Opinion of the Economic and Social Committee on the 'Proposal for a European Parliament and Council Regulation (EC) on orphan medicinal products` () (1999/C 101/10)

On 23 October 1998 the Council decided to consult the Economic and Social Committee, under Article 100a of the Treaty establishing the European Community, on the above-mentioned proposal.

The Section for Employment, Social Affairs, and Citizenship, which was responsible for preparing the Committee's work on the subject, adopted its opinion on 8 December 1998. The rapporteur was Mr Colombo.

At its 360th plenary session (meeting of 27 January 1999), the Economic and Social Committee adopted the following opinion by 121 votes to two with three abstentions.

1. Introduction

1.1. Following a lengthy preparatory phase, the Commission has presented a draft regulation which sets out to meet a strongly-felt need on the part of millions of patients: to create favourable conditions at Community level for research on and development and marketing of medicines, known as orphan medicinal products, to treat rare diseases.

1.2. Patients' associations have for years been calling for this initiative in order to counter what is now the unacceptable marginalization experienced by such patients, who are denied equality in terms of a fundamental right of all citizens: the right to health.

1.3. The proposal also comes in response to the decision taken under the Community framework for action in public health, which identified rare diseases as one of the priority areas for European Union action ().

1.4. Given continuing medical progress - of which medicines are an essential element - and its beneficial effects on the quality and length of life, it is now unacceptable that a sector of the population should be excluded from this process.

1.5. The pharmaceutical industry is not spontaneously interested in meeting the needs of such patients, since the profit principle which governs its choices and programmes corresponds to market criteria.

1.6. It is however understandable that the small scale of the market, invariably involving only a small number of patients, should not be attractive to an industry which expects returns on the heavy investment required for research and development of innovative medicines: the cost is currently in the region of ECU 200 million ().

2. The aim of the proposal

2.1. The primary aim of the Commission proposal, which is based on Article 100a of the EC Treaty and takes the legal form of a Regulation, is then to create conditions likely to encourage the pharmaceutical industry and its research centres to tackle the issue of rare diseases adequately, as already happens in the USA and Japan.

2.2. The two main features of the proposal are:

- the definition of harmonized criteria and the establishment of a Community procedure for the designation of orphan medicinal products;

- the provision of incentives for the research, development and bringing to the market of pharmaceutical products to treat rare diseases.

2.3. The proposal identifies two distinct criteria for the designation of orphan medicinal products:

- a predominant epidemiological criterion, i.e. the incidence of a disease on a given population. Under the proposal, this criterion would apply when a disease affects less than five per ten thousand persons within the Community population, and it can be shown that no satisfactory method of treatment exists;

- an economic criterion, depending on the expected non-profitability of a product which is necessary to treat a life-threatening or seriously debilitating communicable disease in the Community.

2.4. A number of supports are provided under the incentive arrangements:

- the Community guarantees access to the entire EU market via a centralized authorization procedure for designated orphan medicinal products, the main incentive being a ten-year period of market exclusivity throughout the Community, subject to the 'reduction clause` (), to measures to protect patients' interests and to public health imperatives ();

- the costs arising from the overall centralized authorization procedure for these medicines can be partially or fully defrayed by the Community budget;

- support for DG XII's specific Community research programmes, as implemented under the previous 'Biomedicine and Health` (Biomed 2) Programme and as planned in the first specific programme 'Improving the quality of life and the management of living resources` of the fifth research programme (1998-2002), together with the DG V action programme on rare diseases.

2.5. It has been decided to use the instruments put in place by Regulation (EEC) No 2309/93 () to evaluate applications for the designation of orphan medicinal products: specifically the European Agency for the Evaluation of Medicinal Products (EMEA). The London-based EMEA, whose work the ESC has followed since its inception, certainly possesses the infrastructure and professional skills required.

2.6. Designation of orphan medicinal products is to be carried out by a standing committee set up for this purpose within the EMEA, made up of experts appointed by the Member States on the basis of their proven experience in the field of rare diseases, accompanied by six Commission appointees: three representatives of patients' associations and three members recommended by the EMEA .

3. General comments

3.1. Foreword

3.1.1. The ESC welcomes the Commission proposal and supports the basic principles and objectives pursued by the draft regulation. This positive judgement - subject to the reservations set out below - is based on the view that the regulation represents an important move in the direction of solidarity with patients who are left at the margins of medical advances, because they suffer from rare diseases.

3.1.2. The Committee therefore considers that designation of orphan medicinal products - while still subject to the criteria under Article 3 - should be extended to cover specific indications of active substances which have already been authorized for other indications, as well as medicines for treating debilitating, chronic or life-threatening diseases in the Community.

3.1.3. The Committee believes that the choice of a Community dimension () is well-suited to the small number of patients concerned and the consequent low capacity for return on investment. Such an outcome would be hard to achieve at purely national level. Nevertheless, the proposal leaves scope for individual Member States to encourage national initiatives by introducing, in particular, tax incentives for research.

3.1.3.1. The Committee therefore calls upon the Commission to draw up a recommendation promoting the introduction of such incentives.

3.1.4. As stated previously, in its opinion on the Proposal for a European Parliament and Council Decision adopting a programme of Community action 1999-2003 on rare diseases in the context of the framework for action in the field of public health (), the Committee endorses the disease incidence proposed (diseases with a generally-accepted prevalence in the total Community population of less than five per 10 000).

3.1.5. The Committee welcomes the fact that three members of the committee for orphan medicinal products are representatives of patients' organizations, in view of their role as communicators and mediators between researchers, the industry and patients.

3.1.6. The ESC believes that the progress generated by a renewed commitment by Community research to the specific sector of rare diseases - some of which are widespread in other parts of the world - could make a decisive contribution to improving living conditions in the developing countries, where investment in research is almost completely lacking. Such a move would place Europe at the centre of solidarity with the developing countries, and should constitute Europe's preferred approach in the future.

3.1.7. While endorsing the priority given to human patients, on the grounds of urgency, the Committee feels that the question of how to foster the R& D and marketing of veterinary medicinal products should be tackled in the future.

3.2. Incentives

3.2.1. A careful assessment needs to be made as to whether the content of the proposal and the incentives it offers are appropriate and sufficient to provide the pharmaceutical industry with the necessary conditions for encouraging a commitment consistent with patients' legitimate expectations, and to stimulate basic research in the university sector in tandem with applied research in the industrial sector.

3.2.2. The Committee believes that the proposed incentives, which need adequate support through specific research programmes, offer advantages to companies engaged in the field of rare diseases. It views the initiative and the ensuing investment as helping to create new businesses and highly-skilled employment.

3.2.3. The Commission proposal should therefore provide for incentives for an appropriate level of research and marketing with a view to making the European industry - thus far penalized by the lack of legislation on orphan drugs - more competitive.

3.2.4. The ESC approves the content of Article 6 which offers assistance in the development of protocols for the clinical experimentation necessary in order to obtain authorization by demonstrating the quality, safety and efficacy of the medicinal product. This assistance will be of particular value to SMEs, allowing the necessary medicines to be made available to patients as soon as possible.

3.2.5. The 'reduction clause` contained in Article 8(2), reducing the period of market exclusivity from ten to six years at the request of a single Member State, should not be seen as diminishing the incentives. Rather, it should be viewed as an exceptional measure, representing a safeguard in any cases where orphan drugs prove to be 'blockbusters` during the exclusivity period.

3.2.5.1. It is nevertheless felt that the reference in this article to prices could lead to difficulties in implementation.

3.2.6. In the Committee's view, the derogations under Article 8(3) constitute a proper measure in terms of protection of patients' interest and public health imperatives since, inter alia, the Article should ensure sufficient availability of medicines to meet patients' needs.

3.2.7. The Committee agrees that designation does not automatically confer market exclusivity or entitlement to priority. It is the authorization of the medicinal product which entails exclusivity, rewarding the most effective and efficient research. It agrees that there should be no obstacles to further research into medicines with the same therapeutic indication, which may be authorized only if they demonstrate greater safety and practical efficacy.

3.3. Resources

3.3.1. The first point to be looked at must be the size of the resources earmarked for the programme. The proposal's ambitions must be matched by availability of resources. Initial examination suggests that these resources are not enough to prime the entire scheme properly.

3.3.2. The ESC fully supports the possibility of access to the centralized procedure and, with the aim of encouraging companies to engage in research and development of orphan medicinal products, it would urge that the inherent costs to companies of the entire EMEA process be kept as low as possible, and that thought be given to fully defraying the whole cost from the Community budget.

3.3.3. More particularly, given that, in the experiments which have been underway for some time, most demand is from SMEs, the Commission should make specific arrangements for individual SMEs, or groups of SMEs, to use Community funds, which should not be limited to those provided under the fifth framework programme for research and technological development.

3.4. Consistency with other Community policies

3.4.1. The Committee welcomes the fact that the draft regulation presents a comprehensive action programme for combating rare diseases, encompassing and coordinating the work of different DGs (III - V - XII). It is hoped that this coordination will prove more broadly based and more effective in generating the maximum Community 'added value`.

3.4.2. The ESC intends to put pressure on the Commission to ensure that this measure serves as a turning-point in removing the barriers which continue to hamper the free movement of medicinal products in the EU, as argued in several previous Committee opinions.

3.4.3. Firstly, efforts must be made to secure the early adoption of the Directive on good clinical practice () for the pursuit of clinical experimentation with medicinal products for human use and to secure its application in the individual Member States, in order to guarantee rigorous protection of the individuals on whom orphan drugs are tested, and to ensure the quality, safety and efficacy of these products.

3.4.4. In keeping with points 2.7 and 3.4.2 of its opinion on good clinical practice, the Committee calls for a specific procedure to speed up the launch of clinical experiments on orphan medicines and completion of protocols, so as make these drugs available to patients as soon as possible.

4. Specific comments

4.1. Article 3(1)

Add the following sentence at the end 'This also applies to new indications of known substances`.

4.2. Article 3(2)

The expression 'a life-threatening or seriously debilitating communicable disease` may prove too narrow or ambiguous. The following is therefore suggested: 'debilitating, chronic or life-threatening diseases`.

4.3. Article 8(3)(c)

Terminological difficulty in interpreting the term 'clinically superior`.

4.4. Article 8(5)

The definition given of 'similar medicinal product` would appear too narrow, failing to define the concept adequately.

4.5. In order to prevent wording which is ambiguous or difficult to verify reducing the interest of the companies concerned, the ESC recommends that these terms be deleted from the articles of the proposal and that more detailed guidelines be provided at a later stage.

Brussels, 27 January 1999.

The President

of the Economic and Social Committee

Beatrice RANGONI MACHIAVELLI

() OJ C 276, 4.9.1998, p. 7.

() OJ C 388, 31.12.1994; OJ C 203, 3.7.1997 - ESC opinion in OJ C 19, 21.1.1998.

() Communication from the Commission to the Council and the European Parliament on the outlines of an industrial policy for the pharmaceutical sector in the European Community (COM(93) 718 final).

() Article 8(2) provides that this period may be reduced to six years if a product no longer meets the criteria for designation, or if the price charged is such as to allow unreasonable profits.

() Article 8(3) permits marketing authorization for a similar medicinal product with the same therapeutic indication in certain cases.

() OJ L 214, 24.8.1993 - ESC opinion OJ C 269, 14.10.1991.

() Community actions relating to this proposal: 1) OJ C 388, 31.12.1994; 2) COM(93) 718 final; 3) OJ C 350, 30.12.1995; 4) COM(93) 276 final, OJ C 230, 26.8.1993 - ESC opinion OJ C 34, 2.2.1994; 5) OJ C 203, 3.7.1997 - ESC opinion in OJ C 19, 21.1.1998; 6) OJ C 306, 8.10.1997 - ESC opinion in OJ C 95, 30.3.1998; 7) COM(98) 305 final; 8) OJ L 213, 30.7.1998).

() Proposal: OJ C 203, 3.7.1997 - ESC opinion in OJ C 19, 21.1.1998.

() Proposal: OJ C 306, 8.10.1997 - ESC opinion in OJ C 95, 30.3.1998.