2021-06-07-世界卫生组织-WHO_informal_consultation_on_regulatory_considerations_for_evaluation_of_the_quality,_safety_and_efficacy_of_RNA-based_prophylactic_vaccines_for_infectious_diseases_9页_312kb

WHO Informal Consultation on Regulatory Considerations for mRNA Vaccines

Background and Purpose:
The rapid advancement of mRNA vaccines, accelerated by the COVID-19 pandemic, highlights their efficacy in public health emergencies. WHO initiated this consultation to address regulatory convergence for mRNA vaccines, building on prior discussions for DNA vaccines and recognizing differences in manufacturing and clinical evaluation. The goal is to develop interim guidance for evaluating mRNA quality, safety, and efficacy.

Meeting Overview:
Held virtually from 20-22 April 2021, the meeting involved about 90 participants from 24 WHO regions. Key topics included global mRNA vaccine development, regulatory perspectives, and review of WHO draft documents. Discussions focused on manufacturing, nonclinical, and clinical evaluation, emphasizing flexibility and adaptability.

Main Outcomes and Consensus:

• mRNA vaccines are interim guidance due to evolving science and need for case-by-case regulatory consideration to avoid restricting future innovations.
• Early engagement with National Regulatory Authorities (NRAs) is critical for rapid vaccine development and trials, balancing speed and safety.
• Defined terminology was agreed upon, including "drug substance" for mRNA and "final formulated bulk" for storage and dilution. Potential issues, like platform technology definition and variations in manufacturing methods (e.g., LNPs and nucleotide modifications), require further clarification in the next draft.
• Multivalent and multi-strain vaccines may be considered, referencing WHO guidelines on clinical evaluation.

Key Issues Addressed:

• Quality: Controls for mRNA, LNP-based formulations, and manufacturing flexibility under emergency conditions.
• Nonclinical Evaluation: Focus on biodistribution, toxicity, and lifecycle of LNPs, with examples of assays provided.
• Clinical Evaluation: Adverse effects assessment and efficacy in variant scenarios, cautioning against standardized bridging studies.

Next Steps:
The drafting group will revise the WHO document based on consultation feedback. The next draft will undergo editorial review in June, with submission to the WHO Expert Committee on Biological Standardization in July for a second public consultation, aiming to finalize guidance by October 2021.