The causes are related to adherence to European Medicines Agency guidelines and the size of the laboratories developing these drugs. This study retrospectively compares marketing authorisation applications for orphan medicinal products versus applications for products without this designation that have been submitted by the European Medicines Agency (EMA), through its centralised procedure, between 2000 and 2013, i.e. during the first 14 years of the existence of the orphan drug regulatory framework in the European Union. All authors are directly linked to the EMA, except two of them, who belong to CeMSIIS (Centre for Intelligent Systems, Medical Informatics and Statistics) at the Medical University of Vienna.