Scalable technologies for process intensification in the factories of the future
Continuous and intensified bioprocessing is attracting much attention from biopharmaceutical companies seeking to maximize the efficiency of their manufacturing assets. Continuous and intensified bioprocessing promises smaller facilities, reduced scale-up risk, more consistent product quality and higher throughputs.
However there are still many (technical) challenges for practical implementation of intensified and continuous bioprocesses. In the upstream processing, tools for high throughput intensified and continuous cell culture development are limited, furthermore at scale many single use bioreactors may not be suitable to support the high cell densities required for intensified processing. Furthermore current cell retention systems are expensive, suffer from product sieving and long term blocking effects. In addition clarification of extremely high cell density cell cultures is challenging.
In the downstream processing MCC product capture is finding its way into manufacturing, and flow-through polishing steps with e.g. membrane adsorbers are becoming viable options, however scalability, sterility and robustness over longer times are still challenging. Furthermore robust solutions for continuous low pH viral inactivation, continuous virus filtration and continuous diafiltration need further attention.
Finally, when interconnecting unit operations, balancing of flows and feedback control using PAT tools as well as advanced process control remains is required.
Here we will discuss the some of the latest solutions to address these issues, including SUBs designed for extreme cell densities at scale, TFF filtration without product sieving, clarification of extreme cell density harvests, scalable Membrane Adsorbers, PAT tools and Process Automation, showing real life examples and added value with cost modeling data.
About Gerben Zijlstra
Gerben Zijlstra, Platform Marketing Manager, Continuous BioManufacturing, Sartorius Stedim Biotech joined the process platform team in October 2016 as subject matter expert in continuous/intensified bioprocessing
Dr. Gerben Zijlstra received his Ph.D. from the University of Wageningen, The Netherlands, with a thesis on “process integration in the field of animal cell culture”.
Following his Ph.D., Gerben joined DSM Biologics in Groningen, The Netherlands, a Biologics CMO company, in 1994, where he held various positions within the process development, cGMP manufacture, and engineering departments, with a focus on introducing new (platform) processes and new process equipment into the facility and tech transfer of commercial processes to other sites.
Subsequently he was Senior Scientist in the R&D department with responsibility for the process development of several commercial Biologicals, as well as platform process development (e.g. for PER.C6 and CHO) and technology development projects (e.g. introduction of SUBs in 2006). Over the years he has worked extensively in the field of process intensification, integration and Continuous Bio manufacturing in animal cell culture.
He is the first inventor of XD® technology a highly intensified “concentrated Fed-Batch” continuous cultivation mode in which cell densities over 240 mln cells/mL and MAb titers over 27 g/L have been achieved. This technology was licensed by amongst others Amgen to become part of their Continuous Biomanufacturing platform toolkit.
In 2011, together with his team, Gerben received the DSM Innovation Award, a prestigious Award within the company, for the advancement of this technology. He has contributed to the scale-up and tech transfer of XD® technology to the DSM Brisbane site for commercial scale manufacturing at 500 L scale. This site received the 2014 ISPE facility of the year award for process innovation.
Gerben’s most recent job was at Xendo BV in Leiden the Netherlands, a bioprocess consultancy where he was involved in several Continuous BioManufacturing projects. Gerben is a regular speaker on international conferences on the topics of process intensification, process integration and continuous biomanufacturing.