The increase in demand for biologics has led to the need for a large global manufacturing capacity. Improvements to upstream processes over the past two decades have significantly increased this production capability, but often resulting in an increase of biomass from the culture broth that presents challenges to both clarification and purification operations. It is in this framework that technologies such as flocculation are being revisited. This presentation addresses the use of a novel ultra scale-down (USD) methodology for the characterisation of the flocculation of Saccharomyces cerevisiae clarified homogenate. This material was used in order to develop the technique without compromising feed consistency, but also served as a high-solid-level feed for the flocculation and removal of the residual solids present in the centrate. The aforementioned USD method consists of a multiwell, magnetically agitated system that can be fitted on the deck of a liquid handling robot hence fulfilling the need for a high-throughput and automated platform required to accelerate the initial primary recovery development studies. This microwell system was used to mimic the flocculation performance of a pilot-scale vessel thus representing greater than three orders of magnitude scale-up between two non-geometrically matched systems. This presentation will cover a discussion of the importance of different types of mixing (whether macromixing, mesomixing or micromixing) in determining the particle size distribution of the resulting flocs. Furthermore, this work also verifies how these mixing types can modulate the success of some of the scale-up correlations reviewed in the literature, and shows that the data obtained with the USD system closely mimics the flocculation performance obtained at pilot-scale.

Automated ultra scale-down methodology for the characterisation of post-centrifuge flocculation processes and its verification

247th National Meeting (2014)

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