Real Time Process Monitoring in Biologies Development

摘要

Real time monitoring of biopharmaceutical process development has evolved significantly in recent years with the advancement of analytical technologies, cyber-physical systems and advanced-data interrogation tools. Robust platforms for ensuring consistent product quality through Quality by Design (QbD) approaches are becoming a necessity as biologic drugs gained popularity over the last decade. As defined by the International Conference of Harmonization, QbD is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.4 A holistic understanding of the development process is a key prerequisite for designing a QbD roadmap where appropriate analytical technologies and cyber-physical systems must be deployed for real time monitoring of critical product quality attributes (CQAs), critical process parameters (CPPs) at critical control points (CCPs). Per ICH definition, a CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Whereas a CPP is a process parameter that affects CQAs and the critical unit operations at which product quality attributes should be monitored are defined as CCPs. Real time monitoring of bioprocesses involves integration of process analytical sensors, data management, visualization, and advanced data analytics such as machine learning and deep learning (Figure 1).