2011年COS证书申请的10大缺陷

残伤

1. Absence of discussion on the carry-over of impurities/by-products from key materials in the process (i.e. related substances, solvents, catalysts, starting material, intermediates) 没有讨论工艺过程中来源于关键物料的残留杂质/副产品（例如：有关物质，溶剂，催化剂，起始原料，中间体）。

2. Proposed starting material cannot be accepted as such. Starting material is often too similar to the finished product (with regard to the structure and complexity) In such cases, the assessor requires a redefinition of the starting material. 提出的起始物料不能被接受。起始物料与最后产品太相似（结构和复杂性），在这种情况下，审核员要求重新定义的起始物料。

3. Absence of discussion on genotoxic impurities including metallic impurities and class 1 solvents. Limits for these impurities must be set either for the intermediate or the final product. 没有讨论遗传毒性杂质，包括金属杂质和1级溶剂。中间体或最终产品必须限制这些杂质。

4. Absence of comparison of the quality of the final substance obtained with starting materials from different suppliers. Where more than one supplier of starting material(s) is used, it should be demonstrated that the quality of the API manufactured remains equivalent. 缺乏使用不同供应商起始物料进行生产获得产品的质量对比。如果使用多个供应商的起始原料，要证明生产出来的API质量相同。

5.Incomplete specifications for the declared starting materials. Limits for impurities, solvents and catalysts are often not sufficient or inexistent. 提出的起始物料质量标准不完善。没有起始物料的杂质、溶剂和催化剂的限度要求或不充足。

6.Absence of discussion for Class 1 solvents as contaminant of another solvent. Many common solvents like for example acetone, toluene, ethanol, methanol, isopropanol, xylene, hexane and petroleum either may contain benzene as impurity. Benzene is classified as carcinogenic and belongs to the class 1 solvents. 缺少使用溶剂污染1类溶剂的讨论。许多常见溶剂，例如丙酮，甲苯，乙醇，甲醇，异丙醇，二甲苯，正己烷和石油醚可能含有苯杂质，苯属于致癌物，属1级溶剂。

7.Incomplete specifications for reagents/solvents. Particular attention should be paid to the specifications of solvents used during the final purification steps - particularly those of water. 试剂和溶剂的质量规格不完善。应特别注意在最后精制步骤使用的溶剂的质量标准-特别是水。

8.Specifications for key intermediates are not detailed enough. A discussion on the potential impurities likely to arise from the synthesis process is expected. When the proposed starting materials are not accepted by the assessors they should be re-defined as intermediates and indicated with complete specifications. 关键中间体的质量标准不够详细。应讨论合成过程中可能出现的潜在杂质的升高。当起始物料不可接受时，审查员就会要求重新定义中间体，并制定完整的质量标准。

9. Absence of cross validation between PhEur and in-house method for the control of related substances. Basically, alternative methods must have been validated and be equivalent to pharmacopoeial methods. 缺少用EP方法与内部控制方法对相关物质进行的交叉验证。也就是说替代方法必须验证，并等价于EP药典方法。

10. Absence of suitability of the monograph to control the impurity profile of the final substance. The suitability must be demonstrated, even if a suitable in-house method is used. 缺乏使用方法对杂质概况控制的适用性证明。必须证明使用方法的适用性，即使是使用内部方法也如此。

残伤

从别处学习到的 拿来分享一下

liuqygood2005

多谢分享。

镇海铁狮

谢谢楼主分享

巴西木

好资料，谢谢分享

youranzide

谢谢楼主分享！资料很好。

潇湘子

学习一下，谢谢分享！这可是很企业交了不少学费换来了经验教训呀，真可谓“前车之覆轨，后车之明鉴”

残伤

谢谢各位回复

hldmfw

多谢分享。

QQ-0598

谢谢分享！

dhnvu

办毕业证Q2648038977