ISPE+7制药用蒸汽.docx

1、ISPE+7制药用蒸汽PHARMACEUTICAL STEAM制药用蒸气7. PHARMACEUTICAL STEAM7. 制药用蒸气7.1 INTRODUCTION7.1 序论This chapter aims to simplify and standardize the process of selection, programming, and design of pharmaceutical steam systems. Guidelines, information, and options are provided, along with advantages and disad

2、vantages, based on the best and most cost effective of current and proven practices and technologies.本章旨在简化以及标准化制药用蒸气系统的选择、规划和设计。并以现行和已被证明的最好的和成本效应最高的实践和工艺为根据，给出一些指导方针、信息资料和选项，以及优缺点。The absence of regulations governing the use of steam in pharmaceutical processes has resulted in the proliferation of

3、 differing practices and interpretations. Most interpretations are made on the side of conservatism. Unfortunately, in addition to increasing cost without an associated increase in benefits, excessive conservatism can result in system complexity, and possibly reduced reliability. One example is the

4、use of clean steam (non-utility boiler produced steam) where a form of utility steam (utility boiler produced steam) would be adequate to maintain product quality. The installation of a clean steam generator when a simple steam reducing station would suffice results in added equipment and the associ

5、ated impact on cost, complexity, and reliability.在制药工艺中指导蒸气使用的法规缺乏导致衍生出不同实践和理解。大多数理解是保守的。不幸的是，这除了增加成本外没有相应的增加利益，过度的保守能够导致系统复杂并且可能减少其可靠性。举个例子，在一种公用蒸气（公用锅炉产生的蒸气）就足以维持产品质量的地方使用清洁蒸气（非公用锅炉产生的蒸气），在一个普通蒸气简化装置就能满足需要时安装一个清洁蒸气发生器，这导致设备增加并在成本，复杂性以及可靠性方面造成相关影响。In some instances, interpretations are based on ina

6、ccurate assumptions of what is important or critical. An example is the over specifying of pretreatment or using WFI as feed to solve the perceived problem.在某些情况中，理解是建立在不准确假设“什么是重要或关键的”基础上的。举个例子，比如过度规定预处理或使用注射用水作为给水来解决那些已察觉的问题。The chapter establishes standard definitions for terms commonly associate

7、d with pharmaceutical steam and provides information that facilitates making correct and cost effective decisions.本章为制药用蒸气相关的术语制定了标准定义，并为促使作出正确和成本有效的决定提供了信息。7.2 cGMP ISSUES7.2 cGMP出版物The user has the ultimate responsibility for system design and performance, and for ensuring that the proper type of

8、steam is used for a given process.用户对系统的设计和性能拥有最终职责并要确保适当类型的蒸气用于给定的工艺。There is no FDA or USP minimum standard for clean steam. However, cGMPs for large volume parenterals (LVPs) issued in 1976 indicated that feed water for boilers supplying steam that contact components, drug products, and drug prod

9、uct contact surfaces shall not contain volatile additives such as amines or hydrazines.对于清洁蒸气，FDA或USP没有最低标准。然而，1976年发行的cGMP关于大容量注射液部分表明供应蒸气的锅炉的给水、接触组件、药品和药品接触面不能包含挥发性添加剂比如胺或联胺。Few regulations govern the design and construction of clean steam generators. There are also no regulations governing materi

10、als of construction, type or level of instrumentation, surface finishes, or operating temperatures.很少法规管理清洁蒸气发生器的设计和构造，也没有法规管理构造材料、使用仪器的类型和等级、表面抛光或操作温度。Among US Government publications, the FDAs Code of Federal Regulations (CFR) provides culinary steam recommendations and stipulations related to hea

11、t exchanger and tank air vents design and construction. The Culinary steam recommendations apply to food applications only.在美国政府出版物中，FDA的联邦管理法规(CFR)提供厨房用蒸气的优点和关于热交换器及水罐排气口设计、构造的规定。建议厨房用蒸气只用于食品应用。US Public Health Service/Dairy Industry Committee, 3A Sanitary Standards, Number 609-02, adds additional

12、limitations to Culinary steam feed water additives for food applications. It should be noted that boiler feed water additives permitted in food for human consumption may not be acceptable in drinking water or orally ingested drug products.美国公共卫生部门/乳制品工业委员会，3A卫生标准，编号609-02，为食品应用而对厨房用蒸气给水添加剂增加附加限制。应该注

13、意人用食品中的锅炉给水添加剂不能用于饮用水或口服药品。7.2.1 Steam Attributes7.2.1 蒸气特质7.2.1.1 Quality7.2.1.1 质量The term Quality when referring to steam indicates the level of steam saturation. There are no FDA or USP regulations relating to minimum steam quality or the level of non-condensable gasses present in pharmaceutical

14、 steam. (See Section 7.4.)当涉及蒸气时，“质量”术语表示蒸气饱和标准。没有关于最低“蒸气质量”或在制药用蒸气中不可压缩气体标准的FDA或USP法规。（参看7.4部分）European regulators have defined specific criteria for pharmaceutical steam used for equipment sterilization. (European Standard EN 285 - Steam Sterilizers - reference section 13.3) These cover acceptable

15、 levels of saturation or dryness, the level of superheat, and the volume of non-condensable gases present.欧洲法规对用于设备灭菌的制药用蒸气规定了具体标准。(欧洲标准EN 285-蒸气灭菌器-参考13.3部分)。这些包含饱和或干燥标准、过热标准和不可压缩气体体积。7.2.7.2 Purity7.2.7.2 纯度Purity requirements for steam used in pharmaceutical manufacturing and product development

16、are driven by the product characteristics, manufacturing process, and the intended use of the product. The product manufacturer is responsible for ensuring that steam used to process the product is appropriate.用于制药生产和产品研制的蒸气纯度要求由产品特性、生产工艺和产品预期用途决定。药品生产商有责任确保将合适的蒸气用于药品生产。Though steam purity requireme

17、nts are product specific, it may be impractical to reliably produce special steam for each situation. Manufacturing operations typically generate and distribute only one or two steam purity grades, commonly grouped.虽然蒸气纯度要求是因产品特性而不同，但为每个情况可靠地生产特殊蒸气是不实用的。生产操作典型地产生和分配一般分组为一种或两种的蒸气纯度等级。7.3 TYPES OF STE

18、AM7.3 蒸气类型Pharmaceutical steam is classified into two (2) types based on their respective sources. These are:1) Utility-Boiler produced steam, hereafter called Utility Steam.2) Non-Utility Boiler produced steam, hereafter called Clean Steam.根据它们各自的来源，制药用蒸气分为两种类型。它们是：1)公用锅炉产生的蒸气，此后叫做公用蒸气。2)非公用锅炉产生的蒸气

19、，此后叫做清洁蒸气。7.3.1 Utility Steam7.3.1 公用蒸气Utility steam is characterized with usually having: Chemical additives to control scale and corrosion Relatively high pressure with the potential of generating superheat during expansion Relatively high pH公用蒸气通常具有以下特征： 用于控制水垢和腐蚀产物的化学添加剂 伴随在膨胀时产生过热潜在性的相对高压 相对的高p

20、H值Chemical additives: Utility steam is produced, in most cases, using conventional fire-tube steam boilers, normally of steel construction. Such boilers are almost always provided with systems that inject additives in the feed water to protect the boiler and steam distribution piping from scale and

21、corrosion. Some of these scale and corrosion inhibitors may, and often do, include amines and other substances that may not be acceptable in steam being used in pharmaceutical processes. The user must determine what additives are used, and verify if they are acceptable in the particular application,

22、 i.e., do not add any impurities or create a reaction in the drug product.化学添加剂：在多数实例中，使用常规钢结构火管蒸气锅炉产生公用蒸气。这种锅炉几乎总是规定在给水中注入添加剂来保护锅炉和蒸气分配管道以免产生水垢和腐蚀。一部分这些水垢和腐蚀抑制剂可能并且经常使用，包括胺和不适用于制药工艺所用蒸气的其他物质。用户必须决定使用哪种添加剂并且验证它们是否可适用于特定应用，比如，不能在药品中添加任何杂质或产生反应。Utility steam can be filtered to remove particulate matte

23、r, but filtration does not remove dissolved substances and volatiles such as amines.可以过滤公用蒸气除去颗粒物，但是滤器无法去除已溶解物质和挥发物比如胺。Superheat: Superheated steam is produced in water tube boilers by reheating the steam or by generating the steam at a higher pressure in a fire tube boiler and then reducing the pre

24、ssure through a regulating valve. When the pressure is reduced, the energy in the higher temperature steam is dissipated to generate steam at the lower pressure and produce superheated steam above the corresponding saturation temperature. Superheat is dissipated downstream of the regulating valve du

25、e to heat loss in the line.过热：在水管锅炉中通过再加热蒸气产生过热蒸气或者在火管锅炉中通过在更高的压力下产生蒸气然后使用调节阀减低压力来产生过热蒸气。当压力减低时，较高温度蒸气中的能量消散会产生较低压力下的蒸气并同时产生超过相应饱和温度的过热蒸气。由于管线的热损失，过热在调节阀的下游消散。pH control: In order to protect carbon steel from corrosion by the steam, it is necessary to use additives to raise the pH to between 9.5 -10

26、.5.pH控制：为保护碳钢制品不被蒸气腐蚀，有必要使用添加剂将pH值升高到9.5-10.5之间。7.3.2 Clean Steam (CS)7.3.2 清洁蒸气(CS)Pharmaceutical clean steam is generated from treated water free of volatile additives, such as amines or hydrazines, and is used for thermal disinfection or sterilization processes. It is considered especially import

27、ant to preclude such contamination from injectable drug products:制药用清洁蒸气是从不含有挥发性添加剂（例如胺或联胺）的净水中产生，并用于热灭菌或灭菌过程。从注射用药品中清除这类污染是尤其重要的：Clean steam is characterized as having: No additives No generated superheat except when the generated pressure is significantly higher than the use pressure of the steam.

28、 (See Section 7.3.1 - Superheat.) Relatively low pH清洁蒸气具有下列特征： 没有添加剂 不产生过热，除非产生的压力显著高于蒸气使用压力（参看7.3.1部分-过热） 相对低pH值There are many terms used in the pharmaceutical industry to describe Clean Steam. These include Clean Steam, Pure Steam, Pyrogen Free Steam, WFI Steam, and USP Purified Water steam. There

29、 is no standard or accepted definition for any of these terms. However, the most commonly used terms are Pure Steam and Clean Steam. In this Guide, the term Clean Steam is used in lieu of all others.The condensate of Clean Steam has no buffer, and may have a relatively low pH compared to that of uti

30、lity steam.在制药工业中有很多术语用于描述清洁蒸气。这些包括清洁蒸气、纯蒸气、无热原蒸气、注射用水蒸气和USP纯化水蒸气。对任何这些蒸气都没有标准或公认定义。然而，大多数通常使用的术语是“纯蒸气”和“清洁蒸气”。在本指南中，使用“清洁蒸气”术语替代其他所有术语。清洁蒸气的冷凝液没有缓冲系统，并且与公用蒸气相比它具有相对低pH值。7.4 BACKGROUND AND INDUSTRY PRACTICES7.4 背景和工业实践7.4.1 Purity of sterilizing steam7.4.1 灭菌蒸气纯度When steam or the resulting condensed

31、 water comes in direct or indirect contact with the drug product, the purity should be equivalent to the water purity acceptable for final rinsing of the drug contact surfaces.当蒸气或其产生的冷凝水与药品有直接或间接接触时，其纯度应该与最终冲洗药品接触面合格的水纯度相同。Note: A continuous supply of Dry Saturated Steam at the point of use is cons

32、idered necessary for efficient steam sterilization. Water carried by the steam in suspension may cause damp loads and superheated steam is considerably less effective than saturated steam when used for sterilization. Non-condensable gases if contained in the steam may prevent the attainment of sterilization conditions in parts of the sterilizer load.注意：为了有效蒸气灭菌，有必要考虑在用点连续供应干燥饱和蒸气。蒸气带来的悬浮的水可能引起潮湿，当用于灭菌时，过热蒸气比饱和蒸气的效果低的多。如果蒸气中含有不可压缩气体，则可能会防碍灭菌器中的一些部位达到灭菌条件。7.4.2 Steam used for humidifi