生物安全訓(xùn)練-資料課件

LaboratoryBiosafetyandBiosecurityWANG,DER-YUAN

Ph.D.,CHIEFSectionofBloodProducts&IVDsDrugBiologyDivisionBureauofFood&DrugAnalysisDepartofHealth,ExecutiveYuanTaiwan,RepublicofChinaJan30th,20192023/7/221TopicsConceptofBiosafetyBiologicalagentsLaboratory-associatedinfectionChainofinfectionLaboratorybiosafetyRiskGroupsBiosafetylevelsGoodmicrobiologicalpracticeInstituteResponsibilityInstituteBiosafetyCommitteeBiosafetyWorkingTeamBiosafetyOfficerManagementofLaboratoryBiosafetyRisk-basedand4-levelmanagementsystem4-LeveldocumentationsystemHardwareFacility&equipmentDecontaminationSoftwareBioloigicalAgentsPersonnelBiosecurityEmergentResponse2023/7/222ConceptofBiosafetyBiologicalagentsLaboratory-associatedinfectionChainofinfectionLaboratorybiosafetyRiskGroupsBiosafetylevelsGoodmicrobiologicalpractice2023/7/223LaboratorySafetyFiresafetyChemicalsafetyRadiationsafety2023/7/224MoreSubjectsofLaboratorySafetyBiologicalsafetyPersonalprotectionEmergencyresponse2023/7/225BiologicalSafety(Biosafety)?BIOHAZARD2023/7/226BiologicalAgentBiologicalagentmeansany

microorganism

includingbutnotlimitedto

bacteria,viruses,fungi,rickettsiae,orprotozoaorinfectioussubstances,oranynaturallyoccurring,bioengineerred,orsynthesizedcomponentofanysuchmicroorganismorinfectioussubstance,

capableofcausingdeath,disease,orotherbiologicalmalfunctioninahuman,ananimal,aplant,orotherlivingorganism;

deteriorationoffood,water,equipment,suppliesormaterialofanykind;ordeterioratingalterationoftheenvironment.2023/7/227BiologicalToxinsToxinofbiologicalorigin(biologicaltoxin)meansthetoxicmaterialorproductofplants,animals,microorganismsincludingbutnotlimitedtobacteria,virus,fungi,rickettsiae,orprotozoal,orinfectioussubstance,orarecombinantorsynthesizedmolecule,whatevertheoriginandmethodofproduction,andincludinganypoisonoussubstanceorbiologicalproductthatmaybeengineeredasaresultofbiotechnology,producedbyalivingorganism;oranypoisonousisomerorbiologicalproduct,homology,orderivativeofsuchasubstance.2023/7/228BiosafetyApracticewhichisusedforadequatelyhandlingthebiohazardagents.2023/7/229LaboratoryBiosafety(1)Theapplicationofcombinationsoflaboratorypracticeandprocedure,laboratoryfacilities,andsafetyequipmentwhenworkingwithpotentiallyinfectiousmicroorganisms.2023/7/2210LaboratoryBiosafety(2)ProtectWorkers“Products”Co-workersLabsupportpersonnelEnvironment2023/7/2211LaboratoryBiosafety(3)DependonGoodmicrobiologytechniqueSafetyequipmentsLaboratoryfacilitiesDevelopinstitutebiosafetypracticesEstablishinstitute

biosafetymanual2023/7/2212BiosafetyPracticesSurveyoflaboratory-associatedinfection(orcalledlaboratory-acquiredinfection,LAI)Risk-basedanalysisforchainofInfection2023/7/2213LAISurvey(1)UnitedStates1941-MeyerandEddie74LabsassociatedbrucellosisinfectionsinUS(MeyerKFandEddieB.,J.InfectiousDis.1941;63:23-32.)1949–SulkinandPike222viralinfections(21fatal)Only27%relatedtoknownaccidents1976–SulkinandPikeCumulativetotalof3,921casescitedfrom>5,000Labs<20%associatedwithknownaccidentsExposuretoinfectiousaerosolsplausible(butunconfirmed)for>80%ofreportedcasesMostcommonlyreported:Hepatitis,Tuberculosis,Typhoid,VenezuelanEquineEncephalitis,Brucellosis,Tularemia2023/7/2214LAISurvey(2)UnitedStates2019–ShiandWongWestNilevirus(WNV)pandemicinNorthAmericaarea(US&Canada)Typicalinfectionroutes:mosquitobite,bloodtransfusion,organtransplantation,placentatransfer,lactationNewrouteforWNVinfection:LAI(ShiPYandWongSJ.Expert.Rev.Mol.Diagn.2019;3:733-41.)2023/7/2215LAISurvey(3)GermanyMarburgCityin196731labworkersexposedtogreenmonkeysfromUgandaClinicalsymptom:viralhemorrhagefever(VHF)7deathNewfamilymemberoffiloviridae:Marburgvirus2019–Mempeletal.Throughtheidentificationfromelectronicmicroscopicobservation,virusinfection,PCRassay,nucleicacidsequencing,andviralneutralizationtest,thereisalaboratory-associatedinfectionofrecombinantvacciniavirusinGermany.Theauthorssuggestedstronglythatlabworkershouldreceivethevacciniavaccination

beforeoperation.(MempelM,etal.,J.Invest.Dermatol.2019;120:356-8.)2023/7/2216LAIIncidenceinTaiwan(1)國內(nèi)北部某大學(xué)從事重癥型手口足癥之腸病毒71型（enterovirustype71）研究之病毒實(shí)驗(yàn)室實(shí)驗(yàn)室人員抽血送疾病管制局進(jìn)行Baseline數(shù)據(jù)收集，卻從未得過手口足癥的操作人員血液中檢出EV71抗體陽性反應(yīng)。推測該實(shí)驗(yàn)室可能曾經(jīng)發(fā)生過LAI事件。92年12月16日三軍總醫(yī)院通報(bào)疑似嚴(yán)重急性呼吸道癥候群個(gè)案可能於12月05日處理SARS實(shí)驗(yàn)用過器材中發(fā)生操作失誤導(dǎo)致感染。此為我國首例經(jīng)確認(rèn)之LAI事件。2023/7/2217LAIIncidenceinTaiwan(2)95年8月17日南部某醫(yī)院通報(bào)一例桿菌性痢疾個(gè)案經(jīng)疾病管制局於8月22日證實(shí)為實(shí)驗(yàn)室感染事件。個(gè)案為中部某大學(xué)研究所博士班學(xué)生，在發(fā)病前曾於實(shí)驗(yàn)室進(jìn)行痢疾桿菌（Shigellaflexneri）實(shí)驗(yàn)後經(jīng)疾管局研究檢驗(yàn)中心中區(qū)檢驗(yàn)室將其糞便培養(yǎng)菌株及其實(shí)驗(yàn)使用菌株，以pulsed-fieldgelelectrophoresis（PFGE）分子分型法進(jìn)行菌株DNA指紋圖譜分析，確認(rèn)二菌株具有相同PFGE圖譜，證實(shí)為LAI事件。此為疾管局於95年3月26日起正式施行「感染性生物材料管理及傳染病病人檢體採檢辦法」後，經(jīng)該局證實(shí)之首例LAI事件。該校另一間實(shí)驗(yàn)室於92年時(shí)，亦曾發(fā)生登革熱LAI事件。2023/7/2218ChainofInfectionReservoirofpathogenPortalofescapeTransmissionRouteofentry/infectiousdoseSusceptiblehostIncubationperiodPractices/EquipmentsPPEImmunizationSurveillanceRiskAssessment2023/7/2219LaboratoryBiosafetyManual(1)FocusontheprotectionofWorkers“Products”Co-workersLabsupportpersonnelEnvironment2023/7/2220LaboratoryBiosafetyManual(2)Reference國科會(huì)（93.06）基因重組實(shí)驗(yàn)守則、增修版疾病管制局（93.09）生物安全第三等級(jí)實(shí)驗(yàn)室安全規(guī)範(fàn)、第1.0版疾病管制局（94.9.26）署授疾字第0940000614號(hào)令：感染性生物材料管理與傳染病病人檢體採檢辦法WHO(2019)Laboratorybiosafetymanual,3rdeds.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.CSCHAH(2019)LaboratoryBiosafetyGuidelines,3rdeds.2023/7/2221LaboratoryBiosafetyManual(3)RiskclassificationofbiologicalsafetyGoodmicrobiologicalpractice/technique2023/7/2222RiskGroupsforInfectiousBiologicalAgents

每個(gè)國家（地區(qū)）應(yīng)該依照危險(xiǎn)群等級(jí)，並考慮以下因素來制訂該國（該地區(qū)）微生物分類：微生物之致病性。微生物之傳播方式及宿主範(fàn)圍。微生物可能會(huì)受到當(dāng)?shù)厝丝谝汛嬖谥后w免疫程度、宿主人口密度及活動(dòng)、適當(dāng)媒介之出現(xiàn)及環(huán)境衛(wèi)生標(biāo)準(zhǔn)等因素而影響之。當(dāng)?shù)乜墒褂弥行ьA(yù)防方法。這些方法包括：接種疫苗或給予抗血清（被動(dòng)免疫）之預(yù)防措施；清潔衛(wèi)生措施，例如食品及飲水衛(wèi)生；動(dòng)物宿主或節(jié)肢動(dòng)物媒介之管控。當(dāng)?shù)乜墒褂弥行е委煼椒ā＿@些方法包括：被動(dòng)免疫、暴露後疫苗接種以及使用抗生素、抗病毒及化學(xué)治療藥物，必須考慮耐藥性菌株出現(xiàn)之可能機(jī)率。

WHO(2019)Laboratorybiosafetymanual,3rdeds.2023/7/2223RiskGroupClassificationinTaiwan(1)

第一級(jí)危險(xiǎn)群（riskgroup1,RG1）第一級(jí)危險(xiǎn)群微生物與人類健康成人之疾病無關(guān)。例如不產(chǎn)生內(nèi)孢子之Bacilluslicheniformis,Escherichiacoli-K12,adeno-associatedvirus第一型至第四型，及重組的不含潛在致癌基因產(chǎn)物或毒素之a(chǎn)deno-associatedvirus，且在無輔助病毒存在下進(jìn)行培養(yǎng)疾病管制局（94.9.26）署授疾字第0940000614號(hào)令：感染性生物材料管理與傳染病病人檢體採檢辦法2023/7/2224RiskGroupClassificationinTaiwan(2)第二級(jí)危險(xiǎn)群（riskgroup2,RG2）第二級(jí)危險(xiǎn)群微生物在人類所引起的疾病很少是嚴(yán)重的，而且通常有預(yù)防及治療的方法細(xì)菌包括披衣菌等41類真菌12類寄生蟲31類病毒17類疾病管制局（94.9.26）署授疾字第0940000614號(hào)令：感染性生物材料管理與傳染病病人檢體採檢辦法2023/7/2225RiskGroupClassificationinTaiwan(3)第三級(jí)危險(xiǎn)群（riskgroup3,RG3）第三級(jí)危險(xiǎn)群微生物在人類可以引起嚴(yán)重或致死的疾病，可能有預(yù)防及治療之方法細(xì)菌包括立克次氏菌等9類M.tuberculosis,Yersiniapestis,…etc真菌2類寄生蟲0類病毒與變性蛋白（prions）等10類TSE,SARS-CoV,WNV,Poliovirus(alltypes),HIV,HTLV,Monkeypox,Yellowfevervirus,Hantavirus,WEEvirus,…etc疾病管制局（94.9.26）署授疾字第0940000614號(hào)令：感染性生物材料管理與傳染病病人檢體採檢辦法2023/7/2226RiskGroupClassificationinTaiwan(4)第四級(jí)危險(xiǎn)群（riskgroup4,RG4）第四級(jí)危險(xiǎn)群微生物在人類可以引起嚴(yán)重或致死的疾病，但通常無預(yù)防及治療之方法細(xì)菌0類真菌0類寄生蟲0類病毒7類Ebolavirus,Marburgvirus,Lassavirus,Crimean-Congohemorrhagicfevervirus,…,hemorrhagicfeveragentsandvirusesasyetundefined疾病管制局（94.9.26）署授疾字第0940000614號(hào)令：感染性生物材料管理與傳染病病人檢體採檢辦法2023/7/2227BiosafetyLevels(1)生物安全等級(jí)(biosafetylevels,BSLs)由實(shí)驗(yàn)室規(guī)範(fàn)、技術(shù)、安全設(shè)備與實(shí)驗(yàn)室設(shè)施所組成，區(qū)分為四等級(jí)，每種等級(jí)組合實(shí)驗(yàn)室之功能係適用於操作特定危險(xiǎn)群微生物病原或感染性生物材料。Biosafetylevel-1,BSL-1（生物安全第一等級(jí)）Biosafetylevel-2,BSL-2（生物安全第二等級(jí)）Biosafetylevel-3,BSL-3（生物安全第三等級(jí)）biosafetylevel-4,BSL-4（生物安全第四等級(jí)）WHO(2019)Laboratorybiosafetymanual,3rdeds.2023/7/2228RelationofRGstoBiosafetyLevels,PracticesandEquipmentWHO(2019)Laboratorybiosafetymanual,3rdeds.2023/7/2229BiosafetyLevels(2)必須根據(jù)風(fēng)險(xiǎn)評(píng)估結(jié)果來指定微生物病原於某一生物安全等級(jí)實(shí)驗(yàn)室為之。納入RG2之微生物病原，基於安全操作通常需要BSL-2之設(shè)施、設(shè)備、操作及程序。如果特定實(shí)驗(yàn)會(huì)產(chǎn)生高濃度之氣膠時(shí)，此時(shí)BSL-3實(shí)驗(yàn)室之安全程度施可能比較適合，以確保實(shí)驗(yàn)室內(nèi)更高等級(jí)之氣膠防護(hù)。RG4微生物病原及在某一區(qū)域首次出現(xiàn)之RG3微生物病原皆須在該區(qū)域的BSL-4實(shí)驗(yàn)室進(jìn)行處理。微生物病原之危險(xiǎn)群分類，僅可作為評(píng)估其適合在何種生物安全等級(jí)實(shí)驗(yàn)室中操作的風(fēng)險(xiǎn)因子之一。指定特殊實(shí)驗(yàn)工作之生物安全等級(jí)時(shí)，應(yīng)根據(jù)風(fēng)險(xiǎn)評(píng)估結(jié)果來進(jìn)行專業(yè)判斷，而非單純以所使用病原微生物所屬之某一危險(xiǎn)群來指定所需之實(shí)驗(yàn)室生物安全等級(jí)。WHO(2019)Laboratorybiosafetymanual,3rdeds.設(shè)2023/7/2230BiosafetyLevels(3)Safetyequipmentandpersonalprotectiveequipment

(primarybarriers)Safetyequipmentincludesbiosafetycabinets(BSCs),enclosedcontainers,andotherengineeringcontrolsdesignedtoremoveorminimizeexposurestohazardousbiologicalmaterials.Safetyequipmentalsomayincludeitemsforpersonalprotection,suchasgloves,coats,gowns,shoecovers,boots,respirators,faceshields,safetyglasses,orgoggles.Personalprotectiveequipment(PPE)isoftenusedincombinationwithBSCsandotherdevicesthatcontaintheagents,animals,ormaterialsbeinghandled.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.設(shè)2023/7/2231BiosafetyLevels(4)Facilitydesignandconstruction(secondbarriers)Thedesignandconstructionofthefacilitycontributestothelaboratoryworkers‘protection,providesabarriertoprotectpersonsoutsidethelaboratory,andprotectspersonsoranimalsinthecommunityfrominfectiousagentsthatmaybeaccidentallyreleasedfromthelaboratory.Laboratorydirectorsareresponsibleforprovidingfacilitiescommensuratewiththelaboratory'sfunctionandtherecommendedbiosafetylevelfortheagentsbeingmanipulated.Therecommendedsecondarybarrier(s)willdependontheriskoftransmissionofspecificagents.設(shè)CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.2023/7/2232BiosafetyLevel-1BiosafetyLevel1practices,safetyequipment,andfacilitydesignandconstructionareappropriateforundergraduateandsecondaryeducationaltrainingandteachinglaboratories,andforotherlaboratoriesinwhichworkisdonewithdefinedandcharacterizedstrainsofviablemicroorganisms

notknowntoconsistentlycausediseaseinhealthyadulthumans.Suitableforworkinvolvingwellcharacterizedagentsnotknowntocausediseaseinhealthyadulthumansandofminimalpotentialhazardtolaboratorypersonnelandtheenvironment.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.2023/7/22332ndBarriersinBiosafetyLevel-1FacilityDesignLaboratorieshavedoorsSinkforhandwashingWorksurfaceseasilycleanedBenchtopsareimpervioustowaterSturdyfurnitureWindowsfittedwithflyscreensLocation-notseparatedStructure-normalconstructionVentilation-none2023/7/22341stBarriersinBiosafetyLevel-1ProtectiveclothingLabcoatGlovesPersonalprotectiveequipment(PPE)FaceprotectionEyeprotection2023/7/2235StandardMicrobiologicalPracticesinBiosafetyLevel-1RestrictorlimitaccesswhenworkingProhibiteating,drinkingandsmokingProhibitmouthpipettingUsemechanicalpipettindevicesMinimizesplashesandaerosolsDecontaminateworksurfacesdailyDecontaminatewastesMaintaininsect&rodentcontrolprogram2023/7/2236SpecialPracticesinBiosafetyLevel-1Nonerequired2023/7/2237TrainingRequirementsinBiosafetyLevel-1SupervisorScientistwithgeneraltraininginmicrobiologyorrelatedscienceLabPersonnelSpecifictraininginlabprocedures2023/7/2238BiosafetyLevel-2BiosafetyLevel2practices,equipment,andfacilitydesignandconstructionare

applicabletoclinical,diagnostic,teaching,andotherlaboratoriesinwhichworkisdone

withthebroadspectrumofindigenousmoderate-riskagentsthatarepresentinthe

communityandassociatedwithhumandiseaseofvaryingseverity.Withgoodmicrobiologicaltechniques,theseagentscanbeusedsafelyinactivitiesconductedontheopenbench,providedthepotentialforproducingsplashesoraerosolsislow.Suitableforworkinvolvingagentsofmoderatepotentialhazardtopersonnelandtheenvironment.Immunizationorantibiotictreatmentisavailable.Extremeprecautionwithcontaminatedneedlesorsharpinstruments.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.2023/7/22392ndBarriersinBiosafetyLevel-2Facilitydesign(BSL-1facilityplus:)LockabledoorsBiologicalsafetycabinets&autoclaveEyewashstationAdequateilluminationRestrictedaccesswhenworkinprogressLocation-separatedfrompublicareasStructure-normalconstructionVentilation-directional(airflowsintolabwithoutre-circulationtonon-labareas)**,BSL-2plusorenhancedBSL-22023/7/2240CleanCorridor0PaBSL-2Lab-20Pa0PaDirectionalInwardAirflow

(NegativePressuredRooms)2023/7/22411stBarriersinBiosafetyLevel-2InadditiontoBSL-1UseclassIIBSCforworkwithinfectiousagentsinvolving:AerosolsandsplashesLargevolumesHighconcentrations2023/7/2242BiosafetyCabinetsProvidepersonnel,environmental,andproductprotection.Inwardairflowprovidespersonnelprotection.DownwardflowingHEPAfilteredairprovidesproductprotection.HEPAfilteredexhaustairprovidesenvironmentalprotection.Threecategories(WHOBiosafetyManual,3rd,2019):ClassIClassII(A1,A2,B1,B2)ClassIII2023/7/2243ClassIIBiosafetyCabinetsEquipmentlayoutTechnique:avoidgeneratingaerosolsanddisturbingair-flowCleanCulturesWastesandHazardsProcessingArea2023/7/2244ClassIIBiosafetyCabinetsXXX2023/7/2245StandardMicrobiologicalPracticesinBiosafetyLevel-2AsinBSL-1Labeledwithbiosafetylevel2023/7/2246SpecialPracticesinBiosafetyLevel-2(1)SupervisionSupervisorisacompetentscientistwith

increasedresponsibilitiesLimitsaccessifimmunocompromisedRestrictsaccesstoimmunizedLabpersonnelAwareofpotentialhazardsProficientinpractices/techniquesNeedles&sharpsprecautionsUsesharpscontainersDON’Tbreak,bend,re-sheathorreusesyringesorneedlesDON’TplaceneedlesorsharpsinwastecontainersDON’TtouchbrokenglasswithhandsUseplasticwareXXOO2023/7/2247SpecialPracticesinBiosafetyLevel-2(2)BiohazardwarningsignsBiosafetymanualspecifictolabTrainingwithannualupdatesUseleak-prooftransportcontainersImmunizationsBaselineserumsamples*DecontaminateworksurfacesReportspillsandaccidentsNoanimalsinlaboratories*,Storedatleast10yrafterleavinglab2023/7/2248BiosafetyLevel-3BiosafetyLevel3practices,safetyequipment,andfacilitydesignandconstructionareapplicabletoclinical,diagnostic,teaching,research,orproductionfacilities(fluvaccineGMPmanufacture)inwhichworkisdonewithindigenousorexoticagentswithapotentialforrespiratorytransmission,andwhichmaycauseseriousandpotentiallylethalinfection.Mycobacteriumtuberculosis,St.Louisencephalitisvirus,andSARScoronavirus

arerepresentativeofthemicroorganismsassignedtothislevel.Primaryhazardstopersonnelworkingwiththeseagentsrelatetoautoinoculation,ingestion,andexposuretoinfectiousaerosols.Suitableforworkwithinfectiousagentswhichmaycauseseriousorpotentiallylethaldiseaseasaresultofexposurebytheinhalationroute.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.2023/7/22492ndBarriersinBiosafetyLevel-3(1)Facilitydesign(BSL-1&BSL-2facilityplus:)SeparatebuildingorisolatedzoneDoubledoorentry,directionalinwardairflow,single-passair10-12airchanges/hourEnclosuresforaerosolgeneratingequipmentRoompenetrationssealedwalls,floorsandceilingsarewaterresistantforeasycleaning2023/7/2250CleanCorridor0PaBSL-3Lab-35PaAnteroom-20Pa0Pa-20PaDirectionalInwardAirflow:MaintenanceofSingle-PassAir2023/7/22512ndBarriersinBiosafetyLevel-3(1)VacuumlinesprotectedwithliquiddisinfectanttrapsorHEPAfiltersWastedisposalproceduresWastesdecontaminatebeforeremovingfromrooms2023/7/22521stBarriersinBiosafetyLevel-2BSL-1and2safetyequipmentplus:ClassIIorIIIBSCtomanipulateinfectiousmaterialsRespiratoryprotectionmaybeindicated2023/7/2253StandardMicrobiologicalPracticesinBiosafetyLevel-3AsinBSL-1&BSL-22023/7/2254SpecialPracticesinBiosafetyLevel-3(1)WorkincertifiedBSCUsebio-aerosolcontainingequipmentDecontaminatespillspromptly2023/7/2255SpecialPracticesinBiosafetyLevel-3(2)SupervisionSupervisorisacompetentscientistexperiencedworkingwithagentsEstablishescriteriaforentryRestrictsaccessDevelopspolicies/proceduresTrainslabpersonnelLabpersonnelStrictlyfollowguidelinesDemonstrateproficiencyReceiveappropriatetrainingReportincidents*Participateinmedicalsurveillance2023/7/2256InstituteResponsibilityInstituteBiosafetyCommitteeBiosafetyWorkingTeamBiosafetyOfficer2023/7/2257InstituteBiosafetyCommittee(1)感染性生物材料管理及傳染病病人檢體採檢辦法第三條持有、保存或使用感染性生物材料之機(jī)構(gòu)（以下稱設(shè)置單位），其感染性生物材料區(qū)分為二級(jí)以上且其人員達(dá)五人以上者，應(yīng)設(shè)生物安全委員會(huì)（InstituteBiosafetyCommittee,IBC）管理；其人員未達(dá)五人者，應(yīng)指定專人管理。前項(xiàng)委員會(huì)及專責(zé)人員，應(yīng)報(bào)中央主管機(jī)關(guān)核備，並副知地方主管機(jī)關(guān)。2023/7/2258InstituteBiosafetyCommittee(2)感染性生物材料管理及傳染病病人檢體採檢辦法第四條生物安全委員會(huì)之任務(wù)如下：一、持有、保存、異動(dòng)或使用第二級(jí)以上危險(xiǎn)群微生物之感染性生物材料之同意及督導(dǎo)。二、使用感染性生物材料之實(shí)驗(yàn)室生物安全等級(jí)之審議。三、感染性生物材料及實(shí)驗(yàn)室生物安全缺失之內(nèi)部稽核及改善督導(dǎo)。四、生物安全訓(xùn)練之指導(dǎo)。五、生物安全緊急應(yīng)變計(jì)畫之審議。六、生物安全意外事件之處理、調(diào)查及報(bào)告。七、實(shí)驗(yàn)室啟用或關(guān)閉之審議。八、生物安全爭議問題之審議。九、其他有關(guān)感染性生物材料管理事項(xiàng)之審議。前項(xiàng)內(nèi)部稽核每年至少辦理一次。2023/7/2259InstituteBiosafetyCommittee(3)生物安全第三等級(jí)實(shí)驗(yàn)室品質(zhì)管制規(guī)範(fàn)第1.0版第壹章第2.2節(jié)生物安全委員會(huì)之職責(zé)：2.2.1訂定該機(jī)構(gòu)委員會(huì)設(shè)置與作業(yè)要點(diǎn)。2.2.2訂定該機(jī)構(gòu)實(shí)驗(yàn)室管理要點(diǎn)規(guī)範(fàn)細(xì)則。2.2.3訂定該機(jī)構(gòu)實(shí)驗(yàn)室安全違規(guī)處理細(xì)則。2023/7/2260BiosafetyWorkingTeam(1)生物安全第三等級(jí)實(shí)驗(yàn)室品質(zhì)管制規(guī)範(fàn)第1.0版第壹章第2.3節(jié)生物安全工作小組之主管事務(wù)：

承接委員會(huì)決定，負(fù)責(zé)建立、監(jiān)控和執(zhí)行生物安全政策與程序，以便遵守政府所頒布之相關(guān)適用標(biāo)準(zhǔn)、規(guī)範(fàn)或法規(guī)。對(duì)凡違反安全規(guī)則和程序者，有權(quán)要求改善。2023/7/2261BiosafetyWorkingTeam(2)生物安全第三等級(jí)實(shí)驗(yàn)室品質(zhì)管制規(guī)範(fàn)第1.0版第壹章第2.4節(jié)生物安全工作小組之功能：2.4.1建立、監(jiān)督與強(qiáng)化生物材料之所有安全工作政策、操作和程序。2.4.2定期查核實(shí)驗(yàn)室，於執(zhí)行或使用生物材料時(shí)，是否符合適用法規(guī)、標(biāo)準(zhǔn)和法規(guī)。2.4.3依據(jù)國內(nèi)所訂危害生物材料之基準(zhǔn)，評(píng)估該機(jī)構(gòu)現(xiàn)況後，決定是否準(zhǔn)予研究計(jì)畫使用現(xiàn)有之實(shí)驗(yàn)室。2.4.4啟動(dòng)應(yīng)變緊急計(jì)畫，妥善處理生物材料之污染和人員感染之意外，如有重大事故發(fā)生時(shí)，應(yīng)逐級(jí)通報(bào)尋求支援處理。2.4.5調(diào)查任何有嚴(yán)重違反生物安全政策、操作規(guī)範(fàn)所導(dǎo)致感染事故，製成詳細(xì)紀(jì)錄，並由委員會(huì)向機(jī)構(gòu)負(fù)責(zé)人及有關(guān)政府單位提出書面報(bào)告。2.4.6建議該機(jī)構(gòu)採行有關(guān)生物安全設(shè)備之操作及實(shí)施安全措施。2.4.7擬定適合實(shí)驗(yàn)室相關(guān)之各式人員所需訓(xùn)練計(jì)畫書，並定期舉辦相關(guān)人員訓(xùn)練。2.4.8負(fù)責(zé)實(shí)驗(yàn)室研究及其它工作人員之審核及使用權(quán)限之授權(quán)。建議授權(quán)書。2023/7/2262BiosafetyOfficer生物安全第三等級(jí)實(shí)驗(yàn)室品質(zhì)管制規(guī)範(fàn)第1.0版第壹章第2.5節(jié)生物安全官：由機(jī)構(gòu)負(fù)責(zé)人任命，係該機(jī)構(gòu)環(huán)境、衛(wèi)生和安全管理之負(fù)責(zé)人，亦為生物安全委員會(huì)之當(dāng)然委員，其職責(zé)至少包括：2.5.1定期執(zhí)行嚴(yán)格查核，確保正確生物安全操作與程序。2.5.2協(xié)助研究人員制定危害生物材料移轉(zhuǎn)管制計(jì)畫，並提供有助於生物性材料之安全儲(chǔ)存、操作和使用之技術(shù)建議。2.5.3協(xié)助生物安全工作小組、研究人員制定生物材料安全操作方法及程序細(xì)則。2.5.4調(diào)查有關(guān)實(shí)驗(yàn)室意外事故。2.5.5擬定意外事故之污染和人員感染等緊急事件之處理計(jì)畫。2.5.6提供有關(guān)適用於實(shí)驗(yàn)室設(shè)備之選擇、裝機(jī)、維護(hù)之生物安全防護(hù)建議。2.5.7負(fù)責(zé)實(shí)驗(yàn)室管理與維護(hù)等事宜。2023/7/22632023/7/2264ManagementofLaboratoryBiosafetyRisk-basedand4-levelmanagementsystem4-LeveldocumentationsystemHardwareFacility&equipmentDecontaminationSoftwareBioloigicalAgentsPersonnelEmergentResponseBiosecurity2023/7/2265LaboratoryManagementQualitymanagementsystemfortestinglaboratoryCNS/ISO17025QualitymanagementsystemformedicallaboratoryISO15189Qualitymanagementsystemforpre-clinicalanimaltestinglaboratoryofinvestigationofnewdrugGoodlaboratorypractice(GLP)2023/7/2266ManagementofBSL-3/-2

Laboratories(1)WHO(2019)Laboratorybiosafetymanual,3rdeds.CDC(2019)BiosafetyinMicrobiologicalandBiomedicalLaboratories,5theds.,USA.CSCHAH(2019)LaboratoryBiosafetyGuidelines,3rdeds.,CanadaInternationalBiosafetyandBiosecurityLaboratoryStandard

(developmentinitiative,2019)2023/7/2267ManagementofBSL-3/-2Laboratories(2)Risk-basedmanagementsystem4-LevelmanagementsystemDirect-GeneralInstituteBiosafetyCommittee(IBC)BiosafetyWorkingGroupEmergentResponseTeamLabUsersDirect-GeneralInstituteBiosafetyCommittee(IBC)BiosafetyOfficerBiosafetyWorkingTeamEmergentResponseTeamLabUsers2023/7/2268ManagementofBSL-3/-2Laboratories(3)4-LevelmanagementsystemPolicyRegulationGuidelineStandardOperationProcedures(SOP)RecordsBSL-3/BSL-2實(shí)驗(yàn)室生物安全規(guī)範(fàn)藥檢局生物安全要點(diǎn)BSL-3/BSL-2實(shí)驗(yàn)室作業(yè)程序BSL-3/BSL-2實(shí)驗(yàn)室紀(jì)錄感染性生物材料管理及傳染病病人檢體採檢辦法傳染病防治法生物安全訓(xùn)練計(jì)畫生物災(zāi)害緊急應(yīng)變計(jì)畫PolicyRegulationPlanStandardOperationProcedures(SOP)RecordsBSL-3/BSL-2實(shí)驗(yàn)室生物安全規(guī)範(fàn)藥檢局生物安全要點(diǎn)BSL-3/BSL-2實(shí)驗(yàn)室作業(yè)程序BSL-3/BSL-2實(shí)驗(yàn)室紀(jì)錄年度測試、再確效計(jì)畫實(shí)驗(yàn)室品質(zhì)管理計(jì)畫生物安全訓(xùn)練計(jì)畫生物災(zāi)害緊急應(yīng)變計(jì)畫確保實(shí)驗(yàn)室安全2023/7/2269ManagementofBSL-3/-2Laboratories(4)HardwareFacilitiesEquipmentsSoftwarePersonnelMaterialcontrol&accountabilityEmergentresponse2023/7/2270HardwareManagement:

FacilitiesDailycheckMonthlycheck&maintenanceAnnualcheck&maintenancePeriodic/annualdecontaminationAnnualperformancere-validationHVACsystemDDC/PLCsystemPowersupplyFirecontrolRoomintegrity5W1HWHO?WHEN?WHERE?WHICH?WHAT?HOW?2023/7/2271HardwareManagement:DecontaminationBeforechangingtheroomandBI/BOHEPAfiltersofHVACsystemBeforechangingHEPAfilter,fanmotorandcontrolpanelofBSCAftersystemfailureInannuallymaintainingserviceInemergentresponsetobiologicalspillsChoiceofDecontaminationMethodsinBSL-3FacilityFormaldehydeFumigationItiswidelyuseddeconmethodinTaiwan,however,formaldehydeistoxic,carcinogenic,potentiallyexplosiveandrequirescarefullyhandlingprocedures.Electronicsandequipmentscouldnotbetreatedwithformaldehyde.VaporizedHydrogenPeroxide(VHP)VHPhasbecomethenewdecontaminationmethodinthepharmaceuticalandbio-laboratoriesinrecentyears.2023/7/2272HardwareManagement:EquipmentsPeriodicmaintenanceandcalibrationPeriodicperformancere-validationCleaningbefore/afteruseDecontaminationBiologicalsafetycabinetsClassIItypeB1,B2andA2Steamsterilizer(autoclave)Personalprotectiveequipments(PPE)2023/7/2273SoftwareManagement:

PersonnelGeneralrequirementsKnowledgeablesupervisorKnowledgeablepersonnelAwareofpotentialhazardsProficientinpractices&techniquesLabspecificbiosafetymanualOneofthelaboratorybiosecurityissues2023/7/2274BiosafetyTrainingDependontheresultsofbio-riskassessmentIncludegoodmicrobiologicalpractice,goodlaboratorypractice,andentrance/exitproceduresScenariosandproficiencyevaluation

InBFDA:40hrstrainingand20hrsscenariosforBSL-3labusers20hrstrainingand8hrsscenaiosforBSL-2labusers2023/7/2275HealthMonitoringAnnuallyphysicalexaminationVaccination(HBV,OPV,botulinumtoxoid…etc)andantisera(botulinumantitoxin)Baselineserumpreservationfor10yearsafterleavinglabs(atleast2years/TWCDC’sproposedregulation)2023/7/2276SoftwareManagement:

MaterialControl&AccountabilityObjectiveEnsurethecompleteandtimelyknowledgeof:whatmaterialsexistwherethematerialsarewhoisaccountableforthemNottodetectwhethersomethingismissingOneofthelaboratorybiosecurityissues2023/7/2277KeyIssuesWhatbiologicalagentsaresubjecttomaterialcontrol&accountability(MC&A)measuresTheoperatingproceduresassociatedwiththematerials*wheretheycanbestoredandusedhowtheyareidentifiedhowinventoryismaintainedWhatrecordsneedtobekeptforthosematerialsandthetimelinessrequirementsforthoserecordsWhatdoesaccountabilitymeansDocumentationandreportingrequirements***,TWCDCauditsannuallytheinstituteBLS-2/-3MC&Asince2019.**,IBCshouldkeeptherecordsandproceedinternalauditingperiodic.2023/7/2278BiologicalMaterialsDefining“material”iscomplicatedAgentGeneralinfo:nameanddescriptionBiologicalmaterialsafetydatasheet(Bio-MSDS,BSDS)QuantityBasedoncontainersorotherunits,NOTnumberofmicrobes2023/7/2279GeneralInformationAgentWhatagentsarehighrisk?Viable?WholeorganismorDNA?QuantityAnyamountcanbesignificantAthresholdamountfortoxinsFormRepositorystocks,workingsamples,inhost,contaminationDetail—whatlevelisadequateforMC&A?MaterialasitemsEachvialasaseparateinventoryrecord?Capture—whendoesMC&Astart&stop?Naturallyoccurring;clinicalsamples;disposition2023/7/2280AdditionalInformationAttributes:tocharacterizethematerial(“what”)Agent/strainOriginDateDescription:toidentifyaparticularitemofthematerial(“which”)ContainerIdentificationLocation2023/7/2281Bio-MSDSAgentandtoxincharacteristicsDiseaseandclinicalfeaturesMechanismofactionMedicalmanagement,prophylaxis,andtreatmentDecontaminationPersonalprotection2023/7/2282ControlControliseither…Engineered/PhysicalAdministrativeContainmentispartofmaterialcontrolContainmentLab/Freezer/AmpouleProceduresareessentialformaterialcontrolForbothnormalandabnormalconditions2023/7/2283AccountabilityAllmaterialshouldhaveanassociated“accountableperson”ThepersonbestinapositiontoanswerquestionsabouttheassociatedmaterialNotsomeonetoblame!Ensurethatnomaterialis“orphaned”2023/7/2284InfectiousMaterialTransportTransport–movementofbiologicalmaterialoutsideofarestrictedareaResearchlabsSampletransfersarenecessaryforstudyandtofurtherresearchPublichealthlabsanddiagnosticlabsSampletransfersarenecessaryfordiagnosisandanalysisTransportcanoccurAcrossinternationalbordersWithinacountryWithinafacility2023/7/2285InternalTransportMovementofmaterialstoandfromrestrictedareaswithinafacilityMayinvolvepersonnelfromLabsShippingareasReceivingareasDisposalareas(e.g.autoclaveandincineratorrooms)MovematerialssafelyandsecurelySOPsLeak-proofcontainersPre-approval?Chainofcustody?2023/7/2286ExternalTransportMovementofmaterialsfromonefacilitytoanotherfacilityMayinvolvecommercialcarriersOccurwithinawidearrayofinternationalandstateregulationsandstandardsMustbeabletomovefrozenmaterialsefficientlyNeedtobecost-effective2023/7/2287EmergentResponseEmergentincidencesBiologicalspillsMedicalneeds(shock,…)FireEarthquakePowerfailureOtheraccidents2023/7/2288ClassificationofBiologicalSpillsLevel

IInsidethe

equipment(BSC,centrifuge,incubator,freezer,…etc)Contaminatesmallarea,lowriskReporttoIBCLevelIIInsidethecontainment(onfloor,wall,door,…etc)Contaminatemediumarea,moderateriskReporttoIBC,ifpeopleinfected,reporttoTWCDC.LevelIIIOutofthecontainment(spreadtowholebuildingoroutside)Contaminatelargeareas,highriskReporttoIBCandTWCDC.2023/7/2289EmergentResponseofBiologicalSpillDef