title: Mammalian cell culture monitoring using in situ spectroscopy: Is your method really optimised?
abstract: In recent years, as a result of the process analytical technology initiative of the US Food and Drug Administration, many different works have been carried out on direct and in situ monitoring of critical parameters for mammalian cell cultures by Raman spectroscopy and multivariate regression techniques. However, despite interesting results, it cannot be said that the proposed monitoring strategies, which will reduce errors of the regression models and thus confidence limits of the predictions, are really optimized. Hence, the aim of this article is to optimize some critical steps of spectroscopic acquisition and data treatment in order to reach a higher level of accuracy and robustness of bioprocess monitoring. In this way, we propose first an original strategy to assess the most suited Raman acquisition time for the processes involved. In a second part, we demonstrate the importance of the interbatch variability on the accuracy of the predictive models with a particular focus on the optical probes adjustment. Finally, we propose a methodology for the optimization of the spectral variables selection in order to decrease prediction errors of multivariate regressions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:308-316, 2017.
authors.affiliation: LASIR CNRS UMR 8516, Université de Lille - Sciences et Technologies, Villeneuve d'Ascq Cedex, 59655, France.
authors.forename: Silvère
authors.initials: S
authors.lastname: André
authors.affiliation: Merial, 29 Avenue Tony Garnier, Lyon, 69007, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lagresle
authors.affiliation: Merial, 29 Avenue Tony Garnier, Lyon, 69007, France.
authors.forename: Zahia
authors.initials: Z
authors.lastname: Hannas
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, Marcy-l'Étoile, 69280, France.
authors.forename: Éric
authors.initials: É
authors.lastname: Calvosa
authors.affiliation: LASIR CNRS UMR 8516, Université de Lille - Sciences et Technologies, Villeneuve d'Ascq Cedex, 59655, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Duponchel
mesh_terms: D000465:Algorithms; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods / Q000592:standards*; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005602:France; D017408:Guidelines as Topic; D006801:Humans; D008991:Monitoring, Physiologic / Q000379:methods / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods / Q000592:standards*
keywords: Raman spectroscopy; bioprocess monitoring; chemometrics; mammalian cell culture; process analytical technology