In the R&D and production of biopharmaceuticals, virus removal filtration is widely used due to its clear interception mechanism, which improves the virus security of biologic products. With the continuous development of biological drugs, the discovery of various new targets and the emergence of more and more complex molecules, the most commonly used PES polyethersulfone material virus removal filter does not perform well in some complex projects. In order to meet these challenges, Cobetter has developed the regenerated cellulose virus removal membrane Viruclear® RC with independent intellectual property rights, which has better hydrophilicity, high protein recovery rate, and at the same time increases the filtration capacity of complex project materials.
Cobetter's regenerated cellulose virus removal filter features a continuous asymmetric membrane structure, as shown in the cross-sectional electron microscope picture in Figure 1. The upper layer is the liquid inlet surface, and the lower layer is the liquid outlet surface. In actual filtration, the feed liquid enters the pre-filter layer first, where the protein aggregates and impurities of different sizes are intercepted step by step, thereby increasing the filtration capacity, and then the feed liquid enters the precision interception layer. The precision interception layer has a pore size of 20nm to ensure the robustness of virus interception.
Figure 1. Electron micrograph of the cross-section of Viruclear® RC virus removal membrane
Cellulose is the most hydrophilic filter material commonly used in bio-pharmaceutical filtration consumables. Regenerated cellulose inherits this excellent natural property of cellulose, and its low adsorption properties to proteins let Viruclear® RC have higher protein Recovery rate. In addition, cellulose can maintain high virus removal function and filtration flow rate during long-term filtration and is minimally affected by surfactants (as shown in Figure 2 and Figure 3), so customers can choose longer filtration time to reduce costs, and virus removal filtration can be performed after adding excipient stabilizers, which provides more possibilities for process development.
Figure 2. Flow rate diagram of Viruclear® RC virus removal filter filtering 5g/L IgG solution for a long time
Figure 3. Effect of excipients on the performance of Viruclear® RC virus removal filter
Viruclear® RC virus removal filter has better hydrophilicity and dirt-holding ability. It performs well in some difficult-to-filter projects, but its water flow rate is significantly lower than that of PES virus-removal filter. The overall performance of the project will be slightly inferior, so how to screen out the virus filter at the initial stage of the project to save feed liquid and speed up the progress of process development has become a concern. Next, we will introduce some representative practical application of Viruclear® RC virus removal filter.
Blood products with complicated feeding
- Conditions: 2g/L thrombin
- Purity: greater than 96%
- Pre-filter:Viruclear® PNY (Nylon)
- Virus removal filter:Viruclear® RC/Viruclear VF Plus(PES)
Figure 4. Filtration curves of blood products of Cobetter PES and RC virus removal filter
The feed and liquid conditions of blood products are relatively complicated. In addition to the stable virus removal ability, the dirt-holding and anti-clogging ability is another performance indicator that customers value more during virus removal and filtration. The flow rate of Viruclear® VF Plus virus removal filter deteriorated sharply at the initial stage of filtration, and the feed liquid could not be filtered smoothly; the flow rate of Viruclear® RC also decreased during filtration, but its 4-hour capacity can reach 160L/m², which can meet the production needs of customers.
High polymer protein project
- Feed liquid: 23g recombinant protein, 3.5% polymer
- Purity: Greater than94%
- Filter combination: Viruclear® PNY+Viruclear® RC/Viruclear® PDT(Depth Filter) + Viruclear® VF Plus (PES)
Figure 5. Filtration curve of high polymer feed liquid of Cobetter PES and RC virus removal filter
The initial flow rate of the Viruclear® VF Plus virus removal filter is slightly higher, but it kept decreasing, and clogging occurred at about 60 minutes. The initial flow rate of the Viruclear® RC was low, but the decrease was slightly smaller, and its capacity at 120 minutes was similar to that of the PES virus removal filter. But its deterioration is small, and is safer during virus removal validation and production; at the same time, the combination of Viruclear® PNY + Viruclear® RC has less protein adsorption and can achieve a yield of more than 98% which becomes the better choice.
Hydrophobic antibody project
- Feed liquid: 4g/Lof hydrophobic bispecific antibody
- Purity: more than 99%
- Filter combination: Viruclear® SMDA(0.1um)+Viruclear® RC/Viruclear® PDT+Viruclear® VF Plus (PES)
Figure 6. Filtration curve of hydrophobic feed liquid of Cobetter PES and RC virus removal filter
Viruclear® VF Plus virus removal filter has a sharp deterioration of the flow rate at the initial stage of filtration, and cannot filter the feed liquid smoothly. Viruclear® RC can filter at a speed with almost no deterioration 180min, and can reach a higher capacity.
Likewise, with some other hydrophobic molecules, such as Bevac beads, some ADCs with hydrophobic groups, Viruclear® RC will also have excellent filtration performance.
- Feed liquid: 2g/LIgM
- Purity: more than 98%
- Filter combination:Viruclear® SMDA+Viruclear® RC/Viruclear®PDT+Viruclear VF Plus (PES)
Figure 7. IgM filtration curve of Cobetter PES and RC virus removal filter
Similar to the filtration of hydrophobic fluids, the Viruclear® VF Plus Virus Removal Filter deteriorates sharply during the initial phase.
Viruclear® RC was successfully filtered for 90 minutes with only a small amount of deterioration.
|Filter membrane||4.1 cm²||Process development and virus clearance validation|
|Syringe filter||2.5 cm²||Process development and virus clearance validation|
Product Specification Diagram
The Viruclear® RC Virus Removal Filter, a new addition to the Cobetter Life Sciences family, will be an even better choice for virus removal filtration of complex fluids. Together with Cobetter's original Viruclear® VF Plus Virus Removal Filter, it provides customers with a more comprehensive virus removal filtration solution.
Cobetter will keep up with the market demand, continuously improve the product series, and is always committed to providing customers with high-quality and reliable products, helping customers to reduce costs and improve the safety of drug production.