Irritation Testing (ISO 10993-23)
Assess potential inflammatory reactions using ISO-compliant In Vitro methods and specialized In Vivo assays.
Irritation is a local inflammatory response to a single, repeated, or continuous application of a medical device (or its extracts). Unlike sensitization (which is systemic), irritation occurs at the site of contact.
Following the publication of ISO 10993-23:2021, the global regulatory landscape has shifted towards prioritizing In Vitro methods to reduce animal testing. EBI is at the forefront of this change, offering validated alternative methods alongside traditional assays for complex devices.
- The ethical, modern gold standard for skin-contact devices.
In Vitro Skin Irritation (Reconstructed Human Epidermis)
This test is the preferred starting point for evaluating skin irritation. It utilizes Reconstructed Human Epidermis (RhE) models—three-dimensional human skin tissue grown in the lab—to simulate the reaction of human skin without using animals.
- How it works: The test item (or extract) is applied topically to the RhE tissue surface.
- Analysis: We measure cell viability (using MTT assay.
- Advantages: Ethical (animal-free), highly reproducible, and fully accepted by ISO 10993-23 standard and OECD TG 439.
- Standard Turnaround Time: 8 weeks.
- Essential for implants and external communicating devices
Intracutaneous Reactivity Test
While topical irritation tests surface contact, the Intracutaneous Reactivity test evaluates the reaction of the deep dermal tissue to device extracts. This test is mandatory for devices that have prolonged contact with internal tissues or circulating blood.
- Methodology: Extracts are prepared in polar (saline) and non-polar (vegetable oil) vehicles.
- Procedure: Extracts are injected intracutaneously (between skin layers) into rabbits.
- Scoring: Sites are examined at 24h, 48h, and 72h for signs of Erythema (redness) and Edema (swelling).
- Compliance: The test passes if the difference between the mean reaction score of the device and the control is ≤ 1.0.
- Standard Turnaround Time: 4 weeks.
- For devices contacting sensitive membranes.
Mucosal & Special Irritation Tests (In Vivo)
Some devices contact specific mucosal areas where standard skin tests are insufficient. EBI offers specialized in vivo irritation studies tailored to the specific anatomical application of your device.
These studies involve histopathological evaluation to detect microscopic signs of tissue damage.
- Ocular Irritation: For contact lenses and ophthalmic devices.
- Oral / Buccal Irritation: For dental devices and mucosal implants.
- Vaginal Irritation: Evaluation of vaginal tissue reactivity (includes Histology).
- Rectal Irritation: Assessment of mucosal damage in rectal applications (includes Histology).
- Penile Irritation: Specialized assessment for urological devices (includes Histology).
- Standard Turnaround Time: The duration of the study depends on the specific test method and the complexity of the study design (e.g., tests requiring histological analysis typically involve extended timelines). Please contact us for a detailed schedule tailored to your specific testing requirements.
Sample Requirements
Prepare your samples according to the guidelines below.
| Test Type | Material Thickness | Surface Area Required | Weight / Volume | Minimum Quantity |
|---|---|---|---|---|
| In Vitro Irritation (RhE Model) |
< 0.5 mm | 6 cm² | - | 4 items |
| ≥ 0.5 mm | 3 cm² | - | 4 items | |
| Powder / Solid | - | 0.2 grams | - | |
| Liquid | - | 3 ml | - | |
| Intracutaneous (Rabbit) |
< 0.5 mm | 120 cm² | - | 2 items |
| ≥ 0.5 mm | 60 cm² | - | 2 items | |
| Powder / Solid | - | 5 grams | 2 items | |
| Mucosal / Special | - | Consultation Required | - | - |
Note: For Special Irritation tests (Ocular, Vaginal, etc.), sample size depends on the specific device dimensions. Please contact our lab for a custom sampling plan.
Compliance with Global Standards
Our protocols are designed to satisfy the requirements of global notified bodies and health authorities:
- ISO 10993-23: Tests for irritation.
- OECD TG 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method.
How We Work
Discovery & Insight
We begin with an in-depth consultation to understand your needs, challenges, and objectives. This helps us define the right strategy and scientific approach for your project.
Design & Development
Our experts translate your vision into actionable plans — combining innovative research, data, and technology to build precise and reliable solutions.
Delivery & Support
We implement the solution with full transparency and ongoing communication. After delivery, we stay involved — supporting you with optimization, updates, and future improvements.
FAQ: Understanding Irritation Standards
What is the difference between ISO 10993-10 and ISO 10993-23?
Previously, irritation testing was described in Part 10. As of 2021, a dedicated standard, ISO 10993-23, was published specifically for Irritation. Part 10 now covers only Sensitization. EBI reports are fully compliant with the new ISO 10993-23 structure.
Do I have to perform Animal Testing for skin irritation?
ISO 10993-23 encourages a stepwise approach. You should start with In Vitro Characterization and In Vitro Irritation. Animal testing is now usually performed only if the In Vitro results are inconclusive or if the device contacts mucosa/internal tissues where In Vitro models are not yet fully validated.
What is the difference between Irritation and Intracutaneous Reactivity?
- Irritation usually refers to topical application (surface of skin or mucosa).
- Intracutaneous Reactivity involves injecting the extract inside the dermis. It mimics the local reaction to potential leachables from devices that have contact with internal tissues or circulating blood.
What is the difference between ISO 10993-10 and ISO 10993-23?
Previously, irritation testing was described in Part 10. As of 2021, a dedicated standard, ISO 10993-23, was published specifically for Irritation. Part 10 now covers only Sensitization. EBI reports are fully compliant with the new ISO 10993-23 structure.
Do I have to perform Animal Testing for skin irritation?
ISO 10993-23 encourages a stepwise approach. You should start with In Vitro Characterization and In Vitro Irritation. Animal testing is now usually performed only if the In Vitro results are inconclusive or if the device contacts mucosa/internal tissues where In Vitro models are not yet fully validated.
What is the difference between Irritation and Intracutaneous Reactivity?
- Irritation usually refers to topical application (surface of skin or mucosa).
- Intracutaneous Reactivity involves injecting the extract inside the dermis. It mimics the local reaction to potential leachables from devices that have contact with internal tissues or circulating blood.
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Location:
Europejski Instytut Biomedyczny sp. z o.o.
ul. Bartycka 63A lok. 6, 00-716 Warszawa
Mail:
contact@ebi.bio
Phone:
+48 22 780 06 32
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