Modeling virus filtration: Materials, applications, and mechanism.

While various methods are employed to ensure the virus safety of finished products, virus filtration (VF) stands out as the preferred method for virus removal and purification of a wide variety of products owing to its capability of separating product molecules with more than 90% recovery and no change in molecule characteristics. The modeling of the virus removal process for VF membranes is based on the principles of microfiltration (MF) and ultrafiltration (UF), but with modifications for the much narrower separation difference, which is less than 2-fold for the separation of product molecules and virus particles. In this review, we introduce the materials and application of VF highlighting the unique characteristics properties of VF membranes through the steps of invention and subsequent development.

Viral clearance in end-to-end integrated continuous process for mAb purification: Total flow-through integrated polishing on two columns connected to virus filtration.

There are few reports of the adoption of continuous processes in bioproduction, particularly the implementation of end-to-end continuous or integrated processes, due to difficulties such as feed adjustment and incorporating virus filtration. Here, we propose an end-to-end integrated continuous process for a monoclonal antibody (mAb) with three integrated process segments: upstream production processes with pool-less direct connection, pooled low pH virus inactivation with pH control and a total flow-through integrated polishing process in which two columns were directly connected with a virus filter. The pooled virus inactivation step defines the batch, and high impurities reduction and mAb recovery were achieved for batches conducted in succession.

Analysis of filtration behavior using integrated column chromatography followed by virus filtration.

We evaluated filtration behavior and virus removal capability for a monoclonal antibodies (mAb) and plasma IgG under constant flow rate directly following flow-through column chromatography in an integrated process. mAb solution with quantified host cell protein (HCP) content processed in flow-through mode on in-series mixed-mode AEX and modified CEX columns connected to the Planova BioEX filter (pool-less) achieved HCP logarithmic reduction value (LRV) of 2.3 and 93.

Evaluation of an anion-exchange hollow-fiber membrane adsorber containing γ-ray grafted glycidyl methacrylate chains.

It is widely recognized that membrane adsorbers are powerful tools for the purification of biopharmaceutical protein products and for this reason a novel hollow-fiber AEX type membrane adsorber has been developed. The membrane is characterized by grafted chains including DEA ligands affixed to the pore surfaces of the membrane. In order to estimate the membrane performance, (1) dynamic binding capacities for pure BSA and DNA over a range of solution conductivity and pH, (2) virus reduction by flow-through process, and (3) HCP and DNA removal from cell culture, are evaluated and compared with several other anion-exchange membranes.