環(huán)氧乙烷滅菌詳解

1、 Ethylene Oxide Sterilization 環(huán)氧乙烷滅菌(mi jn)共九十二頁TopicsStandards 標(biāo)準(zhǔn)(biozhn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Overview 環(huán)氧乙烷滅菌過程概覽Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation

2、 of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations 環(huán)境保護(hù)共九十二頁TopicsStandards 標(biāo)準(zhǔn)(biozhn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Overview 環(huán)氧乙烷滅菌過程概覽Cycle d

3、evelopment 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations環(huán)境保護(hù)共九十二頁EtO sterilization standards 環(huán)氧乙烷相關(guān)(xinggun)標(biāo)準(zhǔn)ISO 11135-1,-2TIR 14 / TIR 15 / TIR 16 / TIR 20 / TIR 28BI standards 生物指示劑標(biāo)準(zhǔn)ISO 11138-1,-2/ ISO 14161Microbiological

4、 standards微生物標(biāo)準(zhǔn)ISO 11737-1,-2 / AAMI/ST 72 CI standard化學(xué)指示劑標(biāo)準(zhǔn)ISO 11140-1Residual standard殘留標(biāo)準(zhǔn)ISO 10993-7Packaging standard 包裝標(biāo)準(zhǔn) ISO 11607-1，-2Standards 標(biāo)準(zhǔn)(biozhn) 共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要因素Barriers t

5、o Biological Kill 影響微生物殺滅的屏障EtO Process Overview 環(huán)氧乙烷滅菌過程概覽Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理(chl)流程Environmental Considerations環(huán)境保護(hù)共九十二頁 Properties of EtO環(huán)氧乙烷性能(xngnng)Ethylene Oxide Gas (EtO)環(huán)氧乙烷 氣體(qt)Boiling point 10.4沸點(diǎn) 10

6、.4 Extremely reactive活躍性強(qiáng)Highly explosive易爆 共九十二頁How Does EtO Kill?環(huán)氧乙烷是如何(rh)滅菌的?Kills by process called “alkylation”殺滅過程(guchng)稱其為 “烷化”EtO irreversibly binds to key molecules in the cell nucleus環(huán)氧乙烷對細(xì)胞中分子的作用是不可逆的DNA 脫氧核糖核酸Proteins (enzymes) 蛋白質(zhì)（酶）Molecules can no longer function分子喪失其作用Cell can no

7、 longer reproduce細(xì)胞不再被復(fù)制 Cell dies細(xì)胞死亡共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Overview 環(huán)氧乙烷滅菌過程概覽(i ln)Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Pro

8、duct EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations環(huán)境保護(hù)共九十二頁9Basic Factors Affecting EtO Sterilization影響環(huán)氧乙烷滅菌的主要(zhyo)因素Four basic factors interact to product kill影響滅菌(mi jn)的四要素EtO concentration環(huán)氧乙烷濃度Humidity濕度Temperature溫度Time時間共九十二頁EtO Concentration環(huán)氧乙烷濃度(nngd)Concentra

9、tions commonly between 400 and 1000 mg/L濃度通常在 400 與 1000 mg/L 之間As EtO concentration increases at a given temp and RH microbial inactivation (kill) rate increases在給定的溫度與相對濕度條件下,環(huán)氧乙烷濃度增加,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500 mg/L時，殺滅率增加很少Signi

10、ficantly more gas adds cost without much benefit值得注意的是EtO的用量越大只會增加成本(chngbn)對滅菌效率益處不大共九十二頁Humidity濕度(shd)Water is required for ethylene oxide to react (alkylation process) with the critical cell molecules 環(huán)氧乙烷與關(guān)鍵細(xì)胞分子的反應(yīng)過程(烷化過程)中需有水Present as a gas in the sterilization process 在滅菌過程中以氣體(qt)狀態(tài)存在Genera

11、lly measured as Relative Humidity 通常是指相對濕度共九十二頁Temperature溫度(wnd)Kill rate increases with temperature 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100C, 通常(tngchng)孢子的殺活率成倍增加共九十二頁13Time時間(shjin)Amount of kill increases with exposure (EtO gas

12、dwell) time殺滅率會隨著(su zhe)曝露時間（即EO駐留時間）的延長而增加。共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 影響環(huán)氧乙烷滅菌的主要(zhyo)因素Barriers to Biological Kill 影響微生物殺滅的屏障EtO Process Overview 環(huán)氧乙烷滅菌過程概覽Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation

13、 of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations環(huán)境保護(hù)共九十二頁Barriers to Biological Kill影響(yngxing)微生物殺滅的屏障Physical Barriers物理屏障Cardboard Boxes紙板箱Absorb humidity吸濕Inhibit temperature penetration阻礙溫度的穿透(chun tu)Shrink Wrap纏繞膜Inhibits temperatutre, moisture and EtO pene

14、tration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 Enter共九十二頁16Barriers to Biological Kill影響(yngxing)微生物殺滅的屏障Physical Barriers物理(wl)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

15、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(jìn)入產(chǎn)品Wraps like this back table coverinhibit penetration of gases像手術(shù)臺布的這種包裹方式抑制了氣體的滲入共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌

16、機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Overview 環(huán)氧乙烷滅菌過程概覽Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理(chl)流程Environmental Considerations環(huán)境保護(hù)共九十二頁 EtO Process Overview環(huán)氧乙

17、烷滅菌(mi jn)過程概覽Batch Process, typically with 3 phases:主要的3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(yù)處理 滅菌循環(huán)前,在房間或柜內(nèi),使產(chǎn)品達(dá)到一定的溫度與濕度.Sterilization Chamber Enclosed area which only accommodates sufficient produ

18、ct to fill the sterilizer 滅菌柜 裝載待滅菌產(chǎn)品的一個封閉區(qū)域(qy)Aeration Part of the sterilization process during which EtO desorb from the medical device 解析 滅菌過程中醫(yī)療器械釋放環(huán)氧乙烷的階段.共九十二頁P(yáng)reconditioning 預(yù)處理Heat and Humidity Introduced to Load 裝載加熱加濕Air is circulated to assist in heat/humidity transfer空氣流通有助于熱/濕的轉(zhuǎn)移Minimu

19、m time generally between 12-24 hours.一般至少預(yù)熱12-24小時Product can usually stay in preconditioning much longer (2-4 days total)產(chǎn)品進(jìn)行預(yù)處理的時間一般可以(ky)更長 (合計2-4天)共九十二頁Sterilization Chamber - EtO Cycle純環(huán)氧乙烷滅菌(mi jn)工藝 共九十二頁Initial Vacuum初始(ch sh)抽真空Removes air from the load去除裝載中的空氣Air inhibits penetration of wa

20、ter & EtO into the center of the load 空氣會抑制水與環(huán)氧乙烷滲透進(jìn)產(chǎn)品中央Air, when mixed with EtO, creates a flammable mixture 當(dāng)空氣與環(huán)氧乙烷混合(hnh)后會生成一種易燃混合(hnh)物Deep vacuums cycle have some potential drawbacks 深度抽真空循環(huán)具有一些潛在不足Overly deep vacuums may start to remove moisture from the load過度的負(fù)壓可能使產(chǎn)品脫水Potential adverse aff

21、ects on the product and / or packaging對產(chǎn)品和包裝存在潛在的負(fù)面影響 共九十二頁Leak Test測漏Purpose is to detect catastrophic chamber leaks旨在(zh zi)檢測滅菌柜是否有嚴(yán)重的泄漏Has no effect on kill對滅菌沒有影響共九十二頁Humidification加濕Injection of moisture (in the form of steam) to replace any loss during initial vacuum注入濕氣 (蒸汽態(tài))以補(bǔ)充初始抽真空階段丟失(dis

22、)的濕氣。Typically 25 to 50 mBar rise in pressure 通常注入25 至 50 mBar的濕氣共九十二頁Conditioning 處理(chl)Conditioning (Humidity Dwell) is a period of time where the product “dwells” in the moist chamber environment. 處理(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Only change in the “static” environment is when steam is added to keep

23、the chamber environment humidity stable. 只有 “靜態(tài)”環(huán)境發(fā)生變化，才會注入蒸汽(zhn q)，旨在保持滅菌柜中濕氣穩(wěn)定Loss of chamber humidity is due to load absorption of the humidity.滅菌室濕氣的減少是由于產(chǎn)品的吸濕共九十二頁Gas Inject氣體(qt)注入EtO injection into the chamber將環(huán)氧乙烷注入滅菌柜內(nèi)Pressure rise assists in forcing EtO and humidity into the load壓力上升促使(cs

24、h)環(huán)氧乙烷和濕氣進(jìn)入裝載中共九十二頁Gas Dwell氣體(qt)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“停留”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 environment

25、pressure and/or EtO concentration stable.只有當(dāng) “靜態(tài)”環(huán)境才發(fā)生變化時，才會注入環(huán)氧乙烷（或氮?dú)猓?，旨在保持滅菌柜環(huán)境的壓力和/或環(huán)氧乙烷濃度(nngd)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)氧乙烷共九十二頁Gas Dwell氣體(qt)駐留Dwell provides time for:氣體駐留時間-Penetration of EtO into the most difficult portions of the l

26、oad 環(huán)氧乙烷穿透到產(chǎn)品中最難以到達(dá)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：-The EtO has not yet diffused into the most difficult to reach locations環(huán)氧乙烷尚未擴(kuò)散到產(chǎn)品中最難以到達(dá)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

27、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?dú)飧采w于EtO上將(shngjing)顯著提高殺滅率共九十二頁After Vacuum后抽真空(zhnkng)Removes EtO from the chamber and the load 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

28、 (beginning aeration of the load in the chamber)降低柜內(nèi)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(nèi)的初始解析) Deeper vacuums may help remove more EtO residues深度(shnd)抽真空有助于去除環(huán)氧乙烷殘留共九十二頁Gas Washes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Makes the kits safer to handle after sterilization更安全(nqun

29、)地處理滅菌后產(chǎn)品May shorten required aeration time可縮短解析時間 共九十二頁Final Release 恢復(fù)(huf)常壓Brings the chamber to atmospheric pressure to allow opening of the chamber door. The door will not open under vacuum. 滅菌柜柜門處于(chy)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

30、breathable atmosphere in the chamber when the door is opened) 滅菌室必須通過注入空氣恢復(fù)常壓 (當(dāng)門打開時，在滅菌室內(nèi)提供可以呼吸的大氣)共九十二頁Aeration 解析(ji x)Heat Introduced to Load to desorb EtO加熱以去除裝載中的EtOAir is circulated to assist in heat transfer, as well as degassing process空氣循環(huán)(xnhun)流通，有助熱量傳導(dǎo)和解析工藝Time generally 1-5 days for He

31、ated Aeration, typically 2 days.通常解析1-5天，典型的為2天 Ambient aeration generally much longer自然解析時間更長Below: Aeration Room共九十二頁Aeration 解析(ji x)Factors Affecting EtO Aeration 影響EtO解析的因素i.Material in which EtO is dissolved 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 Materia

32、l 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 從中心到表面的擴(kuò)散距離長iii. Temperature溫度Higher temperatures produce faster aeration rates溫度越高解析速率越快iv.Time時間(shjin)Longer times produce lower residual levels解析時間越長殘留越低共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does

33、 EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Overview 環(huán)氧乙烷滅菌過程概覽(i ln)Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations環(huán)境保護(hù)共九十二頁Ste

34、rilization Cycle Development滅菌(mi jn)循環(huán)開發(fā)Identify Product Families/Classifications識別產(chǎn)品(chnpn)族/分類Identify PCD 識別PCDIdentify/Finalize Packaging識別最終包裝Identify Load Configuration識別裝載結(jié)構(gòu)共九十二頁Sterilization Cycle Development滅菌(mi jn)循環(huán)開發(fā)Identify Product Families/Classifications識別產(chǎn)品族/分類Identify product to b

35、e 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(shè)計和功能manufacturing method 生產(chǎn)(shngchn)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,

36、and 大小和/或表面積bioburden 生物裝載共九十二頁Sterilization Cycle Development滅菌(mi jn)循環(huán)開發(fā) Identify PCD 識別PCD Select most difficult to sterilize from family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(nèi)徑High bioburden material 高生物裝載For complex product like cust

37、om kits, there can be more than one type of challenge device 對于復(fù)雜的產(chǎn)品如手術(shù)包，可能不止一類(y li)產(chǎn)品可作為最難滅菌產(chǎn)品共九十二頁Identify PCD 識別(shbi)PCDThere are two types of challenge devices兩種挑戰(zhàn)器Internal 內(nèi)置挑戰(zhàn)器External 外置挑戰(zhàn)器Sterilization Cycle Development滅菌循環(huán)(xnhun)開發(fā)共九十二頁Sterilization Cycle Development滅菌循環(huán)(xnhun)開發(fā)Internal

38、Challenge Device內(nèi)置挑戰(zhàn)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:通常將BI或孢子懸液接種于最難滅菌(mi jn)產(chǎn)品的最難滅菌(mi jn)位置。如The center of long, thin tubing 細(xì)長管子的中間Between

39、the seals on a syringe 注射器密封處共九十二頁Sterilization Cycle Development滅菌(mi jn)循環(huán)開發(fā) Internal Challenge Device內(nèi)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)(chnggu)待滅菌產(chǎn)品。Place the packaged challenge product into a sterilization load of product

40、。 將已包裝的挑戰(zhàn)產(chǎn)品置于滅菌裝載內(nèi)。共九十二頁Sterilization Cycle Development滅菌(mi jn)循環(huán)開發(fā)External Challenge Device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BI的測試包，代替內(nèi)置挑戰(zhàn)器，通常用于常規(guī)生產(chǎn)(shngchn)監(jiān)測Makes it easier to place and retrie

41、ve BIs 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(yīng)大于等于內(nèi)置挑戰(zhàn)器Generally developed using comparative resistance studies通?？赏ㄟ^抗力比較獲得共九十二頁Sterilization Cycle Development滅菌(mi jn)循環(huán)開發(fā)Identify/Finaliz

42、e Packaging識別最終包裝Product packaging 產(chǎn)品包裝Corrugate, box thickness 瓦楞紙箱，盒子(h zi)厚度Pouching materials (Tyvek) 包裝材料 Packing configuration (quantity/box) 包裝結(jié)構(gòu) （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 可影響產(chǎn)品協(xié)助溫度穿透的能力共九十二頁Steril

43、ization Cycle Development滅菌循環(huán)(xnhun)開發(fā)Identify Load Configuration識別裝載結(jié)構(gòu)Palletizing approach 堆垛方式Stretch wrap, corner board, netting? 纏繞膜、護(hù)角、護(hù)網(wǎng)?May affect loads ability to absorb humidity可影響(yngxing)裝載的吸濕能力May affect loads ability to aid temperature penetration可影響裝載協(xié)助溫度穿透的能力共九十二頁Sterilization Cycle D

44、evelopment滅菌(mi jn)循環(huán)開發(fā) Proposed Parameters 建議的參數(shù)Cycle parameters incorporate product-limitation information from customer循環(huán)參數(shù)應(yīng)結(jié)合客戶(k h)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)Rec

45、ommended: Include a fractional cycle in the Validation; 建議：確認(rèn)過程包括部分循環(huán)共九十二頁Sterilization Cycle Development滅菌循環(huán)(xnhun)開發(fā)Validation Method確認(rèn)方法 3 recognised methods for EtO validation 3種認(rèn)可(rnk)的方法Direct enumeration 直接計數(shù)法 Fraction-negative 部分陰性法 Overkill approach 過度殺滅法共九十二頁Direct enumeration直接(zhji)計數(shù)法Mi

46、nimum of 5 cycles needed 5次循環(huán) one run with 0 time exposure 1次曝露(pl)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)共九十二頁Fraction-negative method部分(b fen)陰性法 A minimum of 7 exposure conditions should be used covering:至少7個循環(huán)At least one set of samples in which

47、all tested samples show growth 至少1次循環(huán)，試樣顯示全部生長(shngzhng)。 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 is observed 至少2次循環(huán)，試樣顯示無生長。共九十二頁Fraction-negative method部分(b fen)陰性法The D-value (time needed to reduce micr

48、obial count by at least 1 log) is calculated using the results of the test.根據(jù)測試結(jié)果計算D值（下降1個對數(shù)值所需要的時間(shjin)）。The theoretical exposure time required to achieve the sterility assurance level (SAL) of the test organism is calculated from the D-value.通過D值再計算得到相應(yīng)無菌保證水平的理論曝露時間。共九十二頁Overkill approach (half

49、cycle method) 過度(gud)殺滅法(半時循環(huán)法)Determines minimum time of exposure to EtO at which there are no survivors. (half cycle)測定無存活菌的最短時間-半時循環(huán)(xnhun)3 runs (half cycles) are performed to confirm the minimum time.運(yùn)行3次半時循環(huán)以確認(rèn)此最短時間。All three runs should show no growth on the BIs.所有的三次測試應(yīng)無BI生長。It is recommende

50、d that a fractional cycle also be performed to demonstrate the adequacy of the recovery technique.應(yīng)運(yùn)行一次短時循環(huán)以證明復(fù)蘇技術(shù)的充分性。共九十二頁TopicsStandards 標(biāo)準(zhǔn)Properties of EtO / How does EtO Kill? 環(huán)氧乙烷性能及滅菌機(jī)理Basic Factor Affecting EtO Sterilization 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EtO Process Over

51、view 環(huán)氧乙烷滅菌過程(guchng)概覽Cycle development 循環(huán)開發(fā)Cycle Validation 循環(huán)確認(rèn)Evaluation of Product EtO Residues 殘留評估EtO Process Flow 環(huán)氧乙烷滅菌處理流程Environmental Considerations環(huán)境保護(hù)共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Documented study研究工作文件化Validation protocol to assure cycle is adequate確認(rèn)方案以保證循環(huán)(xnhun)是充

52、分的Acceptance Criteria agreed upon before beginning開始前應(yīng)認(rèn)可接受標(biāo)準(zhǔn)Procedures are documented程序文件化共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Prior to validation確認(rèn)(qurn)前Packaging finalized產(chǎn)品包裝已確定Load configuration identified裝載結(jié)構(gòu)已確定Product Families have been identified (as applicable)產(chǎn)品族已識別（若適用）Bioburde

53、n?生物裝載？共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Parameters to be addressed 待確認(rèn)參數(shù)Transfer time after Preconditioning預(yù)處理結(jié)束后的轉(zhuǎn)移時間Specified ranges for sterilization load (Preconditioning, Chamber, and Aeration)滅菌裝載(zhungzi)規(guī)定的范圍（預(yù)處理，滅菌柜循環(huán)和解析）Verify Gas Sterilant was admitted to chamber驗證氣體滅菌劑注入滅菌

54、柜Gas weight氣體重量共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Fractional短時循環(huán)Run 1 Fractional Run in production chamber在生產(chǎn)用滅菌柜內(nèi)運(yùn)行(ynxng)1個部分循環(huán)Why? New standard states that BI recovery between process facility and testing facility must be demonstrated因為新標(biāo)準(zhǔn)要求必須在生產(chǎn)和測試柜內(nèi)證明BI的復(fù)蘇性。共九十二頁Sterilization Cycle

55、 Validation滅菌(mi jn)循環(huán)確認(rèn)Half Cycles半時循環(huán)(xnhun)Preconditioning time should be less than routine (full cycle) time預(yù)處理時間應(yīng)小于常規(guī)（全時循環(huán)）時間Half cycles should be sub-nominal for at least one parameter半時循環(huán)至少有一個參數(shù)小于常規(guī)Temperature and Humidity Sensors placed within the load溫濕度傳感器置于裝載內(nèi)共九十二頁Sterilization Cycle Vali

56、dation滅菌(mi jn)循環(huán)確認(rèn)Half Cycles半時循環(huán)Run 3 total Half Cycles with parameters established during Cycle Development共運(yùn)行3次半時循環(huán)，使用循環(huán)開發(fā)過程設(shè)定的參數(shù)(cnsh)Remove samples as defined in procedure按程序規(guī)定取出樣品共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Half Cycles半時循環(huán)Test BIs; typically 7 day incubationBI測試，通常7天培養(yǎng)Mast

57、er PCD (spored product or otherwise) must show no growth.主PCD（染菌產(chǎn)品或其他）必須顯示無生長。Confirmation of SAL 無菌保證(bozhng)水平確認(rèn)NO PRODUCT TESTING ON HALF CYCLES!半時循環(huán)勿進(jìn)行產(chǎn)品無菌測試共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Full Cycle 全時循環(huán)Run a minimum of 1 Full Cycle to evaluate:至少運(yùn)行1個全時循環(huán)以評估：Heat history of load

58、 (load contains sensors same as MPQ runs)裝載加熱歷史記錄（裝載帶有傳感器同MPQ循環(huán)）Aeration/EO Residues 解析(ji x)/ EO 殘留Product/packaging functionality 產(chǎn)品/包裝功能測試共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Full Cycle 全時循環(huán)Aeration Requirements/EO Residues 解析要求/ 殘留Develop dissipation curve to establish release time開發(fā)(

59、kif)擴(kuò)散曲線以建立放行時間共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Full Cycle 全時循環(huán)Residual allowable limits are based on application of product殘留的允許限量是基于(jy)產(chǎn)品的應(yīng)用Qualify release time based on three (3) separate lots (cycles)基于3次循環(huán)運(yùn)行建立放行時間共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Full Cycle 全時循環(huán)A s

60、econd (2X) Full Cycle is highly recommended 建議運(yùn)行二次滅菌：Simulates reprocessing by the facility 模擬再處理Test EO residues for 2X processed samples測試二次滅菌樣品(yngpn)殘留共九十二頁Sterilization Cycle Validation滅菌循環(huán)(xnhun)確認(rèn)Validation Report 確認(rèn)報告Report shall be signed by persons designated responsible for preparing, rev