Conclusion

We have successfully demonstrated a next generation continuous purification process for a 14-day operation with bioburden control. The PAK automated system for continuous purification provided the automation control, automation hardware and single-use assemblies required. Advanced control strategies controlled flow from one step to the next and the mass flow rate of the entire process. The control parameters were continuously monitored and set to alarm when limits were reached. No additional automation control or SCADA system was required to perform this work. Automation used was 21CFR Part 11 compliant and all product contact materials met or exceeded USP Class VI specifications. The Low pH continuous viral inactivation method used in this process was supported by off-line virus spiking studies and results are comparable to the batch process. Batch chromatography studies supported the dual column operations performed in the continuous process. Additional studies are required to confirm viral filtration efficacy at the reduced flow rates used in the continuous process. The technology presented enables implementation of continuous fully integrated processes at scales up to 200L of cell culture material per day, which is a significant step towards good manufacturing practice (GMP) implementation of end-to-end continuous purification processes.