ISPE+7.制药用蒸汽

PHARMACEUTICALSTEAM制药用蒸气7.PHARMACEUTICALSTEAM7.制药用蒸气7.1INTRODUCTION7.1序论Thischapteraimstosimplifyandstandardizetheprocessofselection,programming,anddesignofpharmaceuticalsteamsystems.Guidelines,information,andoptionsareprovided,alongwithadvantagesanddisadvantages,basedonthebestandmostcosteffectiveofcurrentandprovenpracticesandtechnologies.本章旨在简化以及标准化制药用蒸气系统的选择、规划和设计。并以现行和已被证明的最好的和成本效应最高的实践和工艺为根据，给出一些指导方针、信息资料和选项，以及优缺点。Theabsenceofregulationsgoverningtheuseofsteaminpharmaceuticalprocesseshasresultedintheproliferationofdifferingpracticesandinterpretations.Mostinterpretationsaremadeonthesideofconservatism.Unfortunately,inadditiontoincreasingcostwithoutanassociatedincreaseinbenefits,excessiveconservatismcanresultinsystemcomplexity,andpossiblyreducedreliability.Oneexampleistheuseofcleansteam(non-utilityboilerproducedsteam)whereaformofutilitysteam(utilityboilerproducedsteam)wouldbeadequatetomaintainproductquality.Theinstallationofacleansteamgeneratorwhenasimplesteamreducingstationwouldsufficeresultsinaddedequipmentandtheassociatedimpactoncost,complexity,andreliability.在制药工艺中指导蒸气使用的法规缺乏导致衍生出不同实践和理解。大多数理解是保守的。不幸的是，这除了增加成本外没有相应的增加利益，过度的保守能够导致系统复杂并且可能减少其可靠性。举个例子，在一种公用蒸气（公用锅炉产生的蒸气）就足以维持产品质量的地方使用清洁蒸气（非公用锅炉产生的蒸气），在一个普通蒸气简化装置就能满足需要时安装一个清洁蒸气发生器，这导致设备增加并在成本，复杂性以及可靠性方面造成相关影响。Insomeinstances,interpretationsarebasedoninaccurateassumptionsofwhatisimportantorcritical.AnexampleistheoverspecifyingofpretreatmentorusingWFIasfeedtosolvetheperceivedproblem.在某些情况中，理解是建立在不准确假设“什么是重要或关键的”基础上的。举个例子，比如过度规定预处理或使用注射用水作为给水来解决那些已察觉的问题。Thechapterestablishesstandarddefinitionsfortermscommonlyassociatedwithpharmaceuticalsteamandprovidesinformationthatfacilitatesmakingcorrectandcosteffectivedecisions.本章为制药用蒸气相关的术语制定了标准定义，并为促使作出正确和成本有效的决定提供了信息。7.2cGMPISSUES7.2cGMP出版物Theuserhastheultimateresponsibilityforsystemdesignandperformance,andforensuringthatthepropertypeofsteamisusedforagivenprocess.用户对系统的设计和性能拥有最终职责并要确保适当类型的蒸气用于给定的工艺。ThereisnoFDAorUSPminimumstandardforcleansteam.However,cGMPsforlargevolumeparenterals(LVPs)issuedin1976indicatedthatfeedwaterforboilerssupplyingsteamthatcontactcomponents,drugproducts,anddrugproductcontactsurfacesshallnotcontainvolatileadditivessuchasaminesorhydrazines.对于清洁蒸气，FDA或USP没有最低标准。然而，1976年发行的cGMP关于大容量注射液部分表明供应蒸气的锅炉的给水、接触组件、药品和药品接触面不能包含挥发性添加剂比如胺或联胺。Fewregulationsgovernthedesignandconstructionofcleansteamgenerators.Therearealsonoregulationsgoverningmaterialsofconstruction,typeorlevelofinstrumentation,surfacefinishes,oroperatingtemperatures.很少法规管理清洁蒸气发生器的设计和构造，也没有法规管理构造材料、使用仪器的类型和等级、表面抛光或操作温度。AmongUSGovernmentpublications,theFDA'sCodeofFederalRegulations(CFR)providesculinarysteamrecommendationsandstipulationsrelatedtoheatexchangerandtankairventsdesignandconstruction.TheCulinarysteamrecommendationsapplytofoodapplicationsonly.在美国政府出版物中，FDA的联邦管理法规(CFR)提供厨房用蒸气的优点和关于热交换器及水罐排气口设计、构造的规定。建议厨房用蒸气只用于食品应用。USPublicHealthService/DairyIndustryCommittee,3ASanitaryStandards,Number609-02,addsadditionallimitationstoCulinarysteamfeedwateradditivesforfoodapplications.Itshouldbenotedthatboilerfeedwateradditivespermittedinfoodforhumanconsumptionmaynotbeacceptableindrinkingwaterororallyingesteddrugproducts.美国公共卫生部门/乳制品工业委员会，3A卫生标准，编号609-02，为食品应用而对厨房用蒸气给水添加剂增加附加限制。应该注意人用食品中的锅炉给水添加剂不能用于饮用水或口服药品。7.2.1SteamAttributes7.2.1蒸气特质7.2.1.1Quality7.2.1.1质量ThetermQualitywhenreferringtosteamindicatesthelevelofsteamsaturation.TherearenoFDAorUSPregulationsrelatingtominimumsteamqualityorthelevelofnon-condensablegassespresentinpharmaceuticalsteam.(SeeSection7.4.)当涉及蒸气时，“质量”术语表示蒸气饱和标准。没有关于最低“蒸气质量”或在制药用蒸气中不可压缩气体标准的FDA或USP法规。（参看7.4部分）Europeanregulatorshavedefinedspecificcriteriaforpharmaceuticalsteamusedforequipmentsterilization.(EuropeanStandardEN285-SteamSterilizers-referencesection13.3)Thesecoveracceptablelevelsofsaturationordryness,thelevelofsuperheat,andthevolumeofnon-condensablegasespresent.欧洲法规对用于设备灭菌的制药用蒸气规定了具体标准。(欧洲标准EN285-蒸气灭菌器-参考13.3部分)。这些包含饱和或干燥标准、过热标准和不可压缩气体体积。7.2.7.2Purity7.2.7.2纯度Purityrequirementsforsteamusedinpharmaceuticalmanufacturingandproductdevelopmentaredrivenbytheproductcharacteristics,manufacturingprocess,andtheintendeduseoftheproduct.Theproductmanufacturerisresponsibleforensuringthatsteamusedtoprocesstheproductisappropriate.用于制药生产和产品研制的蒸气纯度要求由产品特性、生产工艺和产品预期用途决定。药品生产商有责任确保将合适的蒸气用于药品生产。Thoughsteampurityrequirementsareproductspecific,itmaybeimpracticaltoreliablyproducespecialsteamforeachsituation.Manufacturingoperationstypicallygenerateanddistributeonlyoneortwosteampuritygrades,commonlygrouped.虽然蒸气纯度要求是因产品特性而不同，但为每个情况可靠地生产特殊蒸气是不实用的。生产操作典型地产生和分配一般分组为一种或两种的蒸气纯度等级。7.3TYPESOFSTEAM7.3蒸气类型Pharmaceuticalsteamisclassifiedintotwo(2)typesbasedontheirrespectivesources.Theseare:1)Utility-Boilerproducedsteam,hereaftercalledUtilitySteam.2)Non-UtilityBoilerproducedsteam,hereaftercalledCleanSteam.根据它们各自的来源，制药用蒸气分为两种类型。它们是：1)公用锅炉产生的蒸气，此后叫做公用蒸气。2)非公用锅炉产生的蒸气，此后叫做清洁蒸气。7.3.1UtilitySteam7.3.1公用蒸气Utilitysteamischaracterizedwithusuallyhaving:•Chemicaladditivestocontrolscaleandcorrosion•Relativelyhighpressurewiththepotentialofgeneratingsuperheatduringexpansion•Relati