Sterile filtration is widely used among biotherapeutic manufacturers to sterilize drug products, utilizing a 0.2 µm nominal pore size membrane to remove all bacteria. Although the sterile filtration of recombinant protein products is relatively straightforward, live attenuated viral (LAV) vaccines with large particle size (100 – 400 nm), such as the cytomegalovirus vaccine, pose significant challenges during sterile filtration with low yields and capacities. Experimental studies were performed with both an LAV and a previously developed model particle system. Small differences in the average pore size of sterile filters (determined by mercury porosimetry) had a large effect on the particle transmission, with the Sartobran P (average pore size of 0.46 µm) having more than 80% viral particle yield while the Millipore Express SHF (average pore size of 0.33 µm) had a particle yield of &lt;1%. In addition, the filter capacity and particle yield could be significantly increased using appropriate prefilters due to selective removal of larger particles in the feed suspension. Confocal and scanning electron microscopy were used to directly evaluate the extent and location of foulant capture within both the prefilter and sterile filters. Particle yield for the model nanoparticle suspension was also increased by minimizing hydrophobic interactions by adding surfactants like Triton-X 100. This work provides important insights into the factors controlling sterile filtration of large particle vaccines as well as a framework for enhancing the yield and capacity of commercially available sterile filters.

Enhancing the performance of the sterile filtration of vaccines: Proper selection of a prefilter and the role of hydrophobic interactions

ACS Spring 2022

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