Modeling of biopharmaceutical UF/DF from laboratory to manufacturing scale

The development of ultrafiltration and diafiltration (UF/DF) processes in the biopharmaceutical industry is largely empirical and rarely mechanistic. As a result, the full potential of process understanding is not unleashed. In this study, a model for a biopharmaceutical UF/DF process is introduced and applied for a Fab fragment from lab to manufacturing scale using a Ultracel Pellicon® 3 C-Screen cassette. For model calibration viscosity data, membrane permeability and a single ultrafiltration experiment were used. The calibrated model responded correctly to extrapolating process conditions regarding the control parameters crossflow and transmembrane pressure (TMP). This was demonstrated by a multivariate dataset of ultrafiltration experiments ranging from a protein concentration of 5 g/L to 200 g/L. The validated model was used to predict the entire UF/DF process at lab and manufacturing scale.