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. It 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.
This document 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 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
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
Note: GB/T 16886.9-2022, 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 16886.12-2023, Biological evaluation of medical devices - Part 12: Sample preparation and reference materials (ISO 10993-12:2021, 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)
ISO 10993-18 Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process
Note: GB/T 16886.18-2022, Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process (ISO 10993-18:2020, IDT)
ISO 14155 Clinical investigation of medical devices for human subjects - Good clinical practice
OECD 404 Acute Dermal Irritation/Corrosion
OECD 439 In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
——ISO Online browsing platform: available at https://www.iso.org/obp
——IEC Electropedia: available at http://www.electropedia.org/
3.1
blank
solution prepared in the same way as the sample measuring solution but so that it does not contain the analyte to be determined
[SOURCE: ISO 10136-1:1993, 3.8, modified]
3.2
dose
dosage
amount of test sample (3.14) administered (e.g. mass, volume) expressed per unit of body weight or surface area
Note: The terms are often used interchangeably (more commonly dosage).
3.3
erythema
reddening of the skin or mucous membrane
3.4
eschar
scab or discoloured slough of skin
3.5
extract
liquid or suspension that results from exposing a test or control material to an extraction vehicle (3.16) under controlled conditions
3.6
irritant
agent that produces irritation (3.7)
3.7
irritation
localized non-specific inflammatory response to single, repeated or continuous application of a substance/material
Note: Skin irritation is a reversible reaction and is mainly characterized by local erythema (3.3) (redness) and swelling [oedema (3.10)] of the skin.
3.8
necrosis
cell death as a direct result of irreversible changes caused by injury or disease
Note: Tissue repair will occur either resulting in complete functional restoration or resulting in scar formation.
3.9
negative control
well-characterized material or substance that, when evaluated by a specific test method, demonstrates the suitability of the procedure to yield a reproducible, appropriately negative, non-reactive or minimal response in the test system
Note: In practice, negative controls (NC) include blanks (3.1), vehicles (3.16)/solvents and reference materials.
3.10
oedema
swelling due to abnormal infiltration of fluid into the tissue
3.11
positive control
well-characterized material or substance that, when evaluated by a specific test method, demonstrates the suitability of the test system to yield a reproducible, appropriately positive or reactive response in the test system
3.12
skin corrosion
production of irreversible damage to the skin, manifested as visible necrosis (3.8) through the epidermis and into the dermis, following application of a test sample (3.14)
EXAMPLE: The action of a compound, chemical or a test sample resulting in ulceration of skin (see 3.15).
3.13
test material
material, device, device portion or component thereof that is sampled for biological or chemical testing
3.14
test sample
material, device, device portion, component, extract (3.5) or portion thereof that is subjected to biological or chemical testing or evaluation
3.15
ulceration
open sore representing loss of superficial tissue
3.16
vehicle
liquid used to moisten, dilute, suspend, extract (3.5) or dissolve the test substance/material
3.17
vehicle control
extraction vehicle (3.16) not containing the test material (3.13), retained in a vessel identical to that which holds the test material and subjected to identical conditions to which the test material is subjected during its extraction
