Automated mass spectrometry multi-attribute method analyses for process development and characterization of mAbs. 2021

Yvonne Ehwang Song, and Hervé Dubois, and Martin Hoffmann, and Stephen D Eri, and Yann Fromentin, and Jan Wiesner, and Anja Pfenninger, and Séverine Clavier, and Annette Pieper, and Laurent Duhau, and Udo Roth
Sanofi Genzyme R&D, Biologics Development, Five Mountain Road Framingham, MA 01701, USA.

More than 370 biotherapeutics drug products have been approved by regulatory agencies on the US and EU markets and this industry continues to expand. Process change and optimization is necessary to develop new effective biologics in a cost effective and productive way. Consequently, improvement of analytical techniques is required for better product characterization according to Quality by Design (QbD) approach recommended by regulatory agencies. Recently, multi-attribute method (MAM) has emerged to meet such demands using mass spectrometry coupled to liquid chromatography (LC-MS). However, traditional sample preparation or data processing would not be suitable to guide process development, because one of the common challenges during development of analytical platforms is instrument or method variability which can cause deviation in results. Here, we show a new automated analytical platform for MAM implemented on 3 different sites: the components of MAM platform include automated sample preparation, LC-MS based MAM, and data treatment automation. To our knowledge, this is the first study to show global harmonization on automated MAM platforms and the inter-sites comparability including the automated sample preparation and LC-MS instrument. Also, we demonstrate the applicability of MAM to support cell line development, cell culture process development and downstream process development. We expect that this MAM platform will effectively guide process development across multiple projects.

UI MeSH Term Description Entries
D012107 Research Design A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. Experimental Design,Data Adjustment,Data Reporting,Design, Experimental,Designs, Experimental,Error Sources,Experimental Designs,Matched Groups,Methodology, Research,Problem Formulation,Research Methodology,Research Proposal,Research Strategy,Research Technics,Research Techniques,Scoring Methods,Adjustment, Data,Adjustments, Data,Data Adjustments,Design, Research,Designs, Research,Error Source,Formulation, Problem,Formulations, Problem,Group, Matched,Groups, Matched,Matched Group,Method, Scoring,Methods, Scoring,Problem Formulations,Proposal, Research,Proposals, Research,Reporting, Data,Research Designs,Research Proposals,Research Strategies,Research Technic,Research Technique,Scoring Method,Source, Error,Sources, Error,Strategies, Research,Strategy, Research,Technic, Research,Technics, Research,Technique, Research,Techniques, Research
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D001331 Automation Controlled operation of an apparatus, process, or system by mechanical or electronic devices that take the place of human organs of observation, effort, and decision. (From Webster's Collegiate Dictionary, 1993) Automations
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO
D057927 Hydrophobic and Hydrophilic Interactions The thermodynamic interaction between a substance and WATER. Hydrophilic Interactions,Hydrophilic and Hydrophobic Interactions,Hydrophilicity,Hydrophobic Interactions,Hydrophobicity,Hydrophilic Interaction,Hydrophilicities,Hydrophobic Interaction,Hydrophobicities,Interaction, Hydrophilic,Interaction, Hydrophobic,Interactions, Hydrophilic,Interactions, Hydrophobic

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