Mechanistic modeling of minute virus of mice surrogate removal by anion exchange chromatography in micro scale.

Biopharmaceutical products are often produced in Chinese hamster ovary (CHO) cell cultures that are vulnerable to virus infections. Therefore, it is a regulatory requirement that downstream purification steps for biopharmaceuticals can remove viruses from feedstocks. Anion exchange chromatography (AEX) is one of the downstream unit operations that is most frequently used for this purpose and claimed for its capability to remove viruses.

Exploration of fiber-based cation exchange adsorbents for the removal of monoclonal antibody aggregates.

Cation exchange chromatography (CEX) is a widely used technique for the removal of monoclonal antibody (mAb) aggregates. At present, resins are mainly used for this purpose, as convective types of adsorbents such as membrane adsorbers (MAs) have often not demonstrated overall comparable performance for this particular application. Fiber-based adsorbents can overcome the current limitations of MAs with respect to permeability, binding capacity, and adsorbent cost, and could therefore be a viable alternative to resins for the removal of mAb aggregates.

Analysis of complex protein elution behavior in preparative ion exchange processes using a colloidal particle adsorption model.

A fundamental understanding of the protein retention mechanism in preparative ion exchange (IEX) chromatography columns is essential for a model-based process development approach. For the past three decades, the mechanistic description of protein retention has been based predominantly on the steric mass action (SMA) model. In recent years, however, retention profiles of proteins have been reported more frequently for preparative processes that are not consistent with the mechanistic understanding relying on the SMA model.

High throughput screening of fiber-based adsorbents for material and process development.

There has been a growing interest in fibers and fiber-based adsorbents as alternative adsorbents for preparative chromatography. While the benefits of fiber-based adsorbents in terms of productivity have been highlighted in several recent studies, microscale tools that enable a fast characterization of these novel adsorbents, and an easy integration into process development workflows, are still lacking. In the present study an automated high-throughput screening (HTS) for fiber-based adsorbents was established on a robotic liquid handling station in 96 well filter plates.

Packing characteristics of winged shaped polymer fiber supports for preparative chromatography.

Polymer fibers have been identified as a promising alternative support material for liquid chromatography. Area enhanced fibers may overcome the shortcomings of conventional fiber supports with respect to binding capacity and packing efficiency. One type of area enhanced fiber supports are winged shaped microfibers, which have a more than tenfold higher surface area than round fibers, and can be manufactured via inexpensive, conventional extrusion techniques.

Feasibility of using continuous chromatography in downstream processing: Comparison of costs and product quality for a hybrid process vs. a conventional batch process.

The protein A capture step is the main cost-driver in downstream processing, with high attrition costs especially when using protein A resin not until end of resin lifetime. Here we describe a feasibility study, transferring a batch downstream process to a hybrid process, aimed at replacing batch protein A capture chromatography with a continuous capture step, while leaving the polishing steps unchanged to minimize required process adaptations compared to a batch process. 35g of antibody were purified using the hybrid approach, resulting in comparable product quality and step yield compared to the batch process.

A mechanistic model of ion-exchange chromatography on polymer fiber stationary phases.

Fibers are prominent among novel stationary phase supports for preparative chromatography. Several recent studies have highlighted the potential of fiber-based adsorbents for high productivity downstream processing in both batch and continuous mode, but so far the development of these materials and of processes employing these materials has solely been based on experimental data. In this study we assessed whether mechanistic modeling can be performed on fiber-based adsorbents.

IFN-β treatment requires B cells for efficacy in neuroautoimmunity.

IFN-β remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-β, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-β treatment is unclear.