Sartorius has recently acquired the industry-proven BioSMB technology: an integrated single-use device that allows for continuous chromatography. Combined with the company’s established portfolio for upstream processing, this paves the way for new developments in process intensification.
While applications of monoclonal antibodies have surged in recent decades, in the past few years the focus has shifted towards a new class of molecules: biospecifics. These proteins, which can be produced industrially, interact with the patient’s immune system to produce an enhanced and more specific T-cell activation. “These complex proteins are not always suited for classical fed-batch processes”, says Gerben Zijlstra, Platform Manager Continuous BioManufacturing at Sartorius Stedim Biotech. “The molecules tend to aggregate, for instance, or they disintegrate easily. Ideally, you want to minimise the time they’re exposed to bioreactor conditions.”
In cases like this, continuous processing is the solution, says Zijlstra. “One option is continuous capture, for instance with our new BioSMB System.” The BioSMB (simulated moving bed) platform provides a flexible multicolumn chromatography system that uses much less medium when compared to traditional batch methodologies. This is achieved through a single-use, eight-column system architecture that enables a highly flexible flow configuration.
‘It’s high-throughput and high-insight’
The BioSMB platform is fully scalable from process development to commercial manufacturing. There are two commercial scale systems vailable targeted for perfusion and batch processes. Zijlstra: “The combination of upstream perfusion and this new level of continuous downstream processing leads to an entirely new generation of production platforms.”
Sartorius has built up a steady reputation regarding upstream perfusion. Its latest product is the Ambr 250 High Throughput Perfusion System: a parallel, single-use bioreactor system with a fully automated liquid handling platform. This system accelerates the optimisation of intensified cell culture processes, leading to lower production volumes and reduced cost of goods.
“This upstream system can be combined with the latest Raman spectroscopy techniques”, notes Zijlstra. “A statistical model allows you to analyse a large number of metabolites using only one sensor. The more you can measure, the better you can steer your process. It’s high-throughput and high-insight.”
The application of single-use elements is self-evident, as Zijlstra continues: “Bioburden control over longer periods is cumbersome in continuous processes using traditional stainless steel systems”, he says. “Our single-use upstream and downstream solutions, which can be gamma radiated, can remain in place for ten, fourteen days with very limited risk of contamination or interruption of the process.”
Zijlstra emphasises once more: it is this full-platform approach – the smart combination of upstream and downstream, and of established and new technologies – that brings new applications in sight. “That is our strength at Sartorius”, he says. “These ‘platforms of the future’ are ideally suited to produce the ‘molecules of the future’.”