Reviewing the Regulatory CMC Guideline Landscape for mRNA
- Across FDA, EMA, and Japan (MHLW/PMDA), CMC guidelines require sponsors to submit sufficient information to assure identity, quality, purity, and strength (including potency) of the investigational product, supported by descriptions of manufacture and controls (process and in-process controls, specifications/analytical controls, and stability)
- Where guidelines diverge and what sponsors typically align to: EMA has modality-specific quality guidance explicitly scoped to mRNA vaccines for infectious diseases (manufacturing process, characterisation, specifications/analytical control; definition of starting materials/active substance/finished product, and certain platform/change considerations), while the U.S. and Japan rely more on broader biologics/gene therapy quality frameworks for CMC expectations when modality-specific mRNA guidance is not issued for a given category/indication
- Commonalities for ID and oncology CMC expectations and “make it easier” mechanisms described in guidelines: Regardless of indication, guidelines converge on demonstrating a consistent control strategy for materials, process, specifications/analytical controls (incl. potency), and stability, and provide lifecycle tools to manage global CMC change predictably