USP1660翻译

化学试剂常见分类详述试剂（reagent）又称化学试剂或试药。

主要是实现化学反应、分析化验、研究试验、教学实验、化学配方使用的纯净化学品。

一般按用途分为通用试剂、高纯试剂、分析试剂、仪器分析试剂、临床诊断试剂、生化试剂、无机离子显色剂试剂等。

试剂常用规格优级纯或一级品（GR，精密分析和科学研究工作）；分析纯或二级品（AR，重要分析和一般研究工作）；化学纯或三级品（CP，工矿及学校一般化学实验）；实验试剂（LP）。

试剂的品级与规格应根据具体要求和使用情况加以选择。

定级的根据是试剂的纯度（即含量）、杂质含量、提纯的难易，以及各项物理性质。

有时也根据用国标试剂该类试剂为我国国家标准所规定，适用于检验、鉴定、检测。

试剂级（RG，红标签）：作为试剂的标准化学品。

基准试剂（JZ，绿标签）：作为基准物质，标定标准溶液。

优级纯（GR，绿标签）：主成分含量很高、纯度很高，适用于精确分析和研究工作，有的可作为基准物质。

分析纯（AR，红标签）：主成分含量很高、纯度较高，干扰杂质很低，适用于工业分析及化学实验。

化学纯（CP，蓝标签）：主成分含量高、纯度较高，存在干扰杂质，适用于化学实验和合成制备。

实验纯（LR，黄标签）：主成分含量高，纯度较差，杂质含量不做选择，只适用于一般化学实验和合成制备。

教学试剂：可以满足学生教学目的，不至于造成化学反应现象偏差的一类试剂。

指定级（ZD），该类试剂是按照用户要求的质量控制指标，为特定用户订做的化学试剂。

高纯试剂（EP）：包括超纯、特纯、高纯、光谱纯，配制标准溶液。

此类试剂质量注重的是在特定方法分析过程中可能引起分析结果偏差，并对成分分析或含量分析产生干扰的杂质含量，但对主含量不做很高要求。

色谱纯（GC）：气相色谱分析专用。

质量指标注重干扰气相色谱峰的杂质。

主成分含量高。

色谱纯（LC）：液相色谱分析标准物质。

质量指标注重干扰液相色谱峰的杂质。

主成分含量高。

指示剂（ID）：配制指示溶液用。

<1660>玻璃容器内表面耐受性评估目的本章阐述了药用玻璃容器内表面耐受性的影响因素，对预测可能形成的玻屑和脱片提供了推荐的方法，列出可适用于鉴定和控制试验的有用步骤。

范围本章论述模制输液瓶和注射剂瓶，以及安剖瓶、卡式瓶、西林瓶、管制注射剂瓶以及预灌封注射器用玻璃针管等，正如在<660>中定义的玻璃容器。

药用玻璃分为I型硼硅玻璃，II型钠钙玻璃， III型耐水性钠钙玻璃，。

I型玻璃容器适合大部分注射用和非注射用产品。

II型玻璃容器适合于大部分酸性和中性的用于肠胃外和非注射的水溶液产品，并且当碱性肠胃外药品的稳定性数据证明其适用性时同样可以使用。

III型玻璃容器通常不被用于非肠道产品或胃肠外使用的粉末，除非有合适的稳定性试验数据表明III型玻璃是符合要求的。

本章主要侧重于I型玻璃的介绍，因为它在生物制药行业中使用最广泛。

本章适用于以下单位：合作生产和灌装企业；模制和管制玻璃容器制造商及经销商；制药和生物制药公司。

玻璃材质的安剖瓶、试管、卡式瓶、西林瓶和预灌封注射器是注射产品的首选材料，尤其是生物制药产品已经增加了对以上这些小容量玻璃瓶的需求。

玻璃脱片最终会导致外观片晶的出现，是一个可能导致产品召回的严重质量问题。

玻璃脱片是容器结构不稳定的滞后指标。

虽然脱片是可观察到的最明显的不稳定性表现，但它代表了极弱的玻璃表面结构的最终阶段，且仅能在必须预防时被观察到。

此外，震动或瓶与瓶的碰撞产生的机械能可能会使脆弱的内表面产生玻璃碎屑。

应对玻璃容器内表面以及注射液进行检测分析，以预测玻璃内表面脱片的倾向，测定指标包括玻璃表面麻点、裂痕，试验液中的一些变化，包括：SiO2浓度增加量、SiO2/B2O3或Si/Al比值、可见和不可见微粒数，以及pH值下降程度等。

玻璃类型纯化玻璃由熔点约1700℃的二氧化硅组成。

向玻璃中加入氧化钠、氧化钾或氧化硼等添加剂可以降低玻璃的熔化温度；加入氧化钙和氧化铝可以改善玻璃的耐久性。

中文英文缩写或简称优级纯试剂Guaranteed reagent GR 分析纯试剂Analytial reagent AR化学纯试剂Chemical pure CP实验试剂Laboratory reagent LR纯Pure Purum Pur 高纯物质(特纯Extra pure EP特纯Purissimum Puriss超纯Ultra pure UP精制Purifed Purif分光纯Ultra violet Pure UV光谱纯Spectrum pure SP闪烁纯Scintillation Pure研究级Research grade生化试剂Biochemical BC生物试剂Biological reagent BR生物染色剂Biological stain BS生物学用For biological purpose FBP组织培养用For tissue medium purpose微生物用For microbiological FMB显微镜用For microscopic purpose FMP电子显微镜用For electron microscopy涂镜用For lens blooming FLB工业用Technical grade Tech实习用Pratical use Pract分析用Pro analysis PA精密分析用Super special grade SSG合成用For synthesis FS闪烁用For scintillation Scint电泳用For electrophoresis use测折光率用For refractive index RI显色剂Developer指示剂Indicator Ind配位指示剂Complexon indicator Complex ind荧光指示剂Fluorescene indicator Fluor ind 氧化还原指示剂Redox indicator Redox ind 吸附指示剂Adsorption indicator Adsorb ind 基准试剂Primary reagent PT光谱标准物质Spectrographic standard substance SSS原子吸收光谱Atomic adsorption spectorm AAS红外吸收光谱Infrared adsorption spectrum IR核磁共振光谱Nuclear magnetic resonance spectru NMRm有机分析试剂Organic analytical reagent OAS微量分析试剂Micro analytical standard MAS微量分析标准Micro analytical standard MAS点滴试剂Spot-test reagent STR气相色谱Gas chromatography GC液相色谱Liquid chromatography LC高效液相色谱High performance liquid chromatogrHPLCaphy气液色谱Gas liquid chromatography GLC气固色谱Gas solid chromatography GSC薄层色谱Thin layer chromatography TLC凝胶渗透色谱Gel permeation chromatography GPC层析用For chromatography purpose FCP常见质量级别优级纯(GR,绿标签:主成分含量很高、纯度很高,适用于精确分析和研究工作,有的可作为基准物质。

<1058> ANALYTICAL INSTRUMENT QUALIFICATION 分析仪器的确认INTRODUCTION 介绍A large variety of laboratory equipment, instruments, and computerized analytical systems, ranging from simple nitrogen evaporators to complex multiple-function technologies (see Instrument Categories ), are used in the pharmaceutical industry to acquire data to help ensure that products are suitable for their intended use. An analyst 's objective is to consistently obtain reliable and valid data suitable for the intended purpose. Depending on the applications, users validate their procedures, calibrate their instruments, and perform additional instrument checks, such as system suitability tests and analysis of in-process quality control check samples to help ensure that the acquired data are reliable. With the increasing sophistication and automation of analytical instruments, an increasing demand has been placed on users to qualify their instruments.极其多种多样的实验室设备、仪器、计算机分析系统，从简单的氮吹仪到复杂的多功能技术（见仪器种类），被应用于制药工业，以取得数据来确保产品适合其预定用途。

231 HEAVY METALS重金属This test is provided to demonstrate that the content of metallic impurities that are colored by sulfide ion, under the specified test conditions, does not exceed the Heavy metals limit specified in the individual monograph in percentage (by weight） of lead in the test substance， as determined by concomitant visual comparison （see Visual Comparison in the section Procedure under Spectrophotometry and Light—Scattering（851) with a control prepared from a Standard Lead Solution。

［NOTE-Substances that typically will respond to this test are lead， mercury, bismuth, arsenic，antimony， tin， cadmium, silver, copper， and molybdenum. ]本检验是用来测定与硫化物离子作用显色的金属杂质含量，在规定检验条件下，其检测结果不得超过专论中规定的重金属限度供试品中铅的百分比（重量比）,该检验是通过与标准铅溶液配制的对照进行视觉比较来得出结论的(参看分光光度法和光散射法<851>中规程部分的视觉比较）.［注意：与本检验起反应的代表性物质为铅、汞、铋、砷、锑、锡、镉、银、铜和钼。

凡例综合通告和要求部分(凡例)，是为解读与使用USP和NF，提供的基本假设，定义，默认（预先规定）的条件。

除非另有说明，本凡例中的要求适用于USP和NF（“药典”）收载的所有文章和通用章节（以下简称：“附录”）。

如果各论的要求与凡例或附录不同，无论各论是否明确说明了这些不同，均遵循各论而非凡例和附录的要求。

名称和修订本出版物（共4册，包括增补在内）的全称，是美利坚合众国（the United States of America）药典第37版和国家处方集第32版。

可以简写成USP37，或NF32，或USP 37-NF 32。

美国药典第37版和国家处方集第32版，将取代所有比他早的版本。

在它正式生效期间，如果没有更多的限制说明，“USP”和“NF”，仅指USP37和NF32及其增补。

这也适用于这些内容的打印版或电子扫描版。

尽管USP和NF属同一出版物，且共享凡例的内容，但二者分别单独成卷。

如果没有特别说明，本版药典将于2014年5月1日正式生效。

USP和NF的增补定期发布。

过渡修订公告在USP网站发布，是对USP和NF的修订。

过渡修订公告包括正式修订版和生效日期，新USP对照品有效性（批号）的通知和由于USP对照品的有效性待批准而导致涉及的检测项目或方法暂停的通知也可在USP网站的“新官方主题”上获得。

修订公报是要求加快公布的药典文章的修订或延缓生效。

在USP网站上发布；通常，如果没有另外说明，修订公报立即生效。

勘误表是对因排版错误而产生的未经专家委员会批准、且不影响药典规定的错误条款的更正，勘误表出版即生效。

2.药典地位和法律承认2.10. 药典文章药典文章是指USP和NF收载的包括专论，附录和本凡例等文章。

药典文章的修订版在（药典）增补、过渡修订公告和修订公报中发布。

附录中编号1000-1999的章节，是对特定主题进行解释或提供定义或描述的信息，其中不含对药典文章的强制要求，除非本凡例、专论，或附录中编号低于1000的有关章节明确引用。

B RIEFING1660 Evaluation of the Inner Surface Durability of Glass Containers. In response to the recent product recalls that have further increased the pharmaceutical industry’sheightened awareness of glass quality and glass delamination (i.e., the formation of glass flakes in a vial), USP proposes a new general information chapter to recommendapproaches to predict potential formation of glass particles and delamination.(PSD: D. Hunt.) Correspondence Number—C115672Add the following:▪1660 EVALUATION OF THE INNERSURFACE DURABILITY OF GLASSCONTAINERSPURPOSEThis general information chapter provides information about factors that affect the durability of the inner surface of glass containers and recommends approaches to predict the potential of a drug product to cause formation of glass particles and delamination and to detect their occurrence. Useful procedures are listed and can be applied for both characterization and control tests.SCOPEThis chapter addresses molded bottles and vials manufactured by molding; or ampules, cartridges, vials, and prefillable syringes manufactured from tubing glass. Glass for pharmaceutical packaging is classified as Type I borosilicate glass, Type II treated soda-lime-silica glass, or Type III soda-lime-silica glass on the basis of the hydrolytic resistance of the glass, as defined in Containers—Glass 660. Type I glass containers are suitable for most products for parenteral and nonparenteral use. Type II glass containers are suitable for most acidic and neutral aqueous products for parenteral and nonparenteral uses, and can be used for alkaline parenteral products when stability data demonstrate their suitability. Type III glass containers usually are not used for parenteral products or for powders for parenteral use, except when suitable stability test data indicate that Type III glass is satisfactory. This chapter focuses primarily on Type I glass, because it is the most widely used in the biopharmaceutical industry.The chapter should be useful for the following:●Contract manufacturing and filling organizations●Molded and tubing glass container manufacturers and converters●Pharmaceutical and biopharmaceutical companiesGlass, in the form of ampules, bottles, cartridges, vials, and prefillable syringes, is thecontainer material of choice for parenteral products. This is especially true for thebiopharmaceuticals that have increased the demand for small-volume glass cartridges, vials, and prefillable syringes. Glass delamination, which ultimately results in the appearance of lamellae, is a serious quality issue and can result in a product recall. Delamination with the appearance of glass lamellae is a lagging indicator of structural instability. Althoughdelamination is the most obvious visual indicator, it represents the final stage of a seriously weakened glass surface structure, and can be observed only at a point where prevention is no longer an option. In addition, mechanical energy from shaking or vial-to-vial contact may dislodge the lamellae from the weakened internal surface.Tests for delamination combine an examination of the vial surface and analysis of an aggressive test solution to predict the propensity of the internal glass surface of vials to delaminate. Indicators include the appearance of a pitted, fractured surface instead of a smooth surface, as well as a number of changes in the test solution, including increases in SiO 2 concentration, the ratio of SiO 2/B 2O 3 or Si/Al, the number of subvisible particulates in the solution, and a fall in pH.GLASS TYPESGlass in its pure form consists of silicon dioxide with a melting point of approximately 1700°. Added network modifiers, such as sodium and potassium oxides or boric oxide, lower the melting point, while other network stabilizers, such as calcium and aluminum oxides, improve the durability of the glass. Colored glass (e.g., amber glass) is produced by transition metal oxides such as iron oxides. All additives to pure silicon dioxide can be viewed as potential extractables in glass.Glass compositions do not exist at a stoichiometric chemical composition but rather areexpressed over a range of compositions. Thus, there is allowable variation within a glass type, and glass types may vary slightly among glass producers. Soda-lime-silica glass consists of silica (60%–75%), sodium and potassium oxides (12%–18%), and smaller amounts of calcium, magnesium, and aluminum oxides (5%–12%). This glass has a relatively high coefficient of expansion (COE) of 8.4 × 10−5 per degree and is susceptible to damage by thermic shock. Borosilicate glass consists of silica (70%–80%), boric oxide (7%–13%), and smaller amounts of sodium, potassium, and aluminum oxides. The presence of boron provides greater resistance to thermal shock and to hydrolytic attack. Type I glass is available in twoformulations: 33 glass and 51 glass, in reference to their individual COEs of 32.5 × 10−7 per degree and 51.0 × 10−7 per degree, respectively.FORMATION OF MOLDED AND TUBING GLASS CONTAINERSFormation of molded and tubing glass containers requires a number of steps. The quality of the container used in packaging depends on the conditions and the quality control of each step. Both molded and tubing glasses originate from a glass furnace, and different furnaces are dedicated to borosilicate or soda-lime-silica glass. The refractory bricks lining the furnace deteriorate with time and must be replaced. Worn bricks can contribute to cosmetic defects such as stones (inclusions in the glass) that become incorporated into the molded glass containers or glass tubing.Molded glass vials and bottles are manufactured using a stream of molten glass cut to form a piece of glass that then enters a mold that shapes the container. Formation of containers from tubing glass is a two-step process. Glass tubes of a specific diameter are formed from a stream of molten glass that exits the furnace, is cooled, and is sectioned into standard lengths.These tubes are subsequently converted into glass containers (ampules, cartridges, syringes, or vials) by either the glass manufacturer or by independent converters. It is technically difficult to form glass tubing with a diameter sufficient to make bottles containing 100 mL or more, so these containers are produced by molding.Gas flames are used to soften tubing glass to form the neck, to melt the glass to form the ampuls or vial base, and to separate the container from the glass tube. In the case ofcartridges and prefillable syringes, the glass tube is cut to length, and the ends are softened to form the nozzle and flange of the syringe and the neck and rear of the cartridge. Heating rate, maximum glass temperature, and production speed are critical parameters that can beadjusted for individual forming machines. After formation, both tubing and molded containers pass through an annealing oven (lehr) that heats the containers to approximately 570° and then gradually cools them in order to remove stresses in the container due to themanufacturing process. This too is a critical process because poorly annealed containers show reduced durability.The process of forming tubing vials and ampules has an effect on the local surface composition of the glass. During formation of the neck and particularly the base, thetemperature of the inner surface of the containers can exceed the evaporation point of some of the glass components such as alkali borates. Under certain time–temperature conditions, the glass can phase separate during forming, creating nonhomogenous surface chemistry on the interior of the container. Both scenarios are undesirable for the storage of aggressive liquids from a surface durability perspective. Evidence of this can be obtained by appropriately etching the glass with acid, after which an opaque ring will appear above the heel of the container, indicating a negative change in the inner surface chemistry. The same phenomenon can be observed at the shoulder of the container as well, but in many instances this area does not experience prolonged contact with a liquid.Glass also is reheated during depyrogenation and sterilization, both before and after filling during terminal sterilization. The temperatures used for these steps are below those used for forming and annealing (see Table 1), and do not pose an additional risk to the durability of the glass from phase separation volatilization. The chemical durability of the glass can also be compromised by the presence of water during these unit operations, because water can diffuse into the glass and disrupt the silicate structure.Table 1. Temperatures Encountered During Formation and Processing of Type I Tubing Glass ContainersAt times, the inner surfaces of glass ampules, vials, and bottles undergo additionaltreatments. As an example, heating glass propagates sodium oxide toward the inner surface of the container, but washing with water does not remove sodium oxide because of the latter’s Key Operations TypicalTemperatures(°)Furnace 1650Sectioning of tube and base formation 1370Working range 1000–1200Softening 827Annealing 570Depyrogenation range 250–350Terminal sterilization 121limited solubility. Over time, sodium ions migrate into the solution in the container and produce hydroxide ions, resulting in an elevated pH in unbuffered solutions. Treatment with ammonium sulfate converts the sodium oxide on the inner surface and to a depth of a few angstroms into highly soluble sodium sulfate that then can be removed by washing. Although removal of sodium ions from the surface does reduce the propensity for pH shift, published work also has shown that the treatment weakens the inner surface by removing structural elements, leaving a silica-rich layer. The process originally was designed to raise the surface hydrolytic resistance of Type III soda-lime-silica glass to that of Type II glass in order to mimic the hydrolytic resistance of Type I glass. This process also can be applied to Type I glass. In a further example, treatment of the internal container surface of Type I glass with pure silica improves the container’s durability.In summary, the key factors that influence the glass surface durability of containers manufactured from Type I glass (the type most often used for parenteral drugs) are manufacturing conditions such as the forming temperature, the time of exposure to heat, and the annealing conditions, plus any additional treatments after formation, such as the use of ammonium sulfate. Storage in humid conditions and processing operations at the pharmaceutical manufacturer, especially depyrogenation in the presence of water vapor and terminal sterilization via autoclaving, also have been shown to reduce the chemical resistance of glass.GOOD GLASS SUPPLY-CHAIN PRACTICESBefore considering treatment of glass containers, manufacturers should consider the upstream provenance of the containers they purchase. Thus, to maintain and improve container quality over time, manufacturers should take a number of steps when they select a glass container vendor.●Audit supplier (glass manufacturer or converter)●Obtain glass formulation from the supplier●Designate 33 or 51 COE for Type I glass●Determine tubing glass source(s) for converters●Determine production site(s)●Determine if the tubing converting equipment varies in age, design, and manufacturerfrom site to site●Evaluate in-line electronic inspection systems for quality control of glass tubing and forglass containers●Determine whether the containers have been treated with ammonium sulfate●Establish acceptable quality levels for incoming lots with the vendor●Monitor and trend the quality of incoming batches by monitoring the values obtained bythe Surface Glass Test in 660GLASS SURFACE CHEMISTRYAfter manufacturers are assured of the quality and consistency of the glass containers they purchase, they can use the complex aqueous chemistry of surface glass to decide on potential drug product formulation and treatment steps that could increase glass stability. The reaction between the glass surface and an aqueous phase (water or water vapor) involves ion exchange between hydrogen ions and alkaline ions in the glass (Equation 1) and diffusion of water into the glass (Equation 2). This results in hydration of the glass surface and an alkali-depleted, silica-rich layer.The presence of water in the leachate promotes hydrolysis of the Si–O bond (Equation 3) and condensation (Equation 4), forming a silica-gel layer.The mechanical properties of the surface gel that forms are different from those of bulk glass. Repeated hydration and dehydration of the layer leads to the cracking of the gel layer and eventual generation of particles. This process is worsened as the gel layer increases inthickness. This phenomenon is well known in glass exposed to ambient moisture (known as weathering). At higher pH values, the mechanism of glass degradation changes from theleaching of alkali elements to the dissolution of the silicate network as shown in Equation 5and Equation 6.Reaction (Equation 6) increases the solubility of the silicic acid in solution, driving the reaction forward. At some point the limit of solubility is exceeded, and subvisible particles are formed. If the solution is not buffered, a decrease in the solution pH will take place. These reactions and scenarios apply only to the reactions of glass with water; the presence of drug product formulations can complicate the situation considerably.FACTORS THAT INFLUENCE INNER SURFACE DURABILITYA number of factors have the potential to influence the durability of the inner surface of glass containers. These factors include glass composition, the conditions under which the containers were formed, subsequent handling and treatments, and the drug product in the container(Table 2). Not all listed factors influence surface durability to the same degree, and their effects can be additive. Because of the range of variables, end users should examine all relevant variables for an individual drug product and assess the degree of risk for delamination and formation of subvisible and visible glass particles. Delamination is the process whereby thin layers of glass—described as either flakes or lamellae—are detached from the inner surface of a container. In some situations, the accumulation of risk factors indicates that a glass container should not be used for a particular formulation.Table 2. Factors That Influence the Inner Surface Durability of GlassContainer Container Storage,Handling, andProcessing Drug Product●Glass composition ●Molded or tubing ●Post-formation treatments: ●Drug substance●Formulation:SCREENING METHODS TO EVALUATE INNER SURFACE DURABILITYEach lot of Type I glass containers received by a pharmaceutical manufacturer must comply with the Surface Glass Test in chapter 660. This test provides an indication of surface durability but does not appear to provide a clear direct correlation with the propensity to form glass particles or to delaminate. A low surface alkalinity value can be obtained from containers treated with ammonium sulfate; but the treatment itself may reduce the inner surface durability, and the amount of alkalinity comes from the sum of all the internal surfaces. Although this is representative for all internal surfaces of molded glass containers, tubing glass containers can have different degrees of surface durability, depending on the location (e.g., just above the heel vs. the side wall). The most important variable that affects the surface durability is the drug product itself, and because it uses water as the extracting medium, the Surface Glass Test does not take this into consideration. Therefore, the Surface Glass Test represents only a first step in quality control of surface durability, and additional screening methods should be used to demonstrate the suitability of vials for a formulation from a particular source before formal stability studies begin.Predictive Screening MethodsScreening methods help evaluate glass containers from different vendors (molded or tubular), glass formulations (COE 33 or 51), and post-formation treatments. Screening also establishes lot-to-lot variation from individual vendors during the drug development process, as well as lot-to-lot variations for products that have been shown to have a particular propensity to form glass particles or to delaminate. Screening methods can use a number of differenttechnologies to examine three key parameters: visual examination and chemical profile of the inner surface layer, the amount and identity of extracted elements in solution, and the number of subvisible and visible particles in solution. Taken together, these elements are assessed by predictive tests for formation of glass particles and delamination, processes that reflectreduced durability. Predictive tests should look for precursors that lead to delamination rather than flakes themselves, and should be able to quickly provide predictive indication of surface durability. This makes the tests useful not just for vendor selection but also for evaluation of individual lots if necessary. Some of the more commonly used analytical methods for evaluating the three key parameters are shown in Table 3. Table 3. Analytical Methods for Screening Studies container ●Manufacturingprocess:- Convertingspeed- Convertingtemperature - Ammonium sulfate ●Storage conditions: - High humidity- Acetate, citrate, phosphate buffers - Sodium salts of organic acids, e.g., gluconate, malate, succinate, tartrate - High ionic strength, e.g., >0.1 M of alkaline salts - Complexing agents, e.g., EDTA - High pH, e.g., >8.0 ●Terminal sterilization ●Labeled storage conditions (refrigerated or controlled room temperature) ●Shelf lifeParameter Test Parameter Analytical MethodsAggressive Screening ConditionsIn selecting an appropriate primary glass container for pharmaceutical liquids, analysts should consider two approaches. The first is a series of accelerated temperature exposures using aggressive conditions that establish, in rank order, the chemical durability of the container without any specific reference to a given compound. Such testing can be helpful when selecting a packaging kit for which the most chemically durable glass is desired. This testing also can be helpful in determining if changes in glass quality have occurred or inassessing processing changes that have been made by the primary container manufacturer. Table 4 provides some model systems that could be used for this assessment. Table 4. Formulations and Conditions Used to Accelerate DelaminationScreening Strategy for Drug ProductsIf the purpose of the glass screening is to determine the suitability of a given glass container for a specific product, the testing proposed in Table 4 is insufficient. The exposure conditions are too harsh and do not provide a direct link to the product itself. In these instances,accelerated conditions are still relevant, but they must link to the relevant conditions for the given product. For example, if a product will be stored at 5° and accelerated conditions are 30°, then testing should occur at 30°. Many products or formulations cannot withstand the elevated temperatures shown in Table 4. In addition, false positive testing results could be obtained because the unusually high temperatures shown in Table 4 could cause signs of delamination, but moderate exposure at 30° would produce no evidence of glassincompatibility.Because lower temperatures are required for actual product testing, the duration of testing must be longer, ranging from weeks to months. A larger number of vials also is appropriate for this scenario because the goal of the testing is to ensure the results are representative of the Glass surface ●Degree of surface pitting ●Chemical composition as a functionof depth●DIC Microscopy a or EM b ●SIMS c Extracted elements in solution ●Conductivity/pH●Individual and total extractables- SiO 2 concentration- SiO 2/B 2O 3 or Si/Al ratio●Conductivity/pH meter ●IC–MS d or ICP–OES e Visible and subvisibleglass particles●Particle number and size●Particle morphology andcomposition ●Particle size analyzer ●SEM–EDX f a Differential interference contrast microscopy.b Electron microscopy.c Secondary ion mass spectrometry.d Inductively coupled plasma–mass spectrometry.eInductively coupled plasma–optical emission spectrometry. f Scanning electron microscopy–energy-dispersive X-ray spectroscopy.Formulation 0.9% KCl pH 8.03% Citric Acid pH 8.020 mM GlycinepH 10.0Conditions 2 h at 121°24 h at 80°24 h at 50°quality of the glass that will be used for the drug product. Table 5 shows some of the conditions that could be used for testing with a specific product. Table 5. Screening Strategy for Glass VialsCONCLUSIONS Evaluation of the internal surface of glass containers begins with the Surface Glass Test ,which uses water as the extracting medium. A low value is not always an indicator of a durable inner surface because the results are obtained using surface treatments (e.g., ammonium sulfate). Such treatments can lead to a silica-rich surface layer that represents a weakened glass structure, and risk of delamination increases when the vial is filled with formulations that contain aggressive agents such as organic acids, EDTA, or solutions that have high ionic strength or pH. The screening methods and strategies described in this chapter can assist in the evaluation of glass containers from different suppliers and can provide an indication of the propensity of the selected formulation to cause delamination over time. Selection of glass vials intended to contain a drug product with one or more of the formulation risk factors identified in Table 2 should undergo particular scrutiny.ADDITIONAL SOURCES OF INFORMATIONThe references provide additional resources regarding the reaction of glass with solutions. They are not exhaustive but are intended to provide greater depth of information should the need arise.1.Bacon FR. The chemical durability of silicate glass: part one. Glass Ind. 1968;49(8):438–446.2.Bacon FR. The chemical durability of silicate glass: part two. Glass Ind. 1968;49(4):494–499.3.Baer DR, Pederson LR, McVay GL. Glass reactivity in aqueous solutions. J Vac SciTechnol. 1984;A2:738–743.4.Blackmore HS, Dimbleby V, Turner WES. A rapid method of testing the durability ofglassware. J Soc Glass Technol. 1923;7:122–129.5.Branda F, Laudisio G, Constantini A, Piccioli C. Weathering of a Roman glass: a newhypothesis for pit formation on glass surfaces. Glass Technol Eur J Glass Sci Technol Part A. 1999;40(3):89–91.6.Cailleteau C, Angeli F, Devreux F, et al. Insight into silicate-glass corrosionmechanisms. Nat Mater. 2008;7(12):978–983. DOI 10.1038/nmat2301.7.Dimbleby V. Notes on some methods used in the analyses of glasses. J Soc GlassTechnol. 1927;11:153–166.8.Dimbleby V. Chemical durability of glass. Sci Sch Rev. 1937;18:476–489.9.Dimbleby V. Glass for pharmaceutical purposes. J Pharm Pharmacol. 1953;5:969–989.Water Control Stress Test Drug Product Control●Washed, depyrogenated container ●Filled with Water for Injection ●Autoclaved ●Accelerated drug product stability storage conditions●Washed, depyrogenated container ●Filled with stress test solution●Accelerated treatment ●Washed, depyrogenated container●Filled with drug product●Autoclave if applicable ●Accelerated drug product stability storageconditions10.Dimbleby V, Gill HSY, Turner WES. Some effects of storage on the chemical durabilityof glass containers. J Soc Glass Technol. 1935;19:231–243.11.Ennis RD, Pritchard R, Nakamura C, et al. Glass vials for small-volume parenterals:influence of drug and manufacturing processes on glass delamination. Pharm DevTechnol. 2001;6(3):393–405. PMID 11485181.12.Fern S, McPhail DS, Oakley V. Room temperature corrosion of museum glass: aninvestigation using low-energy SIMS. Appl Surface Sci. 2004;231–232:510–514.13.Geisler T, Janssen A, Scheiter D, et al. Aqueous corrosion of borosilicate glass underacidic conditions: a new corrosion mechanism. J Non-crystalline Solids. 2010;356(28–30):1458–1465. DOI 10.1016/j.jnoncrysol.2010.04.033.14.Gillies KJS, Cox A. Decay of medieval stained glass at York, Canterbury, and Carlisle.Glastech Ber. 1988;61:75–84.15.Gillies KJS, Cox A. Decay of medieval stained glass at York, Canterbury, and Carlisle:part 2. Relationship between the composition of the glass, its durability, and theweathering products. Glastech Ber. 1988;61(4):101–107.16.Iacocca RG, Allgeier MA. Corrosive attack of glass by a pharmaceutical compound. JMaterials Sci. 2007;42(3):801–811.17.Iacocca RG, Toltl N, Allgeier M, et al. Factors affecting the chemical durability of glassused in the pharmaceutical industry. AAPS PharmSciTech. 2010;11(3):1340–1349. DOI10.1208/s12249-010-9506-9.18.Iacocca RG. Medical interactions with glass packaging surfaces. Pharm Technol.2011;35(11):s6–s9.19.Rogers P, McPhail D, Ryan J. A quantitative study of decay processes of Venetianglass in a museum environment. Glass Technol Eur J Glass Sci Technol Part A.1993;34(2):67–68.20.Roggendorf H, Syrowatka F, Trempler J. Corrosion of sodium silicate glasses inaqueous solutions—influence of pH. Eur J Glass Sci Technol Part B. 2010;51(Compendex):318–322.21.Schreiner M. Deterioration of stained medieval glass by atmospheric attack. GlastechBer. 1988;61(7):197–204.22.Smets BMJ. On the mechanism of the corrosion of glass by water. Philips Tech Rev.1985;42(2):59–64.23.Wen ZQ, Torance G, Masatani P, et al. Nondestructive detection of glass vial innersurface morphology with differential interference contrast microscopy. J Pharm Sci.2012;DOI 10.1002/JPS23048.24.White WB. Theory of corrosion of glass and ceramics. In: Clark DE, Zoitos BK, eds.Corrosion of Glass, Ceramics and Ceramic Superconductors: Principles, Testing,Characterization, and Applications. Noyes Publications: Park Ridge, NJ; 1992:2–28.▪2S(USP36)。

VALIDATION OF COMPENDIAL PROCEDURES 药典方法的验证Test procedures for assessment of the quality levels of pharmaceutical articles are subject to various requirements. According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards. The Current Good Manufacturing Practice regulations [21 CFR 211.194(a)] require that test methods, which are used for assessing compliance of pharmaceutical articles with established specifications, must meet proper standards of accuracy and reliability. Also, according to these regulations [21 CFR 211.194(a)(2)], users of analytical methods describedin USP–NF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Recognizing the legal status of USP and NF standards, it is essential, therefore, that proposals for adoption of new or revised compendial analytical procedures be supported by sufficient laboratory data to document their validity.用于评估药品质量的检验方法需要满足不同的要求。

usp美国药典等级美国药典级usp calss vi美国药典级（usp）实际上含义：美国药典（usp）是一个非政府组织，通过建立最新的标准来保证药品和其他保健技术的质量，从而支持公共卫生。

该组织与制药和生物技术行业有关。

美国药典规定了质量、纯度、强度和一致性的标准。

这些usp 标准发表在《美国药典》和《国家处方集》（usp nf）中。

usp第四类产品经过一系列的生物试验。

usp第六类化合物必须由具有明确生物相容性历史的成分制成，以满足对渗滤液的严格要求。

动物用来测试材料的毒性。

急性毒性试验:该试验测量试验材料的刺激性，控制其对人体的潜在危害。

毒性由口腔、皮肤和吸入决定。

皮内试验:这种特殊的试验将材料直接注射到正常使用过程中接触到的组织中，不保护皮肤或任何其他身体系统。

这将允许测试团队评估特定组织对材料的响应。

植入试验：植入试验确定植入活体动物时活体组织对材料的反应。

usp六级试验所需的标准植入时间为5天。

如果在5天后没有刺激或毒性的迹象，它将满足试验的植入要求。

温度和时间:用于全身毒性和皮内试验的材料提取物固定在设定的温度和暴露时间，以确保结果符合通用标准。

用三种不同的温度和时间暴露条件处理所有的材料提取物。

前72小时在122°F或50°C下给药，然后在158°F下给药24小时，最后在250°F下给药1小时。

usp第六类塑料试验旨在评价各种塑料材料在体内的生物反应性。

为了测试药物容器，塑料类测试经常在未焊接的塑料树脂和容器上进行。

类塑料测试不是生物相容性测试的替代品，但通常被制造商用来对材料进行分类。

塑料的分类包括三种体内试验。

系统注射试验和皮内试验旨在通过单剂量注射特定提取物来控制对塑料和其他聚合物的全身和局部生物反应。

第三种测试，即植入测试，旨在评估活组织对测试材料的反应。

利用这三个试验和不同提取物的不同排列，完成了六个不同等级的塑料等级试验。

usp定义了六种塑料类别，从i到vi（vi仍然是最严格的）。

中英文度量衡对照表英美制到公制转换Linear Measure 长度1 inch 英寸=25.4 millimetres 毫米1 foot 英尺=12 inches 英寸=0.3048 metre 米1 yard 码=3 feet 英尺=0.9144 metre 米1 (statute) mile 英里=1760 yards 码=1.609 kilometres 千米1 nautical mile 海里=1852 m. 米Square Measure 面积1 square inch 平方英寸=6.45 sq.centimetres 平方厘米1 square foot 平方英尺=144 sq.in.平方英寸=9.29 sq.decimetres 平方分米1 square yard 平方码=9 sq.ft. 平方英尺=0.836 sq.metre 平方米1 acre 英亩=4840 sq.yd.平方码=0.405 hectare 公顷1 square mile 平方英里=640 acres 英亩=259 hectares 公顷Cubic Measure 体积1 cubic inch 立方英寸=16.4 cu.centimetres 立方厘米1 cubic foot 立方英尺=1728 cu.in. 立方英寸=0.0283 cu.metre 立方米1 cubic yard 立方码=27 cu.ft. 立方英尺=0.765 cu.metre 立方米Capacity Measure 容积British 英制1 pint 品脱=20 fluid oz. 液量盎司=34.68 cu.in. 立方英寸=0.568 litre 升1 quart 夸脱=2 pints 品脱=1.136 litres 升1 gallon 加伦=4 quarts 夸脱=4.546 litres 升1 peck 配克=2 gallons 加伦=9.092 litres 升1 bushel 蒲式耳=4 pecks 配克=36.4 litres 升1 quarter 八蒲式耳=8 bushels 蒲式耳=2.91 hectolitres 百升American dry 美制干量1 pint 品脱=33.60 cu.in. 立方英寸=0.550 litre 升1 quart 夸脱=2 pints 品脱=1.101 litres 升1 peck 配克=8 quarts 夸脱=8.81 litres 升1 bushel 蒲式耳=4 pecks 配克=35.3 litres 升American liquid 美制液量1 pint 品脱=16 fluid oz. 液量盎司=28.88 cu.in. 立方英寸=0.473 litre 升1 quart 夸脱=2 pints 品脱=0.946 litre 升1 gallon 加伦=4 quarts 夸脱=3.785 litres 升Avoirdupois Weight 常衡1 grain 格令=0.065 gram 克1 dram 打兰=1.772 grams 克1 ounce 盎司=16 drams 打兰=28.35 grams 克1 pound 磅=16 ounces 盎司=7000 grains 谷=0.4536 kilogram 千克1 stone 英石=14 pounds 磅=6.35 kilograms 千克1 quarter 四分之一英担=2 stones 英石=12.70 kilograms 千克1 hundredweight 英担=4 quarters 四分之一英担=50.80 kilograms 千克1 short ton 短吨(美吨)=2000 pounds 磅=0.907 tonne 公吨1 (long) ton 长吨(英吨)=20 hundredweight 英担=1.016 tonnes 公吨公制到英美制转换Linear Measure 长度1 millimetre 毫米=0.03937 inch 英寸1 centimetre 厘米=10 mm.毫米=0.3937 inch 英寸1 decimetre 分米=10 cm. 厘米=3.937 inches 英寸1 metre 米=10 dm. 分米=1.0936 yards 码=3.2808 feet 英尺1 decametre 十米=10 m. 米=10.936 yards 码1 hectometre 百米=100 m. 米=109.4 yards 码1 kilometre 千米=1000 m. 米=0.6214 mile 英里1 mile marin 海里=1852 m. 米=1.1500 mile 英里Square Measure 面积1 square centimetre 平方厘米=0.155 sq.inch 平方英寸1 square metre 平方米=1.196 sq.yards 平方码1 are 公亩=100 square metres 平方米=119.6 sq.yards 平方码1 hectare 公顷=100 ares 公亩=2.471 acres 英亩1 square kilometre 平方公里=0.386 e 平方英里Cubic Measure 体积1 cubic centimetre 立方厘米=0.061 cu.inch 立方英寸1 cubic metre 立方米=1.308 cu.yards 立方码Capacity Measure 容积1 millilitre 毫升=0.002 pint (British) 英制品脱1 centilitre 厘升=10 ml. 毫升=0.018 pint 品脱1 decilitre 分升=10 cl. 厘升=0.176 pint 品脱1 litre 升=10 dl. 分升=1.76 pints 品脱1 decalitre 十升=10 l. 升=2.20 gallons 加伦1 hectolitre 百升=100 l. 升=2.75 bushels 蒲式耳1 kilolitre 千升=1000 l. 升=3.44 quarters 八蒲式耳Weight 重量1 milligram 毫克=0.015 grain 谷1 centigram 厘克=10 mg. 毫克=0.154 grain 谷1 decigram 分克=10 cg. 厘克=1.543 grains 谷1 gram 克=10 dg. 分克=15.43 grains 谷1 decagram 十克=10 g. 克=5.64 drams 打兰1 hectogram 百克=100 g. 克=3.527 ounces 盎司1 kilogram 千克=1000 g. 克=2.205 pounds 磅1 ton (metric ton) 吨,公吨=1000 kg. 千克=0.984 (long) ton 长吨,英吨=1.1023 短吨,美吨国际制度的单位国际制度（The International System，缩写为SI，是国际制度的法语名称）被1960年的第十一届大会用于度量衡。