There is a growing interest within the biopharmaceutical industry towards intensified cell culture techniques that show the potential to achieve significantly higher product titres compared to traditional fed batch cultures. One method of doing this is termed concentrated fed batch, or perfused fed batch. The cell culture operates similarly to a perfusion reactor but utilizes an ultrafiltration(UF) membrane rather than a microfiltration membrane. The use of the UF membrane still allows waste products to be removed and also allows fresh media to enter the bioreactor. This technique can result in very high cell densities (&gt;200x106/ml) and mAb titer (25-30g/l). The use of the UF membrane means that the mAb is retained within the bioreactor during the process as opposed to traditional perfusion whereby the mAb is harvested continuously. The challenge with this approach is harvesting the mAb and achieving high product yield, due to the very high cell density and also significant cellular debris concentrated in the bioreactor due to the tight rating of the UF membrane. Traditional harvesting techniques such as depth filtration become impractical under these conditions, alternative centrifuge approach is largely not viable In this work we investigate Acoustic Wave Separation for cell harvest using the Cadence™ Acoustic Separator. This is designed for the single use clarification of mammalian cell culture, including high density feeds, containing up to 100x106/ml TCD range or higher. In this study we apply the technology to a concentrated fed batch process and show how to achieve high product yield (&gt;90%) through a combination of dilution and cell washing while minimizing product dilution. The new approach was then verified at a leading Biopharm company.

Aligning acoustic wave separation with concentrated fed batch processing

255th National Meeting (2018)

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