Biocompatibility Testing for Wearable Medical Devices: What ISO 10993-1:2025 Requires
Wearable medical devices — continuous glucose monitors, cardiac monitoring patches, drug delivery wearables, diagnostic biosensors — are regulated medical devices. That means before they reach patients, they go through biological evaluation under ISO 10993-1:2025.
For manufacturers new to the biocompatibility process, the question is usually: what does that actually require? The answer depends on your specific device — its materials, its patient contact, how long it stays on the body, and what existing data already covers. Here's how to work through it.
Wearables Are Surface-Contacting Devices
Under ISO 10993-1:2025, devices are classified by their nature of contact with the body:
Surface-contacting devices — contact with intact skin, mucosal membranes, or breached or compromised surfaces
Externally communicating devices — contact with blood path, tissue/bone/dentin, or circulating blood
Implant devices — contact with tissue/bone or blood
Most wearable medical devices fall under surface-contacting, intact skin. That contact classification is the first input into your biological evaluation; it determines which biological endpoints are relevant and what data sources are applicable.
The contact duration classification is equally important:
Limited — single or multiple contacts totaling 24 hours or less
Prolonged — more than 24 hours and up to 30 days
Long-term — more than 30 days
A continuous glucose monitor worn for 10 to 14 days is a prolonged-contact surface device. A cardiac patch worn for 30 days or longer is long-term. These classifications drive the biological evaluation plan and determine which endpoints receive the most scrutiny.
Biological Evaluation Is Not a Testing Checklist
ISO 10993-1:2025 replaced the prescriptive endpoint matrix that manufacturers were using under the 2018 edition. There is no longer a table that specifies which tests to run based on device type and duration. In its place is a systematic biological risk assessment.
The process works in sequence:
Characterize the device — identify all materials in patient contact, manufacturing chemicals, processing residuals, colorants, adhesives, and any other substances that could be transferred to the patient
Identify biological hazards — determine which hazard types are relevant given the device's contact type, duration, and intended patient population
Estimate biological risks — use available data (existing literature, supplier data, prior testing, chemical characterization) to evaluate whether each hazard poses an acceptable risk
Identify data gaps — determine which risks cannot be adequately assessed with existing information
Plan testing only if needed — biological testing is conducted to fill gaps, not as a default
For a wearable device with well-characterized materials, established suppliers, and existing toxicological data, a gap analysis may determine that little or no new testing is required. For a device using novel adhesives, new polymer formulations, or materials without prior clinical use, the gap analysis is likely to identify endpoints that require data generation.
Biological Endpoints Relevant to Wearables
While ISO 10993-1:2025 no longer specifies mandatory test lists, certain endpoints are consistently relevant for prolonged or long-term skin-contact devices.
Cytotoxicity — a baseline endpoint for virtually all medical devices. It evaluates whether device materials or their extracts cause cell death under in vitro conditions. For wearables with adhesive layers or polymer housings, cytotoxicity is typically among the first data points evaluated.
Sensitization — relevant for any device with prolonged or long-term skin contact. Sensitization testing assesses whether materials cause delayed hypersensitivity reactions. Adhesives, accelerators, and residual processing chemicals are common sensitization concerns in wearable devices.
Irritation — evaluates whether materials cause local skin irritation at the contact site. For wearables worn continuously over days or weeks, this endpoint is directly relevant to patient safety and comfort.
Systemic toxicity (subacute/subchronic) — for prolonged and long-term contact devices, systemic toxicity endpoints are evaluated based on potential leachable levels and patient exposure. Chemical characterization data plays a central role here — if leachable levels are below established thresholds, systemic toxicity testing may not be required.
Genotoxicity — assessed when chemical characterization identifies substances with mutagenic potential or when existing data doesn't adequately address genotoxicity for the materials in use.
Haemocompatibility — generally not applicable to intact-skin surface devices unless there is indirect blood contact through a fluid path or the device contacts compromised or breached skin.
The biological evaluation plan documents which endpoints are relevant, what data addresses each one, and what gaps require additional work.
The Role of Chemical Characterization
Chemical characterization has become central to wearable device biocompatibility packages. For a skin-contact device, the primary exposure concern is leachables — chemicals that migrate from the device into the patient through direct contact or sweat interaction.
A chemical characterization study identifies what's extractable from the device under relevant conditions, determines the levels of identified substances, and feeds those levels into the toxicological risk assessment. That assessment then applies established thresholds — tolerable intake values, analytical evaluation thresholds — to determine whether identified substances pose an unacceptable risk.
For wearables, the extraction conditions matter. Aqueous or sweat-simulating solvents are often more relevant than aggressive organic solvents, depending on the device's design and wear conditions. The study design should reflect realistic patient exposure, not just worst-case extraction for its own sake.
When chemical characterization demonstrates that leachable levels are well below established safety thresholds, it can eliminate the need for systemic toxicity testing and reduce the overall testing burden. When novel materials or uncharacterized substances are present, characterization is the prerequisite for knowing what you're dealing with before any risk assessment is possible.
What FDA Expects to See
FDA's current biocompatibility guidance predates ISO 10993-1:2025 — it still references the matrix-based approach from the 2018 edition. Manufacturers using the 2025 standard need to clearly document their biological evaluation process and the rationale behind their endpoint determinations, because the FDA reviewer may be comparing the submission against an older framework.
A well-built biological evaluation package for a wearable device includes:
Biological evaluation plan — contact classification, duration, identified endpoints, data sources, and gap analysis
Chemical characterization report — extractables/leachables study with relevant solvents and analytical methods
Toxicological risk assessment — endpoint-by-endpoint analysis with safety threshold comparisons
Test reports — for any endpoints where testing was required to close data gaps
Biocompatibility summary — overall conclusion with supporting rationale
The package needs to show the reviewer not just what data exists, but why that data is sufficient to conclude the device is biocompatible for its intended use.
Expert Biocompatibility Consulting for Wearable Medical Devices
At JL Tox Consulting, we help wearable medical device manufacturers build biological evaluation programs that are accurate, efficient, and aligned with current FDA expectations.
Our wearable device biocompatibility services include:
Biological evaluation planning — ISO 10993-1:2025 compliant strategies for surface-contacting and skin-worn devices
Chemical characterization study design — extractables and leachables methodology tailored to wearable device materials and wear conditions
Toxicological risk assessment — expert TRA documentation for FDA submission
510(k)/De Novo biocompatibility package development — integrated documentation from evaluation plan through final summary
Deficiency response — targeted responses to FDA biocompatibility questions
With over a decade of specialized experience in medical device biocompatibility and FDA regulatory submissions, Dr. James Lyons and the JL Tox team provide the toxicological and regulatory expertise needed to move your wearable device through clearance efficiently.
Contact JL Tox Consulting to discuss your wearable device biocompatibility program:
Email: info@JLTox.com
Phone: (877) 899-6568
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