Increasingly, the biocompatibility of medical devices is being evaluated using toxicological risk assessment (TRA) based on chemical characterization, rather than biological testing. This is evident in the publication of ISO 10993-18 Chemical characterization of medical device materials within a risk management process in 2020, and the anticipated publication of ISO 10993-17 “Toxicological risk assessment of medical device constituents” (due in 2023).
If you have been observing industry trends and wondering what extractables and leachables (E&L) are all about, they are chemical characterization (CC) and their sole purpose is to facilitate TRA.
The FDA has now made publicly available two CHemical RISk Calculator (CHRIS) tools to help with this process for Bulk Chemicals, as well as a short list (11 individual and three generic) of Color Additives in polymeric materials/devices. These are the product of the FDA’s Medical Device Development Tools (MDDT) program.
It appears that the FDA has only “qualified” the Color Additives tool. But this is BIG news, as it is qualified for regulatory use by the FDA. It can be reliably used as evidence in support of medical device submissions.
Importantly, these tools do not require “E&L testing,” (information generation). They can also be powered by knowledge of material formulation (information gathering).
These tools are helpful for systemic biocompatibility endpoints (including acute systemic toxicity, subacute/subchronic/chronic toxicity, genotoxicity, carcinogenicity, and reproductive and developmental toxicity). The FDA points out that the tools do not “aid in the biocompatibility evaluation of cytotoxicity, sensitization, irritation, hemocompatibility, material mediated pyrogenicity, or implantation.”
Notwithstanding the FDA’s position on local effects, there are moves afoot to include both irritation and sensitization in the TRA methodology for medical devices, where there is adequate toxicity data. There is also some tension in the industry regarding material mediated pyrogenicity, which is not universally accepted as a credible medical device phenomenon.
Establishing the biocompatibility for a medical device is a complex process, with many aspects to consider, and regulatory “hoops to jump through.” The new FDA CHemical RISk Calculator (CHRIS) for Color Additives will certainly help in the process.
And PharmaLex can certainly help you with your entire biocompatibility program.
Author: James Morrison, Associate Director, Medical Devices / IVD, Biocompatibility
