Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411813EnglishN2026July15Healthcare Global Regulatory Landscape of Orphan Drug Development: An Evaluation of Market Authorizations, Therapeutic Areas and Sponsor Companies     English0109Dipti Vilas SonawaneEnglish Pranjal Pramod ChaudharyEnglish Aparna BhaleraoEnglish Ajay G. PiseEnglish Rare diseases represent a significant global healthcare challenge due to their low prevalence, delayed diagnosis, limited treat ment options, and high treatment costs. Orphan drugs have emerged as an essential therapeutic approach to address these unmet medical needs; however, their development and market authorization require specialized regulatory pathways and sup portive incentives. This review provides a comprehensive overview of orphan drug development, global regulatory pathways, market authorization processes, and regulatory incentives across major regulatory authorities, including the United States Food and Drug Administration (USFDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), Therapeutic Goods Administration (TGA), and Central Drugs Standard Control Organisation (CDSCO). It further discusses the major challenges associated with orphan drug development, including clinical, regulatory, manufacturing, and market access barriers, while highlighting emerging opportunities such as artificial intelligence, gene therapy, precision medicine, and interna tional regulatory collaboration. Overall, strengthening regulatory harmonization, fostering innovation, and enhancing global col laboration are essential to improve the development, approval, and accessibility of safe and effective orphan drugs for patients with rare diseases worldwide. EnglishOrphan Drugs, Rare Diseases, Drug Development, Market Authorization, Regulatory Pathways, Regulatory Incentives, Precision Medicine, Artificial Intelligencehttp://ijcrr.com/abstract.php?article_id=4908http://ijcrr.com/article_html.php?did=4908 1. U.S. Food and Drug Administration. Rare Diseases at FDA. Available from: https://www.fda.gov/industry/developing-prod ucts-rare-diseases-conditions. Accessed on 20 May 2026 2. Rath A, Olry A, Dhombres F, Brandt MM, Urbero B, Aymé S. Representation of rare diseases in health information systems: The Orphanet approach to serve a wide range of end users. Hum Mutat. 2012;33(5):803-8. 3. Rogers HA, Sheikh HZ. The Orphan Drug Act: Legal Overview and Policy Considerations. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411813EnglishN2026July15Healthcare Amiodarone-Induced Thyrotoxicosis in a Patient Undergoing Long-Term Treatment with a Fixed Dose of Amiodarone       English1015Dominika StolarczykEnglish MaSitkoriaEnglish Introduction: This clinical case demonstrates the importance of vigilance, strict control, and monitoring of pharmacological treatment administered consistently over several years with the same drug at a fixed dose. Case presentation: The clinical case concerns a 65-year-old female patient admitted to the Internal Medicine Ward with diar rhoea and progressive weakness lasting for about 3 weeks. Her medical history included weight loss of approximately 5.5 kg in a week and subfebrile conditions up to 38.3 °C. The patient had been under the constant care of a cardiologist for several years due to non-persistent ventricular arrhythmias. She was taking a daily dose of 100 mg of Amiodarone. A Burch–Wartofsky Point Scale score of 35 indicated impending thyroid storm. Given the severity of thyrotoxicosis, the absence of a previously document ed thyroid disorder, the long duration of amiodarone exposure, and the ultrasound findings, amiodarone-induced thyrotoxicosis with a possible mixed/indeterminate phenotype was considered. Results: Amiodarone was discontinued and treatment with thiamazole 20 mg three times daily, sodium perchlorate 300 mg three times daily, and prednisone 40 mg once daily was initiated. Sodium perchlorate was stopped after 7 days because of a fall in platelet count from 351,000/µL to 162,000/µL. During hospitalization, fT3 progressively decreased and reached 7.90 pmol/L at discharge, whereas fT4 remained markedly elevated. After discharge, thyroid hormone concentrations continued to improve; 14 days later, TSH was 0.21 µIU/mL, fT3 6.9 pmol/L and fT4 75.12 pmol/L. The more than 50% reduction in fT3 and subsequent clinical improvement were considered supportive of a predominant destructive component of AIT. Thiamazole was subsequently tapered and discontinued, while prednisone was continued with gradual dose reduction. Conclusion: This case illustrates that severe AIT may occur during apparently stable long-term amiodarone therapy. The clini cal, biochemical and ultrasonographic findings suggested a mixed/indeterminate phenotype, although the subsequent biochemi cal response was more consistent with a predominant destructive component. The case also demonstrates the importance of early recognition and individualized treatment of severe AIT. Because long-term follow-up was unavailable, the subsequent thyroid status and risk of recurrence could not be established. EnglishHyperthyroidism, Thyrotoxicosis, Amiodarone, Diarrhoea, Side effects, Long-term therapyhttp://ijcrr.com/abstract.php?article_id=4916http://ijcrr.com/article_html.php?did=4916 1. 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Evaluation and treatment of amiodarone-induced thyroid disorders. J Clin Endocrinol Me tab. 2021;106(1):226-36. doi:10.1210/clinem/dgaa686. 6. Bartalena L, Bogazzi F, Chiovato L, Hubalewska-Dydejczyk A, Links TP, Vanderpump M. 2018 European Thyroid Asso ciation (ETA) guidelines for the management of amiodarone associated thyroid dysfunction. Eur Thyroid J. 2018;7(2):55-66. doi:10.1159/000486957. 7. Siddoway LA. Amiodarone: guidelines for use and monitoring. Am Fam Physician. 2003;68(11):2189-96. 8. Pazin-Filho A, de Jesus AM, Magalhães PK, Melato LH, Campos D, Maciel BC, et al. How frequently should a pa tient taking amiodarone be screened for thyroid dysfunction? Braz J Med Biol Res. 2009;42(8):744-9. doi:10.1590/S0100 879X2009000800009. 9. Meda N, Saad-Omer S, Matos M, Kinaan M. A case of ami odarone-induced thyrotoxicosis presenting with methimazole induced agranulocytosis. Cureus. 2024;16(7). doi:10.7759/ cureus.63858. 10. Medi? F, Bakula M, Alfirevi? M, Bakula M, Muci? K, Mari? N. Amiodarone and thyroid dysfunction. Acta Clin Croat. 2022;61(2):327-41. doi:10.20471/acc.2022.61.02.20. 11. Rahimi-Bashar F, Vahedian-Azimi A, Dalvand S, Karimi L, Moshkani M, Alimohamadi Y, et al. Prevalence of amiodarone induced hypothyroidism and hyperthyroidism in patients with heart diseases: a systematic review and meta-analysis. Curr Med Chem. 2023;30(23):2690-9. doi:10.2174/092986732966622083 1145651. 12. Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid hormones and cardiovascular function and dis eases. J Am Coll Cardiol. 2018;71(16):1781-96. doi:10.1016/j. jacc.2018.02.045. 13. Trohman RG, Sharma PS, McAninch EA, Bianco AC. Ami odarone and thyroid physiology, pathophysiology, diagnosis and management. Trends Cardiovasc Med. 2019;29(5):285-95. doi:10.1016/j.tcm.2018.09.005. 14. Oktaviono YH, Mustofa A, Saputra PBT, Widiarti W, Faizah NN, Alkaff FF. Exploring current diagnosis and management of amiodarone-induced thyrotoxicosis. 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Akamizu T, Satoh T, Isozaki O, Suzuki A, Wakino S, Iburi T, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012;22(7):661 679. doi:10.1089/thy.2011.0334