VIRAL CLEARANCE CONSIDERATIONS FOR CONTINUOUS VIRAL INACTIVATION

摘要

Continuous low pH viral inactivation has been considered by Boehringer Ingelheim, Pfizer, and other companies who are investing in integrated processing. In continuous viral inactivation, a critical parameter that poses a new challenge is the exact incubation time of the product stream. In a continuous space, the concept of time translates in the product flow rate, incubation volume, and dispersion effects. To address dispersion, we define the minimum residence time, tmin, as the time when the first product element exits the tubular chamber. In this work, we characterize the tmin for a novel, scalable, and sturdy tubular reactor design that can serve as an incubation chamber for a process capable to produce >1 kg of product. In addition, we provide robust data for a scale down model suitable for viral studies. We propose an innovative in-line spiking methodology to validate the minimum residence time using viruses. This methodology can be used as a viral clearance platform for continuous low pH virus inactivation. Finally, we propose a trace response method to be used as a way to verify that the process was properly set up.