GB/T 16886.9-2022 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products
1 Scope
This document provides general principles for the systematic evaluation of the potential and observed degradation of medical devices through the design and performance of in vitro degradation studies. Information obtained from these studies can be used in the biological evaluation described in the GB/T(Z) 16886 series.
This document is applicable to both materials designed to degrade in the body as well as materials that are not intended to degrade.
This document is not applicable to:
a) the 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;
Note: 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.
b) leachable components which are not degradation products;
C) medical devices or components that do not contact the patient's body directly or indirectly.
2 Normative references
The following normative 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 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 10993-2 Biological evaluation of medical devices - Part 2: Animal welfare requirements
Note: GB/T 16886.2- 2011, Biological evaluation of medical devices - Part 2:Animal welfare requirements (ISO 10993-2:2006, IDT)
ISO 10993-13 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices
Note: GB/T 16886.13-2017, Biological 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 10993-15 Biological evaluation of medical devices - Part 15:Identification and quantification of degradation products from metals and alloys
Note: GB/T 16886.15-2022, Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15:2019, IDT)
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:
——ISO Online browsing platform: available at http://www.iso.org/obp；
——IEC Electropedia: available at http://www.electropedia.org/.
3.1
degradation
decomposition of a material
3.2
absorb
action of a non-endogenous (foreign) material or substance passing through or being assimilated by cells and/or tissue over time
3.3
leachable
substances that can be released from a medical device or material during clinical use
3.4
corrosion
attack on metallic materials by chemical or electrochemical reactions
Note: The term is sometimes used in a general sense for the deterioration of other materials but is in this document reserved for metallic materials.
3.5
substance
single chemical element or compound, or a complex structure of compounds
3.6
component
one of the different parts of which a device is composed
3.7
degradation product
particle or chemical compound that is derived from the chemical breakdown of the original material
3.8
service environment
anatomical location for the intended use of the device including surrounding fluids, tissues and biomolecules
4 Principles for design of degradation studies
4.1 General
The approach to the assessment of degradation varies with the nature of the material under investigation, the medical device and the anatomical location of the specific device. The in vitro degradation models chosen for evaluation shall be representative of these factors. The studies to be conducted do not require a biological environment, but one that simulates the conditions of the intended clinical use.
Experience has shown that some in vitro models do not reflect all aspects of the service environment (e.g. mechanical processes) that can influence the degradation process. All such factors should be taken into account when modelling the service environment in vitro.
Experience has also shown that material property changes during degradation can result in different biological responses. The user is urged to be aware of those property changes and apply the relevant materials-specific standards (e.g. crystallization of polymers).
Materials-specific or product-specific degradation standards that address identification and quantification of degradation products should be considered in the design of degradation studies. ISO 10993-13 (for polymers), ISO 10993-14 (for ceramics) or ISO 10993-15 (for metals and alloys) shall apply if no suitable material-specific standard exists. Devices composed of two or more material types should consider all relevant degradation standards.
ISO 10993-13, ISO 10993-14 and ISO 10993-15 consider only those degradation products generated by a chemical alteration of the finished device. They are not applicable to degradation of the device induced during its intended use by mechanical stress, wear or electromagnetic radiation. For such degradation other methods should be considered.
4.2 Preliminary considerations
Careful consideration of the potential for intended or unintended degradation of a material is essential to the evaluation of the biological safety of a device. Part of this consideration is an assessment of the chemical characteristics and known degradation mechanisms, followed by an assessment of the need for, and design of, experimental degradation studies.
Foreword I Introduction III 1 Scope 2 Normative references 3 Terms and definitions 4 Principles for design of degradation studies 4.1 General 4.2 Preliminary considerations 4.3 Test design 4.4 Characterization of degradation products from medical devices 5 Study report Annex A (Normative) Consideration of the need for degradation studies Annex B (Informative) Degradation study considerations Bibliography
