A systematic Quality by Design (QbD) strategy was used to develop and characterize a monoclonal antibody production process. A risk assessment approach incorporating design of experiments (DOE), especially multivariate analyses, was used to define and prioritize laboratory-scale experiments and made it possible to focus on high-risk process parameters and study the interactions of those parameters to define the design space. Scale-up/scale-down strategies, such as the effective characterization of a scale-down bioreactor model, ensured the applicability of small-scale studies, and secondary risk assessment approaches were used to ensure that various unit operations were properly integrated in the development of the design space.
Pfizer has developed a systematic approach to implementing QbD principles for process design for small molecules that encompasses process understanding, process control, and continuous improvement.4 This article explores the strategies for and challenges involved in developing a thorough process understanding and defining the design space for a monoclonal antibody manufacturing process. We briefly summarize Pfizer's strategies for systematic risk assessment to define and prioritize laboratory-scale experiments, scale-up/scale-down strategies to ensure the applicability of the small-scale studies, and secondary risk assessment approaches that integrate various unit operations.
PFIZER'S APPROACH TO QBD FOR PROCESS DESIGN
The QbD process design starts with an intensive characterization of the product through a large array of biochemical and biophysical analyses at normal and stressed conditions and through careful analysis of clinical and nonclinical data. This characterization provides the basis to define the criticality of product quality attributes (QAs), according to knowledge of safety and efficacy of the product. QA criticality is used to prioritize experiments for process understanding and is incorporated into the risk-assessment tools that are used.