While biocompatibility testing is necessary to develop safe MedTech devices, several issues complicate the process. From the initial study setup to deriving accurate conclusions, complications can arise at each testing stage. That’s bad news. Any testing obstacles can delay product launches, escalate costs, and compromise patient safety. 

In this article, we explore the most common issues that arise during biocompatibility assessments. We also share tips on overcoming these issues and developing a smoother testing process. Let’s first unpack the risks posed by testing challenges. 

Are Your Analytical Evaluation Thresholds Sensitive Enough?

Analytical Evaluation Thresholds (AETs) are critical benchmarks in the testing process that determine the lowest concentration of a substance that must be reliably identified and quantified in a sample. When performing tests, technicians need to ensure their methodologies are sensitive enough to meet the required AET. This is difficult.

Each substance extracted from a device may respond differently to various analytical methods, making it a complex task to ensure that all potential compounds are detected at the necessary levels. Uncertainty factors are used to manage this variation and ensure it’s appropriately accounted for in the AET.

The task of accurately detecting compounds is made even more complex by the increasing stringency of regulatory standards. Laboratories conducting biocompatibility testing must therefore keep pace with the latest standards and invest in advanced analytical techniques capable of meeting these evolving requirements.

Failing to meet AETs can result in an underestimation of the risks posed by a medical device, leading to harmful substances going undetected. This endangers patient safety and risks non-compliance with regulatory standards — further delaying product approvals and market entry.

So, what can you do about it? The first step involves staying up to date with the latest standards and regulations. You then need to ensure your teams have a deep understanding of analytical chemistry, thorough knowledge of the device materials, and rigorous testing protocols required to perform accurate tests.

How Do You Manage the Uncertainty Factor?

Materials are complex. They’re so complex that no two material samples are the same. Similarly, human biology is so varied that no two patients will react the same way to materials. For biological tests to have value, they need to manage the inconvenient truth that no two things are alike — and that tests are always subject to a degree of uncertainty. 

Failing to account for uncertainty factors can lead to misleading conclusions about a device's safety. It might result in the overestimation of a material's biocompatibility, overlooking potential risks that could appear in clinical settings. Conversely, excessive caution due to uncertainty might lead to unnecessary testing and resource expenditure, delaying the product development process. Exhaustive testing can also introduce additional analytical errors, especially when a large number of uncertainty factors are being managed. 

To mitigate the impact of uncertainty factors, testing protocols must be robust and comprehensive, especially as materials may respond differently to different methods. Tests should therefore use a range of scientifically validated methods, which are both broadly applicable to all potential extractables and tailored to the specific characteristics of the device. Tests should consider worst-case scenarios and be informed by the latest testing strategies, scientific knowledge, and regulatory guidelines. To save time and resources, you also need a clear idea of when biocompatibility testing is complete. 

How Confident Is Your Compound Identification?

Each material contains a multitude of compounds, including potential contaminants, degradation products, and individual chemical components. For technicians, the challenge is to detect these compounds and to accurately identify and understand them within the context of biological safety.

The limitations of current analytical technologies and the variability in compound responses add to the challenge. Identifying compounds at the trace level, for instance, demands a high degree of sensitivity and specificity that pushes the boundaries of existing methods. In many cases, there are no analytical methods capable of identifying a particular chemical at the needed concentration levels. 

While we may never get the ‘full picture,’ we can overcome the problem of compound identification by introducing confidence levels as an evaluation tool. Confidence levels are a quantifiable measure of certainty assigned to each identification made during the testing. The level of confidence for each identification needs to be backed up by data and sound reasoning. Regulators will carefully examine your confidence levels and analysis when assessing your device. 

Confidence levels also serve as a strategic solution to the broader uncertainty factor in biocompatibility testing. By assigning and justifying confidence levels, technicians introduce transparency into the testing process, where uncertainties are acknowledged and managed, rather than ignored or overlooked. 

Biocompatibility Testing Best Practices

  • Continuously Adapt to Regulatory Changes
    Stay abreast of evolving regulatory expectations, standards, and guidelines. Adapt your testing strategies accordingly to ensure compliance and maintain the highest standards of patient safety.
  • Conduct Early and Thorough Material Characterization
    Begin with a comprehensive understanding of the materials used in your device. Early material characterization helps anticipate potential issues and allows for informed decision-making throughout the development process. Consider redesigning your testing process to better evaluate specific materials and always verify supplier-provided materials. 
  • Implement Robust Analytical Methodologies
    Ensure that your laboratory is using testing methodologies that are sensitive enough to meet the required Analytical Evaluation Thresholds. This involves using advanced analytical techniques, validating these methods to ensure they are fit for purpose, and introducing appropriate controls to ensure the methods remain robust.
  • Embrace Uncertainty with Confidence Levels
    Make sure that your laboratory assigns and justifies confidence levels for each identification made. This enhances the credibility of your findings and helps navigate the inherent uncertainties in biocompatibility testing.
  • Perform Strategic Testing and Documentation
    Perform targeted testing based on a thorough understanding of your materials and their biological interactions. Document every step, from test design to result interpretation, with a clear rationale and robust data.
  • Collaborate with Expert Partners
    Close any knowledge gaps by engaging with partners who have deep expertise in the field. At RQM+, for instance, we help our MedTech partners navigate the complexities of biocompatibility testing, from material selection to regulatory submissions.

How RQM+ Can Help Improve Your Biocompatibility Tests

When performing biocompatibility tests, meticulous planning, robust methodologies, and a deep understanding of both materials and the regulatory landscape are essential to success.

This is where RQM+ can help. As a full-service CRO, RQM+ provides comprehensive testing, analysis, and validation services to support regulatory compliance. Our expert Lab Services team can help you design and perform biocompatibility tests, or navigate any complexities or challenges impacting your tests.

Speak with our experts and ensure your tests achieve and maintain regulatory compliance. Contact our team now to find out how we can support your testing process. 

We are passionate about your success. Tell us more about your regulatory and quality needs to learn about how we can help.

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