Toxicity testing of polymer materials for dialysis equipment: is there any need for in vivo testing?
In an earlier work, slightly more than 650 plastic materials, intended for use in medical devices, were tested with a battery of chemical, as well as in vitro and in vivo biological tests. An analysis showed that only a limited number of the tests used were actually necessary to obtain the same pass or fail decision as that obtained using the full test battery. This prompted us to prescreen all new materials with a small test battery consisting of the two most discriminating chemical tests and an in vitro cell growth inhibition test. The present work is a report of our findings after testing another 155 materials using this prescreen system. For each single one of the 155 tested materials the same decision on whether or not to use the material in the intended medical device would have been reached without any in vivo testing. In no single case in a total of 851 in vivo tests did an eluate that had passed the in vitro cell test give rise to a reaction in vivo. Thus, among the tests on living systems, the cell test alone seems to be sensitive enough to provide sufficient information. Nothing appears to be gained from the in vivo animal tests. However, some of the materials that passed the prescreening tests later failed in one or several of the chemical tests. Both nonspecific chemical tests and tests for specific molecules seem to detect undesirable levels of leachable substances not detected by the prescreening system. Therefore these tests should not be abandoned. Abandoning unnecessary in vivo testing, on the other hand, would save considerable costs.
Gambro AB, Department of Regulatory Affairs and Preclinical Research, Lund, Sweden.
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Kjellstrand
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Lilliehorn
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Rydhög
D000818:Animals; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D011108:Polymers / Q000633:toxicity*; D011817:Rabbits; D006435:Renal Dialysis / Q000295:instrumentation*
D011108:Polymers