Toxic or not toxic? The specifications of the standard ISO 10993-5 are not explicit enough to yield comparable results in the cytotoxicity assessment of an identical medical device

Abstract

BackgroundMedical 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.ObjectiveTo 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.MethodsAn 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.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 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.

Hybrid DIVEMA/PLGA nanoparticles as the potential drug delivery system

“…The cytotoxicity was assessed in vitro in the porcine kidney epithelial cells LLC-PK1 and Hep G2 human hepatocellular carcinoma cells by the МТТ-test. The reduction of viability of both cell types after incubation with the DIVEMA/PLGA NP or plain PLGA NP in the concentration of up to 100 µg/mL did not exceed 20%, which is generally accepted as the non-toxic effect [29].…”

Digital manufacturing techniques and the in vitro biocompatibility of acrylic-based occlusal device materials

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“…Wound dressings designed for human application necessitate a noncytotoxic nature. Our selection of primary cell lines was guided by their heightened sensitivity to potential cytotoxic agents [ 65 ] than immortalized cell lines and the fact that the utility of using the standard cell line (mouse fibroblast L929) employed for cytotoxic evaluations in the registration of a medical device for cytotoxic evaluation is currently questioned [ 66 ]. Furthermore, mesenchymal stem cells, encompassing the UCSC cells employed in this investigation, exhibit a migratory propensity towards sites of tissue and organ injury, thereby orchestrating and overseeing the regenerative processes therein [ 67 ].…”