What Happens If Your Medical Device Fails Biocompatibility Testing? Manufacturer’s Next Steps

Biocompatibility testing is a critical step in medical device development, ensuring that the materials and components used do not cause adverse biological reactions in patients. But what happens if your device fails? A test failure can be a significant hurdle, but it doesn’t necessarily mean the end of your project. Understanding the reasons behind a failure and taking the right corrective actions can help you navigate this challenge effectively.

1. Understanding the Reasons for Failure

Biocompatibility failures can arise from multiple factors. Identifying the root cause is essential for developing a remediation strategy. Common reasons include:

• Material-Related Issues: Some materials, although previously used in medical applications, may still cause unexpected biological reactions due to impurities, surface modifications, or differences in supplier formulations. Inadequate material selection can lead to cytotoxicity, irritation, or sensitization failures.

• Manufacturing Residues & Contaminants: Residual processing aids, cleaning agents, sterilization byproducts, or leachable substances can interfere with test results. Even small traces of contaminants can lead to test failure, particularly in extractables and leachables (E&L) studies.

• Improper Test Selection: Choosing an incorrect test method or an unnecessary test can yield misleading failure results. For example, aggressive extraction conditions in chemical characterization testing may generate artifacts that do not occur under actual clinical use conditions.

• Device Design Changes: Any modifications to a device’s materials, coatings, or manufacturing process can introduce new biocompatibility risks. Even changing suppliers for a seemingly identical raw material can impact test results.

2. Immediate Actions to Take After a Failure

Once a failure occurs, follow these structured steps to minimize delays and costs:

• Consult Your Testing Laboratory: Engage in a detailed discussion with your biocompatibility testing partner to review failure data, identify potential reasons, and strategize the next steps. Testing experts can often provide insights into whether a failure is due to a true biocompatibility issue or an artifact of the test conditions.

• Review Your Material Selection: Analyze whether the failure is linked to a specific material or formulation component. Consider switching to materials with a proven history of safe medical use or conducting additional chemical characterization to better understand material composition.

• Assess Manufacturing Processes: Investigate whether contamination occurred during production, packaging, or sterilization. Reviewing cleaning protocols, material handling, and supplier quality controls can help pinpoint contamination sources.

• Consider Repeat Testing or Alternative Methods: Some failures may be due to test variability rather than an inherent problem with the device. Repeat testing with modified extraction conditions or alternative assessment methods (e.g., in vitro instead of in vivo testing) may be warranted.

3. Developing a Corrective Action Plan

A strategic approach is key to resolving failures efficiently:

• Perform a Root Cause Analysis (RCA): Use a systematic approach to identify whether the failure stems from material composition, processing residues, sterilization effects, or an unexpected interaction between components.

• Modify Device or Manufacturing Process: If a specific material or process step is identified as the root cause, adjust formulations, surface treatments, or sterilization parameters to eliminate the adverse biological response.

• Reassess Biological Evaluation Plan (BEP): Update your biological evaluation strategy to ensure it aligns with ISO 10993-1 requirements while avoiding unnecessary testing. This may involve adjusting chemical characterization thresholds or selecting different biocompatibility endpoints.

• Justify Changes for Regulatory Compliance: Document all corrective actions thoroughly, providing scientific justifications for any modifications or test exemptions to facilitate regulatory approval.

4. Regulatory Considerations and Next Steps

Depending on the market you are targeting, regulatory agencies will expect:

• A risk-based approach to biocompatibility: Justifications for test waivers, material changes, or alternative assessments must be well-supported with scientific data.

• Comprehensive documentation: Any modifications, alternative testing approaches, and risk assessments must be clearly reported in a Biological Evaluation Report (BER) or equivalent regulatory submission.

• Proactive communication with regulators: Engaging with regulatory authorities early—such as through FDA pre-submission meetings or EU Notified Body consultations—can help streamline the approval process and minimize regulatory pushback after a failed test.

Final Thoughts

Failing a biocompatibility test does not mean project failure. With a structured approach and support from an experienced laboratory like EBI, manufacturers can identify issues, implement solutions, and achieve regulatory compliance efficiently. If you need expert guidance, EBI is here to help with strategic testing, corrective actions, and regulatory support.

About the Author: Dr. Damian Matak

Dr. Damian Matak – an expert in medical device biocompatibility testing, serving as the CEO of ISO 17025-accredited and GLP-certified laboratories, including EBI – European Biomedical Institute and NABI – North American Biomedical Institute. As a member of the Polish Society of Toxicology and the I Local Ethical Committee, Dr. Matak contributes significantly to advancing safety standards in the biomedical field.