Messenger RNA (mRNA) has emerged as a transformative therapeutic modality, with established success in prophylactic vaccines and rapidly expanding potential in gene therapy applications, including mRNA-encoded gene editing enzymes. As the scope of mRNA-based medicines broadens, so too do the expectations for robust characterization strategies and fit-for-purpose quality attributes across diverse clinical contexts.

This session will explore evolving quality paradigms for mRNA drug substance and lipid nanoparticle (LNP) excipient components, highlighting similarities and key distinctions between vaccine and gene therapy applications. The session will address critical quality attributes (CQAs) of mRNA therapies, including identity, integrity, purity, sequence fidelity, capping, poly(A) tail characteristics, and residual impurities arising from in vitro transcription and downstream processing. Emphasis will be placed on how application-specific factors—such as administration path, duration of expression, and target tissue—inform analytical development, acceptance criteria, and control strategies. Attention will be given to mRNA used to encode gene editing enzymes, where transient expression, off-target risk, and long-term safety considerations may drive different quality expectations compared to vaccines.

In addition, the session will examine quality considerations for LNP excipients, including ionizable lipids, helper lipids, cholesterol, and targeting lipids. Topics will include lipid composition analysis, impurity profiles, degradation pathways, and the impact of excipient variability on potency, biodistribution, and safety. Strategies for defining and controlling excipient quality across development stages will be discussed, along with emerging expectations from regulatory authorities.

Through perspectives spanning analytical science, process development, and regulatory strategy, this session aims to provide a practical framework for aligning characterization approaches and quality expectations with intended clinical use. Attendees will gain insight into how to design risk-based, application-appropriate quality strategies that support innovation while ensuring patient safety and product consistency across the growing landscape of mRNA therapeutics.

Session Speakers:

Addressing Challenges in the Development and Quality Control of Individualized mRNA Products

Simon Klenk, BioNTech SE

From Insight to Specification: Defining which Assays to Place on Release vs Characterization in mRNA Therapeutics

Elisabeth Boucher, Tessera Therapeutics

Liping Zhou, AstraZeneca

Additional Panelist:

Anurag Sharma, CBER, FDA

May Guo

Appearances