3. Special cases in marketing authorisations: Orphan Medicines

1. Orphan medicines

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The aim of the orphan medicine legislation is to stimulate research and development of medicines for rare diseases (in short 'orphan medicines') to ensure access to treatment for patients. The European Union’s orphan legislation has been designed to help overcome the extra hurdles these medicines face to get on the market and to provide an incentive for companies to invest in the development of respective medicines despite the low number of patients and therefore the limited market.

1.1. Criteria

To qualify for an orphan designation, a medicine must meet a number of criteria (as per the EMA definition):

• It must be intended for the treatment, prevention or diagnosis (also referred to as “medical plausibility”) 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 a network of experts, and it also considers if medicines previously granted orphan designation can continue to be classified as orphan medicines at the time of marketing authorisation and beyond. For Marketing authorisations for designated orphan medicines the centralised procedure is obligatory and applications for marketing authorisation (MAA) go before the Committee for Medicinal Products for Human Use (CHMP). Moreover, MAHs can also apply for an orphan designation for new indications of an already authorised product.

1.2. Incentives

Orphan designation offers incentives to encourage development of orphan medicines and their availability. Incentives for sponsors include

• a 10-year period of market exclusivity once an orphan medicine is authorised, which is extended by two years for medicines that also have complied with an agreed paediatric investigation plan (see below).
• eligibility for Union and member state initiatives which support research and development of orphan medicines (e.g., research grants under EU Framework Programmes for Research and Innovation, E-Rare, a transnational project for research programmes on rare diseases)
• reduced fees for regulatory activities. This includes reduced fees for protocol assistance, marketing-authorisation applications, inspections before authorisation, applications for changes to marketing authorisations made after approval, and reduced annual fees.
• incentives in EU Member States for designated orphan medicines are available in the European Commission's Inventory of Union and Member State incentives to support research into, and the development and availability of, orphan medicinal products — state of play 2015

Of note: Some 60% of designated orphan medicines are intended for paediatric use since many childhood diseases are rare. 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.

Legal Basis:

Regulation (EC) No 141/2000
Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) No 141/2000 on orphan medicinal products setting out its interpretation on certain matters relating to the implementation of the designation and the market exclusivity provisions.
For a detailed inventory of the underlying legal basis see: EMA - Legal framework: orphan designation