Biomedical Engineering Reference
In-Depth Information
Table 9.16
Genotoxicity testing procedures required by ISO 10993-3
ISO 10993-10
Extraction vehicles:
A physiological
medium is used and, where appropriate, a solvent
(e.g. dimethylsulfoxide).
Extraction:
Extract test
material and test the extract or dissolve material in solvent
and conduct test. The conditions of extraction should maximize the
amount of extractable substances, as well as subject the test device or
material to the extreme conditions it may be exposed to, without causing
signifi cant degradation. Extraction ratio is dependent on thickness of test
material.
total life of the test animal (e.g. over 90 days in rats). For an implanted
device, the expectation is that the study will extend to 9-12 months or the
duration of patient implantation (whichever is shorter). It is common to
incorporate interim termination groups at 30 and 90 days into a chronic
implantation study to accommodate the subchronic determinations.
Carcinogenesis bioassay
: The determination of the tumorigenic potential
of test materials and/or extracts from either single or multiple exposures,
over a period of the total life (e.g. 2 years for rat, 18 months for mouse, or
7 years for dog). Evaluation of the response to subcutaneous implantation
in rodents requires consideration of the Oppenheimer effect, specifi c to this
species.
Pharmacokinetics
: These procedures determine the metabolic processes
of absorption, distribution, biotransformation, and elimination of toxic
leachables and degradation products of test materials and/or extracts.
Reproductive and developmental toxicity
: The evaluation of the potential
effects of test materials and/or extracts on fertility, reproductive function,
and prenatal and early postnatal development.
Degradation products, extractables and leachables
: A whole new era has
arisen for the device and biomaterials industries, now that these endpoints
are expected to be assessed for implanted devices and products prior to
any actual clinical implantation (and therefore, actual clinical evaluation).
The tests for leachables such as contaminants, additives, monomers and
degradation products must be conducted by choosing appropriate solvent
'extraction' systems that will yield a maximal concentration of leachable
materials to conduct biocompatibility testing. The effects of sterilization on
device materials and potential leachables, as well as toxic by-products, as a
consequence of sterilization should be considered. Therefore, testing must
be performed on the fi nal sterilized product or representative samples of
the fi nal sterilized product.
