Medical Device Testing

Armstrong, Barbara L., et al. Journal of pharmaceutical and biomedical analysis 74 (2013): 162-170.

The identification and determination of leachable components in implantable medical devices are critical for ensuring patient safety. Regulatory agencies set safety concern thresholds (SCT) for genotoxic or carcinogenic compounds at 0.15 μg/day and for other substances at 1.5 μg/day. This study developed a Stir Bar Sorptive Extraction (SBSE) method coupled with GC–MS/MS to analyze volatile and semi-volatile leachables in orthopedic knee inserts made from ultra-high molecular weight polyethylene. The method was validated to detect antioxidant-related degradation products at levels as low as 150 ng/device, well below the SCT limit.

The SBSE–GC–MS/MS method demonstrated high sensitivity and specificity, with a linear range of 40–6000 pg/mL and excellent precision. It was successfully applied to eleven tibial knee inserts in leachables studies conducted over 24 hours and 30 days. Notably, this method utilizes the entire device for testing, avoiding the need for slicing or grinding, and minimizes the use of solvents, creating a safer testing environment. Although requiring advanced instrumentation, the method is highly recommended for regulatory filings due to its ability to test for low-level impurities and ensure the safety of finished medical products without damaging the integrity of the device.

Wang, Yujie, et al. Journal of pharmaceutical and biomedical analysis 55.5 (2011): 1213-1217.

The determination of residual sterilants and solvents, such as ethylene oxide (EO) and cyclohexanone (CHX), in disposable medical devices (DMDs) is essential for ensuring product safety and compliance with regulatory standards. This study introduces a rapid, sensitive, and non-invasive method using Thermal Desorption Extraction Proton Transfer Reaction Mass Spectrometry (TDE-PTR-MS) for quantifying residual EO and CHX in polyvinyl chloride (PVC) infusion sets. Two novel approaches are proposed: first, EO residues are determined by correlating the concentration of EO gas in the packaging with the residual EO in the infusion sets, while the second method involves integrating the mass emission rates of EO and CHX over time to calculate their levels within the devices.

The methods were validated by comparison with the exhaustive extraction technique, demonstrating high sensitivity, reproducibility, and minimal sample preparation. TDE-PTR-MS provides fast response times and precise absolute concentration measurements, making it a powerful tool for quality inspection. These innovative techniques offer a significant advantage for the detection of residual solvents and sterilants, ensuring that medical devices meet safety standards without the need for time-consuming and potentially hazardous extraction procedures. This advancement highlights the potential of TDE-PTR-MS for enhancing quality control in the medical device industry.

Lecoeur, Marie, et al. Journal of Chromatography A 1417 (2015): 104-115.

The determination of plasticizers in medical device components such as PVC tubing is crucial for ensuring product safety and regulatory compliance. This study investigates the quantitative performance of Supercritical Fluid Chromatography coupled with Evaporative Light Scattering Detection (SFC-ELSD) and compares it with High-Performance Liquid Chromatography with Evaporative Light Scattering Detection (HPLC-ELSD) for the analysis of common plasticizers, including ATBC, DEHA, DEHT, and TOTM.

Both SFC-ELSD and HPLC-ELSD enable fast analysis of plasticizers (<10 min), with HPLC providing better analytical performance in terms of accuracy, trueness, and precision. While the SFC method achieved lower quantification thresholds, HPLC demonstrated superior resolution and precision, particularly for plasticizer separation. The results indicated that the accuracy profiles for plasticizer determination in HPLC were within ±10% of the acceptance limits, whereas SFC validation failed to meet certain criteria.

Despite the lack of precision in SFC-ELSD, it remains a viable option for plasticizer quantification in PVC tubing, though both methods struggled with detecting trace levels of DEHP. The findings emphasize the need for careful selection of analytical techniques based on the specific requirements of medical device testing, with the potential for variations depending on equipment used from different manufacturers.