Quality and Stability Testing of LNP Formulations of mRNA
- Many of approved mRNA medicines are encapsulated in lipid nanoparticles (LNPs: Lipid Nano Particles).
- LNPs is a DDS (Drug Delivery System) formulation composed of pH sensitive lipids, modified lipids, helper lipids, etc. that protect mRNA from degradation by nucleases in vivo and deliver mRNA to target cells.
- To ensure the quality of mRNA medicines in their DDS formulation, analytical evaluations are needed, using multi-component analytical techniques, including lipid content, mRNA encapsulation efficiency, particle size, and particle size distribution, as well as expression verification of the target protein.
- We conduct the quality testing and stability testing of products requested by our clients from the early research and development stage to the commercial stage in compliance with regulatory requirements, such as GMP and the Japan’s Reliability Criteria *1.
Operation system
- We conduct our studies based on ICH guidelines.
- We conform to the Japan’s Reliability Criteria*1, and the GMP (Japan, the USA, and the Europe).
- We comply with the Japanese and global laws, guidance, and guidelines and we ensure the data integrity*2.
Inspection and audit experience
- We have abundant experience in FDA inspections, PMDA inspections, QP audits, and audits by clients worldwide including Japan.
Features
- We develop analytical methods and conduct analytical method validation according to the recent information, such as USP “Analytical Procedures for Quality of mRNA Vaccines and Therapeutics” (Draft Guidelines: 3rd Edition)*3.
- We conduct quality testing, stability testing, and release testing.
- We have extensive experience in analytical method transfer from overseas facilities.
Quality tests and stability studies
- Long term testing, accelerated testing, stress testing, and photostability testing according to ICH Guidelines*4
- Stability storage facilities at our testing sites are monitored by our centralized control systems (NASTER systems).
Samples handling
- We decontaminate the equipment and experimental benches before testing to prevent contamination with ribonuclease, and conduct tests in an RNase-free environment by wearing gloves and masks.
- We prevent contamination with our zone-management system. Reagents (controls) and samples (nucleic acid samples) are therefore handled in different laminar flow cabinets for Sanger sequencing, real-time PCR and other tests.
- Powder containment facilities (EC2) enable our handling of highly potent compounds up to OEL Category 5.
- BSL-2 laboratories enable our handling of biohazard samples.
Test items
| Test items | Methods | Instruments |
|---|---|---|
| Identification, Nucleotide sequence | Real-time PCR | QuantStudio 7 Flex |
| Sanger sequence method | SeqStudio | |
| mRNA content | LC/UV method | Ultimate 3000RS Vanquish flex |
| spectrophotometry | NanoDrop Onec | |
| Purity, mRNA integrity | Agarose gel electrophoresis | E-Gel Power Snap |
| Microchip electrophoresis | Agilent 2100 Bioanalyzer | |
| Capillary electrophoresis | PA 800 plus | |
| Lipid content | LC/CAD method | Ultimate 3000RS/Corona Veo RS Vanquish flex |
| Encapsulation efficiency | Fluorometry | SpectraMax M5 SpectraMax iD5 |
| Particle size, polydispersity | Dynamic light scattering method | Zetasizer Ultra |
| Potency | ELISA, CBA, etc. | SpectraMax M5 SpectraMax iD5 |
References
- *1: Article 43 of Regulation for Enforcement of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices
- *2: FDA 21 CFR Part11
Notification by the Director General of the Pharmaceutical and Food Safety Bureau, MHLW Regarding Use of Electromagnetic Records and Electronic Signatures in Applications for Drug Approval or Licensing, etc. (PFSB Notification No. 0401022)
Annex11 to the EU Guide to GMP Computerized Systems
Notification " Guideline on Management of Computerized Systems for Marketing Authorization Holders and Manufacturers of Drugs and Quasi-drugs" (Pharmaceutical and Food Safety Bureau, Pharmaceutical and Food Safety Bureau, MHLW, PFSB Notification No. 1021-11)
A risk-based Approach to Compliant GxP Computerized Systems (GAMP 5), ISPE/GAMP COP (2008.2) - *3: Analytical Procedures for Quality of mRNA Vaccines and Therapeutics (Draft Guidelines: 3rd Edition)
https://www.uspnf.com/notices/analytical-procedures-mrna-vaccines-20240802 (accessed 2025.11.28) - *4: ICH Guideline, Stability Assay
https://www.pmda.go.jp/int-activities/int-harmony/ich/0038.html (accessed 2025.11.28)
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