product-related data on all medicinal products authorised in the European Economic Area, including product names, authorisation holder and the relevant pharmacovigilance system, type and status of the authorisation, pharmaceutical formulation and strength, route of administration, and on indication, active ingredients and excipients. The EU medicinal product dictionary was to have been complete by 2 July 2012, but is currently usable only to a limited extent.

4.8 A "chargeable unit" means each individual entry in the database in accordance with Article 57(1)(l) of Regulation (EC) No 726/2004 (xEVMPD) based on information from the list of all medicinal products for human use authorised in the Union referred to in Article 57(2) of the Regulation.

5. Legal basis

5.1 The proposal is based on Article 114 and Article 168(4)(c) TFEU. It is based on Article 114 TFEU as differences between national legislative, regulatory and administrative provisions on medicinal products tend to hinder intra-Union trade and therefore directly affect the operation of the internal market.

5.2 In addition, the proposed regulation is based on Article 168(4)(c) TFEU as it aims at supporting the goal of setting high standards of quality and safety of medicinal products.

6. Subsidiarity and proportionality principles

6.1 The EMA is a European decentralised Agency established under Regulation (EC) No 726/2004 and hence the decision on its funding and charging of fees is to be taken at the EU level. The new pharmacovigilance legislation provides a legal base for the Agency to charge fees for pharmacovigilance. Hence, only the Union can act to enable the Agency to charge fees for pharmacovigilance. Only pharmacovigilance activities that are performed at EU level and involving the Agency are covered by the proposal for a regulation. As regards pharmacovigilance activities remaining at national level, the EU is not competent and Member States may still continue charging national fees accordingly.

6.2 The Commission considers that the proposal is in line with the proportionality principle as it does not go beyond what is necessary to achieve the general objective pursued, i.e. to introduce fees in order to allow the proper implementation of the pharmacovigilance legislation that is applicable since July 2012.

7. General comments

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

7.2 The EESC pays tribute to the Commission's efforts, through the amended version of Directive 2001/83/EC and Regulation (EC) No 726/2004, to improve the legal framework for pharmacovigilance and to simplify it in the interests of patients and pharmaceutical manufacturers. In this way the Commission is making a major contribution to the completion and deepening of the internal market in a complex and important area like the medicinal products sector.

7.3 The Committee also acknowledges the important contribution which the EMA makes in this connection, particularly in coordinating the communication of scientifically well-founded and uniform information on the risks of medicinal products to patients in the EU.

7.4 The EESC supports the aim of the Commission proposal to make it possible for the EMA to charge appropriate fees for its pharmacovigilance services.

8. Specific comments

8.1 In this context the EESC in principle welcomes the fee arrangements set out in Articles 4 and 5. Both the PSURs mentioned in Article 4 and the post-authorisation studies (PASS) referred to in Article 5 make an extraordinarily important contribution to the early identification of risks and are thus, from the point of view of patients, to be welcomed unreservedly.

8.2 The Committee assumes that the requirements for submission of documentation, both for PSUR and PASS purposes, will be less onerous for medicinal products with a well-known safety profile than for new, innovative medicinal products. Consequently, the checks and processing carried out by the EMA and the rapporteurs involved will presumably also be less onerous than in the case of new, innovative medicinal products. The Committee calls on the Commission to make provision for a further reduction in the fee for medicinal products with a well-known safety profile, to reflect the documentation required under Articles 4 and 5.

8.3 The Committee does not, however, consider the fees for referrals listed in Article 6 of the Commission proposal to be appropriate. The EESC considers, rather, that assessment procedures of this type should be conducted independently of pharmaceutical industry fees and should be guided purely by the interests of patients. The cost should be covered by the EU budget.

8.4 The EESC also welcomes in principle the annual flat-rate fee proposed in Article 7. The Committee assumes, however, that this fee will be levied only when the EMA is able to provide the full pharmacovigilance services to be financed by the fee to the companies liable to pay it. The Committee does not consider the proposed link with a chargeable unit to be appropriate.

8.5 The EESC also welcomes the proposed fee reductions and exemptions for small and micro-enterprises.

8.6 In effect, only a partial service is currently being provided by the EMA in return for the proposed flat-rate fee; charging this at the full rate is therefore not yet justified. The Committee therefore suggests that the flat-rate fee be suspended pending availability of these services. The date on which these services become available could be confirmed by the EMA Management Board, in accordance with the third paragraph of Article 24(2) of Regulation (EC) No 1235/2010. This article states: "The Management Board of the Agency shall on the basis of an independent audit report that takes into account the recommendation of the Pharmacovigilance Risk Assessment Committee confirm and announce when the Eudravigilance database has achieved full functionality."

8.7 With regard to the "chargeable unit", national conditions may, for example, mean that the same authorisation is issued in a country in several languages, involving several entries in the database. Most pharmacovigilance activities are carried out per active ingredient and not "chargeable unit" and should be charged accordingly. The Committee therefore suggests that the chargeable unit should refer to a European procedure number. National authorisations should not be subject to multiple counting.