Toxic or not toxic? Interlaboratory comparison reveals almost fifty-fifty chance in the cytotoxicity assessment (ISO 10993-5) of an identical medical device

Abstract

AbstractBackgroundMedical 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 ofin vitrocytotoxicity 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.ObjectiveTo determine if the specifications of the standard ISO 10993-5 are sufficient for assessing the comparability of test results and, if not, identify potential influencing factors.MethodsAn interlaboratory comparison was conducted for thein vitrocytotoxicity 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.ResultsTo 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.ConclusionThe results clearly show that the specifications set by the ISO 10993-5 are not sufficient 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.