mRNA Vaccines: How Is Potency Preserved During Scale-Up?

How do manufacturers check mRNA vaccine potency?

The IndexBox outlook links demand for nucleic acid materials to expanding vaccine and gene-therapy development. This commercial forecast provides context for a practical pharmaceutical challenge: producing more doses while maintaining consistent biological activity. Its growth projections do not establish that any experimental treatment works or will receive approval. [IndexBox market analysis](https://www.indexbox.io/blog/nucleic-acid-raw-materials-market-forecast-to-2035-growth-accelerates-on-mrna-vaccine-and-gene-therapy-demand/).

For mRNA vaccines, measuring the amount of RNA alone cannot establish that a formulation functions as intended. The European Medicines Agency's March 2025 draft guidance describes checks on RNA identity, integrity, encapsulation and lipid-particle characteristics, alongside functional testing. Cell-based assays can examine uptake of the formulated RNA and production of its encoded antigen—the protein that trains an immune response. These measurements assess manufacturing quality; clinical studies establish protection against disease. The document is draft guidance focused on vaccines against infectious diseases. [EMA draft guidance](https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-quality-aspects-mrna-vaccines_en.pdf).

Why does removing double-stranded RNA matter?

Manufacturing mRNA involves copying a DNA template into RNA, a process that can also generate unwanted RNA species. In a 2011 laboratory study published in Nucleic Acids Research, Katalin Karikó and colleagues investigated contaminants in laboratory-produced mRNA. Removing contaminants, including double-stranded RNA, using high-performance liquid chromatography reduced unwanted immune activation and improved protein production from nucleoside-modified mRNA in the cells studied. This was mechanistic research, rather than a trial measuring vaccine effectiveness in patients. [Karikó and colleagues](https://doi.org/10.1093/nar/gkr695).

The findings help explain why purification is part of developing a functional RNA medicine. Chemical modification of RNA and removal of manufacturing byproducts address related but distinct problems. However, the study does not establish a universal improvement in vaccine protection, quantify side effects in vaccinated people or demonstrate a defect in any marketed vaccine. Its contribution is narrower: showing experimentally that the composition of an RNA preparation can substantially influence how cells respond to it.

Does changing vaccine manufacturing require another clinical trial?

Moving production to another facility or changing a manufacturing process raises a question called comparability: does the resulting product remain sufficiently comparable to the product already studied? FDA guidance describes comparisons of chemical, physical and biological characteristics, including functional activity. Testing should target the characteristics that the particular change could affect. A matching ingredient list alone cannot answer every question about a complex biological product. [FDA comparability guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstration-comparability-human-biological-products-including-therapeutic-biotechnology-derived).

FDA explains that additional clinical safety or efficacy trials generally are unnecessary when comparability is adequately demonstrated. When uncertainty remains, additional evidence can be needed, potentially including clinical studies. This distinction matters when interpreting announcements about expanded manufacturing: increased capacity and successful clinical development are separate milestones. The practical implication is that production growth must be accompanied by evidence connecting the changed process to the product's established quality and clinical performance.