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      Evaluation of a Novel Methacrylate-Based Protein A Resin for the Purification of Immunoglobulins and Fc-Fusion Proteins

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          Abstract

          Protein A affinity chromatography is a central part of most commercial monoclonal antibody and Fc-fusion protein purification processes. In the last couple years an increasing number of new Protein A technologies have emerged. One of these new Protein A technologies consists of a novel, alkaline-tolerant, Protein A ligand coupled to a macroporous polymethacrylate base matrix that has been optimized for immunoglobulin (Ig) G capture. The resin is interesting from a technology perspective because the particle size and pore distribution of the base beads are reported to have been optimized for high IgG binding and fast mass transfer, while the Protein A ligand has been engineered for enhanced alkaline tolerance. This resin was subjected to a number of technical studies including evaluating dynamic and static binding capacities, alkaline stability, Protein A leachate propensity, impurity clearance, and pressure–flow behavior. The results demonstrated similar static binding capacities as those achieved with industry standard agarose Protein A resins, but marginally lower dynamic binding capacities. Removal of impurities from the process stream, particularly host cell proteins, was molecule dependent, but in most instances matched the performance of the agarose resins. This resin was stable in 0.1 M NaOH for at least 100 h with little loss in binding capacity, with Protein A ligand leakage levels comparable to values for the agarose resins. Pressure–flow experiments in lab-scale chromatography columns demonstrated minimal resin compression at typical manufacturing flow rates. Prediction of resin compression in manufacturing scale columns did not suggest any pressure limitations upon scale up. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1125–1136, 2014

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          Most cited references25

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          THE ADSORPTION OF GASES ON PLANE SURFACES OF GLASS, MICA AND PLATINUM.

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            Recent advances in large-scale production of monoclonal antibodies and related proteins.

            The rapid development of high-yielding and robust manufacturing processes for monoclonal antibodies is an area of significant focus in the biopharmaceutical landscape. Advances in mammalian cell culture have taken titers to beyond the 5 g/l mark. Platform approaches to downstream process development have become widely established. Continuous evolution of these platforms is occurring as experience with a wider range of products is accrued. The increased cell culture productivity has shifted the attention of bioprocess development to operations downstream of the production bioreactor. This has rejuvenated interest in the use of non-chromatographic separation processes. Here, we review the current state-of-the-art industrial production processes, focusing on downstream technologies, for antibodies and antibody-related products and discuss future avenues for evolution. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Industrialization of mAb production technology: the bioprocessing industry at a crossroads.

              Manufacturing processes for therapeutic monoclonal antibodies (mAbs) have evolved tremendously since the first licensed mAb product in 1986. The rapid growth in product demand for mAbs triggered parallel efforts to increase production capacity through construction of large bulk manufacturing plants as well as improvements in cell culture processes to raise product titers. This combination has led to an excess of manufacturing capacity, and together with improvements in conventional purification technologies, promises nearly unlimited production capacity in the foreseeable future. The increase in titers has also led to a marked reduction in production costs, which could then become a relatively small fraction of sales price for future products which are sold at prices at or near current levels. The reduction of capacity and cost pressures for current state-of-the-art bulk production processes may shift the focus of process development efforts and have important implications for both plant design and product development strategies for both biopharmaceutical and contract manufacturing companies.
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                Author and article information

                Journal
                Biotechnol Prog
                Biotechnol. Prog
                btpr
                Biotechnology Progress
                BlackWell Publishing Ltd (Oxford, UK )
                8756-7938
                1520-6033
                September 2014
                24 July 2014
                : 30
                : 5
                : 1125-1136
                Affiliations
                Process Biochemistry, Biogen Idec, Research Triangle Park NC, 27709
                Author notes
                Correspondence concerning this article should be addressed to E. K. Koepf at edward.koepf@ 123456biogenidec.com .

                Current address of Tyler R. McCaw: University of Alabama School of Medicine, 1825 University Boulevard, Birmingham, AL 35294

                Article
                10.1002/btpr.1951
                4415579
                25045034
                f56fdb28-4fa9-4bc4-9c76-2744164c676e
                © 2014 American Institute of Chemical Engineers

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 November 2013
                : 04 April 2014
                Categories
                Bioseparations and Downstream Processing

                protein a chromatography,binding capacities,pressure–flow profiles,alkaline stability,mabs,fc-fusion proteins

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