2023-01-29-世界卫生组织-WHO_BS_2023.2448_WHO_2nd_IS_for_MenC_Polysaccharide_46页_2mb

Summary of the Report on Evaluation of Candidate Material for the 2nd International Standard for Meningococcal Capsular Group C Polysaccharide

Key Findings and Recommendations

1. 💊 The candidate material (NIBSC code: 20/314) was evaluated for its suitability as the 2nd International Standard for meningococcal capsular group C polysaccharide (MenC).

   • Primary method used was quantitative 1H-Nuclear Magnetic Resonance (qNMR), which assigned an average content of 0.965 ± 0.024 mg MenC polysaccharide per ampoule (expanded uncertainty with coverage factor k=2.20, corresponding to a 95% confidence level).

2. 🔬 Secondary methods included:

   • Resorcinol assay (CV: 6.3%)
   • HPAEC-PAD (CV: 9.6%)
   • Immunoassays (CV varies)
   • QNMR demonstrated the lowest inter-laboratory variability (CV: 3.5%), making it the most reliable method.

3. ✅ Fitness-for-purpose was confirmed by:

   • Measuring consistency with the 1st MenC IS (Sample D).
   • Demonstrating that qNMR-derived unitage aligns well with results from other methods.
   • DL Residues of sialic acid were well-characterized, and no significant heterogeneity was observed.

4. 🕒 Stability testing under various conditions (real-time, accelerated thermal degradation, and reconstitution) showed:

   • The candidate material remained stable for 12 months at –20°C.
   • Molecular size distribution showed minimal changes over the study period.
   • A degradation rate of 0.015% per month was predicted for accelerated conditions.

Recommendations

• The candidate material (NIBSC code: 20/314) should be established as the 2nd International Standard for MenC polysaccharide.
• Normal storage conditions are –20°C. A stability evaluation period should continue.
• Use of the candidate standard over in-house standards reduces inter-laboratory variability in replicate studies.

Future Considerations

• Approximately 4945 ampoules are available for distribution.
• QNMR is recommended for primary calibration due to its reproducibility and harmonization with SI units.
• Implementation involves updates to assay protocols to account for unitage assignment differences between methods.