(131a) Filtration of Lipid Nanoparticles: The Importance of Understanding Mechanisms to Improve Performance

In bioprocessing, membrane filtration is used to remove microorganisms from the process stream and to assure the drug product is safe for administration to patients. Sterilizing filters are used to ensure that bacteria do not enter the process stream and that any bacteria present are removed. Most critical is the final 0.2 µm sterilizing-grade filter, which ensures sterility of the final product.

Oily particles, such as the lipids used to encapsule mRNA in some COVID-19 vaccines, have some unique characteristics that can create challenges for sterilizing filtration. Bacteria retention in streams containing oily particles is particularly sensitive to variables that do not impact retention in aqueous streams. Understanding the operating parameters that impact filtration throughput and microbial retention in streams containing oily particles will enable robust process design.

In this study, we review potential mechanisms for the challenges observed during sterile filtration of oily particles and consider the impact of membrane, bacterial challenge, feed composition and process conditions. Data will be presented on factors that can impact capacity, retention, or both. Perhaps the most significant factor is a pressure-dependent, pore blockage phenomenon unique to oily particles. During process design, properties such as processing pressure and temperature, particle size, and membrane selection should be considered to mitigate the challenges that can arise during processing.

By understanding the process and the unique properties of oily nanoparticles, robust processes can be designed for therapeutics or vaccines that rely on these particles as adjuvants and delivery vehicles.