CQA Assessment Of LNP-Encapsulated IVT mRNA Using Agilent Fragment Analyzer Systems

With the advent of the first in vitro transcribed (IVT) mRNA vaccines for COVID-19, various regulatory agencies have issued comprehensive recommendations and guidelines concerning the Critical Quality Attributes (CQAs) of IVT mRNA in vaccines and other biotherapeutic applications. These guidelines encompass both the initial drug substance, which is the IVT mRNA, and the drug product, which is the lipid nanoparticle (LNP) encapsulated IVT mRNA. Encapsulating the IVT mRNA into a delivery vehicle like an LNP is a critical step in the biotherapeutic workflow. This encapsulation is essential as it provides protection to the IVT mRNA and facilitates its delivery in vivo. Consequently, assessing the drug product is crucial to ensure that the drug substance has not undergone degradation during the encapsulation process. However, this assessment poses a challenge because the LNP encapsulation restricts direct access to the IVT mRNA for evaluation.

This application note offers detailed examples of the assessment of sizing, purity, integrity, and quantification of both the drug substance and the drug product using the Fragment Analyzer. Discover how a thorough evaluation is important to maintain the quality and efficacy of IVT mRNA biotherapeutics.