Process Analytical Technology and Quality by Design for Animal Cell Culture

US Food and Drug Administration (FDA) issued a guidance document "PAT-A framework for innovative pharmaceutical development, manufacturing and quality assurance." After that, this strategy was further extended into the initiative of quality by design (QbD), including the concepts of creating a manufacturing knowledge base, risk management principles, process design space, and process analytical technology (PAT). The PAT and QbD approach were firstly adopted in the manufacturing processes of pharmaceuticals with low molecular weights. However, for the biopharmaceuticals, the related work is still at the initial phase and various techniques are being tested at present time for evaluating their feasibility in terms of critical requirements posed by intrinsic complexity of bioprocess. In this study, the challenges and applications of PAT and QbD and related technologies are addressed. Several case studies are included as demonstration of the PAT/QbD implementation in animal cell culture. Future direction and potential technologies, which will derisk regulatory concerns of regulatory agencies and biopharmaceutical industry, are discussed.