Why hasn’t biopharma fully embraced continuous bioprocessing?
Traditionally, continuous processing in the biotech sector has been viewed as more complex to operate and with a higher risk of failure. With the introduction of more robust technology options for upstream and downstream processing, we have seen a resurgence of interest. Yet obstacles to adoption still exist. When we ran a roundtable discussion at a recent conference on this topic (2), several participants mentioned issues such as the lack of reliable scale-down tools for continuous processes and the need for better online process analytical technology, control and hardware reliability than is currently available. Furthermore, companies working with stable antibodies may not have the same incentives as those working with labile products, where continuous processing can be a necessity.How can decision-support tools help?
Decisional tools such as those developed at UCL Biochemical Engineering can act as a testbed to perform in silico evaluations of the technical, financial and risk implications of continuous technologies across a range of scenarios. The cost of experimentation to explore all the options is prohibitive and hence decision-support tools are vital for new technologies to be examined inexpensively, thus saving time and helping to prioritize R&D efforts.How have you have applied decisional tools?
We have developed and applied decisional tools to examine the bioprocess economics of continuous processing and answer topical questions (3-5) such as: How well do continuous perfusion steps need to perform to compete with the traditional fed-batch processes? Does continuous chromatography offer cost savings for clinical manufacture? How does the business case for integrated continuous bioprocessing change from early-phase manufacture to commercial multi-product manufacture? On the upstream front, we illustrated how the choice of fed-batch versus spin-filter and ATF perfusion culture depends on the scale of production, failure rate and cell density increase achievable. ATF perfusion processes were predicted to be more competitive for single-product commercial antibody facilities if the cell density increase was above a critical threshold (three-fold higher in this case) and the process economics savings were considered more important than operational feasibility. In contrast, the tool predicted limited use of spin-filter systems in industrial scale processes since they would struggle to compete on economic, environmental, operational and robustness fronts at most cell culture titres and production scales. Turning to downstream, our integrated techno–economic evaluation of whole bioprocesses that utilise continuous chromatography for product capture predicted that such processes have the ability to offer significant direct cost savings in early clinical phase material generation; this can have a large impact considering the high clinical attrition rates. Looking at integrated continuous bioprocessing, our analysis predicted that an integrated continuous strategy (ATF perfusion, continuous capture, continuous polishing) is cost-effective for early-phase production and small/medium-sized companies. However, the ranking of strategies switches for commercial production and large companies to the hybrid strategy with fed-batch culture, continuous capture and batch polishing since this avoids the need for multiple parallel trains with the scale-limited perfusion systems. Further considerations that could alter those conclusions include factoring in the cost of development when adopting continuous processing.Newsletters
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