Following a safety communication on an increased risk of adverse events associated with incorrect laboratory test results due to biotin interference, the US Food and Drug Administration (FDA) issued draft guidance on Thursday for testing biotin interference and communicating results with end users.
The draft guidance for industry aims to clarify how to test for interference by biotin, also called vitamin B7, on the performance of in vitro
diagnostic devices (IVDs) that use biotin technology and other devices used in donor screening, and how to share testing results with end users, including laboratory personnel.
The six draft recommendations outlined in the 6-page draft guidance apply to device developers and clinicians, although FDA advises manufacturers of currently marketed devices to consider them also.
FDA seeks to address a concern expressed
in a November 2017 safety communication after becoming aware of a spike in the number of reported adverse events related to incorrect test results due to interference by biotin, which is commonly used in multi-vitamins, prenatal vitamins and dietary supplements. The issue stems from patients who consume high levels of biotin from such products, which in turn poses a greater risk of biotin interference that may cause falsely high or falsely low results.
The draft guidance notes that devices that use biotin technology have historically been assessed for biotin interference at biotin’s normal recommended daily dosing regimen of 30 μg per day, resulting in plasma/serum biotin levels of < 1 ng/mL. Yet “several recent reports have described unanticipated biotin interference with the performance of some IVDs due to consumer use of dietary supplements that result in plasma/serum biotin levels of > 1 ng/mL” and “extremely high biotin doses also have been observed.”
FDA’s Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) jointly drafted the recommendations and made them consistent with recent advice the agency has been providing to manufacturers and sponsors inquiring about biotin interference when it occurs. In terms of study designs, there is also consistency with recommendations in the April version of the Clinical Laboratory Standards Institute (CLSI) EP07: Interference Testing in Clinical Chemistry guideline.
To align with the CLSI standard, FDA now proposes to recommend testing biotin concentration levels up to 3500 ng/mL to account for the trends currently seen in biotin consumption and determining the level at which no interference is detected for assays susceptible to biotin interference at concentrations less than 3500 ng/mL.
To communicate the results of the testing to end users, the draft guidance recommends including the information on biotin interference in the device labeling. Per the draft guidance, the labeling should inform of the percent difference or bias at each of the tested concentrations and the potential for falsely elevated or falsely depressed results due to biotin interference with lab tests. “These recommendations should not be interpreted to mean that FDA considers that labeling alone will be sufficient to mitigate the risk of incorrect results from biotin interference in all cases,” the draft guidance clarifies.
Sponsors should include the analyte levels near the medical decision point(s) of the devices in the test samples and contact the appropriate CBER or CDRH review division if biotin interference is detected at clinically relevant analytes and biotin concentrations, according to the draft guidance.