Have you applied PAT and do you find it is easier or more difficult in continuous? Are you able to monitor process conditions and make adjustments real time?


We’ve evaluated various PATs on continuous processes including auto-sampling systems and online probes and analyzers. Implementation of PAT is usually easier for continuous processes since we typically can develop and thus expect steady state conditions. We found PATs quite useful especially those that monitor key process parameters in real-time and others that help to identify and maintain steady state operations. One example is to use online biomass indicators (biomass probes or determination of Oxygen Uptake Rate derived from gas analyzers) to control the cell bleeding rate and therefore maintain a stable viable cell density. Another example is to use a pCO2 probe for adjusting the air sparge rate (for CO2 stripping) to keep the high pCO2 levels within the specified range – which is critical when working with high cell densities in a continuous cell culture process.

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