Digitaldeviations:Improvingsponsor—CMOcollaboration1.0Introduction

1.0引言1.1Deviationstoday

1.1當(dāng)今的偏差管理現(xiàn)狀Tomaintaincompliance,sponsorsandCMOsalikeareresponsibleforensuringthattheproductstheymanufactureareconsistentlyproduced.ThesearecontrolledbythequalitystandardsappropriatetotheirintendeduseandasrequiredbytheMarketingAuthorization,ClinicalTrialAuthorizationorproductspecification.

為持續(xù)保持合規(guī)，申辦方與CMO均負(fù)有責(zé)任，確保所生產(chǎn)的產(chǎn)品始終符合與其預(yù)期用途相適應(yīng)的質(zhì)量標(biāo)準(zhǔn)，并滿足上市許可（MA）、臨床試驗(yàn)許可（CTA）或產(chǎn)品標(biāo)準(zhǔn)的規(guī)定。Thisresponsibilityincludesdeviationmanagement,i.e.,theprocessofidentifying,reporting,investigating,documenting,managingandapprovingunexpectedoccurrencesidentifiedduringaGMPactivity.

該責(zé)任涵蓋偏差管理，即對(duì)在GMP活動(dòng)中發(fā)現(xiàn)的非預(yù)期事件進(jìn)行識(shí)別、報(bào)告、調(diào)查、記錄、處理和最終批準(zhǔn)的全過程。Theseeventsoccurwherethereisnodefinedproceduralresponseinplacetoassurequalityisnotimpacted.

當(dāng)現(xiàn)有程序無法保證質(zhì)量不受影響時(shí)，即視為發(fā)生偏差。TheCMOandsponsorunderstandtheimportanceofidentifyingandunderstandingdeviationsandwanttoresolvethemefficientlyandquicklytoensurepatientsafety.

CMO與申辦方均深知識(shí)別并理解偏差的重要性，并期望高效、迅速地解決偏差，以保障患者安全。Itiscriticaltoapproachthisbusinessprocessasapartnershiptoexecuteiteffectivelyandasquicklyaspossible.

因此，必須以合作伙伴的方式推進(jìn)該業(yè)務(wù)流程，方能實(shí)現(xiàn)高效、快速的執(zhí)行。Ifnot,theoutcomeoftheinvestigationisatriskduetoconcernsofmisalignment,whichbreakdowntrustandconfidencewithintheCMOandsponsorrelationship.

否則，因雙方步調(diào)不一，調(diào)查結(jié)果將存在風(fēng)險(xiǎn)，進(jìn)而削弱CMO與申辦方之間的信任與信心。Accountabilitymustbeaddressed,butitcannotbedoneattheriskofasoundinvestigationandresolution.

問責(zé)必須落實(shí)，但絕不得以犧牲調(diào)查與解決的科學(xué)性和完整性為代價(jià)。WhenadeviationisidentifiedattheCMO,itisdocumentedwithintheirqualitymanagementsystem(QMS).

當(dāng)CMO發(fā)現(xiàn)偏差時(shí)，應(yīng)首先在其質(zhì)量管理系統(tǒng)（QMS）中進(jìn)行記錄。Basedonthelevelorimpactofthedeviationandthequalityagreementrequirements,theCMOwillnotifythesponsor(s)ofthedeviation.

CMO將依據(jù)偏差級(jí)別/影響程度以及質(zhì)量協(xié)議要求，向相關(guān)申辦方發(fā)出偏差通知。Thetimingofnotificationsharingisoneofthemostcriticalstepsinthedeviationprocess,astimelynotificationsdemonstrateaclear,compliantoversightandensureappropriateescalationandcontainmentcanbemade.

通知的時(shí)效性是偏差流程中最關(guān)鍵的步驟之一；及時(shí)的通知可體現(xiàn)清晰且合規(guī)的監(jiān)管，并確保適當(dāng)?shù)纳?jí)與遏制措施得以實(shí)施。Inmostcases,thesponsor'sdeviationmanagementprocesswillrequiredocumentingtheCMO'sdeviationintothesponsor'sQMSviamanualentry.

多數(shù)情況下，申辦方（委托方）的偏差管理流程需通過手工錄入方式，將CMO的偏差記錄導(dǎo)入本企業(yè)的QMS。Thedatashared,levelofdetailandfrequencyofsharinglackconsistencyandstandardizationwithinandacrossthesponsor/CMOpartnerships.

所共享數(shù)據(jù)的范圍、詳細(xì)程度及共享頻率，在申辦方（委托方）與CMO內(nèi)部及彼此之間均缺乏一致性與標(biāo)準(zhǔn)化。Untilthemanualentryhasbeencompleted,deviationdataexistsinanunusableform.

在手工錄入完成之前，偏差數(shù)據(jù)處于不可用的狀態(tài)。Also,errorscanbeintroducedthroughmanualdataentry.

此外，手工錄入可能引入錯(cuò)誤。Thisconsumestimeandcandelaytheinvestigationandresolutionprocess.

這不僅耗時(shí)，還可能延誤調(diào)查與解決進(jìn)程。DeviationsthatoccurataCMOcanimpactmultipleproductstheymanufactureandoneormoreoftheirsponsororganizations.

CMO發(fā)生的偏差可能影響其生產(chǎn)的多個(gè)產(chǎn)品以及一個(gè)或多個(gè)申辦方組織。CMOsmustquicklyassessandperformsufficientinvestigationstoenableappropriatenotificationstotheimpactedsponsororganizations.

CMO必須迅速評(píng)估并開展充分調(diào)查，以便向受影響的申辦方發(fā)出適當(dāng)通知。ThiscreatesdataintegrityandprivacychallengesfortheCMO.

這給CMO帶來了數(shù)據(jù)完整性與隱私保護(hù)方面的挑戰(zhàn)。Theymustmanageandsharetherequiredinformationwiththedifferentsponsorsinawaythatmaintainsandprotectsthesponsor'sintellectualproperty.

他們必須在管理與共享所需信息時(shí)，維護(hù)并保護(hù)各申辦方的知識(shí)產(chǎn)權(quán)。TrackingthestatusofthedeviationprocessismanualandbecomeschallengingacrosstheCMOandsponsororganizationsduetomultipleemails,phonecallsandcopiesofinformationsharedbetweentheorganizations.

偏差流程的狀態(tài)追蹤依賴人工，因組織間頻繁的郵件、電話及信息副本往來，在CMO與申辦方之間變得尤為困難。1.2DISCOVisionandDPMMAlignment

1.2DISCO愿景與DPMM的協(xié)同TheDigitalPlantMaturityModel(DPMM)wasdevelopedbyBioPhorumITDigitalandDataPhorummembercompaniesandiswidelyusedacrosstheindustrytoassessplantmaturity,identifycapabilitiesneedingdevelopment,createstrategicplansandroadmaps,influencesuppliersanddevelophumanresourcescompetencyanddevelopmentframeworks.

數(shù)字工廠成熟度模型（DPMM）由BioPhorumIT數(shù)字與數(shù)據(jù)論壇成員公司共同制定，已在行業(yè)廣泛應(yīng)用，用于評(píng)估工廠成熟度、識(shí)別待發(fā)展能力、制定戰(zhàn)略計(jì)劃與路線圖、影響供應(yīng)商并構(gòu)建人力資源能力框架。TheDPMMdescribesfivelevelsofmaturity:pre-digitalplant,digitalislands,connectedplant,predictiveplantandadaptiveplant.

DPMM將成熟度劃分為五個(gè)層級(jí)：前數(shù)字化工廠、數(shù)字孤島、互聯(lián)工廠、預(yù)測(cè)工廠與自適應(yīng)工廠。TheDPMMconcludesthatorganizationsrequiredigitization,commonprocessesacrossproductsandaggregateddatatomakepredictiveandadaptiveapproachespossible.

DPMM指出，企業(yè)必須通過數(shù)字化、跨產(chǎn)品的統(tǒng)一流程以及聚合數(shù)據(jù)，才能實(shí)現(xiàn)預(yù)測(cè)性與自適應(yīng)的運(yùn)營(yíng)方式。InNovember2022,theBioPhorumITDigitalandDataDISCO(DigitalIntegrationofSponsorandContractOrganizations)workstreampublishedtheVisionfordigitalmaturityintheintegrationbetweenbiomanufacturersandpartnerorganizations.

2022年11月，BioPhorumIT數(shù)字與數(shù)據(jù)論壇的DISCO（申辦方與合同組織數(shù)字化整合）工作組發(fā)布了《生物制造商與合作伙伴間數(shù)字化整合成熟度愿景》。Thispaperdefinesasimplematuritymodelforintegrationsbetweenorganizationsinthesupplychain(seeFigure1).

該白皮書為供應(yīng)鏈上下游組織間的整合定義了一個(gè)簡(jiǎn)潔的成熟度模型（見圖1）。

Atthetimeofwriting,theexchangeofmostdeviationinformationcouldbedescribedasapre-digitalormanualextract.

在撰寫本文之時(shí)，大多數(shù)偏差信息的交換仍處于“前數(shù)字化”狀態(tài)，或僅通過手工提取完成。Thisneedstochangetobringefficiencyandsustainabilitytotheindustry.

行業(yè)必須改變這一現(xiàn)狀，以實(shí)現(xiàn)高效、可持續(xù)的偏差管理。Thetargetintegrationpatternsfordeviationsare4Auto-ingestor5Nearreal-time,asshowninFigure1;however,organizationsstillneedtosupportpartnerorganizationsatlowerlevelsofdigitalmaturity.

如圖1所示，偏差管理的理想集成模式應(yīng)為第4級(jí)“自動(dòng)攝取”或第5級(jí)“近實(shí)時(shí)”；然而，企業(yè)仍需兼顧數(shù)字化成熟度較低的合作伙伴。Thevisionpaperalsooutlinestheneedtoaligninseverallayers:processandrequireddata,datastructure,informationcontainerandsecuretransport.

愿景白皮書進(jìn)一步指出，必須在以下多個(gè)層面達(dá)成一致：業(yè)務(wù)流程與所需數(shù)據(jù)、數(shù)據(jù)結(jié)構(gòu)、信息容器以及安全傳輸。AsFigure2shows,itiscommontohaveasystemforsendingorreceivingdata,i.e.,anintegrationplatformthatmaps,wrapsanddispatchesdatasecurely,withoutnecessarilychangingtheoperationalsystemsanddatastores.

如圖2所示，通常需要一套收發(fā)數(shù)據(jù)的系統(tǒng)——即集成平臺(tái)——負(fù)責(zé)數(shù)據(jù)的映射、封裝與安全分發(fā)，而無需改動(dòng)現(xiàn)有的運(yùn)營(yíng)系統(tǒng)及數(shù)據(jù)存儲(chǔ)。Partnersneedtoagreeonthetouchpointsinthebusinessprocesswheredataisexchangedandthedatapointsthatarerequired.

合作伙伴必須就業(yè)務(wù)流程中數(shù)據(jù)交換的“觸點(diǎn)”以及所需的數(shù)據(jù)項(xiàng)達(dá)成一致。

Severalkeyactionsarerequiredtosupportdigitaldeviationsthataredeliveredwithinthisdocument,includingestablishing:

本文提出的“數(shù)字化偏差”落地需完成若干關(guān)鍵行動(dòng)，包括確立：FoundationalstandardsandexpectationsfordeviationdatathatsponsorsandCMOscansupportwithaminimumofeffort.

偏差數(shù)據(jù)的基礎(chǔ)標(biāo)準(zhǔn)與期望，使申辦方（委托方）與CMO能夠以最小代價(jià)予以支持。Foundationalbusinessprocessessupportingdatastandardsandexpectations.

支撐數(shù)據(jù)標(biāo)準(zhǔn)與期望的基礎(chǔ)業(yè)務(wù)流程。Commonlanguageandcategorizationusedforcriticality,levelofimpact,etc.,ofdeviationsacrosssponsorsandCMOs.

跨申辦方（委托方）與CMO的偏差關(guān)鍵性、影響等級(jí)等通用語(yǔ)言與分類方法。Qualityagreementstandardsthatsupportasharedaccountabilitymodelandcommonoversightexpectations/responsibilitiestofosterthepartnershipmindsetrequiredforeffectivedeviationmanagement.

質(zhì)量協(xié)議標(biāo)準(zhǔn)，用以支撐共同責(zé)任模型及統(tǒng)一的監(jiān)管期望/職責(zé)，從而培育有效偏差管理所需的合作伙伴思維。2.0

Digitaldeviationmanagement

2.0

數(shù)字化偏差管理2.1

Digitaldeviationsdefined

2.1

數(shù)字化偏差定義Whileeachorganizationstrivesforaneffectiveandefficientpathtocompliancewitheachdeviation,everyorganizationhasitsowninterpretationoftheregulatoryrequirementsandexpectations.

雖然各組織都力求對(duì)每一項(xiàng)偏差采取高效且有效的合規(guī)路徑，但每一家組織對(duì)法規(guī)要求和期望的解讀各不相同。Thiscreatesasignificantchallengewhenestablishingthefoundationalstandardsandexpectationsthatarecriticalinsupportingdigitaldeviationmanagement.

這給建立支撐數(shù)字化偏差管理所需的基礎(chǔ)標(biāo)準(zhǔn)和期望帶來了重大挑戰(zhàn)。ThestandardsandexpectationsmusthaveenoughdetailtoenableconsistencyacrosseachnetworkofsponsorsandCMOs,andbetweenthem.

這些標(biāo)準(zhǔn)和期望必須足夠詳細(xì)，以便在申辦方（委托方）網(wǎng)絡(luò)內(nèi)部、CMO網(wǎng)絡(luò)內(nèi)部以及兩者之間實(shí)現(xiàn)一致性。Ontheotherhand,therewillneedtobeflexibilitytosupporttheuniqueneedsofsponsorsandCMOs.

另一方面，標(biāo)準(zhǔn)又需具備靈活性，以滿足申辦方與CMO各自的獨(dú)特需求。Theever-changingcompliancelandscapewillalsopresentchallengesinestablishingandmaintainingstandardsandexpectations,requiringastrongfoundationthatcanbeenhancedandrevisedtoaccommodatefutureneeds.

不斷變化的合規(guī)環(huán)境亦會(huì)對(duì)建立和維護(hù)這些標(biāo)準(zhǔn)和期望帶來挑戰(zhàn)，因此需要一個(gè)可強(qiáng)化、可修訂的堅(jiān)實(shí)基礎(chǔ)，以適應(yīng)未來需求。Overall,theneedfordigitaldeviationsissignificant.

總體而言，對(duì)數(shù)字化偏差的需求極為迫切。Byleveragingthestandardsandexpectationsestablishedwithinthisdocumentfordeviationbusinessprocessesanddata,sponsorsandCMOscannotify,shareandexecutethedeviationmanagementprocessaseffectivelyandefficientlyaspossible.

通過利用本文檔所確立的偏差業(yè)務(wù)流程與數(shù)據(jù)標(biāo)準(zhǔn)及期望，申辦方（委托方）與CMO能夠以盡可能高效的方式完成通知、共享并執(zhí)行偏差管理流程。Thedirectbenefitsofdigitaldeviationmanagementfocusonreducingthetimespentonexecutingmanualstepsofthecurrentdeviationprocessesacrossbothorganizations(seeFigure3),allowingthattimetoberepurposedformorevalue-addedactions.

數(shù)字化偏差管理的直接益處在于減少兩家組織在現(xiàn)有偏差流程中手動(dòng)環(huán)節(jié)所耗費(fèi)的時(shí)間（見圖3），從而將節(jié)省下來的時(shí)間用于更具價(jià)值的活動(dòng)。Also,digitaldeviationmanagementenablestheresolutionofdeviationsquickerandminimizesthepotentialdisruptiontothesupplychainofcriticalmedicinestopatients.

此外，數(shù)字化偏差管理還能加速偏差解決，最大限度降低對(duì)患者關(guān)鍵藥品供應(yīng)鏈的潛在干擾。Thereareindirectbenefits,suchaspromotingtransparencyandimprovedoversightthat,inturn,strengthenthesponsor/CMOrelationship.

間接益處包括提升透明度與監(jiān)管水平，從而進(jìn)一步加強(qiáng)申辦方（委托方）與CMO之間的合作關(guān)系。Assupplychainneedscontinuetoimprovesponsor/CMOrelationships,theneedfordigitaldeviationswillincrease.

隨著供應(yīng)鏈需求對(duì)申辦方（委托方）/CMO關(guān)系的持續(xù)優(yōu)化，對(duì)數(shù)字化偏差的需求也將不斷增長(zhǎng)。

2.2Benefits

2.2收益Oneofthemostcriticalelementstobescrutinizedacrossthemanufactureofpharmaceuticalsisdivergencesfromastandardorexpectedvalue.

藥品制造過程中最受關(guān)注的核心要素之一，就是與標(biāo)準(zhǔn)或預(yù)期值的偏離。Understandingandanalyzingdata,processesandoutcomesisessentialtodeterminingthepotentialimpactonthepatientandproduct.

必須通過數(shù)據(jù)分析、流程梳理與結(jié)果評(píng)估，才能判定偏差對(duì)患者和產(chǎn)品的潛在影響。Thisareaisoneofthehighestprioritiesindatasharing.

該領(lǐng)域是數(shù)據(jù)共享的重中之重。ItisintheinterestofboththeCMOandsponsortodetermineanypotentialriskorimpactduetoadeviation.

CMO與申辦方均須識(shí)別偏差帶來的任何潛在風(fēng)險(xiǎn)或影響，這是雙方的共同利益所在。DrivingdownthetimeittakestocloseoutadeviationinboththeCMOandsponsorsystemswillimprovetheefficiencyofsupply,andtransparencyandalignmentofeventsandtheiroutcomesareessentialtoensuringthatwhatisproducedissafeandefficaciousforthepatient.

縮短CMO（委托方）與申辦方系統(tǒng)內(nèi)偏差的關(guān)閉周期，將提升供應(yīng)效率；事件及其結(jié)果的透明與一致，是確保所生產(chǎn)藥品對(duì)患者安全、有效的關(guān)鍵。Forthesereasons,thetimelysharingofinformationondeviationsisacentralelementofaqualityagreement.

因此，及時(shí)共享偏差信息是質(zhì)量協(xié)議的核心要素。Thisisamatterofcompliance,demonstratingathoroughunderstandingandcontroloverthemanufacturingprocessfromboththeCMOandsponsor'sperspective.

這不僅是合規(guī)要求，更體現(xiàn)了CMO與申辦方對(duì)制造過程的全面理解與掌控。Beyondthecomplianceexpectation,sponsorsandCMOshavesharedgoalswhenitcomestoexecutingdigitaldeviationmanagement.

除合規(guī)外，申辦方與CMO在執(zhí)行數(shù)字化偏差管理方面還擁有共同目標(biāo)。Someofthebenefitsofdigitizingdeviationsinclude:

數(shù)字化偏差帶來的部分收益包括：Improvedtransparencyforsponsors.

提升申辦方（委托方）透明度。IfadeviationhappensattheCMO,theresponsibilityforinvestigatingandunderstandingwhathappenedlieswiththeCMO;thereforethetransparencybenefitisrealizedbythesponsor.

若偏差發(fā)生在CMO，調(diào)查與理解事件的責(zé)任由CMO承擔(dān)，因而透明度收益直接體現(xiàn)在申辦方（委托方）。Alsomeansearlierdetectionofmissinginformation,whichcanimprovethespeedofclosing-outdeviations.

還可提前發(fā)現(xiàn)缺失信息，從而加快偏差關(guān)閉速度。Reviewingtrendsorpatternsthatwillpreventdeviationscanleadtostrengthenedsponsor/CMOpartnerships.

通過回顧趨勢(shì)或模式以預(yù)防偏差，可進(jìn)一步鞏固申辦方（委托方）/CMO合作關(guān)系。Havingadigital,moredigestibleformatallowsorganizationstoanalyzeandcreateafullerpictureofopen/closeddeviations,etc.,allowingyoutomanageyourresourcesbasedonthepriorityofyourbatches.

數(shù)字化、易讀的數(shù)據(jù)格式使組織能夠全面分析已關(guān)閉/未關(guān)閉偏差等，從而按批次優(yōu)先級(jí)調(diào)配資源。Thiscanalsoresultinfewerhumanerrorsandfasterhandlingastherearenomoreemails,onlinecollaborationsystemsnotificationsorpapersbeingcirculated.

同時(shí)減少人為錯(cuò)誤并加速處理，因?yàn)闊o需再頻繁發(fā)送郵件、系統(tǒng)通知或紙質(zhì)文件。Reducedtime-to-batchdisposition,whichcanleadtoshorterend-to-endleadtimes.

縮短批次處置時(shí)間，進(jìn)而壓縮端到端交付周期。Shortleadtimesmeanareductioninsafetystockrequirements,asthesecalculationsaretraditionallybasedonleadtime.

交付周期縮短意味著安全庫(kù)存需求下降，因?yàn)閭鹘y(tǒng)安全庫(kù)存計(jì)算以交付周期為基礎(chǔ)。Thischangereducessupplychainriskandinventorycostsand,overall,resultsinimprovedpatientsupply.

這一變化降低供應(yīng)鏈風(fēng)險(xiǎn)與庫(kù)存成本，最終提升患者用藥供應(yīng)保障。IncreasedrateofbatchapprovalsmeansearlierinvoicingandpaymenttotheCMO.

批次批準(zhǔn)率提高，CMO可提前開票并收回款項(xiàng)。Asmoredataissharedandbecomesavailable,therearemoreopportunitiestoleverageadvancedtechnology—whetherthroughautomationorartificialintelligence—touncovernewinsightsthatwillenablebothsponsorsandCMOstoinnovateandacceleratethedata-drivenbusinessdecision-makingprocesses.

隨著共享數(shù)據(jù)量的增加，企業(yè)可借助自動(dòng)化或人工智能等先進(jìn)技術(shù)挖掘新洞察，推動(dòng)申辦方與CMO共同創(chuàng)新，并加速數(shù)據(jù)驅(qū)動(dòng)的業(yè)務(wù)決策流程。Ontopofthesesharedchallenges,CMOshaveuniquechallengesasmosttransactwithavarietyofsponsorsconcurrently.

除上述共同挑戰(zhàn)外，CMO還面臨獨(dú)特難題：其通常同時(shí)與多家申辦方開展業(yè)務(wù)。Adeviationcaninherentlyaffectmultiplesponsors.

一起偏差可能inherently（固有地）波及多家申辦方（委托方）。StrictfiltercriteriamustbeestablishedwithinaCMO'slocalprocessesandsystemstopreventdataleakagetocompetingsponsors,whilesupportingfullvisibilityofthedeviation.

因此，CMO必須在本地流程與系統(tǒng)中設(shè)定嚴(yán)格的過濾規(guī)則，在防止敏感數(shù)據(jù)泄露給競(jìng)爭(zhēng)申辦方的同時(shí)，確保偏差信息的完整可見。ThisischallengingascertainfieldsintheCMOQMSareusedtoaggregatethefindingsandanalysisofthedeviation.

難點(diǎn)在于，CMOQMS中的某些字段用于匯總偏差的調(diào)查結(jié)果與分析結(jié)論。Beforeanelectronicexchangeofthisdata,itmustbeproperlysanitizedandcontextualizedforeachsponsorreceivingthedata.

在電子交換前，必須對(duì)接收方的每位申辦方分別進(jìn)行數(shù)據(jù)“脫敏”與上下文適配。ThepotentialimpactormisinterpretationofidentifiedrootcausesoftenleadstoarestrictiveapproachtoinformationsharingfromaCMO.

已識(shí)別根因的潛在影響或被誤讀的風(fēng)險(xiǎn)，常導(dǎo)致CMO采取保守的信息共享策略。Thisoftenprohibitstimelysharingofdeviationinformationuntilfullyreviewedandapprovedversionsareavailable.

這往往使得偏差信息只有在完全審核定稿后才能共享，從而延誤了時(shí)效。ThisoftenhamperstheinputfromsponsorSMEs.

進(jìn)而阻礙申辦方主題專家（SME）及時(shí)介入提供輸入。WhiletheCMOisresponsibleforthemanufacturingofthatproduct,theylikelywillnothavevisibilityontheprecedingorsubsequentmanufacturingstagesintheoverallsupplynetwork.

盡管CMO負(fù)責(zé)該產(chǎn)品生產(chǎn)，但其通常對(duì)整個(gè)供應(yīng)網(wǎng)絡(luò)中前后制造環(huán)節(jié)缺乏可見性。Thiscanbeofcriticalimportanceindeterminingtheoutcomeofaninvestigation.

而這一點(diǎn)可能對(duì)調(diào)查結(jié)論的判定至關(guān)重要。Thisconservativeapproachcanfurtherreducevisibilityintotheissuesthatariseduringthemanufacturing.

保守策略進(jìn)一步降低了對(duì)制造過程中出現(xiàn)問題的可見性。BystrictlyadheringtotheQTAs,oftenwhataredeemedbytheCMOtobeminorortrivialdeviations,arenotvisibleuntiltheentirebatchfileissharedfollowingCMOrelease.

由于嚴(yán)格遵守質(zhì)量技術(shù)協(xié)議（QTAs），那些被CMO視為輕微或瑣碎的偏差，往往要等到CMO放行后、完整批檔案被共享時(shí)才得以顯現(xiàn)。AstheresponsibilitiesoftheCMOandsponsoroftendiffer,thesearereviewedpriortomarketrelease.

鑒于CMO與申辦方職責(zé)常存在差異，此類偏差需在上市放行前接受復(fù)核。Questionsorconcernsthatariseduringthisperiodhaveadirectimpactonthepatientsupplyduetothelackofvisibilityovertheproceedingweeksormonths.

在此期間產(chǎn)生的疑問或關(guān)切，由于隨后數(shù)周或數(shù)月內(nèi)信息不透明，將直接影響患者用藥供應(yīng)。Whilemuchofthedeviationchallengesmentionedherearemutuallyshared,therearejustasmanychallengesspecifictotheCMOandsponsoralike.

盡管上述偏差挑戰(zhàn)多為雙方共有，但同樣存在大量各自特有的難題。3.0

Howdowedigitizetheprocess?

3.0

我們?nèi)绾螌⒘鞒虜?shù)字化？3.1

Datatransmissionalignment

3.1

數(shù)據(jù)傳輸對(duì)齊ThedigitalmaturityleveloftheCMOandsponsorwillaffectthetypeoftransactionandfileformattobeused.

CMO與申辦方的數(shù)字化成熟度將決定所采用的交易類型與文件格式。Thelimitingfactorheresitswiththecompanywiththelowerlevelofmaturity,astheexchangeneedstobeinlinewiththislevel.

限制因素在于成熟度較低的一方，數(shù)據(jù)交換必須以該方的能力上限為準(zhǔn)。Resultsofa2022internal,member-onlyDISCOsurveyindicatedindustryaspirationsforprocessingqualityinformationareatMaturityLevel3/4,i.e.,auto-extract/auto-ingestion,includingdeviations.

2022年DISCO內(nèi)部成員調(diào)查顯示，行業(yè)對(duì)質(zhì)量信息處理的期望成熟度為第3/4級(jí)（自動(dòng)提取/自動(dòng)攝取），偏差信息亦包含在內(nèi)。AlthoughorganizationsatlowermaturitylevelswillleveragePDFstoexchangedeviationinformation,theminimumrecommendedapproachforautomateddataingestionisaflatCSVformat.

成熟度較低的組織仍可沿用PDF交換偏差信息，但實(shí)現(xiàn)自動(dòng)攝取的最低推薦格式為扁平CSV。Tobetterfacilitateingestionandaccommodateextendeddatasets,solutionsshoulduseastructureddataserializationformatsuchasXMLorJSON.

為進(jìn)一步提升攝取效率并支持?jǐn)U展數(shù)據(jù)集，應(yīng)采用結(jié)構(gòu)化序列化格式（XML或JSON）。Theapplicationprogramminginterface(API)shouldbepreciselydefinedusingOpenAPIorAsyncAPItofacilitateimplementationoncommonintegrationplatforms.

API須使用OpenAPI或AsyncAPI精確定義，以便在主流集成平臺(tái)上快速落地。3.2

Validationconsiderations

3.2

驗(yàn)證考量Deviationsmanagementhelpsusunderstandhowanon-conformancethathasoccurredcanimpactproductquality.

偏差管理幫助我們了解已發(fā)生的不符合事件對(duì)產(chǎn)品質(zhì)量的潛在影響。TheelectronicexchangesofdeviationdatabetweenthesponsorandCMO,outlinedinthedigitaldeviationmanagementprocess,supportthiscriticalqualitybusinessprocess.

數(shù)字化偏差管理流程中規(guī)定的申辦方與CMO之間的偏差數(shù)據(jù)電子交換，正是支撐這一關(guān)鍵質(zhì)量業(yè)務(wù)流程的基礎(chǔ)。Eachorganizationmustperformtheappropriatevalidationactivitiesforthevalidationresponsibilitiestheyown,asoutlinedintheQualityAgreement.

各方須按照質(zhì)量協(xié)議中劃分的驗(yàn)證責(zé)任，執(zhí)行相應(yīng)的驗(yàn)證活動(dòng)。Toexecutetheoutlinedresponsibilities,eachorganizationwillfollowitscomputersystemsqualityassurance(CSQA)policiesandprocedures.

為落實(shí)上述責(zé)任，各方將遵循自身的計(jì)算機(jī)系統(tǒng)質(zhì)量保證（CSQA）政策與程序。TheQualityAgreementwillbeusedtoestablishalignmentontheextentofCSQApoliciesandprocedureswhensignificantdifferencesinapproachexistbetweenthesponsorandCMO.

當(dāng)申辦方與CMO的CSQA方法存在顯著差異時(shí)，應(yīng)以質(zhì)量協(xié)議為基準(zhǔn)，就各自CSQA政策的適用范圍達(dá)成一致。3.3Industry-standardfieldsforinitialnotificationtransaction

3.3初始通知交易使用的行業(yè)標(biāo)準(zhǔn)字段Thissectioncoversthedatasettobeusedasastandardreferenceforthedeviationnotificationinthedigitaldeviationmanagementprocess.

本節(jié)列出數(shù)字化偏差管理流程中，偏差通知應(yīng)采用的基準(zhǔn)數(shù)據(jù)集。Recommendationstoconsider:

相關(guān)建議如下：Establishingfilteringcriteria:werecommendthattheCMOandsponsordiscussthenecessaryfilteringcriteriaupfront,suchasrelevantproductsorriskcategories,tolimittheamountofdatabeingsharedandtopreventdataleakage.建立過濾條件：建議CMO與申辦方預(yù)先討論必需的過濾條件（如相關(guān)產(chǎn)品或風(fēng)險(xiǎn)類別），以限制共享數(shù)據(jù)量并防止數(shù)據(jù)泄露。Choosingaprimarykey:giventhenatureofdeviationdataandthefrequencyofupdates,itcanbetrickytofindtheappropriateprimarykeythatservesasauniqueidentifieroftherecord,sowerecommendevaluatingacombinationoffieldsthatcanservethispurpose.選擇主鍵：鑒于偏差數(shù)據(jù)特性及更新頻率，單一字段往往難以充當(dāng)唯一標(biāo)識(shí)，建議評(píng)估多字段組合作為主鍵。Handlingchanges:themethodofhandlingmodificationstothedatawithintherecordsisuptothepartiesinvolved,astheunderlyingsystemsandinterfacesmightvary.Westronglyrecommendestablishingajointcenterofexcellencethatmeetsregularly(e.g.bi-monthlyorquarterly)toconductjointimpactassessmentsanddiscusspotential/upcomingchangesandothersignificanttopicsrelatedtodataexchangeandwaysofworking.

強(qiáng)烈建議成立聯(lián)合卓越中心，定期（如雙月或季度）召開例會(huì)，共同評(píng)估影響，討論即將發(fā)生的變更及其他數(shù)據(jù)交換與協(xié)作相關(guān)的重要議題。處理變更：記錄內(nèi)數(shù)據(jù)的修改方式由雙方自行約定，因其底層系統(tǒng)與接口可能存在差異。4Systemdesigndeltas:itisimportanttoacknowledgethatthefunctionaldesignofQMSswillvaryacrosstheindustryduetomultiplefactors.

4系統(tǒng)設(shè)計(jì)差異：必須承認(rèn)，受多種因素影響，行業(yè)內(nèi)的QMS功能設(shè)計(jì)存在差異。Assuch,identicallynameddataelementswillexistbetweenasponsor'sQMSandaCMO'sQMSandtherewillbemoredesignpermutations(e.g.differentdatafieldnamingconventionsthatareusedinthesamemanner)ineachsystem.

因此，申辦方（委托方）QMS與CMOQMS之間會(huì)出現(xiàn)“同名不同義”的數(shù)據(jù)元素，且各系統(tǒng)的設(shè)計(jì)組合（例如同一用途卻采用不同字段命名規(guī)范）更加多樣。Furthermore,allpartiesinvolvedmustconductamoregranularjointanalysisofotherdesignelements,suchaspicklistvalues,toalignonthenextlevelmappingand/orapproach.

此外，雙方還需對(duì)下拉值等其他設(shè)計(jì)要素進(jìn)行更細(xì)粒度的聯(lián)合分析，以就下一層映射匹配方案或?qū)嵤┓绞竭_(dá)成一致。Forexample,datainonesystemmaybeastring/textfield,whilethesamefieldintheothersystemmaybeapicklistvalue.

舉例：同一字段在A系統(tǒng)為字符串/文本型，在B系統(tǒng)卻為下拉值。Picklistvaluesforthesamefieldinbothsystemsmayalsocarrydifferentvalues,e.g.aRiskCategoryfieldinonesystemmaybe'High','Medium'or'Low'whiletheothermayshowas'1','2'or'3'.

同一字段的下拉值也可能不同，如“風(fēng)險(xiǎn)類別”在A系統(tǒng)為“高/中/低”，在B系統(tǒng)卻為“1/2/3”。Thismayresultinextradesignelementreconciliationorpossiblesystemdesignchangestoaccommodatethedataexchange.

這可能需要額外進(jìn)行設(shè)計(jì)要素對(duì)賬，甚至調(diào)整系統(tǒng)設(shè)計(jì)以支持?jǐn)?shù)據(jù)交換。Thesuggesteddatamodelbelowconstitutesanoverarching,logicallayerofdataelementsthatsponsorsandCMOsmaymaptoandusewithoutdesignchangestofacilitatetheexchange.

下文建議的數(shù)據(jù)模型提供了一個(gè)統(tǒng)一的邏輯數(shù)據(jù)元素層，申辦方與CMO可直接映射使用，無需變更現(xiàn)有系統(tǒng)即可實(shí)現(xiàn)交換。ThedataanddescriptionscontainedinTables1and2shouldnotbeconstruedasanexplicitprescription,butratherasaframeworkthatisanticipatedtoevolveovertime.

表1與表2中的數(shù)據(jù)及描述并非強(qiáng)制性處方，而是一個(gè)可隨時(shí)間演進(jìn)的框架。

3.4Controlledvocabularies

3.4受控詞匯表Itisnotonlythenamesofthefieldsthatshouldbealigned,butalsothevaluesthatcanbecontainedinthosefields.

需要對(duì)齊的不僅是字段名稱，還包括字段內(nèi)可填寫的取值。Forexample,thestatusdescriptormustbethesameandmeanthesametoensuredataanalyzedfromdifferentsourcesmakessense.

例如，“狀態(tài)描述符”必須完全一致且含義相同，才能確保來自不同源的數(shù)據(jù)在分析時(shí)具備可比性。Freetextshouldbetheexception.

應(yīng)盡量避免自由文本，僅將其作為例外。Ofcourse,controllingvocabulariesaccordingtoanexternalstandardmeansthatbothpartiesinapartnershipwillneedtomaptoandfromtheiroperationalsystems(ratherthantheCMOmappingtoeachsponsor'srequirements).

當(dāng)然，依據(jù)外部標(biāo)準(zhǔn)對(duì)詞匯進(jìn)行控制，意味著合作雙方均需在自己的運(yùn)營(yíng)系統(tǒng)與標(biāo)準(zhǔn)詞匯之間建立雙向映射（而非由CMO單獨(dú)去適配每一家申辦方的要求）。However,oncedone,thatmappingshouldbegoodforfuturepartnershipsandbequickertoimplement,withimprovedaccuracyforeveryone.

然而，一旦完成該映射，未來與其他伙伴合作時(shí)即可復(fù)用，實(shí)施更快、準(zhǔn)確性更高。Intime,weexpectthedatamanagedbycompaniesindatalakesanddataproductstoincreasinglyconformtocontrolledvocabulariesand,eventually,forcontrolledvocabulariestobeadoptedintooperationalsystems.

展望未來，企業(yè)存放在數(shù)據(jù)湖和數(shù)據(jù)產(chǎn)品中的數(shù)據(jù)將越來越遵循受控詞匯表，并最終把受控詞匯表直接嵌入運(yùn)營(yíng)系統(tǒng)。4.0Casestudy

案例研究ToshowtheoperationalefficiencyoftheproposedstandardsdescribedinChapter4,anautomatedsystembetweenasponsorandCMOwassuccessfullyimplemented.

為驗(yàn)證第4章所述標(biāo)準(zhǔn)的實(shí)際運(yùn)行效率，我們成功落地了一套申辦方與CMO間的自動(dòng)化系統(tǒng)。ThedefinedstandardsstreamlinedthedevelopmentofthepilotbetweentheCMOandsponsor,allowinganexpediteddeploymentwithoutneedingacomprehensiveprojectframework.

既定標(biāo)準(zhǔn)簡(jiǎn)化了雙方試點(diǎn)項(xiàng)目的開發(fā)工作，使系統(tǒng)得以快速上線，而無需構(gòu)建繁復(fù)的項(xiàng)目框架。4.1Development

4.1開發(fā)階段Theprojectwasimplementedwiththefollowingprinciplesinmind,highlightingtheneedforuniforminterfaces:

項(xiàng)目遵循以下原則，重點(diǎn)解決接口統(tǒng)一問題：Compliancewithstandards:theimplementationadheredtothefileformat,encodingandfieldstandardsoutlinedinSection3.Byintegratingthesebestpractices,weensuredseamlessinteroperabilitybetweentheCMOandthesponsor.

通過整合這些最佳實(shí)踐，CMO與申辦方實(shí)現(xiàn)了無縫互操作。Thisformsthefoundationforacommoninterfacethatisessentialforfurtherprocessing.

該通用接口為后續(xù)數(shù)據(jù)處理奠定了堅(jiān)實(shí)基礎(chǔ)。標(biāo)準(zhǔn)合規(guī)：實(shí)施過程嚴(yán)格采用第3章規(guī)定的文件格式、編碼及字段標(biāo)準(zhǔn)。Scalability:thesystemwasdesignedwithscalabilityinmind.Althoughinitiallytailoredforonesponsor/CMOrelationship,itcanbeeasilyadaptedtoaccommodateadditionalclientsinthefuture.

盡管當(dāng)前僅針對(duì)單一申辦方/CMO關(guān)系，未來仍可快速適配更多客戶?？蓴U(kuò)展性：系統(tǒng)按可擴(kuò)展思路設(shè)計(jì)。Terminologyandscopealignment:despitethedefinedstandards,developingacommonglossarywasvitaltoensureauniformunderstandingoftheequivalentofeachdatafield,asdiscrepanciesinterminologybetweentheCMOandsponsorQMSsystemsarose.Itwasestablishedthatadailyexchangefrequencyofdatabesttoensurethetimelytransmissionofdeviationdata.

雙方確認(rèn)以“日”為數(shù)據(jù)交換頻率，保障偏差數(shù)據(jù)及時(shí)傳輸。術(shù)語(yǔ)與范圍對(duì)齊：即便已有標(biāo)準(zhǔn)，仍需共建統(tǒng)一詞匯表，以消除雙方QMS系統(tǒng)對(duì)同名字段理解的差異。Datasanitization:acrucialaspectoftheimplementationwasthefocusondatasanitization.TheCMOQMSsystememployedastructuredapproachforstoringdeviationdata,enablingtheclearseparationofsponsor-specificinformation,evenwhenmultiplesponsorsareaffectedbyacommondeviation.

CMOQMS采用結(jié)構(gòu)化方式存儲(chǔ)偏差數(shù)據(jù)，即便一起偏差涉及多家申辦方，也能清晰區(qū)分各自專屬信息。Toprotectsensitivecustomerdata,alltransmittedinformationwasverifiedbytheintermediarylayer(SAPBusinessWarehouse)beforebeingsent,therebypreventingpotentialdataleaks.

為保護(hù)敏感客戶數(shù)據(jù)，所有外發(fā)信息均經(jīng)中間層（SAPBusinessWarehouse）校驗(yàn)，杜絕潛在泄露。數(shù)據(jù)脫敏：項(xiàng)目核心環(huán)節(jié)之一為數(shù)據(jù)脫敏。4.2Systemoverviewanddataprocessingworkflow

4.2系統(tǒng)概覽與數(shù)據(jù)處理工作流Theautomatedsystemcomprisesthefollowingcomponentsanddataprocessingworkflows:

自動(dòng)化系統(tǒng)由以下組件與數(shù)據(jù)處理流程構(gòu)成：CMO:

CMO側(cè)：QMS:theQMSfunctionsasasourcesystemforallexchangeddata.Inthescopeofthedevelopment,severaldatabaseviewswereestablishedtoprovidetherequiredqualitydataforallpartiesinvolved.

開發(fā)階段已創(chuàng)建若干數(shù)據(jù)庫(kù)視圖，為各方提供所需質(zhì)量數(shù)據(jù)。QMS：作為所有交換數(shù)據(jù)的源系統(tǒng)。DataWarehousing:thisservesasaverifiedintermediarylayertoguaranteedataqualityandconsistency.Therawqualitydataissanitizedtoonlyincludecustomerdataandismappedtotherequiredfields.

原始質(zhì)量數(shù)據(jù)經(jīng)脫敏后僅保留客戶數(shù)據(jù)，并映射至所需字段。數(shù)據(jù)倉(cāng)庫(kù)：作為經(jīng)校驗(yàn)的中間層，確保數(shù)據(jù)質(zhì)量與一致性。Middleware:thesanitizeddataismappedintothetargetdataformat(e.g.,aCSVfile)andthesecuretransmissionofprocesseddatatoanSFTPserver/RESTAPIisperformed,whichmakesitavailablefordownstreamconsumptionbythesponsor.中間件：脫敏數(shù)據(jù)被轉(zhuǎn)換為目標(biāo)格式（如CSV），并通過SFTP/RESTAPI安全傳輸，供申辦方下游系統(tǒng)使用。Sponsor:

申辦方側(cè)：Datacloud:thisactsasaningestionlayerforrawdata,enablingsecurestorageandinitialprocessingofdeviationsdatareceivedfromtheCMO.Thiscomponentensuresthatdataisreadilyaccessibleforfurtheranalysisandintegration.

該組件確保數(shù)據(jù)可被快速訪問，用于后續(xù)分析與集成。數(shù)據(jù)云：作為原始數(shù)據(jù)攝取層，安全存儲(chǔ)并初步處理來自CMO的偏差數(shù)據(jù)。Corporatenetwork:thisfacilitatesdatacleaning,transformationandmapping,ensuringthattheprocesseddatameetstherequiredstandardsforanalysis.Thissecureenvironmentsupportstheoperationaluseofdataacrossvariousapplicationswithinthesponsororganization.

該安全環(huán)境支撐申辦方內(nèi)部各應(yīng)用對(duì)數(shù)據(jù)的運(yùn)營(yíng)級(jí)使用。企業(yè)網(wǎng)：負(fù)責(zé)數(shù)據(jù)清洗、轉(zhuǎn)換與映射，確保處理后數(shù)據(jù)符合分析標(biāo)準(zhǔn)。4.3Impactonthebusinessprocess

4.3對(duì)業(yè)務(wù)流程的影響TheintegrationofdeviationdatafromtheCMOyieldedseveralkeybenefitsfortheoperati