BEUDAMED
    FDA Adverse Event Injury Summary report: N

    FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL

    MDR report key: 20931510 · Received December 13, 2024

    Report

    Report Number
    3002773840-2024-00428
    Event Type
    Injury
    Date Received
    December 13, 2024
    Date of Event
    November 12, 2024
    Report Date
    January 10, 2025
    Manufacturer
    BIOFIRE DIAGNOSTICS, LLC
    Product Code
    PLO
    UDI-DI
    00815381020123
    PMA / PMN Number
    K160462
    Adverse Event
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    FR
    Reporter Occupation
    OTHER HEALTH CARE PROFESSIONAL
    Health Professional
    Yes

    Narratives

    Additional Manufacturer Narrative · 0

    INVESTIGATION: THE PATIENT WAS A 33-YEAR-OLD FEMALE WITH SIGNS AND SYMPTOMS OF SEVERE HEADACHES, MENINGEAL SYNDROME WITH STIFF NECK, AND PHOTOPHOBIA. THE CUSTOMER REPORTED THAT THE HEADACHES HAD BEEN PRESENT FOR 1 WEEK AND THERE WERE NO CLINICAL GROUNDS FOR VZV INFECTION. THE CUSTOMER REPORTED THAT ON (B)(6) 2024, THE PATIENT'S CSF SAMPLE WAS COLLECTED AND TESTED ON THE FILMARRAY ME PANEL AND WAS NEGATIVE FOR ALL ANALYTES. ON (B)(6) 2024, A SECOND CSF SAMPLE WAS COLLECTED ON COLLECTION TUBES. ON (B)(6) 2024, THE CSF SAMPLE FROM ONE OF THE TUBES WAS TESTED ON THE FILMARRAY ME PANEL. THE FILMARRAY ME PANEL REPORTED VZV AS DETECTED. CSF SAMPLE FROM ANOTHER TUBE FROM THE SAME SAMPLING EVENT WAS TESTED ON VZV ELITE MGB® KIT AND WAS NEGATIVE FOR VZV. WHEN ASKED IF THE PATIENT'S MANAGEMENT WAS AFFECTED BY THE FILMARRAY ME PANEL RESULT THE CUSTOMER HAD INITIALLY COMMUNICATED, "ACYCLOVIR 15 MG/KG NEPHROTOXIC, HARM BECAUSE OF CHANGE IN MANAGEMENT". HOWEVER, THE CUSTOMER LATER CONFIRMED THAT THE PATIENT'S KIDNEYS WERE NOT DAMAGED DUE TO THE FILMARRAY ME PANEL RESULT. NO IMPACT DUE TO TREATMENT WITH ACYCLOVIR WAS REPORTED. THE FINAL DIAGNOSIS OF THE PATIENT WAS "EBV INFECTIOUS MONONUCLEOSIS COMPLICATED BY MENINGITIS IN THE CONTEXT OF AN ASYMPTOMATIC COVID INFECTION." THE ANALYSIS OF THE FILMARRAY ME PANEL RUN FILE SHOWED THE ASSAY SIGNATURES FOR THE VZV TARGETS WERE LATE, WHICH COULD BE INDICATIVE OF THE TARGET NUCLEIC ACID BEING PRESENT AT LOW LEVELS. QUALITY CONTROL (QC) RECORDS FOR POUCH LOT#: 3DEG24, (KIT LOT#: 1300324) WERE REVIEWED. THE POUCH LOT PASSED QC CRITERIA AND WAS FOUND WITHIN SPECIFICATIONS. NO RUN MALFUNCTION OCCURRED AT THE CUSTOMER SITE AND THE FILMARRAY INSTRUMENT (SERIAL NUMBER#: (B)(6) WAS WORKING WITHIN DESIGNED SPECIFICATIONS. CONCLUSION: THE INVESTIGATION CONCLUDED THAT THE MOST LIKELY CAUSE FOR THE DISCREPANT VZV RESULT WAS 1) SENSITIVITY/SPECIFICITY DIFFERENCES BETWEEN THE FILMARRAY ME PANEL AND THE COMPARATOR PCR METHOD WITH A LOW-LEVEL ANALYTE OR 2) CONTAMINATION. 1) WHILE RARE, DISCREPANCIES BETWEEN FILMARRAY ME PANEL AND OTHER PCR METHODS ARE PART OF THE NORMAL PERFORMANCE OF THE PRODUCT OBSERVED IN THE FIELD. THESE DISCREPANCIES CAN BE CAUSED BY DIFFERENCES IN CHEMISTRIES, ORGANISM TARGETS, PROCEDURES, SOFTWARE ANALYSIS, AND ASSAY CUT-OFF THRESHOLDS. ADDITIONALLY, THE CUSTOMER REPORTED TESTING TWO DIFFERENT TUBES FROM THE SAME COLLECTION. DIFFERENT SAMPLE TUBES MAY HAVE SOME VARIABILITY BETWEEN THEM. VARIABILITY BETWEEN SAMPLES INCLUDES SAMPLE HANDLING TECHNIQUES AND LEVELS OF ORGANISM/NUCLEIC ACID CONTAINED IN EACH SAMPLE. ACCORDING TO THE FILMARRAY ME PANEL INSTRUCTION BOOKLET (WWW.ONLINE-IFU.COM/ITI0035), VIRAL SHEDDING INTO THE CSF OFTEN OCCURS IN CASES OF ZOSTER (SHINGLES; CAUSED BY REACTIVATION OF VZV). DETECTION OF VZV IN CSF MAY NOT INDICATE THE CAUSE OF CENTRAL NERVOUS SYSTEM (CNS) DISEASE IN THESE CASES. FURTHERMORE, HERPESVIRUSES (CMV, HHV-6, HSV-1, HSV-2, AND VZV) CAN EXIST IN LATENT FORMS THAT MAY BE REACTIVATED DURING INFECTION BY OTHER PATHOGENS, INCLUDING AGENTS NOT DETECTED BY THE FILMARRAY ME PANEL THAT MAY CAUSE MENINGITIS/ENCEPHALITIS (E.G., MYCOBACTERIUM TUBERCULOSIS OR HIV). WHEN DETECTED BY THE FILMARRAY ME PANEL, HERPESVIRUS RESULTS SHOULD BE CONSIDERED AS THE LIKELY CAUSE OF MENINGITIS/ENCEPHALITIS ONLY IN APPROPRIATE CLINICAL CONTEXT AND FOLLOWING EXPERT CONSULTATION. 2) ALTERNATIVELY, THE VZV DETECTION MAY BE DUE TO LOW-LEVEL CONTAMINATION INTRODUCED DURING THE FILMARRAY ME PANEL TESTING PROCESS. AS CONTAMINATION EVENTS OFTEN PRESENT WITH LATE PCR AMPLIFICATION SIGNATURES, IT IS DIFFICULT TO DISTINGUISH A LOW-LEVEL DETECTION FROM A SPORADIC CONTAMINATION EVENT. DUE TO THE HIGH SENSITIVITY OF THE FILMARRAY ME PANEL IN DETECTING NUCLEIC ACID, ORGANISM/AMPLICON CONTAMINATION CAN PRODUCE ERRONEOUS RESULTS. WHILE THE CUSTOMER'S STATED DECONTAMINATION PROCEDURE ALIGNS WITH THE RECOMMENDATIONS PROVIDED BY BIOFIRE, IT IS STILL POSSIBLE SPORADIC CONTAMINATION EVENTS MAY OCCUR. CONTAMINATION CAN BE INTRODUCED VIA THE LABORATORY ENVIRONMENT AND EQUIPMENT SUCH AS PIPETTES, PIPETTE TIPS, ETC., OR PERSONNEL HANDLING THE SAMPLE. IF FALSE POSITIVE RESULTS OCCUR AND CONTAMINATION IS SUSPECTED, BIOFIRE RECOMMENDS PERFORMING ENVIRONMENTAL TESTING/SWABS OF THE AREA WHERE THE FILMARRAY ME PANEL TESTING IS PERFORMED. CLINICAL AND LABORATORY PERSONNEL MAY CARRY OR SHED COMMON PATHOGENS SYMPTOMATICALLY OR ASYMPTOMATICALLY AND CAN INADVERTENTLY CONTAMINATE THE SPECIMEN WHILE IT IS BEING COLLECTED, TRANSPORTED, OR TESTED. PRECAUTIONS MAY INCLUDE ADDITIONAL PERSONAL PROTECTIVE EQUIPMENT (PPE), SUCH AS A FACE MASK, WHEN EXPERIENCING SIGNS OR SYMPTOMS OF AN INFECTION. A BIOSAFETY CABINET USED FOR PERFORMING CSF PATHOGEN TESTING (E.G., CULTURE) SHOULD NOT BE USED FOR SAMPLE PREPARATION OR POUCH LOADING. CAREFUL ADHERENCE TO THE SAMPLE HANDLING AND TESTING PROCEDURES AND PRECAUTIONS DESCRIBED IN THE FILMARRAY ME PANEL INSTRUCTION BOOKLET IS RECOMMENDED TO MINIMIZE THE RISK OF CONTAMINATION THAT COULD LEAD TO ERRONEOUS TEST RESULTS. CLINICAL PERFORMANCE: ACCORDING TO TABLE 9. FILMARRAY ME PROSPECTIVE CLINICAL PERFORMANCE SUMMARY OF THE FILMARRAY ME PANEL INSTRUCTION BOOKLET, THE PERFORMANCE CLAIM FOR THE VZV ASSAYS COMPARED TO PCR WITH BI-DIRECTIONAL SEQUENCING SHOWED AN OVERALL POSITIVE PERCENT AGREEMENT (PPA) OF 100% (95% CI 51.0-100%) AND AN OVERALL NEGATIVE PERCENT AGREEMENT (NPA) OF 99.8% (95% CI 99.4-99.9%). VZV WAS DETECTED IN 1/3 FALSE POSITIVE SPECIMENS USING AN INDEPENDENT PCR ASSAY; THE SUBJECT FROM WHOM THIS SPECIMEN WAS COLLECTED RECEIVED A PHYSICIAN DIAGNOSIS OF HERPES ZOSTER. OF THE REMAINING TWO SPECIMENS WITH FALSE POSITIVE RESULTS, ONE WAS COLLECTED FROM A SUBJECT WHO WAS DIAGNOSED WITH HERPES ZOSTER OTICUS. TO SUPPLEMENT THE RESULTS OF THE PROSPECTIVE CLINICAL STUDY, AN EVALUATION OF 235 PRESELECTED ARCHIVED SPECIMENS (OF WHICH 25 WERE NEGATIVE) WAS PERFORMED. ACCORDING TO TABLE 14. FILMARRAY ME PANEL ARCHIVED SPECIMEN PERFORMANCE DATA SUMMARY OF THE FILMARRAY ME PANEL INSTRUCTION BOOKLET, THE VZV ASSAYS COMPARED TO A CONFIRMATORY MOLECULAR TEST (E.G., PCR WITH BI-DIRECTIONAL SEQUENCING) SHOWED A PPA OF 100% (95% CI 85.1-100%) AND AN NPA OF 98.8% (95% CI 95.7-99.7%).

    Additional Manufacturer Narrative · 0

    INVESTIGATION: WHEN ASKED IF THE PATIENT'S MANAGEMENT WAS AFFECTED BY THE FILMARRAY ME PANEL RESULT THE CUSTOMER COMMUNICATED, "ACYCLOVIR 15 MG/KG NEPHROTOXIC, HARM BECAUSE OF CHANGE IN MANAGEMENT." IT IS UNCLEAR WHETHER THE PATIENT'S KIDNEYS WERE AFFECTED DUE TO THE FILMARRAY ME PANEL RESULT. THEREFORE, BIOFIRE IS REPORTING THIS OUT OF AN ABUNDANCE OF CAUTION. BIOFIRE HAS REQUESTED FURTHER INFORMATION FROM THE CUSTOMER AND IS CURRENTLY INVESTIGATING THIS EVENT. CONCLUSION: INVESTIGATION ONGOING.

    Description of Event or Problem · 0

    SUMMARY: (B)(6) REPORTED A POTENTIAL FALSE POSITIVE VARICELLA ZOSTER VIRUS (VZV) RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A PATIENT CEREBROSPINAL FLUID (CSF) SAMPLE. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT RECEIVED INAPPROPRIATE TREATMENT. THE INVESTIGATION CONCLUDED THAT THE MOST LIKELY CAUSE FOR THE DISCREPANT VZV RESULT WAS 1) SENSITIVITY/SPECIFICITY DIFFERENCES BETWEEN THE FILMARRAY ME PANEL AND THE COMPARATOR PCR METHOD WITH A LOW-LEVEL ANALYTE OR 2) CONTAMINATION.

    Description of Event or Problem · 0

    SUMMARY: (B)(6) (FRANCE) REPORTED A POTENTIAL FALSE POSITIVE VARICELLA ZOSTER VIRUS (VZV) RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A PATIENT CEREBROSPINAL FLUID (CSF) SAMPLE. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT RECEIVED INAPPROPRIATE TREATMENT, WHICH MAY HAVE LED TO NEPHROTOXICITY FOR THE PATIENT. BIOFIRE HAS REQUESTED FURTHER INFORMATION FROM THE CUSTOMER AND IS CURRENTLY INVESTIGATING THIS EVENT.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    2418013 FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL PLO BIOFIRE DIAGNOSTICS, LLC RFIT-ASY-0118 1300324 00815381020123

    Patients

    Seq Age Sex Outcome Treatment
    1 33 YR Female Other