(696e) PAT Applications In Recombinant Protein Production Cell Culture Processes

The regulatory agency’s intent to make Process Analytical Technology (PAT) an industry-regulatory agreement makes this a very challenging and exciting time for both the pharmaceutical and biotechnology industries. In order to achieve the desired process understanding and control, the necessary effort should be used in developing tools and applying them either in the development or industrial stages. PAT is not a new strategy for the biotechnology industry or cell culture processes. Research and process development teams have long invested resources and expertise in process understanding. Nevertheless, PAT is a unique strategy where the final process adapts in real-time has not been applied frequently. This may be due to concerns with the challenges of implementing post-market process changes or costly and complex new technologies. In recombinant protein production processes, product quality is typically determined primarily by the selected cell clone and fermentation process conditions. Thus, upstream PAT process monitoring and control strategies may significantly benefit recombinant protein production processes. Fermentation pH or pO₂ controls are examples of PAT applications that have been applied and improved in the last couple of decades. More difficult to apply PAT strategies involve new sensor technologies or complex feedback approaches. Examples of nutrient controlled feeding and innovative air sparging strategies will be described as PAT applications that permit better process understanding and product quality control.