GMP 检查期间发现的数据完整性和验证问题

1、GMP检查期间发现的数据完整性和验证问题DataIntegrityissues数据完整性问题TheFDAinspectorsfounddiscrepanciesbetweenHMI(humanmachineinterface)dataandbatchrecordsandpracticesofoperatorsnotfollowingbatchinstructions.ThereforetheagencyrequirestoprovideFDA检验员发现HMI(人机界面)数据与批记录数据存在差异，并且操作人员未按批指令操作。因此，FDA要求提供：acomprehensiveinvestigati

2、onintotheextentoftheinaccuraciesindatarecordsandreporting;全面调查数据记录和报告不准确的程度;resultsofthedatareviewfordrugsdistributedtogetherwithadetaileddescriptionofthescopeandrootcausesofthedataintegritylapses.已放行药品的数据审核结果，以及数据完整性失效的范围和根本原因的详细描述。Validationissues验证问题Theagencyobservedalackofprocessvalidationand,in

3、addition,alengthybulkholdtimepriortofillingdrugproductswithoutassuringthatthispracticedoesnotimpactthechemicalandmicrobiologicalquality.该机构注意到未执行工艺验证，此外，漫长的待灌装产品保持时间未能确保这种做法不会影响化学和微生物质量。Theagencythereforerequests因此，该机构要求：adetailedsummaryofthevalidationprogramforensuringastateofcontrolthroughoutthepr

4、oductlifecycle,用以确保在整个产品生命周期中处于受控状态的验证计划的详细摘要，associatedproceduresincludingprocessperformanceprotocol(s),andwrittenprocedures(andaprogram)forqualificationofequipmentandfacilities;相关程序，包括工艺性能方案，以及设备和设施确认的书面程序（和计划）;adetailedprogramfordesigning,validating,maintaining,controllingandmonitoringofmanufactu

5、ringprocessesthatincludesmonitoringofintra-batchandinter-batchvariationtoensureanongoingstateofcontrol.生产工艺设计、验证、维护、控制和监测的详细程序，包括监测批次内和批次间变异，以确保持续受控状态。ParticlesandOOSResults粒子（异物）和00S结果AccordingtoFDA,thecompanyfailedtoadequatelyinvestigateanddocumentthepresenceofparticlesinaproduct.Themanufacturerco

6、ncludedthattheparticleswerefromabrokenbeltonthefillingline,andthecorrectiveaction（CA）wastorejectanumberofunitsofthislot.However,thisCAdidnotexpandtocoverbatchesthatwerepreviouslyfilledatthesamelineorapreventativemaintenanceplantopreventrecurrenceofsimilarincidents.Inaddition,thecompanyfailedtoconduc

7、tanadequateinvestigationintoanOOStestresultforcontent.TheFDAthereforerequeststoprovide据FDA称，该公司未能充分调查和记录产品中是否存在颗粒（异物）。制造商得出结论，颗粒（异物）来自灌装线上断裂的传送带，纠正措施（CA）是拒绝此批次产品。但是，此CA未扩展到涵盖以前在该生产线上灌装的批次，也没有用以防止类似事件再次发生的预防性维护计划。此外，该公司没有对00S测试结果进行充分调查。因此，FDA要求提供acomprehensive,independentassessmentoftheoverallsystemforinvestigatingdeviations,discrepancies,complaints,OOSresults,andfailures,对偏差、差异、投诉、00S和不合格结果调查的整个系统进行全面、独立的评估，anindependentassessmentandremediationplanfortheCAPAprogram,对CAPA程序进行独立评估和补救计划，acomprehensiveassessmentandremediation