Impurities In New Drug Substances新原料药中的杂质
（绝对值），然后约为1.0mg；因此并未超出用每天总摄入量（1.0mg）表示的界定阈值。
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Impurities In New Drug Substances新原料药中的杂质
ATTACHMENT 3 Decision Tree for Identification and Qualification
Is impurity greater than identification thresholdc? Yes No No action Structure identified? Yes Any known human relevant risksd? Yes Reduce to safe level No No Reduce to not more than (?) identification thresholdc? Yes No further action No Yes Reduce to not more than (?) qualification Yes thresholdc? Greater than qualification thresholdc? No No action No Consider patient population and duration of use and consider conducting: ? Genotoxicity studies (point mutation, chromosomal aberration)a ? General toxicity studies (one species, usually 14 to 90 days)b ? Other specific toxicity endpoints, as appropriate Reduce to safe level Yes Any clinically relevant adverse effects? No Qualified Page 22 of 24
Impurities In New Drug Substances新原料药中的杂质
附件3 鉴定和界定判断图杂质是否高于鉴定阈值? 是 否 终止 结构是否鉴定？ 是 是否对人有相关的危险d? 是 降到安全水平 否 能否降至小于等于（≤）鉴定阈值c? 是 终止 是 否 是 终止 能否降至小于等于（≤）界定阈值c? 是 是否大于界c定阈值? 否 否 考虑病例数和使用时间并考虑进行以下研究： a? 遗传毒性研究(点突变，染色体畸变) ? 一般毒性研究 (单个种类, 最少14天，最b多90天) ? 其他特定的毒性终点（酌情而定） 降到安全水平 是 是否有临床相关的不良反应? 否 通过界定 Page 23 of 24
Impurities In New Drug Substances新原料药中的杂质
Notes on Attachment 3 附件3备注
a) If considered desirable, a minimum screen (e.g., genotoxic potential), should be
conducted. A study to detect point mutations and one to detect chromosomal aberrations, both in vitro, are considered an appropriate minimum screen.
如需要，应进行最低限度的筛选试验（如潜在遗传毒性），认为是合适的该类试验包括：体外点突变和染色体畸变试验。
b) If general toxicity studies are desirable, one or more studies should be designed to allow
comparison of unqualified to qualified material. The study duration should be based on
available relevant information and performed in the species most likely to maximise the potential to detect the toxicity of an impurity. On a case-by-case basis, single-dose studies can be appropriate, especially for single-dose drugs. In general, a minimum duration of 14 days and a maximum duration of 90 days would be considered appropriate.
如需进行一般毒理研究，应设计一个或多个研究方案，以将未界定的物质与界定的物质进行比较。研究时间应根据可用的相关信息而定，并使用最能反映某一杂质毒性的动物种属。根据具体情况，单剂量药物可进行单剂量试验，尤其是对单剂量给药的药物。一般最短14天，最长90天。 c)
Lower thresholds can be appropriate if the impurity is unusually toxic. 如果杂质具有特殊毒性，可以采用较低的阈值。
For example, do known safety data for this impurity or its structural class preclude human exposure at the concentration present?
例如，已经的该杂质的安全性数据或其结构的分类是否排除了人接触该浓度杂质的可能？
d)
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