2025-01-06-世界卫生组织-Nonclinical_and_clinical_evaluation_of_monoclonal_antibodies_and_related_products_intended_for_the_prevention_or_treatment_of_COVID-19_33页_232kb

Annex 2: Nonclinical and Clinical Evaluation of Monoclonal Antibodies and Related Products for COVID-19 Prevention/Treatment

Purpose & Scope:

• Provides supplementary guidance for evaluating monoclonal antibodies (mAbs) targeting SARS-CoV-2, including prophylaxis (pre/post-exposure) and treatment.
• Address variant evolution, viral resistance risks, and immune escape mutations.
• Emphasize unique aspects distinct from their use against endogenous human antigens.

Key Considerations:

1. Safety & Efficacy:

   • Prioritize preclinical characterization of target antigens (e.g., RBD) and neutralization against variants.
   • Assess antibody-dependent enhancement (ADE) pathways and complement-dependent cytotoxicity (CDC).
   • Use well-characterized variants and international reference materials (e.g., WHO standards for SARS-CoV-2 antibodies).

2. Nonclinical Evaluation:

   • Pharmacodynamics (PD): Binding affinity, neutralization activity (live/pseudovirus assays), and effector functions (ADCC, ADCP).
   • In Vivo Studies: Prioritize animal models (e.g., Syrian hamsters, transgenic mice, ferrets, non-human primates) reflecting human infection and ACE2 similarity. Recommended alternatives to immunobridging: direct licensing evaluation.

3. Clinical Evaluation:

   • Trial Design: Tailor endpoints for prophylaxis (e.g., prevention of infection/progression) or treatment (e.g., time to symptom alleviation).
   • Target Populations: Include immunocompromised, elderly, and individuals with comorbidities.
   • Ethical Considerations: Pregnant/breastfeeding women require special evaluation. Distinguish between Headline caution regarding real-world immunogenicity data in children.
   • Resistance Risk: Monitor viral mutation emergence in patients treated with suboptimal doses.

Stringent Regulatory Approach:

• Post-authorization surveillance required due to variant-driven resistance and efficacy waning.
• Requires discussion with National Regulatory Authorities (NRA) on modifications, comparator choices, and post-marketing requirements.

Contributors & Links:

• WHO addendum authored by experts from Health Canada, EMA, US FDA, Singapore HSA.
• Draft available via public consultation on WHO Biologicals website; references WHO technical series No.1048.