Next-Gen LNP Pharmaceuticals Analytics: Intact Chromatography for Comprehensive Characterization

Explore the cutting-edge presentation by Tristan Kovačič, Project Manager at BIA Separations, Inc., delivered at PharmSci360 in November 2025. This insightful talk focused on the challenges and advancements in lipid nanoparticle (LNP) pharmaceuticals analytics.

Abstract:

Lipid nanoparticles (LNPs) represent the forefront of in vivo drug delivery for nucleic acids, yet transitioning from development to commercial biopharmaceuticals presents challenges in biology, manufacturing, and characterization. The presentation emphasized the importance of characterizing drug substance purity, excipient purity, and overall drug product purity. Liquid chromatography, particularly using monolithic columns, plays a crucial role in this process, offering low shear stress and large pores for complex biopharmaceuticals.

Key aspects include the characterization of excipients like lipids and RNA drug substances, with a focus on ionizable lipids. These lipids, lacking chromophores and being highly hydrophobic, are difficult to purify, making purity control essential. The interaction of impurities with RNA and the formation and stability of LNPs are critical factors. Chromatography methods developed for RNA-LNPs enhance process speed and quality, allowing direct quantification of RNA by UV and lipids by CAD/ELSD without labeling or sample preparation.

For a comprehensive understanding, download the handouts of Tristan’s presentation, which delve into the intricacies of LNP characterization, including encapsulation efficiency, particle size, heterogeneity, surface charge, morphology, and RNA loading. These parameters, typically requiring advanced biophysical analytics, can be effectively determined through chromatography.