中美欧日药典注射用水（散装 bulk form）控制要求

中美欧日药典注射用水（散装 bulk form）控制要求

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2024-04-30 16:08 作者: 沐清风

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注射用水（散装 bulk form ）的各国药典质量控制要求

各国药典注射用水制备要求

ChP 2020

USP

Ph. Eur. 11.4

JP 18

纯化水经蒸馏所得的水

Water for Injection is water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms. It is prepared from water complying with the U.S. Environmental Protection Agency National Primary Drinking Water Regulations or with the drinking water regulations of the European Union or of Japan or with the World Health Organization’s Guidelines for Drinking Water Quality.

蒸馏或其它等效或更优的纯化工艺，用于制备注射用水的水应满足US环境保护协会国家饮用水法规或欧盟或日本相关饮用水法规或WHO相关饮用水指南要求。

Water for injections in bulk is obtained from water that complies with the regulations on water intended for human consumption laid down by the competent authority or from purified water. It is produced either:

– by distillation in an apparatus of which the parts in contact with the water are of neutral glass, quartz or a suitable metal and which is fitted with an effective device to prevent the entrainment of droplets; or

– by a purification process that is equivalent to distillation.

蒸馏或其它等效或纯化工艺，用于制备注射用水的水应满足相关监管机构规定的生活饮用水要求或使用纯化水。

Water for Injection is prepared by distillation or by reverse osmosis and/or ultrafiltration, either: from the water which is obtained by appropriate pretreatments such as ion-exchange or reverse osmosis on Water: or from Purified Water

蒸馏或反渗透、超滤，用于制备注射用水的水为经过适当的预处理的水，例如离子交换或反渗透等或使用纯化水。

各国药典注射用水（散装 bulk form）质量控制要求
项目	ChP 2020	USP	Ph. Eur. 11.4	JP 18
性状	无色的澄明液体，无臭。	/	无色澄清液体	无色的澄明液体，无臭。
pH	5.0～7.0	/	/	/
重金属	≤0.00001%	/	/	/
氨	≤0.00002%	/	/	/
不挥发物	≤1.0mg/100ml	/	/	/
硝酸盐	≤0.000006%	/	/	/
亚硝酸盐	≤0.000002%	/	/	/
电导率	符合规定（三步法）	符合规定（三步法）	符合规定（三步法）	≤2.1us/cm（25℃）
总有机碳TOC	≤0.50mg/L	≤0.50mg/L	≤0.5mg/L	≤0.50mg/L
微生物限度	≤10cfu/100ml	≤10cfu/100ml	≤10cfu/100ml（行动线）	≤10cfu/ 100ml（行动线）
铝盐	/	/	≤10ppb（透析溶液）	/
细菌内毒素	<0.25EU/ml	<0.25EU/ml	<0.25IU/ml	<0.25EU/ml
控制菌	/	USP 1231 WATER FOR PHARMACEUTICAL PURPOSES 注射用水用于生产非无菌液体或半固体制剂时，需要考虑测试某些条件致病菌，例如铜绿假单胞菌、洋葱伯克霍尔德菌以及其它的一些假单胞菌。 For example, Pseudomonas aeruginosa and Burkholderia cepacia, as well as some other pseudomonads, are known opportunistic pathogens under certain conditions. As such, it may be appropriate to consider these species as objectionable microorganisms for the type of water used to manufacture nonsterile liquid and semi-solid products.	/	/

总结分析：

1、注射用水的制备要求：

中国药典要求必须使用蒸馏的方式，而且原水为纯化水；美国药典、欧洲药典、日本药典中要求注射用水的制备方式为蒸馏或其它等效或者更优方式，原水为符合相关法规要求的饮用水或纯化水。

2、注射用水的检测要求：

2.1 pH、重金属、氨、不挥发物、硝酸盐、亚硝酸盐：这些项目为中国药典单独要求项目，其它药典无要求。

**更新：在最新的0261修订说明中，删除pH、重金属和不挥发物项目；电导率测试满足第一步测试要求时可不进行氨、硝酸盐、亚硝酸盐项目测试。

2.2 电导率项目：中国药典、欧洲药典、美国药典均按照三步测定法，日本药典为直接采用第二步测定法与其它药典不一致，同时在JP 18 Quality Control of Water for Pharmaceutical Use <GZ-2-172>中规定了电导率的监控可以采用USP 645的策略，需要注意的是日本药典只允许两步测定法，两步不合格后，没有第三步pH的测定。

2.3 TOC：各国药典均要求测试该项目，标准上欧洲药典为≤0.5mg/L，其它药典为≤0.50mg/L，基本一致。

2.4 微生物限度：中国药典和USP（微生物的要求索引USP1231）的标准要求为≤10cfu/100ml，需要注意的是USP建议的最少取样量为200ml；而欧洲药典和日本药典对于微生物限度建议的行动线为≤10cfu/100ml，未规定具体标准；同时关于该项目的取水时限，USP和JP有单独的要求如下：

JP 18 Quality Control of Water for Pharmaceutical Use <GZ-2-172>

It is adequate to use the water specimens for the test within 2 hours after sampling. In the case that it is not possible to test within 2 hours, the specimens should be kept at 2 – 89C and be used for the test within 12 hours.

取样后2h内测试，如果2h内无法完成测试，取水后样品在2-8℃最大暂存时间为12小时。

USP 1231 WATER FOR PHARMACEUTICAL PURPOSES

Because the number of organisms in the water can change over time after sample collection, it is best to test the samples as soon as possible. If it is not possible to test the sample within 2 h of collection, the sample should be held at refrigerated temperatures (2℃–8℃) and tested within 24 h. In situations where even 24 h is not possible (such as when using off-site contract laboratories), it is particularly important to qualify the microbiological sample hold times and storage conditions to avoid significant changes in the microbial population during sample storage.

应需尽快测试，取样后2h内测试，2-8℃暂存时应24小时完成测试。在某些情形下，24小时无法完成测试（例如委托实验室检测），应评估放置时间对于微生物的影响，避免微生物数量在储存期间显著变化。

2.5 铝盐：欧洲药典规定了当注射用水用于透析溶液制备时需要控制该项目，其它药典对于该项目无药典。

2.6 细菌内毒素：各国药典均要求测试该项目，标准一致，均为<0.25EU/ml。

2.7 控制菌：对于该项目USP 1231 WATER FOR PHARMACEUTICAL PURPOSES 中有相关的要求, 注射用水用于生产非无菌液体或半固体制剂时，需要考虑测试某些条件致病菌，例如铜绿假单胞菌、洋葱伯克霍尔德菌以及其它的一些假单胞菌,其中洋葱伯克霍尔德菌的测试USP有单独的章节USP〈60〉MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS—TESTS FOR BURKHOLDERIA CEPACIA COMPLEX。

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