Study on the Critical Quality Attribute of Anti-HER2 Monoclonal Antibody
Objective:To study and establish a quality control method for some critical quality attributes of the domestic anti human epidermal growth factor receptor 2(HER2)monoclonal antibodies.Methods:Based on the product characteristics and effects mechanism of trastuzumab,the quality attributes were evaluated and graded.And some critical quality attributes of 7 batches of the domestic anti-HER2 monoclonal antibody were detected using 7 batches of reference trastuzumabs as the control.The charge heterogeneity was analyzed by ion exchange-high performance liquid chromatography(IEC-HPLC).Biological activity was determined by BT474 cell proliferation inhibition assay.Bio-Layer Interferometry(BLI)was used to measure antigen-antibody affinity,monoclonal antibody affinity with FcRn,and Surface Plasmon Resonance(SPR)was used to measure the affinity of monoclonal antibody with FcγRⅢa.Thermal stability was evaluated by Differential Scanning Calorimetry(DSC).Results:The mean±3SD values of IEC main peak areas percent and EC50 of 7 batches of original trastuzumabs were(73.87±2.21)％and(0.20±0.06)μg·mL-1,respectively.The results of the domestic anti-HER2 monoclonal antibodies were(73.54±3.24)％,(0.20±0.05)μg·mL-1,respectively.The KD values of antigen-antibody affinity,antibody-FcγRⅢa affinity and antibody-FcRn affinity were 1×10-10,1×10-6,1×10-7,respectively.The results of 7 batches of the domestic anti-HER2 monoclonal antibodies were 1×10-10,1×10-6,1×10-7,respectively.The thermal stability mappings of the domestic anti-HER2 monoclonal antibodies were consistent with those of the original trastuzumabs.Conclusion:A method for quality study of anti-HER2 monoclonal antibody is developed,which provides a reference for quality control of this class domestic monoclonal antibody.
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维普
