Product adoption and process equivalence for ethylene oxide sterilization灭菌中产品引入及工艺等效

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灭菌中产品引入及工艺等效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：这个技术信息报告不是一个标准，这里提供的材料本身并不分外。委员会有时根据他们在其它标准和/或法规方面的经验使用“应当”这个词。Scope范

3、围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:此技术信息报告应用于传统或参数放行的医疗器械环氧乙烷灭菌过程， 适用于以下条件下的医疗器械灭菌：a new product is bei

4、ng added to the previously validated process,在已经确认过的环氧乙烷灭菌过程中增加新产品；changes to validated products are being evaluated,评估已确认产品的变化；a previously validated process is being moved to a different facility or to different equipment, and已确认过的过程被转移到不同的场地和/或设备；equivalency of a sterilization process is being ev

5、aluated.评估灭菌过程的等效性。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.尽管这里所提供的信息是为了用于指导医疗器械行业，但也可以用于一些其它相关材料或产品的领域。Terms and definitions术语与定义For the purposes of this AAMI TIR,

6、the following terms and definitions apply:以下术语和定义被应用于此AAMI技术信息报告：2.1candidate equipment: New or modified piece of equipment intended to deliver an existing validated process.候选设备：用于已验证过的现有工艺的新设备或经过改装的设备。2.2candidate product: New or modified product, including the packaging system, proposed for inclu

7、sion in the existing validated sterilization process.候选产品：新产品或改组过的产品，包括包装系统，它们将会采用现有已经验证过的灭菌工艺做灭菌处理。2.3EO processing group: Collection of products or product families that can be sterilized in the same EO sterilization process.EO工艺组：一组产品或产品族，可以使用同一EO灭菌工艺进行灭菌处理。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： 必须确定组内所有产品对灭菌工艺的挑战性小于该 组的挑战器械。ANSI/AAM I/ISO 11135-2:20082.4 EO产品族： 用于验证的，确定的、一组相似或等效的产品。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.安装鉴定（IQ）：取得文件与证据，证明已按设备参数提供与安装的过程。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.负载结构：这个结构包括1）产品在灭菌障碍系统（内包装）内的朝向；2）外包装(保护性包装，第二层或第三层)内的内包装数量以及朝向；3)托盘上保护性包装内产品数量、朝向及在托盘上的位置；4）灭菌空间内托盘（或容器）的数量及朝向。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.操作鉴定（OQ）：取得并记录证据，说明已安装设备在按规定操作时，可在预定的极限参数内工作的过程。ANSI/AAM I/ISO TIR1 1139:20062.8packaging system: Combination of the sterile barrier system and protective packaging.包装系统：灭菌障碍和保护性包装的总和。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.性能鉴定（PQ）：是这样一个过程：取得并记录那些资料，证明已安装设备按流程操作时，可持续满足预定标准，并生产出符合参数要求的产品。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.工艺挑战器械（PCD）：专门设计的一件东西，用于确定对一个灭菌工艺的抗性，从而评估一个灭菌工艺的性能。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.工艺等效：评价并记录同一灭菌工艺可使用一件或两件灭菌设备按预定的运行参数完成。2.12 product adoption: Process of formally including a candidate product into an existing validated EO processing gr

16、oup or EO product family.产品引入：将一件候选产品正式纳入一个现有已经验证过的EO工艺组或EO产品族的过程。2.13 requalification: Repetition of part of validation for the purpose of confirming the continued acceptability of a specified process.重鉴定：为了确定某一特定工艺的持续有效性，重复部分验证的过程。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.灭菌确认水平（SAL）：某一器械经灭菌后存在单个活体微生物的概率。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水平时，数值小的能提供更高的灭菌保证水平。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.灭菌工

19、艺设备： 预处理区域（若使用），灭菌腔或灭菌哭，通风区（若使用）以及相应的辅助设备。2.16 sterilization specialist: Person with knowledge of the sterilization technology being utilized and its effects upon materials and microorganisms.灭菌专家：拥有灭菌方面知识与技术，熟悉灭菌技术对材料和微生物的影响的人。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：这些知识包括理论知识与实践知识，且在涉及技术的基本原理方面不需要他人指导。 3Product adoption 产品引入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.一般来说将一件新产品或经过改装的产品（即候选产品）包含到一个已经验证过的灭菌工艺过程中去，就叫做“产品引入”。产品引入原本是用于减少EO产品族或EO工艺组划分时重鉴定次数的。本TIR讲述了产品引入的几个重要方面，也包括建立EO产品族和EO工艺组，以及建议如何维护这些产品族和工艺组。3.1Establishment o

23、f an EO product family 建立EO产品族Products may be grouped into EO product families on the basis of similarities in configuration, materials, density, packaging, or difficulty of sterilization.可根据产品、材料、包装、密度或灭菌难度对其进行分组，划入不同的EO产品族。The following list provides guidance on the elements that may be considered

24、 when placing products into EO product families:下面是进行EO族划分时可能考虑的元素：product design and function,产品设计与功能manufacturing method,生产方法manufacturing environment or area,生产环境或区域material of construction,生产材料e)f)g)h)i)packaging materials, 包装材料sterile barrier or protective packaging configuration, 灭菌障碍或保护性包装结构d

25、ensity,密度size and/or surface area, and 大小 或表面积，以及bioburden.生物负载 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.个个EO产品族可以包含多种相似的产品。例如，一个EO产品族可能有一系列导管，它们只是在尺寸上不同，可能有一系列产品，在同样的环境中生产；可能是一个包类产品，其中可能含有绷带,纱布球,手术器械,纱布片或其他产品, 被列入同一产品族内的包类产品之间的唯一的区别在于包类产品中器械的种类、数量和规格。EO产品族可由一个最坏情况产品（通常叫做 主导产品）；一般认为整个产品族对灭菌工艺的挑战是相同的，或者由于个工艺挑战器械来表示。代表性产品或PCD用作和候选产品进行比较的基础。3.2 Establ

28、ishment of an EO processing group 建立EO工艺组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.一个E

31、O工艺组是一个EO产品族的集合，在划分EO产品族细节如材料或包装材料上可能不一样，但每个EO工艺组中的每个工艺族都应可由一个共同灭菌工艺进行灭菌。例如，一个产品集（静脉内套件）可构成一个EO产品族并被纳入一个EO工艺组，而该工艺组还包含有另一个产品集（如一族注射器）。EO工艺组内的共性可能是表示组内产品微生物挑战性的PCD。这个EO工艺组内的所有产品与最坏情况的产品，代表性成员或PCD相比较时，灭菌挑战性应相同或更低。Grouping of products can also be beneficial when based on attributes such as EO residuals

32、, bioburden, or biocompatibility.根据EO残留，生物负载或生物兼容性等属性对产品进行分组也是有益的。3.3Evaluation for product adoption产品引入时的评价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.在对候选产品行目前已验证过的产品或对现有EO工艺进行验证的PCD进行比较时，应进行技术评审。该评审可在EO产品族或EO工艺组内进行。也可以使用最坏情况的产品或代表性成员进行鉴定研究。附录A为该评审提供了一个指南。附录A并不全面，可能还有一些其它因素需要考虑。相反，其中的某些项目根据候选产品的具体情况可能并不适用。3.3.1 Determination of adverse effects 确定不良效果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.在确定是否可将一件

38、修选产品或包装系统纳入到一个EO产品族或EO工艺组中之前，应先确定候选产品或包装系统（灭菌后 译注）的功能性和有效性。通过设计/变更控制流程系统的评估这些方面，需要考虑其功能性，一致性，稳定性，生物兼容性及环氧乙烷的残留量，还需特别考虑环氧乙烷灭菌过程不会影响器械/组件中含有的药物成分。如果器械/组件中含有的预灭菌过的药物成分，那么队了考虑环氧乙烷可能对涉及的产口的过期日的影响外，制造商需考虑法律法规对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.确定EO工艺而对产品进行的测试应对产品及其包装系统构成代表性的挑战（使用最大挑战的工艺参数）。ANSI/AAMI/ISO 11135-1:2007的7.2.1节中详细地说明了这一要求。文档应说明挑战过程和名义过程有同，产品鉴定应证明这些参数在产品验收时是可接受的。3.3.2 Determination of product design effects 确定产品设计效果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.应仔细审查候选产品看是否有导致比现有产品或PCD对EO、热或湿穿透效果。例如改变可能导致管腔更长，增加密闭空间或更大面积的吻合面。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.审查产品与原产品功能性检测确保更改不会对产品功能造成不良影响。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：这种评估典型地不包括按预期用途的使用中不会暴露在外的密闭空间。例如密封的、空心、模塑件或密封腔。3.3.3 Determination of product material and characteristics effects 确定产品材料与特征效果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.应仔细检查候选产品的特征，看是否有某些不同可能会影响产品的生物负载，如生产方法、生产设施、位置及原材料类别和来源等方面的差异。应审查生产材料以保证产品不会有过高的残留水平以免超出法规规定的水平。3.3.4 Determination of sterile barrier system effects 确定灭菌障碍系统效果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.应仔细审查候选产品的灭菌障碍系统，看是否有某些因素会阻碍EO，热源或湿气穿透。这些因素可包括通风材料孔的减少，通风区域减少，通风区域密闭或其它任何可能导致候选产品灭菌挑战性大于现有产品或PCD的挑战性。此外，产品更改对灭菌障碍系统的生物负载的影响和对

49、残留物的影响 也均应进行评估。3.3.5 Determination of load configuration effects 确定负载结构效果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.应仔细检查候选产品负载结构是否有某种改动会影响灭菌工艺热响应。这些这些改变包括层数增加，重新布置托盘，负载大小改变，负载整体密度改变，或其它任何可能导致候选产品对灭菌工艺造成更大挑战的其它更改。3.4

51、Conclusions of product adoption evaluation 产品引入评估的结论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.若有书面的技术审核证据表明，候选产品和现有产品或PCD相似，它们之间并无显著差异，或者候选产品的灭菌挑战性比当前已验证产品或PCD更小，那么就可以将候选产品纳入到EO产品族或EO工艺组，而无需做进一步研究。若在评审过程中使用附录A，那么附录A中问题的答案应全是“否”。应由灭菌专家给出为何这样做的理由 并归档在案。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若技术审核表明候选产品有可能比目前已经验证过的产品或PCD对灭菌工艺造成更大挑战，即表示应进行更进一步的研究（见3.4.1，3.4.2和3.4.3）。若候选产品对灭菌工艺挑战更大，不满足将其引入到现有EO产品族或EO工艺组中之要求，那么应根据ANSI/AAMI/ISO 11135-1:

56、2007做一次PQ，该PQ可能：establish a new EO product family or EO processing group, with the candidate product as the representative product;建立一个新的EO产品族或EO工艺组，以该候选产品作为代表性产品；establish a new PCD for the sterilization process; or为灭菌工艺过和建立一个新的PCD；或establish a new sterilization process for the candidate product. 为

57、候选产品建立新的灭菌工艺。3.4.1 Comparative resistance study 抗性（耐受性 译注）比较研究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.若技术审查表明候选产品可能会对灭菌工艺造成更大的、可导致灭菌失败的挑战时，应进行灭菌抗性比较研究对候选产品作出评价。这英研究至少应采用候选产品同样产品、现有产品或PCD，按照ANSI/AAMI/ISO 11135-1:2007附录A或附录B做完部分功能周期。若候选产品的微生物抗性小于或等于现有鉴定过的产品或PCD，那么就可以将它纳入到现有EO产品族或EO工艺组。若候选产品不能证明其抗性小于或等于现经鉴定过的产品，那么至少应做