The ISO 10993 working groups, which covers biocompatibility, recently met in Pavia, Italy where three new updates were released.
Sensitization and Irritation
European Center for the Validation of Alternative Methods (ECVAM) conducted a validation for in vitro irritation test for cosmetics and chemicals to replace the rabbit irritation test. Nelson Laboratories is participating in a round-robin study to see if the validation will apply to medical devices in a three-phase process.
Phase 1 – Six unknown chemicals (the same used in the ECVAM validation) – three positive and three negative – will be given to the round-robin participants to see if they can get the required validation. This is used to qualify the labs participating.
Phase 2 – After participating labs pass phase 1, they will get the same six chemicals, but instead of applying directly to the test, they will be placing them into polar and non-polar liquids to see if the chemicals can be detected. The test is to see if they can get results from an extraction since medical devices cannot be placed directly onto the cells.
Phase 3 – The final step will be to validate and determine a positive control – a material known to cause irritation.
A similar process will take place after ECVAM completes a similar validation for sensitization.
The working groups determined they need to find ways to become more efficient with animal testing specifically when looking at polar and non-polar extracts with toxicity studies. Currently the standard states we need to do a polar and non-polar extract. We are looking at instead of doing two extracts and dosing the same animal with the two extracts. This would eliminate the need of separate animals for the polar and non-polar extracts.
Threshold of Toxicological Concern (TTC)
We’re trying to write a document that uses the same concepts in TTC with medical devices in which you look at the chemicals coming off of your device and analyze them using safety information.
The ICH, a drug standard, has come out with a draft guidance called M7, which processes the cause of worry regarding toxicity or the unknowns. With TTC, any impurities that are below a 1.5 microgram per day level is considered safe. This concept is useful for compounds that you cannot derive a tolerable intake, and then the TTC can be used to help determine safety.
The ISP 10993 working groups will be focusing on these three key areas over the next year before the next meeting in Japan.