PDF(Pubmed)
Abstract：
UNASSIGNED: Medical device manufacturers are obliged to prove the biocompatibility of their products when they come into contact with the human body. The requirements for the biological evaluation of medical devices are specified by the international standard series ISO 10993. Part five of this series describes the performance of in vitro cytotoxicity tests. This test evaluates the effects of medical device use on cell health. The existence of the specific standard suggests that the tests will produce reliable and comparable results. However, the ISO 10993-5 offers wide latitude in the test specifications. In the past, we noticed inconsistencies of the results from different laboratories.
UNASSIGNED: To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors.
UNASSIGNED: An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard.
UNASSIGNED: To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC.
UNASSIGNED: The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.
UNASSIGNED: To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors.
UNASSIGNED: An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard.
UNASSIGNED: To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC.
UNASSIGNED: The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.
摘要：
■医疗器械制造商在与人体接触时，有义务证明其产品的生物相容性。医疗器械生物学评价的要求由国际标准ISO10993规定。本系列的第五部分描述了体外细胞毒性测试的性能。本试验评估医疗器械使用对细胞健康的影响。特定标准的存在表明测试将产生可靠和可比的结果。然而,ISO10993-5在测试规范中提供了广泛的自由度。在过去,我们注意到不同实验室的结果不一致。
■要确定ISO10993-5标准的规格是否明确，以确保测试结果的可比性，并且，如果不是,确定潜在的影响因素。
■根据ISO10993-5对体外细胞毒性测试进行实验室间比较。52个国际实验室评估了两个未知样品的细胞毒性。一个是聚乙烯(PE)管材，预计是非细胞毒性的，另一种是聚氯乙烯（PVC）管，推测其具有细胞毒性潜力。要求所有实验室以预定的提取规格进行洗脱测试。其他测试参数由实验室根据标准设定的指南自由选择。
■令我们惊讶的是，只有58％的参与实验室发现了两种材料的细胞毒性潜力。特别是对于PVC，观察到实验室之间的结果存在相当大的差异[平均值=43±30（SD），min=0,max=100]。我们发现提取培养基中补充了百分之十的血清，以及细胞与提取物的孵育时间更长，大大提高了PVC的测试灵敏度。
■结果清楚地表明，ISO10993-5设定的规格不够明确，无法获得相同医疗设备的可比结果。为了设定确保可靠的细胞毒性评估的要求，需要进一步研究以确定特定材料和/或设备的最佳测试条件，并且需要对标准进行相应修订。
■要确定ISO10993-5标准的规格是否明确，以确保测试结果的可比性，并且，如果不是,确定潜在的影响因素。
■根据ISO10993-5对体外细胞毒性测试进行实验室间比较。52个国际实验室评估了两个未知样品的细胞毒性。一个是聚乙烯(PE)管材，预计是非细胞毒性的，另一种是聚氯乙烯（PVC）管，推测其具有细胞毒性潜力。要求所有实验室以预定的提取规格进行洗脱测试。其他测试参数由实验室根据标准设定的指南自由选择。
■令我们惊讶的是，只有58％的参与实验室发现了两种材料的细胞毒性潜力。特别是对于PVC，观察到实验室之间的结果存在相当大的差异[平均值=43±30（SD），min=0,max=100]。我们发现提取培养基中补充了百分之十的血清，以及细胞与提取物的孵育时间更长，大大提高了PVC的测试灵敏度。
■结果清楚地表明，ISO10993-5设定的规格不够明确，无法获得相同医疗设备的可比结果。为了设定确保可靠的细胞毒性评估的要求，需要进一步研究以确定特定材料和/或设备的最佳测试条件，并且需要对标准进行相应修订。
