GMP-Grade mRNA-LNP Vaccine Development

ProMab was the first CRO to offer both off-the-shelf and custom mRNA-LNP products and services. We cover the whole workflow – template design, mRNA synthesis, LNP formulation, quality analysis, preclinical testing and IND support – with over 100 ready-to-use mRNA-LNP products and custom programs from preclinical through clinical stage.

Our GMP-Grade mRNA-LNP Services Include:

All services are tailored to maximize the performance and success of your therapeutic candidates.

GMP production of mRNA-LNP runs through nine tightly controlled steps (Figure 2), all under FDA-compliant standard operating procedures (SOPs). The design decisions made along the way decide how well the final mRNA is expressed.

Key considerations: four design decisions that set expression and stability

We formulate mRNA-LNPs by mixing a lipid phase with an aqueous mRNA phase on microfluidic systems, which gives precise, scalable and consistent particles: size below 150 nm, PDI below 0.3, encapsulation above 90%. The LNPs are then purified into the buffer that suits their use, typically PBS (pH 7.2–7.4) or 10–20 mM TBS (pH 7.2–7.5), with sucrose, Polysorbate 80/20 or EDTA added to prevent aggregation and degradation.

Lipid choice is application-specific. We work with the common ionizable lipids SM-102, DLin-MC3-DMA and ALC-0315 as well as our own proprietary lipids. All of them give robust expression in vitro and in vivo, and the comparison in Figure 3 shows how much the lipid matters.

Stringent QA is what makes an mRNA-LNP safe, consistent and effective, whether it is a vaccine, a cancer immunotherapy or a gene-modulating therapeutic. ProMab validates every step of production, from raw materials to final product, on dedicated analytical platforms (Figure 4).

Our QA testing includes:

Testing covers in-process controls as well as final-product characterization. Residual DNA, protein and enzymes are quantified to ICH and pharmacopeial limits; endotoxin, sterility, pH and osmotic pressure follow GMP and USP requirements.

Bioactivity assays in human cell lines confirm that the mRNA is delivered and functional, and potency is part of the release criteria so every batch performs the same (Figure 5). The QA team works alongside manufacturing and regulatory to keep documentation, traceability and deviation management ready for submissions and clinical trials.

The QA system is aligned with global GMP standards: no mRNA-LNP product reaches patients or investigators without meeting its performance and safety criteria.

Stability sets the shelf-life and the storage conditions. mRNA-LNPs are typically held at 4°C short term (0–3 months) and at −20°C or −80°C long term (over 6 months); stability testing shows how well they keep their physical, chemical and biological integrity in storage and in transit.

We run stability studies to FDA and ICH guidelines on at least three independent GMP batches, under real-time and accelerated conditions, tracking particle size, PDI, encapsulation efficiency, mRNA integrity, biological activity and potency.

Validated protocols and quality systems give reproducible, regulatory-ready data across multiple GMP batches. ProMab mRNA-LNP products are validated as physically and functionally stable for 3 months at 4°C and for more than 6 months at −80°C (Figure 6).

We currently manufacture custom GMP-grade mRNA-LNP drug products for Phase 1 trials, with capacity for up to 50 patients, so a program can move from research to clinical manufacturing in one place.