GB/T 16886.13-2017 Biological evaluation of medical devices — Part 13: Identification and quantification of degradation products from polymeric medical devices
1 Scope
This part of GB/T 16886 provides general requirements for the design of tests in a simulated environment for identifying and quantifying degradation products from finished polymeric medical devices ready for clinical use.
This part describes two test methods to generate degradation products, an accelerated degradation test as a screening method and a real-time degradation test in a simulated environment. For materials that are intended to polymerize in situ, the set or cured polymer is used for testing. The data generated are used in the biological evaluation of the polymer. This part considers only non-resorbable polymers. Similar but appropriately modified procedures may be applicable for resorbable polymers.
This part considers only those degradation products generated by a chemical alteration of the finished polymeric device. It is not applicable to degradation of the device induced during its intended use by mechanical stress, wear or electromagnetic radiation or biological factors such as enzymes, other proteins and cellular activity.
Note: An informative text discussing environmental stress cracking (ESC) of polymers is included as a potential aid to the design of degradation studies (see Annex B).
The biological activity of the debris and soluble degradation products is not addressed in this part, but should be evaluated according to the principles of GB/T 16886.1, GB/T 16886.16 and GB/T 16886.17.
Because of the wide range of polymeric materials used in medical devices, no specific analytical techniques are identified or given preference. No specific requirements for acceptable levels of degradation products are provided in this part.
2 Normative references
The following referenced documents are indispensable for the application 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
ISO 10993-1 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
ISO 10993-9 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products
ISO 10993-12 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials
ISO 10993-16 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables
ISO 10993-17 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
residual monomer
unreacted chemical compound(s) used to build the polymeric chains, which is still present in the final polymeric material
3.2
degradation product
chemical compound derived from the breakdown of the polymeric material, including any compound produced by consecutive chemical reactions
3.3
polymeric material
materials consisting of long-chain and/or crosslinked molecules composed of units called monomers
3.4
hydrolytic degradation
scission of chemical bonds in a polymer by the attack of water
Note: The water can have a neutral, acidic or alkaline pH value and can contain additional chemical compounds or ions.
3.5
oxidative degradation
scission of chemical bonds in a polymer by the attack of one or more oxidizing agents
3.6
debris
particulate material produced by the degradation of a polymeric material
4 Degradation test methods
4.1 General procedures
4.1.1 Test design
In accordance with ISO 10993-9, degradation tests shall be used to generate, identify and/or quantify degradation products. If degradation is observed in an accelerated test, identification and quantification of the degradation products can provide sufficient information for risk analysis. If identification and quantification of degradation products from the accelerated test do not provide sufficient information for the risk analysis, real-time testing shall be performed. The sequence of steps that shall be followed is described in detail in this part of GB/T 16886.
Note: The accelerated degradation test can be used as a screening test. If no degradation is observed in the accelerated test, no real-time degradation test should be necessary.
4.1.2 Sample preparation
When not specifically addressed by the selected method(s), the general aspects of sample preparation shall be in accordance with ISO 10993-12.
4.1.3 Initial material characterization
The analytical methods used for the initial material characterization shall be appropriate for the polymeric material under investigation. The analytical techniques used shall be reported and justified.
Annex A presents a list of analytical methods and their application range for the characterization of polymeric materials.
4.1.4 Test solutions and apparatus
4.1.4.1 Test solutions
4.1.4.1.1 General
All test solution(s) used shall be described and justified in the test report.
The test solution shall be selected to be as similar as possible to the intended environment in which the polymeric medical device is going to be used.
If the service environment cannot be simulated, test solutions given in 4.1.4.1.2 and 4.1.4.1.3 can be used as a first screening for degradation. These test solutions can be more challenging or less challenging to the polymeric material with respect to the intended degradation mechanisms than the in vivo environment.
Other test solutions for a specific polymer or a specific service environment may be chosen.
Note: If a biological assay of the debris or the degradation solution is to be made, then the use of antibacterial or antifungal additives will interfere with these assays and it might be necessary to maintain a sterile environment for the duration of the real-time degradation test.
Foreword II
Introduction V
1 Scope
2 Normative references
3 Terms and definitions
4 Degradation test methods
5 Test procedures
6 Test report
Annex A (Informative) Analytical methods
Annex B (Informative) Environmental stress cracking (ESC) of polymers
Bibliography
