Bioreactor control systems in the biopharmaceutical industry: a critical perspective

Industrial-scale bioprocessing underpins much of the production of pharmaceuticals, nutraceuticals, food, and beverage processing industries of the modern world. The profitability of these processes increasingly leverages the economies of scale and scope that are critically dependent on the product yields, titers, and productivity. Most of the processes are controlled using classical control approaches and represent over 90% of the industrial controls used in bioprocessing industries. However, with the advances in the production processes, especially in the biopharmaceutical and nutraceutical industries, monitoring and control of bioprocesses such as fermentations with GMO organisms, and downstream processing has become increasingly complex and the inadequacies of the classical and some of the modern control systems techniques is becoming apparent. Therefore, with increasing research complexity, nonlinearity, and digitization in process, there has been a critical need for advanced process control that is more effective, and easier process intensification and product yield (both by quality and quantity) can be achieved. In this review, industrial aspects of a process and automation along with various commercial control strategies have been extensively discussed to give an insight into the future prospects of industrial development and possible new strategies for process control and automation with a special focus on the biopharmaceutical industry.