Elemental impurities in marketed products. Recommendati** for implementation
已上市药品中元素杂质实施建议
Products should comply with the ICH/CHMP Guideline for Elemental Impurities under the following timeframe: 药品应按以下时间框架符合ICH/CHMP元素杂质指南:
Product产品 | Should complywith Guideline from: 自以下日期开始要求符合指南 |
New Marketing authorisation for newproduct (containing new active substance) | June 2016 |
新产品新上市申报(含有新活性物质) | 2016年6月 |
New Marketing uthorization forproduct containing an establishedactive substance | June 2016 |
含有已有活性物质的新上市产品 | 2016年6月 |
Marketed products including newmutual recognition applicati** ofalready approved products | December2017 |
已上市产品,包括已批准产品的新互认申报 | 2017年12月 |
1. Classification 分类
Following classes of elemental impurities are defined:
对元素杂质按以下定义进行分类:
· Class 1: elements with high toxicity by all routes of administration; possible from different sources
· 1类:所有摄入途径均具有高毒性的元素,可能有不同来源
· Class 2: elements with route dependent toxicity:
· 2类:毒性依据摄入途径不同有差异的元素,分为2A和2B两子类:
· A: possible from different sources; and
· A类:可能有不同来源,以及
· B: less likely unless intentionally added to the manufacturing process.
· B类:除有意加入生产工艺中以外出现可能性较小
· Class 3: elements with low toxic potential by the oral route
· 3类:口服低毒元素
2.1. In all cases a thorough risk assessment should be performed and documented. It should be available forinspection.
所有情况下,均应实施完整风险评估并记录。检查时应可以提供。
2.2. No variation is necessary if the outcome of the risk assessment is that, in order to comply:
如果风险评估的结果如下,则不需要进行评估:
2.2.1 No further controls on elemental impurities to materials such as the designated active substance starting material, synthesis intermediates, active substance, excipients or the finished product are needed.
对物料元素杂质不需要进一步控制,例如,指定的活性物质起始物料、合成中间体、活性物质、辅料或制剂成品。
2.2.2 No replacement or change of quality of materials such as the designated active substance starting material, synthesis intermediates, active substance, excipients or of the manufacturing equipment isneeded.
不需要替换或改变物料质量,例如,指定的活性物质起始物料、合成中间体、活性物质、辅料或生产设备材质。
2.2.3 No change of the manufacturing process is needed.
不需要改变生产工艺。
2.3. In other cases a variation is needed. It should be categorised according the Variation Guidelines(Official Journal 2013/C 223/01) and accompanied with the documentation required there. In addition,the variation should contain a short summary of the risk assessment and the conclusi** drawn.
其它需要变更的情形。应根据变更指南进行分类(官方杂志2013/C 223/01),提交变更所需的文件。另外,变更中应包括一份风险评估摘要,以及得出的结论。
3. Where a control of an elemental impurity is warranted, an elemental specific method is requested by the guideline.Therefore, a non-specific compendial test for heavy metals will not be accepted.
如果需要对某元素杂质进行控制,指南就要求制订元素杂质专用方法。这时,将不会接受非专属性的重金属药典方法。
来源:网络博客
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