Globalization of orphan drug development: integrating science, regulation, and access

Enrico Costa

Research output: ThesisDoctoral thesis 2 (Research NOT UU / Graduation UU)


This thesis explores the current and future challenges of orphan drugs from a global perspective. The thesis aims to investigate the impact of orphan legislation, regulatory decision-making, and pharmaceutical policies on the development, approval, and access to orphan drugs from a global outlook. Through the lens of autosomal genetic diseases originating from south to north, i.e. hemoglobinopathies, and from north to south of the world, i.e. cystic fibrosis, we focused our analyses on the different phase of the lifecycle of medicines, analyzing: i) the orphan drug development evolved in the United States (US) and the European Union (EU) regulatory space; ii) differences in the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regulatory decision-making for marketing authorization; iii) the global implications of orphan legislation in global health prioritization; iv) the impact of the above on global access. We found that advances in genetics and pathophysiology have provided a major contribution to rare disease diagnosis, comprehension, and treatments. However, after decades of neglect, it was with the passing of Orphan legislation in the global North, that drug discovery and development strategies for rare diseases have dramatically progressed. By exploring the current and future challenges of orphan drugs from a global perspective, we observed a seismic shift of orphan drugs towards the Global South, thus identifying two main domains: (1) the impact of globalization on the geographical distributions of diseases, and (2) the rising interest of the WHO community in rare diseases. The availability of new effective treatments for such diseases poses, however, major challenges in terms of accessibility in low-income countries. Although we observe an increased uptake of orphan drugs in the WHO Essential Medicines List, prioritizing high-priced medicines for treating small populations remains a source of profound debate within the international community. In our analyses, we described the need for strengthening, the whole health and pharmaceutical system. Although treatments are considered the last step in the long journey of patients to care, the availability of new medicines can boost awareness and literacy, so setting grounds for diagnostic facilities and then therapeutics management. By providing preliminary evidence on the potentiality of improving clinical trial capacity and local manufacturing, we confirmed how establishing a strong reliable regulatory system is the game-changer to improving access in low-income countries, including medicines for rare diseases. Future research should provide further insights on global regulatory harmonization to improve access to medicines for rare diseases across the World. 
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Utrecht University
  • Leufkens, Bert, Supervisor
  • van den Ham, Rianne, Co-supervisor
Award date15 Jul 2024
Place of PublicationUtrecht
Print ISBNs978-94-6473-523-9
Publication statusPublished - 15 Jul 2024


  • Globalization
  • Orphan drugs development
  • Regulation
  • Access


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