【文章內(nèi)容簡(jiǎn)介】 bbles were introduced during an injection on a chromatographic system, which other tests indicated was performing properly. Such theories are difficult to prove. However, a reinjection can provide strong evidence that the problem should be attributed to the instrument, rather than the sample or its preparation.如果懷疑設(shè)備瞬間的故障，那么調(diào)查可以重新進(jìn)樣該溶液。如果在色譜系統(tǒng)一次進(jìn)樣期間引入了氣泡，而其它的試驗(yàn)進(jìn)行正常，這是可能發(fā)生的。這樣的推測(cè)很困難去證明。但是，重新進(jìn)樣能有力的證明問(wèn)題與儀器有關(guān)，而不是與樣品或樣品的準(zhǔn)備有關(guān)。! For release rate testing of certain specialized dosage forms, where possible, examination of the dosage unit tested might determine whether it was damaged in a way that affected its performance. Such damage would provide evidence to invalidate the OOS test result, and a retest would be indicated.對(duì)于某一特定制劑的放行檢驗(yàn)，如果可能，檢查一下被測(cè)的這份制劑可以確定是否在什么方面被損壞而影響了其性能。這樣的損壞能提供證據(jù)使OOS檢驗(yàn)結(jié)果無(wú)效，這樣就可以進(jìn)行重新檢驗(yàn)。! Further extraction of a dosage unit can be performed to determine whether it was fully extracted during the original analysis. Inplete extraction could invalidate the test results and should lead to questions regarding validation of the test method.對(duì)一份制劑做進(jìn)一步提取以確定在初次檢驗(yàn)期間是否被充分的提取了。不完全的提取能使檢驗(yàn)結(jié)果無(wú)效，將導(dǎo)致檢驗(yàn)方法驗(yàn)證的問(wèn)題。It is important that each step in the investigation be fully documented. The supervisor should ascertain not only the reliability of the individual value obtained, but also the significance these OOS results represent in the overall quality assurance program. 在調(diào)查的每一步都應(yīng)做充分的記錄，這是很重要的。主管不僅應(yīng)該確定獲得的個(gè)別值的可靠性，也應(yīng)該確定在整個(gè)質(zhì)量保證程序中闡明的OOS結(jié)果的重要性。Supervisors should be especially alert to developing trends.主管應(yīng)該特別警惕發(fā)展趨勢(shì)。Laboratory error should be relatively rare. Frequent errors suggest a problem that might be due to inadequate training of analysts, poorly maintained or improperly calibrated equipment, or careless work. Whenever laboratory error is identified, the firm should determine the source of that error and take corrective action to ensure that it does not occur again. To ensure full pliance with the CGMP regulations, the manufacturer also should maintain adequate documentation of the corrective action.In summary, when clear evidence of laboratory error exists, laboratory testing results should be invalidated. When evidence of laboratory error remains unclear, a failure investigation should be conducted to determine what caused the unexpected results. It should not be assumed that failing test results are attributable to analytical error without performing and documenting an investigation. Both the initial laboratory assessment and the following failure investigation should be documented fully.實(shí)驗(yàn)室錯(cuò)誤應(yīng)該是極少發(fā)生的。頻繁的錯(cuò)誤暗示一個(gè)問(wèn)題，那就是檢驗(yàn)員培訓(xùn)不充分，設(shè)備維護(hù)保養(yǎng)不善或沒(méi)有得到正確校正，或工作粗心。如果實(shí)驗(yàn)室錯(cuò)誤被確定了，企業(yè)應(yīng)該確定錯(cuò)誤的來(lái)源并采取糾正措施去保證錯(cuò)誤不再發(fā)生。為保證完全符合CGMP,生產(chǎn)商應(yīng)該保持充分的糾正措施的記錄。總之，當(dāng)實(shí)驗(yàn)室錯(cuò)誤的證據(jù)已經(jīng)存在，實(shí)驗(yàn)室檢驗(yàn)結(jié)果應(yīng)該作廢。當(dāng)實(shí)驗(yàn)室錯(cuò)誤的證據(jù)仍然不清楚，應(yīng)該進(jìn)行不合格結(jié)果的調(diào)查以確定引起意外結(jié)果的原因。在沒(méi)有進(jìn)行調(diào)查及調(diào)查文件確定之前不應(yīng)該假定失敗的檢驗(yàn)結(jié)果屬于檢驗(yàn)錯(cuò)誤。最初的實(shí)驗(yàn)室評(píng)估和下面的不合格結(jié)果的調(diào)查應(yīng)該被充分的記錄。IV. INVESTIGATING OOS TEST RESULTSOOS結(jié)果調(diào)查When the initial assessment does not determine that laboratory error caused the OOS result and testing results appear to be accurate, a fullscale failure investigation using a predefined procedure should be conducted. The objective of such an investigation should be to identify the source of the OOS result. Varying test results could indicate problems in the manufacturing process, or result from sampling problems. Such investigations present a challenge both to employees and to management and should be given the highest priority.如果最初的評(píng)估不能確定是實(shí)驗(yàn)室錯(cuò)誤造成了OOS結(jié)果且實(shí)驗(yàn)結(jié)果是正確的，應(yīng)按照預(yù)先確定的程序進(jìn)行全方位的不合格調(diào)查。這樣調(diào)查的目的是確定OOS結(jié)果的來(lái)源，變化的試驗(yàn)結(jié)果可能顯示是生產(chǎn)工藝的問(wèn)題或取樣問(wèn)題導(dǎo)致的結(jié)果。這樣的調(diào)查是對(duì)員工和管理者的挑戰(zhàn)應(yīng)給予極高度的重視。The investigation should be conducted by the quality control unit and should involve all other departments that could be implicated, including manufacturing, process development, maintenance, and engineering. Other potential problems should be identified and investigated.調(diào)查應(yīng)該由質(zhì)量控制部門和所有其它相關(guān)的部門完成，包括生產(chǎn)部門，工藝研發(fā)部門，維護(hù)保養(yǎng)和工程部門。其它的潛在問(wèn)題也應(yīng)該被確定和調(diào)查。The records and documentation of the manufacturing process should be fully investigated to determine the possible cause of the OOS results.應(yīng)該充分調(diào)查生產(chǎn)過(guò)程的記錄和文件以判斷引起OOS結(jié)果的可能原因。A. General Investigational Principles一般調(diào)查原則A failure investigation should consist of a timely, thorough, and welldocumented review. 一個(gè)不合格結(jié)果的調(diào)查在于及時(shí)，徹底，和完善的記錄審核 。The written record should reflect that the following general steps have been taken. 記錄應(yīng)該反映通常采取的下列步驟：1. The reason for the investigation has been clearly identified.調(diào)查的原因被清楚的確定。2. The manufacturing process sequences that may have caused the problem should be summarized.對(duì)可能引起問(wèn)題的生產(chǎn)工藝流程進(jìn)行了總結(jié)。3. Results of the documentation review should be provided with the assignment of actual or probable cause.文件審核的結(jié)果提供了實(shí)際的或可能的原因。4. A review should be made to determine if the problem has occurred previously.審核并判斷是否以前發(fā)生過(guò)這類問(wèn)題。5. Corrective actions taken should be described.應(yīng)該描述采取的糾正措施The general review should include a list of other batches and products possibly affected and any required corrective actions taken including any ments and signatures of appropriate production and quality control personnel regarding any material that may have been reprocessed after additional testing.一般性審核應(yīng)該包括可能受影響的其它批和產(chǎn)品的列表，任何必須的糾正行為包括對(duì)復(fù)檢后進(jìn)行返工的物料的適宜的生產(chǎn)和質(zhì)量控制人員的評(píng)論和簽名。B. Laboratory Phase of an Investigation 實(shí)驗(yàn)室階段的調(diào)查A number of practices are used during the laboratory phase of an investigation. These include: (1) retesting a portion of the original sample, (2) testing a specimen from the collection of a new sample from the batch, (3) resampling testing data, and (4) using outlier testing.在實(shí)驗(yàn)室階段的一系列調(diào)查包括：（1）最初樣品一部分的再檢驗(yàn)，（2）從該批中重新取樣樣品的檢驗(yàn)，（3）重新取樣的檢驗(yàn)數(shù)據(jù)，（4）逸出值的檢驗(yàn)1. Retesting重新檢驗(yàn)Part of the investigation may involve retesting of a portion of the original sample. The sample used for the retesting should be taken from the same homogeneous material that was originally collected from the lot, tested, and yielded the OOS results. For a liquid, it may be from the original unit liquid product or posite of the liquid product。 for a solid it may be an additional weighing from the same sampl