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Model-Based Design of Mammalian Cell Culture Media: Demonstration for GS-NS0 Cell Line

Presented at: Bioprocessing 2021
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Professor, BioMedical Systems Engineering Laboratory, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology
    Biography

      Sakis Mantalaris is Professor in the W.H. Coulter Department of Biomedical Engineering at Georgia Tech & Emory. Prior, he was Professor of BioSystems Engineering in the Department of Chemical Engineering at Imperial College London. He received his PhD (2000) in Chemical Engineering from the University of Rochester. His expertise is in modelling of biological systems and bioprocesses with a focus on mammalian cell culture systems, stem cell bioprocessing, and tissue engineering. He has published over 170 original manuscripts, co-edited one book, and holds several patents with several more pending. He has received several awards including the Junior Moulton Award for best paper by the Institute of Chemical Engineers (IChemE) in 2004. In 2012, he was elected Fellow of the American Institute for Medical & Biological Engineering and in 2013 he was awarded a European Research Council (ERC) Advanced Award. In 2015, he was awarded the Donald Medal by the Institution of Chemical Engineers (IChemE) for his contributions to biochemical engineering.


    Abstract

    Demand for high-value biologics, a rapidly growing pipeline, and pressure from competition, time-to-market and regulators, necessitate novel biomanufacturing approaches, including Quality by Design (QbD) principles and Process Analytical Technologies (PAT), to facilitate accelerated, efficient and effective process development platforms that ensure consistent product quality and reduced lot-to-lot variability. Herein, QbD and PAT principles were incorporated within an innovative in vitro-in silico integrated framework for upstream process development (UPD). The central component of the UPD framework is a mathematical model that predicts dynamic nutrient uptake and average intracellular ATP content, based on biochemical reaction networks, to quantify and characterize energy metabolism and its adaptive response, metabolic shifts, to maintain ATP homeostasis. The accuracy and flexibility of the model depends on critical cell type/product/clone-specific parameters, which are experimentally estimated. The integrated in vitro-in silico platform and the model’s predictive capacity reduced burden, time and expense of experimentation resulting in optimal medium design compared to commercially available culture media (80% amino acid reduction) and a fed-batch feeding strategy that increased productivity by 129%. The framework represents a flexible and efficient tool that transforms, improves and accelerates conventional process development in biomanufacturing with wide applications, including stem cell-based therapies.

    Learning Objectives:

    1. Learn metabolic requirements of mammalian cells; Metabolic Shifts

    2. Learn about modelling of mammalian Cells


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