GB/T 16886.15-2022 Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys
1 Scope
This document specifies general requirements for the design of tests for identifying and quantifying degradation products from final metallic medical devices or corresponding material samples finished as ready for clinical use.
This document is applicable to both materials designed to degrade in the body, materials that are not intended to degrade as well as to those degradation products generated by chemical alteration of the final metallic device in an in vitro degradation test.
This document is not applicable to evaluation of degradation which occurs by purely mechanical processes; methodologies for the production of this type of degradation product are described in specific product standards, where available. This document excludes the biological activity of the degradation products.
Note 1: Because of the nature of in vitro tests, the test results approximate the in vivo behaviour of the implant or material. The described chemical methodologies are a means to generate degradation products for further assessments.
Note 2: Purely mechanical degradation causes mostly particulate matter. Although this is excluded from the scope of this document, such degradation products can evoke a biological response and can undergo biological evaluation as described in other parts of GB/T(Z)16886.
Note 3: Because of the wide range of metallic materials used in medical devices, no specific analytical techniques are identified for quantifying the degradation products. The identification of trace elements (<10-6 w/w) contained in the specific metal or alloy is not addressed in this document, nor are specific requirements for acceptable levels of degradation products provided in this document.
2 Normative references
The following documents contain provisions which, through reference in this text, constitute provisions 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 3696 Water for analytical laboratory use - Specification and test methods
Note: GB/T 6682-2008 Water for analytical laboratory use - Specification and test methods (ISO 3696:1987, MOD)
ISO 8044 Corrosion of metals and alloys - Vocabulary definitions
ISO 10993-1 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
Note: GB/T 16886.1-2022 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process (ISO 10993-1:2018, IDT)
ISO 10993-9 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products
Note: GB/T l6886.9-2022 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9: 2019, IDT)
ISO 10993-12 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials
Note: GB/T l6886.12-2017 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials (ISO 10993-12: 2012, IDT)
ISO 10993-13 Bio-logical evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices
Note: GB/T 16886.13-2017 Bio-logical evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13: 2010, IDT)
ISO 10993-14 Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics
Note: GB/T 16886.14-2003 Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14: 2001, IDT)
ISO 10993-16 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables
Note: GB/T 16886.16-2021 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables (ISO 10993-16: 2017, IDT)
3 Terms and definitions
For the purposes of this standard, the terms and definitions given in ISO 8044, ISO 10993-1, ISO 10993-9, ISO 10993-12 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
——ISO Online browsing platform: available at http://www.iso.org/obp;
——IEC Electropedia: available at http://www.electropedia.org/.
3.1
alloy
material composed of a metallic element with one or more addition(s) of other metallic and/or non-metallic elements
3.2
electronyte
medium in which electric current is transported by ions
3.3
open-circuit potential
potential of an electrode measured with respect to a reference electrode or another electrode when no current flows to or from it
3.4
passive limit potential
Ea
electrode potential of the positive limit of the passive range
Note: See Figure 1.
3.5
breakdown potential
Ep
critical electrode potential above which localized or transpassive corrosion is found to occur
Note: See Figure 1.
3.6
absorb
action of a non-endogenous (foreign) material or substance passing through or being assimilated by cells and/or tissue over time
3.7
potentiodynamic test
test in which the electrode potential is varied at a preprogrammed rate and the relationship between current density and electrode potential is recorded
3.8
potentiostatic test
test in which the electrode potential is maintained constant and the current is recorded as a function of time
4 Degradation test methods
4.1 General
To identify and quantify degradation products from metals and alloys in medical devices, two procedures are described. The choice of test procedure shall be justified according to the function of the medical device.
The first procedure described is a combination of a potentiodynamic test and a potentiostatic test. The second procedure described is an immersion test.
The potentiodynamic test is used to determine the general electrochemical behavior of the material under consideration and to determine certain specific points (Ea and Ep) on the potential/current density curve.
The potentiostatic test is used to electrochemically degrade the test material at a constant potential above the breakdown potential to generate degradation products to be analyzed.
The immersion test is used to chemically degrade the test material to generate degradation products to be analyzed.
If there is the possibility of the loss of a coating from a metallic substrate due to degradation, the potential degradation products from the substrate material shall be considered, as well as the coating itself. In addition, if a metallic substrate coated with a non-metallic material is to be tested, the requirements of ISO 10993-13 and/or ISO 10993-14 shall be used in order to determine the potential degradation products of the coating.
The identified and quantified degradation products form the basis for evaluation of biological response. If appropriate, toxicokinetic studies in accordance with ISO 10993-16 shall be used.
For those medical devices composed of or containing nanoscale materials, and for those instances where metallic degradation products are within the nanoscale size range (approximately 1 nm to 100 nm), the user is referred to ISO/TR 10993-22 when creating their risk assessment documents.
Foreword i Introduction iv 1 Scope 2 Normative references 3 Terms and definitions 4 Degradation test methods 4.1 General 4.2 Prerequisites 5 Reagent and sample preparation 5.1 Sample documentation 5.2 Test solution (electrolyte) 5.3 Preparation of test samples 6 Electrochemical test 6.1 Apparatus 6.2 Sample preparation 6.3 Test conditions 6.4 Potentiodynamic measurements 6.5 Potentiostatic measurements 7 Immersion test 7.1 Apparatus 7.2 Sample preparation 7.3 Immersion test procedure 8 Analysis 9 Test report Annex A (Informative) Electrolytes for the electrochemical tests Annex B (Informative) Schematic diagram of the electrochemical measuring circuit Annex C (Informative) Schematic scheme of an electrolytic cell Bibliography
