Genotoxicity tests for medical devices: what’s new in ISO 10993-3: 2014?
By Dr. Hana Hofman-Hüther, BSL BIOSERVICE GmbH (a Eurofins partner laboratory) and Paolo Pescio, Eurofins Medical Device Testing
The International Organisation for Standardisation published in October 2014 the new ISO 10993-3:2014, the most relevant standard to evaluate the potential genotoxicity, carcinogenicity, or reproductive toxicity for medical devices.
Genotoxicity tests are designed to detect substances that induce genetic damages by various mechanisms: gene mutations (point mutations) and chromosomal damage (i.e., translocations, small or large deletions and insertions, and numerical chromosomal aberrations).
A test battery is proposed because no single test method is capable of detecting all types of genotoxic effects, therefore the first in vitro step includes:
a) a test for gene mutations in bacteria (Ames test, OECD 471) and either
b) an in vitro test chromosome aberration test for chromosomal damage (OECD 473), or
c) an in vitro mouse lymphoma tk assay (OECD 476), or
d) an in vitro mammalian cell micronucleus test for chromosomal damage and aneugenicity (OECD 478).
Moreover, in the current version of the standard, the global test strategy is changed by inclusion of an in vivo test and a follow-up evaluation. Another relevant change is the new informative annex about guidance on selecting sample preparation procedure: inappropriate sample preparation could lead to an underestimation of genotoxicity risk, and therefore the selection of the appropriate sample preparation is crucial. Three methods are now described: beside dissolution or suspension of the test item in an adequate solvent and simulated-use extraction, a new challenging method -"Method B" encompassing extraction in two or more solvents is investigated to determine the solvent with the highest extraction residue in percent- is proposed. The selection of appropriate method depends on the chemical and physicochemical composition of the test devices.
A new Supplement to ISO 10993-3:- Guidance on tests to evaluate genotoxicity [Technical Report] will describe the test requirements for medical devices and should be available in 2015.
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