Biocompatibility refers to the ability of a medical device to perform its intended function in contact with the body without eliciting an adverse reaction or compromising normal tissue functions. Internationally recognized guidelines for evaluating biocompatibility are outlined in the ISO 10993 standard series, which requires manufacturers to assess all relevant biocompatibility endpoints. While the assessment does include a review of existing safety data, some additional testing according to ISO 10993 is typically required to demonstrate the biological safety of new medical devices and to bring them to market in the EU, the US, and other major markets.
Measurlabs offers a comprehensive selection of accredited and GLP-certified biocompatibility tests, helping manufacturers comply with the EU Medical Device Regulation (MDR) and FDA 510(k) premarket submission requirements. Our experts are also happy to assist in choosing the most appropriate tests and finding the best testing strategy for your device.
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The ISO 10993 standard family
The general principles for conducting a biocompatibility evaluation are outlined in Part 1 of ISO 10993, which also emphasizes the importance of creating a structured biological evaluation plan (BEP) to document any biological risks inherent to the device and the way they are addressed.1 Some of the subsequent parts provide further guidance on specific aspects of the evaluation, such as animal welfare or sample preparation, while others describe concrete test methods for evaluating different biocompatibility endpoints.
Table 1 provides an overview of selected ISO 10993 standards and the types of devices that typically require testing. You can click the standard numbers for more detailed descriptions of each test, along with indicative pricing.
Table 1: Overview of selected ISO 10993 biocompatibility tests
Standard | Scope | Applicable devices* |
Cytotoxicity | All new medical devices in direct or indirect body contact** | |
Sensitization | All new medical devices in direct or indirect body contact** | |
Irritation | All new medical devices in direct or indirect body contact** | |
Chemical characterization | All new medical devices in direct or indirect body contact | |
Toxicological risk assessment | Devices found to release chemicals above specified safety thresholds during chemical characterization | |
ISO 10993-3 | Genotoxicity, carcinogenicity, and reproductive toxicity | Devices in long-term contact with mucosal membranes or breached surfaces, or long-term indirect contact with blood. Devices that contact circulating blood (any duration) or tissue, bone, or dentin (other than transient contact).*** |
Hemocompatibility | Devices in direct or indirect contact with blood | |
ISO 10993-6 | Implantation effects | Implantable devices and other devices in non-transient direct contact with mucosal membranes, breached surfaces, blood, tissue, bone, or dentin. Devices in indirect long-term contact with the blood path*** |
Ethylene oxide sterilization residuals | Devices sterilized with ethylene oxide | |
Systemic toxicity (acute, subacute, or chronic), material-mediated pyrogenicity | Implantable and externally communicating devices, surface devices in contact with breached surfaces (any duration) or mucosal membranes (short or long-term)*** |
* These are examples of the types of devices that typically require testing. The final decision on whether or not testing is necessary to address any given biocompatibility endpoint depends on several factors, including device characteristics and pre-existing safety data documented in the biological evaluation plan.
** Together, these tests are commonly known as the “Big Three” in biocompatibility testing.
*** Contact duration definitions: transient (≤24 h), short-term (24 h–30 days), long-term (>30 days).
Formulating a biocompatibility testing strategy
As shown in Table 1, the extent of biocompatibility testing recommended by ISO 10993-1 depends on the nature of the medical device, including the type of body contact (e.g., intact skin vs. blood/tissue) and contact duration (transient, short-term, or long-term). More rigorous testing is needed when devices come into contact with blood or internal tissues for a prolonged period. Correspondingly, devices that only contact intact skin for a limited time require fewer tests.
In terms of test method selection, ISO 10993-1 states that non-animal methods, such as chemical analyses and in vitro assays, should be prioritized when they yield equally robust results to in vivo tests.2 In practice, the market area will dictate the extent to which testing can be conducted using non-animal methods, as the FDA still commonly requires in vivo testing to assess irritation and sensitization.3 In the EU, in vitro tests are often sufficient for low-risk devices.
One solution to all your biocompatibility testing needs
Measurlabs is a one-stop shop for all your biocompatibility testing needs, offering everything from the biological evaluation plan (BEP) to individual ISO 10993 tests and the biological evaluation report (BER) to summarize the findings. With experience in tailoring test plans to both EU and FDA requirements, our team can help you select the most appropriate methods for your device and market area. Use the form below to start planning your project with our experts.
References
1 See section 4 “General principles applying to biological evaluation of medical devices” of ISO 10993-1:2020.
2 In the introduction to ISO 10993-1:2020, minimization of “the number and exposure of test animals” is given as the secondary priority of the document, after serving as “a framework in which to plan a biological evaluation.”
3 The FDA does not recognize the clauses and annexes of ISO 10993-10 and ISO 10993-23 that describe in vitro methods. See more: Partial recognition of ISO 10993-10 and ISO 10993-23 on the FDA recognized consensus standard database.