Current Science

Open Access Open Access  Restricted Access Subscription Access

Cell Culture Processes for Biopharmaceutical Manufacturing


Affiliations
1 Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune 411 008, India
 

Recombinant proteins manufactured using animal cell culture processes comprise a significant fraction of biopharmaceuticals. With the expiry of patents on this class of therapeutics, there is also a significant interest in manufacture of biosimilar versions of such therapeutics. This article provides a birds-eye view of upstream process development for animal cell culture processes, with a focus on advances pertinent to the development of processes for biosimilars.

Keywords

Biopharmaceutical, CHO, Cell Line Development, Glycosylation, Monoclonal Antibody.
User
Notifications
Font Size

  • Top drugs by sales revenue in 2015: Who sold the biggest blockbuster drugs?, 2016; http://www.pharmacompass.com/radiocompassblog/top-drugs-by-sales-revenue-in-2015-whosold-the-biggestblockbuster-drugs

  • Apweiler, R., Hermjakob, H. and Sharon, N., On the frequency of protein glycosylation, as deduced from analysis of the swissprot database. Biochim. Biophys. Acta, 1999, 1473, 4–8.

  • Walsh, G., Post-translational modifications of protein biopharmaceuticals. Drug Discov. Today, 2010, 15, 773–780.

  • Meehl, M. A. and Stadheim, T. A., Biopharmaceutical discovery and production in yeast. Curr. Opin. Biotechnol., 2014, 30, 120–127.

  • Falconer, R. J., Jackson-Matthews, D. and Mahler, S. M., Analytical strategies for assessing comparability of biosimilars. J. Chem. Technol. Biotechnol., 2011, 86, 915–922.

  • Jayapal, K. P., Wlaschin, K. F., Hu, W. S. and Yap, M. G. S., Recombinant protein therapeutics from CHO cells – 20 years and counting. Chem. Eng. Prog., 2007, 103, 40–47.

  • Ghaderi, D., Taylor, R. E., Padler-Karavani, V., Diaz, S. and Varki, A., Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat. Biotech., 2010, 28, 863–867.

  • Raju, S., Glycosylation variations with expression systems. BioProcess. Int., 2003, 1, 44–53.

  • Swiech, K., Picanco-Castro, V. and Covas, D. T., Human cells: New platform for recombinant therapeutic protein production. Protein Expr. Purif., 2012, 84, 147–153.

  • Rose, T., Winkler, K., Brundke, E., Jordan, I. and Sandig, V., Alternative strategies and new cell lines for high-level production of biopharmaceuticals. In Modern Biopharmaceuticals: Design, Development and Optimization (ed. Knäblein, J.), Wiley-VCH, Verlag, GmbH, 2005, pp. 761–777.

  • Seth, G., Hossler, P., Yee, J. C. and Hu, W.-S., Engineering cells for cell culture bioprocessing – physiological fundamentals. In Cell Culture Engineering (ed. Hu, W.-S.), Springer, Berlin, Heidelberg, pp. 119–164.

  • Noh, S. M., Park, J. H., Lim, M. S., Kim, J. W. and Lee, G. M., Reduction of ammonia and lactate through the coupling of glutamine synthetase selection and downregulation of lactate dehydrogenase – a in CHO cells. Appl. Microbiol. Biotechnol., 2016, 1–11.

  • Toussaint, C., Henry, O. and Durocher, Y., Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures. J. Biotechnol., 2016, 217, 122–131.

  • Tey, B. T., Singh, R. P., Piredda, L., Piacentini, M. and AlRubeai, M., Influence of bcl-2 on cell death during the cultivation of a Chinese Hamster Ovary cell line expressing a chimeric antibody. Biotechnol. Bioeng., 2000, 68, 31–43.

  • Meng, Y. G., Liang, J., Wong, W. L. and Chisholm, V., Green fluorescent protein as a second selectable marker for selection of high producing clones from transfected CHO cells. Gene, 2000, 242, 201–207.

  • Sinacore, M. S. et al., CHO DUKX cell lineages preadapted to growth in serum-free suspension culture enable rapid development of cell culture processes for the manufacture of recombinant proteins. Biotechnol. Bioeng., 1996, 52, 518–528.

  • Zhang, J. and Robinson, D., Development of animal-free, proteinfree and chemically-defined media for NS0 cell culture. Cytotechnology, 2005, 48, 59–74.

  • Lee, N., Shin, J., Park, J. H., Lee, G. M., Cho, S. and Cho, B.-K., Targeted gene deletion using DNA-free RNA-guided CAS9 nuclease accelerates adaptation of CHO cells to suspension culture. ACS Synth. Biol., 2016, 5, 1211–1219.

  • Yamane-Ohnuki, N. et al., Establishment of FUT8 knockout Chinese Hamster Ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibodydependent cellular cytotoxicity. Biotechnol. Bioeng., 2004, 87, 614–622.

  • Louie, S. et al., Fx knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality. Biotechnol. Bioeng., 2016, 114, 632–644.

  • Chiu, J., Valente, K. N., Levy, N. E., Min, L., Lenhoff, A. M. and Lee, K. H., Knockout of a difficult-to-remove CHO host cell protein, lipoprotein lipase, for improved polysorbate stability in monoclonal antibody formulations. Biotechnol. Bioeng., 2016.

  • Cheng, J. K., Lewis, A. M., Kim, D. S., Dyess, T. and Alper, H. S., Identifying and retargeting transcriptional hot spots in the human genome. Biotechnol. J., 2016, 11, 1100–1109.

  • Ludwig, D., Mammalian expression cassette engineering for high-level protein production: components, strategies, and options. BioProcess Int., 2006, 4, 14–23.

  • Kim, H., Laudemann, J., Stevens, J. and Wu, M., Expression vector engineering for recombinant protein production. In Cell Line Development (ed. Al-Rubeai, M.), Springer, The Netherlands, pp. 97–108.

  • Diepenbruck, C., Klinger, M., Urbig, T., Baeuerle, P. and Neef, R., Productivity and quality of recombinant proteins produced by stable CHO cell clones can be predicted by transient expression in HEK cells. Mol. Biotechnol., 2013, 54, 497–503.

  • Girard, P., Derouazi, M., Baumgartner, G., Bourgeois, M., Jordan, M., Jacko, B. and Wurm, F. M., 100-liter transient transfection. Cytotechnology, 2002, 38, 15–21.

  • Haldankar, R., Li, D., Saremi, Z., Baikalov, C. and Deshpande, R., Serum-free suspension large-scale transient transfection of CHO cells in WAVE bioreactors. Mol. Biotechnol., 2006, 34, 191–199.

  • Geisse, S., Reflections on more than 10 years of TGE approaches. Protein Exp. Purif., 2009, 64, 99–107.

  • Delafosse, L., Xu, P. and Durocher, Y., Comparative study of polyethylenimines for transient gene expression in mammalian HEK293 and CHO cells. J. Biotechnol., 2016, 227, 103–111.

  • Rajendra, Y., Kiseljak, D., Baldi, L., Hacker, D. L. and Wurm, F. M., A simple high-yielding process for transient gene expression in CHO cells. J. Biotechnol., 2011, 153, 22–26.

  • Glover, D. J., Leyton, D. L., Moseley, G. W. and Jans, D. A., The efficiency of nuclear plasmid DNA delivery is a critical determinant of transgene expression at the single cell level. J. Gene Med., 2010, 12, 77–85.

  • Tachibana, R. et al., Quantitative analysis of correlation between number of nuclear plasmids and gene expression activity after transfection with cationic liposomes. Pharm. Res., 2002, 19, 377–381.

  • Pradhan, K. and Gadgil, M., Effect of addition of ‘carrier’ DNA during transient protein expression in suspension CHO culture. Cytotechnology, 2012, 64, 613–622.

  • Rajendra, Y., Kiseljak, D., Manoli, S., Baldi, L., Hacker, D. L. and Wurm, F. M., Role of non-specific DNA in reducing coding DNA requirement for transient gene expression with CHO and HEK-293E cells. Biotechnol. Bioeng., 2012, 109, 2271–2278.

  • Kunaparaju, R., Liao, M. and Sunstrom, N. A., EPI-CHO, an episomal expression system for recombinant protein production in CHO cells. Biotechnol. Bioeng., 2005, 91, 670–677.

  • Wulhfard, S., Tissot, S., Bouchet, S., Cevey, J., De Jesus, M., Hacker, D. L. and Wurm, F. M., Mild hypothermia improves transient gene expression yields several fold in Chinese Hamster Ovary cells. Biotechnol. Prog., 2008, 24, 458–465.

  • Omasa, T., Gene amplification and its application in cell and tissue engineering. J. Biosci. Bioeng., 2002, 94, 600–605.

  • Chen, C. and Chasin, L., Cointegration of DNA molecules introduced into mammalian cells by electroporation. Somatic Cell Mol. Genet., 1998, 24, 249–256.

  • Barnes, L. M., Bentley, C. M. and Dickson, A. J., Advances in animal cell recombinant protein production: GS-NS0 expression system. Cytotechnology, 2000, 32, 109–123.

  • Feary, M., Racher, A. J., Young, R. J. and Smales, C. M., Methionine sulfoximine supplementation enhances productivity in GS–CHOK1SV cell lines through glutathione biosynthesis. Biotechnol. Prog., 2017, 33(1), 17–25; doi:10.1002/btpr.2372.

  • Fan, L., Kadura, I., Krebs, L. E., Hatfield, C. C., Shaw, M. M. and Frye, C. C., Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells. Biotechnol. Bioeng., 2012, 109, 1007–1015.

  • Van Blokland, H. J. M., Hoeksema, F., Siep, M., Otte, A. P. and Verhees, J. A., Methods to create a stringent selection system for mammalian cell lines. Cytotechnology, 2011, 63, 371–384.

  • Barnes, L. M., Moy, N. and Dickson, A. J., Phenotypic variation during cloning procedures: analysis of the growth behavior of clonal cell lines. Biotechnol. Bioeng., 2006, 94, 530–537.

  • Chusainow, J., Yang, Y. S., Yeo, J. H. M., Toh, P. C., Asvadi, P., Wong, N. S. C. and Yap, M. G. S., A study of monoclonal antibodyproducing CHO cell lines: What makes a stable high producer? Biotechnol. Bioeng., 2009, 102, 1182–1196.

  • Lee, J. S., Kallehauge, T. B., Pedersen, L. E. and Kildegaard, H. F., Site-specific integration in CHO cells mediated by CRISPR/CAS9 and homology-directed DNA repair pathway. Sci. Rep., 2015, 5, 8572.

  • Yang, Y., Mariati, Chusainow, J. and Yap, M. G. S., DNA methylation contributes to loss in productivity of monoclonal antibody-producing CHO cell lines. J. Biotechnol., 2010, 147, 180–185.

  • Wirth, D., Gama-Norton, L., Riemer, P., Sandhu, U., Schucht, R. and Hauser, H., Road to precision: Recombinase-based targeting technologies for genome engineering. Curr. Opin. Biotechnol., 2007, 18, 411–419.

  • Kito, M., Itami, S., Fukano, Y., Yamana, K. and Shibui, T., Construction of engineered CHO strains for high-level production of recombinant proteins. Appl. Microbiol. Biotechnol., 2002, 60, 442–448.

  • Zhang, L. et al., Recombinase-mediated cassette exchange (RMCE) for monoclonal antibody expression in the commercially relevant CHOK1SV cell line. Biotechnol. Prog., 2015, 31, 1645–1656.

  • Gaj, T., Gersbach, C. A. and Barbas, C. F., 3rd, ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol., 2013, 31, 397–405.

  • Kwaks, T. H. and Otte, A. P., Employing epigenetics to augment the expression of therapeutic proteins in mammalian cells. Trends Biotechnol., 2006, 24, 137–142.

  • Browne, S. M. and Al-Rubeai, M., Selection methods for highproducing mammalian cell lines. Trends Biotechnol., 2007, 25, 425–432.

  • Brezinsky, S. C. G. et al., A simple method for enriching populations of transfected CHO cells for cells of higher specific productivity. J. Immunol. Methods, 2003, 277, 141–155.

  • Nakamura, T. and Omasa, T., Optimization of cell line development in the GS-CHO expression system using a high-throughput, single cell-based clone selection system. J. Biosci. Bioeng., 2015, 120, 323–329.

  • Frye, C. et al., Industry view on the relative importance of ‘clonality’ of biopharmaceutical-producing cell lines. Biologicals, 2016, 44, 117–122.

  • Kermis, H. R., Kostov, Y., Harms, P. and Rao, G., Dual excitation ratiometric fluorescent pH sensor for noninvasive bioprocess monitoring: Development and application. Biotechnol. Prog., 2002, 18, 1047–1053.

  • Porter, A. J., Dickson, A. J. and Racher, A. J., Strategies for selecting recombinant CHO cell lines for CGMP manufacturing: realizing the potential in bioreactors. Biotechnol. Prog., 2010, 26, 1446–1454.

  • Porter, A. J., Racher, A. J., Preziosi, R. and Dickson, A. J., Strategies for selecting recombinant CHO cell lines for CGMP manufacturing: Improving the efficiency of cell line generation. Biotechnol. Prog., 2010, 26, 1455–1464.

  • Gadgil, M., Development of a mathematical model for animal cell culture without pH control and its application for evaluation of clone screening outcomes in shake flask culture. J. Chem. Technol. Biotechnol., 2015, 90, 166–175.

  • Janakiraman, V., Kwiatkowski, C., Kshirsagar, R., Ryll, T. and Huang, Y.-M., Application of high-throughput mini-bioreactor system for systematic scale-down modeling, process characterization, and control strategy development. Biotechnol. Prog., 2015, 31, 1623–1632.

  • Rameez, S., Mostafa, S. S., Miller, C. and Shukla, A. A., Highthroughput miniaturized bioreactors for cell culture process development: Reproducibility, scalability, and control. Biotechnol. Prog., 2014, 30, 718–727.

  • Legmann, R., Schreyer, H. B., Combs, R. G., McCormick, E. L., Russo, A. P. and Rodgers, S. T., A predictive high-throughput scale-down model of monoclonal antibody production in CHO cells. Biotechnol. Bioeng., 2009, 104, 1107–1120.

  • Bareither, R. and Pollard, D., A review of advanced small-scale parallel bioreactor technology for accelerated process development: Current state and future need. Biotechnol. Prog., 2011, 27, 2–14.

  • Silva, A. K. A., Richard, C., Bessodes, M., Scherman, D. and Merten, O.-W., Growth factor delivery approaches in hydrogels. Biomacromolecules, 2008, 10, 9–18.

  • Jeude, M., Dittrich, B., Niederschulte, H., Anderlei, T., Knocke, C., Klee, D. and Bãchs, J., Fed-batch mode in shake flasks by slow-release technique. Biotechnol. Bioeng., 2006, 95, 433–445.

  • Scheidle, M. et al., High-throughput screening of Hansenula Polymorpha clones in the batch compared with the controlled release fed-batch mode on a small scale. FEMS Yeast Res., 2010, 10, 83–92.

  • Hegde, S., Pant, T., Pradhan, K., Badiger, M. and Gadgil, M., Controlled release of nutrients to mammalian cells cultured in shake flasks. Biotechnol. Prog., 2012, 28, 188–195.

  • Pradhan, K., Pant, T. and Gadgil, M., In situ pH maintenance for mammalian cell cultures in shake flasks and tissue culture flasks. Biotechnol. Prog., 2012, 28, 1605–1610.

  • Sanil, R., Maralingannavar, V. and Gadgil, M., In situ pH management for microbial culture in shake flasks and its application to increase plasmid yield. J. Ind. Microbiol. Biotechnol., 2014, 41, 647–655.

  • Abu-Absi, S., Xu, S., Graham, H., Dalal, N., Boyer, M. and Dave, K., Cell culture process operations for recombinant protein production. In Mammalian Cell Cultures for Biologics Manufacturing (eds Zhou, W. and Kantardjieff, A.), Springer, Berlin, Heidelberg, 2014, pp. 35–68.

  • Croughan, M. S., Konstantinov, K. B. and Cooney, C., The future of industrial bioprocessing: Batch or continuous? Biotechnol. Bioeng., 2015, 112, 648–651.

  • Pollock, J., Ho, S. V. and Farid, S. S., Fed-batch and perfusion culture processes: economic, environmental, and operational feasibility under uncertainty. Biotechnol. Bioeng., 2013, 110, 206–219.

  • Bunnak, P., Allmendinger, R., Ramasamy, S. V., Lettieri, P. and Titchener-Hooker, N. J., Life-cycle and cost of goods assessment of fed-batch and perfusion-based manufacturing processes for mabs. Biotechnol. Prog., 2016, 32, 1324–1335.

  • Wlaschin, K. F. and Hu, W.-S., Fed-batch culture and dynamic nutrient feeding. Adv. Biochem. Eng. Biotechnol., 2006, 101, 43–74.

  • Bibila, T. A. and Robinson, D. K., In pursuit of the optimal fedbatch process for monoclonal antibody production. Biotechnol. Prog., 1995, 11, 1–13.

  • Rathore, A. S., QbD/PAT for bioprocessing: moving from theory to implementation. Curr. Opin. Chem. Eng., 2014, 6, 1–8.

  • Reusch, D. and Tejada, M. L., FC glycans of therapeutic antibodies as critical quality attributes. Glycobiology, 2015, 25, 1325–1334.

  • Goetze, A. M., Liu, Y. D., Zhang, Z., Shah, B., Lee, E., Bondarenko, P.V. and Flynn, G. C., High-mannose glycans on the FC region of therapeutic IgG antibodies increase serum clearance in humans. Glycobiology, 2011, 21, 949–959.

  • Shields, R. L., Lai, J., Keck, R., O’Connell, L. Y., Hong, K., Meng, Y. G., Weikert, S. H. A. and Presta, L. G., Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human fcγriii and antibody-dependent cellular toxicity. J. Biol. Chem., 2002, 277, 26733–26740.

  • Schiestl, M., Stangler, T., Torella, C., Cepeljnik, T., Toll, H. and Grau, R., Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat. Biotech., 2011, 29, 310–312.

  • Lin, N. et al., Chinese Hamster Ovary (CHO) host cell engineering to increase sialylation of recombinant therapeutic proteins by modulating sialyltransferase expression. Biotechnol. Prog., 2015, 31, 334–346.

  • Wong, N. S. C., Yap, M. G. S. and Wang, D. I. C., Enhancing recombinant glycoprotein sialylation through CMP-sialic acid transporter over expression in Chinese Hamster Ovary cells. Biotechnol. Bioeng., 2006, 93, 1005–1016.

  • Ngantung, F. A., Miller, P. G., Brushett, F. R., Tang, G. L. and Wang, D. I. C., RNA interference of sialidase improves glycoprotein sialic acid content consistency. Biotechnol. Bioeng., 2006, 95, 106–119.

  • Zhang, A., Tsang, V. L., Markely, L. R., Kurt, L., Huang, Y.-M., Prajapati, S. and Kshirsagar, R., Identifying the differences in mechanisms of mycophenolic acid controlling fucose content of glycoproteins expressed in different CHO cell lines. Biotechnol. Bioeng., 2016, 113, 2367–2376.

  • Hossler, P., Protein glycosylation control in mammalian cell culture: Past precedents and contemporary prospects. Adv. Biochem. Eng. Biotechnol., 2012, 127, 187–219.

  • Hossler, P., Khattak, S. F. and Li, Z. J., Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology, 2009, 19, 936–949.

  • Restelli, V. and Butler, M., The effect of cell culture parameters on protein glycosylation. In Cell Engineering: Glycosylation (ed. Al-Rubeai, M.), Springer, The Netherlands, 2002, pp. 61–92.

  • Villiger, T. K. et al., High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation. J. Biotechnol., 2016, 229, 3–12.

  • Crowell, C. K., Grampp, G. E., Rogers, G. N., Miller, J. and Scheinman, R. I., Amino acid and manganese supplementation modulates the glycosylation state of erythropoietin in a CHO culture system. Biotechnol. Bioeng., 2007, 96, 538–549.

  • Grainger, R. K. and James, D. C., CHO cell line specific prediction and control of recombinant monoclonal antibody N-glycosylation. Biotechnol. Bioeng., 2013, 110, 2970–2983.

  • Gramer, M. J. et al., Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose. Biotechnol. Bioeng., 2011, 108, 1591–1602.

  • Pacis, E., Yu, M., Autsen, J., Bayer, R. and Li, F., Effects of cell culture conditions on antibody N-linked glycosylation – what affects high mannose 5 glycoform. Biotechnol. Bioeng., 2011, 108, 2348–2358.

  • St Amand, M. M., Radhakrishnan, D., Robinson, A. S. and Ogunnaike, B. A., Identification of manipulated variables for a glycosylation control strategy. Biotechnol. Bioeng., 2014, 111, 1957–1970.

  • Surve, T. and Gadgil, M., Manganese increases high mannose glycoform on monoclonal antibody expressed in CHO when glucose is absent or limiting: Implications for use of alternate sugars. Biotechnol. Prog., 2015, 31, 460–467.

  • Jimenez del Val, I., Nagy, J. M. and Kontoravdi, C., A dynamic mathematical model for monoclonal antibody N-linked glycosylation and nucleotide sugar donor transport within a maturing golgi apparatus. Biotechnol. Prog., 2011, 27, 1730–1743.

  • Hossler, P., Mulukutla, B. C. and Hu, W.-S., Systems analysis of N-glycan processing in mammalian cells. PLoS ONE, 2007, 2, e713.

  • Umana, P. and Bailey, J. E., A mathematical model of N-linked glycoform biosynthesis. Biotechnol. Bioeng., 1997, 55, 890– 908.

  • Krambeck, F. J. and Betenbaugh, M. J., A mathematical model of N-linked glycosylation. Biotechnol. Bioeng., 2005, 92, 711–728.

  • Ben Yahia, B., Malphettes, L. and Heinzle, E., Macroscopic modeling of mammalian cell growth and metabolism. Appl. Microbiol. Biotechnol., 2015, 99, 7009–7024.

  • Sou, S. N., Jedrzejewski, P. M., Lee, K., Sellick, C., Polizzi, K. M. and Kontoravdi, C., Model-based investigation of intracellular processes determining antibody FC-glycosylation under mild hypothermia. Biotechnol. Bioeng., 2017; doi:10.1002/bit.26225.

  • Shukla, A. A. and Gottschalk, U., Single-use disposable technologies for biopharmaceutical manufacturing. Trends Biotechnol., 2013, 31, 147–154.

  • Eibl, R., Kaiser, S., Lombriser, R. and Eibl, D., Disposable bioreactors: The current state-of-the-art and recommended applications in biotechnology. Appl. Microbiol. Biotechnol., 2010, 86, 41–49.

  • Singh, V., Disposable bioreactor for cell culture using waveinduced agitation. Cytotechnology, 1999, 30, 149–158.

  • Okonkowski, J. et al., Cholesterol delivery to NS0 cells: Challenges and solutions in disposable linear low-density polyethylenebased bioreactors. J. Biosci. Bioeng., 2007, 103, 50–59.

  • Altaras, G. M., Eklund, C., Ranucci, C. and Maheshwari, G., Quantitation of interaction of lipids with polymer surfaces in cell culture. Biotechnol. Bioeng., 2007, 96, 999–1007.

  • Kelly, P. S. et al., Process-relevant concentrations of the leachable bdtbpp impact negatively on CHO cell production characteristics. Biotechnol. Prog., 2016, 32, 1547–1558.

  • Wang, X. and Riviere, I., Clinical manufacturing of CAR-T cells: Foundation of a promising therapy. Molec. Ther. Oncolytics, 2016, 3, 16015.

  • Bure, K. et al., Automation of CAR-T cell adoptive immunotherapy bioprocessing: Technology opportunities to debottleneck manufacturing. Bioprocess Int., 2016, 14.


Abstract Views: 436

PDF Views: 113




  • Cell Culture Processes for Biopharmaceutical Manufacturing

Abstract Views: 436  |  PDF Views: 113

Authors

Mugdha Gadgil
Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune 411 008, India

Abstract


Recombinant proteins manufactured using animal cell culture processes comprise a significant fraction of biopharmaceuticals. With the expiry of patents on this class of therapeutics, there is also a significant interest in manufacture of biosimilar versions of such therapeutics. This article provides a birds-eye view of upstream process development for animal cell culture processes, with a focus on advances pertinent to the development of processes for biosimilars.

Keywords


Biopharmaceutical, CHO, Cell Line Development, Glycosylation, Monoclonal Antibody.

References





DOI: https://doi.org/10.18520/cs%2Fv112%2Fi07%2F1478-1488