OOS调查20问答(中英对照)

Out of specification (OOS) FAQs(OOS 问答)

　1. Has the MHRA produced any guidance?A (MHRA 已经发布相关指南了吗？) Out of specification investigations

　(194Kb) OOS 调查指南

　2. Why is there a need to conduct an investigation of an OOS test result if the decision has been taken to reject the batch?( ( 如产品已经拒绝放行了，为什么 还对 S OOS 测试结果进行调查？) ) A phase 1 investigation should always be conducted in order to try and establish an assignable cause and determine whether any other batches may be affected. In determining the assignable and root cause of the problem appropriate corrective and preventative actions can be undertaken. 调查阶段 1 应始终执行，以便查出可明确的原因，并确定是否有受影响的批次。一旦找出引起问题的可明确的原因和根源，就需要承诺进行恰当的纠正和预防行动。

　 3. Who should investigate OOS?( ( 谁应该调查 OOS ？) ) Both the manufacturers and the laboratories should be involved in the investigation.

　生产部门和实验室应参与调查。

　4. How is an out of trend result handled?T (OOT 结果应如何处理？) ) Results that are out-of-trend (OOT) should be handled similarly to OOS investigations.

　OOT 结果处理应该与 OOS 调查类似。

　5. Is it acceptable for a contract laboratory (contract acceptor) to use the contr act givers’ procedure when handling OOS results?( ( 当出现 OOS结果时，合同实验室( ( 受托方) ) 是否需要采用委托方程序进行调查吗？) ) There is an expectation that contract acceptors should follow their own procedures and that these should be flexible enough to accommodate the needs of the contract giver.

　建议受托方采用自己的程序，同时应有足够的说服力以适应委托方的要求。

　It is assumed that the contract giver has assessed the contract acceptor’s procedure for handling of out of specification results and has agreed it as being suitable for their intended purpose. Any issues should have been discussed prior to conducting any analysis.

　假设委托方已经对受托方 OOS 调查程序进行了评估，并同意其是适合他们的预期目的。在进行任何分析前对各种问题进行了讨论。

　6. How is a meaningful OOS investigation conducted?( ( 怎样执行一个严谨的 的 S OOS 调查？) ) A meaningful OOS investigation should be thorough, timely, unbiased, well-documented, and scientifically defensible.

　一个严谨的 OOS 调查应该全面、及时、公正、证据充分和科学合理。

　7. At what point should a manufacturing investigation be initiated?( ( 生产过程调查何时启动？) ) This should be initiated as part of the phase II investigation and as a result of the phase 1 investigation not revealing a conclusive laboratory error or the error remains unclear with no assignable cause.

　调查阶段 1 未证明是实验室错误或为未知错误时，在调查阶段 2 启动。

　8. What should be done if unexpected results are obtained and there is no obvious explanation?( ( 如果出现非期望的结果，且没有明显解释 时，应该如何处理？) ) These are also referred to as aberrant/anomalous. Preliminary laboratory investigation should occur and they should be handled similarly to OOS investigations.

　这种情况属于反常的/例外的结果。应进行实验室预调查，调查方式同 OOS 类似。

　9. Under what circumstances could test resul ts become invalid? If there is clear evidence of a determinant error. Or where the system suitability/method validity checks fail.

　10. What should be done in the case where part way through testing the analyst realises there is an error?( ( 通过部分测试方式，分析员认识 到有错误发生时，应该如何处理？) ) If there is clear evidence of the error and it can be corrected without compromising the results or the validity of the method; for example a dilution error 20 ml volumetric flask used instead of a 25 ml volumetric then it should be handled as a deviation and the results are still valid. If there is any doubt as to the impact of the error which could mean the results may not be accurate, for example sample spillage then the testing should be stopped and the issue handled as a deviation to explain what happened.

　如果错误的证据明显，且不需要对测试结果或验证的方法妥协就可以改正，例如稀释错误(20ml 量瓶，实际用 25ml 量瓶)，应该作为偏差处理，测试结果依然有效。

　如果怀疑错误会引起测试结果不准确，例如样品溢出，测试应该终止，问题按偏差处理，以解释发生了什么。

　11. When should the analyst inform the supervisor that they have an OOS results?( ( 当分析员遇到 S OOS 结果，应在什么时候通知主管？) ) In the first instance, the analyst will be responsible for the preliminary laboratory investigation. This will involve them checking their work and confirming that there is no obvious error prior to informing their supervisor and initiating a phase 1 investigation. This should be done within a timely manner, preferably on the day of generating the results.

　在第一现场，分析员有责任进行实验室预调查。包括检查他们的工作，在通知主管前确认没有明显错误，启动调查阶段 1。这些工作应及时进行，最好在 OOS 结果出现的当天。

　12. What should be done when the phase 1 investigation does not reveal an assignable cause or evidence of error remains unclear?( ( 当调查阶段 1 1未发现明确的原因或错误仍然未知，应 如何处理？) )

　A phase II investigation is initiated, which will involve communication between the laboratory and the manufacturer/contract giver. The decision to undertake any further testing should be agreed and approved within a pre defined testing plan.

　启动调查阶段 2，包括实验室与生产部门/委托方的沟通。执行任何进一步测试均应在经批准事先明确的测试计划内进行。

　13. How many repeat tests should be conducted?( ( 重新测试允许被执行多少次？) ) The minimum number of retests should be documented within the procedure and be based upon scientifically sound principles. Any statistical review with regards to %RSD and repeatability should relate to the values obtained during method validation, ie accuracy, precision and intermediate precision. The number of retests should be statistically valid.

　重新测试最少次数应在程序中规定，基于科学全面原则。对于 RSD 和重复性任何统计评估应与方法验证过程中获得的数值关联，如准确度、精密度和中间精密度。重新测试的次数应符合统计学要求。

　14. What should be done if after retesting there is a combination of OOS results and pass results?( ( 如果重新测试后，产生 S OOS 测试结果组合且 符合规格要求，应该如何处理？) ) All results should be reported unless there is clear evidence of a determinant error or an assignable cause that could invalidate any of the results.

　应报告所有测试结果，除非有明显的决定性错误或能否定任何测试结果的明确原因。

　15. What should happen if the OOS investigations are inconclusive?( ( 如果 果 S OOS 调查没有结果，应该如何处理？) ) The certifying qualified person should fully consider all of the information prior to making any decisions as to the final disposition of the batch. Any decision to release a batch where OOS results have not been invalidated should come only after a full investigation has shown that the OOS result does not reflect the quality of the batch. In making such a decision quality assurance and the Qualified Person should always err on the side of caution.

　在对产品批做出任何最终处置决定前，经认证资格人员应全面评估所有的信息。当 OOS 调查结果没有证明 OOS 无效时，只有当所有调查显示此 OOS 结果不影响产品批质量后，才能做出任何放行决定。

　16. When is it acceptable to average tes t results?( ( 什么时候可以平均测试结果？) ) Where averaging of separate tests is appropriately specified by the test method, a single averaged result can be reported as the final test result. The validity of averaging depends upon the sample and its purpose. Using averages in the case of microbiological assay can provide more accurate results because of the innate variability of the microbiological test system. For example the kinetic scan of individual wells or endotoxin data from a number of consecutive measurements or with HPLC consecutive replicate injections from the same preparation where the determination is considered one test one result.

　当分析方法允许对多个单个测试结果进行平均时，一个平均结果可报告为最终测试结果。平均结果有效性取决于样品和它的目的。在微生物含量测试使用平均结果能带来更高的准确性，因为微生物测试系统的先天变异特点。例如，单井的动态扫描或连续测量的内毒素数据或者 HPLC 用同一样品连续进样的数据均可作为一个测试数据。

　17. When is it not acceptable to average test results?( ( 什么时候不可以平均测试结果？) ) Averaging cannot be used in cases when testing is intended to measure variability within the product, such as powder blend/mixture uniformity or dosage form content uniformity. In the context of additional testing performed during an OOS investigation, averaging the result(s) of the original test that prompted the investigation and additional retest or resample results obtained during the OOS investigation is not appropriate because it hides variability among the individual results.

　当测试产品内在均一性时，不能使用平均值，如粉末混合均匀度或者含量均匀度。就 OOS 调查过程中执行的额外测试而言，平均引起调查的原始测试结果和在 OOS调查中的额外复检或重新取样检验结果是不恰当的，因为在各单个测试结果中隐藏着不均匀。

　18. At what stage should retesting occur?( ( 在什么阶段应进行复检？) ) Retesting occurs at phase II of the investigation. The initial hypothesis testing can involve re-measurement of the original preparation or working solutions, however retesting is when the original sample or composite sample is used to perform analysis. Hypothesis testing and retesting are part of the phase II investigation. Only if the original sample is depleted or compromised should a new sample be used. 复检在调查阶段Ⅱ发生。最初的假设检验可能包括原始标准溶液或样品溶液再测试，然而复检是原始样品或混合样品被用于执行分析时。假设检验或复检是调查阶段Ⅱ的一部分。仅当原始样品不够或被怀疑时，进行重新取样。

　19. At what st age should re- - sampling occur?( ( 在什么阶段进行重新取样？) ) Re-sampling at phase II of the investigation should only occur if the original sample is depleted or compromised and the same method should be used. If the investigation determines that there were errors with the initial sampling method only then should a new accurate sampling method be developed, qualified and documented.

　重新取样在调查阶段Ⅱ只能在发生，且在原始样品不够或被怀疑时启动，取样方法应相同。如果调查发现初始取样方法存在问题，应建立一个新的正确取样方法，并被文件化批准。

　20. When is it appropriate to use outlier tests( ( 什么时候使用离群测试结果 是合适的？) )? ? Statistical analysis for Outlier test results can be as part of the investigation and analysis. However for validated chemical tests with relatively small variance and that the sample was considered homogeneous it cannot be used to justify the rejection of data. 离群测试结果统计分析可以作为调查和分析的一部分。然而，已经验证的相对标准偏差小的化学测试方法，且样品被认为是均匀的，这种情况下，测试结果不能被作为拒绝数据。

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