Systemic toxicity studies for medical devices according to ISO 10993-11

The purpose of reprocessing validation studies is to show that reusable medical devices can be reprocessed effectively between uses so that patients are not exposed to pathogens. Depending on the device’s intended use and classification, appropriate reprocessing steps may include cleaning, disinfection, and/or sterilization. For cleaning validation, more specifically, the testing procedure consists of three steps: Simulated contamination with artificial soils that accurately reflect clinically relevant soils, such as blood and other bodily fluids. , Cleaning (manual and/or automated), carefully following the manufacturer's instructions for parameters such as detergents, cleaning tools, water quality, and temperature. , Inspection, both visually and using quantitative methods relevant to the test soil (e.g., proteins, total organic carbon, or hemoglobin), to assess whether residual contaminants remain on the device.. Successful cleaning validation is often sufficient for non-critical reusable devices, such as blood pressure cuffs, monitors, and clutches. Semi-critical and critical devices will require further disinfection and/or sterilization validation studies, which we can also offer. The displayed example price covers a manual cleaning validation study with 6 reprocessing cycles and cleanability evaluations with visual inspection & protein content measurement. Test protocol formulation and reporting are also included.

ISO 10993-23 is an internationally recognized standard for assessing the irritation potential of medical devices that come into contact with skin, mucosal membranes, or subcutaneous tissues. Irritation tests performed according to the standard are commonly required to demonstrate compliance with EU MDR and FDA requirements with regard to biocompatibility. The appropriate testing approach is chosen based on the body contact site: Skin irritation tests evaluate whether the device or material causes localized skin irritation in direct contact with the skin. Testing can be conducted using in vivo or in vitro methods, depending on the device and the market area., Intracutaneous reactivity tests apply to medical devices or materials that penetrate the skin or come into contact with deeper tissues. The goal is to determine whether the material causes localized inflammatory responses in the dermis or subcutaneous layers.. The device itself is tested with a direct contact method, where possible. Alternatively, polar and non-polar solvents are used to prepare extracts that simulate potential leachables from the device. The displayed example price includes an in vivo direct skin irritation test performed under GLP. In vitro methods, such as the OECD 439 skin irritation test with a reconstructed human epidermis (RhE), are also available. For a more accurate quote, contact us through the form below with a description of your device and any additional requirements you may have for testing (e.g., market area, quality systems, in vivo vs. in vitro methods).

Assessment of skin sensitization potential using the ARE-Nrf2 luciferase test method outlined in OECD Test Guideline 442D and listed in Annex C of ISO 10993-10 as an in-vitro alternative to traditional in vivo sensitization tests. The method has been validated for medical device extracts. The assay models the keratinocyte activation pathway — key event 2 in the skin sensitization adverse outcome pathway (AOP) as described by the OECD. Human keratinocytes are exposed to the test substance at a range of concentrations. If the substance has skin sensitization potential, it activates the Nrf2 transcription factor, which binds to the antioxidant response element (ARE) and induces luciferase expression. The measured luciferase activity thus correlates with the sensitization potential of the substance. According to Annex C of ISO 10993-10, a substance is classified as a skin sensitizer if luciferase activity increases by 50% relative to the solvent control at a concentration where cell viability is not significantly reduced. Two extracts (one polar and one non-polar) are prepared per tested device, and testing is performed in duplicate for each solvent.

We offer comprehensive test packages for verifying the quality of type II and type IIR face masks according to the EN 14683 standard. The tests included in the packages are required to label face masks with the CE marking. Medical face masks are divided into Types I and II according to their bacterial filtration efficiency. Type I masks are not intended for healthcare professionals, but for the public to prevent the spread of infectious diseases. Type II masks are further classified based on whether they are splash-resistant (Type IIR) or not (Type II). To comply with the European Standard EN 14683, Type II face masks must undergo the following quality tests: Bacterial filtration efficiency (BFE) - The ability of the face mask to filter the bacterium Staphylococcus aureus. The BFE is expressed as the percentage of colony-forming units (cfu) that have passed via aerosol through the facemask. If a face mask consists of two or more areas with different characteristics, these areas will be tested separately., Breathability (Differential pressure) - The amount of differential pressure required to draw air through a measured surface area at a constant flow rate., Microbial cleanliness (Bioburden) - The measurement of colony forming units per gram as per EN ISO 11737-1., Biocompatibility - The medical face mask manufacturer shall complete a biocompatibility evaluation according to ISO 10993-1 as a surface device with limited contact. The applicable toxicology testing regimen shall also be determined.. In addition to the above, Type IIR masks require the following test: Splash resistance - Performed according to ISO 22609, this test determines the ability of a face mask to resist penetration of splashes of liquid at different pressures.. The lower displayed price applies to the Type II mask test package, while the higher price also includes the splash resistance test required for Type IIR masks.

The biocompatibility of medical devices with breathing gas pathways is generally assessed according to ISO 18562 standards. Measurlabs offers tests according to this standard family, including the following: ISO 18562-2: Tests for emissions of particulate matter (PM), ISO 18562-3: Tests for emissions of volatile organic substances (VOS), ISO 18562-4: Tests for condensate volume and leachables from condensate. Our experts are happy to help with any questions related to the tests and prepare a quote for you. Describe your testing needs using the form below, and we will get back to you shortly.

The Ames test is an in vitro bacterial reverse mutation assay used to evaluate the mutagenic potential of a medical device or its extract. The test is conducted according to OECD 471 and ISO 10993-3 by exposing a bacterial suspension of Salmonella spp and Escherichia coli to 5 concentrations of the medical device or its pure extracts. The Ames test identifies whether substances leaching from a device induce gene mutations in bacterial strains, which is a key indicator of potential genotoxicity. The Ames test is a preliminary "screening test" for genotoxicity. A full genotoxicity evaluation usually includes testing the device with two in vitro methods, of which Ames is typically performed first, followed by in vivo testing if positive or equivocal results are observed. Measurlabs can support you with the full genotoxicity evaluation. Please contact our experts for a quote.

Pyrogenicity assessment by ISO 10993-11 to evaluate the material-mediated pyrogenic (i.e., fever-inducing) potential of medical devices. Material-mediated pyrogenicity tests focus on non-endotoxin-related substances, including bacterial exotoxins, endogenous pyrogens, prostaglandin, neurotransmitters, and metal salts. These can be studied using in vitro assays, where the fever-inducing potential is evaluated using cells, or in vivo rabbit pyrogen tests, where the animal's body temperature is monitored upon exposure to device extracts. Measurlabs provides testing using the following methods: Material-mediated pyrogenicity - In vivo (rabbit), Material-mediated pyrogenicity - In vitro (MAT, Monocyte Activation Test). Please ask for a quote for your medical device. We also offer Bacterial endotoxin tests (ISO 11737-3) to evaluate endotoxin-related pyrogenicity.

In vitro identification of chemicals not requiring classification for eye irritation or serious eye damage, using the EpiOcular™ Eye Irritation Test (EIT) according to OECD Test Guideline 492. The method uses a reconstructed human cornea-like epithelium (RhCE) tissue construct that closely mimics the histological and physiological properties of the human corneal epithelium, and serves as a non-animal alternative to the in vivo rabbit eye test (OECD 405). The test substance is applied topically to the RhCE tissue. Following exposure and a post-treatment incubation period, tissue viability is measured by the MTT assay and expressed as a percentage of the negative control. A substance is identified as not requiring classification (UN GHS No Category) if tissue viability exceeds 60%. Substances that reduce viability below this threshold are considered to require classification, but the method cannot differentiate between UN GHS Category 1 (serious eye damage) and Category 2 (eye irritation) — further testing is required to make that distinction. OECD TG 492 is accepted for eye irritation and serious eye damage hazard assessment under REACH (Annex VII/VIII information requirements) and the EU Biocidal Products Regulation (Regulation (EU) No 528/2012, Annex II core data set). It is also mentioned alongside other in vitro OECD methods in the latest version of ISO 10993-23 standard on medical device irritation tests, although it is noted that several in vitro tests in a tiered testing strategy may be needed to replace the in vivo OECD 405 test.

The NRU assay is a quantitative test to determine the potential biological reactivity of a mammalian cell culture in response to a medical device extract. It is described in Annex A of ISO 10993-5 and is one of the most commonly used methods for medical device cytotoxicity testing. The test item is extracted in cell culture medium, which is suitable for both polar and non-polar extracts. The cells are exposed to the extract, and their viability is assessed after staining with neutral red (NR) solution. The number of viable cells correlates with the color intensity determined by photometric measurements, as non-viable cells do not absorb NR. The medical device is considered non-cytotoxic if the percentage of viable cells is ≥ 70 % of the untreated control.

Sterility testing measures the growth of microorganisms on a product after the product has been sterilized. ISO 11737-2 is a harmonized standard for evaluating the sterility of medical devices by the EU Medical Device Regulation, as well as an FDA-recognized consensus standard for supporting 510(k) submissions. A sterile device or product is free from viable microorganisms. The purpose of sterilization is to inactivate microbiological contaminants to transform devices from a non-sterilized to a sterilized state. Sterility can be assessed when defining, validating, or maintaining a sterilization process. Testing according to ISO 11737-2 includes method validation by determining the initial bacterial count of control suspensions and testing the suitability of the culture media for aerobic and anaerobic bacteria and fungi. Also, the suitability of the test for the specific product is assessed. This example testing package includes the following: Testing of 3 identical specimens, Detecting the presence of aerobic and anaerobic microbes and fungi (yeast and molds), Validation of the sterility determination technique, The results are given as negative (no growth observed) or positive (growth observed). The price includes one result per micro-organism per product.. We can also offer a custom sterility test package for your needs, especially for large sample volumes. Please ask our experts for a quotation and estimated turnaround time