Real-time monitoring and control of CHO cell cultures

Mammalian cell cultures are used for nearly half of biopharmaceuticals in development and production with the majority produced using Chinese Hamster Ovary (CHO) cells.  Process monitoring and control are essential for optimizing titer yield as well as for producing consistent, high quality product.  Although nutrient/metabolite quantitation are well recognized as critical quality attributes, non-destructive real-time measurement and control during upstream bioprocesses has remained elusive.  Critical criteria for such real-time, on-line monitoring have been documented and include simultaneous multi-analyte quantitation, automated and continuous operation for extended time periods, robust and repeatable performance across multiple batches, and insensitivity to normal operating conditions.  The robustness of such an on-line bioprocess monitor is assessed for the simultaneous, real-time measurement of glucose, lactate, and cell density during CHO cell cultures.  Data evaluating the accuracy and precision of these measurements over the extended run times that characterize CHO cell cultures will be shown as well as batch-to-batch performance characteristics.  Finally, ease of operation and operator expertise required will be appraised.