Characterization of Sterilizing-Grade Membranes/Prefilters and Application to mRNA-LNP Process Development

Area of Science:

• Pharmaceutical manufacturing
• Biotechnology
• Filtration technology

Background:

• Sterile filtration is critical for producing lipid nanoparticles (LNPs) for mRNA vaccines and therapeutics.
• The close particle size of LNPs (50-200 nm) and sterilizing-grade membranes (0.2 µm) presents filtration challenges.

Purpose of the Study:

• To characterize pore size distribution, fouling, and capacity of sterilizing-grade membranes and prefilters for LNP filtration.
• To identify optimal filter configurations for efficient LNP sterile filtration.

Main Methods:

• Mercury intrusion porosimetry was used to determine membrane pore size distributions.
• LNP filtration experiments were conducted to assess filter capacity and fouling behavior.
• Various sterilizing-grade membranes and prefilters were evaluated.

Main Results:

• Significant variability in pore size distribution was observed among 0.2 µm rated membranes.
• LNP filtration capacity strongly correlated with experimentally determined mean pore size.
• Dual-layer membranes (0.8/0.2 µm) and 400-800 nm prefilters significantly improved LNP filtration capacity and reduced fouling.

Conclusions:

• Sterilizing-grade filter selection, particularly membrane pore size distribution and morphology, critically influences LNP filtration capacity.
• Manufacturer-published pore size ratings do not fully capture performance for LNP filtration.
• Dual-layer membranes and appropriate prefilters are recommended for enhanced LNP sterile filtration.