1.1 该实践提供了用于植入应用的可吸收生物材料的组织反应的生物测定的实验方案。本规程仅适用于具有预期临床应用的可吸收材料，其中材料在骨骼或软组织中的停留时间将超过30天且不到三年。具有指定植入时间的其他标准可用于解决较短的时间段。对于停留时间超过三年的缓慢降解材料，应仔细考虑这种做法的适当性。预计组织对降解生物材料的反应将不同于对不可吸收材料的反应。 在许多情况下，在降解阶段可能会观察到慢性炎症反应，但吸收后局部组织学应恢复正常；因此，通常等同于生物相容性的最小组织反应可能需要长时间的植入。 1.2 植入物吸收的时间段可能取决于化学成分、植入物尺寸、植入物位置和动物模型的变量。因此，可以基于吸收速率来选择用于评估组织效应的所选时间点。 1.3 这些方案评估材料对植入的动物组织的影响。他们没有充分评估材料的全身毒性、致癌性、生殖和发育毒性或致突变性。 可以使用其他标准来解决这些问题。 1.4 为了最大限度地利用研究方案中的动物，可以通过这种做法来解决系统毒性的某些方面，包括降解产物对目标部位下游或周围不同器官和组织的影响。 1.5 由于动物模型与人类生物学不同，这种做法无法解释所有潜在的生物危害，例如寡糖a-Gal（Gala 1,3-Galb1-4GlcNAc-R）的影响，即异种材料中存在的“a-Gal”表位对人类的影响。参见ISO 22442。 1.6 本标准并非旨在解决与其使用相关的所有安全问题（如有）。 本标准的使用者有责任在使用前制定适当的安全、健康和环境实践，并确定监管限制的适用性。 1.7 本国际标准是根据世界贸易组织技术性贸易壁垒委员会发布的《关于制定国际标准、指南和建议的原则的决定》中确立的国际公认的标准化原则制定的。 ====意义和用途====== 5.1 本规程是对候选材料进行筛选测试或评估局部组织对预计在三年内完全吸收的可吸收医疗器械的反应的指南。 5.2 本规程类似于对不可吸收的候选材料或医疗器械的研究，如《规程》中规定的 功能763 , 功能981 和 第1408页 ; 然而，对宿主反应的分析必须考虑降解和降解产物对局部组织部位炎症反应和随后植入部位愈合的影响，以及远端组织不良影响的可能性。 5.3 对于可吸收医疗器械的测试，用于植入的供试品应为预期用途的最终成品，包括包装和灭菌（如适用）。可能需要特定于动物研究的配置。 动物模型中供试品的表面积与身体质量或质量与身体质量的比值应根据器械预期临床使用期间人体的表面积和身体质量或质体质量的比值进行计算来确定。在研究设计中应考虑最坏情况下的临床剂量。对于包括局部组织反应和全身毒性评估的植入研究，应考虑与临床使用（例如，最大装置尺寸、最大装置数量）相比夸大的材料表面积或质量与身体质量比（例如，评估监管提交的植入物安全性的2倍至10倍安全系数），除非另有正当理由。 例如，在所选择的动物模型中，夸大剂量的植入可能是不可行的。对于某些设备，如果需要剂量反应信息，则应考虑针对夸大条件的额外动物组。此外，对于一些设备，特定植入部位的夸大剂量也可用于评估局部组织反应。 5.4 设计用于具有 就地 聚合反应的引入方式应确保 就地 发生聚合。在某些情况下，可能需要对单个前体成分或部分聚合材料进行额外测试（例如，如果最终植入物的测试表明存在不良反应或不完全聚合）。

1.1 This practice provides experimental protocols for biological assays of tissue reactions to absorbable biomaterials for implant applications. This practice applies only to absorbable materials with projected clinical applications in which the materials will reside in bone or soft tissue longer than 30 days and less than three years. Other standards with designated implantation times are available to address shorter time periods. Careful consideration should be given to the appropriateness of this practice for slowly degrading materials that will remain for longer than three years. It is anticipated that the tissue response to degrading biomaterials will be different from the response to nonabsorbable materials. In many cases, a chronic inflammatory response may be observed during the degradation phase, but the local histology should return to normal after absorption; therefore, the minimal tissue response usually equated with biocompatibility may require long implantations. 1.2 The time period for implant absorption can depend on variables of chemical composition, implant size, implant location, and animal models. Therefore, the selected time points for assessing tissue effects may be selected based on the rate of absorption. 1.3 These protocols assess the effects of the material on the animal tissue in which it is implanted. They do not fully assess systemic toxicity, carcinogenicity, reproductive and development toxicity, or mutagenicity of the material. Other standards are available to address these issues. 1.4 To maximize use of the animals in the study protocol, some aspects of systemic toxicity, including effects of degradation products on different organs and tissues downstream of or surrounding the target site, can be addressed with this practice. 1.5 Because animal models are not identical to human biology, this practice cannot account for all potential biological hazards, for example the effect of the oligosaccharide a-Gal (Gala 1,3-Galb1-4GlcNAc-R), known as the “a-Gal” epitope present in xenogeneic materials on humans. See ISO 22442. 1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.7 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. ====== Significance And Use ====== 5.1 This practice is a guideline for a screening test of candidate materials or assessment of local tissue response to absorbable medical devices which are expected to undergo complete absorption within three years. 5.2 This practice is similar to those for studies on candidate materials or medical devices that are not absorbable, such as those specified in Practices F763 , F981 , and F1408 ; however, analysis of the host response must take into account the effect of degradation and degradation products on the inflammatory response at the local tissue site and on subsequent healing of the implantation site, as well as the potential for adverse distal tissue effects. 5.3 For testing of absorbable medical devices, the test article for implantation should be in the final finished form as for intended use, including packaging and sterilization (if applicable). Configurations specific to the animal study may be needed. The test article’s surface-area-to-body mass or mass-to-body mass ratios within the animal model should be established by calculating based on surface-area-to-body mass or mass-to-body mass ratios in humans during the device’s intended clinical use. Worst-case clinical dose should be considered in the study design. For implantation studies incorporating evaluation of both local tissue responses and systemic toxicity, exaggerated material surface area or mass-to-body mass ratios (for example, a 2X to 10X safety factor to assess implant safety for regulatory submissions) compared to clinical use (for example, largest device size, maximum number of devices) should be considered, unless otherwise justified. For example, implantation of exaggerated doses may not be feasible in the selected animal model. For some devices, additional animal group(s) for exaggerated conditions should be considered if dose response information is needed. Additionally, for some devices, exaggerated dose at a specific implantation site can also be used to evaluate local tissue responses. 5.4 Materials that are designed for use in devices with in situ polymerization shall be introduced in a manner such that in situ polymerization occurs. Additional testing of individual precursor components or partially polymerized materials may be needed in some cases (for example, if testing of the final implant indicates an adverse response or incomplete polymerization).