【技术交流】20140730 ECA新闻：FDA警告信中的水系统问题

2014-08-07 蒲公英杂志

Water Systems in FDA Warning Letters

FDA警告信中的水系统问题

Taking a look at FDA Warning Letters from the past two years, objections with regard to pharmaceutical water systems are rather seldom. However, when there are complaints, it is the more interesting that the reason for these complaints is mostly the same: missing reliability. What the authority means in this case is the proof that the water system is capable of securely and reliably producing water in the required quality - taking into account for example the fluctuations in the feed water. The necessary means for this purpose are the validation of the water system and the establishment of a monitoring system which continuously verifies the function.  

看一下过去2年中FDA的警告信，关于药用水系统违规的情况确实很少见。但很有意思的是，一旦有问题，违规的原因大部分是相同的：水系统不够可靠。这种情况下，药监局的意思是现有证据不能证明水系统能安全可靠地生产出要求质量的水----例如，考虑到原水的质量波动性。这时，有必要对水系统进行验证，建立程序对水系统进行持续监控，以验证其功能满足要求。

Excerpts from Warning Letters:

以下是警告信的摘要：

1. Failure to validate and monitor the water purification system to ensure that water is of appropriate quality. […]  In your response to the observations noted during the 2012 inspection, you indicated your firm's intention to conduct a comprehensive gap analysis of the purified water system. However, you have failed to indicate when you will initiate this gap analysis and when it will be completed. Your firm also failed to detail how you will determine the source(s) of high endotoxin and TOC in your purified water and how your firm will remedy identified problem(s). We note that, for example, your firm installed an endotoxin removal unit on your purified water system in January 2011 in response to the OOS results for endotoxin in the water used for API. However, your firm has not demonstrated that the water produced by the purified water system is now suitable for use in production. The operational parameters and effectiveness of the new endotoxin removal unit have not been qualified. Your firm does not monitor the microbial and chemical attributes of the feed water, and have no assurances that the purified water system is capable of consistently producing water that meets specifications for a given quality of feed water.

1. 未能对水纯化系统进行验证和监控，以保证产出水具有适当的质量。【……】在你们对2012年现场检查所发现缺陷的回复中，你们说你们公司要对水系统进行综合的差距分析。但是，你们没有说清楚什么时间启动和完成该差距分析。你们公司也没有详细说明你们要如何找出纯化水中内毒性和TOC过高的原因，如何弥补该问题。我们注意到，你们公司于2011年1月，作为对原料药中所用纯化水内毒素超标的回复而在纯化水系统中安装了一个去除内毒素的装置，但是你们公司没有证明现有纯化水系统产生的水适合生产使用。新装的去除内毒素的装置的操作参数和有效性均没有经过确认。你们公司没有监控原水的微生物和化学指标，也不能保证纯化水系统可以使用给定质量的原水时，能够持续生产出符合质量标准的纯化水。

2. Your firm failed to assure that your water system is suitably designed and operated to produce appropriate water quality. Regarding the latter, your firm has not established and validated appropriate cleaning and sanitizing schedules for your purified water system. You have hired a water process subject matter expert and taken other steps to strengthen monitoring of the purified water system. Your response is not acceptable because you have not demonstrated that your purified water system is capable of operating in a continuing state of control.

2. 你们公司未能保证水系统的设计和操作可以生产出适当质量的水。关于操作问题，你们公司的纯化水系统没有建立适当的清洁和消毒周期，并进行验证。你们已经聘请了一位水处理问题的专家来采取其它措施加强对纯化水系统的监控。你们的回复我们不接受，因为你们没有证明你们的纯化水系统可以在持续受控的状态下运行。

3. [...] your firm failed to subject the water to routine microbiological testing. Furthermore, your firm failed to validate the water system to ensure consistent water quality for drug production and implement procedures for maintaining or monitoring the quality of the water produced.

3. 【……】你们公司未对水进行日常微生物检测。还有，你们公司没有对水系统进行验证，以保证药品生产用水质的稳定性，没有遵守程序对产水质量进行维护和监控。

http://www.gmp-compliance.org/enews_04359_Water-Systems-in-FDA-Warning-Letters.html

GMP News

30/07/2014----转自 Julia

谢谢分享，楼主辛苦！