The increase in development and approvals of adeno-associated virus (AAV) gene therapies is providing promising treatment options especially for patients with rare and ultra-rare diseases with unmet medical needs. Patient dosing is dependent on the accurate quantitation of the AAV vectors and often based on the vector genome (vg) titer. PCR methods, such as qPCR and more recently ddPCR, are commonly utilized for vg titer determination, but can pose inherent challenges due to higher variability compared to concentration assays of other modalities. To ensure accurate and consistent patient dosing throughout the product life cycle, vg titer determining methods must perform comparable across all testing sites. Furthermore, inter-site comparability is vital to comply with regulatory expectations for strength determining assays, and to meet product quality and safety standards. This presentation will cover challenges encountered during a ddPCR based vg titer method transfer between testing site, insights into investigational findings, and method improvement strategies for maintaining consistency across sites.
Learning Objectives:
• Understand critical parameters of ddPCR based AAV vg titer methods contributing to result variability.
• Learn to identify and navigate site specific peculiarities to ensure comparability across sites.
• Mitigating future method transfer challenges through implementation of robustness enhancing features during method development.
