GB/T 16886.23-2023 English PDF (GB/T16886.23-2023)

GB/T 16886.23-2023: Biological evaluation of medical devices - Part 23: Tests for irritation
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GB/T 16886.23-2023
GB
NATIONAL STANDARD OF THE
PEOPLE’S REPUBLIC OF CHINA
ICS 11.100.20
CCS C 30
GB/T 16886.23-2023 / ISO 10993-23:2021
Biological Evaluation of Medical Devices – Part 23: Tests for
Irritation
(ISO 10993-23:2021, IDT)
ISSUED ON: NOVEMBER 27, 2023
IMPLEMENTED ON: DECEMBER 1, 2024
Issued by: State Administration for Market Regulation;
Standardization Administration of the People’s Republic of China.
Table of Contents
Foreword ... 5
Introduction ... 7
1 Scope ... 11
2 Normative References ... 11
3 Terms and Definitions ... 12
4 General Principles - Step-Wise Approach ... 15
5 Pre-Test Considerations ... 16
5.1 General ... 16
5.2 Types of material ... 16
5.2.1 Initial considerations ... 16
5.2.2 Ceramics, metals and alloys ... 17
5.2.3 Polymers ... 17
5.2.4 Biologically derived materials ... 17
5.3 Information on chemical composition ... 17
5.3.1 General ... 17
5.3.2 Existing data sources ... 17
6 In Vitro Irritation Tests ... 18
6.1 General ... 18
6.2 In vitro reconstructed human epidermis model ... 18
6.2.1 Test system - Reconstructed human epidermis model ... 18
6.2.2 Principle of the method ... 19
6.2.3 Prediction model ... 20
6.3 Materials ... 20
6.3.1 Reconstructed human epidermis models - Product description ... 20
6.3.2 Preparation of medical device extracts ... 21
6.4 Methods ... 22
6.4.1 General ... 22
6.4.2 Test procedure ... 22
6.4.3 Media and end point solutions ... 24
6.4.4 Test sample and control preparation ... 24
6.5 Considerations for test performance ... 25
6.5.1 Receipt of the reconstructed human epidermis tissues ... 25
6.5.2 Preparation and pre-incubation ... 25
6.6 Application of the test sample and rinsing ... 26
6.6.1 General ... 26
6.6.2 Preparation ... 26
6.6.3 Test extract and controls exposure ... 26
6.7 MTT test for determination of RhE tissue viability after the exposure period ... 27
6.7.1 MTT incubation and isopropanol extraction ... 27
6.7.2 Absorbance measurements ... 28
6.8 Test acceptance criteria ... 29
6.9 Data calculation steps ... 29
6.9.1 General ... 29
6.9.2 Isopropanol background control for OD in RhE assay ... 29
6.9.3 Negative DPBS or PBS treated controls ... 29
6.9.4 Positive control ... 30
6.9.5 Tested extract and VC samples (TTs) ... 30
6.10 Data interpretation - Prediction model ... 30
6.11 Method documentation sheet ... 31
7 In Vivo Irritation Tests ... 32
7.1 General ... 32
7.2 Animal irritation test by skin exposure ... 33
7.2.1 Principle ... 33
7.2.2 Test materials ... 33
7.2.3 Animals and husbandry ... 33
7.2.4 Test procedure ... 33
7.2.5 Observation of animals ... 35
7.2.6 Evaluation of results ... 36
7.2.7 Test report ... 38
7.3 Animal irritation test by intracutaneous (intradermal) administration ... 38
7.3.1 Introduction ... 38
7.3.2 Exclusion from test ... 39
7.3.3 Test sample ... 39
7.3.4 Animals and husbandry ... 39
7.3.5 Test procedure ... 39
7.3.6 Observation of animals ... 40
7.3.7 Evaluation of results ... 41
7.3.8 Test report ... 41
8 Human Skin Irritation Test ... 42
8.1 Introduction ... 42
8.2 Initial considerations ... 43
Annex A (Normative) Preparation of Materials for Irritation Testing ... 44
Annex B (Informative) Test Method Check List for In Vitro Irritation Testing Using
Reconstructed Human Epidermis Models ... 46
Annex C (Informative) Example of Method Documentation Sheet for Reconstructed
Human Epidermis Models ... 48
Annex D (Normative) Special Irritation Tests ... 53
Annex E (Normative) Human Skin Irritation Test ... 73
Annex F (Informative) Background Information on Irritation Tests ... 78
Bibliography ... 80
Foreword
This Document was drafted as per the rules specified in GB/T 1.1-2020 Directives for
Standardization – Part 1: Rules for the Structure and Drafting of Standardizing Documents.
This Document is Part 23 of GB/T (Z) 16886 Biological Evaluation of Medical Devices. GB/T
(Z) 16886 consists of the following parts:
--- 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 leachable;
--- Part 17: Establishment of allowable limits for leachable substances;
--- Part 18: Chemical characterization of medical device materials within a risk management
process;
--- Part 19: Physio-chemical, morphological and topographical characterization of materials;
--- Part 20: Principles and methods for immunotoxicology testing of medical devices;
Biological Evaluation of Medical Devices – Part 23: Tests for
Irritation
1 Scope
This Document specifies the procedure for the assessment of medical devices and their
constituent materials with regard to their potential to produce irritation. This Document includes:
--- pre-test considerations for irritation, including in silico and in vitro methods for dermal
exposure;
--- details of in vitro and in vivo irritation test procedures;
--- key factors for the interpretation of the results.
The tests are designed to predict and classify the irritation potential of medical devices,
materials or their extracts according to ISO 10993-1 and ISO 10993-2.
2 Normative References
The provisions in following documents become the essential provisions of this Document
through reference in this Document. For the dated documents, only the versions with the dates
indicated are applicable to this Document; for the undated documents, only the latest version
(including all the amendments) is applicable to this Document.
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 10993-1 Biological evaluation of medical devices - Part 1: Evaluation and testing
within a risk management process
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 10993-9 Biological evaluation of medical devices - Part 9: Framework for
identification and quantification of potential degradation products
of the assay to detect irritant activity of these forms of materials prior to testing.
6.2.2 Principle of the method
Endpoints: cell viability determination is based on cellular reduction of MTT (3-(4, 5-
dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) and subsequent conversion to a purple
formazan salt that is quantitatively measured after extraction from the tissues. The cell viability
in treated tissues is expressed as a percentage of the negative control. The percent reduction in
viability is used to predict the irritation potential.
NOTE 1: Reduced tissue survival can be accompanied by IL-1α release. Tissue culture media from the
exposure can be collected and kept frozen at ≤-20 °C for possible analysis of cytokines.
Brief procedure: studies performed with polymeric biomaterials specifically manufactured to
contain irritant chemicals at low concentrations indicated that a prolonged exposure is needed
compared to the OECD 439 protocol for neat chemicals. An incubation period of no less than
18 h up to 24 h exposure at 37 °C for exposure to potentially low concentrations of irritants in
extracts from biomaterials is sufficient for predicting irritation in vitro by reduction of tissue
viability below 50 %. Both 18 h and 24 h exposure showed similar results in both RhE models
evaluated in the round robin study using medical device extracts.
Tissues are incubated at 37 °C, 5 % CO2 in a humidified incubator following the addition of the
test and control extracts.
Exposure to the test sample extract is terminated by rinsing with Dulbecco's phosphate buffered
saline (DPBS), or PBS without Ca2+ and Mg2+. After washing, the tissues are manually dried.
The viability is assessed by incubating the tissues for 3 h with MTT solution in a 24-well plate
(1 mg/ml; 300 μl per well). The formazan crystals are extracted using an appropriate amount
(depending on the RhE model used) of isopropanol for at least 2 h at room temperature. Two or
three aliquots (depending on the instructions of the supplier) per tissue of extracted formazan
is then added to 96-well plates (200 μ1/ well) and quantified spectrophotometrically at 570 nm.
For direct inoculation assays, a solution with a 1 % volume fraction of sodium dodecyl sulfate
(SDS, see 6.4.4) in saline solution of NaCl 0.9 % can be used as positive controls (PCs) and
DPBS or PBS without Ca2+ and Mg2+ treated epidermis are used as the negative control,
respectively. For extracted assays, a verified irritant infused control extracted in sesame oil and
in saline solutions of NaCl 0.9 % can be used as positive controls.
NOTE 2: Aliquots of culture media collected after 18 h or 24 h exposure can be stored frozen (at a
minimum of -20 °C) for potential cytokine (IL-1α) measurements as a complementary endpoint to cell
viability. IL-1α measurement determines the inflammation component to the assessment of skin irritation
in addition to the cell damage component determined indirectly by the MTT test for cell viability.
Vehicle controls shall include saline (NaCl 0.9 %) solution and sesame oil that have undergone
the ISO 10993-12 medical device extraction procedure. For each treated tissue the viability is
expressed as a percent relative to negative DPBS or PBS treated control tissues (mean).
GB/T 16886.23-2023
GB
NATIONAL STANDARD OF THE
PEOPLE’S REPUBLIC OF CHINA
ICS 11.100.20
CCS C 30
GB/T 16886.23-2023 / ISO 10993-23:2021
Biological Evaluation of Medical Devices – Part 23: Tests for
Irritation
(ISO 10993-23:2021, IDT)
ISSUED ON: NOVEMBER 27, 2023
IMPLEMENTED ON: DECEMBER 1, 2024
Issued by: State Administration for Market Regulation;
Standardization Administration of the People’s Republic of China.
Table of Contents
Foreword ... 5
Introduction ... 7
1 Scope ... 11
2 Normative References ... 11
3 Terms and Definitions ... 12
4 General Principles - Step-Wise Approach ... 15
5 Pre-Test Considerations ... 16
5.1 General ... 16
5.2 Types of material ... 16
5.2.1 Initial considerations ... 16
5.2.2 Ceramics, metals and alloys ... 17
5.2.3 Polymers ... 17
5.2.4 Biologically derived materials ... 17
5.3 Information on chemical composition ... 17
5.3.1 General ... 17
5.3.2 Existing data sources ... 17
6 In Vitro Irritation Tests ... 18
6.1 General ... 18
6.2 In vitro reconstructed human epidermis model ... 18
6.2.1 Test system - Reconstructed human epidermis model ... 18
6.2.2 Principle of the method ... 19
6.2.3 Prediction model ... 20
6.3 Materials ... 20
6.3.1 Reconstructed human epidermis models - Product description ... 20
6.3.2 Preparation of medical device extracts ... 21
6.4 Methods ... 22
6.4.1 General ... 22
6.4.2 Test procedure ... 22
6.4.3 Media and end point solutions ... 24
6.4.4 Test sample and control preparation ... 24
6.5 Considerations for test performance ... 25
6.5.1 Receipt of the reconstructed human epidermis tissues ... 25
6.5.2 Preparation and pre-incubation ... 25
6.6 Application of the test sample and rinsing ... 26
6.6.1 General ... 26
6.6.2 Preparation ... 26
6.6.3 Test extract and controls exposure ... 26
6.7 MTT test for determination of RhE tissue viability after the exposure period ... 27
6.7.1 MTT incubation and isopropanol extraction ... 27
6.7.2 Absorbance measurements ... 28
6.8 Test acceptance criteria ... 29
6.9 Data calculation steps ... 29
6.9.1 General ... 29
6.9.2 Isopropanol background control for OD in RhE assay ... 29
6.9.3 Negative DPBS or PBS treated controls ... 29
6.9.4 Positive control ... 30
6.9.5 Tested extract and VC samples (TTs) ... 30
6.10 Data interpretation - Prediction model ... 30
6.11 Method documentation sheet ... 31
7 In Vivo Irritation Tests ... 32
7.1 General ... 32
7.2 Animal irritation test by skin exposure ... 33
7.2.1 Principle ... 33
7.2.2 Test materials ... 33
7.2.3 Animals and husbandry ... 33
7.2.4 Test procedure ... 33
7.2.5 Observation of animals ... 35
7.2.6 Evaluation of results ... 36
7.2.7 Test report ... 38
7.3 Animal irritation test by intracutaneous (intradermal) administration ... 38
7.3.1 Introduction ... 38
7.3.2 Exclusion from test ... 39
7.3.3 Test sample ... 39
7.3.4 Animals and husbandry ... 39
7.3.5 Test procedure ... 39
7.3.6 Observation of animals ... 40
7.3.7 Evaluation of results ... 41
7.3.8 Test report ... 41
8 Human Skin Irritation Test ... 42
8.1 Introduction ... 42
8.2 Initial considerations ... 43
Annex A (Normative) Preparation of Materials for Irritation Testing ... 44
Annex B (Informative) Test Method Check List for In Vitro Irritation Testing Using
Reconstructed Human Epidermis Models ... 46
Annex C (Informative) Example of Method Documentation Sheet for Reconstructed
Human Epidermis Models ... 48
Annex D (Normative) Special Irritation Tests ... 53
Annex E (Normative) Hu...