Evaluation of critical quality attributes of an anti-HER2 humanized monoclonal antibody drug / 中国药学杂志

ABSTRACT

OBJECTIVE: To perform a multidimensional study on the critical quality attributes of a therapeutic anti-HER2 humanized monoclonal antibody targeting HER2-positive breast cancer. METHODS: The critical quality attributes such as purity, impurities, structure, and function were evaluated using multidimensional analytical techniques including HPLC, CE-SDS, dynamic light scattering, circular dichroism, differential scanning calorimeter, LC-MS/MS, in vitro bioactivity assay and SPR binding kinetics. RESULTS: The monomer content of the antibody was more than 98% while the polymer impurities were less than 2%. The sum of heavy chain and light chain peak area was over 97% while the non-glycosylated heavy chain impurities area was less than 1% on the CE-SDS electrophoretogram. The antibody drug demonstrated comparable CD spectrum, predicted secondary structure and unfolding temperatures to the reference product. It had highly similar N-glycan profile involving glycosylation site and N-glycan types to the reference product. The analysis showed no significant difference in the functional CQAs like BT474 proliferation inhibiting bioactivity, ADCC efficacy, the binding affinity to HER2 and Fc receptors between the evaluated drug product and the reference. CONCLUSION: The characteristics of the monoclonal antibody drug such as high purity and few impurities indicate homogeneity and low-risk of safety issues. High similarity to the reference has been verified in multiple aspects like higher structure, glycosylation and function. The positive quality evaluation result is a prerequisite for clinical research. Moreover, to some extent, there can be potential correlation between CQAs and clinical safety and efficacy.