2008-01-01-世界卫生组织-Guidelines_on_regulatory_preparedness_for_human_pandemic_influenza_vaccines,_Annex_2,_TRS_963_108页_5mb

Summary of Annex 2: Guidelines on Regulatory Preparedness for Human Pandemic Influenza Vaccines (Adopted 2007)

Annex 2 provides comprehensive guidelines on regulatory preparedness for human pandemic influenza vaccines. It aims to facilitate global cooperation and standardization among national regulatory authorities (NRAs) and vaccine manufacturers to ensure the timely development, licensing, and distribution of effective vaccines during influenza pandemics. The document emphasizes the importance of international harmonization, emergency use provisions, and robust postmarketing surveillance to address challenges like rapidly evolving scientific knowledge and potential shortages in vaccine capacity.

Guiding Principles

• Emergency Response: Strategies focus on accelerating regulatory pathways to shorten the time between pandemic emergence and vaccine availability, prioritizing global health security through collaboration with organizations like WHO.
• Regulatory Harmonization: Efforts are made to align regulatory processes across countries to enable efficient vaccine evaluation and market access, leveraging WHO prequalification to build trust and facilitate distribution.
• Scenarios Covered: Guidelines address various vaccine types, including those for inter-pandemic use, stockpiling, and pandemic-specific vaccines, covering inactivated and live attenuated forms.
• Risk-Based Approach: Decisions are based on risk-benefit analysis, with flexibility in emergency use and data sharing to counter pandemic unpredictability.

Regulatory Pathways and Harmonization

• Comparative Approaches: Different countries (e.g., Australia, Canada, EU, Japan, US) have varied regulatory methods, involving full clinical trials, pre-pandemic core dossiers, and centralized/decentralized review processes.
• Proposed Standard Process: A framework for authorization includes pre-pandemic data submission, quality control, and batch release mechanisms, with emphasis on data harmonization to avoid redundant testing.
• WHO Involvement: WHO plays a key role in prequalifying vaccines and promoting shared standards to enhance global access, especially for developing countries.
• Challenges: Harmonization faces barriers from national laws and varying capacities; emergency options are included to expedite decisions if time allows.

Emergency Use Criteria

• Flexibility in Licensing: Emergency use provisions allow for authorization with limited data during crises, using mechanisms like animal-based approvals or conditional marketing authorizations.
• Priorities: Decisions prioritize population health, with criteria based on data availability, production capacity, and minimization of risks. For example, vaccines against novel human influenza viruses may be deployed before a pandemic if approved.
• Global Consensus: While international guidelines exist, their implementation depends on jurisdictional capabilities; information sharing is critical for rapid response.

Development and Evaluation Considerations

• Quality and Manufacturing: Key aspects include biosafety level adherence, stability testing, and quality specifications for different production systems like cell cultures or recombinant DNA technology.
• Preclinical and Clinical Evaluation: Testing ranges from animal models to human trials, covering immunogenicity, safety, and efficacy. Dose-response studies and pediatric groups are emphasized.
• Novel Technologies: Innovations like cell-based or adjuvanted vaccines require additional safety and immunogenicity assessments, with data pooled for regulatory decisions.
• Postmarketing Surveillance: Essential for ongoing monitoring of real-world safety and effectiveness, including periodic safety reports and signal detection in emergencies.

Quality Control and Postmarketing Surveillance

• Batch Release: Procedures ensure vaccine quality through national control laboratories, with adapted methods for large-scale production during pandemics.
• Postmarketing Commitments: Includes pharmacovigilance for adverse events, effectiveness studies, and risk management plans to address issues like herd immunity and vaccine-drug interactions.
• Global Coordination: Sharing safety data and experiences help refine strategies during pandemics, with tools like WHO's database and regional collaborations.

These guidelines underscore the need for proactive regulatory preparation, international collaboration, and adaptive frameworks to manage influenza pandemics effectively.