ArticleFrontiers in bioengineering and biotechnology2024
Cell clone selection-impact of operation modes and medium exchange strategies on clone ranking.
Article in Frontiers in bioengineering and biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Bioprocessing has been transitioning from batch to continuous processes. As a result, a considerable amount of resource was dedicated to optimising strategies for continuous production. However, the focus has been on developing a suitable and scalable perfusion strategy with little attention given to the selection of optimal cell clones. Cell line development and lead clone selection are critical to bioprocess development. The screening and selection process is typically performed in stages. Microwell plates (MWP) are used to narrow down the number of clone candidates, which will undergo further selective screening in progressively larger small-scale bioreactors (12 mL-3 L) to identify the top clone for GMP production. Perfusion mode is typically applied at bench-scale for optimisation purposes, while process development and cell clone screening studies at mL-scale still commonly use fed-batch methods. The change of operation mode from bolus feeding to perfusion with a regular exchange of medium, leads to questions regarding the reliability and fit of initial clone selection. Is the early-stage clone ranking impacted by the discrepancy in the operation mode, and does this potentially result in the exclusion of cell clones suitable for perfusion processes? To address this question, we evaluated various CHO cell clones expressing two antibody products using MWP methodologies in fed-batch and semi-perfusion mode. We assessed growth, metabolic, and productivity performance, and ranked cell clones using two different strategies. The first strategy evaluated clones based on a single parameter: the cell-specific productivity (q
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