MAUDE Adverse Event Report: BIOFIRE DIAGNOSTICS, LLC FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL; FILMARRAY ME PANEL

Model Number RFIT-ASY-0119

Device Problems False Positive Result (1227); Incorrect, Inadequate or Imprecise Result or Readings (1535)

Patient Problems Death (1802); Meningitis (2389)

Event Date 07/03/2018

Event Type  Death  

Manufacturer Narrative

(b)(6) reported a discrepant cryptococcus result on the filmarray meningitis/ encephalitis (me) panel using a patient ((b)(6), female) cerebrospinal fluid (csf) sample.The filmarray me panel was positive for cryptococcus, but latex antigen testing was negative.The patient went to the hospital (b)(6) 2018 for intense headache and a stiff neck.The csf analysis showed the following: protein: 210 mg/dl, glucose: 21 mg/dl, red blood cell count: 3 rbcs/mm3, complete blood count: 3200 leukocytes/mm3 (95% pmn, 5% mono).Latex antigen testing was negative for cryptococcus.The filmarray me panel was performed on (b)(6) 2018 two hours after sample collection showing positive for the cryptococcus assay.The patient was treated with amphotericin b for 14 days, but the patient did not improve with treatment.The patient had respiratory insufficiency which required mechanical ventilation in the icu.The report also noted that the patient had a tracheostomy that was tolerated well.According to the customer, vasopressor support was necessary and patient had evidence of acute renal injury and that antibiotic was indicated.Customer stated that the contamination protocol was followed and that samples are prepared in a safety chamber that is disinfected between sample preparations.On august 29, 2018, biofire received additional information from the customer indicating that the patient had died.The patient had a history of chronic arterial hypertension and was on pharmacological treatment with poor general condition before the filmarray me panel results were reported.Sample was not sequenced by the customer and was requested for in-house testing but was unavailable.Biofire has requested information about the cause of death, but has not received additional information.Biofire has no information to suggest that use of the filmarray me panel caused or contributed to the patient's death.Qc records for pouch lot# 818718 (kit lot# 506318) were reviewed.This pouch lot passed the qc criteria and was found within specifications.Also, the filmarray instrument (serial# (b)(4)) was working as designed and not suspected as a cause of the discrepancy.Based on the information provided, the investigation concluded that the most likely causes for the positive result was due to: low level organism or nucleic acid contamination that may have been introduced during sample collection/testing or that occurred during manufacturing.The signature of cryptococcus assay observed in the run file showed delayed amplification of the cryptococcus assay that suggests the organism was present at a low concentration near the limit of detection for the assay.One similar complaint was received form the customer site that showed delayed amplification of the cryptococcus assay and was performed one week before this incident.While contamination protocol may have been followed, false positives may occur as a result of introducing the contaminant organism or nucleic acid into the sample from the laboratory environment, equipment such as pipettes, pipette tips, etc., or personnel handling the sample.Caution should be exercised during specimen collection, handling, transportation, storage, and testing as there is a risk of false positive results.Particular attention should be given to the laboratory precautions noted under the warnings and precautions section.Viral, bacterial, and yeast nucleic acid may persist in vivo independently of organism viability.Detection of organism targets does not imply that the corresponding organisms are infectious or the causative agents for clinical symptoms (section: limitations in the me instructional booklet [rfit-prt-0276-03 june 2017]).Comparator sensitivity/specificity difference between filmarray me panel and latex antigen testing on a low level sample.Although rare, sensitivity/specificity differences between filmarray me panel and other comparator methods are part of the normal performance for the system that is observed in the field.In the filmarray me panel instruction booklet [rfit-prt-0276-03 june 2017], the comparator method used to evaluate filmarray me panel c.Neoformans/gattii performance was pcr with bi-directional sequencing.The performance was also calculated in comparison to specific testing for cryptococcus that was performed by the laboratory based upon clinician test requests for a subset of subjects.For data that were available, filmarray me panel performance is shown (table 11 of the me panel instruction booklet) relative to cryptococcal antigen testing (n=196), standard culture (n=1560), and fungal culture (n=23).Notably, seven out of eight crag-positive specimens were discordant with filmarray me panel results.All seven of these specimens were negative for cryptococcus when tested with both pcr comparator assays.Medical chart review indicated that each subject was on antifungal therapy for treatment of cryptococcal meningitis or cryptococcosis at the time of specimen collection and/or had prior history of cryptococcus infection.Therefore, positive antigen results for these patients in the absence of pcr and culture-based organism detection are likely due to antigen persistence rather than the presence of live organism.Clinical performance for cryptococcus neoformans/gattii: sensitivity of 100%(1/1) and sensitivity of 99.7% (95% ci 99.3-99.9%)(table 9 of me instructional booklet).C.Neoformans/gattii was detected in 2/4 fp specimens using a commercially available antigen test.One fp specimen was positive by standard culture.The comparator method use to evaluate filmarray me panel c.Neoformans/gattii performance was pcr with bi-directional sequencing.C.Neoformans/gattii was detected at 100% at a limit of detection concentration of 100 cfu/ml for strains c.Neoformans var.Grubii, type strain, h99 [h99jp, nysd 1649] atcc 208821 and c.Gattii, strain a6mr38, aflp6c, vgiic atcc mya-4877 (table 17 of me instructional booklet).It is important to note that 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.Positive results do not rule out coinfection with organisms not included in the filmarray me panel.The agent detected may not be the definite cause of the disease.Not all agents of cns infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert.

Event Description

(b)(6) reported a discrepant cryptococcus result on the filmarray meningitis/ encephalitis (me) panel using a patient cerebrospinal fluid (csf) sample.Patient care was affected due to the filmarray results.Upon investigation, no malfunction occurred and the system was working within specifications.The investigation concluded that the most likely cause for the discrepant result was due to low level organism in the sample and comparator sensitivity/specificity differences.On (b)(6) 2018, biofire received additional information from the customer indicating that the patient had died.Biofire has requested additional information about the cause of death, but has not received additional information.Biofire has no information to suggest that use of the filmarray me panel caused or contributed to the patient's death.

• Brand Name: FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL
• Type of Device: FILMARRAY ME PANEL
• Manufacturer (Section D): BIOFIRE DIAGNOSTICS, LLC; 515 colorow drive; salt lake city UT 84108
• Manufacturer Contact: kristen kanack ; 515 colorow drive; salt lake city, UT 84108 ; 8017366354
• MDR Report Key: 7858817
• MDR Text Key: 119636362
• Report Number: 3002773840-2018-00002
• Device Sequence Number: 1
• Product Code: PLO
• UDI-Device Identifier: 00815381020130
• UDI-Public: 00815381020130
• Combination Product (y/n): N
• Reporter Country Code: CO
• PMA/PMN Number: K160462
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: health professional
• Reporter Occupation: Physician
• Type of Report: Initial
• Report Date: 09/09/2018

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 09/09/2018
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Expiration Date: 02/02/2019
• Device Model Number: RFIT-ASY-0119
• Device Catalogue Number: RFIT-ASY-0119
• Device Lot Number: 506318
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 08/10/2018
• Was Device Evaluated by Manufacturer?: No
• Date Device Manufactured: 02/09/2018
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Death
• Patient Age: 76 YR