Most of the cell damage which occurs within bioreactors is related to sparged bubbles. For example, high gas entrance velocity (GEV), bubble rupture, and foam accumulations are all common causes of cell death. Even though these causes are currently controlled across all scales including manufacturing, they will present significant challenges for future intensified cell culture processes or sensitive cell lines. In addition, the lot-to-lot variation of the raw material poloxamer 188, which is used to protect cells against bubble damage, adds another level of risk to process performance.<br/><br/>In this presentation, the observed bubble sensitivity variations across multiple cell lines will be shared, along with current risk mitigation strategies. The sensitivity differences by cell line were evaluated using a few small scale models which were developed for the comparisons. Cells from different hosts and multiple stages of cell line development were also studied in order to understand the root causes of bubble sensitivity. In addition to examining cellular characteristics, the impacts of media components were evaluated. The results that will be presented include the latest progress from poloxamer 188 lot variation investigations, as well as data showing significant impacts from other chemicals within media. To complete a thorough investigation into all aspects of bubble sensitivity, sparger design properties and bubble behavior within the bioreactor have also been explored. Through this three-pronged approach of examining cells, media, and equipment design, it is possible to increase overall process robustness and enable the use of future technologies that would otherwise challenge current cell culture capabilities.

Understanding cell line bubble sensitivity and preparing for future challenges

249th National Meeting (2015)

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