Smart Manufacturing Implementation of a Continuous Downstream Precipitation and Filtration Process for Antibody Purification

Recently, continuous bioprocessing has gained momentum in biomanufacturing and can alleviate many of the hurdles faced in batch or semi-batch operations. Moreover, the parallel development of smart manufacturing (SM) allows the rapid small-scale prototyping and large-scale implementation of continuous bioprocesses. With this background, this paper presents the laboratory-scale implementation of a continuous precipitation-filtration process that can ultimately be used for therapeutic protein capture purification. The experimental setup includes four static mixers, four peristaltic pumps, one hollow fiber dewatering filtration module, and multiple pressure sensors and weigh scales. The system also includes an in-line advanced microscopic particle imaging probe that provides real-time images and derived metrics of the precipitate particle morphologies and a fiber optic 880 nm optical absorbance probe. A polyclonal human serum antibody mixture (hIgG) (10 g/L) was used as a stand-in for a monoclonal antibody therapeutic along with 7 % w/v polyethylene glycol (PEG, volume exclusion agent) and 10 mM zinc chloride (cross-linking agent) as the precipitants to demonstrate the principles of operation and control of a precipitation-based process using SM technology. An integrated input/output (I/O) system was used to acquire pressure, flow rate, and weigh scale data and also to communicate with the pumps to change flow rates in real-time. Edge computers communicate with the I/O system and the imaging probe and host the software layer. The software layer enables real-time data acquisition, data-driven and first-principles model predictions, closed-loop control of precipitate particle morphology using pump flow rate of PEG, and cloud communications with the Clean Energy Smart Manufacturing Innovation Institute Smart Manufacturing Innovation Platform. The paper presents the initial results obtained with this integrated system, demonstrating the potential of SM strategies to enhance the production of life-saving biopharmaceutical products.