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Corrective Action and Preventive Action(CAPA)预防纠偏措施GMP Training Module 4What is said in cGMP book?Sec.211.192 Production record review.All drug product production and control records,including those for packaging and labeling,shall be reviewed and approved by the quality control unit to determine compliance with all established,approved written procedures before a batch is released or distributed.Any unexplained discrepancy(including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records)or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated,whether or not the batch has already been distributed.The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.A written record of the investigation shall be made and shall include the conclusions and followup.产品记录复查所有药品生产和控制记录，包括包装和标签记录，须按全部已制订通过的程序复查和认可。此复查和认可应在该批药品发放或销售前完成。一些不可解释性差异（包括超过在主要生产和控制记录中制订的最大或最小百分数的理论产量的百分数）或一批或任何一个成份不符合其规格中任一项，则应作彻底调查则应作彻底调查，不管这批药品是否已销售。这种调查应提高扩展到该同一药品的其他批号和与此具体的不合格或差异相联系的其它药品。调查调查应写成文字记录，包括结论和继续跟踪。应写成文字记录，包括结论和继续跟踪。4What are the symptoms of an effective CAPA system?好的预防纠偏系统有那些特征？A reduction in quality issuesA reduction in the severity of issuesMore preventive actions over timeMore consistent products/processesImproved customer satisfactionBetter business results 5What are the symptoms of a less than effective CAPA system?不好的预防纠偏系统有那些特征？Recurring issues Inability to“manage”the many sources of quality data to understand early trends and issuesMore reaction than preventionResources($)are spent on“handling”failure rather than learning from it and preventing“more of the same”Field issuesWhat are FDA enforcements on CAPA?FDA对不称职的CAPA有何措施Ineffective CAPA system is one of the most commonly found problems in FDA inspection report and warning letters.Nonconformities are cited during inspection,and corrective action plan required.Warning Letter more serious,available to the public Fines,stop product shipmentIs your CAPA system effective?你们的CAPA系统如何？Written procedures?ExampleCAPA team/Investigation committee?有无文件？预防纠偏团队/调查委员会Results?Do you have a log of CAPA?ExampleDo you have a closed CAPA case?ExampleDo you have an active CAPA case?Example8Elements of an Effective CAPA Process有效CAPA流程的组分Documented procedure(s)Defined CAPA inputsRisk assessment and prioritizationInvestigation disciplinesVerification/validationWell defined action planDisseminate informationDocumentation rulesEffectiveness checksComplete?Effective?TimelyDefined criteria for Management ReviewManagement escalationMetrics-ability to monitor progress 9CAPA Simplified简单流程Define the ProblemInitiate CAPAInvestigate CauseSolution(Action Plan)Verify/ValidateConductEffectiveness CheckImplementClose CAPA12Where can CAPA come from?CAPA可以从哪里产生？DiscrepanciesUnexplainable deviationsAudit ResultsRecurring audit observations,internal audits and external auditsQuality RecordsPeriodic reviewProcess controlTesting results,trends,etcPost Market dataFrequency and occurrence as expected?Service RecordsComplaintsReturned Products13Problem Definition描述问题State the problem in measurable termshow often,how much,when,and whereEmphasize the effects(risk)safety,death,injury,rework,cost,etc.The problem statement is the difference between what isis and what should beshould be Focus on facts not emotions whatwhat is wrong,not whywhy its wrongAvoid negative descriptors,inflammatory statements words that are broad and do not describe the conditions or behavior such as careless,complacency,neglect,oversightIs/Is Not Diagram是非表 WHAT WHEN WHERE EXTENT IS IS NOT 16Investigation Methods方法Define method of investigationInclude quality tools usedCause and Effect,6 Ms5 Whys,etc.Document Dates of investigation Data reviewed(data sources,records,dates)Corrections or Containment measuresResults:Statement of Cause17Different Causes不同原因Presumptive Cause可能原因apparent during early investigation,hypotheses that may explain the effect but needs validationContributing Cause侧面原因secondary and possible causesRoot Cause根本原因primary reason for the problem which if corrected will prevent recurrenceMethod 1-Five Whys五个为什么？A questions-asking method used to explore root cause of a problem.Example:My car will not start.(the problem)Why?-The battery is dead.(first why)Why?-The alternator is not functioning.(second why)Why?-The alternator belt has broken.(third why)Why?-The alternator belt was well beyond its useful service life and has never been replaced.(fourth why)Why?-I have not been maintaining my car according to the recommended service schedule.(fifth why,a root cause)Method 2 6 Ms 六个MMethod 3:Pareto Charts 图表Method 4-Fishbone Charts鱼骨图寻找/执行方案集思广益挑战方案短期和长期解决方案28Execution/ImplementationImplementation/Execution is the key!Do you have sufficient resources and management support?Do you have the right people to execute the plan?Do you have a time frame for the CAPA action plan?Do you have regular meetings on progress?Do you have a clear measurement for CAPA effectiveness?Do you let everybody involved know the CAPA actions?重在执行！文件和记录观察效果31Effectiveness and Timeliness ChecksEffectiveness ChecksPlan the effectiveness check specific to the CAPAIf it does not work:Close the CAPA and open a new one?Get an extension?Leave the CAPA open and investigate why?Timeliness ChecksIdentify regular check points to monitor the progressIdentify early detection points to monitor for recurrence/occurrence 是否有效？是否按时检查？可以结束了么？还没有呢！确认/验证33Was the Problem Statement well defined?CAPA Check Flowchart
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