US vs. ISO 10993: A Resilient Biocompatibility Strategy for 2026

In light of potential shifts in US biocompatibility requirements that may not fully align with global standards like the ISO 10993 series by 2026, how should a medical device sponsor develop a resilient and defensible evaluation strategy for FDA submissions? Beyond simply selecting tests from a matrix, what is the best practice for structuring a comprehensive Biological Risk Assessment that prospectively addresses this uncertainty, especially for devices with long-term tissue contact or novel materials? For legacy devices or those using well-characterized materials, what specific evidence and justification should be compiled in the Biological Evaluation Report (BER) to argue that existing data is sufficient and new testing is not clinically relevant? When new data is required, how should sponsors balance standard cytotoxicity, sensitization, and irritation tests with more complex endpoints like systemic toxicity or genotoxicity, and how can chemical characterization data (E/L) be leveraged more aggressively to support the toxicological risk assessment and potentially reduce in vivo studies? Furthermore, how should documentation be prepared to clearly articulate the rationale for the testing strategy chosen, and at what specific development milestones—such as post-design freeze but pre-V&V—is a Q-Submission to the FDA most effective for gaining alignment on a biocompatibility plan for an innovative device intended for the US market? --- *This Q&A was AI-assisted and reviewed for accuracy by Lo H. Khamis.*