翻译：Julia 来自：蒲公英

03.05.2017

Requirements for compressed Air in the Pharmaceutical Industry

制药行业的压缩空气要求

In many cases, gaseous media used such as compressed air contact the product. They are thus quality relevant, and in particular, of course, in the case of sterile products. However, in the pharmacopoeias they are specified relatively inaccurate compared to the pharmaceutical water qualities. Parameters and limits have to be defined by pharmaceutical users themselves.

很多情况下，所用的气态媒体如压缩空气会与产品相接触。因此他们的质量理所当然地会有所相关，尤其是用于无菌药品时。但是，在药典中，相比于制药用水的质量，这些气体就没有那么明确要求。这就要求制药用户自己来定义参数和限度。

There are always mistakes, because requirements are phrased inaccurately. A "classic" specification is "sterile compressed air" without considering the impact on the pipeline network and the necessary sterilization of the entire system. A second "classic" is the requirement "oil-free" for compressed air - without setting a reasonable limit value in mg/m?.

由于要求描述不准确，因此总会有些错误。一个典型错误就是其质量标准是“无菌压缩空气”但没有考虑对管道的影响以及对整个系统进行必要的灭菌。第二个“典型”错误是压缩空气“无油”，但没有设定一个合理的mg/m?限度值。

One specification, as for pharmaceutical water, is comprised in the European Pharmacopoeia.
However, these requirements are valid only if the gas has been legally classified as a medicinal product or as a medical device. The specifications relating to the medicinal product are valid e.g. when patients in the hospital are ventilated with air because then the gas is fed directly to the patient. To adopt the specification in the pharmacopoeia unseen in the specification for a compressed air system for the production of medicinal products can lead to unnecessarily expensive and inefficient designs. Details of the monograph in the European Pharmacopoeia for 'Medical Air' are discussed below.

在欧洲药典里有一份质量标准，就像制药用水一样。但是，这些要求仅在气体是法定药用气体或作为医疗器械时才有效。与医疗用品有关的质量标准是有效的，例如，当医院患者使用气体呼吸时，因为此时气体直接注入患者体内。在医药产品生产用压缩空气系统的质量标准中采用药典质量标准，可能会导致不必要的昂贵无效设计。欧洲药典“医用气体”各论讨论如下。

With regard to oil the European Pharmacopoeia comprises the specification:
"Oil: maximum 0.1mg/m?, determined using an oil detector tube (...), when an oil lubricated compressor is used for the production."

关于油份，欧洲药典包括有以下质量标准：

“油：最大0.1 mg/m?，如果生产中使用了用油润滑的压缩机，采用油检管进行测定（……）。”

These oil detector tubes are not optimal to use. The minimum detectable value is 0.1 mg/m? and the colour change of the sulfuric acid absorber is very difficult to detect. In the "small print", it is often required to know the type of the oil and to use a specific tube for the different oils. A reasonable preventive determination of a warning value of about 0.05 mg/m? of an unknown oil is thus impossible. Today many pharmaceutical companies with oil-critical processes use on-line measuring devices for the oil content in compressed air. The devices work similarly to the TOC measurement in the water: Hydrocarbons are oxidized to CO2 and measured as CO2. However, in the European Pharmacopoeia it is not clearly defined what oil is exactly: oil aerosols, oil vapor, or whether all hydrocarbons in the air are to be regarded as oil. The above phrasing in the European Pharmacopoeia also strengthens the erroneous belief that oil reaches the compressed air only via the compressor. Theoretically, a new oil-free compressor can be connected to an old oiled pipe network according to the above mentioned specifications - and still one does not have to measure. In practice, there are drug productions that exceed 0.1mg/m? because a leakage spray is used in the vicinity of the air intake of the compressor or the emergency diesel generator is being tested - or because of the traffic jam on a nearby highway.

这些油检管并不是一个优选方案。其最低检出值为0.1 mg/m?，硫酸吸收剂的色变是很难检出的。在“最小打印”中，通常要求知道油的类型，对不同的油类使用特定的管。因此对未知油约0.05 mg/m?的警示值合理预防性检测是不可能的。今天，许多油作为关键工艺的制药公司使用在线检测装置用于检测压缩空气中的油份。该装置的工作形式类似于水系统中TOC测量：碳水化合物氧化为CO2，作为CO2被检测。但是，在欧洲药典中，并没有明确定义是什么油：油气溶胶、油蒸气还是只要是空气中的碳水化合物都当作是油。欧洲药典的上述用词也增加了错误的想法认为油只是通过压缩机才到压缩空气里的。理论上来说，一台无油压缩机可以连接到一个旧的有油的管网，根据上述标准，但仍不需要进行测量。在实际操作中，有些药品生产会超过，起因是压缩机进气附近地区所用的泄漏喷雾，或者是应急柴油发动机在测试，或才是由于附近高速公路上堵车。

For the test conditions for the water content there are also particular characterstics (maximum 67ppm V/V for compressed gas cylinders or max. 870ppm V/V for compressed air generated by the compressor).

对于水含量的测试条件，也有一些特殊的性质（压缩空气瓶最大67ppm体积比，或压缩机产生的压缩空气最大870ppm体积比。

The USP (the US Pharmacopoeia) handle the testing of water or oil content quite easily: the so-called mirror test is required. In this case, one lets the gas flow against a clean surface and checks whether oil streaks or water droplets form there. This technologically rather simple requirement of the US colleagues should remind us Europeans to define the limits and the evaluation of excesses with a sense of proportion.

USP（美国药典）处理水或油含量测试则较为简易：要求进行所谓镜面检测。在此情况下，将气体一个出口对准一个洁净的表面，检查是否有油斑或水滴。美国同事这种技术角度非常简单的要求应该提醒我们欧洲定义限度，评估是否失去了分寸。

A further possible compressed air specification is the ISO 8573-1 from the year 2010. For pharmaceutical applications a specification according to class 2 is often useful. However, caution is required with respect to particles, since this standard stipulates that no particles larger than 5 ?m may be contained in classes 1-5. Typical stainless steel pipe systems in the pharmaceutical industry with central filters directly downstream of the production plant do not fulfil this requirement. These compressed air networks are operated at flow velocities up to 80 m/s. Pressure reducers and valves can also discharge particles. The limits for particles should therefore be determined based on the clean room classes themselves.

更深一步的可能的压缩空气质量标准是从2010年开始的ISO 8673-1。对于制药应用，根据二类的质量标准通常就很有用。但是，要注意颗粒度相关的要求，由于此标准制订的是1-5类中没有大于5um的颗粒。制药行业中典型的有中央过滤器的生产车间直接下游不锈钢管道系统，并不满足此要求。这些压缩空气管网是在流速高达80m/s的速度下运行的。减压器和阀门也可能释放颗粒物。因此颗粒物的限度要根据洁净间级别本身来决定。

For classes A and B, a 0.2 ?m point of use filter must ensure the sterility and the required reduction of the particle load for inflowing compressed air. Pneumatic valves seated in such a clean room must then typically also be supplied with this filtered air quality.

对于A级和B级区，在使用点使用0.2 ?m过滤器必须确保无菌，以及达到流入压缩空气颗粒负载降至要求。此类洁净间的气动阀用气一般也要具备这样经过过滤的空气质量。

Microbiological limit values are missing for the compressed air both in the pharmacopoeia and in the ISO 8573. Here it is also recommended to define the limits based on the clean room classes in which the compressed air is used, e.g. for class C the max. permissible 100KBE/m? from Annex 1.

压缩空气的微生物限度值在两个药典中均没有，在ISO8573里也没有。这里也建议根据压缩空气所用洁净区级别定义其限度，例如，根据附录1，C级洁净区内最大允许100KBE/m?。