FDA Watch: Agency Issues New Guidance on Biotin Interference Testing

On June 13, the FDA issued a draft guidance explaining how makers of in vitro diagnostic devices (IVDs) should perform biotin interference testing and communicate testing results to labs, clinicians and other device end-users.

Biotin, aka vitamin B7, is a common ingredient in multi-vitamins, prenatal vitamins and dietary supplements. Falsely high or falsely low test results have been known to occur in patients who consume high levels of biotin from such products. These results can lead to inappropriate patient management or misdiagnosis.

As the guidance points out, devices using biotin/avidin technology have historically been assessed for biotin interference at the normal recommended daily doses of biotin of 30 μg per day, which results in plasma/serum biotin levels of < 1 ng/mL. Nevertheless, “unanticipated biotin interference with the performance of some IVDs due to consumer use of dietary supplements” have in some instances revealed much higher levels; extremely high biotin doses also have been observed of up to 300 mg per day, which results in plasma/serum biotin levels of > 1000 ng/mL.

The FDA’s 6 Recommendations

The FDA recommends that:

  1. Sponsors contact the appropriate Center for Biologics Evaluation and Research (CBER) or Center for Devices and Radiological Health (CDRH) review division when biotin interference at clinically relevant analyte and biotin concentrations is demonstrated;
  2. Studies testing for biotin interference be designed in accordance with Clinical Laboratory Standards Institute (CLSI) EP07, Interference Testing in Clinical Chemistry; Approved Guideline;
  3. Concentrations of biotin be evaluated up to 3500 ng/mL to reflect current trends in biotin consumption;
  4. Test samples include analyte levels near the medical decision point(s) of the device;
  5. The concentration of biotin at which no interference is detected be determined for assays that are susceptible to biotin interference at concentrations less than 3500 ng/mL; and
  6. Listing information on biotin interference testing in the labeling of the device, including the percent difference or bias at each concentration tested for both qualitative and quantitative assays and the consequence of biotin interference, e.g., any falsely elevated or falsely depressed observed.

New FDA Approvals

After a furious month, the pace of new product approvals slowed down from late June through late July. Here’s a look at product approvals announced during the period:  

Manufacturer(s) Product(s)
Foundation Medicine Clearance for FoundationOne CDx test as companion diagnostic for olaparib (AstraZeneca and Merck’s Lynparza) for first-line maintenance therapy in BRCA-mutated advanced ovarian cancer
iCubate Clearance for iC-GN Assay to detect and identify potentially pathogenic gram-negative bacteria associated with bloodstream infection and subsequent sepsis
Abbott Clearance for use of firm’s Alinity s System to conduct screening in US blood and plasma centers
BioMérieux Clearance for Vitek 2 AST Gram Positive Dalbavancin antimicrobial susceptibility test
Ortho Clinical Diagnostics Clearance for its Vitros XT Chemistry Products ALB-TP Slides, a paired albumin and total protein test
Serosep Clearance for EntericBio Dx Assay, a combined panel that testing for salmonella, Shiga toxin-producing Escherichia coli, Shigella, Campylobacter, Cryptosporidium, Giardia, Yersinia, Entamoeba histolytica and Vibrio
AMS Diagnostics Clearance for Liasys 600 Electrolyte Measurement System for measuring sodium, chloride and potassium in human serum
AMS Diagnostics Clearance for Liasys 600 creatinine reagent for diagnosis of renal diseases, monitoring renal dialysis and as a calculation basis for measuring other urine analytes
AMS Diagnostics Clearance for Liasys 600 standalone clinical analyzer
Immunodiagnostic Systems Clearance for IDS SHBG assay for measuring sex hormone binding globulin in human serum and plasma on firm’s IDS System
Microbiologics Clearances for Cepheid Xpert SA Nasal Complete Control Panel and Cepheid Xpert MRSA NxG Control Panel quality control panels for Danaher’s Cepheid Xpert assays
Bühlmann Laboratories 510(k) clearance for fCal Turbo calprotectin test
Lucid Diagnostics 510(k) clearance for EsoCheck Cell Collection Device
Quidel 510(k) clearance for Triage TOX Drug Screen, 94600, fluorescence immunoassay test for simultaneous detection of different drug metabolites in urine

New CE Marks & Global Certifications

Notable European CE certifications during the period:

Manufacturer(s) Product(s)
iCubate CE IVD marking for iC-GN Assay for detection and identification of pathogenic gram-negative bacteria and resistance markers associated with bloodstream infections and subsequent sepsis
Chembio Diagnostics CE marking for DPP Zika/Dengue/Chikungunya point-of-care test
Avioq CE marking for VioOne HIV Profile supplemental assay
NeuMoDx CE-IVD markings for two different assays to detect and quantify levels of hepatitis, one for hepatitis B virus, the other for C virus

Other international clearances announced during the period:

Manufacturer(s) Country(ies) Product(s)
SpeeDx Canada Health Canada approval for ResistancePlus MG, qPCR kit that detects the sexually transmitted infection Mycoplasma genitalium as well as genetic mutations conferring resistance to macrolides, a commonly-prescribed class of antibiotics
Atomo Diagnostics
Remote and underserved markets worldwide World Health Organization prequalification approval for Mylan HIV Self Test, handheld lateral flow immunoassay self-test which can be used in the home
Foundation Medicine Japan Ministry of Health, Labour, and Welfare additional approval of FoundationOne CDx Cancer Genomic Profile as companion diagnostic for entrectinib (Roche’s Rozlytrek), marketed in Japan by Chugai Pharmaceutical

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