PA/PH/OMCL (14) 88 结果的评估和报告附录1B：化验室主管的职责

201410 PA/PH/OMCL(14) 88 结果的评估和报告附录1B：化验室主管的职责

   

OMCL Network of the Council of Europe

QUALITY ASSURANCE DOCUMENT

PA/PH/OMCL (14) 88

Evaluation and Reporting of Results

Annex 1B

ANNEX I B OF THEOMCL NETWORK GUIDELINE

“EVALUATION ANDREPORTING OF RESULTS”

OMCL网络指南“结果的评估和报告”附录1B

RESPONSIBILITIESOF THE LABORATORY SUPERVISOR

化验室主管的职责

Extract from theFDA Guidance for Industry “Investigating Out-of-Specification (OOS) TestResults for Pharmaceutical Production”, chapter III B: Responsibilities of theLaboratory Supervisor

摘自FDA行业指南“药品生产中OOS结果调查”第IIIB“化验室主管的职责”

d timely. Thereshould be no preconceived assumptions as to the cause of the OOS results. Datashould be assessed promptly to ascertain if the results may be attributed tolaboratory error, or whether the results could indicate problems in themanufacturing process. An immediate assessment could include re-examination ofthe actual solutions, test units, and glassware used in the originalmeasurements and preparations, which might provide more credibility forlaboratory error hypotheses.

一旦识别出了一个OOS结果，化验室主管应进行客观及时的评估。不应该对OOS结果的原因有先入为主的想法。应立即对数据进行评估，以确定是否结果可归因于化验室错误，或者结果是否显示生产工艺问题。立即进行的评估可以包括对原始检测和样品制备中所用溶液、检测单元和玻璃仪器的再次检查，这样可以为化验室错误假设获得更多的确定性。

The followingsteps should be taken as part of the supervisor's assessment:

应将以下步骤作为主管评估的一部分来实施：

1.        Discuss the testmethod with the analyst; confirm analyst knowledge of and performance of thecorrect procedure.

1.        与化验员讨论检验方法，确认化验员的是否正确理解检验方法以及是否正确实施检验方法

2.        Examine the rawdata obtained in the analysis, including chromatograms and spectra, andidentify anomalous or suspect information.

2.        检查分析中获得的原始数据，包括图谱，找出其中异常和可疑的信息

3.        Verify that thecalculations used to convert raw data values into a final result arescientifically sound, appropriate, and correct; also determine if unauthorizedor unvalidated changes have been made to automated calculation methods.

3.        确认用于将数据转换为最终结果的计算过程是科学家学合理的、适当的、正确的，还要决定自动计算方法是否有未经授权或无效的变更

4.        Confirm the performanceof the instruments.

4.        确认仪器性能

5.        Determine thatappropriate reference standards, solvents, reagents, and other solutions wereused and that they meet quality control specifications.

5.        确定使用了适当的对照品、溶剂、试剂和其它溶液，且所有的这些化学品均满足其质量标准

6.        Evaluate theperformance of the testing method to ensure that it is performing according tothe standard expected based on method validation data and historical data.

6.        评估检验方法的性能，以保证其实施符合根据方法验证数据和历史数据预期的标准

7.        Fully documentand preserve records of this laboratory assessment.

7.        记录和保留所有这些化验室评估的文件记录

The assignmentof a cause for OOS results will be greatly facilitated if the retained samplepreparations are examined promptly. Hypotheses regarding what might havehappened (e.g. dilution error, instrument malfunction) should be tested.Examination of the retained solutions should be performed as part of thelaboratory investigation.

如果对留下的样品制备物进行及时的检查，将很大程度上帮助找出OOS的原因。如果假设了什么可能发生（例如，稀释错误，仪器故障）的假设，则应进行测试来证明。对留下的溶液的检测应作为化验室调查的一部分来实施。

Examples: 举例

-    Solutions can bere-injected as part of an investigation where a transient equipment malfunctionis suspected. Such hypotheses are difficult to prove. However, reinjections canprovide strong evidence that the problem should be attributed to theinstrument, rather than the sample or its preparation.

-    如果怀疑仪器短时波动，可以重新进样原有溶液，作为调查的一部分。这样的假设很难去证明。但是，重新进样可以提供确凿的证据表明问题应归因于仪器，而不是样品或其制备的溶液。

-    For release ratetesting of certain specialized dosage form drugs that are not destroyed duringtesting, where possible, examination of the original dosage unit tested mightdetermine whether it was damaged during laboratory handling in a way thataffected its performance. Such damage would provide evidence to invalidate theOOS test result, and a retest would be indicated.

-    在对有些特殊的剂型药品测定释放速率时，样品在检测中不会被破坏，如果可能的话，可以对原始制剂样品单元进行测试，可能会确定是否在实验室处理时对其形成损害导致结果差异。这样的损害能提供证据来宣布原OOS结果无效，需要进行复测。

-    Furtherextraction of a dosage unit, where possible, can be performed to determinewhether it was fully extracted during the original analysis. Incompleteextraction could invalidate the test results and should lead to questionsregarding validation of the test method.

-    可能的情况下，可以对一个制剂进行进一步萃取以确定在原来的检测中所进行的萃取是否完全。不完全的萃取可以导致检验结果无效，应质疑检测方法的验证问题。

It is importantthat each step in the investigation be fully documented. Laboratory managementshould ascertain not only the reliability of the individual value obtained, butalso the significance these OOS results represent to the laboratory qualityassurance program. Laboratory management should be especially alert todeveloping trends. As part of an effective quality system, a firm’s uppermanagement should appropriately monitor these trends and ensure that anyproblematic areas are addressed.

调查中的每一步均应进行完整记录。化验室管理不仅应确定所获得的单个值的可靠性，还要确定这些OOS结果代表化验室质量保程序的显著性。化验室管理层应对发展中的趋势保持特别的警觉。作为一个有效的质量体系，一个公司高层管理人员应适当地监测这些趋势，保证对所有有问题的地方都被注意到。

Laboratory errorshould be relatively rare. Frequent errors suggest a problem that might be dueto inadequate training of analysts, poorly maintained or improperly calibratedequipment, or careless work. Whenever laboratory error is identified, the firmshould determine the source of that error and take corrective action to preventrecurrence. To ensure full compliance with the CGMP regulations, themanufacturer also should maintain adequate documentation of the correctiveaction.

化验室错误应相对较少发生。频繁发生错误则表示可能由于以下原因引起了问题，如化验员培训不充分、设备维护不够或仪器校验不适当，或工作粗心。只要识别出了化验室错误，公司则应确定错误的来源，采取纠正措施来预防其再次发生。为保证全面符合CGMP沙堆，生产商还应维护充分的纠正措施的文件记录。

In summary, whenclear evidence of laboratory error exists, laboratory testing results should beinvalidated. When evidence of laboratory error remains unclear, a full-scaleOOS investigation should be conducted by the manufacturing firm to determinewhat caused the unexpected results. It should not be assumed that OOS testresults are attributable to analytical error without performing and documentingan investigation. Both the initial laboratory assessment and the following OOSinvestigation should be documented fully.

总而言之，如果有清楚证据证明化验室存在错误，化验室检测结果应宣布无效。如果化验室错误的证据不清楚，则需要由生产公司展开全面的OOS调查，以决定导致非预期结果的原因。不能假定OOS结果归因于检验错误，而不开展调查和记录。初始化验室评估和随后的OOS调查均应进行完整记录。

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