Every Lab, a Different Answer

Medical devices that contact the body must undergo biocompatibility assessment to ensure they do not cause toxic, immunogenic, or carcinogenic harm. A critical component of this assessment is chemical characterization — identifying and quantifying substances that may leach from the device into the body. Despite the centrality of this testing, the FDA has identified that no existing guidance or consensus standard provides a detailed methodology for how to conduct extractables studies and chemical analysis of device extracts. This gap has caused widespread inconsistency across testing laboratories, leading to deficiencies in premarket submissions, delayed device authorizations, and uncertain safety assessments. The problem is especially acute for novel materials — advanced polymers, nanocomposites, bioresorbable materials — and for combination products.

Every medical device that contacts the body — implants, catheters, surgical instruments, wound dressings, diagnostic devices that draw blood — requires biocompatibility assessment, encompassing hundreds of thousands of device types. Inadequate chemical characterization exposes patients to potentially harmful leachables (residual monomers, plasticizers, degradation products) and delays device authorizations through submission deficiencies. The annual cost of biocompatibility testing deficiency-related submission delays across the device industry likely exceeds hundreds of millions of dollars.

ISO 10993-18 provides a framework for chemical characterization of medical device materials, but it is a framework standard, not a methods standard — different laboratories interpret it differently and produce incomparable results. The FDA issued its first detailed methodology guidance in September 2024, specifically to address what the agency called the "potential cause of variability in how different labs perform analytical chemistry." However, this guidance remains draft (non-binding) and covers only extractable/leachable studies, not the full spectrum of biocompatibility endpoints. Manufacturers described the new guidance as "detailed and burdensome," revealing a substantial gap between current industry practice and what the FDA considers adequate. The FDA held a November 2024 workshop on accreditation schemes for conformity assessment in chemical analysis, exploring third-party testing frameworks, but no accreditation system has been established. Animal testing is still required for many biocompatibility endpoints, though the FDA is encouraging chemical characterization as a means to reduce animal testing.

Validated, standardized analytical methods for the most common device material classes — with prescriptive extraction conditions, analytical techniques, and toxicological thresholds — would eliminate the inter-laboratory variability that currently undermines the system. A tiered testing framework that matches analytical rigor to patient risk (longer contact duration or higher-risk body contact zones requiring more intensive characterization) would make compliance achievable for smaller manufacturers without sacrificing safety.

A student team could conduct a systematic comparison of how different contract testing laboratories interpret ISO 10993-18 for a single device material, documenting the variability in extraction conditions, analytical methods, and reported results. This would produce the kind of empirical evidence that standards bodies need to write prescriptive methods. Alternatively, a team could develop a reference material and standard operating procedure for a specific common device polymer (e.g., medical-grade silicone or PEEK), creating a benchmark that labs could use to calibrate their chemical characterization workflows.