制药水系统和臭氧消毒的考虑点

When ozone is used to sanitize storage and distribution systems, its effectiveness must be proven. On the one hand, this is done indirectly by determining the CFU values and, on the other hand, by proving that the ozone concentration is being measured correspondingly in the water system.当臭氧系统应用于水系统的储存与分配系统消毒，其消毒效果必须经过证实。一方面通过确定CFU的值间接进行，另一方面，通过测定在水系统中相应的臭氧浓度来证明。

For instance, the ISPE Baseline list at least three measuring points for this reason:例如，ISPE基准指南列出至少三个测量点：

•Before the UV system (discharge of the storage tank) 在紫外系统前（储罐的排放）

•After the UV system 紫外系统后

•In the return flow系统回流点

The ozone value before UV indicates that during permanent

ozonisation, the concentration in the storage tank is sufficient and that the ozone generator is working correctly. 紫外前的臭氧值表示在固定的臭氧化过程中，其在储罐中的浓度是足够的且臭氧发生器工作是正常的。

After the UV system, permanent measurements are performed

during operation to indicate that the ozone is removed. 在紫外系统后，在操作期间持续监测臭氧浓度是为了表明臭氧已经被去除。

In the return flow of the piping system, measurements are taken to prove that the ozone concentration is sufficient during sanitization of the pipes after the UV lamp.在管道回流系统，测量臭氧浓度是为了证明在对紫外灯后的管道消毒过程中其臭氧浓度是足够的。

Experts recommend comparing the values before UV and in the return flow in order to calculate the system's specific half-life period of the ozone. This typically amounts to 15 minutes for polluted systems and can amount to over 60 minutes for very clean systems. For technical reasons, it is necessary to know the half-life period, as the UV system

cannot completely break down the ozone and the current

ozone measurement technique has a lower detection limit of 5-10 ppb. For critical applications where the water has direct contact with the product, it is mandatory to know the system-specific half-life period of the ozone for a solid risk assessment. In future, this topic will certainly gain importance when cold WFI will be produced and stored in the course of the European Pharmacopoeia Revision. In case that an upgrade to WFI is planned after April 2017, current HPW systems should be reviewed accordingly even today.

专家建议，比较UV前和回流管道的臭氧浓度值以计算系统中臭氧的半衰期。典型的如对于污染的系统长达15min，对于非常干净的系统可能超过60min。出于技术上的原因，很有必要知道臭氧的半衰期，因为紫外系统不能完全分解臭氧，且在当前臭氧浓度测量技术具有5-10ppb的检测下限。水的关键应用是在生产过程中与产品直接接触，为了可靠的风险评估，水系统中臭氧的半衰期是必须强制性明确的。将来，这已主题一定会变得越来越重要，尤其是在随着欧洲药典修订即将生产和储存低温注射用水时。如果注射用水在2017年4月后升级，那么即便是现在HPW系统也需要审查。