title: At-line NIR spectroscopy as effective PAT monitoring technique in Mab cultivations during process development and manufacturing.
abstract: The application of at-line NIR transmittance spectroscopy on supernatant samples from Chinese Hamster Ovary Cells (CHO) based monoclonal antibody (Mab) cultivation processes spanning several scales from 2.5L to 1000 L, cell-lines and development years is described. The collected and preprocessed spectra were used to do process state estimation and to obtain several culture parameters. Multivariate process trajectories were computed from NIR spectra acquired at-line. These were used to enhance process understanding across different scales up to industrial scale, assess batch-to-batch variability, and examine the relative importance of different sources of process variability. Many parameters of interest in industrial cell culture, like nutrient or product concentrations can be reliably estimated by NIRS with an accuracy of 15% or better, compared to reference methods General calibrations (scale and cell-line independent) are valid across a range of process conditions and different feed regimes. The proposed approach is therefore applicable throughout process development as well as to existing large-scale validated CHO bioprocesses for continuous improvement.
authors.affiliation: Roche Diagnostics GmbH - Pharmaceutical Biotech Production & Development, Nonnenwald 2, Penzberg, 82377 Germany. christian.hakemeyer@roche.com
authors.forename: Christian
authors.initials: C
authors.lastname: Hakemeyer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Strauss
authors.forename: Silke
authors.initials: S
authors.lastname: Werz
authors.forename: Gledson E
authors.initials: GE
authors.lastname: Jose
authors.forename: Francisca
authors.initials: F
authors.lastname: Folque
authors.forename: Jose C
authors.initials: JC
authors.lastname: Menezes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D019149:Bioreactors; D002138:Calibration; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D003412:Cricetulus; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000295:instrumentation*
chemical_list: D000911:Antibodies, Monoclonal