Understanding and predicting aggregation in biopharmaceuticals

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Currently, one of the bottle necks to developing cheaper protein therapeutics is the cost of the downstream bioprocessing and formulation steps. A key problem is the loss of active protein therapeutic to irreversible aggregation throughout the bioprocess. Other problems can arise during chromatography or filtration when encountering high protein concentrations which could lead to high viscosites or even precipitation. The focus of this work is to develop predictive methods for identifying problematic conditions early on in the bioprocess. These could then be used for identifying changes to the protein to minimize the problems. Alternatively, the method could be used for optimizing the solvent properties (pH, buffer type and concentration) or finding other small molecule additives to be used in order to avoid aggregation or increase protein solubility. We benchmark our approach by studying antibodies and antibody fragments due to their growing importance as human therapeutics.