Abstract

Commercial manufacture of AAV vector-based gene therapies for ultra-rare indications faces a distinctive economics: patient populations below 500 globally, yet CMC expectations calibrated for commercial-scale biologics. This paper reviews the process intensification, analytical characterisation, and comparability protocols that recent approvals have relied on, and quantifies the cost-of-goods trajectory across three sponsor case studies. We argue that shared manufacturing platforms and adaptive CMC frameworks are essential to sustain therapy access for indications below 100 patients per year.