2024年4月15日发(作者：腾讯人工客服电话400)

Qualification, Requalification - frequent Obscurities确认、再确认常见的疑问

ECA GMP新闻 2013年10月2日

1、 总则

有关确认、再确认及监测经常会被搞混，尤其是在GMP环境下使用不同的ISO惯用语，

因此以下对于这三个词进行解释并以水系统为例进行举例说明。

根据GMP的大体定义：

确认：确保新的设备、厂房或是即将使用的设备满足既定用途

再确认：保证在变更或是给定周期的周期性设备评估内设备仍处于合格的状态

监测：对于设备或者系统的监督，可以是连续的、也可以是间断的

但是对于再确认而言需要更详细的解释，严格上来说，再确认在欧盟附录十五中并

没有被提及。但是再验证是有相关描述的，而确认常被理解为验证的一部分，再确认也

是必须的，并没有设定的时间标准，但须规定实施定期的再确认。这些并不是需要满足

基本要求，而是与系统相关并要基于风险评估。很多情况下，再确认是3-5年。以注射

剂全自动灯检系统为例，一般是1-2年。很重要的是，再确认不要被理解成验证工作的

重复。经常的，在设备没有变更的范畴内，没必要进行新的测试或测量。再确认就是常

规操作的一个数据回顾。因此，质量相关设备、质量标准参数及一段时期内设备变更及

偏差会被分析到。对于台账的分析也是评估的一部分，还有GMP审查员不会认为年度

质量回顾可代替再确认。

The terms qualification, requalification and monitoring are often mixed up, especially if

the somewhat different language from ISO standards is used in the GMP environment.

Therefore, the three terms will be explained in the following and then differentiated one

from the other by way of the examples watersystem and clean room.

General definitions according to GMP:

Qualification: ensuring in the case of new equipment/facilities or equipment entering

into service that they serve their intended purpose

Requalification*: ensuring that the equipment is still in the qualified state after a change

AND periodical assessment of eqipment within defined time intervals

Monitoring: supervision of equipment or a system - this can be performed continuously

or discontinuously

But the topic of requalification* needs to be considered in more detail. Strictly speaking,

requalification is not mentioned in Annex 15 of the EU Guidelines to Good Manufacturing

Practice which is the guidance document for qualification in Europe. But revalidation is

described (e.g. article 45) and since qualification is considered to be a subset of validation, a

requalification also is required. There is no setting of time standards. But it should be

stipulated when a periodically recurring requalification has to be carried out. These

requirements should not be taken and met on a general basis but system-related and

risk-based. In many cases this is every 3 to 5 years. But in the case of a fully automated

system for the visual inspection of parenterals for example, it could be scheduled already

every 1 to 2 years. It is very important that this requalification is not understood as a

repetition of qualification. Usually, no new tests or measurements are necessary insofar as

the equipment concerned was not changed. Here, requalification is rather a review of data

from routine operation. Hence, the quality-related equipment or specification parameters

are to be considered and analysed as well as the changes in the equipment and the

deviations that took place in the period considered. An analysis of the logbook should also be

part of this evaluation. The document should end with a conclusion that informs about the

equipment's state: equipment still is considered to be qualified: Yes / No. By the way, GMP

inspectors don't consider the annual product review (APR) as substitute for the

requalification.

2、 制药用水为例

在确认中，确认和验证这两个词经常被理解的很模糊。经常的，所谓试机在PQ中执行，

就是用物料代替产品进行设备运行，一般用水来进行。真实的产品至少要在之后的验证

中使用，在水系统中，生产的就是水，因此PQ至少在最后的部分应该被认定为验证。

FDA在很多年前定义的确认三步骤，就是一个企业标准，单独的阶段以取样频次及取样

点数量有所区别，完整的确认持续一年来证明季节波动及不同的操作条件不会影响给水

质量。

一旦变更影响到了水系统的合格状态，再确认须在变更发生后展开。再确认中要阐明这

种情况下须进行风险评估。这些决策的确定过程需要借助于变更控制来明确为什么不去

做确认测试或做哪些再确认测试。

总而言之，再确认由设备相关部分正常运行首次确认阐明的测试所组成，重复再确认对

于整个系统是一个风险，由质量保证来判断是否所有的步骤都被实施。由一个水罐换到

另一个尺寸不同的水罐可能会影响到整个系统，额外的阀门安装可能仅仅是水系统关注

的一小部分，而基于实际情况季节性的影响也是要被评估到的。

如上所述，周期性回顾的再确认应该包括考虑变更、偏差、台账及质量数据的回顾如微

生物、TOC、电导率。

而监测在一定程度上是连续发生的（如在线TOC及电导率），如果系统无连续测试，

是要借助于取样计划的非连续取样（如微生物及TOC）。

Example pharmaceutical water

In the course of the (first) qualification the terms qualification and validation become

blurred. Usually, so-called dry runs are carried out during the performance qualification (PQ).

This means that the equipment is operated with a substitute material instead of the product.

Often the substitute material is water. The real product has to be used in the subsequent

validation at the latest. In a water system, the product manufactured naturally is water.

Therefore, the PQ, at least the later part, also is considered to be a validation. In this case,

the qualification in three steps described by the FDA already many years ago, is industry

standard. But the single phases differ as concerns the frequency of sampling and the number

of sampling points. The complete qualification lasts up to one year in order to prove that

seasonal fluctuations of the feed water's quality as well as different operating conditions

don't influence the quality of the produced water.

A requalification has to be carried out after changes have taken place at the water

system insofar as the change can influence the qualified state of the water system. The risk

analysis carried out in the context of qualification should demonstrate if this is the case. This

decision making process should be carried out by means of the change control system in

order to be able to understand also at a later date why for example no qualification tests

were necessary or why which requalification tests had been determined.

As a general rule, requalification then consists of the tests that have demonstrated

already during the first qualification for the relevant part of the equipment that the

equipment was operating correctly. Should there be a risk for the whole system the