By Amara Osei

Fifteen manufacturers across Latin America, Africa, Eastern Europe, and Asia have received foundational mRNA technology through the World Health Organization's Technology Transfer Programme since its 2021 launch, the agency said on June 13, 2025. Phase 2.0, discussed on the sidelines of the G20 Summit, targets localized production of vaccines and therapeutics for influenza, tuberculosis, HIV, malaria, dengue, and leishmaniasis.

The programme is a stress test for an industry that remains commercially narrow despite the pandemic-era surge in activity. David Sokolowski, global workflow manager for nucleic acid therapeutics at Cytiva, called RNA and lipid nanoparticle (LNP) technologies "a nascent industry with limited applications commercially available."

Why does manufacturability shape every RNA candidate?

RNA design and process economics are inseparable, according to Luis Avila, PhD, a scientist at services firm Novoprotein Scientific. "RNA design fundamentally determines both manufacturability and biological performance, but optimizing for one often comes at the expense of the other," he said.

Avila distinguished three production tracks. Messenger RNA yield hinges on coding-sequence composition, transcript length, GC content, and secondary structure. Self-amplifying RNA carries a large alphavirus replicase cassette that complicates IVT but enables lower therapeutic doses. Circular RNA, Avila said, adds a circularization step whose efficiency "remains a major bottleneck."

Can a single instrument replace chromatography and mass spectrometry workflows?

Current RNA characterization is fragmented, said Matthew Ranaghan, PhD, applications scientist at Refeyn in Waltham, Massachusetts. "Current methods are limited to various types of chromatography, which struggle with poor resolution for large RNAs, or mass spectrometry, which requires digesting samples into smaller oligos with RNases."

Refeyn's mass photometry (MP) system, the company claims, delivers a single readout from nanogram-scale samples in minutes. The platform purportedly measures integrity, fragments, multimers, and purity in one run, work that today spans size exclusion chromatography, ELISA assays for double-stranded RNA, and separate mass-spec protocols.

The claim cuts hands-on time, reagent cost, and method-development overhead, Ranaghan said. Whether MP holds up for saRNA and circRNA, both of which Avila identifies as larger and more complex than standard mRNA, is the next test. The vendor also notes it is "actively building out more applications," a reminder that today's claims are forward-looking.

How far apart are the FDA and EMA on RNA chemistry, manufacturing, and controls?

Far enough to reshape development budgets. Rajiv Gangurde, PhD, vice president of chemistry, manufacturing, and controls (CMC) for cell and gene therapies at contract research organization Parexel International, told us regulators use different definitions and validation timelines.

Gangurde laid out the gaps. "While the FDA accepts real-world experience and surrogate endpoints, particularly for rare or life-threatening diseases, EMA requires more comprehensive clinical data and demonstration of long-term efficacy for approval. The EMA also mandates an appropriate degree of method validation at each stage of development, whereas the FDA does not expect validation of the potency assays during Phase I."

The product-component split is equally stark. The Spikevax lipid nanoparticle uses four components: SM-102, PEG2000-DMG, DSPC, and cholesterol. The FDA calls each a "drug substance." The EMA calls them "novel excipients." Each label triggers a different data-submission package, and developers pursuing both markets face duplicate work.

Will continuous flow IVT define the next decade of RNA production?

Both Avila and Ranaghan expect continuous or flow-based IVT to displace batch processing. Continuous flow minimizes the time that fragile mRNA spends exposed to active reaction components that drive fragmentation and aggregation, Ranaghan said, and creates "a mandate for faster, real-time analytics."

Avila cited three enabling advances: engineered low-dsRNA T7 RNA polymerases, improved co-transcriptional capping chemistries, and integrated continuous purification. Together, he said, they should "improve RNA quality, simplify downstream processing, and accelerate GMP manufacturing."

Whether the WHO's 15 partners can absorb that complexity without sustained technical support is the open question. The Programme's downstream impact will hinge on training pipelines, regulatory convergence, and the willingness of tool vendors to qualify instruments outside the United States and the European Union.