ISO发布胶塞新标准！
近日，ISO发布了ISO 8871-2：2020《非肠道用和制药设备用弹性部件 第二部分:鉴别和特性》，该文件文件取代了ISO 8871-2:2003，并进行了技术修订。
文件规定了适用于人造橡胶部件的鉴别和特性程序，包括用于药品容器和医疗器械的覆膜胶塞。
在ISO 8871系列中指定的弹性体部件由橡胶制成。然而，橡胶不是一个独特的实体，因为橡胶材料的组成可以有很大的变化。基础弹性体和硫化方式对单个橡胶材料的基本性能有重要影响，填料、软化剂和颜料等添加剂也是如此。这些可能会对整个属性产生重大影响。聚合物涂层或薄膜通常应用于橡胶部件的整个或部分表面，以赋予某些物理或化学性能。如果使用的橡胶部件没有得到适当的选择和验证(批准)，在生产、储存和使用过程中药物制剂的有效性、纯度、稳定性和安全处理可能受到不利影响。
文件规定的物理和化学测试程序可以确定弹性体部件的典型特性，包括覆膜和表面处理，并可以作为制造商和用户之间就后续供应的产品一致性达成协议的基础。根据弹性体的类型及其应用，选择一套适当的试验。
部分翻译如下：
ISO 8871-2：2020
Elastomeric partsfor parenterals and for devices for pharmaceutical use —
非肠道用和制药设备用弹性部件—
Part 2:
第二部分:
Identification and characterization
鉴别和特性
Contents
内容
Foreword
前言
Introduction
介绍
1 Scope
范围
2 Normative references
标准参考文献
3 Terms and definitions
术语和定义
4Tests
测试
4.1 General
一般要求
4.2 Hardness
硬度
4.3 Density
密度
4.4 Ash
灼烧残渣
4.5 Infrared spectrum
红外光谱
4.5.1 Material
材料
4.5.2 Coating
覆膜
4.6 Compression set
压缩形变
4.7 Swelling
膨胀
4.8 Development of a fingerprint by gaschromatography
气相色谱法的指纹开发
4.9 Detection of volatile substances by gaschromatography
气相色谱法检测挥发性物质
4.10 Determination of residual moisture
残余水分的测定
4.11Determination of fingerprint by thermogravimetricanalysis (TGA)
热重分析指纹图谱测定法
4.12Determination of extractables inaqueous autoclavates
高压水溶液中可提取物的测定
5 Preparation of samples for testing
测试样品的准备
5.1 Treatment before testing
测试前的处理
5.2 Number of samples needed for the tests
测试所需的样品数量
6 Reagents and materials
试剂和材料
Annex A (informative) Identification ofelastomeric material by pyrolysis IR
附录A（资料性）用热解红外光谱法鉴定弹性体材料
Annex B (informative) Determination ofcompression set
附录 B （资料性）压缩永久形变的测定
Annex C (informative) Swelling behaviour inoils
附录 C （资料性）在油中的膨胀行为
Annex D (informative) Development of a fingerprintby gas chromatography
附录D （资料性）气相色谱法指纹的开发
Annex E (informative) Analysis of volatilecomponents by headspace gas chromatography
附录 E（资料性）通过顶空气相色谱法分析挥发性成分
Annex F (informative) Determination ofresidual moisture
附录 F（资料性）残余水分的测定
Annex G (informative) Determination of afingerprint by thermal gravimetry (TG)
附录G（资料性）用热重分析法(TG)测定指纹图谱
Annex H (informative) Determination of theelastomer identity and verification of the presence of a coating by surfaceinfrared spectroscopy [attenuated total reflection (ATR)]
附录H （资料性）通过表面红外光谱确定弹性体特性并验证覆膜的存在 [衰减全反射（ATR）]
Bibliography
参考文献
Introduction
介绍
The elastomeric parts specified in the ISO 8871series are produced from rubber. However, rubber is not a unique entity, sincethe composition of rubber materials can vary considerably. The base elastomerand the type of vulcanization have a major influence on the principlecharacteristics of an individual rubber material, as do additives such asfillers, softeners and pigments. These might have a significant effect on theoverall properties. Polymer coatings or films are often applied to eitherentire or partial surface(s) of a rubber component to impart certain physicalor chemical properties. The effectiveness, purity, stability and safe handlingof a drug preparation can be affected adversely during manufacture, storage andadministration if the rubber part used has not been properly selected andvalidated (approved).
在ISO 8871系列中指定的弹性体部件由橡胶制成。然而，橡胶不是一个独特的实体，因为橡胶材料的组成可以有很大的变化。基础弹性体和硫化方式对单个橡胶材料的基本性能有重要影响，填料、软化剂和颜料等添加剂也是如此。这些可能会对整个属性产生重大影响。聚合物覆膜或薄膜通常应用于橡胶部件的整个或部分表面，以赋予某些物理或化学性能。如果使用的橡胶部件没有得到适当的选择和验证(批准)，在生产、储存和使用过程中药物制剂的有效性、纯度、稳定性和安全处理可能受到不利影响。
1 Scope
1范围
This document specifies identification andcharacterization procedures applicable to elastomeric parts including coatedstoppers used for drug containers and medical devices.
本文件规定了适用于人造橡胶部件的鉴别和特性程序，包括用于药品容器和医疗器械的覆膜胶塞。
The physical and chemical test proceduresspecified in this document permit the determination of the typicalcharacteristics of elastomeric parts including coatings and surface treatmentsand can serve as a basis for agreements between manufacturer and user regardingthe product consistency in subsequent supplies. Depending upon the type of elastomerand its application, an appropriate set of tests is selected.
本文件规定的物理和化学测试程序可以确定弹性体部件的典型特性，包括覆膜和表面处理，并可以作为制造商和用户之间就后续供应的产品一致性达成协议的基础。根据弹性体的类型及其应用，选择一套适当的试验。
4 Tests
4测试
4.1 General
4.1一般要求
Rubber is a complex material and it is notgenerally definable. The only property which all elastomeric materials have incommon is a special type of resilience or elasticity. When a strip of rubber isstretched, it will extend by up to many times its original length withoutbreaking. On release of the stretching force, it snaps back to its originalsize and shape virtually unaltered. Similarly, one can squeeze it, twist it ordistort it in any direction comparatively easily, and it will virtually springback again to its original shape unchanged.
橡胶是一种复杂的材料，一般是无法定义的。所有弹性材料唯一的共同特性是一种特殊类型的弹性体。当一条橡胶条被拉伸时，它会延伸到原来长度的许多倍而不断裂。一旦释放拉伸力，它就会恢复到原来的大小和形状，几乎不会改变。同样，人们可以相对容易地挤压、扭曲或扭曲它的任何方向，它几乎会弹回原来的形状不变。
Owing to its three-dimensional network, achievedby chemical cross-linking of the elastomer during vulcanization, rubber ispractically insoluble in solvents such as tetrahydrofuran, althoughconsiderable reversible swelling may occur; this characteristic differentiatesrubber from pseudo-elastic materials, such as poly(vinyl chloride) and certainthermoplastic elastomers.
由于橡胶在硫化过程中通过弹性体的化学交联形成三维网络，橡胶实际不溶于四氢呋喃等溶剂，可以发生相当大的可逆膨胀;这一特性使橡胶不同于假弹性材料，如聚氯乙烯和某些热塑性弹性体。
In view of the complexity of rubber, a set oftests is needed for reliable identification.
考虑到橡胶的复杂性，需要进行一系列试验来进行可靠的识别。
The manufacturer shall guarantee that all elastomericparts of current supplies have been produced from the same formulation and thatthey exhibit the same characteristics as the initially supplied samples.
制造商应保证现有供应的所有弹性部件都是用相同的配方生产，并且它们与最初供应的样品具有相同的特性。
4.2 Hardness
4.2硬度
Hardness shall be determined in accordance withISO 48-4.
硬度应按照ISO48-4标准确定。
4.3 Density
4.3密度
Density shall be determined in accordance withthe procedure described in ISO 2781:2018, Clause 4, method A.
密度应按照ISO2781:2018第4条、方法a所规定的程序确定。
4.4 Ash
灼烧残渣
The inorganic residue after combustion shall bedetermined as described in ISO 247-1:2018, 4.1, method A.
燃烧后的无机残留物应按照ISO247-1:2018,4.1，方法a的规定进行测定。
4.5 Infrared spectrum
4.5红外光谱
4.5.1 Material
4.5.1材料
One method to create a fingerprint of a rubbermaterial is to record an infrared (IR) spectrum. The two common methods forobtaining an IR spectrum of a rubber material are pyrolysis IR and surface IR/ATR (attenuated total reflectance)-technique.
一种制作橡胶材料指纹的方法是记录红外光谱。获得橡胶材料红外光谱的两种常用方法是热解红外和表面红外/衰减全反射技术。
The pyrolysis IR can be obtained as described in Annex A. Alternatively, an aliquot of thepyrolysate can be brought on an ATR crystal of an FTIR-spectrometer asdescribed in Annex H. The surfaceIR/ATR can be obtained as described in Annex H.The spectra should be compared with a spectrum obtained by the same IR methodon a reference sample of the material.
热解产物的红外光谱可以按照附件A的说明获得。另外，可以按照附件H的说明，将热解产物的一小部分带到傅立叶红外光谱仪的ATR晶体上。表面红外光谱/衰减全反射的测量结果如附件H所述。光谱应与用同样的红外光谱法的对照样品上获得的光谱进行比较。
In practice, pyrolysis IR requires atime-consuming sample preparation. In addition, it needs the cautious handlingof hazardous vapours and oils.
在实践中，裂解红外光谱需要耗费大量的样品制备时间。此外，它需要谨慎处理的危险蒸汽和油。
In contrast to this, the surface IR/ATRoffers the possibility to obtain a fingerprint from an elastomeric part withminimum or no sample preparation.
与此相反，表面IR/ATR提供了从弹性体部分获得指纹的可能性，只需要很少或不需要样品制备。
4.5.2 Coating
4.5.2覆膜
The presence of a coating (barrier andlubrication coating) can be verified by comparing FTIR spectra of the surfaceand of the core material of the product (see AnnexH). For measuring the coating, the samples do not need to be cut.
覆膜(阻隔层和润滑层)的存在可以通过比较产品表面和核心材料的FTIR光谱来验证(见附件H)。对于测量覆膜，样品不需要切割。
4.6 Compression set
4.6压缩变形
The compression set indicates the degree ofpermanent deformation remaining after compression at a constant deformation anddefined temperature for a defined time. The compression set can be determinedin accordance with Annex B.
压缩永久变形指的是在一定的时间内，在一定的变形量和温度下，压缩后的永久变形程度。压缩永久变形可根据附录B确定。
4.7 Swelling
4.7膨胀
Elastomeric materials are subject to varyingdegrees of swelling when exposed to organic solvents. The degree of volumeand/or mass increase is primarily influenced by the type of elastomer. Swellingrequires special care when the rubber components are in contact with emulsionsor oily vehicles.
弹性材料在暴露于有机溶剂时会有不同程度的膨胀。体积和/或质量增加的程度主要受弹性体类型的影响。当橡胶部件与乳剂或油性车辆接触时，需要特别注意膨胀。
The relevant procedure is specified in Annex C.
相关程序在附录C中有详细说明。
4.8 Development of a fingerprint by gaschromatography
4.8气相色谱法的指纹开发
The elastomeric materials under examination areextracted in a solvent which does not dissolve but might swell the rubber. Theextract is injected into a gas chromatograph. The chromatogram obtainedexhibits a typical profile and can be used as a fingerprint for identificationpurposes. Furthermore, GC-coupling techniques, for example gas chromatography –mass spectrometry (GC-MS), may provide additional information about thecomposition of the extract.
待检的弹性体材料在溶剂中提取，溶剂不溶解，但可能使橡胶膨胀。提取物注入气相色谱仪。所得色谱图呈现出典型的轮廓，可作为鉴别指纹使用。此外，气相色谱耦合技术，例如气相色谱法-质谱法(GC-MS)，可以提供更多关于提取物成分的信息。
The relevant procedure is specified in Annex D.
有关程序载于附录D。
4.9 Detection of volatile substances by gaschromatography
4.9气相色谱法检测挥发性物质
Elastomeric materials may release volatilesubstances. These may originate from one of the following categories ofmaterial:
弹性材料可以释放挥发性物质，这些物质可能来自以下材料类别之一:
— oligomers or process aids present in the base polymer;
存在于基聚合物中的低聚物或加工助剂;
— stabilizers or antioxidants;
稳定剂或抗氧化剂;
— softeners.
软化剂。
The relevant procedure is specified in Annex E.
有关程序载于附录E。
4.10 Determination of residual moisture
4.10残余水分的测定
While undergoing treatments which are typical inthe pharmaceutical industry, elastomeric parts can absorb moisture inconsiderable quantities. During storage of the pharmaceutical product, thetrapped moisture may be released and absorbed by the pharmaceutical product,thus reducing its effectiveness (critical case: Iyophilized drugs). The natureof the absorption and desorption processes is affected by the composition ofthe rubber, the type of treatment (e.g. steam autoclaving) and the efficiencyof any subsequent drying process.
在进行制药工业中典型的处理时，弹性体部件可以大量吸收水分。在药品的储存过程中，被吸收的水分可能被释放并被药品吸收，从而降低其有效性(严重的例子：冻干药物)。吸收和释放过程受橡胶的成分、处理方式(例如蒸汽灭菌)及其后的任何干燥过程的效果影响。
The relevant procedure is specified in Annex F.
有关程序载于附件F。
4.11 Determination of fingerprint bythermogravimetric analysis (TGA)
4.11热重分析测定指纹
Elastomeric parts are composed of componentswhich can be classified relative to their performance under thermal treatment,as follows:
弹性部件由各种组分组成，这些组分可按其在热处理下的性能分类如下:
— basepolymers;
基聚合物;
— inorganic fillers;
无机填料;
— substances volatile at elevated temperatures;
在高温下易挥发的物质;
— carbonblack.
炭黑。
The relevant procedure is specified in Annex G.
有关程序载于附件G。