制药用塑料的通用要求！

General requirements for Plastics in Pharmaceutical Engineering

制药用塑料的通用要求

What are the general requirements forplastics in pharmaceutical plant engineering?

制药工厂工程中塑料的一般要求是什么？

There is no simple answer to thisquestion. There is no 'gold standard' either. The requirementsalways depend on the concrete application purpose.

这个问题没有简单的答案，也没有'黄金标准'。要求始终取决于具体的应用目的。

Three types of plastics are used: softplastics (e.g. foil), hard plastics (e.g. valve bodies) and elastomers (e.g.membranes for membrane valves or o-rings). The essential quality features aresurface finishing and material compatibility.

常用的塑料有三种类型：软塑料（如铝箔）、硬塑料（如阀体）和弹性体（例如膜阀或 O 形环）。基本质量特征是表面光洁度和材料兼容性。

Surfacefinishing

表面光洁度

One GMP requirement forpharmaceutical plants is that they must be easy to clean. Therefore, thesurfaces in contact with products must be smooth. For stainless steel, Ra <=0.8 µm is the usual surface roughness requirement. This value is measuredin some parts of the plant during qualification or documented by certificatesfrom the plant manufacturer. Verification by means of aprofilometer/perthometer is still state-of-the-art.

制药厂的GMP要求之一是它们必须易于清洁。因此，与产品接触的表面必须光滑。对于不锈钢，Ra = 0.8 μm是通常的表面粗糙度要求。这可以通过在验证期间对部件进行测量，或来自于制造商的证书。优先使用量度计/测量仪进行确认。

It is more difficult todetermine the surface of plastics. Indeed, mechanical detectors pose a greatrisk of scratching the plastic surface.

塑料表面的测量则较为困难。事实上，机械检测器在塑料表面存在刮伤的巨大风险。

When specifying average roughness valuesfor plastic parts, manufacturers often use statistical methods, i.e. some partsare measured (and then thrown away). Alternatively, contact-free measuringmethods may be used (e.g. white light scanning).

当指定了塑料零件的平均粗糙度时，制造商通常使用统计方法，即测量某些零件（然后扔掉）。或者，使用非接触的测量方法（例如白光扫描）。

In the case of thermoplastics, which areproduced by means of injection moulding and for which the manufacturers usehighly polished injection moulds, the high surface quality is generally ensuredby the manufacturing process. Here, a surface roughness can be achieved whichis significantly better than the Ra values of stainless steel (e.g. <=0.8 µm). This is also confirmed in material certificates and can be regarded assufficient if the supplier's quality system is trusted. ISO standards for theroughness measurement of stainless steels are DIN ISO 4287 and 4288.

对于通过注塑成型生产的热塑性塑料，制造商使用高度抛光的注塑模具，制造工艺通常确保高的表面质量。在这里，可以达到比不锈钢的 Ra 值（例如≤0.8 μm）更好的表面粗糙度。这在材料证书中也得到确认，如果供应商的质量体系是可信的，则可视为足够。不锈钢粗糙度测量的 ISO 标准为 DIN ISO 4287 和 4288。

The SEMI F57 standard for thesemiconductor industry (ultrapure media technology) deals with the surface ofplastic components. SEMASPEC 92010950B (Preliminary Test Method for VisualEvaluation of Surface Roughness of Plastic Surfaces of UPW Distribution SystemComponents) is used for the verification of surface quality. However, there isno such comparable specification within the pharmaceutical world. In the caseof plastic parts produced by cutting, it is sometimes only possible to achievesurface values of Ra <1 µm with specific additional measures, i.e. it playsan important role whether a component was produced by injection moulding orcutting/milling.

半导体工业（超纯介质技术）的 SEMI F57 标准提及塑料元件的表面。SEMASPEC 92010950B（UPW配电系统组件塑料表面粗糙度可视化评价初步测试方法）用于表面质量确认。然而，在制药界没有这种类似的标准。对于通过切割生产的塑料零件，有时只能通过特定的附加措施实现 Ra ＜1 μm 的表面值，即无论部件是通过注塑成型还是切割/铣削生产，都起着重要作用。

Materialcompatibility

材料兼容性

It is much more difficult to make astatement about material compatibility. The basic GMP requirement is thatthe plant material does not negatively influence the quality of thepharmaceutical product. A certificate of food suitability is often used as aproof - i.e. that the material is not toxic when consumed in small quantities.Certificates with the following reference serve this purpose:

就材料兼容性做出陈述要困难得多。基本GMP要求是材料对药品质量不产生负面影响。食品适宜性（食品级标准）证明通常用作证明 -即，当少量食用时，材料没有毒性。对此有以下参考：

  • US Federal Standard CFR     21.177

  • 美国联邦标准 CFR     21.177

  • The positive list     of the Federal Institute for Risk Assessment 'Recommendations on     Materials for Food Contact' (formerly 'Plastics Recommendations;     Health Safety Food, Commodities and Feedstuffs Code' (LFGB))

  • 联邦风险评估研究所'食品接触材料建议'（原'塑料建议';健康安全食品、商品和饲料代码'（LFGB）中的准许清单

  • EC1935/2004 (Materials     and articles intended to come into contact with food)

  • EC1935/2004（与食品接触的材料和物品）

  • EC2023/2006 (Good     manufacturing practice for materials and articles intended to come into     contact with food).

  • EC2023/2006（食品接触材料和物品GMP标准）。

However, it may also be useful to providespecifications for compliance with further requirements:

此外，提供符合进一步要求的规范可能也很有用：

  • 3A Sanitary Standard

  • 3A卫生标准

  • EHEDG (European Hygienic     Engineering & Design Group)

  • EHEDG（欧洲卫生工程与设计组）

  • DIN 26055 - hose     assemblies or use in the pharmaceutical and biotechnical industry

  • DIN 26055 - 制药和生物技术行业用软管

  • DIN ISO 3601-3 Form and     surface deviations of o-rings (for pharmaceuticals, observe 'Grade     characteristic S')

  • DIN ISO 3601-3 O型环的形态和表面偏差（对于药品，请遵守'等级特性 S'）

The US Pharmacopoeia also makes statementson the pharmaceutical suitability of plastics and divides them into sixbiocompatibility classes. USP Class VI represents the strictest class and isequivalent to a pharmaceutical authorisation for polymer materials. In orderfor a material to receive a Class VI classification, tests are specified whichmust be performed in external test laboratories. For this purpose, animaltesting shall be carried out to determine acute toxicity (irritation whenswallowed or inhaled), intra-cutaneous reactivity (tissue test) or animplantation test.

美国药典还就塑料的药用性发表了声明，并将其分为六个生物相容性类别。USP VI 类代表最严格的类别，相当于聚合物材料的药品许可。VI 类的材料，规定了必须在外部测试实验室执行的测试。为此，应进行动物试验，以确定急性毒性（吞咽或吸入时的刺激）、皮肤内反应（组织测试）或植入试验。

In biotechnological production, it canalso be useful to specify 'ADI free'. This means that no materials ofanimal origin are used in the plant construction (ADI free = raw materialscontain no Animal Derived Ingredients). Such materials are also BSE and TSEfree (BSE = Bovine Spongiform Encephalopathy; TSE = Transmissible SpongiformEncephalopathy).

在生物技术生产中，规定'无ADI'也很有用。这意味着在工厂施工中不使用任何动物原料（无ADI –原材料不含动物衍生成分）。此类材料也不含BSE和TSE（BSE = 牛海绵状脑病毒;TSE = 传播海绵状脑病毒）。

The pharmaceutical manufacturer himselfmust clarify whether the plastic used is chemically not reacting or interactingwith the pharmaceutical material. Furthermore, the leach-out ofplastic materials is critical in biotechnology, i.e. the clarification of whichsubstances can pass from the plastic into the pharmaceutical material. For thispurpose, the plant manufacturers carry out studies in which - in a worst-casescenario using model solutions - it is tested which substances can be extractedfrom the plastic at all (= determination of extractables). In leachablestudies, the pharmaceutical material is used to check which substances actuallyleach out under real conditions. The results of the studies must then beevaluated toxicologically, taking into account the process, product,application, etc. The results of the studies must then be evaluatedtoxicologically. The pharmaceutical user himself determines whetherleachable/extractable studies by means of risk analyses are required.

制药商自身必须清楚所使用的塑料在化学上是否与制药材料没有反应或相互作用。此外，塑料材料的析出在生物技术中至关重要，即清楚哪些物质可以从塑料进入药品中。为此，工厂制造商进行研究，在最坏的情况下，使用模型方案测试哪些物质可以从塑料中析出（= 可萃取物的测定）。在可析出研究中，使用药物材料用于检查哪些物质在实际条件下渗出。然后，结合工艺、产品、使用等方面，必须对研究结果进行毒理学评估。然后，必须从毒理学上评估研究结果。制药用户自己决定是否需要通过风险分析进行可浸出/可提取的研究。

According to the applicable GMPspecifications (e.g. EU GMP Annex 15), verification of the constructionmaterials must be carried out during qualification. The reason for this is toensure that the plant was built from the materials required by thepharmaceutical manufacturer (the material of the plant must not have anynegative influence on the product). Since not every pharmaceutical manufacturerhas the necessary means for material testing or identification, the materialcertificates come into play:

根据适用的 GMP 标准（例如欧盟 GMP 附录 15），必须在验证期间对建筑材料进行确认。这样做的原因是确保工厂采用制药商要求的材料建造（工厂的材料不得对产品产生任何负面影响）。由于并非每个制药商都拥有进行材料测试或鉴定的必要手段，因此材料证书发挥作用：

  • As a rule, 3.1     certificates (according to EN 10204) are required for stainless steel     components. This ensures that the certificate can be traced back to each     component.

  • 通常，不锈钢部件需要 3.1     证书（根据 EN     10204）。确保证书可追溯到每个组件。

  • In the case of plastic     components, 2.1 certificates are generally accepted. In the case of     certificates used, the system manufacturer himself confirms compliance     with the requirements. However, this does not provide one hundred percent     legal certainty. On the other hand, this standard is also intended for     metal products and less for plastics.

  • 对于塑料部件，通常接受 2.1 证书。在使用证书的情况下，系统制造商自己确认符合要求。然而，这并不能提供百分之百的法律确定性。另一方面，该标准也适用于金属产品，较少用于塑料。

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