Ranking bioprocess variables using global sensitivity analysis: a case study in centrifugation

The selection of appropriate operating conditions for bioprocessing is complex due to the large number of interacting stages and variables. Bioprocesses also operate under tight regulation and therefore tools to assist bioprocess design are of significant utility. Conventional approaches for the analysis of variable sensitivities are inadequate. We propose the use of global sensitivity analysis to determine the level of importance of each variable and their interactions. Once key variables have been determined, the designer may focus on the most significant subset. Two case studies are used to demonstrate the applicability of the approach. Each is based on centrifugation and determines the impact of flow-rate, feed viscosity, density difference and particle size, while performance is assessed by supernatant clarification. Significant differences in sensitivities were found between the two studies due to the different feed material properties. Variable sensitivities were found to be system-specific and provide insight for potential operating strategies.