title: In-line and real-time prediction of recombinant antibody titer by in situ Raman spectroscopy.
abstract: The Food and Drug Administration's (FDA) process analytical technology (PAT) framework has been initiated to encourage drug manufacturers to develop innovative techniques in order to better understand their processes and institute high level quality control which allows action at any point in the manufacturing process. While Raman spectroscopy and chemometrics have been successfully used to predict concentration of conventional metabolites in cell cultures, it is really not the case for active substances. Thus, we propose, for the first time, an in-line and real-time prediction of recombinant antibody titer using an immersion probe link to a spectrometer without the tacking of samples. A good robustness of the method is observed on different culture batches and the contamination risk is drastically reduced which is an important issue in biotechnology manufacturing processes.
authors.affiliation: LASIR CNRS UMR 8516, Université de Lille, Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Silvère
authors.initials: S
authors.lastname: André
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
authors.forename: Lydia Saint
authors.initials: LS
authors.lastname: Cristau
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gaillard
authors.affiliation: LASIR CNRS UMR 8516, Université de Lille, Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devos
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
authors.forename: Éric
authors.initials: É
authors.lastname: Calvosa
authors.affiliation: LASIR CNRS UMR 8516, Université de Lille, Sciences et Technologies, 59655 Villeneuve d'Ascq Cedex, France. Electronic address: ludovic.duponchel@univ-lille1.fr.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Duponchel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D019149:Bioreactors; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016018:Least-Squares Analysis; D011786:Quality Control; D011994:Recombinant Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000592:standards; D013059:Spectrum Analysis, Raman / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins
keywords: Antibody production; CHO; Cell culture; Chemometrics; Raman spectroscopy