One of the key challenges in manufacturing viral vectors is to increase the ratio between empty and full capsids.
When the expression in the cell line results in less than 10% full capsid it is quite impossible to reach better than 90% full in the final product. It is therefore mandatory to optimise the USP to result in better empty/full ratio.
This can be efficiently realised by using at-line HPLC to allow for analysis of the full and empty capsids ratio directly in the harvest.
The residual empty capsids can be removed by polishing step using different anion exchange columns.