In order to provide incentives for a potentially uneconomical development and marketing of a medicinal product intended for the diagnosis, prevention or treatment of a rare disease, the European Commission has established a voluntary and free-of-charge orphan designation procedure (Regulation 141/2000), in which benefits for drug development can be applied for. Orphan designation (OD) is a multi-stage process with initial designation and confirmation of the criteria at the time of marketing authorisation or major extensions/variations of the therapeutic indication. Early in the drug development process, in some cases years before clinical development, orphan drug designation can be applied for at the Committee for Orphan Medicinal Products (COMP). The CHMP ultimately issues the authorisation recommendation for medicinal products holding an orphan designation in the centralised authorisation procedure. The assessments of the CHMP and the COMP are carried out separately and can differ from each other (e.g. if a medicinal product is authorised but still loses its orphan status if the required orphan criteria are not (or no longer) met).

Criteria for orphan designation

The requirement for an orphan designation (OD) is that the disease for which the medicinal product is to be developed does not affect more than 5 out of 10,000 people in the EU. As an alternative to the so-called prevalence criterion, it can also be demonstrated by the sponsor that the marketing of the medicinal product would probably not bring sufficient profit to justify the necessary investments (although this criterion has only been discussed in a small number of cases since the regulation came into force). A further criterion for the orphan drug status is that there is either not yet a satisfactory method for the diagnosis, prevention or treatment of the condition, or that the corresponding medicinal product is of “significant benefit” compared to the already available “satisfactory method”.

Benefits for orphan drugs

While the basic rules for a marketing authorisation also apply to orphan drugs, the EMA grants financial reliefs for scientific/regulatory advice and other regulatory fees during development even before marketing authorisation. At initial orphan designation, only possible candidates for a later medicinal product are identified. If the orphan status is confirmed at the time of marketing authorisation, the medicinal product, then called an orphan medicinal product (OMP), is granted a market exclusivity over similar substances for 10 years (for more information on the subject of similarity, see EMA Guideline 2008/C 242/08). Market exclusivity can be extended to 12 years if the requirements of the paediatric regulation have also been fulfilled within the first 10 years (full compliance check and corresponding adaptation of the SmPC).

Market exclusivity and similarity

During the period of market exclusivity of an OMP, the similarity to the authorised OMP in terms of structure, mechanism of action and therapeutic indication must be assessed in each new marketing authorisation application (centralised, decentralised or national; with or without orphan designation) within the same rare disease (see also EMA Guideline 2008/C 242/08). If the new substance is found to be similar by the CHMP, RMS or the national agency, it can only be authorised if one of the following derogations applies: a) the agreement of the marketing authorisation holder of the already authorised medicinal product, b) supply shortages of the already authorised medicinal product, or c) if clinical superiority can be justified compared to the already authorised medicinal product.

Further information can be found on the European Commission's website on OMPs. There you will also find a link to the "Community register", in which all medicinal products with orphan drug status are listed.