Orphan drug development and repurposing: regulatory and clinical perspectives from the USA (FDA), EU (EMA), and India (CDSCO)

Abstract Rare diseases affect millions of individuals worldwide, yet the development of effective treatments remains limited due to high research costs, lengthy development timelines, and small patient populations. Drug repurposing has emerged as a promising strategy to accelerate orphan drug development by utilizing existing drugs for new therapeutic indications. However, differences in regulatory frameworks, market incentives, and industry perspectives continue to influence the adoption of repurposed therapies across regions. This study examines the regulatory frameworks and market challenges associated with repurposed orphan drugs in the United States (US), European Union (EU), and India . In addition to a comparative regulatory analysis, a cross-sectional survey was conducted among pharmaceutical industry professionals in India (n = 118) to assess awareness, perceived advantages, and barriers related to drug repurposing strategies for rare diseases. Survey findings indicate a high level of awareness of drug repurposing among respondents (100%) , with 77.8% considering repurposed orphan drugs an extremely important strategy for addressing rare diseases . Most participants ( 61.1% ) described drug repurposing as a promising approach but noted the presence of development and commercialization challenges. Key barriers identified included limited market size, regulatory uncertainty, and insufficient financial incentives . Participants also highlighted the importance of regulatory flexibility, research funding, and collaboration with healthcare stakeholders in supporting repurposed orphan drug development. Overall, the findings suggest that drug repurposing represents a valuable approach for improving treatment availability for rare diseases , particularly when supported by adaptive regulatory frameworks and targeted policy incentives. Strengthening regulatory harmonization, research investment, and industry collaboration may further enhance the development and commercialization of repurposed orphan drugs.