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      Developments and opportunities in continuous biopharmaceutical manufacturing

      review-article
      ,
      mAbs
      Taylor & Francis
      Biopharmaceuticals, bioprocessing, monoclonal antibodies, continuous manufacturing, perfusion culture, chromatography, biosimilars, filtration, viral inactivation, process analytical technology

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          ABSTRACT

          Today’s biologics manufacturing practices incur high costs to the drug makers, which can contribute to high prices for patients. Timely investment in the development and implementation of continuous biomanufacturing can increase the production of consistent-quality drugs at a lower cost and a faster pace, to meet growing demand. Efficient use of equipment, manufacturing footprint, and labor also offer the potential to improve drug accessibility. Although technological efforts enabling continuous biomanufacturing have commenced, challenges remain in the integration, monitoring, and control of traditionally segmented unit operations. Here, we discuss recent developments supporting the implementation of continuous biomanufacturing, along with their benefits.

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          Most cited references166

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          Antibody structure, instability, and formulation.

          The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.
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            Economic Analysis of Integrated Continuous and Batch Pharmaceutical Manufacturing: A Case Study

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              Advances in recombinant antibody manufacturing

              Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.
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                Author and article information

                Journal
                MAbs
                MAbs
                mAbs
                Taylor & Francis
                1942-0862
                1942-0870
                11 April 2021
                2021
                11 April 2021
                : 13
                : 1
                : 1903664
                Affiliations
                [0001]Department of Chemical and Biomolecular Engineering, University of Delaware; , Newark, DE
                Author notes
                CONTACT Abraham M. Lenhoff lenhoff@ 123456udel.edu Department of Chemical and Biomolecular Engineering, University of Delaware; , Newark, DE19716.
                Author information
                https://orcid.org/0000-0003-2536-0785
                https://orcid.org/0000-0002-7831-219X
                Article
                1903664
                10.1080/19420862.2021.1903664
                8043180
                33843449
                168bb659-49b5-4e8b-b76c-99da7dec2a6f
                © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 2, References: 174, Pages: 1
                Categories
                Review
                Review

                Immunology
                biopharmaceuticals,bioprocessing,monoclonal antibodies,continuous manufacturing,perfusion culture,chromatography,biosimilars,filtration,viral inactivation,process analytical technology

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