目的: 对抗程序性死亡受体1（PD-1）单抗关键质控项目检测结果进行趋势分析,以评价抗PD-1单抗的批间一致性和稳定性。方法: 分别将中国食品药品检定研究院（NIFDC）和某企业对93批抗PD-1单抗关键质控项目检测结果进行统计和趋势分析,包括SEC单体含量、HIC前峰（1+2）含量、生物学活性、蛋白含量和pH,建立警戒限和行动限,并对异常结果进行调查分析。结果: 2家实验室的SEC单体含量测定结果均在99.7%~99.9%;蛋白含量、生物学活性和pH均在行动限范围内;企业和NIFDC检测的HIC前峰（1+2）含量平均值分别是（5.42±0.33）%和（5.44±0.34）%;对2家实验室的生物学活性和蛋白含量测定结果作统计学分析,结果无统计学差异;基于以上趋势分析和统计学分析,发现某企业HIC前峰（1+2）含量检测结果呈现逐年升高的趋势,NIFDC及时告知该企业启动原因调查与风险评估。结论: 本研究采用的趋势分析和统计学分析相结合的质量监测策略有效识别了抗PD-1单抗生产及检测过程中潜在的质量波动风险,为确保抗PD-1单抗批间一致性及临床用药安全性提供了关键质量保障。
Objective：To evaluate the batch consistency and stability of the anti-programmed death receptor 1 (anti-PD-1) monoclonal antibody by conducting a trend analysis of the test results of key quality control items. Methods：Statistical and trend analyses were performed on the detection results of 93 batches of anti-PD-1 monoclonal antibodies for key quality control items from the National Institutes for Food and Drug Control(NIFDC) and the manufacturer. The analyzed items included SEC monomer content, HIC front peak(1+2) content, biological activity, protein content, and pH value. Alert and action limits were established, and abnormal results were investigated. Results：The results of the SEC monomer content by the two laboratories were both between 99.7% and 99.9%. The protein content, biological activity and pH value were all within the action limit range. The average values of the HIC front peak(1+2) content of the enterprise and NIFDC were (5.42±0.33)% and (5.44 ± 0.34)% respectively. The biological activity and protein content by the two laboratories were statistically analyzed, and the results showed no statistical difference. Based on the aforementioned trend and statistical analyses, this study identified a year-on-year increasing trend in the HIC front peak(1+2) content detection results from the manufacturer. NIFDC promptly informed the manufacturer to initiate cause investigation and risk assessment. Conclusion：The quality monitoring strategy combined with trend analysis and statistical analysis used in this study effectively identified potential quality fluctuations during the production and testing of anti-PD-1 monoclonal antibody. This study provided critical quality assurance to ensure batch consistency and clinical safety of anti-PD-1 monoclonal antibody.
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