Typical bioprocess comprises of different unit operations wherein a near optimal environment is required for cells to grow, divide, and synthesize the desired product. However, bioprocess control caters to unique challenges that arise due to non-linearity, variability, and complexity of biotech processes. This article presents a review of modern control strategies employed in bioprocessing. Conventional control strategies (open loop, closed loop) along with modern control schemes such as fuzzy logic, model predictive control, adaptive control and neural network-based control are illustrated, and their effectiveness is highlighted. Furthermore, it is elucidated that bioprocess control is more than just automation, and includes aspects such as system architecture, software applications, hardware, and interfaces, all of which are optimized and compiled as per demand. This needs to be accomplished while keeping process requirement, production cost, market value of product, regulatory constraints, and data acquisition requirements in our purview. This article aims to offer an overview of the current best practices in bioprocess control, monitoring, and automation.
Surge tanks are critical but often overlooked enablers of continuous bioprocessing. They provide multiple benefits including dampening of concentration gradients and allowing process resumption efforts in case of equipment failure or unexpected deviations, which can occur during a continuous campaign of weeks or months. They are also useful in enabling steady‐state operation across a continuous train by facilitating mass balance between unit operations such as chromatography which have periodic loading and elution cycles. In this paper, we propose a design of a system of surge tanks for a monoclonal antibody (mAb) production process consisting of cell culture, clarification, capture chromatography, viral inactivation, polishing chromatography, and single‐pass ultrafiltration and diafiltration. A Python controller has been developed for robust control of the continuous train. The controller has four layers, namely data acquisition, process scheduling, deviation handling, and real‐time execution. A set of general guidelines for surge tank placement and sizing have been proposed together with process control strategies based on the design space of the individual unit operations, failure modes analysis of the different equipment, and expected variability in the process feed streams for both fed‐batch and perfusion bioreactors. The control system has been successfully demonstrated for several continuous runs of up to 36 h in duration and is able to leverage surge tanks for robust control of the continuous train in the face of product variability as well as process errors while maintaining critical quality attributes. The proposed set of strategies for surge tank control are adaptable to most continuous processing setups for mAbs, and together form the first framework that can fully realize the benefits of surge tanks in continuous bioprocessing.
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