FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL

Report

Report Number: 3002773840-2024-00379
Event Type: Injury
Date Received: September 6, 2024
Date of Event: July 7, 2024
Report Date: October 3, 2024
Manufacturer: BIOFIRE DIAGNOSTICS, LLC
Product Code: PLO
UDI-DI: 00815381020123
PMA / PMN Number: K160462
Adverse Event: Yes
Report Source: Manufacturer report
Reporter Location: AS
Reporter Occupation: OTHER HEALTH CARE PROFESSIONAL
Health Professional: Yes

Narratives

Additional Manufacturer Narrative · 0

INVESTIGATION: THE PATIENT WAS A 24-YEAR-OLD FEMALE WITH SIGNS AND SYMPTOMS OF HEADACHE AND FEVER AT THE TIME OF TESTING. THE PATIENT WAS ALSO IMMUNOCOMPROMISED AS THEY PRESENTED WITH RENAL FAILURE REQUIRING DIALYSIS . ON (B)(6) 2024, THE PATIENT'S CSF SAMPLE WAS TESTED ON THE FILMARRAY ME PANEL. THE FILMARRAY ME PANEL REPORTED VZV AS DETECTED. THE CUSTOMER REPORTED AN IN-HOUSE REAL TIME PCR TEST WAS PERFORMED ON THE SAME CSF SAMPLE AND THE DNA FOR VZV WAS NOT DETECTED. THE CUSTOMER REPORTED THAT DUE TO THE FILMARRAY ME PANEL RESULT, TREATMENT WITH ACYCLOVIR WAS INITIATED FOR THE PATIENT AND THEIR CONDITION DETERIORATED. THE PATIENT WAS TREATED WITH CEFTRIAXONE AND VANCOMYCIN PRIOR TO THE FILMARRAY ME PANEL RESULT, WHICH WERE CONTINUED ALONG WITH THE ADDITION OF ACYCLOVIR AFTER THE FILMARRAY ME PANEL RESULT. THE DURATION OF THE PATIENT'S TREATMENT WITH ACYCLOVIR WAS 48 HOURS. THE TREATMENT WAS STOPPED WHEN THE IN-HOUSE REAL TIME PCR TEST RESULT WAS RECEIVED. THE CUSTOMER REPORTED THAT THE NEGATIVE SIDE EFFECTS OF ACYCLOVIR TREATMENT WERE NOT REVERSIBLE AS THE PATIENT SPENT A LONGER DURATION IN THE HOSPITAL. AS OF (B)(6) 2024, THE PATIENT HAD BEEN DISCHARGED FROM THE HOSPITAL. THE ANALYSIS OF THE FILMARRAY ME PANEL RUN FILE SHOWED A LATE AMPLIFICATION SIGNATURE FOR THE VZV ASSAY, SUGGESTING THAT THE TARGET ANALYTE WAS PRESENT IN THE SAMPLE AT A LOW LEVEL. QUALITY CONTROL (QC) RECORDS FOR POUCH LOT# 35JR23 (KIT LOT# 6455123) WERE REVIEWED. THIS 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 IN-HOUSE PCR COMPARATOR OR 2) CONTAMINATION. 1) THE FALSE POSITIVE VZV RESULTS MAY HAVE BEEN DUE TO DIFFERENCES IN SENSITIVITY/SPECIFICITY BETWEEN THE FILMARRAY ME PANEL AND THE PCR COMPARATOR METHOD USED AT THE CUSTOMER SITE. DISCREPANCIES WITH COMPARATOR PCR METHODS AND OTHER STANDARD LABORATORY TECHNIQUES CAN OCCUR AND ARE A PART OF NORMAL SYSTEM PERFORMANCE. ADDITIONALLY, VIRAL, BACTERIAL, AND YEAST NUCLEIC ACID MAY PERSIST IN VIVO INDEPENDENTLY OF ORGANISM VIABILITY AND/OR ACTIVE INFECTION. NOTE THAT A POSITIVE FILMARRAY ME PANEL RESULT (DETECTION OF TARGET NUCLEIC ACID) DOES NOT IMPLY THAT THE CORRESPONDING VIRAL NUCLEIC ACID IS INFECTIOUS VIRUS OR THE CAUSATIVE AGENTS FOR CLINICAL SYMPTOMS. 2) THE FALSE POSITIVE VZV RESULTS MAY HAVE ALSO BEEN DUE TO CONTAMINATION. DUE TO THE SENSITIVE NATURE OF THE FILMARRAY ME PANEL, THERE IS A RISK OF FALSE POSITIVE RESULTS FROM THE INTRODUCTION OF EXOGENOUS ORGANISM OR NUCLEIC ACID. WHILE THE POUCH LOADING INSTRUCTIONS AND RECOMMENDED CLEANING STEPS ARE SUFFICIENT TO ELIMINATE CONTAMINATION THE MAJORITY OF THE TIME, IT IS POSSIBLE THAT SOME ORGANISM/NUCLEIC ACID COULD BE INTRODUCED DURING ANY PART OF THE TESTING AND POUCH HANDLING PROCESS. CONTAMINATION CAN ALSO BE INTRODUCED VIA THE LABORATORY ENVIRONMENT AND EQUIPMENT SUCH AS PIPETTES, PIPETTE TIPS, ETC., OR PERSONNEL HANDLING THE SAMPLE. BIOFIRE RECOMMENDS PERFORMING DECONTAMINATION IN BETWEEN SPECIMENS WITH A SUITABLE DISINFECTANT (E.G., (B)(4) BLEACH) TO REDUCE THE RISK OF CONTAMINATION. BIOFIRE RECOMMENDS REFERRING TO "CONTAMINATION PREVENTION AND DECONTAMINATION" TECHNICAL NOTE [FLM1-PRT-0230] FOR FURTHER DETAILS ON PROPER DECONTAMINATION AND PREVENTION PRACTICES. BIOFIRE ALSO RECOMMENDS LOADING POUCHES INSIDE OF A BIOSAFETY CABINET OR OTHER CONTAINMENT SYSTEM. A BIOSAFETY CABINET THAT IS USED FOR PERFORMING CSF PATHOGEN TESTING (E.G., CULTURE) SHOULD NOT BE USED FOR SAMPLE PREPARATION OR POUCH LOADING. IF FALSE POSITIVE RESULTS OCCUR AND CONTAMINATION IS SUSPECTED, BIOFIRE RECOMMENDS PERFORMING ENVIRONMENTAL TESTING/SWABS OF THE AREA WHERE FILMARRAY ME PANEL TESTING IS PERFORMED. THERE ARE MULTIPLE POTENTIAL SOURCES OR CAUSES OF FALSE POSITIVE AND FALSE NEGATIVE RESULTS. THE FILMARRAY ME PANEL IS INDICATED AS AN AID IN THE DIAGNOSIS OF SPECIFIC AGENTS OF MENINGITIS AND/OR ENCEPHALITIS AND RESULTS ARE MEANT TO BE USED IN CONJUNCTION WITH OTHER CLINICAL, EPIDEMIOLOGICAL, AND LABORATORY DATA. RESULTS FROM THE FILMARRAY ME PANEL ARE NOT INTENDED TO BE USED AS THE SOLE BASIS FOR DIAGNOSIS, TREATMENT, OR OTHER PATIENT MANAGEMENT DECISIONS. NOTES TO BE CONSIDERED: THE PERFORMANCE OF THIS TEST HAS NOT BEEN SPECIFICALLY EVALUATED FOR CSF SPECIMENS COLLECTED FROM IMMUNOCOMPROMISED INDIVIDUALS. THE PERFORMANCE OF THE FILMARRAY ME PANEL HAS NOT BEEN SPECIFICALLY EVALUATED FOR CSF SPECIMENS COLLECTED FROM INDIVIDUALS ON ANTIMICROBIAL TREATMENT. 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. CLINICAL PERFORMANCE: ACCORDING TO TABLE 9. FILMARRAY ME PROSPECTIVE CLINICAL PERFORMANCE SUMMARY OF THE FILMARRAY ME PANEL INSTRUCTIONS FOR USE (IFU) (WWW.ONLINE-IFU.COM/ITI0035) THE PERFORMANCE CLAIM FOR THE VZV ASSAYS COMPARED TO PCR WITH BI-DIRECTIONAL SEQUENCING SHOWED AN OVERALL PPA OF (B)(4) AND AN OVERALL NPA OF (B)(4). VZV WAS DETECTED IN 1/3 FP 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 FP 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 (B)(4) PRESELECTED ARCHIVED SPECIMENS (OF WHICH (B)(4) WERE NEGATIVE) WAS PERFORMED. ACCORDING TO TABLE 14. FILMARRAY ME PANEL ARCHIVED SPECIMEN PERFORMANCE DATA SUMMARY OF THE FILMARRAY ME PANEL IFU, THE VZV ASSAYS COMPARED TO A CONFIRMATORY MOLECULAR TEST (E.G. PCR WITH BI-DIRECTIONAL SEQUENCING) SHOWED A PPA OF (B)(4) AND AN NPA OF (B)(4).

Additional Manufacturer Narrative · 0

INVESTIGATION: THE PATIENT WAS A 24-YEAR-OLD FEMALE WITH SIGNS AND SYMPTOMS OF HEADACHE AND FEVER AT THE TIME OF TESTING. THE PATIENT WAS ALSO IMMUNOCOMPROMISED AS THEY PRESENTED WITH RENAL FAILURE REQUIRING DIALYSIS. ON (B)(6) 2024, THE PATIENT'S CSF SAMPLE WAS TESTED ON THE FILMARRAY ME PANEL. THE FILMARRAY ME PANEL REPORTED VZV AS DETECTED. THE CUSTOMER REPORTED AN IN-HOUSE REAL TIME PCR TEST WAS PERFORMED ON THE SAME CSF SAMPLE AND THE DNA FOR VZV WAS NOT DETECTED. THE CUSTOMER REPORTED THAT DUE TO THE FILMARRAY ME PANEL RESULT, TREATMENT WITH ACYCLOVIR WAS INITIATED FOR THE PATIENT AND THEIR CONDITION DETERIORATED. THE PATIENT WAS ON CEFTRIAXONE AND VANCOMYCIN PRIOR TO THE FILMARRAY ME PANEL RESULT, WHICH WERE CONTINUED ALONG WITH THE ADDITION OF ACYCLOVIR AFTER THE FILMARRAY ME PANEL RESULT. THE DURATION OF THE PATIENT'S TREATMENT WITH ACYCLOVIR WAS 48 HOURS. QUALITY CONTROL (QC) RECORDS FOR POUCH LOT# 35JR23 (KIT LOT# 6455123) WERE REVIEWED. THIS POUCH LOT PASSED QC CRITERIA AND WAS FOUND WITHIN SPECIFICATIONS. NO RUN MALFUNCTION OCCURRED AND THE FILMARRAY INSTRUMENT (SERIAL NUMBER# (B)(6)) WAS WORKING WITHIN DESIGNED SPECIFICATIONS. BIOFIRE'S INVESTIGATION INTO THIS EVENT IS ONGOING AND FURTHER INFORMATION HAS BEEN REQUESTED FROM THE CUSTOMER. THE FULL INVESTIGATION AND ASSOCIATED CONCLUSIONS WILL BE PROVIDED IN THE FINAL REPORT. NO REMEDIAL ACTION, CORRECTIVE ACTION, PREVENTIVE ACTION, OR FSCA HAS BEEN DEEMED NECESSARY AT THIS TIME. CONCLUSION: N/A FOR INITIAL REPORT.

Description of Event or Problem · 0

SUMMARY: (B)(6) MEDICINE ((B)(6), WA) REPORTED A POTENTIAL FALSE POSITIVE VARICELLA ZOSTER VIRUS (VZV) RESULT ON FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A CEREBROSPINAL FLUID (CSF) SAMPLE FROM A 24-YEAR-OLD FEMALE PATIENT. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT WAS TREATED WITH ACYCLOVIR FOR 48 HOURS AND THE PATIENT'S CONDITION DETERIORATED. UPON INVESTIGATION, NO MALFUNCTION OCCURRED AND THE FILMARRAY ME PANEL WAS WORKING WITHIN SPECIFICATION. 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 IN-HOUSE PCR COMPARATOR METHOD OR 2) CONTAMINATION.

Description of Event or Problem · 0

SUMMARY: (B)(6) REPORTED A POTENTIAL FALSE POSITIVE VARICELLA ZOSTER VIRUS (VZV) RESULT ON FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A CEREBROSPINAL FLUID (CSF) SAMPLE FROM A 24-YEAR-OLD FEMALE PATIENT. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT WAS TREATED WITH ACYCLOVIR FOR 48 HOURS AND THE PATIENT'S CONDITION DETERIORATED. BIOFIRE HAS REQUESTED FURTHER INFORMATION FROM THE CUSTOMER AND IS CURRENTLY INVESTIGATING THIS EVENT. NO REMEDIAL ACTION, CORRECTIVE ACTION, PREVENTIVE ACTION, OR FIELD SAFETY CORRECTIVE ACTION (FSCA) HAS BEEN DEEMED NECESSARY AT THIS TIME.

Devices

Seq	Brand	Generic	Product Code	Manufacturer	Model	Lot	UDI-DI
1303470	FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL	FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL	PLO	BIOFIRE DIAGNOSTICS, LLC	RFIT-ASY-0118	6455123	00815381020123

Patients

Seq	Age	Sex	Outcome	Treatment
1	24 YR	Female	Other