"Orphan drugs" are medicinal products intended for the diagnosis, prevention or treatment of life-threatening or very serious diseases affecting less than five in 10 000 persons in the Community. These drugs are called "orphans" because the pharmaceutical industry has little interest, under normal market conditions, in developing and marketing products intended for only a small number of patients suffering from very rare conditions. For the drug companies, the cost of bringing a rare-disease medicinal product to the market would not be covered by the expected sales of the product. For this reason, governments and organisations representing rare disease patients have emphasised the need for economic and regulatory incentives to encourage drug companies to develop and market medicines for the many neglected and "orphaned" rare disease patients.

The Orphan Regulation (Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products) was proposed by the Commission in July 1998 and is in force since 2000. It sets up the criteria for orphan designation in the EU and describes the incentives (e.g. 10-year market exclusivity, protocol assistance, access to the Centralised Procedure for Marketing Authorisation) to encourage the research, development and marketing of medicines to treat, prevent or diagnose rare diseases, thus providing patients. The Regulation does not concentrate on access or research.

In addition, the Commission adopted Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the criteria for orphan designation and defining the concepts of "similar medicinal product" and "clinical superiority".

The European Commission's Enterprise and Industry DG has published an independent study on the price of orphan drugs . The study, conducted by Alcimed, looks at the price of orphan drugs authorised in the EU and how these prices were arrived at. In addition, the study discusses how "sufficient profitability" might be assessed and judged. This latter aspect relates to the operation of Article 8 (market exclusivity) of the Orphan Regulation.

In 2000, a Committee for Orphan Medicinal Products (COMP) was established at the European Medicines Agency (EMEA) to review designation applications from persons or companies intending to develop medicines for rare diseases. This committee is responsible for studying the applications for orphan designation, for giving opinions on the designation as orphan medicinal products, and for advising and assisting the Commission in discussions on orphan drugs.

Drugs designated as orphan are entered in the Community Register for Orphan Medicinal Products.

Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe
Improving access to orphan medicines for all affected EU citizens - Final Conclusions and Recommendations of the EU Pharmaceutical Forum - October 2008

According to a European Medicines Agency EMEA report including Annexes I, II and III carried out 3 years after the application of the Regulation, it has had a successful start: 342 designations as at December 2005 (compared to nearly no EU-developed products before) and 22 orphan medicinal products granted marketing authorisation.

An Index of Public Summaries of Opinions for Orphan designation is publicly available. This information on designations for the general public is a good example of communication with patients and doctors and a good example of the European policy of transparency and communication.

Patients may be able to get early access to a drug before its marketing authorisation is granted to the pharmaceutical industry that develops it, most often during the third phase of the clinical trial and when its safety and efficacy can be confidently assumed. Two cases may arise:

1. an application for marketing approval either had been or is about to be submitted by the pharmaceutical company developing the drug in the country concerned. The company submits a request for compassionate use to the administrative authority for a group of patients [called a cohort temporary regulatory approval (ATU) in France and in Italy] that is valid for a limited time span in the country considered, or
2. the physician asks the administrative authorities for a nominative approval that is valid for a specific patient and for a limited time span in the considered country. Due to differences in legislation, ease and rapidity of access to orphan drugs are not the same in the 25 European countries, as indicated in an EMEA chart .

• the establishment of a new body, the Paediatric Committee, sited at the European Medicines Agency (EMEA);
• for new products and certain changes to the marketing authorization for products still covered by patent protection;
• a requirement for paediatric data based on a paediatric investigation plan (PIP)
• a six-month extension of the supplementary protection certificate if information arising from a completed PIP is incorporated into the Summary of Product Characteristics;
• for orphan medicinal products a two-year extension of market exclusivity if information arising from a completed PIP is incorporated into the Summary of Product Characteristics.