Navigating mRNA Impurities: A Focus on Quality

The quality and purity of mRNA are critical for vaccine and therapeutic safety. As new technologies emerge, bridging analytical methods, especially in impurity detection, remains challenging. Comprehensive characterization is essential for identifying impurities like dsRNA and residual DNA. USP is developing documentary and physical standards which support the mRNA product lifecycle. This presentation explores evolving mRNA analytics and opportunities to enhance impurity detection and improve product reliability

Sarita Kattel, M.S, Principal Scientist, Global Biologics at US Pharmacopeia

Sarita Kattel serves as a Principal Scientist in USP’s Global Biologics Department. At USP, she utilizes her extensive vaccine experience to advance the development of standards supporting vaccine manufacturing. Her role also includes creating new standards for analytical testing of oligonucleotide products and exploring additional opportunities for standards in various other areas.

Ms. Kattel’s career spans over biotech companies, academic institutions, contract research organizations (CROs), and pharmaceutical giants like GlaxoSmithKline (GSK) and Janssen Pharmaceuticals. She has held lab-based roles in method development and validation, Chemistry, Manufacturing, and Controls (CMC) leads, as well as quality control, working on monoclonal antibodies, proteins, and mRNA-based vaccines.

Advancing mRNA Quality Control: Transformative NGS Approaches for Critical Quality Attributes

mRNA technology is rapidly emerging as a transformative strategy in the development of vaccines and therapeutics. Rigorous quality control (QC) testing is needed to assess multiple critical quality attributes (CQAs) of mRNA used for these novel applications. This presents a challenge since QC strategies for mRNA-based products are still evolving, with optimal approaches for different attributes still being determined. Some existing technologies for mRNA analysis require product -specific development and separate workflows for each attribute which can impact development timelines for novel mRNA products, where rapid development is essential to respond to global health challenges. Hence, there is an unmet need for more rapid, fully-platformed approaches for CQA assessment, necessitating the application of new technologies.

Next generation sequencing (NGS), including short and long-read sequencing technologies can analyze mRNAs of varying sequence and lengths. Merck has applied NGS technologies to establish alternatives to traditional approaches for several mRNA CQAs, including Poly(A) tail length and distribution, 5’-capping efficiency, dsRNA impurity detection and sequence identity. NGS assays require no mRNA sample-dependent development work, and streamlined workflows allow for assessment of multiple CQAs in a single sample preparation, reducing turnaround time and the amount of sample required for analysis. The data presented provides direct comparison of the analysis of mRNA molecules between existing mRNA analytical methods, such as Mass spectrometry, against long-read sequencing technology. Merck offers GMP testing with our BioReliance® service offering, now incorporating long-read sequencing technology for mRNA CQAs.

Presented by Melisa Wilson, M.S, Director, Blazar and mRNA QC R&D programs at Merck

Melisa Wilson is the Director of the Blazar and mRNA QC R&D programs for Merck where she manages the development, validation and global transfers of innovative biosafety testing assays. Her 19 years of industry experience ranges from clinical diagnostics (CLIA), certified reference material production (ISO 17025) to global cGMP biosafety testing services with a focus on assay development, next generation sequencing and virology. Melisa earned her B.S. in Chemistry and M.S. in Biology at George Mason University and has been with Merck for 7 years.

and Jeremy Schofield, PhD. Senior Scientist, Blazar and mRNA QC R&D program at Merck

Jeremy Schofield is a Senior Scientist in the Blazar and mRNA QC R&D program at Merck where he develops next generation sequencing-based biosafety testing assays and bioinformatic workflows. Jeremy earned his PhD in Molecular Biophysics and Biochemistry at Yale University, where he developed nascent RNA-sequencing methods (TimeLapse-seq) to assess mRNA transcriptional dynamics and mRNA stability. He then worked as a postdoctoral fellow at Fred Hutch Cancer Center, where he assessed mechanisms of gene regulation in yeast using both nascent single cell RNA-sequencing and large-scale transcriptional reporter assays. Jeremy has been with Merck for 2 years.

Followed by a live Question and Answer session

Sponsored by Merck

Merck is a leading science and technology company. Our BioReliance® biosafety testing and analytical development services deliver risk-mitigating solutions with technical and regulatory expertise. We partner with clients through the product cycle, from early pre-clinical development through licensed production, to help ensure the safety of the world’s therapeutics.