FDA WATCH

FDA Watch: Agency Resounds the Alarm on Biotin Test Interference

In early November 2019, the U.S. Food and Drug Administration (FDA) updated a previous safety communication about the potential of biotin to significantly interfere with diagnostic tests. The update reiterates the warning to laboratory personnel, diagnostic test developers, providers, and patients that biotin can lead to incorrect lab 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 marketed for hair, skin and nail growth. Because biotin bonds with specific proteins that can be measured to detect certain health conditions, many laboratory tests rely on biotin-detection based methods and technology. The problem is that biotin can distort laboratory test results leading false highs and false lows, especially when tested patients consume high levels of biotin. And such high consumption is far from unusual given how much of it producers use. Thus, for example, dietary supplements may contain up to 650 times more biotin than recommended daily values.

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.

Recommendations for Providers

The newly revised communication lays out recommendations for providers to minimize the risk of biotin interference, including:

  • Discussing biotin and multivitamin supplements with patients;
  • Notifying laboratories if patients being tested are taking biotin;
  • Considering biotin interference as a source of error if laboratory test results do not match clinical presentation; and
  • Reporting to the laboratory manufacturer and FDA if they become aware of patients experiencing adverse events following potentially incorrect laboratory test results due to biotin interference.

Recommendations for Laboratories

The communication also recommends that laboratory and testing personnel:

  • Be aware that it is difficult to identify samples that contain biotin if assays are used with biotin technology, and to communicate with health care providers and patients to prevent incorrect test results;
  • Ask patients if they are taking biotin or a biotin-containing supplement when collecting samples;
  • Educate health care providers about biotin interference with laboratory tests;
  • Understand that biotin levels higher than the recommended daily allowance of .03 mg may cause significant interference with laboratory tests;
  • Be aware that specimens collected from patients taking high levels of biotin may contain more than 100 ng/mL biotin;
  • Recognize that currently available data is insufficient to support recommendations for safe testing using affected tests in patients taking high levels of biotin, including about the length of time for biotin clearance from the blood;
  • Communicate with the laboratory test manufacturer if there are questions about biotin interference; and
  • Be aware of certain troponin assays where the risk of biotin interference has not yet been addressed.

Recommendations for Laboratory Manufacturers

Last but not least, the communication calls on laboratory test manufacturers and developers to:

  • Contact the FDA to discuss biotin interference if an assay uses biotin technology;
  • Investigate interference from biotin (up to at least 1200 ng/mL biotin) in assays that use biotin technology and determine the lowest concentration of biotin that may cause clinically significant interference with test(s);
  • Communicate to customers that may be unaware that a test uses biotin technology and how it may be affected; and
  • Contact the FDA with any questions about biotin technology and interference.

For specific measures the FDA wants test makers to implement to manage biotin interference risks, see Diagnostic Testing and Emerging Technologies (DTET), Sept. 23, 2019.

 

The FDA’s Biotin Bad List
In addition to calling out the general laboratory industry for failing to deal with biotin interference risks, the FDA is naming names. The revised communication includes an updated list of troponin tests in the FDA’s listing database for which biotin interference risks have not yet been mitigated—or so the agency claims. The list includes (by 510(k) clearance device name):

  • SPECTRAL’S TROPONIN I
  • NANO-CHECK AMI 3 IN 1 CARDIAC DISEASE TEST FOR CARDIAC TROPONIN I, CREATINE KINASE MB AND MYOGLOBIN
  • NANO-CHECK AMI 3 IN 1 CARDIAC DISEASE TEST FOR CARDIAC TROPONIN I, CREATINE KINASE MB AND MYOGLOBIN
  • NANO-CHECK AMI CTNI CARDIAC MARKER TEST
  • Nano-Check AMI 2 IN 1 Cardiac Marker Test, cTnI and Myoglobin; NANO-CHECK AMI 2 IN 1 CARDIAC DISEASE TEST FOR CARDIAC TROPONIN I AND MYOGLOBIN
  • Elecsys Troponin T Gen 5 STAT Assay, Elecsys Troponin T Gen 5 STAT CalSet, Elecsys PreciControl Troponin, Elecsys Troponin T Gen 5 CalCheck 5
  • THE CARDIAC READER SYSTEM
  • CARDIAC STATUS TROPONIN I

 

New FDA Approvals

Here’s a look at all the important new product approvals announced from late October through mid-November:

NEW FDA APPROVALS

Manufacturer(s) Product(s)
NantHealth 510(k) clearance for Omics Core technology to measure overall tumor mutational burden in cancer tissue and report somatic mutations in 468 cancer-relevant genes
Siemens Healthineers Clearance for Atellica IM Total hCG assay for quantitative measurement of human chorionic gonadotropin in human serum or plasma, using firm’s Atellica IM Analyzer
Thermo Fisher Scientific Clearance received clearance for iSensititre 18-24 hour MIC or Breakpoint Susceptibility System with Imipenem-Relebactam in dilution range of 0.03/4-256/4 µg/mL
DiaSorin Marketing clearance for Liaison XL Zika Capture IgM Assay II for detecting Zika virus IgM antibodies previously cleared for emergency use only
DiaSorin Clearance Liaison Vitamin B12 chemiluminescent immunoassay for quantitative measurement of vitamin B12 on Liaison XL analyzer
Microbiologics Clearance for Cepheid Xpert Respiratory Control Panel
iXensor Clearance for PixoTest POCT Analyzer and PixoTest A1c Test Kit for quantitative measurement of glycated hemoglobin (HbA1c) in fingerstick capillary and venous whole blood samples
Fujirebio Diagnostics Clearance for Lumipulse G CA19-9-N chemiluminescent enzyme immunoassay for quantitative measurement of CA19-9 in human serum or plasma, running on firm’s Lumipulse G System
Lin-Zhi International Clearance for LZI Methadone II Enzyme Immunoassay for qualitative and semi-quantitative determination of methadone in urine
Horiba Clearance for Yumizen C1200 CRP reagent for quantitative measurement of C-reactive protein in human serum and plasma based on immunoturbidimetric assay
GeneOhm Sciences Canada Clearance for BD Max Vaginal Panel running on BD Max System
NG Biotech Clearance for NG-Test Carba 5 multiplex immunochromatographic assay to detect carbapenemase enzymes in bacterial colonies
Alpco Clearance for Calprotectin Chemiluminescence ELISA for quantitative measurement of fecal calprotectin
MRIGlobal Clearance for Applied Biosystems Bacillus anthracis Detection Kit
Exact Sciences Breakthrough device designation for hepatocellular carcinoma test
Vela Diagnostics Clearance for Sentosa SQ HIV Genotyping Assay, NGS-based HIV-1 drug resistance mutation assay
Affinimark Technologies Breakthrough device designation for cerebrospinal fluid test strip
Myriad Genetics Approval of myChoice CDx as companion diagnostic for determining patient’s homologous recombination deficiency (HRD) status and who can benefit from niraparib (GlaxoSmithKline’s Zejula)
Ortho Clinical Diagnostics Clearance for Ortho Sera suite of reagents that enabling extended antigen phenotyping for use with the Ortho Vision analyzer
Cleveland Diagnostics Breakthrough device designation for blood-based prostate cancer test that evaluates structural changes to prostate-specific antigen (PSA) rather than just measuring the level of the biomarker a la traditional PSA tests
OraSure Technologies Clearance for OraQuick Ebola Rapid Antigen Test, first US-approved rapid detection test for Ebola virus
BioMérieux Clearance for ETest Eravacycline assay for determining antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria
Philips Electronics received 510(k) clearance for Philips IntelliSite Pathology Solution (PIPS) with a modified display
Binding Site Group Clearance for Human IgA liquid reagent kit for use on firm’s Spaplus turbidimetric analyzer
Qingdao Hightop Biotech Clearance for Pregnancy Rapid Test to measure human chorionic gonadotropin (hCG) in early pregnancy detection
Bioeasy Biotechnology Clearance for Bioeasy Marijuana Test Dip Card and Bioeasy Marijuana Test Strip lateral flow immunochromatographic assays for preliminary detection of marijuana in urine
Beckman Coulter Clearance for FC 500 MPL and MCL flow cytometers to measure biological and physical properties of cells and other particles as they pass through laser beams in a single file
Beckman Coulter 510(k) clearance for DxA 5000 total laboratory automation solution
Sekisui Diagnostics 510(k) clearance for Acucy Influenza A&B test + CLIA waiver for use on the Acucy Reader
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