Chemical characterization of medical devices
Biological evaluation of medical devices
With ISO 10993-1:2018 (Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process) and ISO 10993-18:2020 (Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process), the importance of material characterization by chemical analysis in the course of biological evaluation of medical devices has greatly increased.
Also, with regard to the 3Rs principle with the aim of completely avoiding animal testing (Replacement), limiting the number of animals (Reduction) and their suffering (Refinement) in tests to the indispensable level, the material characterization of medical devices by means of chemical analyses has become essential.
GBA Medical Device Services from GBA Group Pharma & Medical Devices has been working successfully with numerous medical device manufacturers for many years to improve patient safety through precisely tailored chemical analyses and has been implementing the significantly expanded requirements directly since the publication of ISO 10993-18:2020-01 (DIN EN ISO 10993-18:2021-03) and the updated ISO 10993-18:2020-01 + Amd 1:2022-05 (DIN EN ISO 10993-18:2023-11).
Here is a case study:
For a client, GBA Medical Device Services performed ISO 10993-18:2020 chemical analysis on a titanium alloy surgical implant. In this case, extractions were performed in a polar, semi-polar and non-polar solvent to cover a wide range of extractable organic substances. The extractions were performed at 37 °C (human body temperature) and considered both application-simulating and exaggerated extraction conditions, each with confirmation of exhaustive extraction.
The extracts were analyzed by means of gas chromatography coupled with a mass spectrometer and a flame ionization detector, among others. The focus was on the detection of volatile and semi-volatile organic compounds (VOC and SVOC). GC-MS/-FID analysis showed the following result: caprolactam (CAS 105-60-2), the monomer of polyamide 6, was detected according to its solubility properties in the polar and semipolar extract.
Based on our more than 25 years of material and testing expertise, we were able to assign the substance to the polyamide product packaging used as well as, in an intensive process analysis carried out together with the customer, to certain conditions in the packaging process that favored the release of caprolactam. This contamination was therefore clearly avoidable.
Our customer was subsequently able to eliminate the contamination by adjusting the packaging process to ensure patient safety. Further chemical analysis without positive findings subsequently met all requirements of ISO 10993-18:2020 for a chemically inert and clean medical device, thus avoiding additional animal testing to detect various biological endpoints in accordance with ISO 10993-1:2018. This example shows how important chemical analysis has become in medical technology.
In this context, however, it should also be noted that the type and sensitivity of chemical analyses play a crucial role. For the medical device from our case study, for example, a TOC (Total Organic Carbon) analysis would firstly not have allowed the contamination to be detected at all due to the basic sensitivity of the analytical method, and secondly would not have allowed the contamination to be identified.