49. Rouiller Y, Périlleux A, Vesin M-N, Stettler M, Jordan M, Broly H (2014) Modulation of mAb
quality attributes using microliter scale fed-batch cultures. Biotechnol Prog 30:571–583
50. Yang WC, Lu J, Nguyen NB, Zhang A, Healy NV, Kshirsagar R, Ryll T, Huang Y-M (2014)
Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers.
Mol Biotechnol 56:421–428
51. Torkashvand F, Vaziri B, Maleknia S, Heydari A, Vossoughi M, Davami F, Mahboudi F (2015)
Designed amino acid feed in improvement of production and quality targets of a therapeutic
monoclonal antibody. PLoS One 10:e0140597
52. Ganguly J, Vogel G (2006) Process analytical technology (PAT) and scalable automation for
bioprocess control and monitoring-A case study. Pharm Eng 26
53. Kreutz C, Timmer J (2009) Systems biology: experimental design. FEBS J 276:923–942
54. Smucker B, Krzywinski M, Altman N (2018) Optimal experimental design. Nat Methods
15:559–560
55. Walter É, Pronzato L (1997) Identification of parametric models from experimental data.
Springer, London
56. Anselment B, Schoemig V, Kesten C, Weuster-Botz D (2012) Statistical vs. stochastic experimental design: an experimental comparison on the example of protein refolding. Biotechnol
Prog 28:1499–1506
57. Banga JR, Balsa-Canto E (2008) Parameter estimation and optimal experimental design. Essays
Biochem 45:195–209
58. Chaudhuri P, Mykland PA (1993) Nonlinear experiments: optimal design and inference based
on likelihood. J Am Stat Assoc 88:538
59. Ford I, Titterington DM, Kitsos CP (1989) Recent advances in nonlinear experimental design.
Technometrics 31:49
60. Franceschini G, Macchietto S (2008) Model-based design of experiments for parameter precision: state of the art. Chem Eng Sci 63:4846–4872
61. Moser A; Kuchemüller KB, Deppe S, Hernández Rodríguez T, Frahm B, Pörtner R, Hass VC,
Möller J. Model-assisted DoE software: optimization of growth and biocatalysis in Saccharomyces cerevisiae bioprocesses. under reveision
62. Nargund S, Guenther K, Mauch K (2019) The move toward Biopharma 4.0. Genet Eng
Biotechnol News 39:53–55
63. Möhler L, Bock A, Reichl U (2008) Segregated mathematical model for growth of anchoragedependent MDCK cells in microcarrier culture. Biotechnol Prog 24:110–119
64. Shirsat NP, English NJ, Glennon B, Al-Rubeai M (2015) Modelling of mammalian cell
cultures. In: Al-Rubeai M (ed) Animal cell culture, vol 9. Springer, Cham, pp 259–326
65. Pörtner R, Schäfer T (1996) Modelling hybridoma cell growth and metabolism — a comparison
of selected models and data. J Biotechnol 49:119–135
66. Djuris J, Djuric Z (2017) Modeling in the quality by design environment: regulatory requirements and recommendations for design space and control strategy appointment. Int J Pharm
533:346–356
67. Berry B, Moretto J, Matthews T, Smelko J, Wiltberger K (2015) Cross-scale predictive
modeling of CHO cell culture growth and metabolites using Raman spectroscopy and multivariate analysis. Biotechnol Prog 31:566–577
68. Pörtner R, Platas Barradas O, Frahm B, Hass VC (2016) Advanced process and control
strategies for bioreactors. In: Current developments in biotechnology and bioengineering:
bioprocesses, bioreactors and controls. Larroche C, Pandey A, Du G, Sanroman MA (eds)
Elsevier Science: Saint Louis, 463–493
69. Shirsat N, Mohd A, Whelan J, English NJ, Glennon B, Al-Rubeai M (2015) Revisiting Verhulst
and Monod models: analysis of batch and fed-batch cultures. Cytotechnology 67:515–530
70. Deppe S, Frahm B, Hass VC, Hernández Rodríguez T, Kuchemüller KB, Möller J, Pörtner R
(2020) Estimation of process model parameters. Methods Mol Biol 2095:213–234
71. Storhas W (2013) Bioverfahrensentwicklung. Wiley, Weinheim
Digital Twins and Their Role in Model-Assisted Design of Experiments
59
quality attributes using microliter scale fed-batch cultures. Biotechnol Prog 30:571–583
50. Yang WC, Lu J, Nguyen NB, Zhang A, Healy NV, Kshirsagar R, Ryll T, Huang Y-M (2014)
Addition of valproic acid to CHO cell fed-batch cultures improves monoclonal antibody titers.
Mol Biotechnol 56:421–428
51. Torkashvand F, Vaziri B, Maleknia S, Heydari A, Vossoughi M, Davami F, Mahboudi F (2015)
Designed amino acid feed in improvement of production and quality targets of a therapeutic
monoclonal antibody. PLoS One 10:e0140597
52. Ganguly J, Vogel G (2006) Process analytical technology (PAT) and scalable automation for
bioprocess control and monitoring-A case study. Pharm Eng 26
53. Kreutz C, Timmer J (2009) Systems biology: experimental design. FEBS J 276:923–942
54. Smucker B, Krzywinski M, Altman N (2018) Optimal experimental design. Nat Methods
15:559–560
55. Walter É, Pronzato L (1997) Identification of parametric models from experimental data.
Springer, London
56. Anselment B, Schoemig V, Kesten C, Weuster-Botz D (2012) Statistical vs. stochastic experimental design: an experimental comparison on the example of protein refolding. Biotechnol
Prog 28:1499–1506
57. Banga JR, Balsa-Canto E (2008) Parameter estimation and optimal experimental design. Essays
Biochem 45:195–209
58. Chaudhuri P, Mykland PA (1993) Nonlinear experiments: optimal design and inference based
on likelihood. J Am Stat Assoc 88:538
59. Ford I, Titterington DM, Kitsos CP (1989) Recent advances in nonlinear experimental design.
Technometrics 31:49
60. Franceschini G, Macchietto S (2008) Model-based design of experiments for parameter precision: state of the art. Chem Eng Sci 63:4846–4872
61. Moser A; Kuchemüller KB, Deppe S, Hernández Rodríguez T, Frahm B, Pörtner R, Hass VC,
Möller J. Model-assisted DoE software: optimization of growth and biocatalysis in Saccharomyces cerevisiae bioprocesses. under reveision
62. Nargund S, Guenther K, Mauch K (2019) The move toward Biopharma 4.0. Genet Eng
Biotechnol News 39:53–55
63. Möhler L, Bock A, Reichl U (2008) Segregated mathematical model for growth of anchoragedependent MDCK cells in microcarrier culture. Biotechnol Prog 24:110–119
64. Shirsat NP, English NJ, Glennon B, Al-Rubeai M (2015) Modelling of mammalian cell
cultures. In: Al-Rubeai M (ed) Animal cell culture, vol 9. Springer, Cham, pp 259–326
65. Pörtner R, Schäfer T (1996) Modelling hybridoma cell growth and metabolism — a comparison
of selected models and data. J Biotechnol 49:119–135
66. Djuris J, Djuric Z (2017) Modeling in the quality by design environment: regulatory requirements and recommendations for design space and control strategy appointment. Int J Pharm
533:346–356
67. Berry B, Moretto J, Matthews T, Smelko J, Wiltberger K (2015) Cross-scale predictive
modeling of CHO cell culture growth and metabolites using Raman spectroscopy and multivariate analysis. Biotechnol Prog 31:566–577
68. Pörtner R, Platas Barradas O, Frahm B, Hass VC (2016) Advanced process and control
strategies for bioreactors. In: Current developments in biotechnology and bioengineering:
bioprocesses, bioreactors and controls. Larroche C, Pandey A, Du G, Sanroman MA (eds)
Elsevier Science: Saint Louis, 463–493
69. Shirsat N, Mohd A, Whelan J, English NJ, Glennon B, Al-Rubeai M (2015) Revisiting Verhulst
and Monod models: analysis of batch and fed-batch cultures. Cytotechnology 67:515–530
70. Deppe S, Frahm B, Hass VC, Hernández Rodríguez T, Kuchemüller KB, Möller J, Pörtner R
(2020) Estimation of process model parameters. Methods Mol Biol 2095:213–234
71. Storhas W (2013) Bioverfahrensentwicklung. Wiley, Weinheim
Digital Twins and Their Role in Model-Assisted Design of Experiments
59