This Commission staff working document concerns the fourth inventory of Union and Member State incentives to support research into, and the development and availability of, orphan medicinal products — state of play 2015.

This year marks the 15th anniversary of the Orphan Regulation . In that time, there has been impressive progress , in particular as regards generating significant activity by the pharmaceutical industry in this field.

After 15 years of implementation and significant advances for patients, the Commission wishes now to take stock of progress in this field.

This paper thus represents the fourth version of the inventory.

Main conclusions : the Commission has launched a survey to collect information on national measures to support research into, and the development and availability of, OMPs. This information was based on Member States information validated by the relevant national competent authorities in December 2015. The Commission cannot vouch for its accuracy or completeness.

R&D support : some Member States have introduced reduced fees for registration and academic clinical trials, tax reductions or waivers, public funding for research and free scientific advice.

In France , OMP developers are exempt from certain taxes to be paid by pharmaceutical companies. In the Netherlands , the registration fee can be waived if the medicinal product is already registered in one or more other Member State and the prevalence of the condition is less than 1:150 000. Poland and the United Kingdom , on the other hand, have no specific measures for orphan medicinal products either.

Availability of OMPs to patients : as regards measures to support the availability of OMPs to patients, many Member States have confirmed that they are implementing ‘compassionate-use’ programmes to bring unauthorised medicinal products to market. Such programmes are used for individual patients (‘patient programmes’) on the basis of a doctor’s statement or the company can make products available to a group of patients.

Reimbursement of the product : the cost of the product may or may not be reimbursed, depending on the Member State. In Greece for instance, orphan drugs covered by a compassionate-use programme for individual patients are reimbursed in full. In Germany , all OMPs are reimbursed directly after market authorisation.

The impact of reimbursement on the availability of orphan medicinal products may be a matter of concern in the EU. The budgetary impact of OMPs is expected to rise due to the newly authorised products in the coming years. In this context, it is important to highlight that some Member States have adopted specific measures for the reimbursement of OMPs.

Other measures : most Member States reported other measures that they have taken under national plans on rare diseases that cover not only OMPs, but also the prevention (e.g. pre-natal diagnosis) and detection of rare diseases, the exchange of information and cooperation with patients’ organisations. In this context, most confirmed progress for the implementation of the Orphanet database and of centres of expertise for rare diseases and had registers of patients with particular diseases.

This Commission staff working document sets out the experience required as a result of the application of Regulation 141/2000/EC on orphan medicinal products and account of the public health benefits obtained.

Orphan medicinal products are intended for the diagnosis, prevention or treatment of life-threatening or very rare serious conditions.

The report states that the response to the orphan legislation in the EU has far exceeded initial expectations; more than 450 applications have been submitted in the period between April 2000 and April 2005. Of those, more than 260 have been designated and 2 have gone on to receive a marketing authorisation.

Although more than 5 years of experience with the Regulation has now been gained, the true impact of the EU orphan initiative on public health will only be revealed progressively as longer term experience is accumulated. Already, more than 1 million patients suffering from orphan diseases in the Community may potentially benefit from these new 22 orphan medicines authorised during the first 5 years of application of Regulation 141/2000/EC. In addition, there is good ground to assume that the legislation has stimulated industrial activity leading to company creation with promising high-tech potential.

The full benefits of the EU orphan regulations require optimal synergies between action on Community and on Member State level. Incentives at the European Union level need to be translated into rapid access for patients to the new products throughout the entire Community and they need to be supplemented by incentives at Member States level. In this regard, the past experience was not entirely satisfactory.

‘The Council of the European Union, having regard to the Treaty establishing the European Community; whereas, in its Resolution of 30 November 1995 on the integration of health protection requirements in Community policies, the Council considers that the Community must pay particular attention to the impact on health of action proposed in a number of areas, including free movement of goods; whereas action to improve understanding of and address the impact on human health of the free movement of goods, in particular the free movement of medicinal products, should form part of the Community’s overall strategy for action in the field of public health; whereas there are many diseases from which small numbers of people suffer in the Member States and across the Community as a whole; whereas steps are needed to make it easier for patients suffering from those diseases to have access to treatments, in particular by means of so­-called ‘orphan’ drugs, meeting the same criteria as all medicines; whereas, despite the relative infrequency of such diseases, the nature of their treatment and their particular health, economic and social effects are such as to make it advisable to consider them in a European context; whereas the Commission, in its communication of 24 November 1993 on the framework for action in the field for public health, singled out rare diseases as one of eight priority areas for Community action; whereas, in its Decision of 15 December 1994 adopting a specific programme of research and technological development, including demonstration, in the field of biomedicine and health (1994 to 1998), the Council specified rare diseases and orphan drugs as a specific research area (area 4.6), with actions including an inventory of rare disorders; whereas the Commission in its communication of 2 March 1994 on the outlines of an industrial policy for the pharmaceutical sector in the European Community referred to the work to be undertaken, within the field of research on biomedicine and health, on orphan drugs, where research may not be commercially viable; whereas there are certain drugs which are already marketed and have low commercial interest but are of major importance for the treatment of some rare diseases; whereas a common European approach to rare diseases and orphan drugs holds out advantages in epidemiological, public health and economic terms, CALLS ON the Commission, in close cooperation with the Member States and in the light of the guidelines in the Annex, to look into the situation of orphan drugs in Europe and, if necessary, make appropriate proposals with a view to improving access to medicinal products intended particularly for people suffering from rare diseases. Annex Aspects to be considered 1) The definition of an ‘orphan drug’; 2) The definition of a ‘rare disease’, having regard to its prevalence; 3) The criteria for obtaining ‘orphan drug’ status in Europe, establishing conditions for drugs’ inclusion or exclusion, in the light of any changes in the conditions on the basis of which they were classified; 4) Measures using regulatory provisions (including intellectual property aspects) and financial incentives to promote research, development, marketing authorisation and distribution of orphan drugs; 5) Examination of the health impact of a European policy on orphan drugs in the Member States and its economic impact for European industry.’