The Bioprocessing Network

Listen to our presentation

Speaker: Blaž Bakalar, Product Manager, Sartorius BIA Separations
Time and Date: Wednesday, September 17 , 2025 | 1:50pm – 2:20pm
Title: Monolithic Columns Improve Quality, Recovery, And Facilitate Innovative Analytics For Complex LNP-Based Therapeutics

Presentation abstract:

Lipid nanoparticles (LNPs) are the most established platform for delivering nucleic acid payloads. However, the characterization and manufacturing of these complex and unstable products continue to present significant challenges.

In manufacturing, significant challenges involve accurately forming the drug product, maintaining its integrity, ensuring efficient recovery, and producing a product that is both of high quality and thoroughly characterized. A chromatography-based purification process and a consistently uniform, functional product were achieved using CIM Convective Interaction Media® OH monolithic columns. These CIM® monolithic columns are particularly advantageous for LNP purification due to the low shear stress provided by laminar flow, high recovery rates, and scalability for large-scale industrial needs, which leads to a robust purification process resulting in high recoveries and particle integrity.

This simple and rapid purification process effectively achieves the required particle concentration, ethanol removal, and buffer exchange functions. At the same time, free, non-encapsulated RNA is removed by modifying the buffers and obtaining chromatographic separation. The resulting purified and more uniform lipid nanoparticles (LNPs) demonstrate significantly lower particle heterogeneity and protein expression levels that are up to three times greater than those achieved with existing filtration methods.

Furthermore, it is essential to utilize rapid and reliable analytical methods to assess critical quality attributes (CQAs) of complex LNPs, thus ensuring the safety and effectiveness of these therapeutic approaches.

An analytical method that combines monolithic columns enables the precise characterization of multi-payload lipid nanoparticles (LNPs), which are essential for CAR-T therapy, CRISPR applications, and combination vaccine formulations. The method facilitates the determination of both the multi-payload quantity and integrity within and outside of LNPs, along with the measurement of mRNA-lipid adducts through online LNP disruption. This innovative chromatographic approach delivers unparalleled accuracy in LNP analysis and is well-suited for quality control environments.

Location: Pullman Melbourne Albert Park, Melbourne, Australia