Application of trend analysis in quality control of anti-HER2 monoclonal antibody / 中国药学杂志

ABSTRACT

OBJECTIVE: To analyze the trend in quality control of anti-HER2 monoclonal antibody. METHODS: The biological activity of anti-HER2 monoclonal antibody (mAb) was monitored by the proliferation inhibition with CellTiter 96® AQueous Assay kit using BT474 cells as target, and the potency of anti-HER2 mAbs was calculated by comparison with the reference standard using the method of parallel analysis. Cation exchange chromatography method was used to detect the purity by calculating the area percentage of the main peak according to the area normalization method. Ultraviolet spectrophotometry was used to detect the protein content. And pH was detected by potential method. The warning limit (x±2s) and action limit (x±3s) were defined according to the determination results of several batches of anti-HERmAb by National Institutes for Food and Drug Control (NIFDC) and the quality control laboratory of manufacturer, based on which the trend graph was plotted, and the consistent and periodic trend of anti-HER2 mAb were analyzed. RESULTS: The potencies of 74 batches of anti-HER2 antibodies from a certain enterprise during 2012 to 2014 were analyzed. The products and reference standard both showed a dose-response effect in biological activity, presenting parallel straight lines on semilog coordinate paper. The potencies determined by NIFDC and the manufacturer were (1.04±0.11)×104 and (0.94±0.08)×104U·mg-1, respectively. And the protein contents were (442.15±13.59) and (442.07±6.60) mg·vial-1. The main peak areas of IEC-HPLC were (76.29±1.36)% and (73.76±1.17)%, while the pHs were (6.16±0.11) and (6.22±0.08), respectively. The consistent and periodic trend analysis of the above-mentioned results showed that the total trend was relatively steady. CONCLUSION: This is the first time to conduct trend analysis of critical quality attributes (CQA) of anti-HER2 monoclonal antibody. These results reveal the quality changes of the products, which would help a lot in evaluating the batch consistency and production stability, and also provide reference for trend analysis of critical quality attributes for other monoclonal antibodies.