Implementing high-temperature short-time media treatment in commercial-scale cell culture manufacturing processes.

The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.

Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production.

As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost-of-goods in large-scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor.

Isolation and characterization of therapeutic antibody charge variants using cation exchange displacement chromatography.

In this report, we have demonstrated the isolation and enrichment of charge variants of a monoclonal antibody IgG1 using cation exchange displacement chromatography. We successfully achieved the separation of acidic, main and basic charge variants with high recovery (>70%) and purity (>90%) by using a commercially available stationary phase in conjunction with a commercially available displacer. In addition, we have isolated and enriched a trace methionine-oxidized variant of the monoclonal antibody allowing a secondary means of identification of this variant while providing sufficient enrichment for further analysis, stability tests and potency determination.