Implementing a robust platform analytical procedure for measuring adeno-associated virus vector genome titer.

The vector genome (vg) titer measurement, which is used to control patient dosing and ensure control over drug product manufacturing, is essential for the development of recombinant adeno-associated virus (AAV) gene therapy products. While qPCR and droplet digital PCR technologies are commonly implemented for measuring vg titer, chromatographic techniques with UV detectors represent promising future approaches, in line with traditional biotherapeutics. Here, we introduce a novel vg titer measurement approach using size-exclusion high-performance liquid chromatography with UV detection, which achieves excellent method precision (<2% relative SD), demonstrates linearity across a range of concentrations and varied particle content, is stability indicating, and can be bridged with existing vg titer methods.