Abstract
The advent of gene therapies and Chimeric Antigen Receptor (CAR)-T cell products represents a paradigm shift in modern medicine, offering curative potential for previously intractable genetic disorders and cancers. However, their complex biological nature, personalized manufacturing processes, and unique safety profiles, including risks of cytokine release syndrome and insertional mutagenesis, present significant regulatory challenges. This article provides a comprehensive analysis of the global regulatory frameworks governing these advanced therapies, comparing the expedited pathways and requirements of major agencies including the US FDA (e.g., RMAT designation), European EMA (e.g., ATMP Regulation, PRIME), Japan's PMDA (e.g., Sakigake), and emerging regulators in India (CDSCO) and China (NMPA). Through detailed case studies of landmark therapies such as the successful approvals of Luxturna and Kymriah, the commercial failure of Glybera, and the cost-effective model of India's indigenous NexCAR19 the review identifies critical success factors and common pitfalls in development and commercialization. It further explores the regulatory hurdles facing next-generation "off-the-shelf" allogeneic CAR-T therapies, which, while promising greater scalability and lower costs, introduce new concerns regarding graft-versus-host disease and gene-editing risks. The analysis concludes that the future of this field hinges on the development of adaptive, harmonized regulatory strategies that can keep pace with innovation. Key recommendations include the global standardization of Chemistry, Manufacturing, and Controls (CMC) requirements, the adoption of innovative clinical trial designs for small patient populations, and the implementation of outcome-based pricing models to ensure these groundbreaking treatments are not only safe and effective but also accessible and affordable worldwide.