Abstract:

Rare diseases affect millions worldwide, yet treatment options remain limited, especially in developing countries. This study conducts a comprehensive comparative analysis of orphan drug regulatory frameworks in the United States, European Union, Japan, and India, aiming to identify best practices and propose adaptations for India's evolving rare disease landscape. Through extensive literature review, regulatory document analysis, and cross-country comparisons, we examined key aspects including legislative frameworks, regulatory bodies, incentive structures, clinical trial requirements, and post-approval monitoring. Findings reveal significant disparities between established markets and India, with the latter lacking a formal orphan drug act, specialized regulatory bodies, and robust incentive structures. The study proposes strategic recommendations for enhancing India's rare disease and orphan drug ecosystem, including establishing a clear legislative framework, implementing market exclusivity incentives, creating dedicated regulatory structures, and developing flexible clinical trial requirements. Additionally, we suggest leveraging public-private partnerships, digital health initiatives, and addressing ethical considerations to improve rare disease management. By adapting international best practices to its unique healthcare context, India can bridge the gap in orphan drug availability and rare disease management. This research provides a roadmap for policymakers and stakeholders to enhance India's approach to rare diseases, potentially positioning the country as a leader in orphan drug development in the developing world.

References:

[1].   Nguengang Wakap, S., et al., 2020, Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. European Journal of Human Genetics, 28(2), 165-173.

[2].   Rajasimha, H. K., et al., 2014, Organization for rare diseases India (ORDI) - addressing the challenges and opportunities for the Indian rare diseases' community. Genetics Research, 96, e009.

[3].   Sharma, A., et al., 2010, Orphan drug: Development trends and strategies. Journal of Pharmacy and Bioallied Sciences, 2(4), 290-299.

[4].   Gammie, T., et al., 2015, Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries. PLoS One, 10(10), e0140002.

[5].   Bhattacharya, S., et al., 2016, Rare diseases in India: current knowledge and new possibilities. Proceedings of the Indian National Science Academy, 82(4), 1183-1187.

[6].   Choudhury, M. C., Saberwal, G., 2019, The role of patient organizations in the rare disease ecosystem in India: an interview based study. Orphanet Journal of Rare Diseases, 14(1), 117.

[7].   Ministry of Health and Family Welfare, Government of India, 2021, National Policy for Rare Diseases 2021.

[8].   Orphan Drug Act of 1983, 1983, Pub. L. No. 97-414, 96 Stat. 2049.

[9].   European Parliament and Council of the European Union, 2000, Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products. Official Journal of the European Communities, L18, 1-5.

[10].  Sakushima, K., et al., 2021, Effectiveness of the Orphan Drug Act in Japan: evaluating the first decade of legislation. Drug Discovery Today, 26(4), 1040-1046.

[11].  Ministry of Health and Family Welfare, Government of India, 2019, New Drugs and Clinical Trials Rules, 2019. The Gazette of India: Extraordinary, Part II, Section 3, Sub-section (i).

[12].  Seoane-Vazquez, E., et al., 2008, Incentives for orphan drug research and development in the United States. Orphanet Journal of Rare Diseases, 3, 33.

[13].  Mariz, S., et al., 2016, Worldwide collaboration for orphan drug designation. Nature Reviews Drug Discovery, 15(6), 440-441.

[14].  Nagao, T., et al., 2017, Recent development of orphan drug regulation in Japan. Drug Information Journal, 51(5), 653-659.

[15].  Coté, T., et al., 2010, Orphan products: an emerging trend in drug approvals. Nature Reviews Drug Discovery, 9(1), 84-85.

[16].  Fregonese, L., et al., 2018, Demonstrating significant benefit of orphan medicines: analysis of 15 years of experience in Europe. Drug Discovery Today, 23(1), 90-100.

[17].  Murakami, M., Narukawa, M., 2016, Matched analysis on orphan drug designations and approvals: cross regional analysis in the United States, the European Union, and Japan. Drug Discovery Today, 21(4), 544-549.

[18].  Miller, K. L., Lanthier, M., 2016, Trends in orphan new molecular entities, 1983-2014: half were first in class, and rare cancers were the most frequent target. Health Affairs, 35(3), 464-470.

[19].  Giannuzzi, V., et al., 2017, Failures to further develop orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs. BMJ Open, 7(9), e017358.

[20].  Day, S., et al., 2018, Recommendations for the design of small population clinical trials. Orphanet Journal of Rare Diseases, 13(1), 195.

[21].  Rajasimha, H. K., et al., 2018, Policy recommendations for rare diseases in India: a patient-centered approach. Current Science, 115(6), 1052-1055.

[22].  Fonseca, D. A., et al., 2019, Orphan drugs: major development challenges at the clinical stage. Drug Discovery Today, 24(3), 867-872.

[23].  Gupta, S. K., 2013, Pharmacovigilance: current status and future challenges. Indian Journal of Medical Specialities, 4(1), 1-4.

[24].  US Food and Drug Administration, 2023, Orphan Drug Act Report 2023.

[25].  European Medicines Agency, 2024, Orphan Medicines Figures 2000-2023. EMA/165575/2024.

[26].  Japan Pharmaceutical Manufacturers Association, 2023, Orphan Drug Development in Japan: 2023 Update. JPMA Report.

[27].  Choudhury, M. C., Saberwal, G., 2021, Rare disease research and development in India: present status and future prospects. Journal of Genetic Engineering and Biotechnology, 19(1), 49.

[28].  Dunkle, M., et al., 2010, Advocacy groups and their role in rare diseases research. Advances in Experimental Medicine and Biology, 686, 515-525.

[29].  Kuribayashi, R., et al., 2021, Regulation of orphan drugs in Japan: current status and future perspectives. Clinical Therapeutics, 43(1), 108-117.

[30].  Yin, W., 2008, R&D policy, agency costs and innovation in personalized medicine. Journal of Health Economics, 27(5), 1294-1309.

[31].  Papaluca, M., et al., 2015, White spots in pharmaceutical pipelines-EMA identifies potential areas of unmet medical needs. Nature Reviews Drug Discovery, 14(12), 829-830.

[32].  Nishikawa, A., et al., 2021, Evaluation of the Orphan Drug Program in Japan: a focus on factors associated with development success. Drug Discovery Today, 26(6), 1425-1430.