Exploring Technologies For cGMP Success With Encapsulation Of Nucleic Acid-Based Therapeutics

By Alexander Schwenger, Ph.D., Head of Process Development - LNP, and Telmo Graça, Ph.D., Process and Technology Lead - mRNA

Delivering mRNA therapeutics at clinical and commercial scale requires effective lipid nanoparticle (LNP) encapsulation, but the complexity of producing drug product under current good manufacturing practice (cGMP) conditions can be underestimated. Mixing technologies developed for COVID-19 vaccines may require scale-out rather than straightforward scale-up, while reformulation can delay development programs by months. Selecting appropriate manufacturing processes and analytical methods early can help identify potential critical process parameters and reduce downstream risks.

This paper presents three case studies that examine key considerations in LNP manufacturing. The first explores how lipid supplier quality can influence mRNA-lipid agglomeration. The second demonstrates the practical application of process monitoring and LNP characterization methods. The third evaluates the performance of an oscillation-based mixing device across 34 encapsulation batches, offering data on its use in the manufacturing process. Beyond current approaches, the paper considers emerging opportunities in LNP surface modification, alternative chemistries, and drying technologies, including spray drying and lyophilization. Together, these examples illustrate how material selection, process control, and analytical characterization can inform manufacturing decisions.

Explore the case study data to understand how these methods can support a more robust, lower-risk path to cGMP production.