The manufacturer required a fully automated, disposable chromatography system which was PLC controlled and designed for use in a cGMP environment. The required applications for the chromatography system included contamination removal, and concentration and purification of biologically derived proteins used in the production of research and clinical materials. Finally, there was a requirement that all product contact surfaces be completely disposable, single-use applications.
The Technical Problem:
There were a number of problems with the original valve set-up for the chromatography system that needed to be addressed with an operational solution.
The closure capability of the existing valve and tubing combination was unpredictable and the durometer tolerance variations within the elastomer tubing sets led to frequent valve failures, or leak-by. This also occurred when the valves were unable to overcome the operational pressure resistance generated within the system. If they were able to close, it was at a very low pressure for both the tubing and the valve. When the pressure issues were combined with tubing durometer variances, it was difficult to determine which component was to blame.
Additionally, there was often product degradation caused by convective heat transfer from the actuation of the valve through the liner, and into the product stream. These issues alone compromised the system’s overall integrity and ability to function as needed. Other significant process issues caused by the unpredictable valve operation were associated with the manifold construction. The poor spacing in the original valve manifold – that was required for traditional hand fabrication and over-molding of the liner assembly – led to irregular center-line dimensions with a minimum of 3.5 inches. This led to significant hold-up volume concerns, and combined with the buffer/product precolumn admixing affects ultimately, ended up negatively impacting product yield.
The manufacturer chose the patented ARTeSYN™ Arterial Process Module – a multiple pinch-valve array designed to produce low hold-up volumes and compact actuation. The directional flow path control for the automated cGMP chromatography system was achieved using the ARTeSYN™ multiple pinch-valve array modules. The valve array modules are a compact, pneumatically actuated design using single-use silicone tube liners for quick replacement.
The compact design minimized the risk of unwanted solution cross-mixing and virtually eliminates any possible deadlegs within the process flow path. This was accomplished by moving the valve closure points of the flowpath as close to the main trunk line as possible.
The valve also solved the problem of nominal operational pressures exceeding 30 psi. These pressures had previously been very difficult to achieve – and since the installation of the ARTeSYN™ multiple pinch-valve array modules are no longer a problem. This was accomplished by injection molding the entire flowpath in the pinch- valve array module, thereby supporting the entire circumference of the liner assembly. The valve has been proven to close consistently in excess of 1000 cycles on the matched molded liner.
According to the manufacturer, the ARTeSYN™ process module has led to superior overall system performance and has virtually eliminated:
Unpredictable closure capability
Product yield losses caused by valve leak-by
Product degradation caused by heat transfer from valve actuation
Product yield losses caused by pre-column mixing
Aquasyn’s new concept, the ARTeSYN®, is the new patent pending ”Arterial Process Valve” for your single use applications in the area of ”Single Use” fluid management. The ARTeSYN® valve is available in multiple orientations with a variety of liner materials and end connections. APV’s are easily outfitted with electrical position indicators or positioning devices.
Since it’s inception in 1996, Aquasyn’s goal has been to break new ground, not retrace the steps of others. Our extensive process engineering and manufacturing experience has enabled us to provide the dynamic biotech and pharmaceutical markets with standard, as well as customized, valves and associated components which are highly innovative and of uncompromising quality. For more information, E-mail: firstname.lastname@example.org or visit www.aquasyn.com