Thursday 18th September - Main Conference Day ThreeThursday, 18 September 2025 - ET (Eastern Time, GMT-05:00)

Recombinant adeno-associated virus (rAAV) vectors are increasingly used in gene therapy, but downstream processing remains a key bottleneck, particularly regarding viral clearance. Industry practices for rAAV viral safety are not yet harmonized, and regulatory expectations have recently evolved with ICH Q5A(R2), which now extends guidance to viral vectors. This presentation explores strategies for early-stage viral clearance studies to support rAAV development. Key elements include the selection of appropriate model viruses, leveraging prior knowledge from protein biologics and in-house data, and establishing risk-based approaches to viral burden and log reduction value (LRV) targets. We will also discuss the case study illustrates how orthogonal clearance steps—chromatography, viral inactivation, and filtration—were applied and justified using scale-down models under worst-case scenarios, achieving cumulative clearance consistent with regulatory expectations. The findings highlight the importance of early engagement with regulators, the use of helper virus systems with complementary model viruses, and the integration of prior knowledge to accelerate early-phase submissions.