AACC Calls on Laboratories to Take Measures to Minimize Risks of Biotin Interference

Biotin interference with test accuracy has become a matter of growing concern in recent months. Last November, the U.S. Food and Drug Administration (FDA) updated a previous safety communication warning laboratory personnel, diagnostic test developers, providers and patients that biotin can lead to incorrect laboratory test results. And now the laboratory community has responded with the American Association for Clinical Chemistry (AACC) issuing new guidance to help clinicians, laboratory professionals and patients keep biotin from interfering with test results.

Biotin Blinding

Biotin, or Vitamin B7, is a water-soluble vitamin commonly used as an ingredient in multi-vitamins, prenatal vitamins and dietary supplements that are marketed for hair, skin and nail growth. Biotin’s property of bonding with specific proteins that can be measured to detect certain health conditions, make it a natural for laboratory testing. For example, biotin is a key ingredient in many immunoassays.

The problem with biotin-based detection methods and technology is that biotin can also distort laboratory test results and generate both false highs and false lows. This is especially true when testing is performed on patients that consume high levels of biotin. And because of B7’s widespread use in commercial products, high biotin consumption is far from unusual. At least 20 percent of Americans take biotin in some form, according to the AACC.

FDA Reaction to Biotin Interference

In 2017, the FDA issued a safety communication addressing biotin interference with certain in vitro diagnostic tests and has since issued recommendations for laboratory personnel and test manufacturers to minimize the potential for interference. The FDA expressed specific concern about biotin interference resulting in falsely low levels of troponin—the biomarker that aids in diagnosis of heart attacks. Misleading diagnoses as a result of incorrect laboratory results could lead to potentially serious clinical implications, the FDA cautioned.

Since the 2017 safety communication, some laboratory test developers have been successful at minimizing biotin interference of their assays, according to the updated safety communication, but others have not yet addressed it. The troponin problem remains of particular concern as the FDA continues to receive adverse events reports indicating that biotin interference caused falsely low troponin results.

Accordingly, the agency resounded the alarm in November by issuing new and more specific guidance. For more details, see Diagnostic Tests & Emerging Technologies (DTET), Jan. 2, 2020.

AACC Biotin Communication Recommendations

The AACC Guidance Document on Biotin Interference Laboratory Tests guidance explains the mechanics and extent of the problem in clinical detail. It calls on laboratories to determine which of their immunoassays may be affected by biotin interference and educate clinicians and patients about their findings. Recommended methods of communicating with the former include the use of formal memos and laboratory bulletins and participation in conferences and clinical rounds. Methods of notifying patients could include the use of placards in outpatient phlebotomy centers, with information on biotin use. Other suggestions:

• Healthcare systems could include questions about the use of biotin and nutritional supplements during the inpatient/outpatient registration process;
• Clinicians could ask patients about their use of food supplements and explain the relevance;
• Electronic health records could be updated to display an alert to clinicians at the time of test order whenever tests with known biotin interference are ordered; and
• Clinicians should contact the laboratory when laboratory results do not fit the patient’s clinical picture or if the patient is known to have consumed a dose of biotin of more than 5 mg.

AACC Verification Recommendations

The AACC says laboratories should also take measures to verify suspected biotin interference. Recommended methods:

• Use of a specimen diluent for the assay;
• Removal of excess biotin via streptavidin-coated beads; and
• Biotin quantification via chromatography (LC-MS/MS) or other procedure.

Ideally, a specimen suspected of biotin interference should be analyzed with a different assay that does not use biotin in its format, according to the AACC guidance. Alternatively, the laboratory may request a new specimen after the patient has abstained from biotin for a time.

Recommendations for Patients

Patients also need to play a role in preventing biotin interference, starting with being aware of the problem and their own biotin intake levels. The AACC’s recommendations:

• Patients who have consumed 5–10 mg biotin should wait at least eight hours before having blood collected for laboratory tests;
• Longer washout periods of up to 72 hours may be required to prevent interference in assays with interference thresholds <30 ng/mL (<122.8 nmol/L); and
• Unless medically contraindicated, patients prescribed a high-dose biotin therapy (≥100 mg/day) should abstain from biotin for at least 72 hours before blood collection. ;

Laboratories and clinicians also need to keep in mind that patients with renal impairment may exhibit higher circulating biotin concentrations and prolonged elimination rates. The AACC also recommends against reporting patient results after dilution or biotin removal unless the procedure has been validated by the laboratory.

Takeaway

“The recent increase in the use of high-dose biotin supplements requires that laboratorians and clinicians be mindful of the potential for biotin interference in biotinylated immunoassay-based laboratory tests,” noted the AACC guidance document authors Danni Li, Angela Ferguson, Mark Cervinski, Kara Lynch and Patrick Kyle in a statement. “Ideally, manufacturers will reformulate assays that are sensitive to biotin. Given that the timeline from initial assay design to reformulation and governmental approval requires months to years, laboratorians and clinicians will have to remain mindful of this issue for some time to come … [and] should work together to ensure accurate laboratory results.”