title: Generic Raman-based calibration models enabling real-time monitoring of cell culture bioreactors.
abstract: Raman-based multivariate calibration models have been developed for real-time in situ monitoring of multiple process parameters within cell culture bioreactors. Developed models are generic, in the sense that they are applicable to various products, media, and cell lines based on Chinese Hamster Ovarian (CHO) host cells, and are scalable to large pilot and manufacturing scales. Several batches using different CHO-based cell lines and corresponding proprietary media and process conditions have been used to generate calibration datasets, and models have been validated using independent datasets from separate batch runs. All models have been validated to be generic and capable of predicting process parameters with acceptable accuracy. The developed models allow monitoring multiple key bioprocess metabolic variables, and hence can be utilized as an important enabling tool for Quality by Design approaches which are strongly supported by the U.S. Food and Drug Administration.
authors.affiliation: Advanced Manufacturing Technology, Pfizer Inc., Peapack, NJ.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Mehdizadeh
authors.affiliation: Advanced Manufacturing Technology, Pfizer Inc., Peapack, NJ.
authors.forename: David
authors.initials: D
authors.lastname: Lauri
authors.affiliation: Advanced Manufacturing Technology, Pfizer Inc., Peapack, NJ.
authors.forename: Krizia M
authors.initials: KM
authors.lastname: Karry
authors.affiliation: Advanced Manufacturing Technology, Pfizer Inc., Peapack, NJ.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Moshgbar
authors.affiliation: Bioprocess R&D, Pfizer Inc., Andover, MA.
authors.forename: Renee
authors.initials: R
authors.lastname: Procopio-Melino
authors.affiliation: Bioprocess R&D, Pfizer Inc., Andover, MA.
authors.forename: Denis
authors.initials: D
authors.lastname: Drapeau
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002138:Calibration; D018929:Cell Culture Techniques / Q000379:methods* / Q000592:standards*; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D003470:Culture Media
keywords: CHO cell culture; Raman spectroscopy; bioprocess monitoring; multivariate modeling; process analytical technology