FDA finalizes biotin interfering testing guidance
A guidance document from the US Food and Drug Administration (FDA) that addresses biotin interference testing for in vitro diagnostic devices (IVDs) has been finalized. The agency left the 2019 draft guidance largely unchanged, recognizing but declining to address industry concerns seeking a lower biotin cutoff level for interference testing and asking for more explicit information about mitigation measures.Biotin is used in many IVD scenarios, such as tests for cardiac troponin markers, where unexpectedly high serum biotin levels can cause inaccurate test results that can have serious clinical implications. Biotin supplementation is becoming more common among American consumers, who are also consuming the substance, also known as vitamin B7, at higher levels than had previously been seen.
The June 2019 draft guidance on biotin interference testing addressed the concerns of inaccurate test results by recommending sponsors contact the appropriate review division when biotin interference is detected. The draft also laid out recommendations for interference testing and communication of test results. These recommendations all carried through to the final guidance document. (RELATED: FDA Draft Guidance Seeks to Mitigate Risk of Biotin Interference, Regulatory Focus, 12 June 2019)
AdvaMed, the medical technology and device professional society, submitted comments to the docket in August 2019 requesting that the recommended biotin level for interference testing be dropped from 3,500 ng/mL to 1,200 ng/mL. AdvaMed put forward the rationale that an earlier 2017 safety communication had recommended the lower level as a threshold for evaluation. Also, the higher concentration exceeds levels observed in the scientific literature, said the society in its comments.
In the Federal Register notice of the availability of the final guidance, FDA noted that it “considered comments on the recommended level of biotin concentration for evaluation.” In the end, the agency declined to recommend evaluating a concentration level less than 3,500 ng/mL. “Further, this level is consistent with best practices among the industry to test at three times the highest concentration levels observed, as recommended in the FDA-recognized standard published by the Clinical Laboratory Standards Institute,” said FDA.
Device labeling, said FDA, should include results of biotin interference testing; the label should indicate percent differences in test results at tested biotin concentrations and indicate whether results were falsely elevated or depressed by high biotin concentrations.
Though the Agency declined to specify which additional mitigation measures might be needed, the guidance reflects “FDA’s thinking that labeling alone may not be sufficient to mitigate the risk of incorrect results from biotin interference in all cases.” Adds the guidance, “Additional mitigation strategies may be considered when the risk of potentially incorrect results from biotin interference could significantly affect patient or public health.”
FDA