Optimization Of Monoclonal Antibody Production Employing Noninvasive Sensor TechnologySource: Sartorius Stedim Biotech
Large scale high density fermentation and high yield production of monoclonal antibodies are major aims of process development in biopharmaceutical industry. On the other hand there is an increasing demand for highly flexible and scalable production processes adapted to lab scale single-use culture vessels, e.g. to generate sufficient material for R&D or for preclinical applications. The classical fed-batch process is characterized by three different phases: the exponential growth phase with accumulation of cell mass, the stationary phase with ongoing protein synthesis and the declining phase, when the number of viable cells decreases. Efforts in process optimization aim at the real-time monitoring of the onset of these process phases that could be followed by direct and indirect parameters (Sitton and Srienc, 2008). Novel non-invasive fluorescent probes allow the continuous detection of the pH value and dissolved oxygen (DO) saturation during cultivation of animal cells even in lab scale culture formats. This new non-invasive technology featured in SENSOLUX® stand-alone offers the opportunity to follow the effects of nutritional state and it allows the identification of starvation conditions. Aim of the present study was to monitor the effects of supplementary feeding strategies in real time in order to develop robust cultivation and production procedures in single use shaker flasks.