MAUDE Adverse Event Report: NANOSPHERE, INC. VERIGENE GRAM NEGATIVE BLOOD CULTURE NUCLEIC ACID TEST (BC-GN); VERIGENE SYSTEM, BC-GN

Model Number 10-0000-07

Device Problems Electrical /Electronic Property Problem (1198); Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Bacterial Infection (1735); Death (1802); Sepsis (2067)

Event Date 10/09/2019

Event Type  Death  

Manufacturer Narrative

Per the initial reporting on 10/25/19, the lab technician speculated that verigene's result contributed to patient death.Luminex made multiple requests for clarification from the medical director, however no response was received.The medical director did not provide a statement regarding the delay of treatment based on verigene reporting.Therefore, luminex was unable to determine if the additional zebaxa treatment was delayed due to the verigene reporting.It should be noted that per the verigene bc-gn package insert, "bc-gn is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, is not used to monitor these infections" (pg.1 of document 027-00039-01).Luminex's investigation has determined that this product is adequately labeled.Although the verigene testing resulted in "all targets not detected" for the applicable resistance markers, the bc-gn pi states "a not detected result for any of the antimicrobial resistance markers does not indicate susceptibility, as resistance may occur by other mechanisms.Sub-culturing and ast testing is required in order to assign a resistant and/or susceptible phenotype to each isolate recovered from the blood culture sample".In addition, it should be noted that the bc-gn package insert states "bc-gn will only report resistance marker gene results when an organism is also detected by the assay".The verigene bc-gn consumable lots used at the time of the noted discrepancy were released with 100% call accuracy.At the time of reporting, no additional customer sites reported false negative results for pseudomonas aeruginosa or resistance markers with the bc-gn consumable lots listed.The consumable data was reviewed and documentation showed no indication of a consumable malfunction.After the customer reported the discrepant false negative results on the verigene sp instrument (sn 19057002), a luminex field service engineer went to the customer site and determined that the sonication horns were not functioning properly.In addition, the field service engineer verified that the hybridization heater required recalibration.Following the replacement of the sonication board, sonication horns and recalibration of the hybridization heater, all associated tests for functionality passed.Following the initial repair, the customer continued to see unexpected results and it was determined that the instrument was unable to be repaired per the field service manual and was returned to luminex for additional inspection.A new, verigene processor sp was installed at the customer site.Upon receipt, the luminex vrf determined that verigene processor sp 19057002 passed all associated testing.

Event Description

On (b)(6) 2019, customer reported that sample 419306 was processed using the test cartridge id 02113752 for use on the verigene gram-negative blood culture nucleic acid test (bc-gn) on the verigene system.The verigene result was "all targets not detected".This was reported out to a physician on (b)(6) 2019 @ 23:00.The patient sample was cultured for morphology identification.The customer tested on the microscan platform for resistance and susceptibility testing.The culture result was received on 10/6/19 as pseudomonas aeruginosa identified.On (b)(6) 2019, the microscan identified pseudomonas aeruginosa with resistance to the following: cefepime, ceftazidime, ciprofloxacin, meropenem, piperacillin/tazobactam; treatment was amended on (b)(6) 2019.The hospital facility notified luminex (parent company of nanosphere) of the discrepancy between the verigene bc-gn and culture/microscan results on (b)(6) 2019 and provided details of the treatment.The expected result was "pseudomonas aeruginosa detected and imp, vim, oxa, ndm, kpc and ctx-m detected".The patient was treated with zosyn and tobramycin on 10/3/19 to treat the initial blood infection following admission, which was not amended for approximately 72 hours following the verigene result reporting.Following the microscan result, treatment was altered to include zerbaxa on (b)(6) 2019.On (b)(6) 2019, the patent expired at 22:43 from sepsis.

Manufacturer Narrative

Corrected data regarding the evaluation of the verigene processor sp, serial number: (b)(6), by the luminex vrf has been included in this report.The initial report stating that verigene processor sp, serial number: (b)(6), passed all associated testing is categorically false.Evaluation into the returned system indicated that there was a localized power event that led to the failure of the sonication board pcba, which contributed to the "all targets not detected" assay result.

Event Description

Verigene processor sp, serial number: (b)(6), was returned to the luminex vrf for investigation on november 8, 2019.Upon investigation into the verigene system, it was found that a hardware failure contributed to the "all targets not detected", false negative result.As an element of the investigation performed under work order: (b)(4), the system nap log for verigene processor sp (serial number: (b)(6) was reviewed historically, with a beginning date of (b)(6) 2019.During the course of this investigation, it was determined that an unexpected verigene system power loss and "reboot" occurred on (b)(6) 2019 while performing systematic sonication steps in the midst of an assay run.Prior to this "reboot" event, the verigene system was recording an appropriate level of utilized current for the sonication horns but following the event, subsequent assay runs did not have adequate sonication current levels (current was recorded in the nap logs as 0.000a).Recorded sonication current of 0.000a is an indication of a sonication board (pcba) failure.Subsequent investigation on the impact of a sonication board failure upon performed bc-gn assays indicated that bc-gn assay results would be negatively impacted by a board failure.The bc-gn assay requires the function of the sonication board to drive the sonication horn, which is responsible for the fragmentation of bacterial dna extracted from an organism present in a positive blood culture.The failure to fragment bacterial dna from a positive blood culture would result in a false negative result for a patient sample, as the performance controls within the bc-gn assay function without requiring dna fragmentation and would not indicate an assay processing failure.A luminex molecular applications specialist consulted with the customer site to determine if there were any local, facility related issues that could have led to the unexpected power loss event on (b)(6) 2019 and to determine if the customer is meeting the mechanical requirements as defined in verigene system user manual 89-00002-00-591, revision a.The luminex molecular applications specialist determined that at the time of theunexpected power loss event, the verigene instrument was not plugged into an uninterruptible power supply (ups), it was plugged directly into a 110v wall outlet.Following this unexpected power loss event, the customer relocated the verigene system and currently has the verigene system correctly installed with ups power protection as described in the verigene system user manual 89-00002-00-591, revision a.Additional investigation associated with work order: (b)(4) was conducted to determine if there was any potential impact or contribution from the verigene system hybridization heater to the reported adverse event.Scrutiny of the hybridization heater indicated that the heater passed verification using a validated hybridization test fixture, illustrating that the hybridization heater is functioning as intended.In addition, the verigene system nap logs were reviewed relative to the function of the hybridization heater.There was no indication within the verigene system nap logs that the hybridization heater was not functioning as intended.Visual inspection of the hybridization heater and functional testing of the heater wiring harness were also performed and both passed with no noted anomaly.Through this investigation, it was concluded that there is no indication the verigene hybridization heater contributed to the adverse event.

• Brand Name: VERIGENE GRAM NEGATIVE BLOOD CULTURE NUCLEIC ACID TEST (BC-GN)
• Type of Device: VERIGENE SYSTEM, BC-GN
• Manufacturer (Section D): NANOSPHERE, INC.; 4088 commercial ave.; northbrook, il IL 60062
• MDR Report Key: 9363438
• MDR Text Key: 167629405
• Report Number: 3006028115-2019-00002
• Device Sequence Number: 1
• Product Code: PEN
• UDI-Device Identifier: 00857573006140
• UDI-Public: 00857573006140
• Combination Product (y/n): N
• PMA/PMN Number: K132843
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: company representative,health
• Remedial Action: Recall
• Type of Report: Initial,Followup
• Report Date: 06/16/2020

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 11/22/2019
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 02/02/2020
• Device Model Number: 10-0000-07
• Device Catalogue Number: 10-0000-07
• Device Lot Number: 080219021A
• Was Device Available for Evaluation?: Device Returned to Manufacturer
• Date Returned to Manufacturer: 11/08/2019
• Date Manufacturer Received: 10/25/2019
• Is This a Reprocessed and Reused Single-Use Device?: No
• Removal/Correction Number: 3006028115-6/16/20-001-C
• Patient Sequence Number: 1
• Patient Outcome(s): Death
• Patient Age: 64 YR