ISPE 酸洗钝化.doc

11.3 PASSIVATION11.3 钝化作用11.3.1 Introduction11.3.1 简介Pharmaceutical equipment and high purity water systems are designed so that product contact surfaces are not reactive, additive, or absorptive so the drug product is not adversely altered. High purity water systems are primarily composed of austenitic stainless steel (SS) materials due to their corrosion resistant and contaminant free properties. Passivation is performed to maximize the metals corrosion resistance. The stainless steel is sulfuric/nitric/hydrofluoric acid pickled at the mill to remove manganese sulfide inclusions, scale, and other impurities or imperfections from the surface of the steel. As the steel is removed from the pickling bath, a thin oxide layer forms immediately over the surface. This oxide layer is what renders the stainless steel passive and non-reactive to corrosion. Any 300 series chromium steels containing 17% or more chromium that has been handled, welded, or worked should be passivated prior to service and suitably cleaned prior to passivation.为了使得药品没有不利变化，在设计制药设备和高纯水系统时，保证它们和产品的接触面是不具有反应性、添加性和吸收性的。考虑到铬镍不锈钢（SS）的抗腐蚀和防污染性，高纯水系统基本上都是由铬镍不锈钢材料构成。钝化作用要做到材料抗腐蚀性的最大程度。不锈钢是将钢浸在硫酸/硝酸/氢氟酸打磨，以去除钢表面的硫化锰类物质、污垢、杂质和缺陷。当从酸浸浴中取出钢时，其表面就会立即形成一层薄薄的氧化物。该氧化物层能使得不锈钢表面不活泼并不具反应性从而不易于腐蚀。300系列的铬钢中，任何系列都含有17或更多的经处理或焊接的铬，这些铬钢在使用前应钝化，并且在钝化前要做适当的清洁。Passivation is the method used to fortify the steel surface by strong oxidizing chemicals such as nitric acid. The acid depletes the steel surface of acid soluble species, leaving the highly reactive chromium on the surface in a compounded oxide form.钝化作用是通过强氧化性的化学试剂如硝酸，来强化钢表面的。酸可减少钢表面的酸可溶性物质，使得表面的高反应性的铬处于复合氧化物形式。11.3.2 Advantages of Passivation11.3.2 钝化作用的优点When SS systems are fabricated, the welding process destroys the existing passive film and compromises the metals ability to ward off the corrosive process. This is particularly applicable in those zones that are either heat affected or have had residues remain in contact with the metal surface for prolonged periods. Passivating then provides a method to restore the integrity of the metals corrosion resistant surfaces that were disturbed. Passivation must be proceeded by a cleaning process.铬镍不锈钢系统建立后，焊接处理会破坏存在的钝化膜，并降低材料抗腐蚀的性能。这尤其会出现在以下地带：受热侵袭的地方或者需延长和材料表面接触时间的残留物存在处。这样，钝化就会修复那些被破坏的抗腐蚀材料表面的完整性。11.3.3 The Chemical Process11.3.3 化学加工Excessive electron depletion of the upper film and an inadequate supply of oxygen (molecular O2) will ensure the formation of surface corrosion products. When this occurs, the chromium (Crn+) separates from the surface and opens the way for oxidation of the iron (Fe) and nickel (Ni), lower in the metal lattice.表面膜的过度电排除以及氧化剂（O2分子）的供应不足会形成表面腐蚀产物。当出现这种情况时候，铬（Crn+）就会和表面分离，将材料筛格下层的铁（Fe）和镍（Ni）暴露氧化。Establishing a passive surface or film on austenitic SS is essential to maximize the corrosion resistance that the metals offer. Passive surfaces on these metals occur naturally when exposed to an oxidizing environment. Sources of oxygen include air, aerated water, and other oxidizing atmospheres. Formation of a substantial uniform oxidized corrosion resistant surface or film is the result of passivation.在铬镍不锈钢表面形成一个钝化的表面或膜是非常重要的，它可以将材料的抗腐蚀性提高到最大。当暴露在氧化的环境下，这些材料会自发形成钝化表面。氧的来源包括：空气、充氧的水以及其他氧化的大气。钝化的结果是形成了经氧化的均匀的抗腐蚀表面或膜。Besides natural occurring passivation, chemical and electro-chemical processes can be used to obtain an anodic oxide film. Nitric acid solution (HNO3), is an oxidizing acid (depletes electron from the metal surface) which erodes the metal. This initial reaction or oxidation resists further chemical reaction on the metal surface. Metals that have such a state are called passive and the phenomenon itself is called passivity.除了自发形成的钝化外，化学和电化学加工都可用于形成氧化物膜。硝酸溶液（HNO3）是氧化性酸（去除材料表面的电子），它可以腐蚀材料。初始的反应或氧化可以抵制材料表面再进行化学反应。处于这种状态的材料被称为“经钝化的”，这种现象的本身被称为“钝化性”。The chromium oxide film thickness typically ranges from 0.5-5.0 nm, averaging 2.0-3.0 nm. The chrome to iron ratio measured in atomic percent within the chromium oxide should be at least one with ratios of two or more being optimal.铬氧化物膜的厚度范围通常是0.5-5.0 nm，平均在2.0-3.0 nm。铬氧化物中的铬和铁的原子百分数比例至少是1:2（或2以上）。11.3.4 Passivation Procedures11.3.4 钝化操作Numerous procedures are available for passivating; they share the commonality of consisting of four main steps which are:钝化操作有很多种，但它们有共同的主要步骤：1) Wash (Solvent Degreasing) 洗（去油溶剂）2) Water Rinse 水冲洗3) Acid Wash (Passivation Step) 酸洗（钝化步骤）4) Final Water Rinse 最终的水洗Proper preparation of the metal surface to obtain a uniform non-defective passive film mandates metal surface be completely clean and void of any organic or inorganic soils, free iron metallic contaminant, or corrosive products.为了形成均一的、无缺陷的钝化膜就要对材料表面进行预处理，这就要求材料表面应是完全的清洁，并且没有任何有机或无机污物、自由金属离子污染物，或腐蚀产物。The First Step (Degreasing) of the procedure is designed to remove dirt, dust, oil and grease. A water-soluble detergent is used to accomplish this, or a solvent.第一步（去油）：去除污垢、灰尘、油和脂。使用水溶性去污剂或溶剂来完成该步骤。The Second Step (Water Rinse) is required to remove dissolved and freed soils and the detergent itself from the metal being cleaned.第二步（水冲洗）：去除溶解的和游离的污物，以及清洁剂本身。The Third Step (Acid Wash) is to remove free iron, metallic residues, oxides, and other corrosion products from the surface of the metal. By removing these soils from the metal surface and providing an oxidizing atmosphere, the passive film is allowed to form and the passivation is accomplished. Inorganic acids are typically used in this step of the procedure.第三步（酸洗）：去除金属表面的自由离子、金属残渣、氧化物和其他腐蚀产物。将金属表面的这些污物去除并提供氧化的环境后，就形成了钝化膜并实现了钝化作用。该步骤通常使用无机酸。The Fourth Step (Final Water Rinse) - The acidic solution is flushed and the system is rinsed until the quality of the effluent is equal to that of the influent.第四步（最终水洗）将酸性溶液冲洗掉，并不断冲洗系统直到出来的水和进去的水的性质相同时。The American Society for Testing and Materials, ASTM A 380-96, Standard Recommended Practice for Cleaning and Descaling Stainless Steel Parts, Equipment and Systems, is an excellent source of information about passivation. It includes cleaning and passivation procedures, chemical applications, methodology, and testing procedures. The standard is valuable in establishing specific passivation and other specialized cleaning procedures.美国试验与材料协会，ASTM A 380-96，“不锈钢零件、设备和系统的清洗和除垢的标准规程”是关于钝化的极好的资料。它包括：清洁和钝化规程、化学试剂的应用、方法论以及检测规程。该标准对于建立特定的钝化和其他专门的清洁规程来说是很有价值的。Establishing an effective passivation procedure can be obtained by using the following guidelines：可通过下述指导来建立有效的钝化规程：Start with an accepted or specified procedure. (See the chart on the next page.)以公认的或特定的规程开始（见下页的图表）Obtain weld coupons from the system or have weld coupons made for testing purposes.从系统中取得焊接处样品或者为检验制作一个焊接处样品。Perform specified procedure along with alternate procedures to offer a choice, meeting specific situations, or requests.按照特定的规程执行，并备有可选择的规程可供选择，以满足特殊的情况和要求。Confirm the effectiveness of the procedures tested with specified field and/or laboratory testing.通过特定的区域和/或实验室的检验，确定该规程的效果。This process for confirming the effectiveness of a specified procedure or qualifying alternative procedures should be included in the passivation documentation being submitted as part of the final validation package.应将确定特定的规程或合格的可供选择的规程的效果的程序包括在钝化文件中，并作为最终验证整套文件的一部分提交。11.3.5 Passivation Chemical Alternatives11.3.5 钝化的化学试剂选择Nitric acid, a strong oxidizing acid, is the most common acid specified for passivation. Besides its ability to produce a free iron surface, the acid supplies the oxidizing atmosphere needed for passivation to occur. Because nitric acid is a corrosive chemical, extreme care must be used with handling, storage, and use. Federal Specification QQ-P-35C (1988) is an excellent reference for obtaining guidelines when using nitric acid on a variety of stainless steel alloys.硝酸是一种强氧化酸，它是钝化作用最常用的酸。它除了能产生游离铁表面，还能提供钝化作用所需的氧化环境。由于硝酸是腐蚀性的化学试剂，在装卸、存储和使用时必须小心谨慎。在对各种合金不锈钢应用硝酸时，联邦规格QQ-P-35C (1988)是极好的参考指导。Although nitric acid has traditionally been the preferred passivating acid, the trend in use of passivating solutions is to reduce chemical aggressiveness and to make safety, cost, and the environmental waste solution effluents a consideration.尽管传统上硝酸是首选的钝化酸，钝化溶液的应用趋势是减少化学侵占性，并考虑到安全、成本以及废液流的环境问题。Citric acid and ammonium citrate (ammoniated citric acid) are gaining popularity as alternatives to using nitric acid. The safety these chemicals offer the personnel and the work environment are desirable qualities. The ASTM Standard A 380 (1996) refers to these acids as cleaning acids, not passivating acids. This distinction has probably been made because the acids are not oxidizers as is nitric acid. The standard states that the citric acid-sodium nitrate treatment is the least hazardous for removal of free iron and other metallic contamination and light surface contamination. To achieve a true oxidation chelating agents in conjunction with citric acid and ammonium citrate has recently been introduced to the pharmaceutical/biotech industry.柠檬酸以及铵基柠檬酸盐（合氨的柠檬酸）正逐渐的被用作硝酸的替代物。这些化学试剂给人员合工作环境提供的安全性是比较理想的。ASTM标准A 380 (1996) 将这些酸归为清洁用酸而不是钝化用酸。做出这种区别的原因可能是这些酸不象硝酸一样是氧化剂。该标准声明：柠檬酸-硝酸钠处理在去除游离铁合其他金属污染和轻的表面污染物时，危险性最低。最近，已经向制药/生物技术产业引进了将正确的氧化螯合剂连接在柠檬酸和柠檬酸铵上。Phosphoric acid is a weak oxidizing acid sometimes specified in passivation procedures; however, there is no formal documentation referencing the use of phosphoric acid as a passivating acid.磷酸是一种弱氧化酸，有时也用于特定的钝化操作中；但，没有任何正式的文件说明磷酸可作为钝化用酸。Chelants, otherwise known as sequestering agents or coordination compounds, which include all the standard water softening compounds such as Sodium tri-polyphosphate (STPP), Nitrilotriacetic acid (NTA), and Ethylene Diamine Tetra Acetic acid (EDTA) may be compounded into acid passivation solutions to enhance metal ion extraction.螯合剂，又称为隔离剂或配位化合物，包括所有的标准的水软化化合物，如：可能将三聚磷酸钠（STPP）、氮基三乙酸（NTA）以及乙二胺四乙酸（EDTA）复合到酸钝化溶液中以加强金属离子的浸出。Orbital welding in conjunction with the increased use of electropolished tubing decreases the aggressiveness required of the passivating acids during the initial passivation. Decreasing acid contact time, temperature, and/or concentration accommodates the quality of the welds and already passive surface of the electropolished stainless steel.电解法抛光配管的环形轨道焊接降低了在初始钝化中使用的钝化酸的侵占性要求。根据焊接特性和电解法抛光不锈钢的已钝化的表面性质来减少酸接触时间、温度，和/或浓度。11.3.6 Chemical Application Methods11.3.6 化学试剂的应用方法Passivation can be accomplished using a variety of applications. Among these are:可通过一系列应用方法来实现钝化。包括：Circulation 循环Recirculating through distribution systems 在分配系统中再循环Long one way pipe runs systems 长的单向管道运行系统One Way Intermittent Flow 间歇式单向流Large non-recirculating distribution 大量的非循环分配Spraying 喷射Tank interiors 槽内部Tank Immersion 槽浸洗Numerous small parts 各种小零件Prefabricated tubing 预制的配管Swabbing/Wiping 擦洗/擦拭Isolated Areas/Tank/Equipment Exteriors 隔离区/槽/设备外表Equipment that does not allow spraying or other applications 不允许喷射或其他应用方法的设备When detergent washing, agitation or impingement provides the best results. During the acid wash step, chemical contact is usually sufficient. Recirculation is the preferred application method for performing passivation procedures. Recirculating allows flow rate criteria, usually specified at 5 feet per second (1.5 m/sec), to be achieved. Meeting flow rate requirements of a procedure should not be confused with particle removal. Many people assume when high flow rates are used that particle removal will be achieved. This is not true. Particle removal is achieved by including the total linear feet of the system into the appropriate mathematical equation. A recirculating water system of 1000 feet (300 meters) with a consistent tube diameter would require as much as 25 hours of filtered recirculation time for total particle removal.在去垢剂洗涤时，搅拌或冲击能得到最好的效果。在酸洗过程中，化学试剂的接触通常式充分的。在执行钝化作用操作中首选的应用方法是再循环。再循环能达到流速标准（通常是5英尺每秒，即1.5 m/sec）。不要将满足操作要求的流速和微粒去除混淆。许多人认为：当采用高流速时就可以达到微粒去除的效果。这是不正确的。微粒去除是通过将系统的总线性英尺数算入适当的数学方程式中来完成的。一个1000英尺（300米）的再循环水系统，并且其配管的直径一致，则需要25小时的经过滤的再循环来去除总微粒。11.3.7 Tests for Cleanliness and Passivity11.3.7 清洁和钝化检测There are several tests available to determine an acceptable level of cleanliness. Should confirmation of cleanliness be required prior to continuing with the passivation procedure, the water break free surface test, wipe test, or ultraviolet light testing are just a few of the tests that could be performed. These tests are gross cleanliness inspections as stated in the ASTM Standard A 380 (1996).有许多检测来确定合适的清洁水平。在接下来的钝化操作之前应要求确认清洁，切断水的自由表面检测、擦拭检测或者紫外光检测只是可执行的检测的几种。如ASTM 标准A 380 (1996)中所述这些检测只是清洁的粗检查。Once the passivation procedure is completed, a test method should be used to confirm or establish confidence that the passivation procedure has been successful. One inexpensive method is the Ferroxyl Test for free iron as set forth in the A380 (1996). The test is used to detect surface iron contamination, i.e., iron salt residue from pickling, iron tool scratches on the stainless steel surface, iron deposits at weld areas, and iron oxides. The testing solution is applied to the surface being tested. A blue stain appearing within 15 seconds of application indicates presence of free iron.一旦完成了钝化操作，应建立检测方法用于证实或建立可信度表明钝化操作是成功的。如A380 (1996)中所述，滤纸斑点试验是检测游离铁的一种廉价的方法。该检测用于检测表面的铁的污染，如浸酸中铁盐残留，不锈钢表面的铁制工具的刮痕，焊接区的铁沉积以及铁的氧化物。检测溶液用于待测的表面。如果有游离铁，指示剂就会在15秒之内出现蓝色染色。Testing for a passive surface is usually accomplished by looking for traces of free iron on the metal surface. The assumption is made that if there is no detectable free iron, the metal surface is clean enough for a uniform oxide film to develop. Another excellent source for specific testing methods is the Military Standard 753B (1985). Both Standards discuss specific tests for detecting free iron. They include Water Immersion/Water Wetting and Drying Test, High Humidity Test, Copper Sulfate Test, and Ferroxyl/Potassium Ferricyanide-Nitric Acid Test.钝化表面的检测通常是通过查看金属表面的游离铁的踪迹来完成的。假定如果没有探测到游离铁，则金属表面就是足够清洁以形成均一的氧化物膜的。特定检测方法的其他的极好的来源是：军用标准753B (1985)。上述两个标准都讨论了探测游离铁的特定检测方法。包括：水浸洗/水湿润和干燥检测，高湿度检测，硫酸铜检测以及滤纸斑点试验/铁氰化钾-硝酸检测。Direct testing for a passive surface can be accomplished by X-ray Photoelectron Spectroscopy (XPS) testing which is used to measure the oxidation states of elements found on the metal surface. Another direct, destructive testing method is Auger Electron Spectroscopy (AES) which measures the elemental chrome/iron ratio on the metal surface and sub-surface with depth profiling. The direct testing methods for passivity supply detailed information about the oxide film itself rather than indirect observations. XPS or AES testing offers direct evidence as to whether the passivation procedure being used is effective or not. These methods of testing are more costly than the other above mentioned tests and are ideal for use with weld coupons to determine the effectiveness of the passivation procedure for the system.钝化表面的直接检测可通过X射线光电子光谱法（XPS）检测来实现，该方法通常用于金属表面发现的元素的氧化状态。其他的直接的、破坏性的检测方法是欧杰电子光谱术（AES），它是用于测量金属表面和深度剖面下的元素铬和铁的比率。该钝化直接检测方法能提供关于氧化物膜的详细信息而不是间接的观测。这些方法比上述检测方法费用要大，但它们是检测焊接样管以确定系统的钝化操作的效果的理想方法。11.3.8 Modified Passivation Procedures11.3.8 修改的钝化规程A passivation procedure can be modified to deal with a variety of soils, surface finishes and weld area conditions. Adjusting contact times and solutions temperature and concentration would be the simplest way to modify a specific procedure. Sometimes detergent wash or acid wash chemicals are changed or modified with additives to remove certain soils. For example, when removing rouge, solutions containing sodium hydrosulfite can be substituted for the detergent wash step of the procedure. Citric and Phosphoric Acid also could be used as they do have some ability to remove light rouging. Another example would be the use of Hydrofluoric Acid, or more specifically, Ammonium Bifluoride to remove silica scale. The descaling step and associated rinse would necessitate additional steps being added to the standard procedure.可修改钝化规程以处理污垢、表面抛光以及焊接区域的各种情况。修改一份特定的规程的最简单的方法是调整接触时间以及溶液温度和浓度。有时可通过添加去除特定污垢的试剂来改变或修改去垢剂洗液或酸洗化学试剂。例如：在去除水锈时，可用含有次硫酸钠的溶液代替去垢剂冲洗步骤。也可以用柠檬酸和磷酸，因为它们具有去除轻微的水锈的功能。其他的例子是使用氢氟酸，或者更明确的说是用氟化氢氨来去除二氧化硅污垢。除垢步骤及其附带的清洗步骤使得必须向标准规程中添加额外的步骤。It is important when developing a passivation procedure, that laboratory testing is performed to determine the effectiveness of your procedure. Without preliminary laboratory testing, an educated guess would have to be made and the results may not prove satisfactory.在开发一个钝化规程时，执行实验室检测以确定规程的效果是重要的。如果没有初期的实验室检测，则应做出有根据的推测并且该结果可能不能证明。Below is a guide that can be used for passivating and derouging stainless steel components, piping, and equipment. The chart has some possible options for determination of the contamination and a course of action.以下内容可用于指导不锈钢组件、管线和设备的钝化和除锈。该图表有一些用于确定可能的污染的选项以及采取的措施。Cleaning and Passivation清洁和钝化Condition/Status情况/状态Contamination Analytical Method污染分析方法Cleaning& Passivation Method清洁和钝化方法System Chemistry系统化学作用Procedure操作New Component Electropolished电解抛光的新组件N/A2,432Component Newly Welded新焊接的组件N/A1,3,41,2,31,2New System Tubing新系统-配管N/A22,3,42Component/System Discolored (Gold Color)变色（金色）的组件/系统11,2,3,41,2,3,4,62Component/System Discolored (Brown, Red/Brown Color)变色（棕、红色/棕色）的组件/系统1,22,34,5,63Component/System Discolored (Black, Blue/Black Color)变色（黑、蓝色/黑色）的组件/系统2,32,34,5,6311.3.9 Contamination Analysis11.3.9 污染分析Method 1 Filtration of 1 liter sample through a 0.2-0.5 um filter and inspect.方法1：用0.2-0.5um的过滤器过滤1升样品并检查。Method 2 Quantitative analysis of the specified metals and organic compounds with wet chemistry techniques or as available.方法2：用湿化学技术或其他有效方法定量分析特定的金属和有机化合物。Method 3 SEM or Auger Electron microprobe/spectroscopy for analysis of surface chemistry and contamination.方法3：用SEM或欧杰电子影像能谱仪/光谱法来分析表面化学作用和污染。11.3.10 Clean