Strategies for Controlling the Quality of mRNA

The emergence of mRNA modality as a therapeutic alternative for treatment of viruses, infectious disease, and various therapies has highlighted the need for high quality mRNA. To meet the quality requirement, developers continue to examine raw material quality, process controls and appropriate analytical methods to ensure the manufacturability of high quality mRNA. As such, we will discuss various strategies to ensure the manufacturability and characterization of high-quality mRNA.

Presented by Khaled Yamout, Analytical Sciences, Quality and Manufacturing Consultant, Yamout Chem Consulting, LLC

Khaled Yamout is a thought leader in Analytical Sciences, Quality and Manufacturing.  Previously held a position as a Senior Director, Analytical Services and Quality Control at TriLink Biotechnologies where he oversaw the Analytical Sciences Center of Excellence and all analytical aspects of method development and validation to product release and stability to support regulatory filings for both small and large molecules. Prior to TriLink, Khaled held various positions in Quality Control, Research and Development, and Manufacturing where he supported several Drug substances and Drug products (both small molecules and biologics) from clinical phase to commercial. These include diverse experience and expertise ranging from discovery to manufacturing with Fortune 500 firms, as well as small entrepreneurial businesses in the areas of synthetic, analytical, colloidal, surface modification, protein, and antibody modification and purification covering both manufacturing and analytical testing and characterization.

Quality control of therapeutic mRNA with liquid chromatography methods

 This seminar will present recent advances in therapeutic mRNA quality control (QC) with liquid chromatography (LC). Several modes of LC are applicable to analysis of intact and digested mRNA. We will show the applications of ion-pair reversed-phase LC (IP RPLC) method with mass spectrometry detection (MS), hydrophilic interaction chromatography (HILIC) for analysis of mRNA formulated with lipid nanoparticles (LNP), and application of new class of size exclusion chromatography (SEC) columns with highly inert particle and hardware surfaces for intact mRNA and LNP. Complementary detection techniques to MS, such as multi-angle light scattering (MALS) will be featured. Finaly, the utility of affinity LC technique with immobilized oligodeoxythymidine will be demonstrated for quantitation of polyA tailed mRNA.

We will discuss the applications for mRNA QC include analysis of 5’-capping, mRNA mapping, intact mRNA SEC-MALS sizing, mRNA quantitation, HILIC formulation analysis, and affinity LC analysis of tailless/polyA tailed mRNA.

Presented by Martin Gilar, PH.D. Research Fellow, Separations R&D group at Waters Corporation

Dr. Martin Gilar received his Ph.D. in analytical chemistry from Institute of Chemical Technology in Prague (1996). He spent postdoc years in Hybridon Inc. (1996-1998) and Northeastern University in Boston (1998) developing separation methods for antisense oligonucleotides and fraction collector for DNA molecules. Since 1998 he has worked at Waters Corp. in Milford, Massachusetts, participating in column, sample preparation and instrument research. Dr. Martin Gilar is a Research Fellow in the Separations R&D group at Waters Corporation. He has 30+ years of experience in the separation sciences, including chromatography, electrophoresis, and mass spectrometry. His research interest is the analysis of biopolymers, peptides, and nucleic acids. He has published over 75 peer reviewed papers. Dr. Gilar is the recipient of Jaroslav Janak 2022 medal and Chromatographic Society Jubilee medal in 2023.

Followed by a live Question and Answer session

Sponsored by Waters Corporation

Waters Corporation, headquartered in Milford, Massachusetts, is a leading provider of analytical instruments, software, and services for scientists worldwide. Founded in 1958, the company specializes in high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography (UPLC), and mass spectrometry (MS) systems. 

Waters Corporation’s tools are essential for chemists, enabling precise and accurate analysis of complex mixtures. Their liquid chromatography systems are widely used for separating, identifying, and quantifying components in chemical samples. These systems are crucial in various fields, including pharmaceuticals, environmental testing, food safety, and clinical diagnostics. 

In addition to chromatography, Waters offers mass spectrometry solutions that provide detailed molecular information, aiding chemists in understanding the composition and structure of substances. Their integrated software solutions enhance data analysis, ensuring that chemists can efficiently interpret results and maintain compliance with regulatory standards 

Waters Corporation’s commitment to innovation and quality has made them a trusted partner for laboratories around the globe. Their comprehensive range of products and services supports chemists in achieving reliable and reproducible results, driving advancements in scientific research and development.