2013-05-24-世界卫生组织-Recommendations_to_Assure_the_Quality,_Safety_and_Efficacy_of_Recombinant_Hepatitis_B_Vaccines,_Annex_4,_TRS_No_978_52页_692kb

The WHO recommendations for assuring the quality, safety, and efficacy of recombinant hepatitis B vaccines replace previous guidelines and cover key aspects including manufacturing, nonclinical evaluation, clinical assessment, and regulatory considerations.

Part A. Manufacturing Recommendations

• Focus on yeast and mammalian cell substrates, requiring thorough cell bank characterization and control.
• Processes must include strict fermentation control, single harvest protocols, and extensive purification steps with validated methods.
• Documentation, retained samples, labeling, and distribution protocols must follow global health standards to ensure product consistency.

Part B. Nonclinical Evaluation

• Requires detailed genetic engineering data and characterization of HBsAg.
• Includes rigorous product analysis (e.g., size, carbohydrate, lipid content) and immunogenicity testing in animals.
• Specifies use of nonclinical models like chimpanzees for proof of efficacy and regulatory safety assessments.

Part C. Clinical Evaluation

• Trials must assess immunogenicity (anti-HBs concentration ≥10 mIU/ml post-vaccination) and persistence of immunity.
• Suggests age-stratified studies, dose-ranging analyses, and persistence testing, particularly in high-risk groups.
• Post-marketing pharmacovigilance plans are required to monitor long-term safety and effectiveness.

Part D. Recommendations for National Regulatory Authorities

• Requires approval of production methods, control procedures, and release of vaccines based on adherence to international standards.
• Emphasizes detailed exchange protocols and certificate formats to facilitate international vaccine distribution.