【正文】 成品的混合物。 for a solid it may be an additional weighing from the same sample posite that had been prepared by the analyst. 調(diào)查部分工作包括最初檢驗(yàn)樣品的再檢驗(yàn)。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。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。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。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)過程的記錄和文件以判斷引起OOS結(jié)果的可能原因。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。這樣調(diào)查的目的是確定OOS結(jié)果的來源，變化的試驗(yàn)結(jié)果可能顯示是生產(chǎn)工藝的問題或取樣問題導(dǎo)致的結(jié)果。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。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。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。頻繁的錯(cuò)誤暗示一個(gè)問題，那就是檢驗(yàn)員培訓(xùn)不充分，設(shè)備維護(hù)保養(yǎng)不善或沒有得到正確校正，或工作粗心。Supervisors should be especially alert to developing trends.主管應(yīng)該特別警惕發(fā)展趨勢(shì)。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。! 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。! 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。這樣的推測(cè)很困難去證明。Examples:例如! Solutions can be reinjected as part of an investigation where a transient equipment malfunction is suspected. This could occur if bubbles 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。可以對(duì)所發(fā)生的事情的假設(shè)（如：稀釋錯(cuò)誤、儀器故障）進(jìn)行檢測(cè)。6. Document and preserve evidence of this assessment.記錄并保存評(píng)估的證據(jù)。3. Confirm the performance of the instruments.確認(rèn)儀器性能4. Determine that appropriate reference standards, solvents, reagents, and other solutions were used and that they meet quality control specifications.確定使用了合適的參照標(biāo)準(zhǔn)品、溶媒、試劑和其它溶液，并且它們符合質(zhì)量控制標(biāo)準(zhǔn)。 confirm analyst knowledge of and performance of the correct procedure.與檢驗(yàn)員討論檢測(cè)方法；確認(rèn)檢驗(yàn)員知道并執(zhí)行了正確的程序。The following steps should be taken as part of the supervisor39。應(yīng)該迅速評(píng)估數(shù)據(jù)以確定結(jié)果是否屬于實(shí)驗(yàn)室錯(cuò)誤，或該結(jié)果是否顯示是生產(chǎn)過程的問題。s assessment should be objective and timely. There should be no preconceived assumptions as to the cause of the OOS result. Data should be assessed promptly to ascertain if the results may be attributed to laboratory error, or whether the results could indicate problems in the manufacturing process. An immediate assessment could include reexamination of the actual solutions, test units, and glassware used in the original measurements and preparations, which would allow more credibility to be given to laboratory error theories.一旦OOS結(jié)果被確定，主管應(yīng)該客觀的和及時(shí)的進(jìn)行評(píng)估。這些相同的責(zé)任適用于合同實(shí)驗(yàn)室的檢驗(yàn)員。If errors are obvious, such as the spilling of a sample solution or the inplete transfer of a sample posite, the analyst should immediately document what happened. Analysts should not knowingly continue an analysis they expect to invalidate at a later time for an assignable cause (., analyses should not be pleted for the sole purpose of seeing what results can be obtained when obvious errors are known). These same responsibilities extend to analysts at contract testing laboratories.如果錯(cuò)誤是明顯的，如：樣品溶液有灑出或樣品成分的未完全轉(zhuǎn)移，檢驗(yàn)員應(yīng)該立即記錄所發(fā)生的情況。當(dāng)獲得意想不到的結(jié)果且沒有明顯的理由時(shí)，應(yīng)該保留樣品制備液且檢驗(yàn)員應(yīng)該通知主管。在決定是否使用可疑期間之前的數(shù)據(jù)前，應(yīng)鑒別故障的原因并予以糾正。例如：在色譜系統(tǒng)中，在進(jìn)行色譜檢測(cè)期間內(nèi)間隔一段時(shí)間進(jìn)樣對(duì)照品溶液去測(cè)定漂移、噪聲和重復(fù)性。 (b)(4))，檢驗(yàn)員應(yīng)該保證只有符合既定標(biāo)準(zhǔn)的儀器才能使用和所有的儀器都經(jīng)過的校正。In accordance with the CGMP regulations (167。A. Responsibility of the Analyst檢驗(yàn)員的責(zé)任 The first responsibility for achieving accurate laboratory testing results lies with the analyst who is performing the test. The analyst should be aware of potential problems that could occur during the testing process and should watch for problems that could create OOS results.從事測(cè)試的檢驗(yàn)員的首要責(zé)任是取得正確實(shí)驗(yàn)室檢驗(yàn)結(jié)果。調(diào)查的最初階段應(yīng)該在試驗(yàn)溶液丟棄前，對(duì)實(shí)驗(yàn)室數(shù)據(jù)正確性進(jìn)行最初評(píng)估，這樣，假定認(rèn)為是實(shí)驗(yàn)室錯(cuò)誤或儀器故障，可以用原溶液測(cè)定。To be meaningful, the investigation should be thorough, timely, unbiased, welldocumented, and scientifically defensible. The first phase of such an investigation should include an initial assessment of the accuracy of the laboratory39。即使因OOS結(jié)果判斷了不合格批，仍必須進(jìn)行調(diào)查以確定該結(jié)果是否影響到同種產(chǎn)品其它批號(hào)或其它產(chǎn)品。(f)章節(jié)規(guī)定不符合既定標(biāo)準(zhǔn)和其它相關(guān)質(zhì)量控制標(biāo)準(zhǔn)的產(chǎn)品不得放行。有關(guān)實(shí)驗(yàn)室操作一般性CGMP法規(guī)可以在211部分，分目I (實(shí)驗(yàn)室控制)和分目 J (報(bào)告和記錄)找到。 如果是非申請(qǐng)產(chǎn)品的質(zhì)量標(biāo)準(zhǔn)，可以在法定標(biāo)準(zhǔn)中找到或由企業(yè)自已建立。CGMP要求的實(shí)驗(yàn)室檢驗(yàn)，必須確定成分、容器和封口材料、生產(chǎn)用輔料、成品符合標(biāo)準(zhǔn)要求，包括穩(wěn)定性。II. BACKGROUND 背景FDA considers the integrity of laboratory testing and documentation records to be of fundamental importance during drug manufacturing. Laborat