Continuous biopharmaceutical manufacturing is currently a field of intense research due to its potential to make the entire production process more optimal for the modern, ever-evolving biopharmaceutical market. Compared to traditional batch manufacturing, continuous bioprocessing is more efficient, adjustable, and sustainable and has reduced capital costs. However, despite its clear advantages, continuous bioprocessing is yet to be widely adopted in commercial manufacturing. This article provides an overview of the technological roadblocks for extensive adoptions and points out the recent advances that could help overcome them. In total, three key areas for improvement are identified: Quality by Design (QbD) implementation, integration of upstream and downstream technologies, and data and knowledge management. First, the challenges to QbD implementation are explored. Specifically, process control, process analytical technology (PAT), critical process parameter (CPP) identification, and mathematical models for bioprocess control and design are recognized as crucial for successful QbD realizations. Next, the difficulties of end-to-end process integration are examined, with a particular emphasis on downstream processing. Finally, the problem of data and knowledge management and its potential solutions are outlined where ontologies and data standards are pointed out as key drivers of progress.
Keywords: continuous biomanufacturing; knowledge management; process integration; process intensification; quality by design.
Published 2023. This article is a U.S. Government work and is in the public domain in the USA.