Orphan designation: status for medicines for rare conditions

Regulation (EC) No 141/2000 sets the criteria in Article 3. The product must be intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in ten thousand people in the Union, or a condition for which marketing would not generate sufficient return to justify the investment, and there must be no satisfactory method authorised in the Union, or the product must be of significant benefit to those affected. The sponsor applies to EMA before submitting the marketing authorisation application; the Committee for Orphan Medicinal Products (COMP) gives an opinion and the European Commission grants the designation.

Designation brings access to protocol assistance, which is scientific advice at reduced fees, fee reductions for the marketing authorisation application and for post-authorisation procedures, access to the centralised procedure, and, on authorisation, ten years of orphan market exclusivity under Article 8, during which no similar medicinal product for the same indication can be authorised unless an exception applies. The exclusivity extends to twelve years where the paediatric investigation plan has been completed. Designation can be withdrawn if the criteria are no longer met, and the COMP checks them again at the time of the marketing authorisation.

The prevalence calculation is the heart of the application. It has to rely on published epidemiology for the Union, be expressed as the number of people living with the condition at the time of application, and cover the whole condition rather than a subset created to fit the threshold. Significant benefit, where a treatment already exists, must be argued with data or a justified expectation of clinically relevant advantage.

What goes wrong: prevalence estimates built on incidence or on non-EU data; conditions defined by response to the product rather than by medicine; a designated indication that later differs from the authorised indication, so the exclusivity covers less than planned; and failure to reconfirm the criteria at authorisation, when a new treatment authorised in the meantime raises the bar for significant benefit.

Under the new pharma package (not yet in force), orphan market exclusivity becomes nine years as standard, eleven for products addressing a high unmet medical need and four for products authorised on bibliographic data; see exclusivity changes.