环氧乙烷灭菌剖析课件

Ethylene Oxide Sterilization 环氧乙烷灭菌环氧乙烷灭菌TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations 环境保护环境保护TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护EtO sterilization standards 环氧乙氧乙烷相关相关标准准ISO 11135-1,-2TIR 14/TIR 15/TIR 16/TIR 20/TIR 28BI standards 生物指示生物指示剂标准准ISO 11138-1,-2/ISO 14161Microbiological standards微生物微生物标准准ISO 11737-1,-2/AAMI/ST 72 CI standard化学指示化学指示剂标准准ISO 11140-1Residual standard残留残留标准准ISO 10993-7Packaging standard 包装包装标准准 ISO 11607-1，-2Standards 标准标准 TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护 Properties of EtO环氧乙烷性能环氧乙烷性能Ethylene Oxide Gas(EtO)环氧乙烷环氧乙烷 气体气体Boiling point 10.4沸点 10.4 Extremely reactive活跃性强Highly explosive易爆 How Does EtO Kill?环氧乙烷是如何灭菌的环氧乙烷是如何灭菌的?Kills by process called“alkylation”杀灭过程称其为杀灭过程称其为“烷化烷化”EtO irreversibly binds to key molecules in the cell nucleus环氧乙烷对细胞中分子的作用是不可逆的环氧乙烷对细胞中分子的作用是不可逆的DNA 脱氧核糖核酸Proteins(enzymes)蛋白质（酶）Molecules can no longer function分子丧失其作用Cell can no longer reproduce细胞不再被复制 Cell dies细胞死亡TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护9Basic Factors Affecting EtO Sterilization影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Four basic factors interact to product kill影响灭菌的四要素影响灭菌的四要素i.EtO concentration环氧乙烷浓度ii.Humidity湿度iii.Temperature温度iv.Time时间EtO Concentration环氧乙烷浓度环氧乙烷浓度Concentrations commonly between 400 and 1000 mg/L浓度通常在浓度通常在 400 与与 1000 mg/L 之间之间As EtO concentration increases at a given temp and RH microbial inactivation(kill)rate increases在给定的温度与相对湿度条件下在给定的温度与相对湿度条件下,环氧乙烷浓度增加环氧乙烷浓度增加,微生物的灭活率也会增加微生物的灭活率也会增加At concentrations above about 500 mg/L,there is little increase in kill rate浓度大于浓度大于500 mg/L时，杀灭率增加很少时，杀灭率增加很少Significantly more gas adds cost without much benefit值得注意的是值得注意的是EtO的用量越大只会增加成本对灭菌效率益处不大的用量越大只会增加成本对灭菌效率益处不大Humidity湿度湿度Water is required for ethylene oxide to react(alkylation process)with the critical cell molecules 环氧乙烷与关键细胞分子的反应过程环氧乙烷与关键细胞分子的反应过程(烷化过程烷化过程)中需有水中需有水Present as a gas in the sterilization process 在灭菌过程中以气体状态存在Generally measured as Relative Humidity 通常是指相对湿度相对湿度Temperature温度温度Kill rate increases with temperature 杀灭率会随温度的增加而增加杀灭率会随温度的增加而增加For each 100C rise in temperature,the spore inactivation rate will generally double 温度每增加温度每增加100C,通常孢子的杀活率成倍增加通常孢子的杀活率成倍增加13Time时间时间Amount of kill increases with exposure(EtO gas dwell)time杀灭率会随着曝露时间（即杀灭率会随着曝露时间（即EO驻留时间）的延长而增加。驻留时间）的延长而增加。TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护Barriers to Biological Kill影响微生物杀灭的屏障影响微生物杀灭的屏障Physical Barriers物理屏障物理屏障Cardboard Boxes纸板箱Absorb humidity吸湿Inhibit temperature penetration阻碍温度的穿透Shrink Wrap缠绕膜Inhibits temperatutre,moisture and EtO penetration抑制温度、湿度和EtO的渗透Gas(N2/EtO/RH/Air)Can Easily EnterGas(N2/EtO/RH/Air)Can ExitGas(N2/EtO/RH/Air)Cant Easily Enter16Barriers to Biological Kill影响微生物杀灭的屏障影响微生物杀灭的屏障Physical Barriers物理屏障Packaging包装Inhibits temperature penetration抑制温度渗透May inhibit moisture or EtO penetration可能抑制EtO和湿气的渗透Mylar cannot be penetratedby process gases气体不能穿透聚酯薄膜All process gases enter the productsthrough either Tyvek patches,headersor sides所有气体通过Tyvek进入产品Wraps like this back table coverinhibit penetration of gases像手术台布的这种包裹方式抑制了气体的渗入TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护 EtO Process Overview环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Batch Process,typically with 3 phases:主要的主要的3个阶段个阶段Preconditioning Treatment of product prior to the sterilization cycle in a room or chamber to attain a specified temperature and RH.预处理预处理 灭菌循环前,在房间或柜内,使产品达到一定的温度与湿度.Sterilization Chamber Enclosed area which only accommodates sufficient product to fill the sterilizer 灭菌柜灭菌柜 装载待灭菌产品的一个封闭区域Aeration Part of the sterilization process during which EtO desorb from the medical device 解析解析 灭菌过程中医疗器械释放环氧乙烷的阶段.Preconditioning 预处理预处理Heat and Humidity Introduced to Load 装载加热加湿装载加热加湿Air is circulated to assist in heat/humidity transfer空气流通有助于热空气流通有助于热/湿的转移湿的转移Minimum time generally between 12-24 hours.一般至少预热一般至少预热12-24小时小时Product can usually stay in preconditioning much longer(2-4 days total)产品进行预处理的时间一般可以更长产品进行预处理的时间一般可以更长(合计合计2-4天天)Sterilization Chamber-EtO Cycle纯环氧乙烷灭菌工艺纯环氧乙烷灭菌工艺 Initial Vacuum初始抽真空初始抽真空Removes air from the load去除装载中的空气去除装载中的空气Air inhibits penetration of water&EtO into the center of the load 空气会抑制水与环氧乙烷渗透进产品中央Air,when mixed with EtO,creates a flammable mixture 当空气与环氧乙烷混合后会生成一种易燃混合物Deep vacuums cycle have some potential drawbacks 深度抽真空循环具有一些潜在不足深度抽真空循环具有一些潜在不足Overly deep vacuums may start to remove moisture from the load过度的负压可能使产品脱水Potential adverse affects on the product and/or packaging对产品和包装存在潜在的负面影响 Leak Test测漏测漏Purpose is to detect catastrophic chamber leaks旨在检测灭菌柜是否有严重的泄漏旨在检测灭菌柜是否有严重的泄漏Has no effect on kill对灭菌没有影响对灭菌没有影响Humidification加湿加湿Injection of moisture(in the form of steam)to replace any loss during initial vacuum注入湿气注入湿气(蒸汽态蒸汽态)以补充初始抽真空阶段丢失的湿气。以补充初始抽真空阶段丢失的湿气。Typically 25 to 50 mBar rise in pressure 通常注入通常注入25 至至 50 mBar的湿气的湿气Conditioning 处理处理Conditioning(Humidity Dwell)is a period of time where the product“dwells”in the moist chamber environment.处理处理(湿气驻留湿气驻留)指产品驻留在潮湿的灭菌柜环境中的一段时间指产品驻留在潮湿的灭菌柜环境中的一段时间Only change in the“static”environment is when steam is added to keep the chamber environment humidity stable.只有只有“静态静态”环境发生变化，才会注入蒸汽，旨在保持灭菌柜中湿气稳定环境发生变化，才会注入蒸汽，旨在保持灭菌柜中湿气稳定Loss of chamber humidity is due to load absorption of the humidity.灭菌室湿气的减少是由于产品的吸湿灭菌室湿气的减少是由于产品的吸湿Gas Inject气体注入气体注入EtO injection into the chamber将环氧乙烷注入灭菌柜内将环氧乙烷注入灭菌柜内Pressure rise assists in forcing EtO and humidity into the load压力上升促使环氧乙烷和湿气进入装载中压力上升促使环氧乙烷和湿气进入装载中Gas Dwell气体驻留气体驻留Gas Dwell consists of a period of time where the product“dwells”in the EtO laden chamber environment after gas injection.气体驻留是指注入气体后产品气体驻留是指注入气体后产品“停留停留”在充满环氧乙烷的灭菌柜中的一段时间在充满环氧乙烷的灭菌柜中的一段时间Only change in the“static”environment is when EtO(or nitrogen)is added to keep the chamber environment pressure and/or EtO concentration stable.只有当只有当“静态静态”环境才发生变化时，才会注入环氧乙烷（或氮气），旨在保持灭环境才发生变化时，才会注入环氧乙烷（或氮气），旨在保持灭菌柜环境的压力和菌柜环境的压力和/或环氧乙烷浓度稳定或环氧乙烷浓度稳定Loss of chamber pressure is due to product absorption of the EtO.灭菌柜压力的下降是由于产品吸收了环氧乙烷灭菌柜压力的下降是由于产品吸收了环氧乙烷Gas Dwell气体驻留气体驻留Dwell provides time for:气体驻留时间气体驻留时间-Penetration of EtO into the most difficult portions of the load 环氧乙烷穿透到产品中最难以到达的位置Kill generally occurs slowly at the start of dwell due to the fact that:杀灭作用在气体驻留的初期阶段会比较慢的原因：杀灭作用在气体驻留的初期阶段会比较慢的原因：-The EtO has not yet diffused into the most difficult to reach locations环氧乙烷尚未扩散到产品中最难以到达的位置-The temperature in the core of the load is still rising产品中心部位的温度仍在上升The efficiency of kill can be significantly increased with by injecting nitrogen on top of the EtO in the gas injection phase.在气体注入阶段，注入氮气覆盖于在气体注入阶段，注入氮气覆盖于EtO上将显著提高杀灭率上将显著提高杀灭率After Vacuum后抽真空后抽真空Removes EtO from the chamber and the load 去除灭菌柜和装载中的环氧乙烷去除灭菌柜和装载中的环氧乙烷Lowered chamber EtO concentration allows EtO to begin to outgas from solids(beginning aeration of the load in the chamber)降低柜内环氧乙烷浓度，使EO开始从产品中释放出来(装载在柜内的初始解析)Deeper vacuums may help remove more EtO residues深度抽真空有助于去除环氧乙烷残留Gas Washes洗气洗气Help remove high concentrations of EtO from the product有助产品去除高浓度的环氧乙烷有助产品去除高浓度的环氧乙烷Makes the kits safer to handle after sterilization更安全地处理灭菌后产品May shorten required aeration time可缩短解析时间 Final Release 恢复常压恢复常压Brings the chamber to atmospheric pressure to allow opening of the chamber door.The door will not open under vacuum.灭菌柜柜门处于常压下时才可开启。柜门在真空状态下打不开。灭菌柜柜门处于常压下时才可开启。柜门在真空状态下打不开。The chamber must always return to atmospheric using air(to provide a breathable atmosphere in the chamber when the door is opened)灭菌室必须通过注入空气恢复常压灭菌室必须通过注入空气恢复常压(当门打开时，在灭菌室内提供可以呼吸的当门打开时，在灭菌室内提供可以呼吸的大气大气)Aeration 解析解析Heat Introduced to Load to desorb EtO加热以去除装载中的加热以去除装载中的EtOAir is circulated to assist in heat transfer,as well as degassing process空气循环流通，有助热量传导和解析工艺空气循环流通，有助热量传导和解析工艺Time generally 1-5 days for Heated Aeration,typically 2 days.通常解析通常解析1-5天，典型的为天，典型的为2天天 Ambient aeration generally much longer自然解析时间更长自然解析时间更长Below:Aeration RoomAeration 解析解析Factors Affecting EtO Aeration 影响影响EtO解析的因素解析的因素i.Material in which EtO is dissolved 产品材料产品材料Some materials give up EtO faster than others不同材料释放EtO的速度不同ii.Thickness of Material 材料的厚度材料的厚度Thicker materials hold more EtO 材料越厚吸附越多的EtOLonger to diffuse to surface from center 从中心到表面的扩散距离长iii.Temperature温度温度Higher temperatures produce faster aeration rates温度越高解析速率越快iv.Time时间时间Longer times produce lower residual levels解析时间越长残留越低TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护Sterilization Cycle Development灭菌循环开发灭菌循环开发Identify Product Families/Classifications识别产品族识别产品族/分类分类 Identify PCD 识别识别PCDIdentify/Finalize Packaging识别最终包装识别最终包装Identify Load Configuration识别装载结构识别装载结构Sterilization Cycle Development灭菌循环开发灭菌循环开发Identify Product Families/Classifications识别产品族品族/分分类Identify product to be sterilized in the EtO process识别待灭菌产品Put product into product families by grouping similar products.将相似产品归入产品族中product design and function 产品设计和功能manufacturing method 生产方法manufacturing environment 生产环境material of construction 材料组成packaging materials 包装材料density 密度size and/or surface area,and 大小和/或表面积bioburden 生物装载Sterilization Cycle Development灭菌循环开发灭菌循环开发 Identify PCD 识别识别PCD Select most difficult to sterilize from family从产品族中选择最难灭菌的产品从产品族中选择最难灭菌的产品High density 高密度Most torturous pathways 最多弯曲路径Longest tubing,smallest lumen最长的管路，最小的内径High bioburden material 高生物装载For complex product like custom kits,there can be more than one type of challenge device 对于复杂的产品如手术包，可能不止一类产品可作为最难灭菌产品Identify PCD 识别PCDThere are two types of challenge devices两种挑战器Internal 内置挑战器External 外置挑战器Sterilization Cycle Development灭菌循环开发灭菌循环开发Sterilization Cycle Development灭菌循环开发灭菌循环开发Internal Challenge Device内置挑内置挑战器器Generally the most difficult to sterilize device,is seeded with a BI or liquid suspension in the most difficult to sterilize location.Examples of inoculation positions include places like:通常将BI或孢子悬液接种于最难灭菌产品的最难灭菌位置。如The center of long,thin tubing 细长管子的中间Between the seals on a syringe 注射器密封处Sterilization Cycle Development灭菌循环开发灭菌循环开发 Internal Challenge Device内置挑内置挑战器器Package the challenge product in the same manner as products would routinely be sterilized 挑战性产品的包装方式同常规待灭菌产品。Place the packaged challenge product into a sterilization load of product。将已包装的挑战产品置于灭菌装载内。Sterilization Cycle Development灭菌循环开发灭菌循环开发External Challenge Device外置挑战器外置挑战器A BI containing test pack that is a replacement for the internal challenge device,and generally may be used for routine processing含有含有BI的测试包，代替内置挑战器，通常用于常规生产监测的测试包，代替内置挑战器，通常用于常规生产监测Makes it easier to place and retrieve BIs during routine processing在常规生产过程中使得BI的取放更容易。Should be an equal or more difficult challenge to the process than the internal challenge device.对处理过程的挑战性，应大于等于内置挑战器Generally developed using comparative resistance studies通常可通过抗力比较获得Sterilization Cycle Development灭菌循环开发灭菌循环开发Identify/Finalize Packaging识别最终包装识别最终包装Product packaging 产品包装Corrugate,box thickness 瓦楞纸箱，盒子厚度Pouching materials(Tyvek)包装材料 Packing configuration(quantity/box)包装结构（数量/箱）May affect products ability to absorb humidity 可影响产品吸湿的能力May affect products ability to aid temperature penetration 可影响产品协助温度穿透的能力Sterilization Cycle Development灭菌循环开发灭菌循环开发Identify Load Configuration识别装载结构识别装载结构Palletizing approach 堆垛方式Stretch wrap,corner board,netting?缠绕膜、护角、护网?May affect loads ability to absorb humidity可影响装载的吸湿能力May affect loads ability to aid temperature penetration可影响装载协助温度穿透的能力Sterilization Cycle Development灭菌循环开发灭菌循环开发 Proposed Parameters 建议的参数建议的参数Cycle parameters incorporate product-limitation information from customer循环参数应结合客户提供的产品局限性信息。Use an existing cycle(previously developed)for a product使用已存在的灭菌循环（以前开发的）Select a general cycle that works for similar product types:选择一个用于相似产品的通用循环Recommended:Include a fractional cycle in the Validation;建议：确认过程包括部分循环Sterilization Cycle Development灭菌循环开发灭菌循环开发Validation Method确认方法确认方法 3 recognised methods for EtO validation 3种认可的方法种认可的方法i.Direct enumeration 直接计数法直接计数法ii.Fraction-negative 部分阴性法部分阴性法iii.Overkill approach 过度杀灭法过度杀灭法Direct enumeration直接计数法Minimum of 5 cycles needed 5次循环次循环i.one run with 0 time exposure 1次曝露时间为0的循环ii.one run with 4 SLR 1次SLR下降4的循环iii.at least three runs between i and ii 介于i和ii之间的3个循环Fraction-negative method部分阴性法 A minimum of 7 exposure conditions should be used covering:至少至少7个循环个循环At least one set of samples in which all tested samples show growth 至少1次循环，试样显示全部生长。At least 4 test sets in which a fraction of the samples show growth 至少4次循环，试样显示部分生长。At least 2 test sets of samples in which no growth is observed 至少2次循环，试样显示无生长。Fraction-negative method部分阴性法The D-value(time needed to reduce microbial count by at least 1 log)is calculated using the results of the test.根据测试结果计算根据测试结果计算D值（下降值（下降1个对数值所需要的时间）。个对数值所需要的时间）。The theoretical exposure time required to achieve the sterility assurance level(SAL)of the test organism is calculated from the D-value.通过通过D值再计算得到相应无菌保证水平的理论曝露时间值再计算得到相应无菌保证水平的理论曝露时间。Overkill approach(half cycle method)过度杀灭法过度杀灭法(半时循环法半时循环法)Determines minimum time of exposure to EtO at which there are no survivors.(half cycle)测定无存活菌的最短时间测定无存活菌的最短时间-半时循环半时循环3 runs(half cycles)are performed to confirm the minimum time.运行运行3次半时循环以确认此最短时间。次半时循环以确认此最短时间。All three runs should show no growth on the BIs.所有的三次测试应无所有的三次测试应无BI生长。生长。It is recommended that a fractional cycle also be performed to demonstrate the adequacy of the recovery technique.应运行一次短时循环以证明复苏技术的充分性。应运行一次短时循环以证明复苏技术的充分性。TopicsStandards 标准标准Properties of EtO/How does EtO Kill?环氧乙烷性能及灭菌机理环氧乙烷性能及灭菌机理Basic Factor Affecting EtO Sterilization 影响环氧乙烷灭菌的主要因素影响环氧乙烷灭菌的主要因素Barriers to Biological Kill 影响微生物杀灭的屏障影响微生物杀灭的屏障EtO Process Overview 环氧乙烷灭菌过程概览环氧乙烷灭菌过程概览Cycle development 循环开发循环开发Cycle Validation 循环确认循环确认Evaluation of Product EtO Residues 残留评估残留评估EtO Process Flow 环氧乙烷灭菌处理流程环氧乙烷灭菌处理流程Environmental Considerations环境保护环境保护Sterilization Cycle Validation灭菌循环确认灭菌循环确认Documented study研究工作文件化研究工作文件化Validation protocol to assure cycle is adequate确认方案以保证循环是充分的Acceptance Criteria agreed upon before beginning开始前应认可接受标准Procedures are documented程序文件化Sterilization Cycle Validation灭菌循环确认灭菌循环确认Prior to validation确认前确认前Packaging finalized产品包装已确定Load configuration identified装载结构已确定Product Families have been identified(as applicable)产品族已识别（若适用）Bioburden?生物装载？Sterilization Cycle Validation灭菌循环确认灭菌循环确认Parameters to be addressed 待确认参数待确认参数Transfer time after Preconditioning预处理结束后的转移时间Specified ranges for sterilization load(Preconditioning,Chamber,and Aeration)灭菌装载规定的范围（预处理，灭菌柜循环和解析）Verify Gas Sterilant was admitted to chamber验证气体灭菌剂注入灭菌柜Gas weight气体重量Sterilization Cycle Validation灭菌循环确认灭菌循环确认Fractional短时循环短时循环Run 1 Fractional Run in production chamber在生产用灭菌柜内运行1个部分循环Why?New standard states that BI recovery between process facility and testing facility must be demonstrated因为新标准要求必须在生产和测试柜内证明BI的复苏性。Sterilization Cycle Validation灭菌循环确认灭菌循环确认Half Cycles半时循环半时循环Preconditioning time should be less than routine(full cycle)time预处理时间应小于常规（全时循环）时间Half cycles should be sub-nominal for at least one parameter半时循环至少有一个参数小于常规Temperature and Humidity Sensors placed within the load温湿度传感器置于装载内Sterilization Cycle Validation灭菌循环确认灭菌循环确认Half Cycles半时循环半时循环Run 3 total Half Cycles with parameters established during Cycle Development共运行3次半时循环，使用循环开发过程设定的参数Remove samples as defined in procedure按程序规定取出样品Sterilization Cycle Validation灭菌循环确认灭菌循环确认Half Cycles半时循环半时循环Test BIs;typically 7 day incubationBI测试，通常7天培养Master PCD(spored product or otherwise)must show no growth.主PCD（染菌产品或其他）必须显示无生长。Confirmation of SAL 无菌保证水平确认NO PRODUCT TESTING ON HALF CYCLES!半时循环勿进行产品无菌测试半时循环勿进行产品无菌测试Sterilization Cycle Validation灭菌循环确认灭菌循环确认Full Cycle 全时循环全时循环Run a minimum of 1 Full Cycle to evaluate:至少运行1个全时循环以评估：Heat history of load(load contains sensors same as MPQ runs)装载加热历史记录（装载带有传感器同MPQ循环）Aeration/EO Residues 解析/EO 残留Product/packaging functionality 产品/包装功能测试Sterilization Cycle Validation灭菌循环确认灭菌循环确认Full Cycle 全时循环全时循环Aeration Requirements/EO Residues 解析要求/残留Develop dissipation curve to establish release time开发扩散曲线以建立放行时间Sterilization Cycle Validation灭菌循环确认灭菌循环确认Full Cycle 全时循环全时循环Residual allowable limits are based on application of product残留的允许限量是基于产品的应用Qualify release time based on three(3)separate lots(cycles)基于3次循环运行建立放行时间Sterilization Cycle Validation灭菌循环确认灭菌循环确认Full Cycle 全时循环全时循环A second(2X)Full Cycle is highly recommended 建议运行二次灭菌：Simulates reprocessing by the facility 模拟再处理Test EO residues for 2X processed samples测试二次灭菌样品残留Sterilization Cycle Validation灭菌循环确认灭菌循环确认Validation Report 确认报告确认报告Report shall be signed by persons designated responsible for preparing,reviewing,and accepting the report确认报告应由指定负责准备、审核、批准的人签署。Validation Report will contain specifications for EO process.确认报告应包含EO过程规范。Will include value and tolerances for the following:包括以下参数值和公差：Sterilization Cycle Validation灭菌循环确认灭菌循环确认Validation Report 确认报告确认报告Preconditioning,conditioning 预处理，处理Examples-time,temp,humidity,chamber transfer time例-时间，温度，湿度，转移时间Sterilization 灭菌Examples-chamber temp,exposure time例-柜温，曝露时间Aeration 解析 Examples-time,temp 例-时间，温度 Requalification再鉴定再鉴定Critical step in overall validation 整个过程确认的关键步骤整个过程确认的关键步骤Periodic requalification studies designed to detect inadvertant process changes定期的再鉴定以发现未注意的过程变化。Recommended upon introduction of new or significant changes in;新产品的追加或以下方面有显著变化建议进行再鉴定Product 产品Process 过程Packaging 包装Equipment 设备Requalification再鉴定再鉴定Options:Perform one(1)micro PQ run in each qualified chamber在已鉴定的柜室内运行一个MPQEstablish chamber Equivalency per TIR 28:2009,along with reduced PQ requirements依据TIR28：2009和简化的PQ要求建立灭菌柜室等效性Paper Revalidation:Documented evaluation of process to verify no process shifts throughout year.文件式再确认：过程评估文件化以验证在过去的一年中无过程偏移。Requalification再鉴定再鉴定New Requirement 新要求新要求Appropriateness of BI to be verified at defined intervals在规定的时间间隔内验证BI的