Protein Refinery Operations Lab (PRO Lab): A Sandbox For Continuous Protein Production & Advanced Process Control
Abstract
Significant strides towards implementation of continuous bioprocessing are being made at an ever increasing rate. Advances in technology for traditional unit operations such as cell-retention devices in perfusion cell culture, continuous multi-column chromatography (CMCC) and single-pass tangential flow filtration have led to demonstrations of both semi-continuous and fully-continuous protein production processes operating at periodic steady states at the pilot-scale. Previous proof of concept work at Merck & Co., Inc. has shown an automated (DeltaV) and single-use monoclonal antibody (mAb) purification scheme through Protein A CMCC and pH viral inactivation with minimal human interaction for 30 days fed from a perfusion bioreactor1. This automation scheme has since been expanded to encompass an integrated mAb upstream and platform downstream process, resulting in an entirely automated ‘protein refinery’ sandbox.
In this presentation a vision for a continuous bioprocessing facility of the future will be presented wherein the integration of Process Analytical Technologies (PAT), Multivariate Data Analysis, (MVDA), and feedback control strategies will lead to more streamlined plant operations and high product quality consistency. A discussion of how the control strategies put into place in PRO Lab lays the groundwork for this vision and how PRO Lab will be used to pilot PAT, MVDA, and feedback control as they become mature enough for integration into the continuous platform will be provided. These tools, working together, and validated in the sandbox environment, will ultimately enable real-time-release of drug substance. PRO Lab will also enable better holistic process understanding by enabling perturbation analysis and propagation throughout the production line. Process and product quality consistency data through a period of >30days will be presented from PRO Lab as an initial step towards toward the ultimate vision of an automated well-controlled, well characterized protein refinery.