環(huán)氧乙烷滅菌（課堂PPT）

1、1 Ethylene Oxide SterilizationEthylene Oxide Sterilization 環(huán)氧乙烷滅菌環(huán)氧乙烷滅菌2TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Process Overview

2、環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations 環(huán)境保護環(huán)境保護3TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Aff

3、ecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Process Overview 環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Consider

4、ations環(huán)境保護環(huán)境保護4 EtO sterilization standards 環(huán)氧乙烷相關標準環(huán)氧乙烷相關標準ISO 11135-1,-2TIR 14 / TIR 15 / TIR 16 / TIR 20 / TIR 28 BI standards BI standards 生物指示劑標準生物指示劑標準ISO 11138-1,-2/ ISO 14161 Microbiological standards微生物標準微生物標準ISO 11737-1,-2 / AAMI/ST 72 CI standard化學指示劑標準化學指示劑標準ISO 11140-1 Residual standard

5、殘留標準殘留標準ISO 10993-7Packaging standard 包裝標準包裝標準 ISO 11607-1，-2Standards Standards 標準標準 5TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Pr

6、ocess Overview 環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護6 Properties of EtOProperties of EtO環(huán)氧乙烷性能環(huán)氧乙烷性能 Ethylene Oxide Gas (EtO)環(huán)氧乙烷環(huán)氧乙烷 氣體氣體 Boilin

7、g point 10.4沸點 10.4 Extremely reactive活躍性強 Highly explosive易爆 7How Does EtO Kill?環(huán)氧乙烷是如何滅菌的環(huán)氧乙烷是如何滅菌的? ? Kills by process called “alkylation”殺滅過程稱其為殺滅過程稱其為 “烷化烷化” EtO irreversibly binds to key molecules in the cell nucleus環(huán)氧乙烷對細胞中分子的作用是不可逆的環(huán)氧乙烷對細胞中分子的作用是不可逆的 DNA 脫氧核糖核酸 Proteins (enzymes) 蛋白質（酶）Molec

8、ules can no longer function分子喪失其作用Cell can no longer reproduce細胞不再被復制 Cell dies細胞死亡8TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Proce

9、ss Overview 環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護9Basic Factors Affecting EtO SterilizationBasic Factors Affecting EtO Sterilization影響環(huán)氧乙烷滅菌的主要因素

10、影響環(huán)氧乙烷滅菌的主要因素 Four basic factors interact to product kill影響滅菌的四要素影響滅菌的四要素EtO concentration環(huán)氧乙烷濃度Humidity濕度Temperature溫度Time時間10EtO ConcentrationEtO Concentration環(huán)氧乙烷濃度環(huán)氧乙烷濃度 Concentrations commonly between 400 and 1000 mg/L濃度通常在濃度通常在 400 與與 1000 mg/L 之間之間 As EtO concentration increases at a given te

11、mp and RH microbial inactivation (kill) rate increases在給定的溫度與相對濕度條件下在給定的溫度與相對濕度條件下,環(huán)氧乙烷濃度增加環(huán)氧乙烷濃度增加,微生物的滅活率也會增加微生物的滅活率也會增加 At concentrations above about 500 mg/L, there is little increase in kill rate濃度大于濃度大于500 mg/L時，殺滅率增加很少時，殺滅率增加很少 Significantly more gas adds cost without much benefit值得注意的是值得注意的是

12、EtO的用量越大只會增加成本對滅菌效率益處不大的用量越大只會增加成本對滅菌效率益處不大11HumidityHumidity濕度濕度 Water is required for ethylene oxide to react (alkylation process) with the critical cell molecules 環(huán)氧乙烷與關鍵細胞分子的反應過程環(huán)氧乙烷與關鍵細胞分子的反應過程(烷化過程烷化過程)中需有水中需有水 Present as a gas in the sterilization process 在滅菌過程中以氣體狀態(tài)存在 Generally measured as R

13、elative Humidity 通常是指相對濕度相對濕度12TemperatureTemperature溫度溫度 Kill rate increases with temperature 殺滅率會隨溫度的增加而增加殺滅率會隨溫度的增加而增加 For each 100C rise in temperature, the spore inactivation rate will generally double 溫度每增加溫度每增加100C, 通常孢子的殺活率成倍增加通常孢子的殺活率成倍增加13TimeTime時間時間Amount of kill increases with exposure

14、(EtO gas dwell) time殺滅率會隨著曝露時間（即殺滅率會隨著曝露時間（即EO駐留時間）的延長而增加。駐留時間）的延長而增加。14TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Process Overview

15、環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護15Barriers to Biological KillBarriers to Biological Kill影響微生物殺滅的屏障影響微生物殺滅的屏障 Physical Barriers物理屏障物理屏障 Cardb

16、oard Boxes紙板箱 Absorb humidity吸濕 Inhibit temperature penetration阻礙溫度的穿透 Shrink Wrap纏繞膜 Inhibits temperatutre, moisture and EtO penetration抑制溫度、濕度和EtO的滲透Gas (N2/EtO/RH/Air) Can Easily EnterGas (N2/EtO/RH/Air) Can ExitGas (N2/EtO/RH/Air) Cant Easily Enter16Barriers to Biological KillBarriers to Biologi

17、cal Kill影響微生物殺滅的屏障影響微生物殺滅的屏障 Physical Barriers物理屏障 Packaging包裝 Inhibits temperature penetration抑制溫度滲透 May inhibit moisture or EtO penetration可能抑制EtO和濕氣的滲透Mylar cannot be penetratedby process gases氣體不能穿透聚酯薄膜All process gases enter the productsthrough either Tyvek patches, headersor sides所有氣體通過Tyvek進入

18、產(chǎn)品Wraps like this back table coverinhibit penetration of gases像手術臺布的這種包裹方式抑制了氣體的滲入17TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Proce

19、ss Overview 環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護18 EtO Process OverviewEtO Process Overview環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Batch Process, typically with 3

20、phases:主要的主要的3個階段個階段 Preconditioning Treatment of product prior to the sterilization cycle in a room or chamber to attain a specified temperature and RH. 預處理預處理 滅菌循環(huán)前,在房間或柜內,使產(chǎn)品達到一定的溫度與濕度. Sterilization Chamber Enclosed area which only accommodates sufficient product to fill the sterilizer 滅菌柜滅菌柜 裝載

21、待滅菌產(chǎn)品的一個封閉區(qū)域 Aeration Part of the sterilization process during which EtO desorb from the medical device 解析解析 滅菌過程中醫(yī)療器械釋放環(huán)氧乙烷的階段.19Preconditioning Preconditioning 預處理預處理 Heat and Humidity Introduced to Load 裝載加熱加濕裝載加熱加濕 Air is circulated to assist in heat/humidity transfer空氣流通有助于熱空氣流通有助于熱/濕的轉移濕的轉移 Mi

22、nimum time generally between 12-24 hours.一般至少預熱一般至少預熱12-24小時小時 Product can usually stay in preconditioning much longer (2-4 days total)產(chǎn)品進行預處理的時間一般可以更長產(chǎn)品進行預處理的時間一般可以更長 (合計合計2-4天天)20Sterilization Chamber - EtO CycleSterilization Chamber - EtO Cycle純環(huán)氧乙烷滅菌工藝純環(huán)氧乙烷滅菌工藝 21Initial VacuumInitial Vacuum初始抽真

23、空初始抽真空 Removes air from the load去除裝載中的空氣去除裝載中的空氣 Air inhibits penetration of water & EtO into the center of the load 空氣會抑制水與環(huán)氧乙烷滲透進產(chǎn)品中央 Air, when mixed with EtO, creates a flammable mixture 當空氣與環(huán)氧乙烷混合后會生成一種易燃混合物 Deep vacuums cycle have some potential drawbacks 深度抽真空循環(huán)具有一些潛在不足深度抽真空循環(huán)具有一些潛在不足 Over

24、ly deep vacuums may start to remove moisture from the load過度的負壓可能使產(chǎn)品脫水 Potential adverse affects on the product and / or packaging對產(chǎn)品和包裝存在潛在的負面影響 22Leak TestLeak Test測漏測漏 Purpose is to detect catastrophic chamber leaks旨在檢測滅菌柜是否有嚴重的泄漏旨在檢測滅菌柜是否有嚴重的泄漏 Has no effect on kill對滅菌沒有影響對滅菌沒有影響23Humidification

25、Humidification加濕加濕 Injection of moisture (in the form of steam) to replace any loss during initial vacuum注入濕氣注入濕氣 (蒸汽態(tài)蒸汽態(tài))以補充初始抽真空階段丟失的濕氣。以補充初始抽真空階段丟失的濕氣。 Typically 25 to 50 mBar rise in pressure 通常注入通常注入25 至至 50 mBar的濕氣的濕氣24Conditioning Conditioning 處理處理 Conditioning (Humidity Dwell) is a period of

26、 time where the product “dwells” in the moist chamber environment. 處理處理(濕氣駐留濕氣駐留)指產(chǎn)品駐留在潮濕的滅菌柜環(huán)境中的一段時間指產(chǎn)品駐留在潮濕的滅菌柜環(huán)境中的一段時間 Only change in the “static” environment is when steam is added to keep the chamber environment humidity stable. 只有只有 “靜態(tài)靜態(tài)”環(huán)境發(fā)生變化，才會注入蒸汽，旨在保持滅菌柜中濕氣穩(wěn)定環(huán)境發(fā)生變化，才會注入蒸汽，旨在保持滅菌柜中濕氣穩(wěn)定 Lo

27、ss of chamber humidity is due to load absorption of the humidity.滅菌室濕氣的減少是由于產(chǎn)品的吸濕滅菌室濕氣的減少是由于產(chǎn)品的吸濕25Gas InjectGas Inject氣體注入氣體注入 EtO injection into the chamber將環(huán)氧乙烷注入滅菌柜內將環(huán)氧乙烷注入滅菌柜內 Pressure rise assists in forcing EtO and humidity into the load壓力上升促使環(huán)氧乙烷和濕氣進入裝載中壓力上升促使環(huán)氧乙烷和濕氣進入裝載中26Gas DwellGas Dwell

28、氣體駐留氣體駐留 Gas Dwell consists of a period of time where the product “dwells” in the EtO laden chamber environment after gas injection.氣體駐留是指注入氣體后產(chǎn)品氣體駐留是指注入氣體后產(chǎn)品“停留停留”在充滿環(huán)氧乙烷的滅菌柜中的一段時間在充滿環(huán)氧乙烷的滅菌柜中的一段時間 Only change in the “static” environment is when EtO (or nitrogen) is added to keep the chamber enviro

29、nment pressure and/or EtO concentration stable.只有當只有當 “靜態(tài)靜態(tài)”環(huán)境才發(fā)生變化時，才會注入環(huán)氧乙烷（或氮氣），旨在保持滅環(huán)境才發(fā)生變化時，才會注入環(huán)氧乙烷（或氮氣），旨在保持滅菌柜環(huán)境的壓力和菌柜環(huán)境的壓力和/或環(huán)氧乙烷濃度穩(wěn)定或環(huán)氧乙烷濃度穩(wěn)定 Loss of chamber pressure is due to product absorption of the EtO. 滅菌柜壓力的下降是由于產(chǎn)品吸收了環(huán)氧乙烷滅菌柜壓力的下降是由于產(chǎn)品吸收了環(huán)氧乙烷27Gas DwellGas Dwell氣體駐留氣體駐留 Dwell provide

30、s time for:氣體駐留時間氣體駐留時間-Penetration of EtO into the most difficult portions of the load 環(huán)氧乙烷穿透到產(chǎn)品中最難以到達的位置 Kill generally occurs slowly at the start of dwell due to the fact that:殺滅作用在氣體駐留的初期階段會比較慢的原因：殺滅作用在氣體駐留的初期階段會比較慢的原因：-The EtO has not yet diffused into the most difficult to reach locations環(huán)氧乙烷尚

31、未擴散到產(chǎn)品中最難以到達的位置-The temperature in the core of the load is still rising產(chǎn)品中心部位的溫度仍在上升 The efficiency of kill can be significantly increased with by injecting nitrogen on top of the EtO in the gas injection phase.在氣體注入階段，注入氮氣覆蓋于在氣體注入階段，注入氮氣覆蓋于EtO上將顯著提高殺滅率上將顯著提高殺滅率28After VacuumAfter Vacuum后抽真空后抽真空 Rem

32、oves EtO from the chamber and the load 去除滅菌柜和裝載中的環(huán)氧乙烷去除滅菌柜和裝載中的環(huán)氧乙烷 Lowered chamber EtO concentration allows EtO to begin to outgas from solids (beginning aeration of the load in the chamber)降低柜內環(huán)氧乙烷濃度，使EO開始從產(chǎn)品中釋放出來 (裝載在柜內的初始解析) Deeper vacuums may help remove more EtO residues深度抽真空有助于去除環(huán)氧乙烷殘留29Gas W

33、ashesGas Washes洗氣洗氣 Help remove high concentrations of EtO from the product有助產(chǎn)品去除高濃度的環(huán)氧乙烷有助產(chǎn)品去除高濃度的環(huán)氧乙烷 Makes the kits safer to handle after sterilization更安全地處理滅菌后產(chǎn)品 May shorten required aeration time可縮短解析時間 30Final Release Final Release 恢復常壓恢復常壓 Brings the chamber to atmospheric pressure to allow o

34、pening of the chamber door. The door will not open under vacuum. 滅菌柜柜門處于常壓下時才可開啟。柜門在真空狀態(tài)下打不開。滅菌柜柜門處于常壓下時才可開啟。柜門在真空狀態(tài)下打不開。 The chamber must always return to atmospheric using air (to provide a breathable atmosphere in the chamber when the door is opened) 滅菌室必須通過注入空氣恢復常壓滅菌室必須通過注入空氣恢復常壓 (當門打開時，在滅菌室內提供可

35、以呼吸的當門打開時，在滅菌室內提供可以呼吸的大氣大氣)31Aeration Aeration 解析解析 Heat Introduced to Load to desorb EtO加熱以去除裝載中的加熱以去除裝載中的EtO Air is circulated to assist in heat transfer, as well as degassing process空氣循環(huán)流通，有助熱量傳導和解析工藝空氣循環(huán)流通，有助熱量傳導和解析工藝 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

36、為天，典型的為2天天 Ambient aeration generally much longer自然解析時間更長自然解析時間更長Below: Aeration Room32Aeration Aeration 解析解析 Factors Affecting EtO Aeration 影響影響EtO解析的因素解析的因素i.Material in which EtO is dissolved 產(chǎn)品材料產(chǎn)品材料Some materials give up EtO faster than others不同材料釋放EtO的速度不同ii.Thickness of Material 材料的厚度材料的厚度Thi

37、cker materials hold more EtO 材料越厚吸附越多的EtOLonger to diffuse to surface from center 從中心到表面的擴散距離長iii. Temperature溫度溫度Higher temperatures produce faster aeration rates溫度越高解析速率越快iv.Time時間時間Longer times produce lower residual levels解析時間越長殘留越低33TopicsTopics Standards 標準標準 Properties of EtO / How does EtO K

38、ill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Process Overview 環(huán)氧乙烷滅菌過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow

39、 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護34Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā)Identify Product Families/Classifications識別產(chǎn)品族識別產(chǎn)品族/分類分類Identify PCD 識別識別PCDIdentify/Finalize Packaging識別最終包裝識別最終包裝Identify Load Configuration識別裝載結構識別裝載結構35Sterilizat

40、ion Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Identify Product Families/Classifications識別產(chǎn)品族識別產(chǎn)品族/分類分類 Identify product to be sterilized in the EtO process識別待滅菌產(chǎn)品 Put product into product families by grouping similar products.將相似產(chǎn)品歸入產(chǎn)品族中product design and function 產(chǎn)品設計和功能manufactu

41、ring method 生產(chǎn)方法manufacturing environment 生產(chǎn)環(huán)境material of construction 材料組成packaging materials 包裝材料density 密度size and/or surface area, and 大小和/或表面積bioburden 生物裝載36Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Identify PCD 識別識別PCD Select most difficult to sterilize from f

42、amily從產(chǎn)品族中選擇最難滅菌的產(chǎn)品從產(chǎn)品族中選擇最難滅菌的產(chǎn)品 High density 高密度 Most torturous pathways 最多彎曲路徑 Longest tubing, smallest lumen最長的管路，最小的內徑 High bioburden material 高生物裝載 For complex product like custom kits, there can be more than one type of challenge device 對于復雜的產(chǎn)品如手術包，可能不止一類產(chǎn)品可作為最難滅菌產(chǎn)品37Identify PCD 識別識別PCD Ther

43、e are two types of challenge devices兩種挑戰(zhàn)器 Internal 內置挑戰(zhàn)器 External 外置挑戰(zhàn)器Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā)38Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Internal Challenge Device內置挑戰(zhàn)器內置挑戰(zhàn)器Generally the most difficult to sterilize d

44、evice, is seeded with a BI or liquid suspension in the most difficult to sterilize location. Examples of inoculation positions include places like:通常將BI或孢子懸液接種于最難滅菌產(chǎn)品的最難滅菌位置。如The center of long, thin tubing 細長管子的中間Between the seals on a syringe 注射器密封處39Sterilization Cycle DevelopmentSterilization Cy

45、cle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Internal Challenge Device內置挑戰(zhàn)器內置挑戰(zhàn)器Package the challenge product in the same manner as products would routinely be sterilized 挑戰(zhàn)性產(chǎn)品的包裝方式同常規(guī)待滅菌產(chǎn)品。Place the packaged challenge product into a sterilization load of product。 將已包裝的挑戰(zhàn)產(chǎn)品置于滅菌裝載內。40Sterilization Cycle DevelopmentSt

46、erilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) External Challenge Device外置挑戰(zhàn)器外置挑戰(zhàn)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的測試包，代替內置挑戰(zhàn)器，通常用于常規(guī)生產(chǎn)監(jiān)測的測試包，代替內置挑戰(zhàn)器，通常用于常規(guī)生產(chǎn)監(jiān)測Makes it easier to place and retrieve BI

47、s during routine processing在常規(guī)生產(chǎn)過程中使得BI的取放更容易。Should be an equal or more difficult challenge to the process than the internal challenge device.對處理過程的挑戰(zhàn)性，應大于等于內置挑戰(zhàn)器Generally developed using comparative resistance studies通?？赏ㄟ^抗力比較獲得41Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)

48、滅菌循環(huán)開發(fā)Identify/Finalize Packaging識別最終包裝識別最終包裝Product packaging 產(chǎn)品包裝Corrugate, box thickness 瓦楞紙箱，盒子厚度Pouching materials (Tyvek) 包裝材料 Packing configuration (quantity/box) 包裝結構 （數(shù)量/箱） May affect products ability to absorb humidity 可影響產(chǎn)品吸濕的能力 May affect products ability to aid temperature penetration 可

49、影響產(chǎn)品協(xié)助溫度穿透的能力42Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā)Identify Load Configuration識別裝載結構識別裝載結構 Palletizing approach 堆垛方式 Stretch wrap, corner board, netting? 纏繞膜、護角、護網(wǎng)? May affect loads ability to absorb humidity可影響裝載的吸濕能力 May affect loads ability to aid temperature

50、 penetration可影響裝載協(xié)助溫度穿透的能力43Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Proposed Parameters 建議的參數(shù)建議的參數(shù) Cycle parameters incorporate product-limitation information from customer循環(huán)參數(shù)應結合客戶提供的產(chǎn)品局限性信息。 Use an existing cycle (previously developed) for a product使用已存在的滅菌循環(huán)（以前開

51、發(fā)的） Select a general cycle that works for similar product types:選擇一個用于相似產(chǎn)品的通用循環(huán)Recommended: Include a fractional cycle in the Validation; 建議：確認過程包括部分循環(huán)44Sterilization Cycle DevelopmentSterilization Cycle Development滅菌循環(huán)開發(fā)滅菌循環(huán)開發(fā) Validation Method確認方法確認方法 3 recognised methods for EtO validation 3種認可的方

52、法種認可的方法Direct enumeration 直接計數(shù)法直接計數(shù)法 Fraction-negative 部分陰性法部分陰性法 Overkill approach 過度殺滅法過度殺滅法45Direct enumeration直接計數(shù)法 Minimum of 5 cycles needed 5次循環(huán)次循環(huán) one run with 0 time exposure 1次曝露時間為0的循環(huán) one run with 4 SLR 1次SLR下降4的循環(huán) at least three runs between i and ii 介于i和ii之間的3個循環(huán)46Fraction-negative met

53、hod部分陰性法 A minimum of 7 exposure conditions should be used covering:至少至少7個循環(huán)個循環(huán) At least one set of samples in which all tested samples show growth 至少1次循環(huán)，試樣顯示全部生長。 At least 4 test sets in which a fraction of the samples show growth 至少4次循環(huán)，試樣顯示部分生長。 At least 2 test sets of samples in which no growth

54、 is observed 至少2次循環(huán)，試樣顯示無生長。47Fraction-negative method部分陰性法 The D-value (time needed to reduce microbial count by at least 1 log) is calculated using the results of the test.根據(jù)測試結果計算根據(jù)測試結果計算D值（下降值（下降1個對數(shù)值所需要的時間）。個對數(shù)值所需要的時間）。 The theoretical exposure time required to achieve the sterility assurance l

55、evel (SAL) of the test organism is calculated from the D-value.通過通過D值再計算得到相應無菌保證水平的理論曝露時間值再計算得到相應無菌保證水平的理論曝露時間。48Overkill approach (half cycle method) Overkill approach (half cycle method) 過度殺滅法過度殺滅法( (半時循環(huán)法半時循環(huán)法) ) Determines minimum time of exposure to EtO at which there are no survivors. (half cy

56、cle)測定無存活菌的最短時間測定無存活菌的最短時間-半時循環(huán)半時循環(huán) 3 runs (half cycles) are performed to confirm the minimum time.運行運行3次半時循環(huán)以確認此最短時間。次半時循環(huán)以確認此最短時間。 All three runs should show no growth on the BIs.所有的三次測試應無所有的三次測試應無BI生長。生長。 It is recommended that a fractional cycle also be performed to demonstrate the adequacy of t

57、he recovery technique.應運行一次短時循環(huán)以證明復蘇技術的充分性。應運行一次短時循環(huán)以證明復蘇技術的充分性。49TopicsTopics Standards 標準標準 Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機理環(huán)氧乙烷性能及滅菌機理 Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素影響環(huán)氧乙烷滅菌的主要因素 Barriers to Biological Kill 影響微生物殺滅的屏障影響微生物殺滅的屏障 EtO Process Overview 環(huán)氧乙烷滅菌

58、過程概覽環(huán)氧乙烷滅菌過程概覽 Cycle development 循環(huán)開發(fā)循環(huán)開發(fā) Cycle Validation 循環(huán)確認循環(huán)確認 Evaluation of Product EtO Residues 殘留評估殘留評估 EtO Process Flow 環(huán)氧乙烷滅菌處理流程環(huán)氧乙烷滅菌處理流程 Environmental Considerations環(huán)境保護環(huán)境保護50Sterilization Cycle ValidationSterilization Cycle Validation滅菌循環(huán)確認滅菌循環(huán)確認Documented study研究工作文件化研究工作文件化Validation

59、 protocol to assure cycle is adequate確認方案以保證循環(huán)是充分的Acceptance Criteria agreed upon before beginning開始前應認可接受標準Procedures are documented程序文件化51Sterilization Cycle ValidationSterilization Cycle Validation滅菌循環(huán)確認滅菌循環(huán)確認Prior to validation確認前確認前Packaging finalized產(chǎn)品包裝已確定Load configuration identified裝載結構已確定P

60、roduct Families have been identified (as applicable)產(chǎn)品族已識別（若適用）Bioburden?生物裝載？52Sterilization Cycle ValidationSterilization Cycle Validation滅菌循環(huán)確認滅菌循環(huán)確認Parameters to be addressed 待確認參數(shù)待確認參數(shù)Transfer time after Preconditioning預處理結束后的轉移時間Specified ranges for sterilization load (Preconditioning, Chamber, an