Scope 范围

The scope of this document and accompanying attachments is limited to the biological evaluation of sterile and non-sterile medical devices that come into direct or indirect contact with the human body. This document specifically covers the use of ISO 10993-1 but also is relevant to other biocompatibility standards (e.g., other parts of the ISO#footnote[1] 10993 series of standards, ASTM[2], ICH[3], OECD[4], USP[5]).

本文件及附件的范围仅限于直接或间接与人体接触的无菌和非无菌医疗器械的生物评价。本文件特别涵盖了 ISO 10993-1 的使用，但也适用于其他生物相容性标准（例如，ISO[1:1] 10993 系列标准的其他部分，ASTM[2:1]，ICH[3:1]，OECD[4:1]，USP[5:1]）。

This document discusses the following topics:

本文件讨论以下主题：

  • use of risk assessments for biocompatibility evaluations for a proposed medical device;
    对拟议医疗器械进行生物相容性评价的风险评估使用；
  • use of ISO 10993-1 and the FDA-modified matrix (Attachment A) to determine the relevant biocompatibility endpoints for an evaluation;
    使用 ISO 10993-1 和 FDA 修改后的矩阵（附件 A）确定评价的相关生物相容性终点；
  • general biocompatibility testing considerations, including test article preparation;
    一般生物相容性测试考虑事项，包括试验品的制备；
  • specific considerations for the following testing: cytotoxicity, sensitization, hemocompatibility, pyrogenicity, implantation, genotoxicity, carcinogenicity, reproductive and developmental toxicity, and degradation assessments;
    以下测试的特定考虑事项：细胞毒性，致敏性，血液相容性，致热原性，植入，遗传毒性，致癌性，生殖和发育毒性以及降解评估；
  • chemical assessment recommendations#footnote[6]; and
    化学评估建议[6:1]；以及
  • considerations for labeling devices as “-free.”
    标记设备为“无某物”的考虑事项。

In addition, this guidance includes the following attachments that are intended to serve as resources:

此外，本指南还包括以下附件，旨在作为资源使用：

  • Attachment B: Device Master Files (MAFs) for Biocompatibility Evaluations, which includes information that we recommend including in an MAF;
    附件 B：用于生物相容性评价的设备主文件（MAFs），其中包含我们建议在 MAF 中包含的信息。
  • Attachment C: Summary Biocompatibility Documentation, which includes an example table that we recommend using to summarize the biocompatibility information used to support a submission;
    附件 C：汇总生物相容性文件，其中包括一个示例表格，我们建议使用该表格汇总用于支持提交的生物相容性信息；
  • Attachment D: Biocompatibility Evaluation Flow Chart, which illustrates how to proceed with a biocompatibility evaluation;
    附件 D：生物相容性评估流程图，说明如何进行生物相容性评估；
  • Attachment E: Content of a Biocompatibility Test Report, which includes the recommended contents of a test report;
    附件 E：生物相容性测试报告内容，包括测试报告的推荐内容；
  • Attachment F: Component and Device Documentation Examples, which outlines example documentation language that we recommend using when comparing the composition of a test article to the composition of a finished medical device or in comparing the composition of a previously legally US-marketed device to the composition of a current device; and
    附件 F：组件和器械文件示例，概述了在比较测试样品的组成与成品医疗器械的组成或在比较先前在美国合法上市的器械与当前器械的组成时，我们推荐使用的文件语言示例；
  • Attachment G: Glossary, which includes terms and definitions used in this guidance.
    附件 G：术语表，包括本指南中使用的术语和定义。

If there are other FDA-recognized consensus standards#footnote[7] that address biocompatibility issues for particular types of devices (e.g., ISO 7405 “Dentistry - Evaluation of biocompatibility of medical devices used in dentistry”), the recommendations in the more device-specific standard should be followed. In some cases, such as for dental devices, the biocompatibility recommendations in the device-specific standard should be used instead of the recommendations outlined in ISO 10993-1. In contrast, some device-specific guidances include recommendations regarding biocompatibility evaluations, that should be considered in conjunction with ISO 10993-1. For example, the FDA guidance “Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers”#footnote[8] specifies that subcomponent testing is recommended due to the high surface area of the membrane component of a hemodialyzer, and testing of the complete device is only recommended if “the extraction conditions (i.e., volume of solvent used per surface area of test article) are more rigorous than those recommended in ISO 10993.” In this case, if biocompatibility testing of a hemodialyzer is conducted on the final device, FDA recommends that the hemodialyzer be filled to capacity with the solvent, resulting in a much higher surface area to extract volume ratio, as compared to recommendations from ISO 10993-12 “Biological evaluation of medical devices-Part 12: Sample preparation and reference materials.” However, if non-membrane components are tested separately, then use of ISO 10993-12 recommendations for test article preparation would apply.

如果有其他 FDA 认可的共识标准@fn:10 针对特定类型的器械地址生物相容性问题（例如，ISO 7405 “牙科 - 评估牙科医疗器械的生物相容性”），应遵循更具体器械标准中的建议。在某些情况下，例如牙科器械，应使用器械特定标准中的生物相容性建议，而不是 ISO 10993-1 中概述的建议。相反，一些器械特定的指南包括关于生物相容性评估的建议，应与 ISO 10993-1 一起考虑。例如，FDA 指南 “常规和高渗透性血透器的市前通知内容”@fn:11 指定了推荐进行亚组件测试，这是由于血透器膜组件的大表面积所决定的，仅当 “提取条件（即，溶剂用量与测试样品表面积之比）比 ISO 10993 中推荐的更严格时” 才推荐进行整个器械的测试。在这种情况下，如果对血透器进行了最终器械的生物相容性测试，FDA 建议将血透器填满溶剂，从而产生比 ISO 10993-12 中的建议更高的表面积与提取体积比率。然而，如果对非膜组分进行单独测试，那么应使用 ISO 10993-12 中有关测试样品准备的建议。

Note that if your product is a combination product with a device constituent part[9], the general principles of this guidance would apply, although additional or modified testing may be[10] needed. For example, sample preparation of biologic-device combination products may be dependent on the type of product and the endpoint being assessed, and such detailed guidance specific to biocompatibility evaluation of combination products are not within the scope of this document. As such, we encourage you to discuss combination products with the appropriate Center and review division who will initiate proper consultation on combination product-specific biocompatibility concerns as appropriate.

请注意，如果您的产品是含有器械成分[9:1]的组合产品，本指南的一般原则仍然适用，尽管可能[10:1]需要额外或修改后的测试。例如，生物-器械组合产品的样品制备可能取决于产品类型和评估的终点，而有关生物相容性评估的组合产品的详细指导不在本文件的范围内。因此，我们鼓励您与适当的中心和审评部门讨论组合产品，并根据需要进行有关组合产品特定生物相容性问题的咨询。

We also recognize that an ISO standard is a document that undergoes periodic review and is subject to revision. Through the FDA standards recognition process, we provide information regarding the extent of recognition of the ISO 10993 series of standards and other biocompatibility standards through Supplemental Information Sheets published on the FDA website[11]. FDA recommends that complete test reports be provided for all tests performed because the ISO 10993 series of standards include general methods with multiple options, and in some cases do not include acceptance criteria or address assessment of results[12]. Therefore, when a declaration of conformity is submitted for an FDA-recognized standard in the ISO 10993 series, a copy of the supplemental information used to support the declaration (e.g., a copy of the study test report as described in Attachment E) should also be provided[13]. FDA will make updates to this guidance document as appropriate, should future revisions to ISO 10993-1 or other FDA recognized biocompatibility standards result in significant changes to the recommendations in this document.

我们也认识到 ISO 标准是一份经过定期审查并可能进行修订的文件。通过 FDA 标准认可流程，我们通过在 FDA 网站[11:1]上发布的补充信息表格提供有关 ISO 10993 系列标准和其他生物相容性标准的认可程度的信息。FDA 建议提供所有测试的完整测试报告，因为 ISO 10993 系列标准包括多种选项的通用方法，并且在某些情况下不包括验收标准或结果[12:1]评估。因此，当向 FDA 承认的 ISO 10993 系列标准提交符合性声明时，还应提供用于支持声明的补充信息的副本（例如，如附件 E 所述的研究测试报告的副本）[13:1]。如果 ISO 10993-1 或其他 FDA 认可的生物相容性标准的未来修订对本文件中的建议产生重大变化，FDA 将适时更新本指南文件。

Sponsors are advised to initiate discussions with the appropriate Center and review division prior to the initiation of long-term testing of any new device to ensure that, if testing is needed, the proper testing will be conducted.

在开始对任何新设备进行长期测试之前，建议主办方与相应的中心和审评部门进行讨论，以确保必要时能够进行适当的测试。

  1. ISO stands for International Organization for Standardization, an international standards development organization. See http://www.iso.org/iso/home.html for more information.
    ISO 代表国际标准化组织，是一个国际标准制定组织。有关更多信息，请参阅 http://www.iso.org/iso/home.html。 ↩︎ ↩︎

  2. ASTM stands for American Society for Testing and Materials, an international standards development organization. See http://www.astm.org/ABOUT/overview.html for more information.
    ASTM 代表美国材料试验协会，是一个国际标准制定组织。有关更多信息，请参阅 http://www.astm.org/ABOUT/overview.html。 ↩︎ ↩︎

  3. ICH stands for International Conference on Harmonisation, an international standards development organization. See http://www.ich.org/about/vision.html for more information.
    ICH 代表国际协调会议，是一个国际标准制定组织。有关更多信息，请参阅 http://www.ich.org/about/vision.html。 ↩︎ ↩︎

  4. OECD stands for Organisation for Economic Co-operation and Development, an international standards development organization. See http://www.oecd.org/for more information.
    OECD 代表经济合作与发展组织，是一个国际标准制定组织。有关更多信息，请参阅 http://www.oecd.org/。 ↩︎ ↩︎

  5. USP stands for U.S. Pharmacopeial Convention, a United States standards development organization. See http://www.usp.org/about-usp for more information.
    USP 代表美国药典委员会，是一个美国标准制定组织。有关更多信息，请参阅 http://www.usp.org/about-usp。 ↩︎ ↩︎

  6. All issues specific to the evaluation of color additives in medical devices included in the draft version of this guidance were removed, and the intent is for these items to be addressed in a separate guidance document.
    关于在本指南草案中包含的医疗器械中颜料添加剂评价的所有问题已被移除，意图是将这些问题在单独的指南文件中解决。 ↩︎ ↩︎

  7. Refer to FDA’s “Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices: Guidance for Industry and Food and Drug Administration Staff,” available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices for information regarding the recognition and use of national and international consensus standards during the evaluation of premarket submissions for medical devices.
    请参考 FDA 的《医疗器械前市场提交中志愿共识标准的适当使用：行业和食品药品管理局人员指南》，获取有关在评估医疗器械前市场提交时识别和使用国家和国际共识标准的信息。网址: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices ↩︎

  8. Available at https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/content-premarket-notifications-conventional-and-high-permeability-hemodialyzers-guidance-industry
    请参考: https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/content-premarket-notifications-conventional-and-high-permeability-hemodialyzers-guidance-industry ↩︎

  9. Please refer to 21 CFR 3.2(e) for the definition of a combination product.
    请参考 21 CFR 3.2(e) 中关于组合产品的定义。 ↩︎ ↩︎

  10. The term “may” is used here and throughout the document to indicate that the final determination on whether additional information should be provided will depend on the specifics of the final device under consideration.
    此处及本文件中的术语“可能”表示最终是否需要提供额外信息将取决于最终考虑的设备的具体情况。 ↩︎ ↩︎

  11. See FDA’s Database on Recognized Consensus Standards and input “10993-1” for the Supplemental Information Sheet.
    请参考 FDA 公认共识标准数据库，并输入“10993-1”获取补充信息表格。 ↩︎ ↩︎

  12. In the case of Abbreviated 510(k)s, a summary of the methods often is needed to ensure that the test was conducted in the same way as for a predicate device, and that the same evaluation criteria were used. If it is easier for the sponsor to submit a copy of the test report, which is not required by FDA, this would be acceptable. For Special 510(k)s, refer to the guidance “The Special 510(k) Program,” available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/special-510k-program, for more information about FDA’s recommended biocompatibility information that should be included.
    对于简化 510(k) 的情况，通常需要提供方法摘要，以确保测试与参比器械相同，并使用相同的评估标准。如果主办方更容易提交测试报告的副本（FDA 不要求），这也是可以接受的。对于特殊 510(k)，请参考“特殊 510(k) 计划”的指南，了解 FDA 建议包括的生物相容性信息。网址: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/special-510k-program ↩︎ ↩︎

  13. Refer to FDA’s “Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices: Guidance for Industry and Food and Drug Administration Staff” for information regarding the recognition and use of national and international consensus standards, including declarations of conformity to these standards, during the evaluation of premarket submissions for medical devices.
    请参考 FDA 的《医疗器械前市场提交中志愿共识标准的适当使用：行业和食品药品管理局人员指南》，了解在评估医疗器械前市场提交时识别和使用国家和国际共识标准，包括对这些标准的符合性声明的信息。 ↩︎ ↩︎