Proceedings of the 2017 Viral Clearance Symposium, Session 6: Ensuring Viral Safety in Continuous Processing

Abstract

To ensure successful scale-up of continuous processing to large-scale production, it is necessary to seamlessly incorporate viral testing and clearance/inactivation into representative small-scale models. For the first time, a session devoted to the adaptation of standard viral clearance/inactivation unit operations to continuous processing was held at the Viral Clearance Symposium (VCS), with an emphasis on design of valid small-scale models. In this session, the presentations and subsequent discussions identified challenges as well as pathways forward for these emerging technologies. In the first two talks, two different strategies on how to validate continuous low pH viral inactivation (VI) were discussed, focusing on molecule stability and XMuLV inactivation kinetics in the lower residence times of continuous manufacturing, in addition to mathematics-based modeling of continuous viral inactivation processes. The third talk in the session presented a strategy to adapt weak anion exchange chromatography to a continuous manufacturing process by taking advantage of the elution pulses from bind and elute chromatography. The final and fourth talk provided data from novel spiking strategies in consideration of the high, but fluctuating, product titers in the context of continuous flow encountered in continuous manufacturing processes.

LAY ABSTRACT: To ensure successful scale-up of continuous processing to large-scale production, it is necessary to seamlessly incorporate viral testing and clearance/inactivation into representative small-scale models.

For example, in this session, strategies to validate continuous low pH viral inactivation were discussed.

In addition, data from novel spiking strategies in consideration of the high, but fluctuating, product titers in the context of continuous manufacturing processes were presented.