Control of Continuous Manufacturing Processes for Production of Monoclonal Antibodies

This chapter aims to put forth a range of examples for continuous control of the most commonly used unit operations in manufacturing of monoclonal antibodies (mAbs). Continuous manufacturing of biotherapeutics is currently of significant interest to both academic and industrial groups in the biotherapeutic industry. The chapter focuses on surge tanks, which are key in-process vessels placed strategically between individual unit operations to allow constant flow throughout the continuous process. It draws on Chinese hamster ovary (CHO) cell expression system, which is the current workhorse of mAb production. Various case studies have been published on monitoring and control of continuous capture chromatography using a range of analytical tools. Viral inactivation is a critical step in mAb manufacturing as most processes use CHO cells that are susceptible to contamination by adventitious viruses. Artificial Intelligence tools include expert systems, fuzzy approach, neural networks, case-based reasoning, genetic algorithms, or ambient intelligence.