Virus removal filtration is widely used in the biopharmaceutical industry for products such as antibodies, recombinant proteins, and other biological products expressed in murine cell lines, as well as blood products and biochemical extracts. It is a key component of virus safety strategies during the production process.

It has been over three years since Cobetter launched its virus removal products in 2021 During this period, we have continuously achieved technological progress to address more complex biological feed streams and improve filtration capacity. Currently, Cobetter offers three series of Polyethersulfone (PES) virus removal filters as well as two series of regenerated cellulose (RC) filters. The virus removal filter based on PVDF is also under development.

In this article, we will explain and introduce several types of virus removal filters sold by Cobetter, so that you can better understand our related products and layout.

Part I Cobetter Virus Removal Products

The Viruclear Polyethersulfone (PES) material virus removal filter features high throughput and is suitable for most proteinaceous materials, with antibodies as the representative. The Viruclear VF series products ensure robust retention of endogenous, exogenous viruses, and virus-like particles, allowing for large-volume protein material viral filtration operations within a controlled timeframe.

On the other hand, Viruclear Regenerated Cellulose (RC) material virus removal filters exhibit excellent hydrophilicity and strong anti-clogging capabilities. They offer irreplaceable advantages in virus filtration for plasma-derived biological products such as intravenous immunoglobulins and coagulation factors.

Based on different protein application secarios, Viruclear VF Plus, VF Plus X and RC H are high recommended, respectively.

PartII Polyethersulfone (PES) Material Virus Removal Filter

Upgraded welded version of the virus removal filtration syringe filter

The virus removal filtration syringe filter is primarily used in the process development stage of virus removal filtration in downstream purification of biopharmaceuticals. It is used for filter selection and process parameter exploration during small-scale trials, as well as for the validation and assessment of virus clearance capabilities. Cobetter's newly introduced Viruclear VF WD (welding type) series syringe filters will completely replace the original polypropylene shell material virus removal filtration syringe filters. They will be used for laboratory-scale process development testing and the relevant evaluation of virus clearance validation.

The upgraded welded version of the syringe filter uses the same housing material as the pilot and production scale plastic housing filters, ensuring material consistency for product scale-up. At the same time, the upgraded syringe filters apply the same membrane welding and component welding processes as the larger components, ensuring more robust structural stability and virus removal.

Part III Regenerated Cellulose (RC) Virus Filter

• Made of regeneratedcellulose
• Naturally hydrophilic.
• Continuous asymmetric membrane cross-section

Viruclear RC (H) series of virus removal filters can withstand higher protein concentrations and are suitable for the virus removal of ultra-high protein concentrations (e.g. IVIG, SCIG, etc.).

Part IV Virus Removal Pre-filters

PNY Virus Removal Nylon Prefilters

Nylon based pre-virus filtration
Structure: Nylon material, 0.1μm nominal microporous membrane, similar to dead-end sterilizing filters.
Principle: Size exclusion hydrophobic adsorption
Advantage: Adsorption is not much affected by pH and conductivity of the sample, suitable for hydrophobic materials with controllable E/L, small retention volume.

PDT Virus Removal Depth Prefilters

Based on depth-method pre-filtration (secondary depth filtration)
Structure: cellulose skeleton, diatomaceous earth filter aid, positively charged resin modification
Principle: Size exclusion + charge, hydrophobic adsorption
Advantage: High flux, high loading capacity, depth filters are usually more effective in protection.

Part V Integrated Virus Removal Systems

The virus removal filtration system consists of two main components: hardware holder and software systems. It is equipped with a variety of configurations and integrates installation points for viral pre-filters. Customers can personalize their setups according to their specific usage needs.

Case Study

Finally, through experimental cases, we will intuitively observe the performance of Cobetter's marketed and in-development virus removal filters in a 4g/L bispecific antibody solution.

In the experiment, we employed virus removal filters of different materials, each connected inline with a prefilter, to perform constant-pressure filtration at 30 psi.

From the data below, it can be seen VF Plus suffered very rapid fouling, while VF Plus X, the Regenerated Cellulose (RC) and Polyvinylidene fluoride (PVDF) material virus removal filters exhibit strong anti-clogging capabilities, maintaining relatively stable flux. VF Plus X becomes the best choice as it had the highest average processing flux.

Test Conditions:
Sample Concentration: 4.0 g/L bispecific neutral antibodies
Constant Pressure: 30 psi
Serial Filtration with PDT and SMD
After filtration, top washing is performed with 30 L/m2 of buffer solution.

Relevant Qualification

Currently, Cobetter has four viral filtration product series (including viral pre-filters) with Drug Master Files (DMFs), with the file numbers as shown in the table below. These DMFs have been formally submitted to the Food and Drug Administration (FDA) of the United States in eCTD format and have passed FDA administrative review. This signifies that in the future, users can directly reference the relevant information data of Cobetter's viral filtration product series when registering products according to their actual needs. The content of these DMFs can support New Drug Applications (NDAs), Investigational New Drug Applications (INDAs), etc.

According to the United States Code of Federal Regulations §314.420, Cobetter periodically maintains these DMFs and authorizes customers in both China and the United States to quickly reference the information of concern to regulatory authorities through the issuance of authorization letters, thereby assisting customers in successfully obtaining registrations.

In addition, Cobetter engineers have assisted over a hundred clients in completing more than 600 viral filtration process developments. This support has successfully facilitated clients in completing over a hundred batches of scale-up and production tasks. Moreover, Cobetter has conducted virus clearance validation work in over 50 instances through third-party execution of Investigational New Drug (IND) and Biologics License Application (BLA) studies.