Advantages of the GS Xceed™ System

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GSLonza@lonza.com

  • Introduction

    With Manufacturability in Mind

    High titer, reproducible/robust process and reduced time to market are essential for any successful development program.  At Lonza, we are always looking for new ways to advance your mammalian expression to the next level.  Most recently, we have improved our original GS mammalian expression system with the introduction of CHOK1SV GS Knockout (KO) host cell line.  This new cell line has both alleles of the endogenous glutamine synthetase gene “knocked out."  It is a derivative of Lonza’s suspension adapted CHOK1SV host cell line and is part of the new GS Xceed™ Gene Expression System.  The new GS-KO cell line can be used directly with our current Version 8 (v8) Media and Feed Platform, with little optimization needed to achieve high titers.  Our v8 Commercial Process Platform has proven scalability up to 20 000 L and has shown similar titer and gylcoslyation profiles as compared to our original GS System™.

    *A regulatory dossier including traceability and safety testing is available to support IND filings.

  • Productivity

    Maximum titer production is a crucial element to any commercial expression system.  Our new GS Xceed™ Gene Expression System has been shown to achieve titers of up to 6 g / L with viable cell concentrations of  2-5 x 106, typically achieved after 4 days of subculture. Cell lines are selected to fit our Version 8 (v8) manufacturing process. This immediate adaptation to our v8 Commercial Platform ensures faster scale-up to a cGMP manufacturing environment and ultimate speed in the generation of clinical supply material.

    Figure 1: Productivity in 10 L bioreactors using the chemically defined, animal component-free v8 GS-CHO Commercial Platform Process for Lonza’s model antibody cB72.3
  • Speed

    Decreasing your time to first in human studies is a clear advantage for a successful clinical pipeline.  Rapid selection of high producing clones significantly reduces the time required to generate a cell line suitable for cGMP manufacture.  Our new GS Xceed™ System enables the identification of a lead cell line in less than 17 weeks from transfection. This is a 6 week reduction in cell line development time when compared with our CHOK1SV host cell line.

    This 6 week reduction in development time consists of several new advancements:

    • Transfection and Pool Selection – The GS selection of pooled transfectants is completed in suspension culture resulting in a 1-2 week time savings.
    • Cloning - Cloning is in the absence of MSX resulting in colony formation 1-2 weeks quicker.
    • Suspension Evaluation – The CHOK1SV GS-KO cell line adapts quickly to suspension culture and the Version 8 (v8) Commercial Platform, allowing for over a week in time savings.
    • Suspension Expansion – No MSX is required resulting in increased cell growth and faster expansion

    Lonza’s Cell Line Construction Programs include an initial assessment of manufacturability.  Candidate cell lines are assessed for productivity, product characteristics and cell growth in our v8 Platform Process.

     

    Cell line construction

     

    Figures 1 and 2: Timeline of steps performed to select high-yielding clonal GS-CHO cell lines adapted to chemically defined, animal component-free v8 GS-CHO Commercial Platform Process for both the existing CHOK1SV cell line and the new CHOK1SV GS-KO Cell Line.

  • Stability

    Product stability is critical to any product release.  The new GS Xceed System™  provides you with stable and consistent results during your manufacturing process.

    Cell line stability studies performed on CHOK1SV GS-KO cell lines maintained in the absence of MSX over a period of over 50 generations demonstrated consistent product titer in fed-batch shake-flask cultures established every 15-20 generations. The product quality of a monoclonal antibody product also remained consistent across the study.

    Our stability studies show consistency across the following attributes:

    • Size variants (reduced and non-reduced SDS-PAGE)
    • Charge variants (IEF)
    • Monomer and aggregate proportions (GP-HPLC)
    • Glycan profiles (MALDI-TOF-MS) - See Figure 2 below

     

     

    Figure 1: Stability of productivity for CHOK1SV GS-KO derived cell lines assessed in a shake-flask model of Lonza’s v8 GS-CHO Commercial Platform Process. Data are average titers from duplicate lineages for each cell line.

     

    Figure 2: Samples from a stability study were used for a Glycosylation stability study. Samples were produced in fed-batch shake-flask cultures using the chemically defined, animal component-free Version 8 Commercial Platform Process

  • Comparability

    Lonza's new GS Xceed™ System has shown similar results in both average titer and glycosylation patterns to the existing CHOK1SV cell line

    Figure 1: CHOK1SV and GS-KO Cell lines expressing a model antibody (cB72.3) evaluated in 10 L model of production fed-batch bioreactor, using Lonza's Version 8 Media and Feeds Platform.

     

    Figure 2.  Comparability of glycan structure for CHOK1SV GS-KO and CHOK1SV derived cell lines assessed in a shake-flask model of Lonza’s v8 GS-CHO Commercial Platform.