Optimizing Virus Filtration with Prefilters
Why Use Virus Prefilters?
In biologics production, virus filtration is a critical step in ensuring drug safety. However, achieving efficient virus filtration can be challenging, as protein aggregates and other impurities can lead to premature filter fouling. To mitigate this impact, many virus filtration operations include prefilters to improve virus filter throughput, enhance run-to run consistency, and minimize filtration area requirements. By reducing filtration areas, these prefilters lower costs and improve process economics.
Our Viresolve® Pro Solutions offer a comprehensive approach to virus filtration including two specialized devices, either Viresolve® Pro Device or Viresolve® Pro-S Device, each paired with their respective adsorptive membrane prefilters. Adsorptive depth filters offer an additional prefiltration option that can be used with either of the virus filters:
- Viresolve® Pro Device: Ideal for most monoclonal antibodies (mAbs).
- Viresolve® Pro-S Device: Specifically designed for high concentration, hydrophobic or more complex mAbs that need enhanced filtration capabilities.
This article explores key criteria to consider when selecting prefilters to improve throughput and capacity in virus filtration operations.
Section Overview
How Prefilters Improve Filter Capacity
In general, adsorptive binding is more effective than size-exclusion based retention for removing plugging aggregates from mAb process streams.
Our prefilter portfolio includes surface-modified membrane prefilters designed to pair with the Viresolve® Pro or Viresolve® Pro-S Devices, and adsorptive depth filters that can be used with either virus filter. The selection of a prefilter depends on the characteristics of the fluid and specific process requirements.
Adsorptive prefilters are effective across a broad range of pH and conductivity levels in process streams. Figure 1 shows capacity improvements on the Viresolve® Pro Device with human IgG (4 g/L) fluid streams of various pH and conductivities and the different prefilters. All prefilters increased virus filter capacity, but the extent of improvement was highly dependent on both the prefilter and the characteristics of the fluid streams.
Figure 1.Viresolve® Pro Device capacity at 75% flow decay with different prefilters.
Fluid Characteristics for Prefilter Selection
Prefilter performance is often defined by fluid stream characteristics.
The operating windows of the surface modified membrane prefilters are shown in Figure 2. While this contour plot highlights optimal performance conditions for the prefilters, favorable performance is also observed at the margins of these operating windows.
Figure 2.Contour plot showing optimal pH and conductivity conditions for Viresolve® Pro Shield, Viresolve® Pro-S Shield, Viresolve® Pro Shield H, Viresolve® Pro-S Shield H.
Adsorptive filters such as the Millistak+® HC Pro X0SP depth filters have broad operating windows. Read our Technical Article to explore how Millistak+® HC Pro X0SP depth filters provide a platform approach to virus filtration.
Other Considerations for Prefilter Selection
Hardware
The membrane prefilters, Viresolve® Pro Shield or Viresolve® Pro Shield H, can be co-implemented with the Viresolve® Pro Device in the same holder.
The Millistak+® HC Pro X0SP depth filter requires a dedicated holder and cannot be stacked in the same holder as the Viresolve® Pro Device.
Scaling and Screening Tools
Each prefilter is offered in a small-scale format for process development and viral clearance studies.
The small-scale devices for the Viresolve® Pro-S Shield and Viresolve® Pro-S Shield H prefilters are the Micro 40 formats which have the same 3.4 cm2 area as the Viresolve® Pro and Viresolve® Pro-S Devices.
The small-scale formats for the Viresolve® Pro Shield and the Viresolve® Pro Shield H prefilters have membrane areas of 3.1 cm2.
The small-scale device for the Millistak+® HC Pro X0SP depth filters is the NanoPod (NP6) format with 6 cm2 filtration area.
Compliance and Control: Many of our filters are supported by the Emprove® Program which offers access to product and testing information to help you stay ahead of constantly evolving regulatory requirements. This information supports different steps in your raw material and component risk assessment continuum – streamlining your supplier selection, material qualification, process optimization and patient safety evaluation.
Key Takeaways
Prefilters improve virus filter throughput, enhance run-to run consistency, minimize filtration area requirements and result in more predictable, lower cost filtration operations.
- Adsorptive or charge-based binding is more effective than size-exclusion for removing plugging aggregates from mAb process streams.
- Prefilter options include surface-modified membrane prefilters that pair with their respective Viresolve® Pro or Viresolve® Pro-S Devices and adsorptive depth filters that are compatible with either virus filter. Each prefilter option has small scale device formats for easy screening.
- Adsorptive depth filters offer a broad operating range; however, they need standalone holders for large-scale implementation.
- Membrane prefilters with surface-modified chemistry have narrower operating ranges and can be implemented in the same holder with the virus filters.
For help screening prefilters Contact Us.
How do I know which Viresolve® Pro Solution is best for my molecule?
For most antibody molecules, Viresolve® Pro-S Solution would be recommended. Our process development engineers and MSAT teams are available to help you evaluate options and optimize your process.
Can I sterilize the Viresolve® Pro-S Devices and Prefilters?
Viresolve® Pro-S Solution is offered in gamma-irradiated formats.
Which filter is best for a high concentration mAb?
We recommend you evaluate Viresolve® Pro-S Solution first. Performance will depend on multiple factors including concentration, hydrophobicity, buffer characteristics, etc. Both filters will provide reliable and effective virus retention.
How is the membrane in Viresolve® Pro-S different from Viresolve® Pro?
The surface of the Viresolve® Pro-S PES membrane is modified to minimize protein binding.
Is Viresolve® Pro-S manufactured without PFAS containing materials?
Yes, Viresolve® Pro-S is manufactured without intentionally added PFAS.
Have we looked at the effect of process interruption on Viresolve® Pro-S Device?
Yes, Viresolve® Pro-S Devices show the same insensitivity to process interruption as Viresolve® Pro Device under most operating conditions.
Do I need to use prefilters for Viresolve® Pro-S Solutions?
Yes, prefilters are recommended for any virus filtration operation to improve capacity and process consistency by reducing the impacts of batch-to-batch variability.
What prefilters should I use for Viresolve® Pro-S virus filter?
Viresolve® Pro-S Shield and Shield H membrane prefilters. These prefilters have different operating ranges so you can select a prefilter based on your process characteristics. Another option is the Millistak+® HC Pro X0SP depth filter, that may be an option for more templated process.