Regulatory path transitioning from transient to stable cell lines for AAV manufacturing

AAV manufacturing is transitioning from transient transfection to stable producer cell lines for improved scalability and cost–effectiveness. This framework addresses regulatory considerations for implementing this manufacturing change during clinical development. Risk assessment encompasses technical, regulatory, and business factors. Early-stage transitions pose lower risks with safety-focused comparability studies, while late-stage changes require extensive data addressing both safety and efficacy. Key recommendations include comprehensive cell line characterization with genetic stability evaluation, leakiness assessment, and tier-based acceptance criteria. Master cell bank testing should monitor cell viability, expression levels, titer, and capsid ratios through stability studies. Proactive regulatory communication with agencies like FDA’s CBER is essential for successful implementation, particularly for late-stage manufacturing changes, to ensure regulatory approval while maintaining product quality.