['To assess the methodological quality of OMP dossiers and to discuss possible reasons for the small number of products licensed.', 'Information about orphan drug designation and approval was obtained from the website of the European Commission-Enterprise and Industry DG and from the European Public Assessment Reports.', 'Out of 255 OMP designations, only 18 were approved (7.1%). Their dossiers often showed methodological limitations such as inappropriate clinical design, lack of active comparator where available and use of surrogate end-points.'] Is orphan drug development progressing too slowly?