Abstract
Lab-scale purification and formulation of recombinant adeno-associated viruses (rAAV) is a critical and time-sensitive step in gene therapy development. Ultrafiltration and diafiltration (UF/DF) are required to concentrate purified viral particles and exchange them into a compatible buffer. Traditional approaches, however, present significant trade-offs. Dead-end filtration (DEF) units are widely used at the lab scale but suffer from low filtration rates, manual handling, and manual process monitoring. Conventional tangential flow filtration (TFF) systems, while more efficient, are impractical at lab scale due to high hold-up volumes.
The µPulse performed faster diafiltration compared to DEF units
This study evaluated the µPulse, a miniaturized TFF system, for single-step automated formulation of rAAVs. Compared to DEF units, the µPulse reduced diafiltration and the hands-on time by 67 and 50%, respectively, while delivering viral yields comparable to those achieved with DEF. The weight-based automated volume control of the µPulse eliminates the risk of over-concentration that arises from manual volume monitoring in DEF workflows. Moreover, integrated real-time data logging throughout each run enables process optimization and supports process documentation, traceability, and technology transfer. These results establish the µPulse as a fast, gentle, automated, and data-rich platform for rAAV formulation, with direct applicability to gene therapy discovery and lean manufacturing operations.