The demand of high-throughput approaches in biopharmaceutical for process development are increasing. Development of a robust biopharmaceutical manufacturing process plays an important role in early phase development, which leads to a shorter time scale for antibody production. However, technical challenges beneficially met by obtaining more process performance knowledge during development. The Computational Fluid Dynamics (CFD) techniques are increasingly used to predict and optimize the performance of these high-throughput approaches. Several choices of input parameters in this process results in more simulation. The design of experiments (DOE) approach helps to optimize the performance of development over a complete range of design. In this study, a DOE-based CFD approach has been used to optimize the process development.