Risk-benefit evaluation of on-line high-performance liquid chromatography analysis for pooling decisions in large-scale chromatography.

In the production of a human therapeutic protein from inclusion bodies, product related impurities of very similar size and charge to the product are created as byproducts of the refold process. Their removal is usually challenging even when using chromatography with high performance resins and elution by shallow linear gradients. Additionally, performing this type of separation for commercial production adds increased complexity.

Implementation of advanced technologies in commercial monoclonal antibody production.

Process advancements driven through innovations have been key factors that enabled successful commercialization of several human therapeutic antibodies in recent years. The production costs of these molecules are higher in comparison to traditional medicines. In order to lower the development and later manufacturing costs, recent advances in antibody production technologies target higher throughput processes with increased clinical and commercial economics.

Viral clearance using disposable systems in monoclonal antibody commercial downstream processing.

Once highly selective protein A affinity is chosen for robust mAb downstream processing, the major role of polishing steps is to remove product related impurities, trace amounts of host cell proteins, DNA/RNA, and potential viral contaminants. Disposable systems can act as powerful options either to replace or in addition to polishing column chromatography to ensure product purity and excellent viral clearance power for patients' safety. In this presentation, the implementation of three disposable systems such as depth filtration, membrane chromatography, and nanometer filtration technology in a commercial process are introduced.

pH-conductivity hybrid gradient cation-exchange chromatography for process-scale monoclonal antibody purification.

The commercial production of recombinant human monoclonal antibody therapeutics demands robust processes. In this article we describe the development of a pH-conductivity hybrid gradient for a cation-exchange chromatography step to obtain high binding capacity and consistent purification resolution in scale process. Operational parameters and their ranges were characterized with DOE statistical method.

Downstream processing of monoclonal antibodies--application of platform approaches.

This paper presents an overview of large-scale downstream processing of monoclonal antibodies and Fc fusion proteins (mAbs). This therapeutic modality has become increasingly important with the recent approval of several drugs from this product class for a range of critical illnesses. Taking advantage of the biochemical similarities in this product class, several templated purification schemes have emerged in the literature.

New Q membrane scale-down model for process-scale antibody purification.

Process-scale antibody production requires polishing steps with extremely high product throughput and robust operation. In this communication, the Sartobind Q membrane adsorber for process-scale antibody production is evaluated as an alternative to Q column chromatography. Although the capacity seen with large-scale membrane adsorbers is competitive with column chromatography, the same throughput is not achieved with the current scale-down models.

Basic concepts in Q membrane chromatography for large-scale antibody production.

The large-scale production of recombinant human monoclonal antibodies demands economical purification processes with high throughputs. In this article we briefly describe a common antibody process and evaluate the Q membrane adsorber for process-scale antibody production as an alternative to a Q-packed-bed column in a flow-through mode. The scientific concepts underlining Q membrane technology and its application are reviewed.