Medical device irritation test - biocompatibility assessment according to EN ISO 10993-23
Medical devices come into direct contact with the human body for diagnostic, therapeutic or monitoring purposes. For this contact to be safe, the product must neither be toxic nor irritating. The irritation test is a crucial biocompatibility test used to assess whether a medical device or substances released from it cause local damage to the skin, eyes or mucous membranes.
These tests are performed within the framework of the internationally recognized standard EN ISO 10993-23 (Biological evaluation of medical devices - Part 23: Irritation tests). This standard, published in 2021, has extracted the sections on irritation and sensitization from the former standard ISO 10993-10 and thus provides a more specific and up-to-date framework for irritation tests. For MDR (2017/745) and FDA 510(k) applications, it is mandatory that these tests are performed in accordance with the GLP principles (Good Laboratory Practice).
What is irritation and why is it tested?
Irritation is a local inflammatory reaction that is triggered by contact of a substance with the skin, eyes, or mucous membranes and is not attributable to the immune system. It is characterized by redness (erythema), swelling (edema), dryness, fissures, and sometimes necrosis. Irritation can occur after a single contact (acute) or after repeated contact (cumulative).
The risk of irritation in medical devices is assessed in particular in the following cases:
- Products that come into contact with the skin: wound dressings, electrodes, bandages, sensors, portable devices
- Products that come into contact with the mucous membrane: Nasal sprays, dental materials, bladder catheters
- Devices that come into contact with the eye: contact lenses, intraocular lenses (IOL), surgical instruments
- Implantable devices: Orthopedic implants, stents, screws
- External communication devices: Blood bags, infusion sets, catheters
These tests can be carried out on the device itself (in solid form) or on extracts obtained from the device (in liquid form). Which approach is chosen depends on the purpose of the device and the duration of contact.
Irritation test procedure under EN ISO 10993-23
EN ISO 10993-23 offers both in-vivo (living animals) and in-vitro (cell culture) methods for assessing irritation. In accordance with the 3R principles (replacement, reduction, refinement), in vitro methods are increasingly preferred.
1. In vitro irritation tests (priority method)
The modern approach gives priority to in vitro models to minimize the use of animals. EN ISO 10993-23 accepts the following in vitro methods:
- Models of reconstructed human epidermis (RHE): Three-dimensional tissue models made from human skin cells are used. The test substance is applied to the tissue and cell viability (MTT test) is measured. A viability loss of more than 50 % is considered an irritant effect.
- EpiDerm™, EpiSkin™, SkinEthic™: Commercially available, validated human skin equivalents.
- OECD TG 439: Internationally recognized test guideline for in vitro skin irritation.
- HET-CAM (chicken embryo-chorioallantoismembrane test): A method used in particular to test eye irritation. The test substance is applied to the vascular net of a fertilized chicken egg and attention is paid to vascular damage.
2. In vivo irritation tests (if necessary)
In-vivo tests are used when no matching results can be achieved with in vitro methods or if there are special regulatory requirements:
- Skin irritation test (rabbit): The test substance is applied to the shaved skin of healthy rabbits. After 24, 48 and 72 hours, erythema and edema are evaluated.
- Eye irritation test (rabbit): The test substance is applied to the rabbit eye, and damage to the conjunctiva, iris and cornea is evaluated.
- Mulchium irritation test: Examinations on the vaginal, rectal or oral mucosa.
3. Corrosion test (OECD TG 431)
The corrosion potential is usually evaluated in vitro. Models of the reconstructed human epidermis (RHE) are used as part of the OECD TG 431. The test substance is applied to the tissue for 3 minutes, 1 hour and 4 hours, and cell viability is measured. A viability of less than 35% is classified as corrosion.
Comparison of the stimulus test methods
The following table summarizes the test procedures used in EN ISO 10993-23:
| Test procedure | Model | Application time | Evaluation criterion | Advantages |
|---|---|---|---|---|
| RHE (Epiderm™) | Human skin equivalent | 18-24 Hours | Cell viability (MTT) | No animal experiments, fast, reproducible |
| OECD TG 439 | Human skin equivalent | 18-24 Hours | Cell viability | Internationally recognized, validated |
| Het cam | Chicken embryo | 5 Minutes | Vascular damage score | Alternative to eye irritation |
| In vivo skin irritation | Rabbit | 4 Hours contact + 72 hours observation | Erythem/edema score (0–4) | Clinical data, officially recognized |
| OECD TG 431 (corrosive effect) | Human skin equivalent | 3 Min, 1 hour, 4 hours | Cell viability (<35% = etching effect) | Determination of corrosion, no animal experiments |
How does the stimulus test procedure work?
Carrying out an irritation test on a medical device includes the following steps:
- 1. Extraction: The product is extracted in accordance with ISO 10993-12 using polar (water, saline solution) and non-polar (plant oil, DMSO) solvents.
- 2. Dose setting: The extract concentration is calculated based on the surface-to-volume ratio of the product.
- 3. Test performance: Depending on the chosen method (in vitro or in vivo), the test substance is applied.
- 4. Observation and Measurement: The reactions are evaluated at specified points in time.
- 5. Rating and Classification: The results are classified as "non-irritating/non-corrosive", "slightly irritating", "severely irritating" or "corrosive".
- 6. Report generation: A GLP-compliant report with test approval is created.
GLP compliant irritation test services with nano test
The biocompatibility assessment of your medical device is possible by selecting the right test method and presenting the results in an acceptable format for the approval authorities. Nano-Test is your reliable partner in this process with its GLP-compliant irritation tests in accordance with EN ISO 10993-23.
Nano-Test – Performance Description
Nano-Test offers Irritation tests for medical devices in accordance with EN ISO 10993-23. In our labs accredited to GLP (Good Laboratory Practice) and ISO/IEC 17025, both in-vitro procedures (RHE, OECD TG 439, HET-CAM) and In vivo procedure (skin and eye irritation in rabbits) applied.
Our service process includes ISO 10993-12-compliant extraction of your product, dosage optimization, testing, and observation and evaluation. All work is carried out with the approval of the ethics committee for test animals and under veterinary supervision. The results are provided as GLP compliance reports with full traceability, which you can use for your MDR and FDA-510(K) applications.
In Nano-Test, we attach great importance to the 3R principles and recommend in vitro methods whenever possible. We support you in the creation of your biocompatibility strategy (Biological Evaluation Plan - BEP) and provide you with sound data for communication with the approval authorities.
Advantages of the Nano Test Irritant Test:
- Competence in both methods: Both in-vitro and in-vivo irritation tests from a single source.
- GLP Certified Infrastructure: All investigations are carried out in accordance with GLP principles and Alcoa+ requirements.
- Fast Results: In-vitro testing reporting within 3-5 working days.
- Specialist staff: A team with experience in toxicology and histopathology.
- Compliance with legal regulations: Complete compliance with the requirements according to EN ISO 10993-23, OECD TG 431/439 and MDR.
Local irritation caused by medical devices poses a significant risk that directly affects patient comfort and safety. Irritation Test - EN ISO 10993-23 is a crucial step to scientifically demonstrate whether your product carries this risk. Choosing the right test method, performing the extraction properly and reporting the results in accordance with the GLP standards are prerequisites for a smooth running of the regulatory approval process.
With its laboratory infrastructure, its specialist staff and its GLP-compliant processes, Nano-Test comprehensively meets the requirements of medical device manufacturers in the field of irritation tests. Collaborate with Nano Test to increase the safety of your product and speed up market access.