The acceleration of protein-interface interactions was identified as the critical factor leading to protein particle formation during ultrafiltration/diafiltration (UF/DF) of biopharmaceuticals. Our systematic study of independent components of the UF/DF process revealed that simply stirring in the retentate tank induced the same level of particle formation as recirculation in the full UF/DF unit, eliminating several pump or membrane-specific hypotheses on the mechanism of particle formation for the products under study. Small-scale stirring experiments revealed that low conductivity conditions decreased particle formation by enabling electrostatic repulsion, as did surfactants by providing interfacial protection. Taken together, these findings suggest that UF/DF-induced particle formation results from the accelerated trafficking of protein molecules to and from particle-inducing interfaces, and that this stress can be simulated by stirring. Bench-scale UF/DF concentration and diafiltration operations revealed that surfactant addition limits particle formation in an actual UF/DF operation, improving the filterability of the concentrated product.

Control of particle formation during ultrafiltration/diafiltration through the modulation of interfacial interactions

245th National Meeting (2013)

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