Demonstrating Analytical Similarity of Trastuzumab Biosimilar HLX02 to Herceptin® with a Panel of Sensitive and Orthogonal Methods Including a Novel FcγRIIIa Affinity Chromatography Technology

This paper details a comprehensive analytical similarity assessment between the trastuzumab biosimilar HLX02 and its originator reference product, Herceptin®, sourced from both Europe (EU-Herceptin®) and China (CN-Herceptin®). The study employed a quality-by-design (QbD) approach and a tier-based evaluation of quality attributes. A key aspect of the methodology involved a panel of highly sensitive and orthogonal analytical techniques, notably a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography. This advanced chromatographic method allowed for the quantitative comparison of glycan effects on effector function, a critical factor in biosimilarity. To ensure robust data, ten batches of HLX02 were compared against 39 batches of the reference product, spanning a wide range of expiry dates from August 2017 to March 2021. The results demonstrated that HLX02 exhibited high analytical similarity to both EU-Herceptin® and CN-Herceptin®. Interestingly, the study observed fluctuations in %afucose, %galactose, and FcγRIIIa affinity in the reference product batches over time, which allowed for their subgrouping based on FcγRIIIa affinity chromatograms. HLX02 was found to be particularly similar to the high FcγRIIIa affinity subgroup of Herceptin®, underscoring the power and utility of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation.

This paper details a comprehensive analytical similarity assessment between the trastuzumab biosimilar HLX02 and its originator reference product, Herceptin®, sourced from both Europe (EU-Herceptin®) and China (CN-Herceptin®). The study employed a quality-by-design (QbD) approach and a tier-based evaluation of quality attributes. A key aspect of the methodology involved a panel of highly sensitive and orthogonal analytical techniques, notably a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography. This advanced chromatographic method allowed for the quantitative comparison of glycan effects on effector function, a critical factor in biosimilarity. To ensure robust data, ten batches of HLX02 were compared against 39 batches of the reference product, spanning a wide range of expiry dates from August 2017 to March 2021. The results demonstrated that HLX02 exhibited high analytical similarity to both EU-Herceptin® and CN-Herceptin®. Interestingly, the study observed fluctuations in %afucose, %galactose, and FcγRIIIa affinity in the reference product batches over time, which allowed for their subgrouping based on FcγRIIIa affinity chromatograms. HLX02 was found to be particularly similar to the high FcγRIIIa affinity subgroup of Herceptin®, underscoring the power and utility of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation. Research Background and Significance The development of biosimilars has become increasingly critical in the biopharmaceutical industry to provide cost-effective alternatives to expensive biologic therapies while ensuring comparable efficacy and safety. Trastuzumab, commercially known as Herceptin®, is a monoclonal antibody widely used in the treatment of HER2-positive breast cancer. HLX02 is a trastuzumab bio