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I摘要研究背景：偏差是药品生产过程中常见的一种现象，生产过程中的人、机、料、法、环、测各个方面的异常均会引起偏差的出现。偏差的急时上报、系统调查、正确处理及制定改进措施是保证产品质量的有力措施。但是由于生产环节的复杂多样，许多偏差由于缺乏系统性调查，最终未能找到偏差产生的根源，致使偏差反复出现。针对上述情况，本文试图以氟康唑片溶出度异常的偏差调查为例，建立一整套系统偏差调查流程，为今后在大生产中出现的偏差，建立标准偏差调查模板。研究方法：采用风险管理的方法，利用鱼刺图法，对可能引起偏差的人、机、料、法、环各个因素时行评估和分析，最终确定关键控制参数，并对其时行分析。研究结论：本次偏差主要发生在原辅料相溶性存在一定问题，实验结果显示不同厂家的原辅料由于不同的生产工艺，所含杂质不同，经过生产过程中的湿热处理后会发现一定的反应，可能会产生新的物质，导致药品质量发现变化。通过总结本次偏差调查过程，我们针对生产过程偏差建立了偏差标准调查模板。在对偏差进行分析时，应依据风险评估的原则，对人、机、料、法、环、测各个方面进行评估，确定关键控制参数，再针对这此关键控制参数进行调查分析，避免盲目的用主观经验去判断偏差的发生原因。关键词：偏差调查；氟康唑；溶出度IIEstablishaDeviationInvestigationProcedureforOOTResult—ApplytheRiskManagementToolAbstractBackground:Itisverycommontofinddeviationsduringpharmaceuticalmanufacturingprocessbecauseofvariousabnormalaspectsofthemachine，material，method，ring，measuringandsoon.Itisnecessarytoreportdeviationstimely，investigatethesystemanddevelopimprovementmeasurescorrectlytoensurethequalityoftheproduct.However，duetothecomplexityanddiversityoftheproductionchain，manydeviationsrecuragainandagainbecauseoflackingofsystematicinvestigationandfailingtofindtherealcausesofdeviations.Thispaperattemptstotaketheabnormaldissolutiondeviationsurveyoffluconazoletabletsforexampletoestablishasetofsystemofdeviationinvestigationprocess.Wehopethismodelwillbethestandarddeviationsurveyinfuturelarge-scaleproductiondeviationinvestigation.Researchmethods:Thispaperusesriskmanagementmethodsandfishbonediagrammethodstoassessandanalyzevariousaspectsofthemachine，material，method，ring，measuringandsoon.Wewanttoultimatelydeterminethecriticalcontrolparameterandanalyzeitstimelinebythesemethods.Conclusions:Thedeviationoccursmainlyincompatibilityofdifferentrawmaterials.Theexperimentalresultsshowsthatdifferentproductionprocesseswillgeneratedifferentimpuritieswhichwouldleadtoreactionsaftermoistheattreatmentintheproductionprocessandtheninducethechangesofdrugquality.Weestablishastandarddeviationsurveymodelbysummarizingthedeviationinvestigationprocess.Weshouldbaseontheprinciplesofriskassessmenttoassessvariousaspectsofthehuman，machine，material，method，ringandmeasuringandsoonandtodeterminethecriticalcontrolparameters.Itisnecessarytoinvestigatethesecriticalcontrolparameterstoavoidjudgingthecauseofthedeviationbyourblindandsubjectiveexperience.Keywords:deviationinvestigation，Fluconazoledissolution3目录第1章引言...............................................................................................................................................11.1研究背景............................................................................................................................11.1.1偏差概念及分类：..........................................................................................................11.1.2偏差管理的重要性及意义..............................................................................................11.1.3偏差管理的一般步骤及难点：......................................................................................21.1.4我国偏差管理现状：......................................................................................................21.1.5常见偏差调查缺陷：......................................................................................................41.2研究目的及意义.................................................................................................................51.3研究结果.............................................................................................................................5第2章研究方法.....................................................................................................................................62.1生产过程偏差调查流程简介.............................................................................................62.2实例演示：以氟康唑片溶出度异常为例阐述偏差调查流程..........................................72.2.1氟康唑片溶出度异常偏差的背景描述.........................................................................72.2.2氟康唑片工艺处方：.................................................................................................72.2.3氟康唑片工艺流程图......................................................................................................82.2.4氟康唑片生产工艺介绍..................................................................................................92.2.5溶出度概念及偏差内容的理解......................................................................................92.2.6列举影响溶出度的生产工序评估..................................................................................92.2.7.1起始物料检查：.........................................................................................................112.2.7.2氟康唑片前处理工序的偏差调查............................................................................132.2.7.3氟康唑片原辅料称量、干混工序偏差调查：.........................................................152.2.7.4氟康唑片粘合剂的配制及加入工序偏差调差：......................................................162.2.7.5氟康唑片湿混、制粒工序偏差调差：.....................................................................172.2.7.6氟康唑片干燥工序偏差调差：.................................................................................172.2.7.7氟康唑片整粒、总混工序偏差调查：.....................................