The inactivation of virus contaminants can be achieved by subjecting the bioprocess fluid to conditions that denature the virus protein but not the active ingredient. In the production of biologic therapies, the two most commonly employed inactivation methods are the use of low pH or addition of detergents. The efficiency of these processes is clearly linked to the effectiveness of mixing, to bring the virus quickly into intimate contact with the denaturant, and the hold time at these conditions. Deactivation with detergents is more common in blood plasma processing, whereas low pH inactivation is more frequently applied to mAb processing. In the latter case, a low pH hold of 1 hour at a pH of 3.5 is typically applied and is effective against enveloped viruses.
Pall has developed automated system technology that enables the viral inactivation at low pH to be carefully controlled in either a single-use batch or a single-use continuous mode. The Allegro™ MVP single-use system can be used in combination with Pall single-use mixing technology over a range of batch volumes to provide an automated solution for acid and base dosing, ensuring pH control that will inactivate viruses whilst avoiding denaturing conditions for the mAb.
Virus Inactivation in Continuous Bioprocessing
For small batch or continuous bioprocessing, we have developed the Cadence™ Virus Inactivation System. The system employs two parallel mixers and recirculation loops that work synchronously and alternately so that one set is involved in the low pH viral inactivation step, whilst the other is filling with bioprocess fluid. The system is specifically designed so that it can work with the elution from an upstream continuous capture chromatography step and can also operate in batch mode.
Cadence Virus Inactivation System
The Cadence Virus Inactivation (VI) system is a fully automated system that provides the ability to perform low pH virus inactivation to an incoming elution stream continuously, with minimal operator involvement.