High throughput screening systems are of considerable use for the development of downstream purification processes. These systems allow for the parallel evaluation of many process conditions while also reducing material requirements compared to traditional experimental setups. While currently these systems are employed as screening tools to identify optimal windows of operation to be tested on the traditional benchtop systems, it is desirable to be able to predict scale-up performance from this high throughput experimentation to further reduce the number of required experiments, time, and material needed for process development. In addition to these reductions, this understanding would potentially allow for evaluation of more process variables during the development stage of a product. MiniColumns have emerged in recent years as a high throughput system that closely resemble operation and performance of the traditional benchtop systems. These systems typically employ robotic liquid handling or electronic pipettes to automate chromatography processes which results in a semi-continuous liquid flow.<br/>In this work, a simulation tool was employed to help understand the transformation of data from miniaturized columns to traditional scale-down models. The model is shown to be well suited to account for system differences such as lack of a precolumn mixer and semi-continuous operation as well as discontinuous, off-line detection. This simulation tool provides an understanding of how these operational system differences affect the chromatographic profile and the process performance which allows for more direct prediction of large scale performance from the higher throughput MiniColumn data. The work presented increases our understanding of system differences and enables the reliable prediction of large scale performance directly from parameters obtained at the MIniColumn scale.

Understanding minicolumn system operational differences and their impact on process performance and scale-up using column simulations

249th National Meeting (2015)

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