Orphan designation: Overview
About 30 million people living in the European Union (EU) suffer from a rare disease. The European Medicines Agency (EMA) plays a central role in facilitating the development and authorisation of medicines for rare diseases, which are termed 'orphan medicines' in the medical world.
United Kingdom's (UK) withdrawal from the EU
EMA has published important information to help users of the centralised procedure prepare for the expected consequences of 'Brexit', including their obligations related to establishment within the European Economic Area (EEA). For more information, see UK's withdrawal from the EU.
Orphan designation in the product lifecycle
EMA's role in orphan designation
- it must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating;
- the prevalence of the condition in the EU must not be more than 5 in 10,000 or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development;
- no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorised, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition.
Applications for orphan designation are examined by the EMA's Committee for Orphan Medicinal Products (COMP), using the network of experts that the Committee has built up. The evaluation process takes a maximum of 90 days from validation.
For information on how to apply, see how to apply for orphan designation.
The Agency sends the COMP opinion to the European Commission, which is responsible for granting the orphan designation. The full list of orphan designations is available in the Community register of orphan medicinal products for human use.
After orphan designation
Developing medicines intended for small numbers of patients has little commercial incentive under normal market conditions. Therefore, the EU offers a range of incentives to encourage the development of designated orphan medicines.
Sponsors who obtain orphan designation benefit from protocol assistance, a type of scientific advice specific for designated orphan medicines, and market exclusivity once the medicine is on the market. Fee reductions are also available depending on the status of the sponsor and the type of service required.
Sponsors must submit an annual report to the Agency summarising the status of development of the medicine.
Some 60% of designated orphan medicines are intended for paediatric use. Medicines authorised across the EU with the results of studies from a paediatric investigation plan included in the product information are eligible for an extension of their supplementary protection certificate. For designated orphan medicines, the incentive is an additional two years of market exclusivity.
Marketing authorisation stage
Marketing authorisation applications for designated orphan medicines must be submitted to EMA for assessment through the centralised procedure. They are assessed by EMA's Committee for Medicinal Products for Human Use (CHMP).
Designated orphan medicines are eligible for conditional marketing authorisation. In some cases, designated orphan medicines may be allowed to be administered to patients under compassionate use, a treatment option that allows the use of an unauthorised medicine outside a clinical study.
At the time of marketing authorisation, sponsors also need to submit an application for maintenance of the orphan designation in order to be eligible for the ten-year market exclusivity incentive. Sponsors may also need to submit an evaluation of orphan similarity.
For more information, see activities after orphan designation.
The Agency encourages companies developing orphan medicines to check if they can be classified as a micro, small or medium-sized enterprise (SME). Such companies benefit from further incentives, including administrative and procedural assistance from the Agency's SME office and fee reductions.
Because rare diseases are a global issue, the Agency works closely with its international partners on the designation and assessment of orphan medicines, in particular:
- the United States Food and Drug Administration (FDA), sharing information on orphan medicines under their confidentiality arrangement. The two authorities have also developed common procedures for applying for orphan designation and for submitting annual reports on the status of development of designated orphan medicines.
- the Japanese Ministry for Health, Labour and Welfare (MHLW) on issues related to orphan medicines.
The Agency works with organisations representing patients with rare diseases through the European Organisation for Rare Diseases (EURORDIS).
Rare diseases at a glance
- Between 5,000 and 8,000 distinct rare diseases exist, affecting between 6% and 8% of the population in total – in other words, between around 27 million and 36 million people in the EU. Most people suffer from diseases affecting fewer than 1 in 100,000 people.
- 80% of rare diseases have identified genetic origins, and affect between 3% and 4% of births. Other rare diseases are due to degenerative and proliferative causes.
- Symptoms of some rare diseases may appear at birth or in childhood, including spinal muscular atrophy, lysosomal storage disorders, patent ductus arteriosus (PDA), familial adenomatous polyposis (FAP) and cystic fibrosis. More than half of rare diseases appear during adulthood, such as renal-cell carcinoma, glioma and acute myeloid leukaemia.
- Medical and scientific knowledge about rare diseases is lacking. The number of scientific publications about rare diseases continues to increase, with an average of 5 new diseases described every week in the medical literature. However, fewer than 1,000 diseases benefit from even minimal amounts of scientific knowledge. These tend to be the rare diseases that occur most frequently.