Testing for Biotin Interference in In Vitro Diagnostic Devices Using Biotin/Avidin Technology

What You Need to Know? 👇

What biotin concentration should be tested for interference in IVD devices?

FDA recommends testing biotin interference up to 3500 ng/mL, which is three times the maximum expected clinical concentration. This level reflects current trends in biotin consumption from dietary supplements and follows CLSI EP07 guidelines for comprehensive interference testing.

Which IVD devices are affected by biotin interference?

IVD devices that use biotin/avidin technology are susceptible to biotin interference. This includes hormone tests, cardiac markers like troponin, and other assays that utilize biotin’s ability to bond with specific proteins for detection and measurement purposes.

What information must be included in IVD labeling regarding biotin interference?

Labeling should include the percent difference or bias at each tested concentration for both qualitative and quantitative assays, and the consequence of biotin interference (falsely elevated or depressed results). This information helps clinical laboratories and clinicians interpret results appropriately.

When should manufacturers contact FDA about biotin interference?

Sponsors should contact the appropriate CBER or CDRH review division when biotin interference is demonstrated at clinically relevant analyte and biotin concentrations in patient samples. This ensures proper regulatory oversight and risk mitigation strategies.

What testing standards should be followed for biotin interference studies?

FDA recommends following designs similar to CLSI EP07 (Interference Testing in Clinical Chemistry). Studies should include analyte levels near medical decision points and determine the biotin concentration threshold where no interference occurs.

Why is biotin interference a clinical concern for IVD devices?

High biotin levels from dietary supplements can cause falsely high or low test results, potentially leading to inappropriate patient management or misdiagnosis. Consumer use of high-dose biotin supplements has created plasma levels exceeding traditional testing parameters.

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What You Need to Do 👇

Recommended Actions

1. Implement biotin interference testing following CLSI EP07 guidelines
2. Test biotin interference up to 3500 ng/mL concentration
3. Determine the no-interference concentration level for susceptible assays
4. Update device labeling to include comprehensive biotin interference information
5. Contact FDA if interference is found at clinically relevant concentrations
6. Develop additional mitigation strategies beyond labeling if significant patient risk exists
7. Ensure test samples include analyte levels near medical decision points
8. Document and communicate all interference testing results to end-users

Key Considerations

Clinical testing

• Samples should include analyte levels near medical decision point(s)
• Testing should follow designs similar to CLSI EP07 guidelines
• Biotin should be evaluated up to 3500 ng/mL (3x maximum expected clinical concentration)

Labelling

• Must include information on biotin interference
• Should state percent difference or bias at each concentration tested
• Should indicate consequence of biotin interference (falsely elevated/depressed)
• Should communicate findings to clinical laboratories and clinicians

Safety

• For assays susceptible to biotin interference at concentrations less than 3500 ng/mL, determine the concentration at which no interference is detected
• Additional mitigation strategies may be needed when risk of incorrect results could significantly affect patient health

Other considerations

• Sponsors should contact CBER or CDRH review division if biotin interference is demonstrated at clinically relevant concentrations
• Labeling alone may not be sufficient to mitigate risks in all cases

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Relevant Guidances 🔗

• In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements
• Migration Studies for In Vitro Diagnostic Devices Moving to New Systems

Related references and norms 📂

• CLSI EP07: Interference Testing in Clinical Chemistry; Approved Guideline

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Original guidance

• Testing for Biotin Interference in In Vitro Diagnostic Devices Using Biotin/Avidin Technology
• HTML / PDF
• Issue date: 2020-10-16
• Last changed date: 2021-06-11
• Status: FINAL
• Official FDA topics: Medical Devices, Blood, IVDs (In Vitro Diagnostic Devices), Biologics, Blood Products
• ReguVirta ID: 2afbc35ebbc2998543363ca7ac2da721