If chemical analytical testing and the toxicological risk assessment fails to demonstrate that leachables of a medical device are associated with an acceptable risk for genotoxicity, genotoxicity tests are required to assess the potential presence of toxins that can impact the genetic material of cells. Since no single test can detect all genotoxins, the standard for medical device genotoxicity testing (ISO 10993-3) describes an approach that considers a battery of in vitro and under certain circumstances also in vivo tests.
The standard test battery comprises a reverse mutation assay conducted in bacterial cells and a genotoxicity assay conducted in a mammalian cell system. The Bacterial Reverse Mutation Assay is typically conducted according to the OECD 471 “Guidelines for Testing of Chemicals – Bacterial Reverse Mutation Test” with strains of Salmonella typhimurium and Escherichia coli designed to detect all possible single base pair changes as well as frameshift mutations. For the in vitro Mammalian Genotoxicity Assay one of the following tests is chosen:
- Mouse Lymphoma Gene Mutation Assay (OECD 476 “Guidelines for the Testing of Chemicals – In Vitro Mammalian Cell Gene Mutation Test”), which is preferred since it detects the broadest set of genotoxic mechanisms associated with carcinogenic activity.
- In Vitro Chromosomal Aberration (CA) Assay (OECD 473 “Guidelines for the Testing of Chemicals – In Vitro Mammalian Chromosome Aberration Test”), assesses DNA damage through structural changes of chromosomes that are called as aberration.
- In Vitro Micronucleus Assay (OECD 487 “Guidelines for the Testing of Chemicals – In Vitro Mammalian Cell Micronucleus Test”). Evaluates the genotoxic potential of a compound by evaluating the presence of micronuclei, which are a result of DNA damage. A micronuclei may contain chromosome fragments as a result of DNA breakage or whole chromosomes. As such, the test provides information on the clastogenic and anuegenic potential of compounds.