title: Fingerprint detection and process prediction by multivariate analysis of fed-batch monoclonal antibody cell culture data.
abstract: This work presents a sequential data analysis path, which was successfully applied to identify important patterns (fingerprints) in mammalian cell culture process data regarding process variables, time evolution and process response. The data set incorporates 116 fed-batch cultivation experiments for the production of a Fc-Fusion protein. Having precharacterized the evolutions of the investigated variables and manipulated parameters with univariate analysis, principal component analysis (PCA) and partial least squares regression (PLSR) are used for further investigation. The first major objective is to capture and understand the interaction structure and dynamic behavior of the process variables and the titer (process response) using different models. The second major objective is to evaluate those models regarding their capability to characterize and predict the titer production. Moreover, the effects of data unfolding, imputation of missing data, phase separation, and variable transformation on the performance of the models are evaluated.
authors.affiliation: Dept. of Chemistry and Applied Biosciences, ETH Zurich, Institute of Chemical and Bioengineering, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Sokolov
authors.affiliation: Dept. of Chemistry and Applied Biosciences, ETH Zurich, Institute of Chemical and Bioengineering, Zurich, Switzerland.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soos
authors.affiliation: Dept. of Chemistry and Applied Biosciences, ETH Zurich, Institute of Chemical and Bioengineering, Zurich, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Neunstoecklin
authors.affiliation: Dept. of Chemistry and Applied Biosciences, ETH Zurich, Institute of Chemical and Bioengineering, Zurich, Switzerland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
authors.affiliation: Dept. of Chemistry and Applied Biosciences, ETH Zurich, Institute of Chemical and Bioengineering, Zurich, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Butté
authors.affiliation: Dept. of Pharmacy, University of Genova, Genova, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Leardi
authors.affiliation: Biotech Process Sciences, Merck Serono S.A., Corsier-sur-Vevey, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Solacroup
authors.affiliation: Biotech Process Sciences, Merck Serono S.A., Corsier-sur-Vevey, Switzerland.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Stettler
authors.affiliation: Biotech Process Sciences, Merck Serono S.A., Corsier-sur-Vevey, Switzerland.
authors.forename: Hervé
authors.initials: H
authors.lastname: Broly
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D061249:Batch Cell Culture Techniques / Q000145:classification* / Q000379:methods*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D025341:Principal Component Analysis
chemical_list: D000911:Antibodies, Monoclonal
keywords: cell culture process; multivariate data analysis; partial least squares regression; principal component analysis; quality by design