Product adoption and process equivalence for ethylene oxide sterilization滅菌中產(chǎn)品引入及工藝等效

1、AAMIAAMISingle user license only. Copying, networking, and distribution prohibited.AAMIAAMISingle user license only. Copying, networking, and distribution prohibited.Product adoption and process equivalence for ethylene oxide sterilizationOE滅菌中產(chǎn)品引入及工藝等效NOTEThis technical information report is not a

2、standard and the material contained herein is not normative in nature. The committee has in a few places used the term shall based on their knowledge of requirements contained in relevant standards and/or regulatory requirements.注：這個技術(shù)信息報告不是一個標準，這里提供的材料本身并不分外。委員會有時根據(jù)他們在其它標準和/或法規(guī)方面的經(jīng)驗使用“應當”這個詞。Scope范

3、圍This TIR addresses medical devices that are processed by ethylene oxide (EO) sterilization using conventional or parametric product release. The document applies to the following situations for the sterilization of medical devices:此技術(shù)信息報告應用于傳統(tǒng)或參數(shù)放行的醫(yī)療器械環(huán)氧乙烷滅菌過程， 適用于以下條件下的醫(yī)療器械滅菌：a new product is bei

4、ng added to the previously validated process,在已經(jīng)確認過的環(huán)氧乙烷滅菌過程中增加新產(chǎn)品；changes to validated products are being evaluated,評估已確認產(chǎn)品的變化；a previously validated process is being moved to a different facility or to different equipment, and已確認過的過程被轉(zhuǎn)移到不同的場地和/或設(shè)備；equivalency of a sterilization process is being ev

5、aluated.評估滅菌過程的等效性。Although the information presented was developed for application to medical devices, the content of this guideline may also be applied to other relevant products or materials.盡管這里所提供的信息是為了用于指導醫(yī)療器械行業(yè)，但也可以用于一些其它相關(guān)材料或產(chǎn)品的領(lǐng)域。Terms and definitions術(shù)語與定義For the purposes of this AAMI TIR,

6、the following terms and definitions apply:以下術(shù)語和定義被應用于此AAMI技術(shù)信息報告：2.1candidate equipment: New or modified piece of equipment intended to deliver an existing validated process.候選設(shè)備：用于已驗證過的現(xiàn)有工藝的新設(shè)備或經(jīng)過改裝的設(shè)備。2.2candidate product: New or modified product, including the packaging system, proposed for inclu

7、sion in the existing validated sterilization process.候選產(chǎn)品：新產(chǎn)品或改組過的產(chǎn)品，包括包裝系統(tǒng)，它們將會采用現(xiàn)有已經(jīng)驗證過的滅菌工藝做滅菌處理。2.3EO processing group: Collection of products or product families that can be sterilized in the same EO sterilization process.EO工藝組：一組產(chǎn)品或產(chǎn)品族，可以使用同一EO滅菌工藝進行滅菌處理。NOTEAll products within the processing

8、group have been determined to present an equal or lesser challenge to the sterilization process than the challenge device for that group.注： 必須確定組內(nèi)所有產(chǎn)品對滅菌工藝的挑戰(zhàn)性小于該 組的挑戰(zhàn)器械。ANSI/AAM I/ISO 11135-2:20082.4 EO產(chǎn)品族： 用于驗證的，確定的、一組相似或等效的產(chǎn)品。ANSI/AAM I/ISO 11135-2:20082.5installation qualification (IQ): Process

9、of obtaining and documenting evidence that equipment has been provided and installed in accordance with its specification.安裝鑒定（IQ）：取得文件與證據(jù)，證明已按設(shè)備參數(shù)提供與安裝的過程。ANSI/AAM I/ISO TIR1 1139:20062.6 load configuration: Totality of attributes defining the presentation of the product to the sterilization proces

10、s. This configuration includes (a) the orientation of the product within the sterile barrier system (primary package); (b) the quantity and orientation of the primary package within the protective packaging (secondary or tertiary package); the carriers); and (d) the quantity and placement of the pal

11、lets (or carriers) within the vessel or area.負載結(jié)構(gòu)：這個結(jié)構(gòu)包括1）產(chǎn)品在滅菌障礙系統(tǒng)（內(nèi)包裝）內(nèi)的朝向；2）外包裝(保護性包裝，第二層或第三層)內(nèi)的內(nèi)包裝數(shù)量以及朝向；3)托盤上保護性包裝內(nèi)產(chǎn)品數(shù)量、朝向及在托盤上的位置；4）滅菌空間內(nèi)托盤（或容器）的數(shù)量及朝向。2.7operational qualification (OQ): Process of obtaining and documenting evidence that installed equipment operates within predetermined limits

12、when used in accordance with its operational procedures.操作鑒定（OQ）：取得并記錄證據(jù)，說明已安裝設(shè)備在按規(guī)定操作時，可在預定的極限參數(shù)內(nèi)工作的過程。ANSI/AAM I/ISO TIR1 1139:20062.8packaging system: Combination of the sterile barrier system and protective packaging.包裝系統(tǒng)：滅菌障礙和保護性包裝的總和。2.9 performance qualification (PQ): Process of obtaining and

13、 documenting evidence that the equipment, as installed and operated in accordance with operational procedures, consistently performs in accordance with predetermined criteria and thereby yields product meeting its specification.性能鑒定（PQ）：是這樣一個過程：取得并記錄那些資料，證明已安裝設(shè)備按流程操作時，可持續(xù)滿足預定標準，并生產(chǎn)出符合參數(shù)要求的產(chǎn)品。ANSI/AA

14、M I/ISO TIR1 1139:20062.10 process challenge device (PCD): Item designed to constitute a defined resistance to a sterilization process and used to assess performance of the process.工藝挑戰(zhàn)器械（PCD）：專門設(shè)計的一件東西，用于確定對一個滅菌工藝的抗性，從而評估一個滅菌工藝的性能。ANSI/AAM I/ISO TIR1 1139:20062.11 process equivalence: Documented ev

15、aluation that the same sterilization process can be delivered by two or more pieces of sterilization process equipment within defined parameters.工藝等效：評價并記錄同一滅菌工藝可使用一件或兩件滅菌設(shè)備按預定的運行參數(shù)完成。2.12 product adoption: Process of formally including a candidate product into an existing validated EO processing gr

16、oup or EO product family.產(chǎn)品引入：將一件候選產(chǎn)品正式納入一個現(xiàn)有已經(jīng)驗證過的EO工藝組或EO產(chǎn)品族的過程。2.13 requalification: Repetition of part of validation for the purpose of confirming the continued acceptability of a specified process.重鑒定：為了確定某一特定工藝的持續(xù)有效性，重復部分驗證的過程。ANSI/AAM I/ISO TIR1 1139:20062.14 sterility assurance level (SAL):

17、Probability of a single viable microorganism occurring on an item after sterilization.滅菌確認水平（SAL）：某一器械經(jīng)滅菌后存在單個活體微生物的概率。NOTEThe term SAL takes a quantitative value, generally 10-6 or 10-3. When applying this quantitative value to assurance of sterility, an SAL of 1 0- has a lower value but provides a

18、 greater assurance of sterility than an SAL of 1 0-3.注：SAL采用定量衡量，一般是10-6或10-3。使用定量值衡量SAL水平時，數(shù)值小的能提供更高的滅菌保證水平。ANSI/AAM I/ISO TIR1 1139:20062.15 sterilization process equipment: Preconditioning area (if used), chamber or sterilizer, aeration area (if used), and their respective ancillary equipment.滅菌工

19、藝設(shè)備： 預處理區(qū)域（若使用），滅菌腔或滅菌哭，通風區(qū)（若使用）以及相應的輔助設(shè)備。2.16 sterilization specialist: Person with knowledge of the sterilization technology being utilized and its effects upon materials and microorganisms.滅菌專家：擁有滅菌方面知識與技術(shù)，熟悉滅菌技術(shù)對材料和微生物的影響的人。NOTEThis level of knowledge has been obtained by both practical and theo

20、retical means and the person does not require guidance on the basic principles of the technology involved.注：這些知識包括理論知識與實踐知識，且在涉及技術(shù)的基本原理方面不需要他人指導。 3Product adoption 產(chǎn)品引入The term usually associated with the introduction of a new or modified product (candidate product) into a validated sterilization pr

21、ocess is “product adoption.” Product adoption has traditionally been used to reduce the level of performance qualification (PQ) required by grouping products into either EO product families or EO processing groups. This TIR describes the important aspects to the approach for product adoption, which

22、also includes the establishment of EO product families and EO processing groups and the recommended maintenance of those families and groups.一般來說將一件新產(chǎn)品或經(jīng)過改裝的產(chǎn)品（即候選產(chǎn)品）包含到一個已經(jīng)驗證過的滅菌工藝過程中去，就叫做“產(chǎn)品引入”。產(chǎn)品引入原本是用于減少EO產(chǎn)品族或EO工藝組劃分時重鑒定次數(shù)的。本TIR講述了產(chǎn)品引入的幾個重要方面，也包括建立EO產(chǎn)品族和EO工藝組，以及建議如何維護這些產(chǎn)品族和工藝組。3.1Establishment o

23、f an EO product family 建立EO產(chǎn)品族Products may be grouped into EO product families on the basis of similarities in configuration, materials, density, packaging, or difficulty of sterilization.可根據(jù)產(chǎn)品、材料、包裝、密度或滅菌難度對其進行分組，劃入不同的EO產(chǎn)品族。The following list provides guidance on the elements that may be considered

24、 when placing products into EO product families:下面是進行EO族劃分時可能考慮的元素：product design and function,產(chǎn)品設(shè)計與功能manufacturing method,生產(chǎn)方法manufacturing environment or area,生產(chǎn)環(huán)境或區(qū)域material of construction,生產(chǎn)材料e)f)g)h)i)packaging materials, 包裝材料sterile barrier or protective packaging configuration, 滅菌障礙或保護性包裝結(jié)構(gòu)d

25、ensity,密度size and/or surface area, and 大小 或表面積，以及bioburden.生物負載 contain a series of catheters that differ only in their sizes; a variety of products that are made in the same environment with the same material; or kits that contain various combinations of sponges, bowls, instruments, towels, the kit

26、s. The EO product family may be represented by a worst-case product (often called the “master product”); the entire family is considered an equivalent challenge to the sterilization process, or it is represented by a process challenge device (PCD). The representative product or PCD would then be use

27、d as the basis for comparison of any candidate product.個個EO產(chǎn)品族可以包含多種相似的產(chǎn)品。例如，一個EO產(chǎn)品族可能有一系列導管，它們只是在尺寸上不同，可能有一系列產(chǎn)品，在同樣的環(huán)境中生產(chǎn)；可能是一個包類產(chǎn)品，其中可能含有繃帶,紗布球,手術(shù)器械,紗布片或其他產(chǎn)品, 被列入同一產(chǎn)品族內(nèi)的包類產(chǎn)品之間的唯一的區(qū)別在于包類產(chǎn)品中器械的種類、數(shù)量和規(guī)格。EO產(chǎn)品族可由一個最壞情況產(chǎn)品（通常叫做 主導產(chǎn)品）；一般認為整個產(chǎn)品族對滅菌工藝的挑戰(zhàn)是相同的，或者由于個工藝挑戰(zhàn)器械來表示。代表性產(chǎn)品或PCD用作和候選產(chǎn)品進行比較的基礎(chǔ)。3.2 Establ

28、ishment of an EO processing group 建立EO工藝組An EO processing group is a collection of EO product families that can be dissimilar in the details used to establish the EO product family, such as material of construction or packaging, but each of the EO product families within an EO processing group shoul

29、d be qualified in a common sterilization process. For example, a collection of products (intravenous sets) may constitute an EO product family and may be placed in an EO processing group that includes a separate collection of products (e.g., a family of syringes). The commonality within the EO proce

30、ssing group may be the PCD that represents the microbial challenge for those products in that group. All products within this EO processing group should present an equivalent or lesser challenge to the sterilization process when compared with the worst-case product, representative member, or PCD.一個E

31、O工藝組是一個EO產(chǎn)品族的集合，在劃分EO產(chǎn)品族細節(jié)如材料或包裝材料上可能不一樣，但每個EO工藝組中的每個工藝族都應可由一個共同滅菌工藝進行滅菌。例如，一個產(chǎn)品集（靜脈內(nèi)套件）可構(gòu)成一個EO產(chǎn)品族并被納入一個EO工藝組，而該工藝組還包含有另一個產(chǎn)品集（如一族注射器）。EO工藝組內(nèi)的共性可能是表示組內(nèi)產(chǎn)品微生物挑戰(zhàn)性的PCD。這個EO工藝組內(nèi)的所有產(chǎn)品與最壞情況的產(chǎn)品，代表性成員或PCD相比較時，滅菌挑戰(zhàn)性應相同或更低。Grouping of products can also be beneficial when based on attributes such as EO residuals

32、, bioburden, or biocompatibility.根據(jù)EO殘留，生物負載或生物兼容性等屬性對產(chǎn)品進行分組也是有益的。3.3Evaluation for product adoption產(chǎn)品引入時的評價A technical review should be performed comparing the candidate product with the currently validated product or PCD that was used to validate the existing EO process. This review may be conduct

33、ed within each EO product family or EO processing group. Alternatively, a worst-case product or representative member may be selected for the qualification study. Annex A is a guide that can be used in this review. Annex A is not all inclusive; there may be other factors that should be considered. C

34、onversely, some of the items might not apply, depending on the candidate product.在對候選產(chǎn)品行目前已驗證過的產(chǎn)品或?qū)ΜF(xiàn)有EO工藝進行驗證的PCD進行比較時，應進行技術(shù)評審。該評審可在EO產(chǎn)品族或EO工藝組內(nèi)進行。也可以使用最壞情況的產(chǎn)品或代表性成員進行鑒定研究。附錄A為該評審提供了一個指南。附錄A并不全面，可能還有一些其它因素需要考慮。相反，其中的某些項目根據(jù)候選產(chǎn)品的具體情況可能并不適用。3.3.1 Determination of adverse effects 確定不良效果Before determinin

35、g whether a candidate product or packaging system can be adopted into an EO product family or EO processing group, one should determine whether the candidate product or packaging system will remain functional and effective. A system to evaluate these aspects should be addressed by the design or chan

36、ge control process. Consideration should be given to functionality, integrity, stability, biocompatibility, and residuals, with special consideration given to determining the effect that the sterilization process might have on drugs that could be included in devices or components. For products that

37、contain certain types of finished components (e.g., kits with drugs), the manufacturer should consider regulatory requirements with regard to the safety and efficacy of these components in addition to the impact the sterilization process may have on the expiry date of the products involved.在確定是否可將一件

38、修選產(chǎn)品或包裝系統(tǒng)納入到一個EO產(chǎn)品族或EO工藝組中之前，應先確定候選產(chǎn)品或包裝系統(tǒng)（滅菌后 譯注）的功能性和有效性。通過設(shè)計/變更控制流程系統(tǒng)的評估這些方面，需要考慮其功能性，一致性，穩(wěn)定性，生物兼容性及環(huán)氧乙烷的殘留量，還需特別考慮環(huán)氧乙烷滅菌過程不會影響器械/組件中含有的藥物成分。如果器械/組件中含有的預滅菌過的藥物成分，那么隊了考慮環(huán)氧乙烷可能對涉及的產(chǎn)口的過期日的影響外，制造商需考慮法律法規(guī)對有效性和安全性方面的要求。The EO process for which the product will be tested should constitute a representati

39、ve challenge (using the most challenging process parameters) to the product and its packaging system. This requirement is detailed within 7.2.1 of ANSI/AAMI/ISO 11135-1:2007. Documentation should address how the challenge process differs from the nominal process, and the product qualification should

40、 demonstrate that these parameters are acceptable for product acceptance.NOTEThe candidate product and its packaging should be evaluated for EO residuals, and any changes to either should be evaluated for the impact on product release. ANSI/AAMI/ISO 10993-7:2008 should be used as guidance for making

41、 this evaluation.確定EO工藝而對產(chǎn)品進行的測試應對產(chǎn)品及其包裝系統(tǒng)構(gòu)成代表性的挑戰(zhàn)（使用最大挑戰(zhàn)的工藝參數(shù)）。ANSI/AAMI/ISO 11135-1:2007的7.2.1節(jié)中詳細地說明了這一要求。文檔應說明挑戰(zhàn)過程和名義過程有同，產(chǎn)品鑒定應證明這些參數(shù)在產(chǎn)品驗收時是可接受的。3.3.2 Determination of product design effects 確定產(chǎn)品設(shè)計效果The design of the candidate product should be carefully reviewed for any changes or differences t

42、hat could present greater obstacles to EO, heat, or humidity penetration than the existing product or PCD. Examples of possible changes include longer lumens, the addition of closures, or a larger number of mated surfaces.應仔細審查候選產(chǎn)品看是否有導致比現(xiàn)有產(chǎn)品或PCD對EO、熱或濕穿透效果。例如改變可能導致管腔更長，增加密閉空間或更大面積的吻合面。Review the pr

43、oduct design against the original product functionality testing to ensure that the changes do not adversely affect the function of the product.審查產(chǎn)品與原產(chǎn)品功能性檢測確保更改不會對產(chǎn)品功能造成不良影響。NOTEThis evaluation typically does not include areas of the device that are hermetically sealed and cannot be exposed during i

44、ntended use. Examples are items such as sealed, hollow, molded parts or sealed lumens.注：這種評估典型地不包括按預期用途的使用中不會暴露在外的密閉空間。例如密封的、空心、模塑件或密封腔。3.3.3 Determination of product material and characteristics effects 確定產(chǎn)品材料與特征效果The characteristics of the candidate product should be carefully examined for any dif

45、ferences that could potentially affect the product bioburden, such as manufacturing production methods, facilities, location, and raw material types and sources. The materials of construction should be reviewed to ensure that the product will not retain higher residual levels or levels that will exc

46、eed the regulated limits.應仔細檢查候選產(chǎn)品的特征，看是否有某些不同可能會影響產(chǎn)品的生物負載，如生產(chǎn)方法、生產(chǎn)設(shè)施、位置及原材料類別和來源等方面的差異。應審查生產(chǎn)材料以保證產(chǎn)品不會有過高的殘留水平以免超出法規(guī)規(guī)定的水平。3.3.4 Determination of sterile barrier system effects 確定滅菌障礙系統(tǒng)效果The sterile barrier system of the candidate product should be carefully examined for any factors that could presen

47、t obstacles to EO, heat, or humidity penetration. These factors may be a decrease in porosity of the venting material, a smaller venting surface area, the occlusion of the venting area, or any other feature that would make the candidate product a greater challenge to the sterilization process than t

48、he existing product or PCD. In addition, the effects of changes to the sterile barrier system on the bioburden of the product and any effects on residuals should be evaluated.應仔細審查候選產(chǎn)品的滅菌障礙系統(tǒng)，看是否有某些因素會阻礙EO，熱源或濕氣穿透。這些因素可包括通風材料孔的減少，通風區(qū)域減少，通風區(qū)域密閉或其它任何可能導致候選產(chǎn)品滅菌挑戰(zhàn)性大于現(xiàn)有產(chǎn)品或PCD的挑戰(zhàn)性。此外，產(chǎn)品更改對滅菌障礙系統(tǒng)的生物負載的影響和對

49、殘留物的影響 也均應進行評估。3.3.5 Determination of load configuration effects 確定負載結(jié)構(gòu)效果The load configuration of the candidate product should be carefully examined for any changes that could affect the thermodynamic response to the sterilization process. These changes could include additional layers, a reconfigur

50、ation of the pallet, a change in the load size, a change to the overall density of the load, or any other change that would make the candidate product a greater challenge to the sterilization process.應仔細檢查候選產(chǎn)品負載結(jié)構(gòu)是否有某種改動會影響滅菌工藝熱響應。這些這些改變包括層數(shù)增加，重新布置托盤，負載大小改變，負載整體密度改變，或其它任何可能導致候選產(chǎn)品對滅菌工藝造成更大挑戰(zhàn)的其它更改。3.4

51、Conclusions of product adoption evaluation 產(chǎn)品引入評估的結(jié)論If the results of the written technical review show that the candidate product and existing products or PCD are similar and that the differences between them are determined to be insignificant or to present a lesser challenge than the currently val

52、idated product or PCD, then the candidate product may be adopted into the EO product family or EO processing group without further study. If Annex A was used for the review, this decision would be supported by virtually all “No” answers to the questions. The rationale for this decision should be mad

53、e by a sterilization specialist and shall be documented.若有書面的技術(shù)審核證據(jù)表明，候選產(chǎn)品和現(xiàn)有產(chǎn)品或PCD相似，它們之間并無顯著差異，或者候選產(chǎn)品的滅菌挑戰(zhàn)性比當前已驗證產(chǎn)品或PCD更小，那么就可以將候選產(chǎn)品納入到EO產(chǎn)品族或EO工藝組，而無需做進一步研究。若在評審過程中使用附錄A，那么附錄A中問題的答案應全是“否”。應由滅菌專家給出為何這樣做的理由 并歸檔在案。If the technical review indicates that the candidate product has the potential to be a

54、greater challenge to the sterilization process than the currently validated product or PCD, then further studies are indicated (see 3.4.1, 3.4.2, and 3.4.3). If the candidate product is determined to represent a greater challenge to the sterilization process, then it does not meet the requirements f

55、or adoption into an existing EO product family or EO processing group, and a PQ shall be performed in accordance with ANSI/AAMI/ISO 11135-1:2007. This PQ may若技術(shù)審核表明候選產(chǎn)品有可能比目前已經(jīng)驗證過的產(chǎn)品或PCD對滅菌工藝造成更大挑戰(zhàn)，即表示應進行更進一步的研究（見3.4.1，3.4.2和3.4.3）。若候選產(chǎn)品對滅菌工藝挑戰(zhàn)更大，不滿足將其引入到現(xiàn)有EO產(chǎn)品族或EO工藝組中之要求，那么應根據(jù)ANSI/AAMI/ISO 11135-1:

56、2007做一次PQ，該PQ可能：establish a new EO product family or EO processing group, with the candidate product as the representative product;建立一個新的EO產(chǎn)品族或EO工藝組，以該候選產(chǎn)品作為代表性產(chǎn)品；establish a new PCD for the sterilization process; or為滅菌工藝過和建立一個新的PCD；或establish a new sterilization process for the candidate product. 為

57、候選產(chǎn)品建立新的滅菌工藝。3.4.1 Comparative resistance study 抗性（耐受性 譯注）比較研究A comparative resistance study may be performed to evaluate the candidate product if the technical review indicated that it may present a greater lethality challenge to the sterilization process. This study is conducted performing at leas

58、t one fractional cycle with replicates of the candidate product and existing product or PCD according to the requirements of Annex A or Annex B of ANSI/AAMI/ISO 11135-1:2007. If the microbiological resistance of the candidate product demonstrates an equal or lesser resistance than does the qualified

59、 product or PCD, then the candidate product can be adopted into the existing EO product family or EO processing group. When the candidate product fails to demonstrate an equal or lesser resistance to the qualified product, then at least a microbiological PQ would be required, and it does not meet th

60、e requirements for adoption into an existing EO product family or EO processing group.若技術(shù)審查表明候選產(chǎn)品可能會對滅菌工藝造成更大的、可導致滅菌失敗的挑戰(zhàn)時，應進行滅菌抗性比較研究對候選產(chǎn)品作出評價。這英研究至少應采用候選產(chǎn)品同樣產(chǎn)品、現(xiàn)有產(chǎn)品或PCD，按照ANSI/AAMI/ISO 11135-1:2007附錄A或附錄B做完部分功能周期。若候選產(chǎn)品的微生物抗性小于或等于現(xiàn)有鑒定過的產(chǎn)品或PCD，那么就可以將它納入到現(xiàn)有EO產(chǎn)品族或EO工藝組。若候選產(chǎn)品不能證明其抗性小于或等于現(xiàn)經(jīng)鑒定過的產(chǎn)品，那么至少應做