Optimization and scale up strategies for reproducible AAV enrichment step on CIMmultus® QA HR line

Abstract

The advancement of adeno-associated virus (AAV) gene therapy applications faces significant challenges, particularly in the separation of empty, full, and intermediate capsids during manufacturing, as well as scaling up downstream processing. This study demonstrates the effectiveness of monolithic chromatography in maintaining high flow rates without sacrificing resolution across scales, making it ideal for large-scale applications. The CIMmultus® HR columns ensure high reproducibility at various purification scales. The optimized AAV polishing method was successfully scaled up from 1 to 8000 mL monolith using step elution approach.