2014-11-05-世界卫生组织-Recommendations_to_assure_the_quality,_safety_and_efficacy_of_poliomyelitis_vaccines_oral,_live,_attenuated_,_Annex_2,_TRS_No_980_92页_568kb

Annex 2 Summary

• Introduction:
  WHO's recommendations for OPV were established first in 1962 and revised multiple times (1965, 1971, 1982, 1989, 1999). Updates in 2010-2013 addressed scientific advances, including the use of transgenic mice for neurovirulence testing and acknowledging monovalent/bivalent OPVs for endemic and outbreak scenarios.

• General Considerations:
  OPV is a safe vaccine but rare risks like VAPP exist. Production requires stringent GMP, and WHO retains custody of the seed strains. Key recommendations include defining terms like "cell seed," "virus master seed," and controls for adventitious agents.

• Scope:
  The Recommendations apply to all OPV strains derived from Sabin seeds, regardless of history. They include nonclinical and clinical evaluations and are to be read alongside other WHO guidelines.

• Part A: Manufacturing Recommendations:
  Established based on GMP principles. Includes definitions, control of source materials (cells and virus seeds), and detailed tests for safety, potency, and consistency (e.g., MAPREC assay). Applies to both cell lines and primary monkey kidney cells (Part E).

• Part B: Nonclinical Evaluation:
  Involves characterization of virus seeds (master, submaster, working) and neurovirulence testing in monkeys and transgenic mice (e.g., TgPVR mice). Includes identity, molecular characterization (genotype sequencing, passage limits), and replacement of old tests like MNVT with TgmNVT where applicable.

• Part C: Clinical Evaluation:
  Covers safety (VAPP), immunogenicity studies (neutralizing antibodies), dose-response and type-specific formulations, and post-marketing surveillance to monitor vaccine performance in real-world use.

• Part D: Recommendations for NRAs:
  NRAs are to authorize and implement these Recommendations for manufacturers. Release certification based on GMP, sterility, potency, and consistency tests. NRAs may adopt modified tests if they ensure safety/efficacy.

• Part E: Recommendations for Primary Monkey Kidney Cell Cultures:
  Additional or alternative controls specific to monkey cell use, including quarantine protocols, animal health checks, and tests for adventitious agents like herpes B virus and SV40.

• Appendices:
  Provide supplementary details, including virus seeds overview, neurovirulence test summaries, fill/flow sheets, and model protocols/certificates for use during manufacturing, testing, and release.