Inter-laboratory study for extraction testing of medical devices.

Area of Science:

• Medical device manufacturing
• Analytical chemistry
• Materials science

Background:

• Biocompatibility evaluation of medical devices is crucial.
• Chemical testing per ISO 10993-18 is a key component.
• Precision of non-targeted chemical characterization is not well-established.

Purpose of the Study:

• To characterize intra-laboratory (repeatability) and inter-laboratory (reproducibility) variability in chemical testing of medical device extractables.
• To assess the precision of chemical characterization methods used in biocompatibility assessments.

Main Methods:

• Two polymers with nine intentionally compounded chemicals were used.
• Eight laboratories performed extraction testing in two solvents.
• Gas chromatography and liquid chromatography methods were employed for extract characterization.

Main Results:

• The central 90% range for repeatability and reproducibility relative standard deviations were (0.09, 0.22) and (0.30, 0.85), respectively.
• Results indicate potential differences up to 240% between laboratories with 95% confidence.
• Analytical method variability is a substantial contributor to overall variability.

Conclusions:

• High variability in chemical testing of medical device extractables was observed.
• Large reproducibility limits have significant implications for biocompatibility risk evaluation.
• Variability impacts exposure dose estimation and chemical equivalence assessments.