There is a growing interest within the biopharmaceutical industry in adopting continuous processing in place of current batch processing for biological molecules and primarily monoclonal antibodies (mAbs), particularly with intensified upstream cell culture cycles. With the intensified upstream productivity the challenge for the initial clarification step increases significantly. At total cell densities(TCD) above 40x106/ml, the use of well understood depth filtration becomes impractical, alternative centrifuge approach is largely not viable, other options being explored include enhanced settling using flocculants, but have numerous draw backs, not least of which the time required to achieve adequate settling. The Cadence Acoustic Separator (CAS) was launched during 2016, targeted for single use mammalian clarification applications in the 20 to 50x106/ml TCD range. Following on from the momentum generated by the launch of this exciting disruptive technology, development of the technology was investigated to target higher cell density feeds that are becoming more common place within the industry. In this study we put theory into practice and explore the possibility of using expanded frequency transducers to target more efficient biomass removal up to cell densities of 90x106/ml. Removal efficiencies were determined for different frequency transducers across a wide range of TCD’s, from this an optimal frequency train is determined based on the starting TCD to achieve greater than 90% clarification efficiency whilst maintaining high product yield. The new approach was then benchmarked against the standard launched transducer for a range of TCD’s and shown to offer benefits across a wide range of feed materials up to 90x106/ml TCD, therefore offering a new solution to these challenging feed conditions. The new approach was then verified at a leading Biopharm company on multiple feed streams and at varying scales.

Exploring the limits of clarifying high cell density feeds with Cadence™ acoustic separator

253rd National Meeting (2017)

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