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.