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WATER,PURIFIED纯化水H2OMr18.12DEFINITIONWaterforthepreparationofmedicinesotherthanthosethatarerequiredtobebothsterileandapyrogenic,unlessotherwisejustifiedandauthorized.定义制药用水不同于其它用水，要求它是无菌的、无热源的，除非另有调整或授权。Purifiedwaterinbulk散装纯化水PRODUCTIONPurifiedwaterinbulkispreparedbydistillation,byionexchange,byreverseosmosisorbyanyothersuitablemethodfromwaterthatcomplieswiththeregulationsonwaterintendedforhumanconsumptionlaiddownbythecompetentauthority.Purifiedwaterinbulkisstoredanddistributedinconditionsdesignedtopreventgrowthofmicro-organismsandtoavoidanyothercontamination.生产：散装纯化水是经合格的当局规定的适宜人类使用的水经蒸馏、离子交换、反渗透膜或其他任何适合的方法制备。散装纯化水存储和分配于可防止微生物生长和可避免其他任何污染的条件下。MicrobiologicalmonitoringDuringproductionandsubsequentstorage,appropriatemeasuresaretakentoensurethatthemicrobialcountisadequatelycontrolledandmonitored.Appropriatealertandactionlevelsaresetsoastodetectadversetrends.Undernormalconditions,anappropriateactionlevelisamicrobialcountof100CFU/mL,determinedbyfiltrationthroughamembranewithanominalporesizenotgreaterthan0.45μm,usingR2Aagarandincubatingat30-35°Cfornotlessthan5days.Thesizeofthesampleistobechoseninrelationtotheexpectedresult.微生物监测在生产和其后的存储过程中，采取适当的方式以确保水的微生物数受到足够的控制和监测。设置适当的警戒限和行动限以检测不利趋势。在正常条件下，用公称孔径不大于0.45μm微孔滤膜过滤后，采用R2A琼脂于30-35°C下培养至少5天，微生物限度的行动限是100CFU/mL。检测所用的样品量根据期望的结果进行选择。Yeastextract/酵母膏0.5gProteosepeptone/蛋白胨0.5gCaseinhydrolysate/水解酪蛋白0.5gGlucose/葡萄糖0.5gStarch/淀粉0.5gDipotassiumhydrogenphosphate/磷酸氢二钾0.3gMagnesiumsulfate,anhydrous/无水硫酸镁0.024gSodiumpyruvate/丙酮酸钠0.3gAgar/琼脂15.0gPurifiedwater/纯化水可达1000mLAdjustthepHsothataftersterilisationitis7.2±0.2.Sterilisebyheatinginanautoclaveat121°Cfor15min.适当调整pH，使灭菌后的pH为7.2±0.2。通过121°C高压灭菌锅中加热15分钟进行灭菌。GrowthpromotionofR2Aagar—Preparationofteststrains.UsestandardisedstablesuspensionsofteststrainsorpreparethemasstatedinTable0008.-1.Seedlotculturemaintenancetechniques(seed-lotsystems)areusedsothattheviablemicro-organismsusedforinoculationarenotmorethan5passagesremovedfromtheoriginalmasterseed-lot.GroweachofthebacterialstrainsseparatelyasdescribedinTable0008.-1.Usebufferedsodiumchloride-peptonesolutionpH7.0orphosphatebuffersolutionpH7.2tomaketestsuspensions.Usethesuspensionswithin2h,orwithin24hifstoredat2-8°C.AsanalternativetopreparingandthendilutingafreshsuspensionofvegetativecellsofBacillussubtilis,astablesporesuspensionispreparedandthenanappropriatevolumeofthesporesuspensionisusedfortestinoculation.Thestablesporesuspensionmaybemaintainedat2-8°Cforavalidatedperiodoftime.R2A琼脂促生长试验：测试菌株的制备：使用标定过的稳定的测试菌悬浮液或按表0008.-1中所述的方法制备。采用适当的菌株批保藏技术以保证菌株从原始菌株中传代次数不超过5代。根据表0008.-1描述，每次菌株分开培养。使用pH为7.0的氯化钠-蛋白胨缓冲溶液或pH为7.2的磷酸盐缓冲液制备测试悬浮液。悬浮液应在2小时内使用，如保存在2-8°C则可在24小时内使用。作为制备并稀释枯草芽孢杆菌营养细胞新鲜悬浮液的替代方法，也可以制备稳定的孢子悬浮液，然后使用体积适合的孢子悬浮液进行接种测试。孢子悬浮液需在2-8°C、且已验证的期限内保存。—Growthpromotion.Testeachbatchofready-preparedmediumandeachbatchofmedium,preparedeitherfromdehydratedmediumorfromtheingredientsdescribed.InoculateplatesofR2Aagarseparatelywithasmallnumber(notmorethan100CFU)ofthemicro-organismsindicatedinTable0008.-1.Incubateundertheconditionsdescribedinthetable.Growthobtainedmustnotdifferbyafactorgreaterthan2fromthecalculatedvalueforastandardizedinoculum.Forafreshlypreparedinoculum,growthofthemicro-organismsmustbecomparabletothatobtainedwithapreviouslytestedandapprovedbatchofmedium.促生长试验：测试每批已制备好的培养基,以及使用脱水培养基制备或按指定成分制备的培养基。分别将表0008.-1中指定的少量菌悬液（不超过100CFU）接种在R2A琼脂上。按表中指定条件进行培养。所得的培养结果，不可超过已标定培养液的培养结果加上2的因子。对于新鲜制备的培养液，微生物的生长必须与先前测试并且已认可的批次的培养基的培养结果有可比性。Table0008.-1.–GrowthpromotionofR2Aagar表0008.-1.R2A琼脂培养基Micro-organism微生物Preparationoftheteststrain测试菌株的制备Growthpromotion促生长试验Pseudomonasaeruginosasuchas/铜绿假单孢菌，例如:ATCC9027Caseinsoyabeandigestagarorcaseinsoyabeandigestbroth/大豆酪蛋白消化物琼脂培养基或液体培R2Aagar/R2A琼脂NCIMB8626CIP82.118NBRC13275养基30-35°C18-24h≤100CFU30-35°C≤3daysBacillussubtilissuchas/枯草芽孢杆菌，例如:ATCC6633NCIMB8054CIP52.62NBRC3134Caseinsoyabeandigestagarorcaseinsoyabeandigestbroth/大豆酪蛋白消化物琼脂培养基或液体培养基30-35°C18-24hR2Aagar/R2A琼脂≤100CFU30-35°C≤3daysTotalorganiccarbonoroxidisablesubstances.Carryoutthetestfortotalorganiccarbon(2.2.44)withalimitof0.5mg/Loralternativelythefollowingtestforoxidisablesubstances:to100mLadd10mLofdilutesulfuricacidRand0.1mLof0.02Mpotassiumpermanganateandboilfor5min;thesolutionremainsfaintlypink.总有机碳或易氧化物：按（2.2.44）所描述的方法测试总有机碳，应不超过0.50mg/L；或按下述方法测试易氧化物：取本品100mL，加稀硫酸R10mL和0.02M高锰酸钾溶液0.1mL，煮沸5min，溶液仍然略显粉红色。Conductivity.Determinetheconductivityoff-lineorin-lineunderthefollowingconditions.电导率：按下列条件进行离线或在线电导率测试。EQUIPMENTConductivitycell:-electrodesofasuitablematerialsuchasstainlesssteel;-cellconstant:thecellconstantisgenerallycertifiedbythesupplierandissubsequentlyverifiedatsuitableintervalsusingacertifiedreferencesolutionwithaconductivitylessthan1500μS·cm-1orbycomparisonwithacellhavingacertifiedcellconstant;thecellconstantisconfirmedifthevaluefoundiswithin2percentofthecertifiedvalue,otherwisere-calibrationmustbeperformed.设备电导池：适合的材料的电极，如不锈钢；电导池常数：电导池常数通常由供应商鉴定，且应以适当的周期、用电导率已鉴定低于1500μS·cm-1的参照溶液或者用一个导电池常数已鉴定的电导池进行确认；如果测得值在鉴定值的2%以内，则符合规定，否则必须重新校准。Conductometer:accuracyof0.1μS·cm-11orbetteratthelowest