Whitepaper: From Guidance to Practice: Translating FDA Draft guidance into Actionable Analytical Strategies Aligned with ISO 10993-18:2020

Summary:

Chemical characterisation is a critical step in assessing the biological safety of medical devices, especially when existing data is incomplete. The FDA’s 2024 Draft Guidance, Chemical Analysis for Biocompatibility Assessment of Medical Devices, offers a more detailed and structured approach than ISO 10993-18 alone. This whitepaper from Eurofins Medical Device Services translates the FDA’s recommendations into actionable strategies, covering extraction protocols, analytical methods, and toxicological evaluation, while highlighting practical implementation across Eurofins laboratories.

Key Sections Covered:

• Extraction Conditions: Use of polar, non-polar, and semi-polar solvents; exaggerated and exhaustive extraction protocols
• Mass Comparison: Reporting total mass via NVR and semi-quantification to ensure extractables are not lost
• Triplicate Testing: Formal requirement unless justified; pooling options discussed for cost efficiency
• Pooling Strategy: Technically acceptable but not preferred; evaluated based on AET values
• Solvent Compatibility: Swelling now considered acceptable if integrity is maintained
• Solvent Selection: Preference for neat solvents over mixtures; validated alternatives available
• Elemental Analysis: Water-based extraction with acidification for ICP-MS
• Temperature Justification: Elevated extraction temperatures required unless damage occurs
• Analytical Sensitivity: LOQ must be below AET; adjustments and justifications provided
• AET Calculation: Inclusion of dilution/concentration factor (D) in AET formula
• Recovery Verification: Spike-and-recovery studies required; 80–120% recovery range
• Identification Standards: Differentiation between confirmed, confident, tentative, and unknowns for TRA

This document is an essential guide for manufacturers and regulatory professionals aiming to align with evolving FDA expectations, enhance biocompatibility assessments, and ensure the safety and compliance of medical devices through robust chemical characterisation practices.