Understanding the Impact of Device Modifications on Biocompatibility Testing Needs

Medical device development is an iterative process, and modifications are often necessary due to design improvements, material changes, manufacturing optimizations, or regulatory feedback. However, even minor modifications can impact a device’s biocompatibility profile and may require additional testing. In this comprehensive guide, we explore how modifications affect biocompatibility requirements and how manufacturers can effectively manage testing needs to stay compliant while minimizing costs and delays.

1. Why Device Modifications Matter for Biocompatibility

Regulatory agencies require manufacturers to assess whether modifications impact the safety of a device. Changes that alter the biological response or introduce new risks may necessitate new or additional biocompatibility testing.

Typical modifications that may affect biocompatibility include:

• Material changes (new suppliers, alternative polymers, coatings, adhesives, or additives)
• Manufacturing process changes (new sterilization methods, different production environments, or altered surface treatments)
• Design changes (altered dimensions, different surface roughness, or additional components)
• Supplier changes (even with the same specifications, different suppliers may introduce variability)
• Changes in intended use (longer exposure durations, different patient populations, or new contact sites)

Understanding the regulatory implications of these changes is key to determining the necessary level of re-evaluation.

2. Assessing the Need for Biocompatibility Re-Evaluation

Before conducting new tests, a thorough risk assessment should be performed. The ISO 10993-1 standard outlines a structured approach to determine if additional testing is required:

• Compare with the original design – Identify differences in materials, manufacturing, or intended use.
• Use available data – Assess existing biocompatibility data for the materials and processes.
• Perform a Biological Risk Assessment (BRA) – Justify whether new testing is necessary based on scientific and regulatory rationale.
• Consult regulatory guidelines – Follow FDA, MDR, and ISO 10993 guidance on device modifications.

At NABI, our experts provide manufacturers with tailored biological evaluations to determine whether testing is required, ensuring a cost-effective and compliant strategy.

3. Key Biocompatibility Tests Affected by Modifications

When changes are made, certain biocompatibility tests may need to be repeated or newly conducted. Key areas to assess include:

• Cytotoxicity – Required if new materials, coatings, or sterilization processes could introduce cytotoxic components.
• Sensitization and Irritation – Needed if chemical composition, residuals, or contact surfaces change.
• Systemic Toxicity – Necessary if extractable chemicals from materials change.
• Genotoxicity – Required if any new material or process could introduce mutagenic risks.
• Hemocompatibility – Important for blood-contacting devices with new coatings or material compositions.
• Implantation Studies – Needed for implantable devices with modified surfaces or material properties.

By working with a trusted laboratory like NABI, manufacturers can ensure the right tests are selected without unnecessary duplication, optimizing both cost and regulatory compliance.

4. Strategies to Minimize Retesting and Costs

Manufacturers can take proactive steps to reduce unnecessary biocompatibility testing while maintaining compliance:

• Leverage material data – If a specific material from a particular manufacturer has an established safety profile, additional testing may not be required. However, this should always be evaluated in the context of the device and its intended use.
• Use chemical characterization – Extractables & leachables (E&L) testing can often justify reduced biocompatibility testing.
• Justify equivalency – Demonstrating that new materials or processes are equivalent to previously tested ones can avoid redundant testing.
• Consult your laboratory early – Engaging with NABI’s biocompatibility experts early in the modification process ensures a strategic testing plan that saves time and costs.

5. In What Modification Cases Re-Testing May Not Be Required?

Not all device modifications trigger the need for new biocompatibility testing. In certain cases, scientific justification and regulatory guidance may support using existing data to avoid unnecessary re-testing:

• Equivalent Materials – If the new material has a well-documented biocompatibility profile and is chemically identical to the previously used material, it may be considered equivalent. However, it’s important to clearly demonstrate this equivalence, which can sometimes be challenging or even impossible, depending on the material and its intended use.
• Minor Manufacturing Changes – If manufacturing process adjustments do not introduce new residuals, contaminants, or material changes.
• Same Intended Use and Exposure – If the modified device maintains the same patient contact duration, exposure type, and use conditions as the original.
• Validated Supplier Changes – If a new supplier provides the same material under identical specifications, verified through material characterization.
• Sterilization Process Adjustments – If sterilization modifications do not alter material integrity or introduce toxic by-products, as demonstrated by validation studies.

In these scenarios, a strong biological risk assessment (BRA) supported by material characterization and scientific literature can often justify that no additional testing is required. NABI provides expert guidance in preparing such justifications, helping manufacturers streamline regulatory approval while minimizing testing costs.

6. Documentation and Regulatory Submissions

When modifications are made, proper documentation is critical for regulatory submissions. Key elements include:

• Updated Biological Evaluation Plan (BEP) – A structured plan outlining the biocompatibility approach for the modified device.
• Material equivalency justifications – Scientific rationale proving new materials are comparable to previously tested ones.
• Regulatory correspondence – Documentation demonstrating compliance with FDA, MDR, and ISO requirements.

At NABI, we provide full regulatory support, ensuring that all modifications are properly documented and that regulatory submissions meet FDA and EU requirements.

7. Choosing the Right Biocompatibility Partner

Selecting the right testing laboratory is crucial for managing device modifications efficiently. NABI offers:

• Accreditations and certifications – Full compliance with FDA, ISO 17025, and GLP standards.
• Regulatory expertise – Ensuring efficient test selection and documentation.
• Cost- and time-effective solutions – Helping manufacturers avoid unnecessary testing while meeting compliance requirements.
• Comprehensive support – From biological risk assessments to final regulatory submissions.

Final Thoughts

Device modifications are an inevitable part of medical device development, but they don’t have to result in excessive biocompatibility testing or regulatory delays. By conducting thorough risk assessments, leveraging existing data, and consulting with a trusted laboratory like NABI, manufacturers can efficiently manage biocompatibility requirements while keeping costs and timelines under control.

If you’re making changes to your device and need expert guidance, NABI is here to help. Contact us to ensure your modifications remain compliant and cost-effective!

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 North American Biomedical Institute (NABI) and European Biomedical Institute (EBI). 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.