Viral filtration and removal

Remove virus from the mAb downstream process

Viral contamination is an important issue that must be controlled during the process development of monoclonal antibodies (MAbs) produced from mammalian cell lines.

Viral filtration

Virus filtration uses a membrane barrier to remove both enveloped and non-enveloped viruses. This method retains virus particles on the filter's surface and within the pores and is based on virus size. The advantage of virus size exclusion is its ability to be performed on a lab scale and then effectively scaled up to production standards.

Note that the level of virus removal is dependent on the size of the filter pores. In some cases, extremely small viruses will not be excluded. It is also necessary to consider the potential effects of pressure and flow rate variation.

Products for virus filtration  

Description Product No. Application
Pellicon® XL Ultrafiltration Module Biomax 300 kDa 0.005 m2 
PXB300C50 Ultrafiltration / Diafiltration
Pellicon® 2 Mini Ultrafiltration Module Biomax-100 C 0.1 m2
P2B100C01 Ultrafiltration / Diafiltration
Pellicon® 2 Mini Ultrafiltration Module Biomax-300 C 0.1 m2 
P2B300C01 Ultrafiltration / Diafiltration
Durapore® 0.22 µm membrane in 25 mm Optiscale® devices 
SVGLA25NB6 Downstream Sterile Filtration
Millipore Express® SHC membrane in 25 mm Optiscale® devices 
SHGEA25NB6 Downstream Sterile Filtration

 

Biomax® Membranes for viral filtration

Biomax® Membrane Code NMWL* (kDa)
Application
PBHK 100
Small viruses, antigens
PBHK 300
IgMs, large viruses
PBVK 500
Large viruses, colloids, particulates
PBXK 1,000 Large viruses, cells, colloids, particulates

*Nominal molecular weight limit

Note that viral clearance services are required by regulatory authorities for investigational new drug (IND) submissions. The viral clearance team has performed thousands of studies for biopharmaceutical clients.
Learn more about our viral clearance and viral safety services.

 

Viral filtration and removal research papers

An operator setting up a virus filtration step. Virus filtration removes both enveloped and non-enveloped viruses.

 

 

P Misra,A Sinha,AS Rathore,A Shukla,FQ Mir
Biotechnology progress 2017-07-21
Viral filtration is an expensive regulatory requirement in downstream processing of monoclonal antibodies (mAbs). This process step is typically operated with an overdesigned filter in order to account for any batch to batch variability in the filter, as well as the feed characteristics. Here, we propose a simple, six-parameter Read More
WJ Rayfield,DJ Roush,RA Chmielowski,N Tugcu,S Barakat,JK Cheung
Biotechnology progress 2015-06-22
Controlling viral contamination is an important issue in the process development of monoclonal antibodies (MAbs) produced from mammalian cell lines. Virus filtration (VF) has been demonstrated to be a robust and effective clearance step which can provide ≥4 logs of reduction via size exclusion. The minimization of VF area by incRead More
DJ Roush,A Myrold,MS Burnham,JV And,JV Hughes
Biotechnology progress 2015-02-24
Virus filtration (VF) is a key step in an overall viral clearance process since it has been demonstrated to effectively clear a wide range of mammalian viruses with a log reduction value (LRV) > 4. The potential to achieve higher LRV from virus retentive filters has historically been examined using bacteriophage surrogates, whicRead More
J Bach,L Connell-Crowley
Biotechnology and bioengineering 2015-03-02
Protein A chromatography is the most common unit operation used in the manufacture of therapeutic monoclonal antibodies (mAbs) due to its high affinity and specificity for the IgG Fc domain. However, protein A chromatography is often not effective for viral clearance. Typical log reduction values (LRV) for the model retrovirus XRead More
E Gefroh,H Dehghani,M McClure,L Connell-Crowley,G Vedantham
PDA journal of pharmaceutical science and technology 2016-10-21
Typical platform processes for biopharmaceutical products derived from animal cell lines include a parvovirus filtration unit operation to provide viral safety assurance of the drug product. The industry has adopted this platform unit operation and gained a wider understanding of its performance attributes, leading to the possibRead More
JG Barnard,D Kahn,D Cetlin,TW Randolph,JF Carpenter
Journal of pharmaceutical sciences 2016-11-25
Filtration to remove viruses is one of the single most expensive steps in the production of mAb drug products. Therefore, virus filtration steps should be fully optimized, and any decline in flow rates warrants investigation into the causes of such membrane fouling. In the current study, it was found that freezing and thawing ofRead More
J Stuckey,D Strauss,A Venkiteshwaran,J Gao,W Luo,M Quertinmont,S O'Donnell,D Chen
Biotechnology progress 2014-02-07
Viral filtration is routinely incorporated into the downstream purification processes for the production of biologics produced in mammalian cell cultures (MCC) to remove potential viral contaminants. In recent years, the use of retentive filters designed for retaining parvovirus (~20 nm) has become an industry standard in a consRead More
J Parrella,Y Wu,DW Kahn,P Genest
PDA journal of pharmaceutical science and technology 2016-10-21
The traditional approach to virus filter spiking studies (virus added to the feed solution before the start of filtration) can lead to oversized viral filtration systems because of the non-representative volumetric throughputs (L/m2) that can be seen with the addition of the virus spike. The reduction in throughput is thought toRead More
DM Strauss,J Gorrell,M Plancarte,GS Blank,Q Chen,B Yang
Biotechnology and bioengineering 2013-11-21
The mammalian cell-lines used to produce biopharmaceutical products are known to produce endogenous retrovirus-like particles and have the potential to foster adventitious viruses as well. To ensure product safety and regulatory compliance, recovery processes must be capable of removing or inactivating any viral impurities or coRead More
DM Strauss,S Lute,Z Tebaykina,DD Frey,C Ho,GS Blank,K Brorson,Q Chen,B Yang
Biotechnology and bioengineering 2009-08-27
During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell culture, it is important to ensure that viral impurities and potential viral contaminants will be removed during downstream purification. Anion exchange chromatography provides a high degree of virus removal from mAb feedstocks, but the mechanism by Read More
M Zhang,GR Miesegaes,M Lee,D Coleman,B Yang,M Trexler-Schmidt,L Norling,P Lester,KA Brorson,Q Chen
Biotechnology and bioengineering 2015-04-23
Protein A chromatography is widely used as a capture step in monoclonal antibody (mAb) purification processes. Antibodies and Fc fusion proteins can be efficiently purified from the majority of other complex components in harvested cell culture fluid (HCCF). Protein A chromatography is also capable of removing modest levels of vRead More
S Caballero,JM Diez,FJ Belda,M Otegui,S Herring,NJ Roth,D Lee,R Gajardo,JI Jorquera
Biologicals : journal of the International Association of Biological Standardization 2014-03-28
In this study, the virus-removal capacity of nanofiltration was assessed using validated laboratory scale models on a wide range of viruses (pseudorabies virus; human immunodeficiency virus; bovine viral diarrhea virus; West Nile virus; hepatitis A virus; murine encephalomyocarditis virus; and porcine parvovirus) with sizes fromRead More