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

Model Number RFIT-ASY-0118

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

Patient Problem Death (1802)

Event Date 07/17/2018

Event Type  Death  

Manufacturer Narrative

Investigation: (b)(6) reported a (b)(6) result on the filmarray me panel using two csf collections from a pediatric patient.The initial csf sample was collected from the patient on (b)(6) 2018 and tested within 30 minutes on the filmarray me panel, where (b)(6) results for (b)(6) were obtained.The customer then performed a second lumbar puncture on the patient on (b)(6) 2018 and the filmarray me panel results from the second sample were again (b)(6) for (b)(6).After the second collection, both csf samples were tested on a comparator pcr method (altona real star kit) specific for (b)(6) detections.Results were (b)(6) for (b)(6) using the altona method.No additional comparator testing was performed on these samples.The customer stated that clinical findings indicated that the patient suffered from encephalitis.Csf analysis for both samples were the following: (b)(6).Due to the filmarray results, the patient treatment was changed from (b)(6).The patient later died and biofire was notified on july 24, 2018.The customer stated that the patient was not immunocompromised but suffered from hermansky-pudlak-syndrome.Biofire has been unable to obtain additional information on the status of the patient, duration of treatment, and other underlying conditions despite multiple attempts.Qc records for pouch lot# 835018 (kit lot# 527018) were reviewed and this lot passed the qc criteria and was found within specifications.Current field reports for the filmarray me panel in 2018 show a discrepant positive rate concordant with the claimed performance of the assay.No run malfunction was observed and filmarray instrument 2fa00476 was working within design specifications and is not suspected as a cause of the discrepancy.Conclusion: based on the information received, the most likely cause for the (b)(6) discrepancy include: 1- sensitivity/specificity differences between pcr methods with a low level clinical sample.Late (b)(6) amplification in both runs indicates this target was detected at or below the filmarray me panel's limit of detection.As with all pcr-based tests, results are dependent on the level of target present in the sample used.The filmarray detected (b)(6) in both samples that were collected three days apart.However, detection of an organism with a low sample concentration might vary between other qpcr comparator methods.Discrepant results between pcr methods can also be due to differences in chemistry, dna/rna regions targeted, mismatches within the assay target regions, software analysis, nucleic extraction methods, technical procedures, etc.These differences in hhv-6 detection by different pcr-based methods have also been documented previously [1-2].Most importantly, since hhv-6 was also detected in the second csf sample obtained almost three days following initial csf collection, it is likely that this result was due to low level organism present within the sample.Hhv-6 can exist in latent form that is reactivated during infection due to other pathogens, including agents not detected by the filmarray me panel that may cause meningitis/encephalitis.When detected by the filmarray me panel, hhv-6 should be considered as the likely cause of meningitis/encephalitis only in appropriate clinical settings and following expert consultation [3-4].Results from the filmarray me panel must be correlated with the clinical history, epidemiological data, and other data available to the clinician evaluating the patient.2- low level organism/nucleic acid.The detection of organism nucleic acid is dependent upon proper sample collection, handling, transportation, storage, and preparation.It is also possible that the discrepancy was the result of low level nucleic acid/organism introduced to the sample or pouch from the laboratory environment or from the lab personnel during the collection, handling or testing processes.Particular attention should be given to the laboratory precautions noted under the warnings and precautions section.Finally, it is also possible that low level contamination could have been introduced during the manufacturing process.Biofire diagnostics' quality control for the filmarray me panel kit reagents involves screening for organism and nucleic acid contamination using a high confidence statistical sampling of each lot of reagents and other kit components.Therefore, 100% of very low level or sporadic contamination events may not be detected by this process in every instance.The run signature observed in the customer run is not similar to the low rate unexpected positives observed in the qc process.Clinical performance for the filmarray me panel's hhv-6 assay during the clinical trial showed a 95% detection rate at limit of detection (1x10^4 copies/ml).Overall hhv-6 sensitivity was 85.7% (ci 65.4 - 95 %) and specificity was 99.7% (ci 99.3 - 99.9%).Hhv-6 was detected in 2/3 fn and 1/4 fp using an independent pcr assay.Table 20 of the filmarray me panel ifu [rfit-prt-0276, https://www.Online-ifu.Com/iti0035] shows the hhv-6 strains detected during the inclusivity testing of the filmarray me panel.Analytical sensitivity for the altona realstar hhv-6 assay was found at 1.49 copies/¿l eluate [95% confidence interval (ci): 0.98 - 2.63 copies/l] [5] the sample was requested from the customer for further evaluation.Reference: 1- flamand l, et al.2008.Multicenter comparison of pcr assays for detection of human herpesvirus 6 dna in serum.J clin microbiol.Vol 46(8):2700-06.2- govind s, et al.2017.Collaborative study to establish the 1st who international standard for human herpes virus 6b (hhv-6b) dna for nucleic acid amplification technique (nat)-based assays.Retrieved from the who ecbs report on hhv-6 on 7/26/18 from: http://www.Who.Int/biologicals/expert_committee/bs2321_hhv-6_who_ecbs_report_v5.Pdf.3- ogata, m., et al., human herpesvirus 6 (hhv-6) reactivation and hhv-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study.Clin infect dis, 2013.57(5): p.671-81.4- green da, et al.2018.Clinical significance of human herpesvirus 6 positivity on the filmarray meningitis/encephalitis panel.Clin infec diseases.Published online.Https://academic.Oup.Com/cid/advance-article-abstract/doi/10.1093/cid/ciy288/4964815?redirectedfrom=fulltext 5- retrieved from altona diagnostics on 7/26/2018 from: https://www.Altona-diagnostics.Com/files/public/content%20homepage/-%2002%20realstar/man%20-%20ce%20-%20en/realstar%20hhv-6%20pcr%20kit%201.0_web_ce_en-s02.Pdf.

Event Description

Biofire received a complaint from the (b)(6) regarding a (b)(6) result using patient cerebrospinal fluid (csf) with the filmarray meningitis/encephalitis (me) panel.The first csf sample was collected from a (b)(6) male with signs of encephalitis on (b)(6) 2018 and tested (b)(6) for (b)(6).A second csf sample was collected on (b)(6) 2018 and again tested (b)(6) for (b)(6) on the filmarray me panel.Both csf samples were then tested with an alternative method (altona real star kit).The csf samples were 24 hours and 72 hours old when they were tested with the altona test kit.Both csf samples were (b)(6) for (b)(6) using the alternative method.The customer claimed that due to the (b)(6) filmarray result, the patient's therapy was switched from (b)(6).The patient later died (exact date of death unknown).It is unclear if the change in treatment due to the filmarray me panel result caused or contributed to the patient's death.Multiple attempts to obtain additional information regarding the patient's symptoms at admission and cause of death were unsuccessful.

Manufacturer Narrative

Mdr 3002773840-2018-00001 (submitted july 31, 2018) was incorrectly marked as a 5-day report.Mdr 3002773840-2018-00001 should be listed as a 30-day report.

• Brand Name: FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL
• Type of Device: FILMARRAY® MENINGITIS/ENCEPHALITIS (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: 7736450
• MDR Text Key: 115606202
• Report Number: 3002773840-2018-00001
• Device Sequence Number: 1
• Product Code: PLO
• UDI-Device Identifier: 00815381020123
• UDI-Public: 00815381020123
• Combination Product (y/n): N
• Reporter Country Code: GM
• 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,Followup
• Report Date: 07/31/2018

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 07/31/2018
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Expiration Date: 02/16/2019
• Device Model Number: RFIT-ASY-0118
• Device Catalogue Number: RFIT-ASY-0118
• Device Lot Number: 527018
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 07/24/2018
• Was Device Evaluated by Manufacturer?: No
• Date Device Manufactured: 02/28/2018
• 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: 34 MO