The availability of material for experimental studies is a key constraint in process development, especially during the early stages and when using high concentration monoclonal antibody (mAb) solutions. Using a combination of critical flow regime analysis, bioprocess modelling and experimentation at the millimeter scale, ultra scale-down (USD) technologies can significantly reduce the amount of process material, time and cost of process development enabling a more effective process development approach. The ability to predict the performance of membrane separation operations at manufacturing-scale, including the flux profile characteristics and changes in protein structure, will help focus pilot-scale runs during process development. In this study, a USD set-up comprising of a sheared cell unit with a rotating disc is used to predict the performance of a tangential flow filtration (TFF) set-up using a membrane cassette. The USD set-up was designed to reduce effective membrane area, process material and buffer volume requirements of TFF set-up by 520-fold. By characterizing average shear rate using experimental and computational fluid dynamic tools for TFF and USD set-ups respectively, we defined the average shear rate over the membrane surface as the scaling parameter for ultrafiltration/diafiltration (UF/DF) stages. We performed a series of trials at each scale across a typical range of average shear rates, mAb feed concentrations and membrane loadings. The predicted effect of changing shear rate and mAb concentration on flux using the USD set-up matched that found in the TFF set-up during buffer exchange operations. Good agreement in flux performance data at both scales was also found when evaluating membrane loadings, from 200 to 800 g/m<sup>2</sup>, during UF/DF stages. Future studies will include expanding this ultra scale-down method to new modalities.

Predicting membrane performance for the concentration and diafiltration of mAb solutions using an ultra scale-down method

255th National Meeting (2018)

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