March 25, 2021
What If…. I Fail Cytotoxicity
Cytotoxicity is a biocompatibility test that every single medical device and material needs to undergo during its development. It is a critical test to ensure that your device or the materials in your device do not cause cell death or inhibit cell growth. So, what happens if your device fails this crucial first test?
Why It Failed
The first critical step after a cytotoxicity failure is establishing why the device failed. Since cytotoxicity tests are so sensitive, there are a variety of common reasons a failure could occur, ranging from your device containing a cytotoxic material to improper sample preparation or a manufacturing process.
To determine why the device failed, it is critical to understand if the entire device caused the problem or if a single component did.
To isolate the component that is triggering the failure, you need to break out your device and evaluate the individual components for cytotoxicity. Once you identify the problematic component, you can move forward in addressing the failure.
The question that needs to be addressed is should this component have been included in testing? If it is not a patient contacting piece of your device and/or was only exposed due to cutting your device during sample preparation, then you should review your sample preparation instructions provided to the lab, and if needed, revise them to exclude the component from testing. However, if this piece is patient contacting, then you need to continue to evaluate the failure.
Risk Assessments & Chemical Characterization
If you determine that the component causing the failure is patient contacting and was appropriately included in testing, then it may be time to conduct a chemical characterization study for the component to understand what is in the material as often unexpected materials will be found.
Once you know what is in your component, you can evaluate whether you can determine if the cytotoxic material is occurring during manufacturing or is in the material, and in that case, further evaluation through a risk assessment.
A trained toxicological risk assessor will be able to look at the data generated from your chemical characterization study and determine the level of risk your device presents to the patient based on established Safety Thresholds (SCTs) for the type and length of exposure of your device to the patient and compare it to similar predicate devices already on the market. From there, you will know if the material needs to be replaced or if it falls within the safety limits.
Your Devices Purpose
The final piece to consider when you are evaluating a cytotoxicity failure is what is the context of the device being evaluated; some devices are designed to be cytotoxic. If your device contains an anti-microbial component or is used for wound healing and is expected to keep an infection at bay, then in these cases, a failure can often be triggered as these devices are intended to prevent growth.
For these types of devices, you can prepare a justification as to why the device failed cytotoxicity. Furthermore, conducting a follow-up acute systemic toxicity study can provide data needed to show that although the device is cytotoxic, it is not toxic systemically, even at large doses.
Failing a cytotoxicity test can throw a wrench in the development of your device, so it is important to know how to react when it happens. Failures are not uncommon and moving deliberately will help you isolate the problem and determine how to best move forward from the failure.
ISO 10993-5:2009 – Biological evaluation of medical devices — Part 5: Tests for in vitro cytotoxicity