The rapid growth of mRNA therapeutics highlights the need for consistent, science-based quality standards to support raw-material testing, manufacturing, and release testing. USP is developing an integrated framework of documentary and physical standards to support reliability, comparability, and regulatory confidence throughout the mRNA–LNP lifecycle. This presentation will discuss key considerations for raw-material quality and outline emerging USP standards that help ensure the development of high-quality mRNA therapeutics.

Self-amplifying RNA (saRNA) is a promising biotherapeutics research area due to the low dosage requirements compared to non-replicating mRNA. Upon saRNA entry into a host cell, the alphavirus-derived replicase is translated by host machinery and the replicase complex then amplifies the antigen sequence of interest. We are leveraging NGS approaches to deeply characterize each stage of saRNA replication and host response. These methods may ultimately facilitate regulatory documentation and saRNA design.

With the adoption of mRNA as a therapeutic alternative for the treatment of viruses, infectious diseases, and various therapies, there have been numerous advancements in technologies to generate raw materials and analytical methods for the analysis and characterization of mRNA to advance and improve the quality of mRNA products. To understand how these advancements in these technologies impact the quality of mRNA, we will present and discuss some of these technologies and present case studies on how these advancements impact the quality of mRNA products.

LNP drug product development topic will provide an insight into the critical considerations in lipid nanoparticle (LNP) drug product development. It will cover LNP formulation strategies, buffer system optimization, manufacturing process development, and/or container closure system considerations to ensure product quality and stability.

This presentation focuses on the transition of LNP manufacturing from early-stage process development to full-scale GMP production. It covers practical scale-up challenges, lessons learned from case studies, and strategies for standardizing platforms across binder modalities.

Akagera Medicines has developed a highly efficient ligand-targeted mRNA LNP vaccine platform composed of a novel biodegradable ionizable cationic lipid with rapid in vitro and in vivo degradation kinetics combined with rapid uptake and expression by antigen presenting cells. Here, we describe the mechanistic understanding of how these LNPs perform, as well as their production, physical characterization, and stability. We have demonstrated dramatically increased antibody titers compared to commercial controls at relatively low mRNA doses, low reactogenicity, and rapid degradation in the presence of esterases. These properties allow for the production of an affordable and accessible mRNA vaccine candidate.

A major bottleneck in translating mRNA therapies to market is the seamless scale-up from bench to manufacturing. We present a "size- and morphology-control" technique to produce bleb-like mRNA-LNPs that scales from microfluidic systems to manufacturing-relevant turbulent mixers, while preserving critical quality attributes and efficacy—enabling both personalized medicines and large-scale vaccine production.

This presentation will explore emerging non-lipid nanoparticle technologies designed to expand delivery strategies for nucleic acid therapeutics and other advanced modalities. The session will examine how alternative nanoparticle systems may address current limitations in stability, storage, and distribution. By highlighting advances in formulation and delivery design, the talk will consider how new platforms could broaden therapeutic reach and improve patient accessibility across diverse healthcare settings.

Lipid-nanoparticles (LNPs) are highly sensitive to processing conditions, making it difficult to reproducibly achieve target quality attributes. This talk will examine the physicochemical origins of this sensitivity in the context of LNP self-assembly pathways. We will demonstrate how mechanistic insight enables the design of more robust processes that selectively tune specific quality attributes without compromising others. This rational method also supports predictive manufacturing by integrating mechanistic models with data-driven approaches.