Enhancing the performance of sterile filtration for viral vaccines and model nanoparticles using an appropriate prefilter

Prefilters are widely used to enhance the performance of normal flow filtration steps in bioprocessing; however little is known about the potential benefits of prefiltration in the sterile filtration of viral vaccines and other large particle biotherapeutics. Sterile filtration experiments were performed with a live-attenuated viral vaccine and model nanoparticle suspension, both of which have a size distribution of 100 – 400 nm. The results demonstrated that the outstanding performance of the Sartobran P sterile filter was directly due to the effective prefiltration provided by the 0.45 μm prefilter in this dual layer filter. The 0.45 μm prefilter dramatically improved particle transmission and capacity for other 0.2 μm sterile filters. The key foulants were removed primarily on the basis of size, which was confirmed using a nanoparticle tracking analyzer. Larger pore size prefilters were found to be much less effective in protecting the 0.2 μm sterile filter. The support structure of asymmetric sterile filters also provided significant prefiltration; however, some of these asymmetric membranes had size-selective pores that were too small to provide significant transmission of the viral particles. These results provided important insights into the role of the prefilter layer and membrane pore structure in enhancing the performance of the sterile filtration step for the processing of viruses and other large particle biotherapeutics.