Current initiatives within the biopharmaceutical industry to adopt PAT (Process Analytical Technology) approaches in manufacturing, include activities in early process development. With adherent cell lines, online sampling for real‐time process monitoring and process adjustment is challenging due to the viscosity of the cell culture and potential blockages to sampling systems caused by microcarriers. In this study, we have tested the BioProfile® FLEX analyser and online autosampler with OPC (Open Productivity & Connectivity) for continuous feedback control of metabolite concentrations in lab‐scale bioreactors.
The first part of the study demonstrated that glutamine, glucose and glutamate consumption was dependent on cell growth phase. In the second part of the study, metabolite concentrations were analysed and controlled in the bioreactor using the OPC enabled BioProfile® FLEX analyser. Sampling was performed via sterile online sampling; allowing automated nutrient feed control. Once established on non‐viral infected cells, the system was further applied to a model of a virus (rabies) production process for 14 days. Cell culture experiments were carried out with automated sampling and analysis performed every hour to control and monitor the viral production process at Sanofi Pasteur in Lyon, France.
This study demonstrates that it is possible to effectively control and adjust (in real‐time) the required concentration of metabolites to sustain controlled cell metabolism, as viral infection and production progresses. The BioProfile® FLEX online autosampler and analyser, in conjunction with an OPC enabled bioreactor controller, provided reliable results and improved process control for development activities