Updates from ISO 10993 Working Groups’ Italy Session
The ISO 10993 working groups, which covers biocompatibility, recently met in Pavia, Italy where three new updates were released.
Sensitization and Irritation
The European Center for the Validation of Alternative Methods (ECVAM) performed 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 given to the round robin participants to see if they can get the required validation. They will see if it is reproducible.
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 into the liquid.
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.
Localized toxicity is not as concerning to a toxicologist as something that is systemic. The new test will look at chemicals that are systemic. Additionally, the working groups determined they need to find ways to become more efficient 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 separate tests with two sets of animals, finding ways of combining the two polar extracts into the same animal model to eliminate the unnecessary use of animals.
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The ICH, a drug standard, has come out with a draft guidance called M7, which processes the cause of worry regarding toxicity or the unknowns.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, you calculate the impurities that are there and if it is below 1.5 micrograms you do not have to worry about toxicity. If it is above the threshold, you do need to worry. The whole idea is to determine the TI or tolerable intake. A good resource for more information is the ICH M7.
The ISP 10993 working groups will be focusing on these three key areas over the next year before the next meeting in Japan.