Validation deviations are just a part of life when you are working through validation protocols and test scripts; it’s highly unlikely that you will ever complete a full validation project without raising the odd validation deviation here and there.

 

执行验证方案或测试文档的过程中，验证偏差会是其中的一部分；在完成一个完整的验证项目时，几乎不可能不产生一些奇怪的验证偏差。

 

Simple Deviations

 

简单偏差

 

Simple deviations are usually classified as documentation or protocol errors, these errors are usually found prior to execution or are “obvious” errors or typos. These deviations have no impact on the validation and offer to real risk to the validation process.

 

简单偏差通常被归类为文档或方案错误，这些错误通常在执行之前被发现，或者是“明显的”错误或打字错误。这些偏差对验证没有影响，没有给验证过程带来真正的风险。

 

Examples of simple deviations include:

 

简单偏差的示例包括：

 

Incorrect specification for product

 

产品标准不正确

 

Loss of power to the equipment being tested

 

被测试的设备断电

 

Non Critical Deviations

 

非严重偏差

 

Non-critical deviations are errors in the protocol or execution of the validation which have no impact on the validation, there errors are normally found during or after the execution. It is good practice to carry out an assessment to determine if the deviation has any impact.

 

非严重偏差是方案或验证执行中的错误，对验证没有影响，通常在执行期间或之后发现错误。最好的做法是进行评估，以确定偏差是否有任何影响。

 

Examples of non-critical exceptions include:

 

非严重偏差的示例包括：

 

Operator not trained to perform the operation

 

操作人员未接受操作培训

 

Critical Deviations

 

严重偏差

 

Critical deviations are errors which have an impact on the validation, these errors are found during or after execution. It is good practice in this scenario to carry out an assessment to determine the impact if any.

 

严重偏差是对验证有影响的错误，这些错误在执行期间或之后发现。在这种情况下，最好的做法是进行评估，以确定是否有影响。

 

Examples of critical exceptions include:

 

严重偏差的示例包括：

 

Acceptance criterion failure

 

不符合接受标准

 

Deviation Process Flow

 

偏差处理流程

 

SME involvement throughout the deviation process is critical. A CAPA may not be needed for simple events, but consider a CAPA if there are many of them or the same ones repeatedly.

 

SME参与整个偏差过程至关重要。简单的事件可能不需要CAPA，但如果有许多事件或重复的相同事件，则考虑使用CAPA。

 

General Process Considerations

 

一般流程考虑

 

It is advisable to commence with the resolution process as soon as the event is observed. Involve the SME’s/QA throughout the process as appropriate and get agreement on next steps and/or results prior to execution, or after the completion. Immediately notify the relevant SME/QA if there is any potential Product/Material impact. Conduct a risk assessment to determine the impact and actions to be taken.

 

一旦观察到事件，建议立即开始解决过程。在适当的情况下让SME /QA参与整个过程，并在执行前或完成后就后续步骤和/或结果达成一致。如果有任何潜在的产品/物料影响，立即通知相关的SME/QA。进行风险评估，以确定影响和应采取的措施。

 

Types of Deviations

 

偏差的类型

 

Typographical errors

 

排字错误

 

These errors are found prior to execution or are “obvious” errors or typos.

 

这些错误是在执行之前发现的，或者是“明显的”错误或打字错误。

 

External Issues

 

外部错误

 

Failures caused by factors external to the process or system under test.

 

由被测试过程或系统的外部因素引起的故障。

 

Execution Errors

 

执行错误

 

Failures to follow instructions within the Test Document or referenced procedures.

 

未能遵循测试文档或引用程序中的说明。

 

Document Generation Errors

 

文件错误

 

Incorrect detail in procedures, acceptance criteria or referenced documentation.

 

程序、接受标准或所引用文件中的细节不正确。

 

Acceptance Criteria Failures

 

不符合接受标准

 

Pre-defined acceptance criteria have not been achieved.

 

不符合既定的接受标准。

 

Should the Testing Stop?

 

是否应该停止验证？

 

This is always a questions that raises a lot of debate within the validation testing world. The decision to stop a validation mid-execution is something that will cost of the company both time and money so a process needs to be in place to make a critical decision like this.

 

这是一个在验证测试领域引起很多争论的问题。在执行过程中停止验证的决定将花费公司的时间和金钱，因此需要一个适当的流程来做出这样的关键决策。

 

Initially the Impact Score should be analysed to determine the severity of the deviation (Event severity X Testing Stage = Impact), then a consultation with the SEM’s and QA is required to see if they are willing to live with such a failure. Usually this will open more questions than it solves so be prepared to have your own timelines impacted as a result.

 

最初应该分析影响的程度以确定偏差的严重程度（事件严重性X测试阶段=影响），然后需要与SEM和QA商量，看看他们是否愿意忍受这样的失败。通常这会带来比它解决的问题更多的问题，所以准备好你自己的时间线会因此受到影响。

 

Example l

 

案例1

 

Deviation - Product temperatures are recorded during the validation run using 10thermocouples placed in the product, evenly distributed throughout the load and linked toa data logger. At the completion of the cycle, it is discovered that one of thethermocouples has fallen out of the product container it had been placed in.

 

偏差：在验证运行期间使用放置在产品中的10个热电偶记录产品温度，均匀分布在整个负载并连接到数据记录器。在循环完成时，发现其中一个热电偶从放置它的产品容器中掉了出来。

 

Investigation & corrective actions - The other 9 thermocouples have provided valid dataThe location of the thermocouple that fell out of the product container is assessed todetermine if this location is a "worst-case’location within the load. If it is a worst-caselocation, then repetition of the study may be warranted. If not, then it may be possible to write a rationale that explains why the missing data point does not negate the validation.

 

调查和纠正措施：其他9个热电偶已提供有效数据。评估从产品容器中掉落的热电偶的位置，以确定该位置是否为负载内的“最差情况”位置。如果这是一个最差情况，那么重复研究可能是必要的。如果不是，那么可以论证解释为什么丢失的数据点不会否定验证。

 

Example 2

 

案例2

 

Deviation - In the process validation of a solid oral dosage product, 3 samples are to betaken from each shift (beginning, middle and end) during compression. The compressionstep for the proposed batch size takes on average 8 shifts to complete. During validationbatch #2, the samples are forgotten during the night shift.

 

偏差-在固体口服制剂产品的工艺验证中，压片过程中每班（开始、中间和结束）取3个样品。验证的批量大小的压片步骤平均需要8个班次才能完成。在验证第2批的过程中，夜班期间忘记取样。

 

Investigation & corrective actions - A temporary corrective action is put in place toensure that all samples from all shifts are collected for the remainder of validation batch#2 and #3. It is determined that a sufficient amount of data has been obtained to allowextrapolation of the data to cover the 3 missing samples from validation batch #2.particularly since samples were neither the start nor the end of the batch. Had the missingsamples been from a potentially critical stage in the compression the deviation may haverequired a 4th batch to replace the missing samples.

 

调查和纠正措施-采取临时纠正措施，以确保第2批剩余部分和第3批所有班次的样品都被收集。确定已获得足够数量的数据，以允许对数据进行外推，以覆盖验证批#2中的3个缺失样本。特别是因为样品既不是批次的开始也不是结束。如果丢失的样品来自压片的潜在关键阶段，则偏差可能需要第4批来替换丢失的样品。

来源：GMP办公室

关键词： 验证偏差