AAMI ISO 10993-3:2003 pdf download – Biological evaluation of medical devices
4.1 General
Before a decision to perform a genotoxicity test is made, ISO 10993-1 and the chemical characterization of materials (ISO 10993-18) shall be taken into account. The rationale for a test program, taking into consideration all relevant factors, shall be documented. ISO 10993-1 indicates circumstances where the potential for genotoxicity is a relevant hazard for consideration in an overall biological safety evaluation (see ISO 10993-1:1997, Table 1). Testing for genotoxicity, however, is not necessary for medical devices, and components thereof, made only from materials known to show no genotoxicity. Testing for genotoxicity is indicated where a review of the composition of the materials reveals the possible presence in the final medical device of compounds that might interact with genetic material, or when the chemical composition of the medical device is unknown. In such circumstances, the genotoxic potential of suspect chemical components should be assessed, bearing in mind the potential for synergy, in preference to carrying out genotoxicity tests on the material or medical device as a whole. When the genotoxicity of a medical device has to be experimentally assessed, a series of in vitro tests shall be used. This series shall include either two tests if 4.2.1.2 is performed, which uses the mouse lymphoma assay incorporating colony number and size determination, or three tests if 4.2.1.1 is performed. When tests are performed, at least two tests, investigating different endpoints, shall use mammalian cells.
4.2.2 If the results of all in vitro tests performed in accordance with 4.2.1 are negative, further genotoxicity testing in animals is not normally justified and should not be performed, in the interest of preventing undue use of animals. In vivo testing shall be performed in accordance with ISO 10993-2.
4.2.3 If any of the in vitro tests is positive, either in vivo mutagenicity tests shall be performed (see 4.2.4) or the presumption shall be made that the compound is mutagenic.
4.2.4 Any in vivo test shall be chosen on the basis of the most appropriate endpoint identified by the in vitro tests. An attempt shall be made to demonstrate that the test substance has reached the target organ. If this cannot be demonstrated, a second in vivo test in another target organ may be required to verify the lack of in vivo genotoxicity.
4.3.1 Where genotoxicity tests are carried out on the material or a medical device or as a whole, sample preparation shall be in accordance with ISO 10993-12. Tests shall be performed on extracts, exaggerated extracts, or the individual chemical compounds of the material/medical device. The highest test concentration shall be within OECD guidelines. If exaggerated extraction conditions are used, care shall be taken that this does not alter the chemical characteristics.
4.3.2 An appropriate solvent shall be chosen on the basis of its compatibility with the test system and its ability to maximize extraction of the material or medical device. The rationale for the choice of solvent shall be documented.
4.3.3 Where relevant, two appropriate extractants shall be used, one of which is a polar solvent, the second a non-polar solvent or liquid appropriate to the nature and use of the medical device, both of which are compatible with the test system.