New Challenges and Opportunities in the Sterile Filtration of Biopharmaceuticals

Sterile filtration is one of the critical steps in the production of parenteral drug products, ensuring sterility for drug formulations that cannot be sterilized by heat / chemicals. However, the development of lipid nanoparticle (LNP) systems for delivery of mRNA vaccines, the use of nanoemulsions for drug delivery and as vaccine adjuvants, and the application of inactivated and attenuated viruses have created new challenges for sterile filtration due to the large size (typically >100 nm) and complex biophysics of these products. This talk highlights how these challenges are being addressed through research that has provided new understanding of the fundamental mechanisms controlling the filter capacity, the rate of fouling, and product yield during sterile filtration through 0.2 µm pore size-rated sterile filters. LNP fouling occurs through pore blockage that leads to fusion of LNP particles, resulting in a thin lipid film that covers the surface of the sterile filter and reduces the area available for flow. Nanoemulsion filtration is governed by the forces required to deform and push the soft nanodroplets through the membrane pores; these forces can be significantly altered by changing the surface chemistry of the sterile filter by pretreatment with surfactants to alter the surface hydrophobicity. In both cases, the use of appropriate pore size prefilters can significantly enhance the sterile filtration performance by removing larger particles / aggregates that serve as key foulants. These results not only provide new insights into the sterile filtration behavior of these complex biotherapeutics, but they also provide guidelines for process design / optimization as well as strategies that can be used to develop next generation sterile filters that can effectively address the unique challenges in processing these large biopharmaceutical products.