Aldevron Breakthrough Blog
LNPs, analytics and mRNA
September 13, 2023 / by Michael Jepperson
Working toward advanced analytical techniques
Guten tag from Berlin! As an analytically minded-person, it’s fascinating to connect with colleagues from around the world to discuss cutting-edge techniques and strategies for ensuring the quality, efficacy, and safety of mRNA-based therapeutics. That fascination led me to the mRNA Analytical Development Summit, held in Germany's capital city.
The summit kicked off with two enlightening workshops on standards, regulations, and the crucial role of lipid nanoparticles (LNPs) in enabling mRNA delivery. It was valuable to review the developing regulatory landscape and benchmark the latest advances in LNP stabilization, storage, screening, and targeted delivery.
The experience was a reaffirmation that Aldevron's innovative approach of procedure-based partial-validations is leading the way to accelerated success by streamlining the process from conception to commercialization.
A major theme was the lack of correlation between in vitro assays and in vivo efficacy, indicating potential hidden critical quality attributes that impact therapeutic efficacy but go undetected by current test methods.
Understanding the intricate biophysics of LNPs and their interactions with mRNA is essential to identify and control these attributes. Presenters also stressed the complexity of selecting optimal lipid components and the need to thoroughly examine mRNA quality attributes like higher order structure and size distribution.
While advanced orthogonal techniques can provide critical insights for process development, ultimately a holistic understanding of relationships between synthesis, encapsulation and clinical efficacy is needed. This conference has opened my eyes to analytical techniques that, while not always necessary for formal release, will be pivotal to assisting our clients in gaining a comprehensive characterization of their mRNA vaccines and therapeutics.
There are still analytical gaps when working with LNP particles in the “colloidal size range,” too small for visualization yet too large for many traditional techniques. This hinders full characterization and obscures understanding of these “hidden” CQAs. The path forward relies on an array of advanced analytical techniques paired with in vivo experiments to construct a comprehensive biophysical profile.
By uniting knowledge, we can overcome hurdles to supply a high-quality, robust and simplified mRNA supply chain. The summit truly sparked excellent conversations on fostering international collaboration to bring life-changing mRNA therapies to patients worldwide.
Bis zum nächsten Mal, Deutschland!
