Accelerating Characterization of a Biomanufacturing Process Using a New DOE Approach: Definitive Screening Designs

Process characterization is an important step in Quality by Design (QbD). Traditionally, a bioprocess is characterized using a two-step approach involving factor screening designs followed by response surface designs. This approach is very costly and time consuming since it requires a significant number of runs. Jones and Nachtscheim (2011) introduced a new class of efficient experimental designs referred to as Definitive Screening designs that can allow factor screening as well as the estimation of quadratic effects and two-way interactions within a single experiment. 

In this study Quality by Design principles were used to characterize a fermentation biomanufacturing process. Using scientific and process knowledge, potential critical and key process parameters were determined during failure mode and effect analysis (FMEA) exercise. Six parameters were determined to have a possible impact on product quality and process performance. A definitive screening design was employed to describe the effects of the six input process parameters on biomass and titer production, and product quality. This design required only 15 experimental runs to accomplish both screening and response surface design through a single set of experiment. The design provides substantial cost and time savings over more traditional experimental approaches, and hence can accelerate the characterization of biomanufacturing process. Details of the model construction and results will be covered in this talk.