title: Multivariate PAT solutions for biopharmaceutical cultivation: current progress and limitations.
abstract: Increasingly elaborate and voluminous datasets are generated by the (bio)pharmaceutical industry and are a major challenge for application of PAT and QbD principles. Multivariate data analysis (MVDA) is required to delineate relevant process information from large multi-factorial and multi-collinear datasets. Here the key role of MVDA for industrial (bio)process data is discussed, with a focus on progress and limitations of MVDA as a PAT solution for biopharmaceutical cultivation processes. MVDA based models were proven useful and should be routinely implemented for bioprocesses. It is concluded that although the highest level of PAT with process control within its design space in real-time during manufacturing is not reached yet, MVDA will be central to reach this ultimate objective for cell cultivations.
authors.affiliation: Crucell Holland BV, Process Development Department, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Mercier
authors.affiliation: Crucell Holland BV, Process Development Department, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Diepenbroek
authors.affiliation: Wageningen University, Bioprocess Engineering, P.O. Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: Rene H
authors.initials: RH
authors.lastname: Wijffels
authors.affiliation: Wageningen University, Bioprocess Engineering, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. Electronic address: mathieu.streefland@wur.nl.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Streefland
mesh_terms: D001702:Biopharmaceutics / Q000379:methods*; D001709:Biotechnology / Q000379:methods*; D018929:Cell Culture Techniques / Q000379:methods*; D016208:Databases, Factual; D015233:Models, Statistical; D015999:Multivariate Analysis; D013678:Technology, Pharmaceutical / Q000379:methods*
keywords: biopharmaceutical industry; cell cultivation; process analytical technology; quality by design