2022-04-21-世界卫生组织-Guidelines_on_evaluation_of_Biosimilars,_TRS_1043,_Annex_3_52页_842kb

WHO Annex 3: Guidelines on Evaluation of Biosimilars

Overview

• Purpose: To provide scientifically sound principles for the licensing of biosimilars, ensuring comparable quality, safety, and efficacy to the reference product (RP).
• Scope: Applies to well-characterized biological products (e.g., therapeutic peptides/proteins), excluding vaccines and plasma-derived products.

Key Terminology

1. Biosimilar: A biological product highly similar to an already licensed RP.
2. Comparability Exercise: Direct head-to-head comparison of the biosimilar with the RP.
3. Similarity Range: Predefined allowable differences in physicochemical properties or biological activity.

Core Principles for Licensing Biosimilars

1. Comprehensive characterization of the RP’s quality attributes.
2. Demonstration of structural, functional, and clinical similarity through analytical and clinical data.
3. Risk-based approach for data requirements based on the assessed similarity level.
4. Regulatory oversight by National Regulatory Authorities (NRAs) is essential.

Components of Evaluation

1. Quality

• Use of orthogonal analytical methods to assess similarity in primary/ higher-order structure, post-translational modifications, biological activity, and impurities.
• Comparability demonstrated through statistical analysis of data from multiple RP and biosimilar batches.
• Stability studies to support shelf-life determination.

2. Nonclinical Evaluation

• In vitro studies to assess binding and functional properties.
• In vivo animal studies waived if nonclinical data and quality analysis demonstrate high similarity.

3. Clinical Evaluation

• Pharmacokinetic (PK): Comparability studies to assess absorption, distribution, and elimination.
• Pharmacodynamic (PD): Functional assays if PK studies are inconclusive.
• Immunogenicity: Assessment of antibody formation and its impact on efficacy and safety.
• Efficacy and Safety: Clinical trials to confirm similar clinical outcomes if necessary.

Regulatory Considerations

• Role of NRAs: Ensure biosimilars meet safety and efficacy standards.
• Use of Non-local RPs: Allowed if NRAs determine the RP meets scientific and regulatory standards.
• Post-Approval Surveillance: Pharmacovigilance to monitor long-term safety.

Conclusion

• The guidelines aim to streamline regulatory processes, enhance global harmonization, and facilitate affordable access to high-quality biosimilars while ensuring patient safety and efficacy.