Filter preconditioning enables representative scaled-down modelling of filter capacity and viral clearance by mitigating the impact of virus spike impurities

Navid Z Khan, Joseph J Parrella, Paul W Genest, Michael S Colman
Biotechnology and Applied Biochemistry 2009, 52 (Pt 4): 293-301
Endogenous and adventitious virus removal by size-exclusion membrane filtration is a critical dedicated step in an overall viral clearance strategy employed by biologics manufacturers as required by industry regulators. However, the addition of impurities from virus spike preparations used in validation studies can significantly reduce filter capacity, resulting in an oversized and suboptimal virus filtration step. The hydraulic filter performance and virus retention observed in conventional scaled-downed validation models may not necessarily represent performance observed during process development, nor be predictive of manufacturing performance. Using filter flow decay as a relevant processing endpoint, an alternative and more comprehensive approach to virus filter validation has been developed to overcome the limitations imposed by virus spike impurities. With a model feedstream, we have demonstrated comparable virus removal using the conventional virus spiking approach and a complementary preconditioned virus challenge. Similar to a currently accepted method used in the validation of sterilizing-grade filters, this method entails processing non-spiked feed to a volumetric throughput target, followed by processing virus-spiked feed to a final flow decay endpoint to determine viral clearance. This comprehensive approach yields predictive virus retention data under protein-dominant fouling conditions that better model the hydraulic performance of the manufacturing-scale virus filtration operation.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"