GMP 檢查期間發(fā)現(xiàn)的數(shù)據(jù)完整性和驗(yàn)證問(wèn)題

1、GMP檢查期間發(fā)現(xiàn)的數(shù)據(jù)完整性和驗(yàn)證問(wèn)題DataIntegrityissues數(shù)據(jù)完整性問(wèn)題TheFDAinspectorsfounddiscrepanciesbetweenHMI(humanmachineinterface)dataandbatchrecordsandpracticesofoperatorsnotfollowingbatchinstructions.ThereforetheagencyrequirestoprovideFDA檢驗(yàn)員發(fā)現(xiàn)HMI(人機(jī)界面)數(shù)據(jù)與批記錄數(shù)據(jù)存在差異，并且操作人員未按批指令操作。因此，F(xiàn)DA要求提供：acomprehensiveinvestigati

2、onintotheextentoftheinaccuraciesindatarecordsandreporting;全面調(diào)查數(shù)據(jù)記錄和報(bào)告不準(zhǔn)確的程度;resultsofthedatareviewfordrugsdistributedtogetherwithadetaileddescriptionofthescopeandrootcausesofthedataintegritylapses.已放行藥品的數(shù)據(jù)審核結(jié)果，以及數(shù)據(jù)完整性失效的范圍和根本原因的詳細(xì)描述。Validationissues驗(yàn)證問(wèn)題Theagencyobservedalackofprocessvalidationand,in

3、addition,alengthybulkholdtimepriortofillingdrugproductswithoutassuringthatthispracticedoesnotimpactthechemicalandmicrobiologicalquality.該機(jī)構(gòu)注意到未執(zhí)行工藝驗(yàn)證，此外，漫長(zhǎng)的待灌裝產(chǎn)品保持時(shí)間未能確保這種做法不會(huì)影響化學(xué)和微生物質(zhì)量。Theagencythereforerequests因此，該機(jī)構(gòu)要求：adetailedsummaryofthevalidationprogramforensuringastateofcontrolthroughoutthepr

4、oductlifecycle,用以確保在整個(gè)產(chǎn)品生命周期中處于受控狀態(tài)的驗(yàn)證計(jì)劃的詳細(xì)摘要，associatedproceduresincludingprocessperformanceprotocol(s),andwrittenprocedures(andaprogram)forqualificationofequipmentandfacilities;相關(guān)程序，包括工藝性能方案，以及設(shè)備和設(shè)施確認(rèn)的書(shū)面程序（和計(jì)劃）;adetailedprogramfordesigning,validating,maintaining,controllingandmonitoringofmanufactu

5、ringprocessesthatincludesmonitoringofintra-batchandinter-batchvariationtoensureanongoingstateofcontrol.生產(chǎn)工藝設(shè)計(jì)、驗(yàn)證、維護(hù)、控制和監(jiān)測(cè)的詳細(xì)程序，包括監(jiān)測(cè)批次內(nèi)和批次間變異，以確保持續(xù)受控狀態(tài)。ParticlesandOOSResults粒子（異物）和00S結(jié)果AccordingtoFDA,thecompanyfailedtoadequatelyinvestigateanddocumentthepresenceofparticlesinaproduct.Themanufacturerco

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

7、tanadequateinvestigationintoanOOStestresultforcontent.TheFDAthereforerequeststoprovide據(jù)FDA稱，該公司未能充分調(diào)查和記錄產(chǎn)品中是否存在顆粒（異物）。制造商得出結(jié)論，顆粒（異物）來(lái)自灌裝線上斷裂的傳送帶，糾正措施（CA）是拒絕此批次產(chǎn)品。但是，此CA未擴(kuò)展到涵蓋以前在該生產(chǎn)線上灌裝的批次，也沒(méi)有用以防止類似事件再次發(fā)生的預(yù)防性維護(hù)計(jì)劃。此外，該公司沒(méi)有對(duì)00S測(cè)試結(jié)果進(jìn)行充分調(diào)查。因此，F(xiàn)DA要求提供acomprehensive,independentassessmentoftheoverallsystemforinvestigatingdeviations,discrepancies,complaints,OOSresults,andfailures,對(duì)偏差、差異、投訴、00S和不合格結(jié)果調(diào)查的整個(gè)系統(tǒng)進(jìn)行全面、獨(dú)立的評(píng)估，anindependentassessmentandremediationplanfortheCAPAprogram,對(duì)CAPA程序進(jìn)行獨(dú)立評(píng)估和補(bǔ)救計(jì)劃，acomprehensiveassessmentandremediation