GB/T 16886.16-2021 Biological evaluation of medical devices—Part 16: Toxicokinetic study design for degradation products and leachables
This document is Part 16 of GB/T 16886 under the general title of Biological evaluation of medical devices. The following sections of GB/T 16886 have been issued:
- Part 1: Evaluation and testing within a risk management process;
- Part 2: Animal welfare requirements;
- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity;
- Part 4: Selection of tests for interactions with blood;
- Part 5: Tests for in vitro cytotoxicity;
- Part 6: Tests for local effects after implantation;
- Part 7: Ethylene oxide sterilization residuals;
- Part 9: Framework for identification and quantification of potential degradation products;
- Part 10: Tests for irritation and skin sensitization;
- Part 11: Tests for systemic toxicity;
- Part 12: Sample preparation and reference materials;
- Part 13: Identification and quantification of degradation products from polymeric medical devices;
- Part 14: Identification and quantification of degradation products from ceramics;
- Part 15: Identification and quantification of degradation products from metals and alloys;
- Part 16: Toxicokinetic study design for degradation products and leachables;
- Part 17: Establishment of allowable limits for leachable substances;
- Part 18: Chemical characterization of materials;
- Part 19: Physico-chemical, morphological and topographical characterization of materials;
- Part 20: Principles and methods for immunotoxicology testing of medical devices;
This document replaces GB/T 16886.16-2013 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables.
Biological evaluation of medical devices
Part 16: Toxicokinetic study design for degradation products and leachables
1 Scope
This document provides principles on designing and performing toxicokinetic studies relevant to medical devices. Annex A describes the considerations for inclusion of toxicokinetic studies in the biological evaluation of medical devices.
This document is applicable to the toxicokinetic study for degradation products and leachables of medical devices.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes requirements of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
- IEC Electropedia: available at http://www.electropedia.org/
- ISO Online browsing platform: available at http://www.iso.org/obp
3.1
absorption
process of uptake of substance into or across tissue, blood and/or lymph system
3.2
bioavailability
extent of systemic absorption (3.1) of specified substance
3.3
biodegradation
degradation due to the biological environment
Note: Biodegradation might be modelled by in vitro tests.
3.4
bioresorption
process by which a biomaterial is degraded in the physiological environment and the product(s) eliminated and/or absorbed
3.5
clearance
rate of removal of a specified substance from the body or parts of the body by metabolism (3.14) and/or excretion (3.9)
3.6
c max
maximum concentration of a specified substance in plasma
Note: When the maximum concentration in fluid or tissue is being referred to, it should have an appropriate identifier, e.g. c max , liver, and be expressed in mass per unit volume or mass.
3.7
degradation product
product of a material which is derived from the chemical breakdown of the original material
3.8
distribution
process by which an absorbed substance and/or its metabolites circulate and partition within the body
3.9
excretion
process by which an absorbed substance and/or its metabolites are removed from the body
3.10
extract
liquid that results from extraction of the test substance (3.15) or control
3.11
half-life
t 1/2
time for the concentration of a specified substance to decrease to 50 % of its initial value in the same body fluid or tissue
3.12
leachable
chemical that can migrate from a device or component under storage conditions or conditions of use
Note: A leachable (e.g. additives, monomeric or oligomeric constituent of polymeric material) can be extracted under laboratory conditions that simulate normal conditions of exposure.
3.13
mean residence time
statistical moment related to half-life (3.11) which provides a quantitative estimate of the persistence of a specified substance in the body
3.14
metabolism
process by which an absorbed substance is structurally changed within the body by enzymatic and/or non-enzymatic reactions
Note: The products of the initial reaction can subsequently be modified by either enzymatic or non-enzymatic reactions prior to excretion (3.9).
3.15
test substance
degradation product (3.7) or leachable (3.12) used for toxicokinetic study
3.16
t max
time at which c max (3.6) is observed
Foreword I
Introduction III
1 Scope
2 Normative references
3 Terms and definitions
4 Principles for design of toxicokinetic studies
5 Guidance on test methods
5.1 General considerations
5.2 Guidelines for specific test types
5.2.1 General
5.2.2 Absorption
5.2.3 Distribution
5.2.4 Metabolism and excretion
Annex A (normative) Circumstances in which toxicokinetic studies shall be considered
Bibliography
