FDA Warns About Biotin Interference With Lab Tests

In late November the U.S. Food and Drug Administration issued a safety communication warning that the supplement biotin (Vitamin B7) may interfere with laboratory testing results. The warning comes after Roche Diagnostics (Indianapolis, Indiana) published a study online Sept. 14 in the International Journal of Pharmacokinetics demonstrating that an eighthour wait time or washout period is necessary for accurate test results when using streptavidin–biotin immunoassays following high doses of biotin (more than 5 mg/day).

The FDA says it has received a report that one patient taking high levels of biotin died following falsely low troponin results on a test for heart attacks known to have biotin interference. There have been previous case reports of biotin interference leading to incorrect diagnoses in both adults and children, particularly for cardiovascular diagnostic tests and hormone tests. However, there is increasing use of over-the-counter (OTC) biotin supplements that purportedly strengthen hair, skin, and nails. These products range in biotin doses from 50 μg in multivitamin to as high as 10 mg in some biotin-only products. The FDA notes these high-dose OTC products may contain biotin levels up to 650 times the recommended daily intake of biotin (30 μg/day). Additionally, physicians recommend extremely high doses for treatment of neuropathy and multiple sclerosis. Thus, there is increasing evidence that the risk of biotin interference with laboratory testing is also increasing.

FDA Recommendations for Laboratories

In order to cut the risk of adverse events associated with biotin interference with laboratory tests the FDA is recommending that laboratory personnel:

• Be aware that biotin levels higher than the recommended daily allowance may cause significant interference with affected lab tests

• Communicate with health care providers and patients regarding use of assays with biotin technology

• At draw centers, ask patients if they are taking biotin

• Educate health care providers about biotin interference with specific tests

• Communicate with the lab test manufacturer if you have questions about biotin interference

High-sensitivity immunoassays made by companies like Abbott, Beckman Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics are all susceptible to biotin interference. Excess biotin in patient samples can result in falsely high test results with competitive assay design and falsely low results with sandwich assay design. The study in the International Journal of Pharmacokinetics found that manufacturers provide a "spectrum of guidance" in package inserts ranging from no mention or vague generic warnings of biotin interference to comprehensive specification on serum biotin concentrations.

The Roche study sought to characterize the pharmacokinetic properties of biotin and establish a model simulating the effective half-life of biotin and biotin metabolites with different high-dose regimens (1 mg daily to 300 mg). Participants were divided into three different dosing groups (5, 10 or 20 mg taken orally once a day) for five days. Participants were required to fast for 8 hours prior to and 1 hour after biotin intake and blood samples were collected prior to biotin intake on days 1, 2, and 7, and at 1, 3, 6, 8 and 12 hours postdose on days 3 and 7. Samples were analyzed using the cobas e 411 analyzer (Roche Diagnostics) using an in-house competitive Elecsys research assay. The researchers identified the necessary washout periods for biotin concentrations to reach thresholds ranging from 10 to 100 ng/mL.

"It is important for clinicians and pathologists to be aware of which immunoassays are streptavidin-biotin-based and therefore when an abnormal result may be the result of interference and require repeat analysis before a diagnosis is made," write the authors led by Paul Grimsey, from Roche Innovation Center in the United Kingdom. "It is important to understand the time taken for the serum biotin concentration to fall below a specific threshold, to allow calculation of the washout period required before collection of serum samples for assessment using biotin-streptavidin based assays."

The researchers found that biotin has linear pharmacokinetics over the range of doses studied, is rapidly absorbed with a maximum serum concentration of less than 1 hour, and has an effective serum half-life of 15 hours.

• For biotin doses up to daily doses of 1 mg (e.g., in a multivitamin) serum biotin levels fall below an in vitro threshold of 10 ng/ml (one of the lowest recommended biotin interference thresholds) after 2 hours.

• For doses of biotin of up to 10 mg/day, an in vitro serum biotin threshold of 30 ng/ml could be consistently reached after 8 hours of washout.

• For extremely high doses of biotin (more than 20 mg), the residual biotin serum concentration did not drop to 30 ng/ml until 31 hours after last intake and took 73 hours to drop to 10 ng/ml, indicating an extended washout periods would be needed for immunoassays with a low in vitro interference threshold (less than 30 ng/ml) and following extremely high doses of biotin.

The authors caution that the study is not able to give information as to the size of any potential effect of biotin interference on test results or the proportion of laboratory values that are potentially vulnerable to interference.

Takeaway: The potential for supplementary biotin consumption to interfere with test results is a real concern and is something that laboratories need to work with providers on to ensure accurate diagnosis.