OBJECTIVES: To compare the characteristics and regulatory actions of orphan drugs approved by FDA and EMA between 2000 and 2022.

METHODS: We extracted the regulatory data for the orphan and non-orphan new molecular entities and new therapeutic biologics from the FDA and EMA websites for the study period. We classified the drug using the WHO Anatomical Therapeutic Chemical Classification System. We use descriptive analysis to characterize the differences in characteristics of orphan drugs authorized by each agency.

RESULTS: The FDA approved 789 drugs of which 533 (67.6%) were also authorized by EMA in the period from implementation of the European Union Orphan Regulation in 2000 to 2022. The FDA granted orphan designation to 310 (39.3%) of the approvals, while the EMA granted such designation to 106 (20.0%) of the authorizations during the study period. EMA approved with orphan designation 9.1% (n-=6) of the orphan drugs approved by the FDA in the 2000s, 66 (40.7%) in the 2010s, and 34 (41.5%) in the 2020s. The EMA authorized with orphan designation 45 (56.8%) of the alimentary tract and metabolism, 8 (40.0%) of the blood and blood forming organs products, and 21 (30.4%) of the antineoplastic and immunomodulating agents orphan drugs approved by the FDA. Of the orphan drugs approved by the FDA, 126 (40.6%) had orphan authorization in EMA, 103 (33.2%) had non-orphan authorization, 76 (26.1%) were not listed by EMA, 7 (2.3%) were refused by EMA, 3 (1.0%) had orphan designation in EMA and not the FDA, and 2 (0.6%) applications were withdrawn by the sponsor companies.

CONCLUSIONS: The EMA authorized approximately one-third of the orphan drugs approved by the FDA due to differences in the requirements for orphan designation in both agencies, EMA's refusal of approval for certain drug applications, withdrawal of applications, and sponsor companies' decisions,