• 1
    Schügerl, K., Bioreaction Engineering, Bioprocess Monitoring, Volume 3. John Wiley & Sons, Chichester, UK, 1997.
  • 2
    Sonnleitner, B., Instrumentation of biotechnological processes. Adv. Biochem. Eng. Biotechnol. 1999, 66, 164.
  • 3
    Mandenius, C. F., Recent developments in monitoring, modelling and control of biological production systems. Bioproc. Biosys. Eng. 2004, 26, 347351.
  • 4
    United States Federal Food and Drug Administration (USA). Guidance for industry, process analytical technology, FDA, 2004.
  • 5
    European Medicines Agency, EMA-FDA pilot program for parallel assessment of Quality by Design applications. Document EMA/172347/2011, 2011.
  • 6
    International conference on Harmonization (ICH) Document ICH Q8–Q10, 2005–2010. Available at
  • 7
    Glassey, J., Gernaey, K.V., Oliveria, R., Striedner, G. et al., PAT for biopharmaceuticals. Biotechnol. J. 2011, 6, 369377.
  • 8
    Mandenius, C.-F., Graumann, K., Schultz, T. W., Premsteller, A., Quality-by-Design (QbD) for biotechnology-related phamaceuticals. Biotechnol. J. 2009, 4, 600609.
  • 9
    Kadlec, P., Gabrys, B., Strandt, S. et al., Data-driven soft sensors in the process industry. Comput. Chem. Eng. 2009, 33, 795814.
  • 10
    Chéruy, A., Software sensors in bioprocess engineering. J. Biotechnol. 1997, 52, 193199.
  • 11
    Zamprogna, E., Barolo, M., Seborg, D. E., Development of a soft sensor for a batch distillation column using linear and nonlinear PLS regression techniques. Contr. Eng. Pract. 2004, 12, 917929.
  • 12
    Choi, D. J., Park, H., A hybrid artificial neural network as a software sensor for optimal control of a wastewater treatment process. Water Res. 2001, 35, 39593967.
  • 13
    Montague, G. A., Morris, A. J., Tham, M. T., Enhancing bioprocess operability with generic software sensors, J. Biotechnol. 1992, 25, 183201.
  • 14
    Kiviharju, K., Salonen, K., Moilanen, U., Eerikäinen, T., Biomass measurement online: the performance of in situ measurements and software sensors. J. Ind. Microbiol. Biotechnol. 2008, 35, 657665.
  • 15
    Sundström, H., Enfors, S.O., Software sensors for fermentation processes. Bioproc. Biosyst. Eng. 2008, 31, 145152.
  • 16
    Ödman, P., Lindvald Johansen, C., Olsson, L., Gernaey, K. V., Eliasson Lantz, A., On-line estimation of biomass, glucose and ethanol in Saccharomyces cerevisiae cultivations using in-situ multi-wavelength fluorescence and software sensors. J. Biotechnol. 2009, 144, 102112.
  • 17
    Warth, B., Rajkai, G., Mandenius, C. F., Evaluation of software sensors for on-line estimation of culture conditions in an Escherichia coli cultivation expressing a recombinant protein. J. Biotechnol. 2010, 147, 3745.
  • 18
    Qin, S. J., Yue, H., Dunia, R., Self-validating inferential sensors with application to air emission monitoring. Ind. Eng. Chem. Res. 1997, 36, 16751685.
  • 19
    Han, C., Lee, Y. H., Intelligent integrated plant operation system for six sigma. Ann. Rev. Contr. 2002, 26, 2743.
  • 20
    Goodwin, G. C., Predicting the performance of soft sensors as a route to low cost automation. Ann. Rev. Contr. 2000, 24, 5566.
  • 21
    Van Impe J. F. M., Vanrolleghem P. A., Iserentant D. M. (Eds.), Advanced Instrumentation, Data Interpretation, and Control of Biotechnological Processes. Kluwer Academic Publishers, Dordrecht, The Netherlands, 1998.
  • 22
    Scarff, M., Arnold, S.A., Harvey, L.M., McNeil, B., Near infrared spectroscopy for bioprocess monitoring and control: current status and future trends. Crit. Rev. Biotechnol. 2006, 26, 1739.
  • 23
    Papini, M., Olsson, L., Eliasson-Lantz, A., van den Berg, F. et al., Monitoring of heterologous protein production in yeast using on-line measurements and multivariate data analysis J. Biotechnol. 2007, 131, S183S183.
  • 24
    Navratil, M., Norberg, A., Lembrén, L., Mandenius, C. F., Online multianalyzer monitoring of biomass, glucose, and acetate for growth rate control of a Vibrio cholerae fed-batch cultivation. J. Biotechnol. 2005, 115, 6779.
  • 25
    Peuker, T., Riedel, M., Kaiser, C., Ellert, A. et al., At-line determination of glucose, ammonium and acetate in high cell density cultivations of Escherichia coli. Eng. Life Sci. 2004, 4, 138143.
  • 26
    Kaiser, C., Carvell, J. P., Luttmann, R., A sensitive, compact, in situ biomass measurement system. BioProc. Intern. 2007, 5, 5256.
  • 27
    Cornelissen, G., Bertelsen, H.-P., Lenz, K., Hahn, B. et al., Production of recombinant proteins with Pichia pastoris in integrated processing. Eng. Life Sci. 2003, 3, 361370.
  • 28
    Fricke, J., Pohlmann, K., Tatge, F., Lang, R. et al., A multi-bioreactor system for optimal production of malaria vaccines with Pichia pastoris in integrated processing. Biotechnol. J. 2011, 6, 437451.
  • 29
    Luttmann, R., Bitzer, G., Hartkopf, J., Development of control strategies for high cell density cultivation. Math. Comp. Simul. 1994, 37, 153164.
  • 30
    Glassey, J., Montague, G.A., Ward, A.C., Kara, B., Enhanced supervision of recombinant E.coli fermentations via artificial neural networks, Proc. Biochem. 1994, 29, 387398.
  • 31
    Aehle, M., Kuprijanov, A., Schaepe, S., Simutis, R., Lübbert, A., Simplified off-gas analyses in animal cell cultures for process monitoring and control purposes. Biotechnol. Lett. 2011, 33, 21032110.
  • 32
    Bachinger, T., Mandenius, C.F., Review: Searching process information in the aroma of cell cultures. Trend. Biotechnol. 2000, 18, 494500.
  • 33
    Turner, C., Rudnitskaya, A., Legin, A., Monitoring batch fermentations with an electronic tongue. J. Biotechnol. 2003, 103, 8791.
  • 34
    Scheper, T., Hitzmann, B., Stärk, E., Ulber, R., Faurie, R., Sosnitza, P., Reardon, K.F., Bioanalytics: detailed insight into bioprocesses. Anal. Chim. Acta 1999, 400, 121134.
  • 35
    Bracewell, D.G., Brown, R.A., Hoare, M., Addressing a whole bioprocess in real-time using an optical biosensor - from a recombinant E. coli host. Bioproc. Biosys. Eng. 2004, 26, 271282.
  • 36
    Sellick, C., Hansen, R., Jarvis, R., Maqsood, A. et al., Rapid monitoring of recombinant antibody production by mammalian cell cultures using Fourier transform infrared spectroscopy and chemometrics. Biotechnol. Bioeng. 2010, 106, 432442.
  • 37
    Brewster, V. L., Ashton, L., Goodacre, R., Monitoring the glycosylation status of proteins using Raman spectroscopy Anal. Chem. 2011, 83, 60746081.
  • 38
    Ignova, M., Glassey, J., Ward, A.C., Montague, G.A., Multivariate statistical methods in bioprocess fault detection and performance forecasting. Trans. Inst. MC, 1997, 19, 271279.
  • 39
    Albiol, J., Robustr , ., Casas, C., Poch, M., Biomass estimation in plant cell cultures using an extended Kalman filter. Biotechnol. Prog. 1993, 9, 174178.
  • 40
    Arnold, S.A., Crowley, J., Woods, N., Harvey, M. L. et al., In-situ near infrared spectroscopy to monitor key analytes in mammalian cell cultivation. Biotechnol. Bioeng. 2003, 84, 1319.
  • 41
    Roychoudhury, P., O'Kennedy, R., McNeil, B., Harvey, L.M., Multiplexing fibre optic near infrared (NIR) spectroscopy as an emerging technology to monitor industrial bioprocesses, Anal. Chim. Acta 2007, 590, 110117.
  • 42
    Faergestad, E.M., Oyaas, J., Kohler, A., Berg, T., Næs, T., The use of spectroscopic measurements from full scale industrial production to achieve stable end product quality. J. Food Sci. Technol. 2011, 44, 22662272.
  • 43
    Gao, Y., Yuan, Y.-J., Comprehensive quality evaluation of corn steep liquor in 2-keto-L-gulonic acid fermentation. J. Agric. Food Chem. 2011, 59, 98459853.
  • 44
    Cunha, C.C.F., Glassey, J., Montague, G.A., Albert, S., Mohan, P., An assessment of seed quality and its influence on productivity estimation in an industrial antibiotic fermentation. Biotechnol. Bioeng. 2002, 78, 658669.
  • 45
    Jiang, C., Flansburg, L., Ghose, S., Jorjorian, P., Shukla, A.A., Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles, Biotechnol. Bioeng 2010, 107, 985997.
  • 46
    Gao, Y., Kipling, K., Glassey, J., Willis, M. et al., Application of agent-based system for bioprocess description and process improvement, Proc. Biochem. 2010, 26, 706716.