Overview
ISO 10993-16:2017 - Biological evaluation of medical devices, Part 16 provides principles for designing and performing toxicokinetic (TK) studies for degradation products and leachables from medical devices. The standard helps manufacturers, toxicologists and regulators assess the absorption, distribution, metabolism and excretion (ADME) of chemical species released from device materials and defines when TK data should be included in a device’s biological evaluation (see Annex A).
Key technical topics and requirements
- Scope & purpose: Guidance on TK study design tailored to medical-device-specific exposure scenarios and material-derived substances (leachables, degradation products).
- Case-by-case design: Studies should be planned per device and substance, documented in a written protocol prior to start.
- Integration with extraction data: Results from extraction studies (ISO 10993-12, ISO 10993-18) and material characterisation must inform TK methods.
- Analytical method expectations:
- Methods capable of detecting and characterizing parent substances, degradation products and metabolites in biological matrices.
- Quantitative assays must be specific, sensitive, reproducible; limits of detection/quantification defined and justified; validation/qualification required.
- Study conduct:
- Selection of appropriate species/sex (often same as systemic toxicity studies) and humane care per ISO 10993-2.
- Choice of administration route relevant to device use; vehicles and test-substance stability must be reported.
- Use of radiolabelling when necessary (radiochemical purity and specific activity reported).
- Sample collection plans (blood, tissues, excreta) with adequate timepoints to derive kinetic parameters (e.g., Cmax, Tmax, half-life, clearance, volume of distribution).
- Good Laboratory Practice (GLP) recommended.
- Data reporting requirements: The study report should include animal details, substance purity and formulation, administration conditions, assay/validation details, recovery, time-point results, discussion and interpretation.
Practical applications and users
ISO 10993-16 is used to:
- Design TK studies to support safety and risk assessment of medical-device materials.
- Decide whether TK data are required for regulatory submissions or to explain observed adverse effects.
- Inform selection of analytical approaches, sampling schedules and reporting content.
Typical users:
- Medical device manufacturers and material suppliers
- Biocompatibility and toxicology scientists
- Contract research organizations (CROs)
- Regulatory affairs specialists and notified bodies
Related standards
- ISO 10993-1 (biological evaluation framework) - normative reference
- ISO 10993-2 (animal care)
- ISO 10993-12 (sample preparation/extraction)
- ISO 10993-18 (chemical characterization & analytical methods)
- Guidance added for nano-objects in this edition
Keywords: ISO 10993-16, toxicokinetic study design, leachables, degradation products, ADME, medical device biocompatibility, analytical validation, GLP, ISO 10993 series.
Open preview (PDF)Biological evaluation of medical devices — Part 16: Toxicokinetic study design for degradation products and leachables