2004-11-14-世界卫生组织-Poliomyelitis_vaccine_live_attenuated_28页_141kb

Summary of the Collaborative Study on the Suitability of a Replacement International Standard for Oral Polio Vaccine

Core Content

This report details a collaborative study conducted to assess the suitability of a candidate replacement for the current International Standard (IS) for trivalent oral polio vaccine (OPV), NIBSC reference 85/659. The study involved 13 laboratories from five OPV manufacturers and eight National Control Authorities. Five different samples were tested: the current IS (85/659), the candidate replacement (NIBSC reference 02/306), the European Pharmacopoeia Biological Reference Preparation (BRP), a commercial vaccine (Sample E), and a heat-stressed version of the commercial vaccine (Sample F). The study aimed to evaluate the consistency and reliability of the candidate preparation and determine its potency for use as a replacement.

Main Points

• Study Aim: To assess the suitability of the candidate 2nd IS (NIBSC reference 02/306) as a replacement for the current IS (85/659) and to assign a potency value.
• Participants: 14 laboratories agreed to participate, with 13 submitting results. These included 8 National Control Laboratories (NCLs) and 5 manufacturers.
• Study Design:
  • Each laboratory tested five coded samples (A-F) on three separate occasions.
  • Laboratories could use their own in-house antisera or the NIBSC monoclonal antibodies (MAb's) provided.
  • Duplicate samples (C and D) were used to assess within-assay variability.
• Candidate Preparation:
  • The candidate 2nd IS was formulated from monovalent Sabin virus bulks (SO + 3 for types 1 and 2, RSO + 3 for type 3).
  • It was prepared in MEM with 1% bovine albumin and sodium bicarbonate buffer without thermal stabilizers.
  • The preparation was filled into 4600 neutral borosilicate glass ampoules with a mean fill weight of 0.8031 g and a coefficient of variation of 0.09%.
  • The NIBSC reference number for the candidate is 02/306.
• Stability Testing:
  • The candidate was tested for stability at various temperatures (4°C, 20°C, 37°C, 45°C) and compared to the current IS.
  • Real-time stability data showed the candidate to be stable at -70°C, similar to the current IS.
  • No significant differences in potency were observed between the candidate and the current IS over 18 years of storage.
• Potency Results:
  • The overall mean titres for the candidate 2nd IS were 6.51, 5.51, 5.87, and 6.66 log₁₀ TCID₅₀/0.1 ml for types 1, 2, 3, and total virus content respectively.
  • These values were converted to log₁₀ TCID₅₀/ml for the IS potency assignment: 7.51, 6.51, 6.87, and 7.66.
• Variability:
  • Within-assay variability: The average root mean square (r.m.s.) difference between duplicate samples C and D was 0.18 log₁₀ TCID₅₀.
  • Within-laboratory variability: The average coefficient of variation (CV) across all samples and polio types was 2.50%, indicating high consistency.
  • Between-laboratory variability: The range of titres between laboratories was within 0.5 log₁₀ TCID₅₀ of the mean, showing good inter-laboratory agreement.
• Antisera Comparison:
  • No substantial differences were found between titres obtained using NIBSC monoclonal antibodies and in-house antisera.
  • The study confirmed that both types of antisera produced consistent results.
• Sample Performance:
  • The current IS (Sample A) and Ph. Eur. BRP (Sample B) showed titre estimates very close to their assigned values.
  • Sample E (commercial vaccine) met or exceeded the UNICEF specifications for most types, though some laboratories reported titres slightly below the release criteria for type 3.
  • Sample F (heat-stressed commercial vaccine) showed reduced potency, as expected, with titre estimates lower than the original specifications.

Key Information

• Candidate 2nd IS (NIBSC 02/306):
  • Formulated to be slightly more potent than the current IS to align better with current vaccines.
  • Maintained similar formulation to allow for direct comparison.
  • Available for up to 30 years based on the fill size.
• Stability:
  • The candidate showed comparable stability to the current IS under long-term storage at -70°C.
  • Stability data will continue to be monitored annually.
• Recommendation:
  • The candidate is recommended to be established as the 2nd IS for trivalent OPV.
  • The assigned potency values are: 7.51, 6.51, 6.87, and 7.66 log₁₀ TCID₅₀/ml for types 1, 2, 3, and total virus content respectively.
• Future Actions:
  • Additional real-time stability data will be generated and reported to the committee in five years.

Conclusion

The study confirmed the candidate 2nd IS (NIBSC reference 02/306) is suitable for use as a replacement for the current IS (85/659). The results demonstrated high consistency in potency estimates across laboratories, with low variability in both within and between assays. The candidate preparation behaves predictably and is stable under various conditions, making it a reliable reference material for future potency testing of trivalent OPV.