ISO 10993-3:2014 pdf download – Biological evaluation of medicaldevices — Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
ISO 10993-3:2014 pdf download – Biological evaluation of medicaldevices — Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity.
When considering whether a carcinogenicity study should be performed, the role of the study In the evaluation of human risk shall be described, and the need for the study and the study design shall be justified. This justification shall take into account the uncertain role implantation carclnogeniclty studies play in the evaluation of biological safety along with the significant number of animals.
If according to ISO 10993.1. chronic toxicity and carcinogenicity is considered relevant, and It is determined that testing is necessary, testing shall be performed in accordance with OECD 453. llpossible.
If according to ISO 10993.1, only a carcinogenicity study is considered relevant, and it is determined that testing is necessary testing shall be performed in accordance with OECD 451,
One animal species is typically sufficient for testing medical devices. The choice of species shall be in accordance with ISO 10993-2 and shall be justified and rationale documented,
6.3 Sample preparation
When carcinogenicity tests are necessary as part of an evaluation of biological safety these studies shall be performed with either materials, defined chemicals or characterized extracts of medical devices.
The medical device shall be tested in a form representative of the finished device state Additional testing may be warranted for additional states of the device such as. wear debris generated from the device or materials that cure in situ (e.g. cements, adhesives and pre-polymer mixtures). For guidance on in situ curing devices, see 10993-12.
The selection of the test sample (device material, device material extracts or defined chemical) shall be justified and documented.
The highest dose used in the animals is eitherthe maximum tolerated dose orthatlimited hythe physical constraints of the animals model. This dose shall be expressed as a multiple of the estimated maximum human exposure (in weight and/or surface area per kilogram).
6.4 Test methods
If testing of an extract is considered relevant, the carcinogenicity tests shall be performed in accordance with OECD 451 or OECD 453.
TIssues evaluated shall Include relevant tissues from the list Indicated In OECD 451 or OECD 453, as well as the implantation site and adjacent tissues.
For studies using device material extracts or defined chemicals, an explanation shall address why the material’s surface properties are not a carcinogenic consideration. The considerations for the performance of implantation studies (see Annexk) shall be taken into account and the role of surface properties In the evaluation of human risk shall be described and documented,
For implantation studies to evaluate carcinogenicity, the amount of material implanted shall be representative of an exaggerated human dose which provides a sufficient margin-of-safety. The highest dose will be limited by the physical constraints of the animal model. This dose shall be expressed as a multiple of the estimated maximum human exposure (in weight and/or surface area per kilogram).
A 100 times safety factor is applied to the estimated maximum human exposure (in weight and/or surface area per kilogram). however, the dose should be physiologically compatible with the model. The negative control group will generally receive a comparable shape and form of a clinically acceptable material or reference control material whose lack of carcinogenic potential has been documented (e.g. polyethylene).
When appropriate, a suitably formed implant in accordance with ISO 10993-6 shall be made of the test materials, with appropriate consideration being given to the possibility of inducing solid state carcinogenicity.
The polymer can be tested in disc form. A disc not exceeding approx. Fifteen mm in diameter and 2 mmto 3 mm in thickness is recommended.However, for materials with high density, these dimensions mayneed to be reduced to avoid tissue damage related to weight of the sample. Multiple samples may beimplanted to obtain the desired dose. Thus, in the above example, two disc-shaped implants containing0.2g of polymer per implant would be implanted in each mouse.