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73. von Stosch M, Hamelink J-M, Oliveira R (2016) Hybrid modeling as a QbD/PAT tool in
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74. Lei F, Rotbøll M, Jørgensen SB (2001) A biochemically structured model for Saccharomyces
cerevisiae. J Biotechnol 88:205–221
75. Brüning S, Gerlach I, Pörtner R, Mandenius C-F, Hass VC (2017) Modeling suspension
cultures of microbial and mammalian cells with an adaptable six-compartment model. Chem
Eng Technol 40:956–966
76. Orth JD, Thiele I, Palsson BØ (2010) What is flux balance analysis? Nat Biotechnol
28:245–248
77. Lularevic M, Racher AJ, Jaques C, Kiparissides A (2019) Improving the accuracy of flux
balance analysis through the implementation of carbon availability constraints for intracellular
reactions. Biotechnol Bioeng 116:2339–2352
78. Mantzaris NV, Daoutidis P, Srienc F (2001) Numerical solution of multi-variable cell population balance models. II. Spectral methods. Comput Chem Eng 25:1441–1462
79. Jandt U, Barradas OP, Pörtner R, Zeng A-P (2015) Synchronized mammalian cell culture: part
II--population ensemble modeling and analysis for development of reproducible processes.
Biotechnol Prog 31:175–185
80. Sanderson CS, Barford JP, Barton GW (1999) A structured, dynamic model for animal cell
culture systems. Biochem Eng J 3:203–211
81. Jang JD, Sanderson CS, Chan LC, Barford JP, Reid S (2000) Structured modeling of recombinant protein production in batch and fed-batch culture of baculovirus-infected insect cells.
Cytotechnology 34:71–82
82. Kontoravdi C, Wong D, Lam C, Lee YY, Yap MGS, Pistikopoulos EN, Mantalaris A (2007)
Modeling amino acid metabolism in mammalian cells-toward the development of a model
library. Biotechnol Prog 23:1261–1269
83. Jones B, Goos P (2012) I-optimal versus D-optimal split-plot response surface designs. J Qual
Technol 44:85–101
84. Lawson J (2010) Design and analysis of experiments with SAS. CRC Press, Hoboken
85. Johnson RT, Montgomery DC, Jones BA (2011) An expository paper on optimal design. Qual
Eng 23:287–301
86. Kenett R, Steinberg D (2007) New frontiers in the design of experiments. IEEE Eng Manag Rev
35:91
87. Steinberg DM, Lin DKJ (2006) Amendments and corrections. Biometrika 93:1025
88. Bursztyn D, Steinberg DM (2006) Comparison of designs for computer experiments. J Stat Plan
Infer 136:1103–1119
89. Vining GG, Kowalski SM (2011) Statistical methods for engineers.3rd edn. Brooks/Cole
Cengage Learning, Boston
90. Moser A. mDoE-toolbox
91. Beckmann TF, Krämer O, Klausing S, Heinrich C, Thüte T, Büntemeyer H, Hoffrogge R, Noll
T (2012) Effects of high passage cultivation on CHO cells: a global analysis. Appl Microbiol
Biotechnol 94:659–671
92. Wippermann A, Rupp O, Brinkrolf K, Hoffrogge R, Noll T (2015) The DNA methylation
landscape of Chinese hamster ovary (CHO) DP-12 cells. J Biotechnol 199:38–46
93. Ulonska S, Kroll P, Fricke J, Clemens C, Voges R, Müller MM, Herwig C (2018) Workflow for
target-oriented parametrization of an enhanced mechanistic cell culture model. Biotechnol J 13:
e1700395
94. Taylor KE (2001) Summarizing multiple aspects of model performance in a single diagram. J
Geophys Res 106:7183–7192
95. Gagnon M, Hiller G, Luan Y-T, Kittredge A, DeFelice J, Drapeau D (2011) High-end
pH-controlled delivery of glucose effectively suppresses lactate accumulation in CHO
fed-batch cultures. Biotechnol Bioeng 108:1328–1337
60
K. B. Kuchemüller et al.
Akad. Verl, Heidelberg
73. von Stosch M, Hamelink J-M, Oliveira R (2016) Hybrid modeling as a QbD/PAT tool in
process development: an industrial E. coli case study. Bioprocess Biosyst Eng 39:773–784
74. Lei F, Rotbøll M, Jørgensen SB (2001) A biochemically structured model for Saccharomyces
cerevisiae. J Biotechnol 88:205–221
75. Brüning S, Gerlach I, Pörtner R, Mandenius C-F, Hass VC (2017) Modeling suspension
cultures of microbial and mammalian cells with an adaptable six-compartment model. Chem
Eng Technol 40:956–966
76. Orth JD, Thiele I, Palsson BØ (2010) What is flux balance analysis? Nat Biotechnol
28:245–248
77. Lularevic M, Racher AJ, Jaques C, Kiparissides A (2019) Improving the accuracy of flux
balance analysis through the implementation of carbon availability constraints for intracellular
reactions. Biotechnol Bioeng 116:2339–2352
78. Mantzaris NV, Daoutidis P, Srienc F (2001) Numerical solution of multi-variable cell population balance models. II. Spectral methods. Comput Chem Eng 25:1441–1462
79. Jandt U, Barradas OP, Pörtner R, Zeng A-P (2015) Synchronized mammalian cell culture: part
II--population ensemble modeling and analysis for development of reproducible processes.
Biotechnol Prog 31:175–185
80. Sanderson CS, Barford JP, Barton GW (1999) A structured, dynamic model for animal cell
culture systems. Biochem Eng J 3:203–211
81. Jang JD, Sanderson CS, Chan LC, Barford JP, Reid S (2000) Structured modeling of recombinant protein production in batch and fed-batch culture of baculovirus-infected insect cells.
Cytotechnology 34:71–82
82. Kontoravdi C, Wong D, Lam C, Lee YY, Yap MGS, Pistikopoulos EN, Mantalaris A (2007)
Modeling amino acid metabolism in mammalian cells-toward the development of a model
library. Biotechnol Prog 23:1261–1269
83. Jones B, Goos P (2012) I-optimal versus D-optimal split-plot response surface designs. J Qual
Technol 44:85–101
84. Lawson J (2010) Design and analysis of experiments with SAS. CRC Press, Hoboken
85. Johnson RT, Montgomery DC, Jones BA (2011) An expository paper on optimal design. Qual
Eng 23:287–301
86. Kenett R, Steinberg D (2007) New frontiers in the design of experiments. IEEE Eng Manag Rev
35:91
87. Steinberg DM, Lin DKJ (2006) Amendments and corrections. Biometrika 93:1025
88. Bursztyn D, Steinberg DM (2006) Comparison of designs for computer experiments. J Stat Plan
Infer 136:1103–1119
89. Vining GG, Kowalski SM (2011) Statistical methods for engineers.3rd edn. Brooks/Cole
Cengage Learning, Boston
90. Moser A. mDoE-toolbox
91. Beckmann TF, Krämer O, Klausing S, Heinrich C, Thüte T, Büntemeyer H, Hoffrogge R, Noll
T (2012) Effects of high passage cultivation on CHO cells: a global analysis. Appl Microbiol
Biotechnol 94:659–671
92. Wippermann A, Rupp O, Brinkrolf K, Hoffrogge R, Noll T (2015) The DNA methylation
landscape of Chinese hamster ovary (CHO) DP-12 cells. J Biotechnol 199:38–46
93. Ulonska S, Kroll P, Fricke J, Clemens C, Voges R, Müller MM, Herwig C (2018) Workflow for
target-oriented parametrization of an enhanced mechanistic cell culture model. Biotechnol J 13:
e1700395
94. Taylor KE (2001) Summarizing multiple aspects of model performance in a single diagram. J
Geophys Res 106:7183–7192
95. Gagnon M, Hiller G, Luan Y-T, Kittredge A, DeFelice J, Drapeau D (2011) High-end
pH-controlled delivery of glucose effectively suppresses lactate accumulation in CHO
fed-batch cultures. Biotechnol Bioeng 108:1328–1337
60
K. B. Kuchemüller et al.