Medical devices undergo degradation processes once they are present for long periods of time in the human body. This holds especially true for those patients, where medical devices are chronically exposed to blood, serum or interstitial liquids that provoke polymers to be degraded. As an example, saponification of ester groups in polymers may occur. Spallation particles may be released as observed in the case of silicon tubing. During the selection process of polymers for new medical devices engineers should focus on the presence of possible degradation products: Of paramount importance is the use of appropriate extraction media and test systems for their identification already in the early phase of development.
The toxicological evaluation of extractable substances/compounds from medical devices is usually done in compliance with ISO 10993-17 “Biological evaluation of medical devices -- Part 17: Establishment of allowable limits for leachable substances”: this international standard provides tools to calculate the tolerable intake and the tolerable exposure for each compounds. Along with this approach, the TTC (Threshold of Toxicological Concern) concept is also used to establish limits and cut-off values for leached compounds. Moreover some predictive in silico models are used to establish limits in case of few/limited toxicological data.
This picture is further complicated because, the AET (Analytical Evaluation Threshold) concept, defined as the threshold at or above which a chemist should begin to identify a particular leachable and/or extractable and report it for potential toxicological assessment, and is very common in pharmaceutical application is sometimes inapplicable for certain medical devices where the “daily dose” is inapplicable (i.e., implanted medical devices).
In the medical devices session at E&L Europe, Paolo Pescio, Chairman of the UNI U4201 Committee for non-active medical devices for transfusion and biological evaluation and Head of Medical Device Testing at Eurofins Biopharma Product Testing will give clarity on the toxicological evaluation of substance leaching out from medical devices presenting an integrated approach.
Professor Joerg Vienken, who worked for 11 years at AKZO NOBEL Membrana as Director for Clinical Research and Science Services followed by a position as Vice President BioSciences in Fresenius Medical Care, will also be providing examples of leachables from medical devices and related clinical adverse reactions that he has come across during his years of work in this session.