How to Align Your Biocompatibility Strategy with Both FDA and MDR Requirements

For medical device manufacturers aiming for global market access, aligning biocompatibility testing strategies with both FDA (U.S.) and MDR (Europe) requirements is crucial. While both frameworks follow ISO 10993-1 as the foundation for biological evaluation, key differences exist in regulatory expectations, documentation, and risk assessment approaches.

This guide explores how manufacturers can effectively navigate both FDA and MDR requirements to ensure compliance, streamline regulatory approvals, and avoid unnecessary testing costs.

  1. Understanding the Common Framework: ISO 10993-1

Both the FDA and MDR recognize ISO 10993-1 as the primary standard for biocompatibility evaluation. It provides a risk-based approach for determining required tests based on:

  • Device type and intended use – Whether a device is surface-contacting, externally communicating, or implantable directly affects testing needs.

  • Duration of patient contact – Biocompatibility requirements increase with exposure duration: limited (≤60 min), prolonged (24h–30d), or permanent (>30d).

  • Material composition and history of safe use – If materials have a well-documented history of safe medical use, some tests may be reduced or waived.

While the core principles are shared, differences in implementation mean that a single approach may not always satisfy both regulators.

  1. Key Differences Between FDA and MDR Biocompatibility Expectations
  2. Risk Assessment and Justification
  • FDA Approach:
    • The FDA follows a structured approach based on its biological endpoints table and expects manufacturers to address each endpoint through testing or scientific justification.
    • If chemical characterization demonstrates safety, some tests may be waived.
    • Biological effects listed in the FDA guidance tables (https://www.fda.gov/media/142959/download) must still be addressed through relevant studies.

  • MDR Approach:
    • The MDR places a stronger emphasis on comprehensive documentation.
    • The Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER) are mandatory under MDR.
    • Notified Bodies often require additional testing unless manufacturers provide a strong and well-documented scientific rationale.
    • The burden of proof is higher, meaning that even devices with known materials may still require further testing.

  1. Chemical Characterization & Extractables/Leachables (E&L) Testing
  • FDA:
    • Encourages the use of chemical characterization as a primary risk assessment tool.
    • If extractables and leachables (E&L) testing supports safety, some in vivo testing may be reduced or eliminated.

  • MDR:
    • Often mandates E&L testing even when materials have an established safety history.
    • Regulatory bodies may require additional chemical analysis to confirm safety, particularly for long-term implants or devices with complex material compositions.

  1. Biological Testing Requirements
  • FDA:
    • Biological endpoints listed in the FDA guidance must be addressed with appropriate testing or justification.
    • Some tests recognized under MDR (e.g., LLNA for sensitization or in vitro irritation) are not accepted by the FDA.

  • MDR:
    • Generally requires biological testing, especially for devices with prolonged or permanent contact.
    • Manufacturers often need to justify why a test is not performed rather than assuming a waiver will be granted.

  1. Documentation & Submission Requirements
  • FDA:
    • A formal Biological Evaluation Plan (BEP) is not mandatory but may be developed as part of an internal risk-based strategy or pre-submission discussions.
    • The FDA may expect a Biological Risk Assessment (BRA) as part of the regulatory submission.
    • All biological effects identified in FDA guidance must be either tested or scientifically justified with supporting data.

  • MDR:
    • The Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER) are mandatory parts of the technical documentation under MDR.
    • These documents must demonstrate a risk-based approach per ISO 10993-1 and show clear compliance with the General Safety and Performance Requirements (GSPR).
    • Comprehensive documentation is expected, even for materials with a known history of safe use.

  1. Strategies to Align Biocompatibility Testing with Both FDA and MDR

To create an efficient biocompatibility strategy that satisfies both regulators, consider the following:

  1. Develop a Comprehensive Biological Evaluation Plan (BEP)
  • Define test requirements upfront based on ISO 10993-1 risk assessment principles.

  • Identify and justify test selections using material data, previous studies, and clinical experience.

  • Ensure alignment with both FDA and MDR by considering regional variations in test acceptance.

  1. Utilize Chemical Characterization Proactively
  • Perform extractables & leachables (E&L) testing early to avoid unnecessary biological testing later.

  • Use chemical characterization data to demonstrate material safety and reduce redundant testing.

  • Leverage historical data from similar devices or materials to strengthen justifications for test waivers.

  1. Work with a Testing Lab Experienced in Both FDA & MDR
  • Ensure the lab understands both U.S. and EU regulatory landscapes to create a single, cost-effective testing plan.

  • Choose a partner that provides complete support, including risk assessments and regulatory consulting.

  • Look for a lab that offers strategic testing solutions to minimize redundancy while maximizing compliance.

  1. Maintain Regulatory Flexibility
  • Plan a modular testing approach, allowing additional tests to be performed as needed rather than committing to all tests upfront.

  • Engage regulatory consultants early to address differences between FDA and MDR expectations proactively.

  • Monitor regulatory updates, as MDR and FDA guidance may evolve over time.

  1. Selecting the Right Biocompatibility Testing Partner

A laboratory with expertise in both FDA and MDR requirements can help streamline your compliance strategy. When selecting a partner, look for:

  • Regulatory experience – Ensure familiarity with both U.S. and European submission requirements.

  • Accreditation – Look for ISO 17025 accreditation, GLP and FDA 21CFR58 compliance.

  • Comprehensive support – A lab that offers risk assessments, documentation preparation, and regulatory consulting.

Final Thoughts

Harmonizing your biocompatibility strategy with both FDA and MDR requirements can be complex, but with the right approach, manufacturers can optimize testing, reduce costs, and accelerate market approval.

At NABI, we specialize in biocompatibility testing that meets both U.S. and European regulatory expectations. Our expertise ensures that your testing strategy is efficient, compliant, and tailored to your global market needs. Contact us today to streamline your path to approval.

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 NABI – North American Biomedical Institute and EBI – European 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.

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