Optimization of a flocculation step using a scale-down model with 3D-printed impellers and Focused Beam Reflectance Measurement (FBRM) particle-size monitoring

Conference Dates

June 17-22, 2018


Flocculation is frequently employed in the purification of biopharmaceuticals to improve the efficiency of downstream clarification steps. This operation entails adding an agent to the cell culture broth that causes debris and other impurities to aggregate into larger particles called “flocs”. Due to their size, these “flocs” can be more readily separated from the product stream via centrifugation or filtration.

To develop an efficient flocculation step, it is necessary to identify the minimum amount of flocculating agent that causes particle aggregation to occur. This concentration can be affected by multiple parameters, most notably the mixing environment of the flocculation vessel. Thus, a scale-down model that closely approximates the geometry and mixing characteristics of the commercial-scale vessel with real-time particle-size monitoring would be an ideal tool for flocculation process development.

This poster describes the development and implementation of such a scale-down model. Custom 3D-printed impellers were created that mimic the geometry and mixing characteristics of future commercial scale options and Focused Beam Reflectance Measurement (FBRM) technology was used to track particle size evolution in real-time. By combining these technologies, the model was able to reduce volume requirements 18-fold when compared to off-the-shelf options while quantitatively determining optimal flocculant concentrations under multiple conditions.

This work relates to the themes in this year’s Vaccine Technology conference in two key ways. First, it describes a process development improvement that led to higher throughput experimentation versus traditional methods, enabling faster movement of the vaccine candidate through the development lifecycle. Second, through consideration of the future commercial-scale in the early stages of development, a robust and realistic process was delivered, decreasing time and money wasted on operations that do not translate to the factory floor.

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