Skin Irritation and Corrosion Testing of Medical Devices: A Critical Step in Biocompatibility Assessment

The safety of medical devices is directly related not only to their performance and technical specifications, but also to their compatibility with the patient’s body. Medical devices that come into contact with the skin encompass a wide range of products, including wound dressings, adhesive tapes, electrodes, catheters, ostomy products, orthopedic supports, and surgical drapes. The scientific evaluation of these devices’ potential to cause irritation, redness, swelling, pain, or—in more severe cases—corrosion and tissue damage on the patient’s skin is mandatory under the ISO 10993-23 standard. Our laboratory conducts skin irritation and corrosion tests for medical devices in accordance with GLP and GMP principles, using the most up-to-date scientific approaches.

The Importance of Skin Irritation and Corrosion in Medical Devices

Irritation is a localized, reversible inflammatory response resulting from a substance’s contact with the skin. Clinically, it manifests as erythema (redness), edema (swelling), dryness, peeling, itching, or a burning sensation. Corrosion, on the other hand, is a more severe condition in which a substance causes irreversible damage to skin tissue; it is characterized by necrosis, ulceration, and scar tissue formation. For medical devices, the distinction between these two conditions is of critical importance; because a device with corrosion potential poses an unacceptable risk to patient safety.

The potential for skin irritation from medical devices does not stem solely from the raw materials used to manufacture the device. Mold release agents used in the manufacturing process, sterilization residues (ethylene oxide, radiation byproducts), adhesives, coatings, and packaging materials can also cause skin reactions. Furthermore, the device’s clinical usage scenario—including factors such as contact duration, contact area, skin integrity, and patient population (e.g., newborns, the elderly, or patients with sensitive skin)—directly influences the risk of irritation. Therefore, a comprehensive biocompatibility assessment must take into account all components of the device and its conditions of use.

The ISO 10993-1 standard adopts a risk-based approach to the biological evaluation of medical devices. Within this framework, the assessment of skin irritation and corrosion becomes mandatory depending on the device’s duration of skin contact and type of contact (surface device, externally connected device, or implantable device). Different test strategies are applied for devices with short-term (less than 24 hours), long-term (24 hours – 30 days), and permanent (more than 30 days) contact. This tiered approach ensures both patient safety and the efficient use of the manufacturer’s resources.

Innovations Introduced by the ISO 10993-23 Standard

ISO 10993-23 is an international standard specifically developed for the evaluation of skin irritation caused by medical devices and introduces significant innovations compared to previous versions. The most notable feature of this standard is the priority it gives to in vitro methods. The standard recommends the use of validated reconstituted human epidermis (RhE) models as the first choice for skin irritation assessment. These models are three-dimensional tissue cultures that mimic the structural and functional characteristics of human skin. The test is based on the direct application of the device extract or material to this tissue model and the measurement of cell viability using the MTT assay. If cell viability falls below a certain threshold value, the material is classified as “irritating.” This approach completely eliminates the use of animals while allowing for more direct extrapolation to human skin.

Another important innovation of the standard is the standardization of extraction conditions. ISO 10993-23 has clarified the extraction temperatures and durations to reflect the device’s clinical usage scenario. For example, while an extraction of 24–72 hours at 37°C is generally recommended for surface devices, different protocols have been defined for devices requiring more aggressive conditions. This standardization enhances the alignment of test results with clinical reality and reduces the risk of false-positive or false-negative results.

ISO 10993-23 has also expanded the evaluation criteria. In addition to cell viability, parameters such as morphological changes, tissue integrity, and pro-inflammatory cytokine release have been included in the scope of evaluation. This enables clearer decision-making, particularly in borderline cases. The standard specifies that in vivo skin irritation testing (patch testing on rabbits or human volunteers) may be used as an alternative in situations where the in vitro method is not appropriate or the results are inconclusive. However, in line with modern regulatory approaches and ethical principles, the in vitro methods are encouraged as the preferred option.

Test Methods and Application Strategies

In the evaluation of skin irritation and corrosion for medical devices, different test methods are applied depending on the device’s physical form and clinical usage scenario. In vitro The RhE model is ideal for extracts or materials in liquid form. For solid devices and surface coatings, direct material application or specialized extraction protocols are used. This flexibility demonstrates the standard’s adaptability to different device types.

The extraction process is performed in accordance with the ISO 10993-12 standard. Extraction is performed at temperatures and for durations that reflect clinical use, using specific volumes of polar (serum-containing medium) and non-polar (vegetable oil) solvents per unit surface area or mass of the device. Polar extracts represent water-soluble components, while non-polar extracts represent lipophilic components.

By testing both types of extracts separately, all potential irritant components of the device are evaluated.

In vivo testing is performed using a rabbit model when it is unavoidable. The test substance is applied to the shaved back skin of the rabbit and kept under a semi-occlusive dressing for 4 hours. Erythema and edema scores are then assessed at 1, 24, 48, and 72 hours. The Primary Irritation Index (PII) is calculated by averaging the scores, and the device is classified as “irritating” or “non-irritating.” The patch test on human volunteers is another alternative, particularly for cosmetics and devices intended for prolonged skin contact; however, it requires meticulous attention to ethical approval processes and patient selection.

The table below summarizes the basic methods and areas of application used in the evaluation of skin irritation and corrosion for medical devices.

Which Devices Require Skin Irritation Testing?

The ISO 10993-1 standard adopts a risk-based approach to the biological evaluation of medical devices. Within this framework, skin irritation and corrosion assessments are required for all medical devices that come into contact with the skin.

However, the scope and method of the test vary depending on the device’s contact duration and type of contact.

Surface devices are those that come into direct contact with the skin and are typically used for either short-term (less than 24 hours) or long-term (24 hours – 30 days) periods. Wound dressings, electrodes, adhesive tapes, transdermal patches, and surgical drapes fall into this category. For these devices, the in vitro RhE model is generally sufficient; however, additional evaluation may be required for devices used in long-term contact or in patients with sensitive skin.

External-connection devices are those that penetrate the skin surface and enter the body but remain connected to the external environment. Catheters, drainage tubes, ostomy products, and infusion sets fall into this category. These devices may come into contact with both skin and mucosal tissue; therefore, irritation assessments must be conducted for both the skin and the mucosa.

Implantable devices are those that remain inside the body for an extended period or permanently. Orthopedic implants, stents, heart valves, and dental implants fall into this category. For these devices, skin irritation assessment is typically evaluated in conjunction with the local tissue response at the implantation site; implantation testing is conducted in accordance with ISO 10993-6.

Contact duration is a critical factor in determining the testing strategy. While in vitro testing is generally sufficient for devices in short-term contact, more comprehensive evaluation may be required for devices in long-term or permanent contact. Additionally, the patient population for which the device is intended must be considered. Newborns, the elderly, immunocompromised patients, and individuals with sensitive skin may be more susceptible to irritant effects. Therefore, a more rigorous evaluation approach should be adopted for devices intended for these populations.

Conducting Medical Device Skin Irritation Tests in Our Laboratory

In our GLP- and GMP-certified laboratory, we conduct skin irritation and corrosion tests for medical devices in full compliance with international standards. For in vitro skin irritation tests, we use validated reconstituted human epidermis models; in cases where in vivo testing is unavoidable, we operate in full compliance with the 3R principles under the supervision of experienced veterinarians and toxicologists.

Our testing process begins with a comprehensive preliminary evaluation. The device’s material composition, manufacturing process, sterilization method, and clinical usage scenario are examined in detail. Based on this information, the most appropriate extraction protocol and test method are determined. The extraction process is performed in accordance with ISO 10993-12, using a specific volume of solvent per unit surface area or mass of the device. Polar and non-polar extracts are prepared and tested separately.

In the in vitro RhE test, extracts or materials are applied directly to a tissue model, and after a specified incubation period, cell viability is measured using the MTT assay. Results are interpreted by comparing them to negative and positive controls. Materials with cell viability below the threshold value are classified as “irritating.” In vivo tests, on the other hand, use a rabbit model to evaluate erythema and edema scores; the Primary Irritation Index is calculated.

One of our laboratory’s key advantages is that test results can be directly integrated into your regulatory submissions. Our reports, prepared in accordance with ISO 10993-23, meet the requirements of the EU MDR (2017/745), FDA 510(k), ISO 10993-1, and other regulatory frameworks. In addition, we provide a comprehensive assessment that is consistent with the other components of your device’s biocompatibility dossier (cytotoxicity, sensitization, implantation).

Frequently Asked Questions

One of the most common questions we receive regarding skin irritation testing for medical devices is whether an in vitro test is always sufficient. In the vast majority of cases, yes; however, if the test results are inconclusive, if the device’s specific usage scenario cannot be modeled in vitro, or if the regulatory authority specifically requests it, in vivo testing may be required. This decision is made in light of the risk assessment and scientific rationale.

Another common question is how the device extract is prepared. In accordance with ISO 10993-12, extraction is performed using specific volumes of polar (serum-containing medium) and non-polar (vegetable oil) solvents per unit surface area or mass of the device, at temperatures and for durations that reflect clinical use. Extraction conditions are determined based on the device’s contact time and usage scenario.

Regarding the test duration, the in vitro RhE test typically yields results within 1–2 weeks; the in vivo test takes 3–4 weeks. Including reporting and quality assurance reviews, the total duration is generally 3–6 weeks. Another frequently asked question is which devices are subject to this test. A skin irritation assessment under ISO 10993-1 is required for all medical devices that come into contact with the skin. The duration and type of contact determine the scope of the test. Finally, there is often curiosity about the formats in which results are reported. A full test report compliant with ISO 10993-23 can be presented in the MDR technical file format or in the specific format required by the regulatory authority.

The skin compatibility of your medical device is the cornerstone of patient safety and regulatory approval. A rigorous skin irritation and corrosion evaluation conducted in accordance with ISO 10993-23 directly impacts your device’s safety, performance, and market acceptance. Our laboratory provides services in accordance with GLP and GMP standards across a wide range of services, from in vitro RhE models to in vivo validation tests. To be your trusted partner on your medical device’s biocompatibility journey, contact us.