什么是符合 GMP 的设备设计？
It's a frequent question whatGMP-compliant equipment design is or how a system has to be made up inorder to be GMP compliant and suitable for the manufacturing of medicinalproducts/APIs.
这是一个常见问题，什么是符合 GMP 的设备设计？或者一个系统如何构建才能符合 GMP标准并适合药品/API生产？
The short answer is: thesystem has to be qualifiable.
简而答之：系统必须是可确认的。
Since this requires someclarification, here comes a more elaborate answer. To be clear from the start,though, there is no regulatory document or general GMP certification forequipment. This is simply impossible as pharmaceutical manufacturing processesare quite different: dry granulation, tableting, fermentation, sterile fillingand others, for example. And if you add manufacturing processes of the classic(chemical) API production, there are clearly more. Even the product itself canpose various requirements for the production equipment. It makes a bigdifference for the design of a system whether or not the manufactured producthas to be sterile or whether the product is temperature or oxygen sensitive.This certainly has an impact on the system design as well. But even thoughthese requirements are quite diverse, there are some general specificationsthat apply to every GMP compliant equipment design in the GMP regulations:
这里给出一个更详细的答案进行说明。关于设备，并没有针对的监管文件或通用的GMP 认证。这简直是不可能的，因为不同药品生产工艺完全不同：例如，干法制粒、压片、发酵、无菌灌装等。如果再加上(化学)API 的生产工艺，显然还有更多。甚至产品本身也会对生产设备提出各种要求。它对系统的设计有很大的影响，包括生产的产品是否无菌，产品是否对温度或氧气敏感等。这当然也对系统设计有影响。但是，尽管这些要求非常多样，但在 GMP法规中每个符合 GMP 标准的设备设计中，仍有一些通用标准:
The system may not have a negative impact on product quality
该系统不得对产品质量产生负面影响
The system must be easy to clean
系统必须易于清洁
The system has to comply with applicable technical rules
系统必须遵循适当的技术规范
The system must be suitable for its purpose
系统必须符合其用途
These four points are still sovague that further explanation is in order.
这四点仍然含糊不清，需要进一步解释。
The system maynot influence the product quality in a negative way.
系统不得对产品质量产生负面影响。
This simply means that theremay no negative interaction between product-contact surfaces and the product.Neither may the system emit substances, nor may components of the product beabsorbed. Also, there may be no chemical reactions on the surface.
这意味着产品接触表面和产品之间不得有负面的相互作用。系统既不能释放物质,也不能对产品组分有吸附。此外，接触表面不得有化学反应。
The system mustbe easy to clean.
系统必须易于清洁。
This generally applicablesentence can be found in almost every GMP guidance of every country orauthority. Behind it, there are two objectives: for one, all surfaces (in mostcases the product-contact inner surfaces) should be smooth. Cleaning the systemby wiping or rinsing is a lot easier with smooth surfaces than with surfacesshowing score marks. In these score marks, bacteria could survive the cleaningor disinfection, for one; what's more, product residues could also remain thereand merge into a subsequent product. This is called cross contamination.
这句普遍适用的句子可以在几乎每一个国家或机构的GMP指南中看到。其背后包含两个目的：第一，所有表面（主要指与产品接触的内表面）应光洁。这样通过擦拭或冲洗来清洁光洁的设备表面要比划痕的表面容易的多。在这些划痕中，一方面，细菌在清洁消毒后仍能幸存下来。另一方面，产品也会残留在其中并污染后续批次产品。这就是交叉污染啦。
Even worse than rough surfaces in a system are spots which are hard to reach.Most feared are so-called dead spots; places in a system which aren't wetted bythe cleaning agent or which the cleaning agent cannot reach at all. In systemconstruction, these are referred to as dead legs. Dead legs are flooded worseor not at all; they are thus harder to clean, and in the thermal sanitisationthese "branches" take longer to reach the required temperature.
系统中比粗糙表面更严重的是那些难以触及的地方。更加严重的就是盲点和一些清洗剂无法润湿或清洗剂无法触及的地方。在系统构造中，这些地方被称为死脚。死脚要么很湿要么很干。因此难以被清洁，在热消时，这些支路需要更长的时间才能到达所要求的温度。
This requirement also applies to equipment like packaging lines. These machinesalso have to be easily cleanable, so that remaining product but also leafletsand labels can be seen and removed during line clearance.
这个要求也适用于包装线等设备。这些设备同样要求易于清洁，这样剩余产品、说明书、标签可以在清场时被看到并清除。
The system hasto comply with applicable technical rules.
系统应符合相应的技术规范
Legally binding GMPregulations are quite vague, especially when it comes to technical matters.Therefore, the question is: which technical rules have to be followed? This ofcourse depends on the nature of the equipment. In some cases, pharmacopoeias orauthority guidelines can be helpful. Also, it's always good to know therespective ISO standards or VDI guidelines (in Germany). Documents with furtherinformation are frequently published by associations such as the ECA, ISPE, PDAor VDMA, for example. It's important to know here that those rules are rarelybinding. Nevertheless, they are very often used to prove that one's ownprocedure is compliant with or better than the official rules.
具有法律约束的GMP条款是想当模糊的，特别是对技术问题。因此，问题是：应该遵循哪一个技术规范？这当然取决于设备的特性。在很多情况下，药典和当局的指南是有用的。还有，了解相关ISO标准或VDI指南（德国）也有所帮助。ECA、ISPE、PDA和VDMA等协会也常常发布一些更详尽的文件。要知道的是这些要求很少具备约束力。尽管如此，它们常常被用于证明一个公司符合或优于官方要求。
The system mustbe suitable for its purpose.
系统应符合其既定用途
This is one of the mostimportant specifications and at the same time one of hardest to generalize. Itsimply means that the product the system is manufactured with has to satisfythe predetermined quality requirements and therefore has the effect the patientrequires. This point pretty much covers all the other mentioned points, aswell.
这是最重要的一条并且同时是最难概括的标准之一。这意味着系统所生产的产品需要符合既定质量要求，以达到病人要求的疗效。这点几乎涵盖上述所有其他的要求。
The suitability of a system is proven by its qualification. Here too, thequalification depends on the product. A system which is qualified for product Aisn't necessarily suitable for product B, as well. The qualification processbegins with the user requirement specification (URS) and continues in thephases DQ, IQ, OQ and PQ. And this is also the reason why GMP-compliance of asystem or equipment can only be achieved together with the user.
系统的适用性通过其确认来证实。这里，确认取决于产品。一个已经确认过适用于产品A的系统不一定也适用于产品B。确认的流程开始于用户需求（URS）并在DQ、IQ、OQ、PQ阶段继续。这也是为什么一个系统或设备的GMP符合性需要与用户一起来达到。