Design of Experiments for Biopharmaceutical Process Optimization

Designed experiments (DoE) is an effective statistical method that is being used within the biopharma industry to optimize complex manufacturing procedures. This chapter discusses how DoE has been used in the process development of biopharmaceuticals with its role in defining critical process parameters (CPPs) and the interactions among them to improve product quality, productivity, and process robustness. It focuses on the Quality by Design (QbD), where DoE is part of systematic process knowledge and risk management. Major experimental designs including factorial, fractional factorial, response surface methodologies (RSM) and definitive screening designs (DSDs) appropriate in diverse levels of process development, i.e., cell culture and fermentation to purification and also for formulation are discussed in the chapter. Various case studies illustrating the effective application of DoE in order to overcome a process bottleneck, help reduce a process variability, and speed process scale up and technology transfer has been provided. Besides various problems, which include model overfitting, design space constraints, and the interpretation of results, appropriate practices of effective experimental planning are also discussed. Putting DoE into biomanufacturing processes, organizations can accomplish further uniformity, regulatory conformity and economic affordability of biologics as well as biopharmaceuticals.