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What the EMA’s 2025 draft mRNA quality guideline means for manufacturers

In 2025 the European Medicines Agency published a draft guideline on the quality of mRNA vaccines. Here is what it says about RNA integrity, and why that matters for testing during production.

By Samkit Shah3 min read

In March 2025, the European Medicines Agency (EMA) released a draft guideline on the quality aspects of mRNA vaccines, reference EMA/CHMP/BWP/82416/2025.1 Its public consultation ran from 31 March to 30 September 2025. It is still a draft, and details may change before it is final. But it is the clearest statement yet of what a European regulator expects from mRNA quality control, and one theme runs all the way through it: the mRNA has to be shown to be intact.

What the guideline covers

The draft applies to mRNA vaccines against infectious diseases, including self-amplifying mRNA. Other mRNA medicines are formally out of scope, although the document says relevant parts may apply to them.1 It covers how the product is made, how it is characterised, what goes into its specifications and how it is tested.

It also fills a gap. As the draft explains, mRNA vaccines follow the general guidelines for human vaccines, but those guidelines do not specifically address this technology.1

Integrity is a critical quality attribute

A critical quality attribute, or CQA, is a property that has to stay within defined limits for a product to be safe and effective. The draft lists the CQAs that should, at a minimum, be controlled when the mRNA active substance is released. mRNA integrity is on that list, alongside mRNA content, impurities, functionality and several other attributes.1

The draft defines integrity plainly: the proportion of mRNA molecules that are intact and full length. It asks for a method with enough resolution to detect shorter or longer molecules, such as degraded fragments or incomplete transcripts, and names capillary gel electrophoresis, agarose gel electrophoresis and liquid chromatography as suitable techniques.1

This is not a new idea. The World Health Organization’s regulatory considerations for mRNA vaccines, published in 2022, also state that the integrity of the mRNA is a critical quality attribute for release.2 What the EMA draft adds is detail, and reach.

Integrity shows up at every stage

Read the draft end to end and integrity appears again and again:

  • Active substance release. Integrity is a listed CQA for the mRNA itself.1
  • Finished product release. The proportion of intact, full-length mRNA should be determined for the formulated vaccine too. Potency is judged through a combination of tests that includes RNA content, mRNA integrity and encapsulation efficiency.1
  • Stability. The stability programme should include testing of purity, meaning mRNA integrity, including quantitative detection of degradation.1
  • In-use handling. In-use stability studies should look at the effect of freeze and thaw cycles on integrity when the product may be stored under different conditions after thawing.1

Integrity is no longer one test at the end. It is a release attribute, a stability attribute and part of how potency is judged.

What it means for manufacturers

The draft does not require integrity testing between every production step. Its explicit requirements are about release, stability and characterisation. But it does point toward stronger process control in two ways.

First, for some process-related impurities it allows control either at release or through in-process controls, and accepts omitting routine testing where process validation shows they are consistently removed.1 Second, the WHO document asks manufacturers to develop tests and acceptance criteria for critical steps of the manufacturing process, to ensure, and provide feedback on, control of that process.2

Put together, the direction is clear. WHO’s guidance and the EMA draft both point toward integrity measured carefully at release and over shelf life, and toward manufacturers who understand their process well enough to keep it in control.

What follows is our view rather than the regulator’s. A degraded intermediate caught early costs far less than a batch that fails at release, after formulation and fill have added their own time and expense. That is why we think fast, routine integrity checks during production will become more valuable as more mRNA products reach the market and as guidance like this is finalised.

What to watch

The EMA’s Biologics Working Party lists finalisation of its guideline on the quality aspects of RNA vaccines among its activities for 2026.3 When the final text appears, the parts worth reading closely are the release specifications, the stability requirements, and anything that shifts the balance between release testing and in-process control.

The draft is also a useful checklist today. If your quality strategy can already answer its questions on integrity, at release, on stability and in use, you are well placed for whatever the final version says.

Footnotes

  1. European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on the quality aspects of mRNA vaccines (draft). EMA/CHMP/BWP/82416/2025, 27 March 2025. ema.europa.eu ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10

  2. World Health Organization. Evaluation of the quality, safety and efficacy of messenger RNA vaccines for the prevention of infectious diseases: regulatory considerations. Annex 3, WHO Technical Report Series No. 1039, 2022. who.int ↩ ↩2

  3. European Medicines Agency. 3-year work plan for the Biologics Working Party, 2026 to 2028. 5 November 2025. ema.europa.eu ↩

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