Chemical Characterization of Polymeric Medical Devices: Unveiling the Identity and Risks

If the preliminary chemical characterization fails to establish the equivalence of the medical device under consideration with any established medical device with the same intended use, one should check the hypothetical worst-case chemical release of the medical device in consultation with a toxicologist. Hypothetical worst-case release considers the complete release or total exposure of device components into the patient system. The health risks associated with the total exposure of the components should be assessed in line with the appropriate safety thresholds. If the worst-case release didn’t exceed the safety threshold for any of the components, the chemical characterization can be completed with the conclusion of acceptable health risks. If it fails and the chances of potential degradation products are present one should continue the chemical characterization with extractable analysis.

Extractable analysis is the method in which the chemical release from a medical device is evaluated under laboratory conditions. Here the device is extracted with suitable extraction vehicles at specific temperatures for specific time periods directed by ISO 10993-12. Different types of extractions like simulated extraction, exaggerated extraction, and exhaustive extraction are outlined in the standard which should be selected based on the type of medical device and duration of clinical use. The extraction of a medical device is mainly influenced by factors like extraction time, temperature, the polarity of the extraction vehicle, surfaceto- volume ratio, and partitioning behavior of the components. For the estimation of extractable, the medical device needs to be extracted either fully or a representative portion of the device, if it’s huge. In the case of multi-component devices, the representative portion should be selected in such a way that all the components are present in the portion with the same relative ratio. The selection of extraction vehicle should be done sensibly to avoid evaporative losses, alteration of the test article, and swelling of the test specimen. Loss of extraction vehicle due to evaporation or swelling may lead to incorrect estimations. The extract should be analyzed for the qualitative and quantitative estimation of volatiles, semi-volatiles, non-volatiles, trace elements, and ions.

During the analysis of extracts using the chromatographic methods, the analytical evaluation threshold (AET) is to be considered for screening the analytes for quantitative estimation. AET is a concentration-dependent threshold that depends on a number of factors such as the number of medical devices used for extraction (A), the volume of extraction vehicle (B), the number of devices a user would expose in a day (C), dose-based threshold (DBT) or threshold toxicological concern (TTC) of the device, and the uncertainty factor of the analytical method (UF) used. AET can be calculated using the equation,

The value of DBT varies with the mode of contact and duration of contact of medical devices and the list of DBT values is available in ISO/TS 21726. During the extractable analysis, all the analytes with concentrations greater than or equal to AET have to be identified and quantified as these analytes may have potential toxicity risk. In the case of extremely toxic substances like aflatoxins, azo compounds, organophosphorus compounds, etc. quantitative estimation is mandatory even though they are below the AET level. These substances are commonly called cohorts of concern (CoC). If the risk assessment of the medical device based on the extractable analysis suggests that the device has an acceptable health risk, the chemical characterization can be completed. However, if the analysis suggests potential risk, the chemical characterization needs to be continued for leachable analysis.

Leachable analysis is used to study the chemical release from a medical device during its actual clinical use. In this case, the extraction has to be conducted in a simulated condition mimicking actual clinical use. Water, physiological saline, ethanol-water, DMSO, etc. are the media commonly used in the leachable analysis. Leachable analysis should be done to estimate the volatiles, semi-volatiles, non-volatiles, ions, and metals leached from the medical device under simulated conditions. The potential analytes observed during extractable study should give preference while performing leachable analysis. Chemical characterization of medical devices ends with leachable analysis. If the leachable analysis data supports equivalence or acceptable health risk, the outcome can be used to support the biological evaluation of medical devices. If the data suggests there’s a potential health risk associated with the medical device, the chemical characterization outcome cannot support biological evaluation, and further biological testing and mitigation activities have to be performed.

Being one of the pioneering institutes in the country in the field of advanced healthcare and medical device technology, Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) follows a comprehensive medical device evaluation in line with international standards. In addition to the  characterization of in-house medical technologies and devices, the facilities are open for external customers to complete their device characterization to fulfil the regulatory requirements. For further details visit the website of SCTIMST ( www.sctimst.ac.in ) and contact the customer service cell (csc@sctimst.ac.in).

References

1. ISO 10993-1: 2018 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process.

2. ISO 10993-18: 2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process.

3. ISO 10993-12: 2021 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials.

4. ISO/TS 21726: 2019 Biological evaluation of medical devices. Application of the threshold of toxicological concern (TTC) for assessing biocompatibility of medical device constituents..