ISPE指南：关键公用系统GMP合规性翻译讨论

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2.1.1Minimum Water Purity Requirements for API and Finished Product Manufacturing

API和成品生产的水纯度最低要求

According to ICH Q7 [5], the minimum water quality to be used for API manufacture and in the pharmaceutical facility in general, is water that complies with WHO Guidelines for Drinking-Water Quality[ Although the attributes specified in WHO Guidelines for Drinking-Water Quality are considered goals and not necessarily mandatory for human consumption, compliance with all attributes is mandatory when used in API manufacture as well as for general pharmaceutical uses [5].

尽管《 WHO饮用水水质指南》中指定的属性被视为目标，并且不一定对人类食用是强制性的，但在API生产以及一般药物用途中使用时，必须遵守所有属性[5]。] [8].
根据ICH Q7 [5]，用于原料药生产和制药厂的最低水质是符合WHO饮用水水质指南的水[8]。

Depending on the nature of the API processing and its final microbial and chemical attributes, water of a purity level higher than potable quality may be needed. This is particularly important in the latter stages of synthesis or purification, where removal of impurities introduced with the water may not be accomplished by these final API processing steps [5].

根据API加工的性质及其最终的微生物和化学特性，可能需要纯度高于饮用水质量的水。这在合成或纯化的后期阶段尤其重要，在这些阶段中，通过这些最终的API处理步骤[5]，可能无法去除水中引入的杂质。

Most pharmacopeias require the minimum water quality used for API and excipient manufacture to be potable or drinking water. USP General Notices Section 8.230.20 states[ Official substances” is USP’s [12] term for monographed drug substances [APIs], excipients, dietary ingredients, other ingredients, or a component of a finished device and other finished product ingredients.

“官方物质”是USP的[12]术语，指专论的药物成分[API]，辅料，膳食成分，其他成分或制成品的组成部分以及其他制成品成分。] [12]:
大多数药典要求用于API和辅料生产的最低水质必须是饮用水。USP凡例第8.230.20节规定[12]：

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“When used in the manufacture of official substances, water shall meet the requirements for drinking water as set forth in the U.S. Environmental Protection Agency National Primary Drinking Water Regulations (NPDWR) or in the drinking water regulations of the European Union or of Japan, or in the World Health Organization’s Guidelines for Drinking Water Quality. Additional specifications may be required in monographs.”
“在用于生产正式物质时，水应满足美国环境保护局国家主要饮用水条例（NPDWR），或欧盟或日本的饮用水条例中规定的饮用水要求，或世界卫生组织的饮用水水质指南。专论中可能需要其它质量标准。”

This means that if a pharmaceutical manufacturer is in a jurisdiction other than the US, a member state of the EU, or Japan, the drinking water quality used in manufacturing must comply with the one of these jurisdictions’ drinking water regulations or WHO drinking water guidelines [8]. Compliance with a different jurisdiction’s drinking water regulations, if not one of those four, is irrelevant to USP as well as FDA.

这意味着，如果制药厂位于美国、欧盟成员国或日本以外的其它司法管辖区，则生产工艺中使用的饮用水质量必须符合这些司法管辖区的饮用水法规、或WHO饮用水指南中的一个 [8]。如果遵守其它管辖区的饮用水法规，而不是这四个管辖区之一，则与USP和FDA无关。

The Ph. Eur. [13] defines the minimum quality of water for use in API manufacture as:

欧洲药典[13]将用于API生产的最低水质定义为：

“complies with the regulations on water intended for human consumption laid down by the competent authority.”
“符合主管当局制定的有关供人类食用的水的规定。”

Ph. Eur. does not explain who a competent authority is; however, it is understood to be the national entity in charge of the subject. It is the manufacturer’s responsibility to identify the applicable drinking water regulations of the country in which the product will be marketed and ensure that the drinking water used in manufacturing meets those requirements.

欧洲药典没有解释谁是主管当局；但是，应理解为负责该主题的国家实体。生产商有责任确定产品销售所在国家/地区的适用饮用水法规，并确保生产中使用的饮用水符合这些要求。

峰行天下

感谢楼主分享！！

蒲公英

2.1.2Source Water for Purification Systems 纯化系统源水

Another important use of drinking water is as source water for an on-site purification system that produces compendial grades of water, such as PW or WFI. When starting with one of the pharmacopeial drinking waters, all unsafe levels of impurities have theoretically been removed. So unless there is a possibility that these impurities could be reintroduced into the water, there is no need to test for their absence in the further purified water. Instead, for finished water (i.e., PW or WFI), general non-specific tests for ionic and organic impurities, that is, Conductivity and Total Organic Carbon (TOC), can be used to broadly define the finished water quality; however, several jurisdictions mandate additional tests (see Appendix 4). It is noteworthy that the microbial content of the water undergoing purification is also monitored, and, depending on the treatments selected, it may be that the levels of culturable bacteria in the non-compendial pretreatment water increase due to certain unit operations, and that this is acceptable.
饮用水的另一个重要用途是用作工厂纯化系统的源水，该系统可生产药典级的水，例如PW或WFI。从一种药典饮用水开始时，从理论上讲，所有不安全含量的杂质都已被清除。因此，除非有可能将这些杂质重新引入水中，否则在进一步纯化的水中，无需检验是否存在这些杂质。相反，对于成品水（即PW或WFI），可以使用离子和有机杂质的一般非特异性检验，即电导率和总有机碳（TOC），来广泛定义成品水的质量；但是，一些辖区要求进行附加检验（请参阅附录4）。值得注意的是，纯化过程中水的微生物含量也受到监控，并且取决于所选择的处理方法，可能是由于某些单元操作导致非药典预处理水中可培养细菌的含量增加，这是可以接受的。

2.1.3Source Water Compliance Standards 源水合规标准

Similarly to the water requirements described for APIs in USP General Notices, the USP [12] monographs for PW, WFI, and Pure Steam specify using one of the same four regional drinking water specification sets as the source water.

与USP凡例中描述的API水需求类似，PW、WFI和纯蒸汽的USP [12]专论指定使用相同的四个区域饮用水质量标准集之一，作为源水的要求。

In Europe [13] and Japan [18], a globally accepted source water quality for purification into PW is WHO Drinking Water [8]. However some pharmacopeia require that PW is used to supply the final purification step that generates WFI. (See Appendix 4 for the requirements of the major pharmacopeias.)

在欧洲[13]和日本[18]中，用于纯化为PW的全球公认的源水质量是WHO饮用水[8]。但是，有些药典要求使用PW来提供产生WFI的最终纯化步骤。（有关主要药典的要求，请参见附录4. ）

豫胜

谢谢楼主分享

蒲公英

豫胜 发表于 2020-12-12 10:55
谢谢楼主分享

希望参与一些有观点的讨论，谢谢分享这些客气话，如果多了会占用别人阅读的屏幕资源

豫胜

蒲公英 发表于 2020-12-12 10:43
2.1.2Source Water for Purification Systems 纯化系统源水

Another important use of drinking wat ...

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2.1.4Public Water Compliance 公共用水合规

When a public drinking water source is used, the responsibility for complying with the drinking water regulations of the region usually falls to the drinking water provider. However, it remains the user’s responsibility to ensure that compliance of all drinking water attributes has been achieved for water used at the pharmaceutical facility; this responsibility includes year-round verification as there may be seasonal variability in water supply quality.
当使用公共饮用水水源时，遵守该地区饮用水法规的责任通常由饮用水提供者承担。但是，用户有责任确保制药厂使用的水达到所有饮用水属性的要求；该职责包括全年验证，因为供水质量可能存在季节性变化。

2.1.4.1Public Water Provider Certification and Verification 公共供水机构的证书和确认

ICH Q7 [5] requires identity testing on manufacturing materials in most cases:

ICH Q7 [5]在大多数情况下要求对生产物料进行鉴别：

“At least one test to verify the identity of each batch of material should be conducted….A supplier’s Certificate of Analysis can be used in place of performing other tests, provided that the manufacturer has a system in place to evaluate suppliers.”

“应至少进行一项检验以验证每批物料的鉴别……。只有生产商拥有评估供应商的系统，才可以使用供应商的分析证书代替进行其它检验。”

According to the GMPs, a certificate of compliance for any raw material should never be accepted without verification of authenticity and accuracy. That verification may involve an audit of the facility to view operations and the raw data associated with the certification, with organizations checking some attributes with their own testing. These rules apply to any public drinking water provider including local, regional, or other drinking water authority. If the local water provider refuses to allow a site visit/audit, then the level of risk is potentially increased and the level of monitoring by the organization should increase to compensate.

根据GMP，未经确认真实性和准确性，不能接受任何原材料的合格证书。该确认可能涉及对机构的审计，以查看运营情况和与证书相关联的原始数据，并由组织使用自己的检验来检查某些属性。这些规则适用于任何公共饮用水提供者，包括地方、区域或其他饮用水主管部门。如果当地水供应商拒放允许进行现场访问/审计，则风险级别可能会增加，应增加监控级别，以进行补偿。

Also, drinking water compliance applies primarily to the water at the source, prior to entering the delivery piping network. Water may travel great distances during an extended period through piping of unknown integrity resulting in reduced quality at the destination.

同样，饮用水的符合性主要适用于进入输送管道网络之前的源水。在很长一段时间内，水可能会通过完整性未知的管道流过很长一段距离，从而导致终点处的质量下降。

It is the user’s responsibility to verify that any provided certification of compliance with drinking water regulations is accurate. Therefore, it may be appropriate for the pharmaceutical facility to periodically verify the drinking water’s compliance. This includes sampling the drinking water at the manufacturer’s site in one or more locations to verify that quality criteria are being met. The number of locations and frequency of sampling should be determined based on a risk assessment.

用户有责任确认所提供的任何符合饮用水法规的证明是准确的。因此，对于制药厂来说，定期回顾饮用水的合规性可能是合适的。这包括在生产商工厂一个或多个位置对饮用水进行取样，以确认是否满足质量标准。应根据风险评估确定取样点的数量和频率。

Not all quality attributes in a set of drinking water regulations are required to be tested annually nor with every sample, particularly where a history of compliance has been demonstrated by the manufacturing firm through analysis of the incoming supply water. The selection of parameters for testing should be based on a combination of risk assessment and the drinking water regulations applied to the manufacturing site. It may be appropriate during a drinking water compliance audit of a water authority’s facility and its testing data to observe consecutive years of historical testing data in order to confirm that all attributes have been tested at least at the required frequency.

并非每年都需要对饮用水法规中的所有质量属性进行检验，也不要求对每个样品都进行检验，特别是在生产公司通过对进水进行分析证明其符合历史的情况下，尤其如此。检验参数的选择应基于风险评估，并结合适用于生产工厂的饮用水法规。在对水务部门的设施及其检验数据进行饮用水合规性审计时，可能需要连续观察历史检验数据，以确认是否已至少按要求的频率，对所有属性进行了检验。

蒲公英

2.1.4.2Absence of Reliable Certification or Use of a Private Water Source 没有可靠的证书或使用私人源水

There are scenarios where a pharmaceutical facility may have its own private water source for use in manufacturing and further purification. There may also be instances where the documentation supporting a drinking water provider’s certification of compliance is absent, incomplete, untrustworthy, or not one of the acceptable standards. In these scenarios, the pharmaceutical facility is responsible for demonstrating compliance to an acceptable set of drinking water regulations.
在某些情况下，制药厂可能拥有自己的私人水源，用于生产和进一步纯化。在某些情况下，缺少支持饮用水提供者合规性证明的文档，或者该文档不完整、不可信或不是可接受的标准。在这些情况下，制药厂需要负责证明该源水符合一组可接受的饮用水法规。

The potential for variability, or when variability has been demonstrated, in drinking water quality in these situations is a factor in how often testing should be performed. Minimally, during the first year of source testing, the robustness of the supplied water and any treatment needed to bring the source water into compliance should be performed multiple times (e.g., quarterly or monthly, depending on the risk assessment of the water supply) until such time as the quality variability is discerned. Thereafter, an appropriate sampling frequency depends on a further risk analysis.

在这些情况下，饮用水质量中可能存在变化的可能性，或者已经证明存在变化的可能性，这是多久应执行一次检验的考虑因素之一。至少在源水检验的第一年，对于供水的稳定性和使源水达到合规性所需的任何处理，应多次进行检验（例如，每季度或每月一次，取决于供水的风险评估），直至已经识别了质量的波动性时。此后，适当的取样频率取决于进一步的风险分析。

For example, in a situation with a high-risk water supply, the first year may include weekly water sampling. If all data is acceptable, in the second year sampling frequency may be reduced to monthly, and if results are good, may be reduced to quarterly in the third year. However, in a jurisdiction where a manufacturer has existing operations fed from the same water supply with consistently good quality, reduced sampling frequency may occur much more rapidly.

例如，在供水风险高的情况下，第一年可能包括每周一次的水取样。如果所有数据都可以接受，则第二年的取样频率可以减少到每月一次，如果结果良好，则可以将其减少到第三年的季度一次。但是，在某个辖区中，生产商有单一供水源，且该水源拥有始稳定的良好质量，降低取样频率的速度可能会更快。

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2.1.4.3Source Water Pretreatment and Sampling Location 源水预处理和取样点

It may be necessary to treat the water in order to comply with the drinking water standards. The nature of that treatment depends on the nature of the noncompliance in the source water. Ideally, compliance with the selected drinking water regulations should be shown with the water entering the purification system. However, it is generally acceptably compliant to obtain samples taken from as far into the water system as the furthest Point of Use (POU); however, sampling may be required at other locations that are deemed high risk due to infrequent usage, or due to the nature of the use of the water dispensed. It is noteworthy that in large facilities there may be branches (not recirculating) of potable water that see infrequent use and could be prone to microbial contamination if not regularly flushed. If there are secondary storage tanks for potable water with their own distribution networks, this risk then increases, and sampling from the POU of these systems should be done.
为了符合饮用水标准，可能需要对水进行处理。该处理的性质取决于源水不合规的性质。理想情况下，水进入纯化系统时，应表明符合所选饮用水法规。从最远的使用点（POU）取水系统的样品，通常是可接受的。但是，由于不经常使用或所分配的水的使用性质，对于其它被认为具有高风险的点，可能需要取样。值得注意的是，在大型设施中，可能会有不经常使用的饮用水分支（不循环），如果不定期冲洗，则很容易受到微生物的污染。如果在分配网络中，存在饮用水辅助的储水箱，则这种风险会增加，因此应从这些系统的POU中取样。

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2.2Compendial Water Pretreatment 药典水预处理

The term pretreatment typically indicates unit operations chosen to prepare drinking water for conversion to a higher quality by a primary treatment method. Pretreatment most often is used to either reduce the contaminant load on primary treatment equipment or to extend the interval between equipment servicing.
术语“预处理”通常表示选择的单元操作，以准备通过初级处理方法，将饮用水的质量提高。预处理通常用于减少初级处理设备上的污染物负荷、或延长设备维修间隔。

Hence, pretreated water is not required to meet drinking water nor PW chemical or microbial standards; it is simply an interim quality that allows for primary treatment equipment to operate under less demanding conditions and at reduced operational costs. Pretreatment is significantly less costly to operate than primary treatment equipment and extends the time between service events for the primary treatment components. Pretreatment systems must receive a similar level of care as compendial systems proper in terms of their maintenance (leaks or other dysfunctions) as they are an integral part of the overall treatment. From a compliance perspective, a poorly maintained pretreatment system is a poorly maintained compendial water treatment system.

因此，不需要预处理水来满足饮用水或PW化学或微生物标准；它只是一种过渡质量，它允许初级处理设备在要求较低的条件下、以较低的运营成本运行。与主要处理设备相比，预处理的运行成本大大降低，并且延长了主要处理组件需要维修事件的间隔时间。预处理系统在维护（泄漏或其它功能障碍）方面，必须获得与药典系统相似的维护级别，因为它们是整体处理的组成部分。从合规性的角度来看，不良维护的预处理系统就是不良维护的药典水处理系统。

Pretreatment systems that are not properly maintained may force primary treatment components to bear the additional load resulting in greater downtime, unscheduled outages, and increased cost. Each type of unit operation selected for use as pretreatment requires Preventive Maintenance (PM) and possibly routine service specific to its function.
预处理系统不当维护，可能会迫使主要处理组件承受额外的负载，从而导致更长的停机时间、计划外的停机和增加的成本。对于选择用作预处理的每种类型的单元操作，都需要预防性维护（PM）以及可能针对其功能的日常维修。

For example, softeners typically need maintenance at a minimum annually for proper operation; however, depending on the water quality and age of the system may require more frequent maintenance. Nonetheless, in addition to regular maintenance, softeners need constant monitoring of salt used for regeneration, often needing additional salt every few days. Failure to maintain salt levels could result in hardness fouling a downstream Reverse Osmosis (RO) system and an unplanned outage.

例如，软化系统通常需要每年最少维护一次，以保证正常运行。但是，根据系统的水质和使用年限，可能需要更频繁地维护。除了定期维护外，软化系统还需要不断监控再生盐的使用量，通常每隔几天需要添加额外的盐。无法维持盐分含量，可能会导致下游反渗透（RO）系统的硬度积垢和计划外的停机。

The pretreatment system water may not meet the requirements of drinking water, but in order for the system to be GMP compliant, it should be operated in a state of control; that is, parameters are maintained within specified ranges. The nature of the parameters to be monitored depends on the technologies deployed in the pretreatment (e.g., hardness testing to verify softener performance).

预处理系统的水可能不满足饮用水的要求，但是为了使系统符合GMP要求，应在可控状态下运行；即参数保持在指定范围内。要监测的参数的性质取决于预处理中使用的技术（例如，硬度检验以确认软化系统性能）。

Proper maintenance and operation of pretreatment equipment help to ensure optimal overall system operation, and help to reduce events that could jeopardize the compliance of the system.

预处理设备的正确维护和操作，有助于确保最佳的整体系统运行，并有助于减少可能危害系统合规性的事件。

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2.3Purified Water 纯化水
2.3.1General通则

PW is normally used in cleaning operations as well as in the manufacture of APIs, oral solutions, topicals, oral solid dosage products, and medical devices. In most of these cases, PW is a raw material that requires testing to demonstrate quality and compliance.
PW通常用于清洁操作以及API、口服溶液、局部用药、口服固体制剂和医疗器械的生产中。在大多数情况下，PW是一种原材料，需要进行检验才能证明其质量和合规性。

2.3.2Applicable Requirements 适用要求

PW, as defined by compendial monographs, requires compliance with specifications for chemical and microbial quality. Chemical quality requirements are defined by conductivity and TOC specifications. Microbial quality requirements for PW are usually defined in published standards. Several pharmacopeias specify a variety of other parameters, which are summarized in Appendix 4.

根据药典各论的定义，PW要求符合化学和微生物质量质量标准。化学质量要求由电导率和TOC质量标准定义。PW的微生物质量要求通常在已发布的标准中定义。几种药典指定了其它各种参数，这些参数在附录4中进行了概述。

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2.4Water for Injection 注射用水
2.4.1General 通则

WFI is typically used in cleaning operations, and in the manufacture of inhaled products and injectable products. It is a raw material, and therefore requires adequate testing to demonstrate quality and compliance.
WFI通常用于清洁操作以及吸入产品和可注射产品的生产中。它是原材料，因此需要进行充分的检验以证明质量和合规性。

2.4.2Applicable Requirements 适用要求

WFI, as defined by compendial monographs, requires compliance with specifications for chemical and microbial quality. Chemical quality requirements are defined by conductivity and TOC specifications. Microbial requirements for WFI are usually defined in published standards. Endotoxin limits are also applicable to WFI. Appendix 4 summarizes the requirements for most of the major pharmacopeias.

根据药典各论的定义，WFI要求符合化学和微生物质量质量标准。化学质量要求由电导率和TOC质量标准定义。WFI的微生物要求通常在已发布的标准中定义。内毒素限度也适用于WFI。附录4总结了大多数主要药典的要求。

WFI is the product of drinking water that has been pretreated and primary treated to meet the final required chemical and microbial specifications. There is inconsistency worldwide about the allowed treatment techniques and the water that may be used as the feed water to a WFI generation process. Europe [13], North America [12], and Japan [18] allow for the use of non-distillation based techniques for the generation of WFI, and for the use of potable water as the starting material. The Chinese Pharmacopoeia [19] specifies that distillation must be used with PW as the starting material, but is currently considering allowing generation techniques other than distillation.

WFI是从饮用水开始制备的，饮用水需要经过预处理和初级处理，以符合最终所需的化学和微生物质量标准。世界范围内，对于关于允许的处理技术和WFI生成过程供的源水要求是不一致的。欧洲[13]、北美[12]和日本[18]允许使用基于非蒸馏的技术来产生WFI，并允许使用饮用水作为起始原料。《中国药典》[19]规定必须以PW为原料并使用蒸馏技术，但目前正在考虑允许使用除蒸馏技术以外的其它生产技术。

gaoyuanlai

谢谢分享，好好学习！

蒲公英

1.1 Pure Steam 纯蒸汽
2.5.1 General 通则

Steam is classified as Pure Steam when it is intended to be used for direct and indirect product contact, for sterilization of product or material, or for sanitization of surfaces.

如果打算将蒸汽用于直接和间接的产品接触、产品或材料的灭菌或表面消毒，则将其分类为纯蒸汽。

2.5.2 Applicable Requirements

适用要求

Pure Steam should meet the requirements of the applicable pharmacopeia (i.e., USP [12], Ph. Eur. [13]).

纯蒸汽应符合适用的药典的要求（如USP [12]，欧洲药典[13]）。

Many pharmacopeias do not include a Pure Steam monograph; therefore, often the relevant WFI monograph specifications are applied. These are, for instance, the requirements for the feed water, a built-in component to retain droplets, and the required test parameters for WFI that may be tested on the Pure Steam condensate. Due to the lethality of Pure Steam, culturing of microbial samples is not required, although endotoxin testing is required.

许多药典不包含纯蒸汽专论；因此，通常会使用相关的WFI各论质量标准。例如，这些是对源水的要求、用于截留液滴的内置组件、以及可以在纯蒸汽冷凝液检验上使用WFI检验参数。由于纯蒸汽的致死性，尽管需要进行内毒素检验，但无需培养微生物样品。

Pharmacopeias may not define certain parameters such as steam saturation, dryness, and non-condensable gases; however, guidance is provided by the EN285 [20] and the British HTM 01-01 Part C [21] standards. It is recommended to conduct a risk analysis that includes specifics related to these qualities. EN285 may support a decision as to whether or not these parameters are applicable, and to define limits and test procedures.

药典可能没有定义某些参数，例如蒸汽饱和度、干燥度和不凝性气体。但是，在EN285 [20]和英国HTM 01-01 C部分 [21]标准提供了相关指南。建议进行包括与这些品质有关的细节的风险分析。EN285可以支持有关这些参数是否适用的决定，并定义限度和检验程序。

The testing for steam quality is most often done at the POU to an autoclave unit and requires specialized test elbows and equipment. If future quality testing is likely, considerations during the design phase should be made to provide the necessary spool pieces.

蒸汽质量的检验通常是在高压灭菌器的POU上进行的，需要专门的检验弯头和设备。如果将来可能进行质量检验，则应在设计阶段考虑提供必要的线轴件。

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2.6Clean Compressed Air 洁净压缩空气
2.6.1General 通则

Compressed air intended for use in product-impact applications include:
用于影响产品的压缩空气包括：

•Steam sterilizer overpressure 蒸汽灭菌器超压

&#8226ressure equilibration after steam sanitization of piping and equipment 管道和设备经过蒸汽消毒后的压力平衡

•Transfer of product 产品转移

•Blow down of equipment after clean in place/steam in place for drying 就地清洗/灭菌后吹干设备

•Air supply to fermenters 向发酵罐供气

In addition, compressed air is used whenever there is air contact with a product-contact surface not cleaned in a subsequent operation, and in all classified manufacturing space into which the process compressed air is exhausted.

另外，压缩空气应用在以下场合：空气与在随后的操作中未清洁的产品接触表面接触，和需要将工艺压缩空气排出的洁净生产空间中。

Compressed air may be obtained in cylinders based on volume needs, although it is typically produced on site using compressors. This puts it into a category different than most other gases and justifies its description separate from other gases.

尽管可以根据需求，按体积使用气罐中获得压缩空气，但通常使用压缩机在工厂内产生压缩空气。这将其归类为与大多数其它气体不同的类别，并有理由将其描述与其它气体分开。

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2.6.2Applications 应用

Some pharmacopeias include monographs for medical air. Standards such as “breathing air” (for example, the NFPA 99 Standard [22]) are available. ISO 8573 [23] is sometimes employed by manufacturers as a standard.
一些药典包括医用空气各论。可以使用诸如“呼吸空气”之类的标准（例如，NFPA 99标准[22]）。生产商有时会使用ISO 8573 [23]作为标准。

In most cases medical grade gases are not required in pharmaceutical manufacturing since medical gases and breathing gases are typically intended for direct use by people or animals. The gene and cell therapy medicines industry along with biotechnology manufacturing utilize medical gases and process air for product contact.

在大多数情况下，在制药生产中不需要医用级气体，因为医用气体和呼吸气体通常旨在供人或动物直接使用。涉及到产品接触，基因和细胞疗法药物行业以及生物技术生产，会使用医用气体和工艺空气。

When used in a pharmaceutical process with direct product contact, the purity requirements should be based on product and process needs. These product requirements are usually defined in the manufacturer’s regulatory filings.

在直接接触产品的制药工艺中使用时，纯度要求应基于产品和工艺的需求。这些产品要求通常在生产商的法规注册文件中定义。

When applicable, preparation of a risk analysis is prudent.

如果适用，应谨慎进行风险分析。

It is generally accepted that a critical quality parameter for clean compressed air is the dew point/relative humidity with the expectation that the level of humidity in the air will be non-condensable in the temperature ranges to which the compressed air piping is exposed. Maintaining dryness essentially eliminates the possibility for microbial growth since without water, bacteria are not able to reproduce.

人们普遍认为，洁净压缩空气的关键质量参数是露点/相对湿度，并期望空气中的湿度水平在压缩空气管道所处的温度范围内不可凝结。保持干燥基本上消除了微生物生长的可能性，因为没有水，细菌将无法繁殖。

In addition, requirements applied to environmental air can be used to support decisions documented in the risk analysis. This is especially true in cases where the air is used and exhausted within a classified space. As such, a reason for the decision on the maximum allowed amount of particles or microbes in the compressed air may be based on Table 2.1.

此外，针对环境空气的要求可用于支持风险分析中记录的决策。在洁净空间内使用和排出空气的情况下尤其如此。这样，决定压缩空气中颗粒或微生物的最大允许量的原因可以基于表2.1.

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Table 2.1: Clean Room and Clean Air Device Classification
表2.1：洁净室和洁净空气设备分类
(Adapted from EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1 “Manufacture of Sterile Medicinal Products” [24])
（根据《欧盟人和兽用药品GMP指南》附录1“无菌药品的生产” [24]）

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A risk analysis should consider the need for POU filters or decentralized filters for each production room, whether the use of an oiler or other equipment necessitates the need for backflow prevention, and if air should be exhausted from the room.
风险分析应考虑每个生产室是否需要POU过滤器或分散式过滤器，是否使用加油器或其它设备是否需要防止回流，以及是否应将空气从生产车间排出。

To adequately address compliance it may be necessary, confirmed by risk analysis, to monitor and record important parameters from properly defined sampling points using proper equipment, such as instruments to measure particles, humidity, oil, and temperature, as well as a system and procedure to test for microbes. Often the limits in ISO 8573 [23] are applied for humidity and oil content testing.

为了充分解决合规性问题，可能需要通过风险分析来确认，并使用适当的设备（如用于测量颗粒、湿度、油和温度的仪器）以及检验微生物的系统和程序，来监控并记录来自正确定义的取样点的重要参数。ISO 8573 [23]中的限度通常适用于湿度和油含量检验。

It is ultimately the responsibility of the user to determine the needs for their product and situations. This should consider and document the requirements of the product and appropriate and applicable regulatory requirements respective limits and tests as necessary.

用户负有最终责任，来确定其产品和情况的需求。这应该考虑并记录产品的要求、以及适当和适用的法规要求，必要时设置限度并检验。

During the risk analysis, it may be appropriate to evaluate the origin of the compressed air, how it is produced, why compressed air is being used, critical characteristics/quality of the compressed air and why they have been defined (as applicable), which parameters will be tested and why, where filters are installed in the system, which parameters to control, precision of instruments, redundancy of measurements, recording of data, etc.

在风险分析过程中，可能需要评估压缩空气的来源、产生方式、为什么使用压缩空气、压缩空气的关键特性/质量以及为何对其进行了界定（如适用）、检验参数及原因、系统中的过滤器安装位置、控制参数、仪器精度、测量冗余度和数据记录等。