Advanced continuous upstream manufacturing of biotherapeutics

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Project Summary/Abstract. The overall goal of this proposal is to develop and implement a platform technology-based testbed of a fully automated and integrated continuous upstream bioprocess. The testbed will incorporate integrated components of process models, sensors (physical and virtual), control software and hardware, and data management and will serve as a platform to develop the necessary scientific, technological and regulatory framework. This output of the proposed effort can then be used as a pre-cursor to fully integrated continuous commercial biomanufacturing, by academics, industrial practitioners and regulators alike, as we collectively collaborate to put the pieces into place for advanced manufacturing of biological based products made by continuous biomanufacturing. To this effect, the overall goal will be realized by focusing on the following specific aims: Specific Aim 1: Mammalian cell biosynthetic behavior manipulation via in-process corrective feedback through the rapid detection of key process and cell-culture parameters. Specific Aim 2: Process model development and validation for failure mode identification, risk assessment, comparison of process alternatives and in-silico model-based analyses. Specific Aim 3: Integrated (soft)-sensing, control, data management and implementation in a continuous upstream bioprocess to demonstrate increased real-time product quality assurance. The proposed work addresses an emerging advanced manufacturing approach (i.e., continuous bioprocessing) and the critical barriers to its adoption by providing further scientific knowledge captured into predictive models that can be used to develop subsequent process control and automation. Performing such work under FDA sponsorship in conjunction with industry interactions provides a pathway to commercial adoption with an accompanying regulatory framework. Furthermore, there is a growing interest in realizing the benefits of continuous bioprocessing where initial work has pointed to the benefits of this technology. Together with the recent guidance(s) expressed by the FDA on continuous (bio)-processing in both the large and small-molecule space, and the recent trend of industrial companies moving toward a more biologic drug based portfolio, there is an immediate need to advance the state of the technology for more expeditious adoption and regulation. The proposed work is aligned with Rutgers University's strategic direction and the University's commitment to supporting work in this field at the institutional level. Finally, part of the investigative team are also key members of the C-SOPS team that have successfully worked with a pharmaceutical companies, vendors and the FDA as part of the NSF-ERC infrastructure to develop and implement a proof-of-concept continuous manufacturing (CM) drug product tested at Rutgers that eventually formed the basis for Janssen Pharmaceuticals Prezista drug approval via CM.