Bioprocessing 4.0: a pragmatic review and future perspectives

In the dynamic landscape of industrial evolution, Industry 4.0 (I4.0) presents opportunities to revolutionise products, processes, and production. It is now clear that enabling technologies of this paradigm, such as the industrial internet of things (IIoT), artificial intelligence (AI), and Digital Twins (DTs), have reached an adequate level of technical maturity in the decade that followed the inception of I4.0. These technologies enable more agile, modular, and efficient operations, which are desirable business outcomes for particularly biomanufacturing companies seeking to deliver on a heterogeneous pipeline of treatments and drug product portfolios. Despite the widespread interest in the field, the level of adoption of I4.0 technologies in the biomanufacturing industry is scarce, often reserved to the big pharmaceutical manufacturers that can invest the capital in experimenting with new operating models, even though by now AI and IIoT have been democratised. This shift in approach to digitalisation is hampered by the lack of common standards and know-how describing ways I4.0 technologies should come together. As such, for the first time, this work provides a pragmatic review of the field, key patterns, trends, and potential standard operating models for smart biopharmaceutical manufacturing. This analysis aims to describe how the Quality by Design framework can evolve to become more profitable under I4.0, the recent advancements in digital twin development and how the expansion of the Process Analytical Technology (PAT) toolbox could lead to smart manufacturing. Ultimately, we aim to summarise guiding principles for executing a digital transformation strategy and outline operating models to encourage future adoption of I4.0 technologies in the biopharmaceutical industry.