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A Three-Arm, Tiered Comparability Strategy Bridging Post-Approval Process Changes for an Omalizumab Biosimilar
Chenguang Wang1,2,3,4, Chaoxin Zhou1,2,3,4, Sheng Hou1,2,3,4
1State Key Laboratory of Macromolecular Drugs and Large-Scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Pharmaceuticals (Basel, Switzerland)
|May 27, 2026
Summary
Manufacturing changes for the omalizumab biosimilar CMAB007 were assessed using a novel tiered strategy. The study confirmed the biosimilar
Area of Science:
- Biopharmaceutical manufacturing
- Biosimilarity assessment
- Regulatory science
Background:
- Post-approval manufacturing changes for biologics necessitate rigorous comparability assessments to maintain quality and clinical performance.
- CMAB007 (Aomaishu®), an omalizumab biosimilar approved in China (2023), underwent process enhancements including media optimization and chromatography substitution, increasing production fivefold without altering the host cell line.
Purpose of the Study:
- To evaluate the comparability of post-change CMAB007 against pre-change CMAB007 and the reference product (Xolair®) following manufacturing process enhancements.
- To confirm the pharmacokinetic (PK) and safety equivalence of post-change CMAB007 to the reference product (Xolair®) to mitigate "biological drift" risks.
Main Methods:
- A novel three-arm tiered strategy was employed, classifying critical quality attributes (CQAs) by risk impact with tier-specific acceptance criteria.
- Comprehensive analytical methods assessed structural attributes, post-translational modifications, purity, impurities, activity, and Fc-mediated functions.
- Pharmacokinetic (PK) and safety comparability was evaluated in a randomized, double-blind, two-arm study in healthy males (N=114).
Main Results:
- Post-change CMAB007 demonstrated analytical similarity within tiered acceptance criteria for all CQAs.
- Stability studies indicated enhanced robustness under stress conditions.
- PK equivalence was confirmed for AUC0-inf, AUC0-t, and Cmax, with comparable immunogenicity and safety profiles between post-change CMAB007 and Xolair®.
Conclusions:
- The study successfully pioneered a tiered three-arm comparability strategy for post-approval manufacturing changes, integrating advanced analytics, risk-based assessment, and clinical validation.
- This approach effectively mitigates "biological drift" risks, ensuring biosimilar quality, efficacy, and safety while enabling scalable and sustainable production.
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