Overview
EN ISO 10993-16:2017 (ISO 10993-16:2017) is part of the ISO 10993 series on the biological evaluation of medical devices. It provides principles for the design and conduct of toxicokinetic (TK) studies focused on degradation products and leachables from medical device materials. The standard explains when TK data are needed and gives guidance on study planning, sampling and interpretation to support biocompatibility and risk assessment.
Key topics
- Scope and objectives: Principles for designing toxicokinetic studies relevant to devices that may release degradation products or leachables.
- Study-design principles: Framework for defining study questions, selecting species or models, exposure routes and sampling strategies.
- Guidance on test methods: General considerations plus targeted guidance for specific ADME endpoints:
- Absorption - evaluating how released substances enter systemic circulation.
- Distribution - assessing tissue distribution and potential accumulation.
- Metabolism and excretion - identifying metabolic pathways and elimination routes.
- Annex A (normative): Circumstances in which TK studies should be considered as part of the biological evaluation.
- Regulatory context: Alignment with ISO 10993‑1, references to risk management (ISO 14971) and informative annexes (ZA/ZB) describing relationships to EU medical device Directives.
Applications
EN ISO 10993-16 supports practical decisions across device development and regulatory submission:
- Biocompatibility programs - determine whether leachables or degradation products require TK assessment.
- Preclinical testing - design ADME studies that inform toxicity testing and safety margins.
- Material selection & design changes - evaluate potential systemic exposure from new polymers, coatings or additives.
- Regulatory dossiers - provide rationale and data for notified bodies, regulators or technical files, including conformity arguments referenced in Annex ZA/ZB.
- Contract Research Organizations (CROs) and toxicologists use the standard to align study protocols with accepted principles for medical device–specific TK work.
Who should use it
- Medical device manufacturers and R&D teams
- Biocompatibility scientists and toxicologists
- Regulatory affairs specialists preparing submissions
- CROs and preclinical laboratories conducting ADME/TK studies
- Notified bodies and assessors evaluating device safety
Related standards
- ISO 10993-1 - Biological evaluation framework (normative reference)
- ISO 14971 / EN ISO 14971 - Risk management for medical devices (referenced for risk-based decisions)
- Other parts of the ISO 10993 series covering chemical characterization and specific endpoints
EN ISO 10993-16:2017 is an essential reference for anyone designing toxicokinetic studies to characterize systemic exposure from medical device materials and to support robust, risk‑based biological evaluations.
