Microfiltration is an essential step during biopharmaceutical
manufacturing. However, unexpected flux decay can occur. Although the
flux decay profile and initial flux are important factors determining
microfiltration filterability, predicting them accurately is challenging
since the root cause of unexpected flux decay remains elusive. In this
study, the methodology for developing a prediction model of flux decay
profiles was established. First, the filtration profiles of different
monodisperse polystyrene latex and silica beads of various sizes were
evaluated. These results revealed that the size and surface
electrostatic properties of the beads affect the flux decay profile.
Taking the size and surface electrostatic properties of protein
aggregates into account, we constructed a predictive model using model
bead filtration profiles. We showed that this methodology was applicable
to two different microfiltration filters to predict the flux decay
profile of therapeutic proteins. Since this prediction model is based on
normalized flux, the initial flux must be predicted. We therefore
successfully developed a method to predict initial flux based on the
Hagen-Poiseuille equation using sample viscosity values for both
filters. These prediction models can be used for effective
microfiltration scale-up assessment and can be applied during early
stage of process development.