Viral Clearance

Pall’s product offering for viral clearance consists of membrane technology and chromatography, which are both vital elements in ensuring virus safety for therapeutics, such as plasma-derivatives, recombinant proteins or monoclonal antibodies derived from cell cultures.    Viral Filtration Virus filtration characterizes one approach among membrane technologies available to the pharmaceutical industry, and is normally performed by Direct Flow Filtration (DFF). Ultipor® VF Grade UDV20 and DV50 filter cartridges and Pegasus™ Grade LV6 Virus Removal Filter Cartridges are robust, reliable, highly efficient and well-established viral reduction technologies, thanks to their efficiency, ease of implementation and cost-effectiveness.

Based on size exclusion, virus filtration applies an ‘orthogonal removal mechanism’ that is complementary to inactivation and chromatography technology. Increased manufacturing volumes and protein concentrations have increased the importance of using virus filters which offer robust and high- capacity performance, and of optimizing large-scale virus filter processes with the ability to be incorporated into fully automated integrated virus filtration systems.

Large-Scale Virus Filter Systems

Large-scale virus filtration has specific requirements:

• Robust and stable performance in the expected range of process parameters (protein concentration, impurities etc.) over a longer process time (four to twelve hours for example)
• Clean-In-Place (CIP) and Steam-In-Place (SIP) procedures suitable for automated large-scale systems
• Virus filter integrity testing in large scale systems has special requirements (integrity arrangement)

Pall offers fully-automated integrated virus filter systems, which provide the highest level of process safety due to very precise and consistent automated process steps in combination with improved process efficiency, leading to a reduction in labor costs.

Column Chromatography

Several chromatography mechanisms have proven very effective in the removal of viruses in the downstream purification processes of biopharmaceuticals.

Anion-exchange chromatography, which is widely used in biopharmaceutical manufacturing, can be a robust viral clearance step when operated in flow-through mode.

Membrane Chromatography

The benefit of using membrane chromatography is receiving increased recognition and is now becoming a routine process step in large-scale biopharmaceutical manufacturing processes. It opens the opportunity for interesting new application areas, such as removal of impurities and viruses. Mustang® membrane adsorbers have demonstrated the capacity to remove most viruses by adsorptive removal. The high flow-rate, high-capacity performance characteristics can overcome existing technical limitations of column chromatography.

Virus Inactivation - Solvent/Detergent (S/D) Removal

Solvent/detergent (S/D) inactivation is a robust, well-established viral clearance method applied to numerous biological products. S/D viral inactivation procedures often consist of incubating protein solutions in the presence of an organic solvent, typically tri-(n-butyl) phosphate (TnBP) and of one or several detergents (Tween-80 and, increasingly, Triton X-100). An important technical challenge associated with S/D treatment is the removal of the solvent and detergent, subsequent to the viral inactivation step.

Pall’s SDR HyperD® Solvent-Detergent Removal Chromatography Sorbent - a specifically designed three-dimensional cross-linked hydrophobic acrylic polymer, is regarded as an effective material to achieve satisfactory removal of S/D agents. SDR HyperD® Solvent-Detergent Removal chromatography sorbent is used to capture the S/D agents, while hydrophilic proteins are directly recovered in the chromatographic flow-through.

Service and Technical Support

Pall can assist you and help with the following services as part of your processes, along with many other Technical Services, including:

• Filterability studies
• Phage Retention validation studies
• Virus Retention validation support