The Challenge of Validating a Viable Biomass Probe for cGMP Processes
Live cell concentration is one of the most critical parameters to monitor in any bioreactor. Capacitance based biomass probes have become the standard in processes for on-line viable cell density. If a capacitance based probe is being used in a cGMP facility for critical decisions or process control it is essential to verify the performance of each probe prior to a production run. Capacitance probes cannot be simply verified against known standards of viable biomass and there are no suitable national standard capacitance solutions or suspensions that are representative of the large capacitance values recorded during a cell culture process. In some high density processes where the cells are grown on carriers, or in a fixed bed, values in excess of 108 cells/ml and 100 pF/cm have been recorded. We present a novel device and method for validating a viable biomass probe used with an Aber Biomass Monitor that provides a range of capacitance and conductivity values similar to those experienced in cell culture. The device developed by Aber Instruments has been termed the “Capacitance Standard Reference Port” or CSRP. It uses an electrical method to generate the capacitance signature and thus avoids the handling of biological material. This method will allow rigid procedures to be developed for thoroughly testing the biomass probe for a range of cell culture environments prior to use in a cGMP process.