A QbD Approach in the Development and Scale-Up of Mixing Processes

Abstract

Mixing processes are complex, multifaceted in nature, and require understanding of fluid dynamics. The relationship between the design of the equipment and solution properties influences the process performance, which in turn impacts the product quality attributes. In this chapter, it is demonstrated through the mock case study how Quality by Design (QbD) elements could be applied to understand all issues and variables characterizing mixing processes and physical properties of the fluid prior to determining optimal operational conditions. Determining optimum operating conditions at production scale is not desirable as it is expensive and time consuming. In this case study, dilution of X-mAb bulk drug substance with diluent/buffer to produce bulk drug product has been chosen to illustrate the mixing characterization study design to identify operating conditions at pilot scale (50 L). The use of models for scale-up coupled with the data obtained at 50 L scale is used to predict operating conditions at the 300 L scale.