Immunological Testing for Medical Devices: Evaluation and Assessment of Adverse Effects

What You Need to Know? 👇

What is immunotoxicity testing and why is it required for medical devices?

Immunotoxicity testing evaluates adverse effects of medical devices on the immune system structure or function. It’s required to assess risks like hypersensitivity, immunosuppression, chronic inflammation, immunostimulation, and autoimmunity that could impair host defense or cause tissue damage.

When is immunotoxicity testing not required for medical device materials?

Testing may not be needed if the device material is identical to a legally marketed device with same body contact, dose, and duration, plus has a long history of safe use or published safety data supporting lack of toxicity.

What are the five main immunotoxic effects evaluated in medical device testing?

The five effects are: hypersensitivity (allergic reactions), chronic inflammation, immunosuppression (reduced immune function), immunostimulation (inappropriate immune activation), and autoimmunity (immune response against body’s own tissues).

How does contact duration affect immunotoxicity testing requirements?

Contact duration is classified as Limited (<24 hours), Prolonged (24 hours to 30 days), or Permanent (>30 days). Longer contact durations typically require more comprehensive immunotoxicity testing across multiple immune system parameters.

What types of tests are considered most reliable for immunotoxicity assessment?

Functional assays are most important, including guinea pig maximization test, mouse local lymph node assay, immunoassays for antibody response, and phagocytosis tests. These provide direct measures of immune system activity rather than just biomarkers.

Is routine autoimmunity testing recommended for all medical device materials?

No, routine autoimmunity testing is not recommended. Testing for autoimmune disease induction should only be considered in rare cases where long-term biomaterial use is suspected of causing autoimmune disease in humans, requiring FDA consultation.

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What You Need to Do 👇

Recommended Actions

1. Use the flow chart to determine if immunotoxicity testing is needed
2. Review existing data and history of use before conducting new tests
3. Use Tables 1-3 sequentially to determine appropriate testing when needed:
   • Table 1: Identify potential immunotoxic effects based on device contact and duration
   • Table 2: Determine critical immune responses to evaluate
   • Table 3: Select appropriate tests based on identified responses
4. Focus on functional assays over soluble mediators and phenotyping
5. Ensure statistical validity in study design
6. Consider consulting with FDA immunologists/immunotoxicologists when needed
7. Document and evaluate any signs of immune system dysfunction
8. Include immune function studies in clinical trials if preclinical testing shows significant immunotoxicity

Key Considerations

Non-clinical testing

• Use appropriate animal models as they may provide a more accurate picture of immune system competence
• Ensure sound statistical basis in study design (p<0.05 level)
• Mimic intended use regarding exposure route, dose and duration
• Consider host resistance assays to bacteria, viruses and tumors

Biocompatibility

• Evaluate five main immunotoxic effects:
  • Hypersensitivity (Type I and IV reactions)
  • Chronic inflammation
  • Immunosuppression
  • Immunostimulation
  • Autoimmunity
• Consider material type (plastics, metals, ceramics, biological materials)
• Consider duration of body contact (limited, prolonged, permanent)

Safety

• Monitor for signs of immune system dysfunction
• Document any signs of illness (allergy, skin rash, urticaria, edema, lymphadenopathy)
• Evaluate functional assays as they provide more direct measure of immune system activity

Other considerations

• Use available data when possible to minimize testing
• In vitro tests can be used if scientifically justified
• Focus on standardized and commonly used reliable tests
• Consider discussing proposed testing with FDA

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Relevant Guidances 🔗

• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Chemical Analysis in Medical Device Biocompatibility Assessment (Draft)

Related references and norms 📂

• ISO 10993: Biological Evaluation of Medical Devices-Part 1: Evaluation and Testing

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Original guidance

• Immunological Testing for Medical Devices: Evaluation and Assessment of Adverse Effects
• HTML
• Issue date: 1999-05-05
• Last changed date: 2020-03-18
• Status: FINAL
• Official FDA topics: Medical Devices, Premarket
• ReguVirta ID: 487d5fa274d43e4a3f01df2e579200ec