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| 试论异常毒性作为药品质量控制指标的合理性 |
| Dissertate the rationality of abnormal toxicity test as quality control |
| 投稿时间：2020-04-22 修订日期：2020-05-28 |
| DOI： |
| 中文关键词: 异常毒性 质量控制 安全性评价 药典要求 |
| 英文关键词: abnormal toxicity quality control safety pharmacopoeia requirements |
| 基金项目: |
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| 中文摘要: |
| [摘要] 异常毒性最初是一种确保复杂成分制剂生产工艺一致性及安全性的辅助检测手段，后来成为针对外源性毒性污染物的通用安全性检测项，曾在世界范围内被各国药典收载。由于该检测与药品质量、安全性之间的关联性受到质疑，各国药典逐渐在各论及通则中删除该检测项，目前仅中国药典保留异常毒性。由于该检测存在设定限值难以统一、给药体积及给药剂量不合理、结果易受干扰且缺乏明确的判定标准等试验原理及设计上的缺陷，导致其试验结果没有实际参考意义。基于对历史数据的回顾分析，国际监管机构及卫生组织对异常毒性有了更为科学的认知，并已逐渐形成统一的监管共识：严格的生产控制措施和有效的质量检测手段，比异常毒性检测更为重要；异常毒性检测结果或与产品质量及污染不具相关性；在异常毒性检查中使用大量动物不符合动物福利和“3R”原则。本文从科学角度试论异常毒性作为药品质量控制指标的合理性，并总结异常毒性修订的科学原则，希望能为我国监管机构、制药行业修订异常毒性相关内容提供思考角度。 |
| 英文摘要: |
| [Abstract] Abnormal toxicity testing was initially considered as an auxiliary detection measure to ensure the consistency of manufacturing processes and the safety standard for multiple-ingredients products. Later the test became a universally-accepted safety measure for exogenous toxic pollutants. And this abnormal toxicity testing has therefore been listed in the pharmacopoeia of various countries around the world. Due to the correlation between this testing result and the quality and/or safety of the medication has long been questioned，Pharmacopoeia of all countries have gradually eliminated this testing method from their general guidance, except that of the Chinese Pharmacopoeia where the abnormal toxicity test still listed. Since the test has numerous limitations: such as difficulty of unifying the setting limits; unreasonable administration volume and dosage; susceptible testing results and lack of clear evaluation standards and defects from experimental principles and design, the test results of abnormal toxicity deemed to have no significance reference. Based on the retrospective analysis of historical data, international regulatory agencies and the health organizations have an advanced scientific understanding of the abnormal toxicity, and have gradually formed a unified regulatory consensus: More important than the abnormal toxicity test is strict manufacturing control measures and effective quality testing methods; as well, there exhibit no correlation between the abnormal toxicity testing results and quality of the product and contamination levels; furthermore, utilize a large number of animals in the abnormal toxicity test does not comply with animal welfare and the "3R" principle . To promote the 2020 edition of Chinese Pharmacopoeia in the content of abnormal toxicity revisions, this abstract attempts to discuss the rationality whether the abnormal toxicity test can be used as a standard quality control test from scientific perspective. It will provide a consideration basis for Chinese regulatory agencies and the pharmaceutical industry to revise the content related to abnormal toxicity. |
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