Autonomous operation and quality monitoring of a continuous antibody downstream process.

The transition from batch-wise to integrated continuous manufacturing of biopharmaceuticals has gained significant attention over the past decade. While this concept has been thoroughly studied, there remains significant room for improvement in terms of process automation and real-time monitoring. This study showcases the implementation of an integrated downstream process at a lab scale, operating continuously and autonomously. The purification process included solvent/detergent-mediated virus inactivation in a packed bed reactor, Protein A capture via a three-column periodic counter-current chromatography process with UV-based loading, and a mixed-mode chromatography polishing step in flow-through mode. Support systems for at-line automated sample collection and high-performance-liquid chromatography analysis for near-real-time quality monitoring, along with autonomous buffer management, were introduced. The process operated for over five days, with two disturbances introduced: decreased capture column capacity and increased harvest titer. The high level of automation and control allowed the process to adapt to these disturbances. Throughout the run, the product was sampled, and quality analyses were performed, achieving an average monomer content of >98.5 % and an overall yield >90 %. This study demonstrates the feasibility of introducing autonomous integrated continuous downstream processes at a lab scale, enabling users to concentrate on process and control development.