英国药监局OOS翻译 - 图文(6)

- If a sample is invalidated the remaining level of assurance needs to be carefully considered, is their sufficient residual information? -如果一个样品宣告无效，应认真考虑其残留的保证水平，其是否残留有足够的信息？ - Corrective actions may be appropriate for more than one root cause. -纠正措施应适合一个以上的根本原因。

Stability – OOS/OOT:稳定性-OOS/OOT

Stability OOS/OOT situations should be escalated as soon as the

suspect result is found. Follow the investigation as above for Phase I and Phase II. For OOS Situations Regulatory agencies will require notification within a short time point of discovery due to recall potential. 一旦可疑的结果被发现，稳定性OOS/OOT状态应被升级。按照上述步骤l及步骤ll调查程序开展。OOS管理部门要求在发现后最短时间通知，因为有潜在的召回工作。

If abnormal results are found at any stability interval which predicts that the test results may be OOS before the next testing interval, schedule additional testing before the next scheduled testing interval. This will help better determine appropriate actions to be taken. The stability OOS should link to the Product Recall procedures. 在下一个检测时间段之前的任何稳定性考察时间段如果发现异常结果表明试验结果为OOS，应在下一个时间点检测之前计划增加试验。这将有助于采取更合适的行动。稳定性OOS应与产品召回程序关联。

OOT

To facilitate the prompt identification of potential issues, and to ensure data quality, it is advantageous to use objective (often statistical) methods that detect potential out-of-trend (OOT) stability data quickly. OOT alerts can be classified into three categories to help identify the appropriate depth for an investigation. OOT stability alerts can be referred to as: 为有利于潜在问题的快速识别及确保数据的质量，使用客观方法（经常为统计方法）快速确定潜在的OOT是有益的。OOT警报可分为三类以帮助识别调查的合适深度。OOT稳定性警报可被称为： ? analytical,分析的

? process control, and 过程控制，和 ? compliance alerts, 合规性 警报

As the alert level increases from analytical to process control to compliance alert, the depth of investigation should increase. 警报水平从分析警报、过程控制警报到合规性警报逐渐增加，调查深度也逐步增加。

Stability:

– A compliance alert defines a case in which an OOT result suggests the

potential or likelihood for OOS results to occur before the expiration date within the same stability study (or for other studies) on the same product. - 合规性警报定义为此种情况：OOT结果暗示在有效期之前该产品用该稳定性考察方法会有潜在的或

可能的OOS结果。

– The stability OOS should link to the Product Recall procedures. -稳定性OOS应与产品召回程序关联。

– Historical data are needed to identify OOT alerts. -需要用历史数据来识别OOT警报

– An analytical alert is observed when a single result is aberrant but within specification limits (i.e., outside normal analytical or sampling variation and normal change over time). - 分析警报触发：当单个结果异常但是在标准范围内（即 超出正常分析结果或取样差异及随时间的正常变化。

Phase III Investigation

The phase 3 investigation should review the completed manufacturing

investigation and combined laboratory investigation into the suspect analytical results, and/or method validation for possible causes into the results obtained. 步骤lll调查应当检查完成的生产调查，及与可疑结果关联的实验室调查，和/或与结果关联的为寻找可能原因而开展的方法验证。

? To conclude the investigation all of the results must be evaluated. 所有的结果必须得到评估后才能结束调查，

? The investigation report should contain a summary of the investigations performed; and a detailed conclusion. 调查报告应包含调查执行过程的概要，以及详细的结论。

? For microbiological investigations ,where appropriate, use risk analysis tools to support the decisions taken and conclusions drawn. It may not have been possible to determine the actual root cause therefore a robust most probable root cause may have to be given. 对于微生物实验调查，应适当的使用风险分析工具以支持做决定和下结论。可能不会找到真正的原因，因此最可能的根本原因应找到。

? The batch quality must be determined and disposition decision taken. 该批产品质量必须给予确定，并制定处理措施。

? Once a batch has been rejected there is no limit to further testing to determine the cause of failure, so that corrective action can be taken. 一旦该批产品判定不合格，没有限制开展进一步的试验以确定失败原因，以便执行纠正措施

? The decision to reject cannot be reversed as a result of further testing. 不合格的决定不能因为进一步的试验结果而得到逆转。

? The impact of OOS result on other batches, on going stability studies, validated processes and testing procedures should be determined by Quality Control and Quality Assurance and be documented in the

conclusion, along with appropriate corrective and preventive actions. OOS结果对其他批次、进行中的稳定性研究的影响，应有QC和QA确定验证过程和试验程序，并在结论中书面说明，并附适当的CAPA活动。

Conclusion:

– If no laboratory or calculation errors are identified in the Phase I and Phase II there is no scientific basis for invalidating initial OOS results in favour of passing retest results. All test results, both passing and suspect, should be reported (in all QC documents and any Certificates of Analysis) and all data has to be considered in batch release decisions. -如果在步骤l及步骤ll中未发现实验室或者计算错误，那么就没有科学的根据使原OOS结果无效而支持过去的复检结果。所有试验结果，包括以往的和此怀疑结果应报告（在所有QC记录中及任何的检验报告中），所有数据应在批放行决定时予以考虑。

– If the investigation determines that the initial sampling method was inherently

inadequate, a new accurate sampling method must be developed, documented, and reviewed and approved by the Quality Assurance responsible for release. A consideration should be given to other lots sampled by the same method. -如果调查确定原来的取 …… 此处隐藏：4962字，全部文档内容请下载后查看。喜欢就下载吧 ……