Why a Risk-Based Approach to Biocompatibility Saves You Time and Money

In the realm of medical device development, ensuring biological safety is essential to protect patient health and to comply with regulatory requirements. However, the traditional approach of performing a full battery of biocompatibility tests for every new device iteration is no longer sustainable.
Modern regulatory frameworks, including ISO 10993-1:2023 and the European Medical Device Regulation (MDR 2017/745), endorse a risk-based approach — a strategic, scientific methodology that streamlines biological evaluations without compromising patient safety.

Adopting a risk-based approach can significantly reduce the time and cost associated with market access while maintaining regulatory compliance and scientific credibility.

This article outlines the foundations, implementation strategies, and tangible benefits of a risk-based approach to biocompatibility for medical device manufacturers.

 

1. Understanding the Risk-Based Approach in Biocompatibility

A risk-based approach means making biological safety decisions based on a structured assessment of the specific risks associated with the device’s materials, design, intended use, and manufacturing processes — rather than automatically conducting exhaustive biological testing.

Key principles include:

• Evaluating the nature and duration of body contact
• Understanding material composition and processing
• Leveraging existing chemical and biological data
• Conducting chemical characterization to identify potential hazards
• Performing toxicological risk assessments where appropriate
• Designing targeted biological testing only when necessary

This systematic evaluation aligns with ISO 14971 principles for general medical device risk management and integrates biological risk into the broader device risk profile.

 

2. Regulatory Endorsement of the Risk-Based Approach

Both European and U.S. regulatory frameworks strongly encourage a scientific, risk-based strategy for biological evaluation:

• ISO 10993-1:2023 explicitly states that unnecessary animal testing should be avoided and that scientific rationale can replace testing where justified.

• European MDR (Annex II and Annex III) requires manufacturers to document a thorough biological evaluation as part of the device’s technical file.

• FDA guidance (Use of ISO 10993-1) also supports minimizing testing through well-documented risk assessments and leveraging existing data.

Importantly, a poorly justified or incomplete risk assessment can delay regulatory approvals just as much as missing biological tests. The risk-based approach must be methodical, well-documented, and scientifically defensible.

 

3. Core Elements of an Effective Risk-Based Biological Evaluation

To execute a risk-based approach effectively, manufacturers must integrate the following elements:

3.1 Thorough Material Characterization

Every material and substance that contacts the patient must be fully characterized chemically. Unknowns are risks; regulators expect comprehensive material data and extractables/leachables studies when necessary.

3.2 Toxicological Risk Assessment

A toxicologist evaluates chemical constituents against known toxicological thresholds to determine if potential patient exposure exceeds safe limits. A Margin of Safety (MoS) is calculated to support risk acceptability.

3.3 Critical Assessment of Existing Data

Historical biocompatibility data, literature, and clinical experience can sometimes obviate the need for new biological tests — provided that:

• Material equivalence is demonstrated
• Processing and sterilization conditions are unchanged
• Clinical use scenarios are similar

Data must be current, relevant, and appropriately validated.

3.4 Gap Analysis and Justification

Identify any data gaps systematically and provide scientific justifications for why no further testing is necessary — or outline plans for targeted testing if needed.

3.5 Targeted Testing Only When Necessary

Biological tests should be performed only when specific risks are identified that cannot be otherwise mitigated through material characterization or risk assessment. Testing should be strategically chosen to address critical endpoints.

 

4. Benefits of a Risk-Based Approach

4.1 Reduced Time to Market

Strategically avoiding unnecessary testing saves months in the regulatory pathway. Biological testing — especially for complex endpoints like implantation or systemic toxicity — can be time-consuming and resource-intensive.

4.2 Lower Development Costs

Comprehensive biological testing programs can cost tens of thousands of euros or dollars. A well-structured risk-based evaluation reduces these costs significantly by focusing only on scientifically necessary activities.

4.3 Enhanced Scientific Credibility

A well-argued biological risk assessment demonstrates technical competency to regulators, increasing confidence in the overall device safety profile and reducing the likelihood of additional questions or deficiencies during review.

4.4 Ethical Compliance

Minimizing unnecessary animal testing aligns with the “3Rs” principle (Replacement, Reduction, Refinement) endorsed in ISO standards and by regulatory agencies globally.

 

5. Common Pitfalls in Risk-Based Approaches — and How to Avoid Them

While the benefits are clear, poorly executed risk-based strategies can result in regulatory setbacks. Common pitfalls include:

• Insufficient chemical characterization, leading to gaps regulators cannot overlook

• Over-reliance on material declarations without independent verification

• Inadequate toxicological assessments, lacking proper thresholds or rationales

• Failure to update evaluations after manufacturing or design changes

• Poor documentation, making it difficult for regulators to follow the risk logic

To avoid these issues, manufacturers must apply rigorous scientific methods, involve qualified toxicologists, and ensure that every risk-based decision is traceable and justified.

 

Conclusion

A risk-based approach to biocompatibility is not a shortcut — it is a structured, scientifically grounded strategy that aligns with global regulatory expectations and modern quality management principles.
When implemented correctly, it significantly reduces development timelines and costs, minimizes unnecessary testing, and enhances the regulatory defensibility of the device’s biological safety.
Medical device manufacturers who embrace risk-based biological evaluations are not only ensuring compliance but are also optimizing innovation, patient safety, and market success.

 

About the Author: Prof. Łukasz Szymański

 

Prof. Łukasz Szymański is an expert in medical device biocompatibility testing, serving as the Chief Scientific Officer (CSO) of the ISO 17025-accredited and GLP-certified European Biomedical Institute (EBI) and North American Biomedical Institute (NABI). As a dedicated researcher and a key contributor to advancing safety standards in the biomedical field, Prof. Szymański plays an integral role in shaping scientific innovations and regulatory compliance within the industry.