Abstract
In the past decade, we have seen a rapid expansion in mammalian cell based therapeutic proteinsreaching clinical applications. This increased demand has been met with much increased productivity throughintensive process development. During this time, fedbatch culture processes have emerged as the predominantmode for producing recombinant proteins. In this review, we discuss the fundamentals of fedbatch cultureprocess design, focusing on the use of stoichiometric nutrient requirements for feed medium formulation,and articulating the need and potential means for devising rational dynamic feeding schemes. Incorporationof on-line nutrient measurement will play a key role in further refinement of process control for thedevelopment of a much sought after generic feeding strategy that can respond to the changing demandsof different cell lines in a fluctuating culture environment. The future of process engineering willlikely require a combination of current process engineering strategies along with a better understandingand control over cell physiology. Process development will likely to entail not only optimizing traditionalengineering parameters but also engineering cell lines with desired characteristics. The integration ofcell engineering and process intensification will likely provide the stimuli that propel the limits of growthand productivity to the next high level.
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References
Ozturk SS, Riley MR, Palsson BO (1992) Biotechnol Bioeng 39:418
Yang M, Butler M (2002) Biotechnol Prog 18:129
Zielke HR, Ozand PT, Tildon JT, Sevdalian DA, Cornblath M (1976) Proc Natl Acad Sci USA 73:4110
Zielke HR, Ozand PT, Tildon JT, Sevdalian DA, Cornblath M (1978) J Cell Physiol 95:41
Reitzer LJ, Wice BM, Kennel D (1979) J Biol Chem 254
Fleischaker RT (1982) An experimental study in the use of instrumentation to analyze metabolism and product formation in cell culture. Massachusetts Institute of Technology
Glacken MW, Fleischaker RJ, Sinskey AJ (1986) Biotechnol Bioeng 28:1376
Zhou WC, Rehm J, Hu WS (1995) Biotechnol Bioeng 46:579
Zhou W-C, Rehm J, Europa A, Hu W-S (1997) Cytotechnology 24:99
Europa AF, Gambhir A, Fu P, Hu W-S (2000) Biotechnol Bioeng 67:25
Gambhir A, Korke R, Lee J, Fu P-C, Hu W-S (2003) J Biosci Bioeng 95:317
Zeng AP, Hu WS, Deckwer WD (1998) Biotechnol Prog 14:434
Bibila TA, Ranucci CS, Konstantin G, Buckland BC, Aunins JG (1994) Biotechnol Prog 10:87
Eagle H (1955) Science 122:501
Eagle H (1959) Science 130:432
Andersen DC, Goochee CF (1994) Curr Opin Biotechnol 5:546
Xie LZ, Nyberg G, Gu XJ, Li HY, Mollborn F, Wang DIC (1997) Biotechnol Bioeng 56:577
Nyberg GB, Balcarcel RR, Follstad BD, Stephanopoulos G, Wang DIC (1999) Biotechnol Bioeng 62:336
Wong DCF, Wong KTK, Goh LT, Heng CK, Yap MGS (2005) Biotechnol Bioeng 89:164
Darnell J, Lodish H, Baltimore D (1986) Molecular Cell Biology. Scientific American Books, New York
Okayasu T, Ikeda M, Akimoto K, Sorimachi K (1997) Amino Acids 13:379
Edelman GE, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, Waxdal MJ (1969) Proc Natl Acad Sci USA 63:78
de Zengotita VM, Miller WM, Aunins JG, Zhou W (2000) Biotechnol Bioeng 69:566
Dempsey J, Ruddock S, Osborne M, Ridley A, Sturt S, Field R (2003) Biotechnol Prog 19:175
Spens E, Haggstrom L (2005) Biotechnol Prog 21:87
Swartz JR (1996) In: Neidhardt FC (ed) Escherichia coli and Salmonella: cellular and molecular biology. Ame Soc Microbiol, Washington DC, p 1693
Ozturk SS, Thrift JC, Blackie JD, Naveh D (1997) Biotechnol Bioeng 53:372
Wang J, Honda H, Lenas P, Watanabe H, Kobayashi T (1995) J Ferment Bioeng 80:107
Kurokawa H, Park YS, Iijima S, Kobayashi T (1994) Biotechnol Bioeng 44:95
Larson TM, Gawlitzek M, Evans H, Albers U, Cacia J (2002) Biotechnol Bioeng 77:553
Hu W-S, Zhou W, Europa LF (1998) Korean J Microbiol Biotechnol 8:8
Gambhir A, Europa AF, Hu WS (1999) J Biosci Bioeng 87:805
Zhou W, Hu W-S (1994) In: Galindo E, Ramirez OT (eds) Advances in Bioprocess Engineering. Kluwer Academic Publishers, Netherlands, p 109
Konstantinov KB, Pambayun R, Matanguihan R, Yoshida T, Perusich CM, Hu W-S (1992) Biotechnol Bioeng 40:1337
Wu P, Ozturk SS, Blackie JD, Thrift JC, Figueroa C, Naveh D (1995) Biotechnol Bioeng 45:495
Zhou WC, Chen C-C, Buckland B, Aunins JG (1997) Biotechnol Bioeng 55:783
Hu WS, Oberg MG (1990) Bioprocess Technol 10:451
Lin JQ, Takagi M, Qu YB, Yoshida T (2002) Biochem Eng J 11:205
Li L, Li M, Feng Q, Liu R, Tang H, Xie L, Yu X, Chen Z (2005) Biotechnol Appl Biochem 42:73
Sauer PW, Burky JE, Wesson MC, Sternard HD, Qu L (2000) Biotechnol Bioeng 67:585
Palermo DP, DeGraaf ME, Marotti KR, Rehberg E, Post LE (1991) J Biotechnol 19:35
Oh SKW, Vig P, Chua F, Teo WK, Yap MGS (1993) Biotechnol Bioeng 42:601
Kaufmann H, Mazur X, Fussenegger M, Bailey JE (1999) Biotechnol Bioeng 63:573
Mimura Y, Lund J, Church S, Dong S, Li J, Goodall M, Jefferis R (2001) J Immunol Methods 247:205
Kim MS, Kim NS, Sung YH, Lee GM (2002) In Vitro Cell Dev Biol – Animal 38:314
Yoon SK, Kim SH, Lee GM (2003) Biotechnol Prog 19:1383
Sun Z, Zhou R, Liang S, McNeeley KM, Sharfstein ST (2003) Biotechnol Prog
Yoon SK, Hong JK, Lee GM (2004) Biotechnol Prog 20:1293
Sung YH, Lim SW, Chung JY, Lee GM (2004) Appl Microbiol Biotechnol 63:527
Fox SR, Patel UA, Yap MG, Wang DI (2004) Biotechnol Bioeng 85:177
Zhou W, Hu W-S (1994) Biotechnol Bioeng 44:170
Portner R, Schwabe J-O, Frahm B (2004) Biotechnol Appl Biochem 40:47
Barnes LM, Bentley CM, Dickson AJ (2000) Cytotechnology 32:109
Bebbington CR, Renner G, Thompson S, King D, Abrams D, Yarranton GT (1992) Bio/technology 10:169
Cockett MI, Bebbington CR, Yarranton GT (1990) Biotechnology (NY) 8
Pu H, Cashion LM, Kretschmer PJ, Liu Z (1998) Mol Biotechnol 10
Hassell T, Butler M (1990) Journal of Cell Science 96:501
Schneider M, Marison IW, Vonstockar U (1996) J Biotechnol 46:161
Genzel Y, Ritter JB, Konig S, Alt R, Reichl U (2005) Biotechnol Bioeng 21:58
Eagle H, Barban S, Levy M, Schultze HO (1958) J Biol Chem 233:551
Low K, Harbour C (1985) Dev Biol Stand 60
Petch D, Butler M (1996) Appl Biochem Biotechnol 59
Martinelle K, Doverskog M, Jacobsson U, Chapman BE, Kuchel PW, Haggstrom L (1998) Biotechnol Bioeng 60
Imamura T, Crespi CL, Thilly WG, Brunengraber H (1982) Anal Biochem 124:353
Reitzer LJ, Wice BM, Kennell D (1979) J Biol Chem 254:2669
Barngrover D, Thomas J, Thilly WG (1985) J Cell Sci 78
Petch D, Butler M (1996) Appl Biochem Biotechnol 59:93
Altamirano C, Illanes A, Casablancas A, Gamez X, Cairo JJ, Godia F (2001) Biotechnol Prog 17:1032
Altamirano C, Paredes C, Cairo JJ, Godia F (2000) Biotechnol Prog 16:69
Altamirano C, Cairo JJ, Godia F (2001) Biotechnol Bioeng 76:351
Altamirano C, Paredes C, Illanes A, Cairo JJ, Godia F (2004) J Biotechnol 110:171
Mochizuki K, Sato S, Kato M, Hashizume S (1993) Cytotechnology 13:161
Tachibana H, Taniguchi K, Ushio Y, Teruya K, Osada K, Murakami H (1994) Cytotechnology 16:151
Jeong D, Kim TS, Lee JW, Kim KT, Kim HJ, Kim IH, Kim IY (2001) Biochem Biophys Res Commun 289:1141
Chen K, Liu Q, Xie L, Sharp PA, Wang DI (2001) Biotechnol Bioeng 72:55
Irani N, Wirth M, van den Heuvel J, Wagner R (1999) Biotechnol Bioeng 66:238
Fogolin MB, Wagner R, Etcheverrigaray M, Kratje R (2004) J Biotechnol 109:179
Elias CB, Carpentier E, Durocher Y, Bisson L, Wagner R, Kamen A (2003) Biotechnol Prog 19:90
Noguchi Y, Saito A, Miyagi Y, Yamanaka S, Marat D, Doi C, Yoshikawa T, Tsuburaya A, Ito T, Satoh S (2000) Cancer Lett 154:175
Al-Khalil IL, Cartee GD, Krook A (2003) Biochem Biophys Res Commun 307:127
Acknowledgments
The support of the cell culture research from Pfizer, Inc., Bayer Health Care, and Merck Co. is gratefully acknowledged. KFW was supported by the NIH Biotechnology Training Grant (GM08347).
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Wlaschin, K.F., Hu, WS. (2006). Fedbatch Culture and Dynamic Nutrient Feeding. In: Hu, WS. (eds) Cell Culture Engineering. Advances in Biochemical Engineering/Biotechnology, vol 101. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_015
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DOI: https://doi.org/10.1007/10_015
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