The Xcellerex Automated Perfusion System (APS) simplifies processes and reduces risk when intensifying upstream operations, Cytiva says. We speak with Andreas Castan, strategic technology partnerships leader, to find out why.
Bioprocess Insider (BPI): How common is cell cultivation using perfusion?
Andreas Castan (AC): There are a number of perfusion-based products on the market, especially unstable proteins like coagulation factors (e.g. Factor VIII), but also mAbs (e.g. Infliximab). Some of these have been around for 20 years or more.
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The use of perfusion is not new to our industry. Recent surveys suggest more than 50% of the industry are investigating perfusion in new processes they are developing, and perfusion is regarded as a route to achieve higher productivities and improve product quality. The regulators are actively championing the adoption of continuous processing and the market is reflecting that.
BPI: How does your new Xcellerex APS work?
AC: Xcellerex APS is an automated, single-use perfusion skid with up to two filters. The cell suspension in the bioreactor is pumped with a low-shear pump over a hollow fiber filter, a filtrate is removed, and the concentrated cell suspension is going back to the bioreactors. The automation includes flow kit installation, feed addition, harvest removal, bleed control and switch to the second hollow fiber filter. This altogether gives a turn-key perfusion system that removes the headaches with perfusion in seed train intensification or steady-state perfusion.
BPI: You claim it simplifies processes and reduces risk when intensifying upstream operations. What does this mean from a practical point of view?
AC: The APS does this by automating and integrating all the different components to reduce risk. Everything is single use and uses standard disposable aseptic connector. It allows one supplier for all components including automated filter switching on one system. There is no need for a second back up assembly with a skilled operator ready to make the switch at the right time. Same for bin switching for both media and permeate collection. And all controlled from one system that fully integrates with the bioreactor. In essence, it’s a complete operation rather than three or four separate ones.
BPI: Where are the potential cost-savings for the manufacturer when using this tech over other perfusion technologies?
AC: This will depend on our customers individual processes and the costs savings that can be realised. As we are using standard off-the-shelf components including single-use hollow fiber filters consumable costs are significantly lower than similar filtration-based perfusion technologies. In addition, the redundant hollow fiber filter connected to the flow kit, makes the switch to a new filter an easy and safe operation, without the need of additional hardware or consumables. This reduces the risk of batch failure.
BPI: Is the large amount of media needed to manufacture via perfusion an issue, and if so does this new tech overcome it?
AC: It is correct that perfusion cultures will require more cell culture media than a fed batch culture producing the same amount of product, a ratio of media consumption between fed-batch to perfusion of 1:5 is not completely unrealistic. However, the volumetric productivity gains, i.e. the amount of product produced in a culture volume and time, are significantly higher and will outweigh the increased media costs and handling requirements. The volume of media required comes down to the optimization of the media composition to ensure that the VVD (vessel volumes per day) of media is kept to a minimum (typically around 1).
In addition, the use of media concentrates can also help to reduce the volume of media prepared and achieve a dilution with water-for-injection at the point of use, i.e. the bioreactor. The APS system automates the switch over to a new media bin once one has been emptied ensuring an uninterrupted operation and an optimal utilization of the prepared medium.