Continuous, real-time measurement and control of key chemicals (e.g. glucose and lactate) is an important advance in the development and manufacture of a wide range of bioproducts, including biologics as well as consumer and industrial products. The driving goal for the development of these technologies, in addition to enhanced process efficiency, is consistent product quality through discovery, process development, scale up, and manufacturing. These processes are, by their very nature, complex multicomponent environments and the ability to quantitate key chemicals in real time during upstream processing is essential to the continuous control and optimization of these dynamic processes. Critical criteria for such real-time, on-line monitoring have been well 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.). A novel on-line bioprocess monitor is presented for the simultaneous, real-time measurement of key analytes during recombinant protein production during upstream bioprocesses. This automated monitor uses a completely sealed and sterilized closed loop to continuously circulate a small sample from the bioreactor, through the monitor, and back to the bioreactor. There is zero sample lost from monitoring and the measurement method is completely nondestructive. In contrast with some previous approaches, very little operator expertise is required and long-term stability without repeated calibration is demonstrated. Data from this robust on-line bioprocess monitor is presented for multiple CHO processes and direct run-to-run comparison. Results from these CHO fed batch runs illustrate the critical performance criteria required for simultaneous, real-time measurements of glucose and lactate concentration. Additionally, the ability of the monitor to maintain closed-loop feedback control at multiple concentration set points will be presented.

Process analytical technology solutions for real-time monitoring and control of CHO bioprocesses

251st National Meeting (2016)

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