Author Archives: Naveenganesh Muralidharan

Shear-Proof Design Space: Scaling Stirred-Tank Bioreactors for Cell Culture Processes

Establishing a cell culture process across different scales and models of bioreactors involves maintaining constant scale-independent parameters such as pH, temperature, and dissolved oxygen (DO). However, nonlinear and scale-dependent criteria (impeller agitation and gas flow rates) are adjusted on the basis of multiple normalized engineering parameters to accommodate the geometrical and design differences among bioreactors (1–3). Normalized engineering approaches for scaling parameterization often are based on the shear generated by impeller speed and gas flow rates. Kinetic energy transmitted into…

Statistical Method for Establishing Control Limits for Nonnormal Data Distribution: Focus on Continued Process Verification Monitoring

According to the US Food and Drug Administration’s (FDA’s) process validation guidance, critical quality attributes (CQAs) and critical process parameters (CPPs) are used to assess the statistical stability of a bioprocess and its ability to meet acceptable criteria as a part of a continued process verification (CPV) program using control charts (1). For those control charts, control limits are used to assess the statistical stability of process parameters and attributes. When data are normally distributed, control limits are established straightforwardly…