Medical Plastic Data Service Magazine



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Cover Story

More Than Materials: A Risk-Based Framework For Biocompatibility Assessment

(Courtesy : Lubrizol Life Science Driven by Innovation, Powered by Partnership)


The safety of a medical device is of utmost concern and importance at all times during its development, manufacturing, regulatory submission and use. One critical step in establishing the safety of a device is to evaluate how the device interacts with the body. This is better known as the device biocompatibility. Evaluation of biocompatibility can be a complex topic involving many considerations, starting from the materials of construction through device design, processing, sterilization and
intended use. The evaluation can be at the material level and the device level.

At the material level, USP Class VI is a group of tests developed to evaluate materials intended for use in medical applications. These rigorous tests evaluate materials and their extractable substances for the potential to cause toxicity and irritation. The process provides basic assurances that the materials are not inherently toxic when used in medical applications. The tests include three in vivo biological reactivity evaluations, generally performed on mice or rabbits to
mimic use in humans.

ISO 10993 is a standard that covers evaluation of medical devices that come into direct or indirect contact with the human body for biocompatibility using a risk-based approach. The biological evaluation of the devices (and their materials of construction) based on the overall device risk depends on a large number of considerations, which are explored in part 1 of ISO 10993 (ISO 10993-1) and in the FDA’s recently finalized updated guidance document on this standard.


Device makers’ materials suppliers may be helpful in conducting the evaluations at both the material and device levels.

A risk-based approach

ISO 10993 guidance emphasizes using a risk-based approach. What exactly is a “risk-based approach?”

ISO 14971 defines the term “risk” as “the combination of the probability of occurrence of harm and the severity of that harm.” The standard defines harm primarily as physical injuries and damage to health, but it also includes harm to goods and to the environment.

The risk-based approach adds the harm resulting from regulatory non-compliance and bureaucracy. It is about weighing the likelihood and the consequence of the identified risks and adapting the expenditure of resources accordingly.

As stated in ISO 10993-1 (page 9), “The biological evaluation of a medical device (or a material component of such) should be conducted within the framework of a risk management process. Such a process should generally begin with assessment of the device, including the material components, the manufacturing processes, the clinical use of the device including the intended anatomical location, and the frequency and duration of exposure. Considering this information, the potential risks from a biocompatibility perspective should be identified. Once the risks have been identified, the [OEM] should assess what information is already available regarding those risks and identify the knowledge gaps that remain. Considering the potential biological impact, a plan should be developed to address the knowledge gaps either by biocompatibility testing or other evaluations that appropriately address the risks.” The new, risk-based guidance moves away from a check-the box approach to biocompatibility testing. One of the FDA’s goals is to reduce unnecessary testing, particularly animal testing, by giving preference to chemical constituent testing and in vitro models where these methods yield equally relevant information.

As intended by the FDA, more OEMs seem to be adopting chemical characterization assessments as part of their biocompatibility evaluation process. If an OEM has a good, comprehensive chemical and physical characterization of a material, it may not be necessary to conduct testing for all or a portion of the biocompatibility endpoints suggested by the FDA.

Chemical assessments

Because an understanding of all the chemicals that could contact a patient during the use of a device is critical to the evaluation of biocompatibility, a chemical assessment of the device and its materials of construction may be informative. This assessment may be needed not only during initial development of the device, but also upon any changes, such as manufacturing process or material supply changes. An OEM’s material supplier can support the OEM’s chemical assessment in two ways:

• by providing information on chemical composition
• by providing guidance to ensure materials are converted with minimal chance for degradation or creation of unintended byproducts during the OEM’s processing and sterilization cycles

For example, some thermoplastics contain chemical building blocks that are susceptible to degradation under extreme environmental conditions. The high heat, temperature, and pressure of an autoclave can degrade some thermoplastics and create potential for harmful byproducts. So, even though the material coming from the supplier passes all the biocompatibility testing, the sterilization process should be carefully considered to prevent creation of additional risk.

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