Real-time monitoring and control of upstream bioprocesses

Continuous, real-time measurement and control of key chemicals (e.g. glucose) is an important advance in the development and manufacture of a wide range of bioproducts, including biologics as well as consumer and industrial products.   Upstream processes are, by their very nature, complex multicomponent environments that are continuously changing throughout the growth and expression phases.  The ability to quantitate key chemicals in real time is essential to the continuous control and optimization of these dynamic processes.  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 (agitation rates, pH changes, etc.).  Data from such a robust on-line bioprocess monitor is presented for industrial processes using mammalian cells as well as yeast-based expression platforms.  Results from CHO fed batch runs illustrate these critical performance criteria for simultaneous, real-time measurements of glucose and lactate concentration for runs in excess of 400 hours.  Bioprocess monitor performance across multiple batches conducted over several months will be shown.  Likewise, results from protein expression using the yeast Pichia pastoris demonstrate the reliable, accurate measurement of glycerol and methanol during more than a year of operation in bioprocess development.  In contrast with some previous approaches, the measurement is completely nondestructive and requires no expertise and very little operator time.