MAUDE data represents reports of adverse events involving medical devices. This maude entry was filed from a distributor,foreign,health pr report with the FDA on 2019-02-15 for FILMARRAY? MENINGITIS/ENCEPHALITIS (ME) PANEL RFIT-ASY-0119 manufactured by Biofire Diagnostics, Llc.
[136336798]
A customer (through (b)(4)) reported a discrepant c. Neoformans/gattii result on the filmarray me panel after testing a csf sample from a (b)(6), immunocompromised, male patient. The patient was admitted to the er due to headache and confusion on (b)(6) 2018. The patient had cirrhosis of the liver and leukopenia of unknown cause. Aseptic meningitis was suspected, and the patient was put on antibiotics and acyclovir upon arrival. A csf sample was then collected, tested on the filmarray me panel within an hour, and the result was negative for c. Neoformans/gatti. The sample was not centrifuged or incubated prior to testing. Due to the negative filmarray me panel result, the treatment was changed to supportive therapy. The customer did not indicate if any other tests were performed at this time. The patient was released from the hospital on (b)(6) 2018. On (b)(6) 2018, the patient was readmitted to a second hospital ((b)(6) medical center [(b)(6)]) with severe symptoms (the customer did not specify what symptoms). A new csf sample was collected for culture and was positive for c. Neoformans. The patient's condition continued to worsen and the patient died (date deterioration began and date of death are unknown). The customer stated that the cause of death was cryptococcal meningitis. The customer reported that due to the negative filmarray me panel result, appropriate treatment was delayed and ultimately the patient's condition deteriorated followed by death. Despite multiple attempts by biofire, more information regarding the patient's death has not been provided. The initial hospital performed retrospective testing on the csf sample (collected and frozen on (b)(6) 2018). Retrospective testing included crag and a regular pcr method. Both tests were positive and confirmed c. Neoformans. Biofire has offered to test the original csf sample that was collected and frozen on (b)(6) 2018. The customer has not responded to this request for in-house investigation. Quality control (qc) records for pouch lot#103318 (kit lot# 695118) were reviewed. This pouch lot passed the qc criteria and was found within specifications. No run malfunction was observed and the filmarray instrument (serial# (b)(4)) was working within specifications. Conclusion: the investigation concluded the discrepancy is most likely due to: sensitivity/specificity differences between antigen and pcr methods. An antigen test can be more sensitive than a nucleic acid test as crag is shed in large amounts in blood and csf and can be detected even prior to onset of clinical symptoms. Pcr methods can differ in many ways including chemistry, nucleic acid extraction/purification, assay target regions, software analysis, limits of detection (lod), and many other factors causing potential discrepancies when comparing two pcr methods. The performance of pcr can be affected by the level of genetic material present in the sample. Organism concentrations below threshold may amplify at much later cycles and not be detected. No amplification or melt signatures were observed in the filmarray me panel test run file, so it is possible that the nucleic acid target was not present in the sample or it was below the lod of the system. Different assay gene target regions can also lead to discrepant results with other pcr based methods and test performance may not be concordant. Clinical performance of cryptococcus showed a lod of 100 cfu/ml with a ppa of 100% and npa of 99. 7% (ci 99. 3-99. 9%) as compared to pcr/sequencing. The comparator method use to evaluate filmarray me panel c. Neoformans/gattii performance was pcr with bidirectional sequencing. Filmarray panel performance for detection of cryptococcus 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. 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. (table 21 and 11 of the filmarray me panel instruction booklet [https://www. Online-ifu. Com/iti0035]). Potential sample handling error. Although the filmarray is an automated, multiplex pcr system that integrates sample preparation, amplification, detection, and analysis, user error is a potential risk for discrepant results. The detection of organism nucleic acid is dependent upon proper sample collection, handling, transportation, storage, and preparation. Failure to observe proper procedures in any one of these steps can lead to false positive or false negative results. The rna process control and the pcr 2 control will not indicate whether or not nucleic acid has been lost due to inadequate collection, transport or storage of specimens. In this instance, the instrument and pouch were operating as expected and a malfunction of these is not suspected as the cause of the discrepancy, and sample handling error cannot be ruled out. Notably, the customer indicated that the patient was on antibiotic and antiviral treatment prior to sample collection and was immunocompromised. These factors may also have contributed to the missed detection of cryptococcus on the filmarray me panel ("limitations" section of the filmarray me panel instruction booklet [https://www. Online-ifu. Com/iti0035]). It is also important to note that a trained healthcare professional should carefully interpret the results from the filmarray me panel in conjunction with a patient's signs and symptoms and results from other diagnostic tests. A negative filmarray me panel result does not exclude the possibility of cns infection and should not be used as the sole basis for diagnosis, treatment, or other management decisions. There is a risk of false negative values due to the presence of sequence variants or rearrangements in the gene targets of the assay, procedural errors, inhibitors in specimens, technical error, sample mix-up, or infection caused by an organism not detected by the filmarray me panel. Test results may also be affected by concurrent antimicrobial therapy or levels of organism in the sample that are below the lod. The filmarray me panel is 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.
Patient Sequence No: 1, Text Type: N, H10
[136336799]
A customer (through (b)(4)) reported a discrepant cryptococcus neoformans/gattii (c. Neoformans/gattii) result on the filmarray meningitis/encephalitis (me) panel after testing a cerebrospinal fluid (csf) sample from a (b)(6), immunocompromised, male patient. According to the customer, the discrepant filmarray me panel result led to inappropriate patient treatment, subsequent patient deterioration and death. Upon investigation, it was found that no malfunction occurred and the filmarray me panel system was working within specifications. The investigation concluded that the most likely causes for the discrepant result were: sensitivity/specificity differences between antigen and pcr methods, and/or sample handling error.
Patient Sequence No: 1, Text Type: D, B5
| Report Number | 3002773840-2019-00001 |
| MDR Report Key | 8345345 |
| Report Source | DISTRIBUTOR,FOREIGN,HEALTH PR |
| Date Received | 2019-02-15 |
| Date of Report | 2019-02-15 |
| Date of Event | 2018-09-30 |
| Date Mfgr Received | 2019-01-16 |
| Device Manufacturer Date | 2018-07-03 |
| Date Added to Maude | 2019-02-15 |
| Event Key | 0 |
| Report Source Code | Manufacturer report |
| Manufacturer Link | Y |
| Number of Patients in Event | 0 |
| Adverse Event Flag | 3 |
| Product Problem Flag | 3 |
| Reprocessed and Reused Flag | 3 |
| Reporter Occupation | OTHER HEALTH CARE PROFESSIONAL |
| Health Professional | 3 |
| Initial Report to FDA | 3 |
| Report to FDA | 3 |
| Event Location | 3 |
| Manufacturer Contact | KRISTEN KANACK |
| Manufacturer Street | 515 COLOROW DRIVE |
| Manufacturer City | SALT LAKE CITY UT 84108 |
| Manufacturer Country | US |
| Manufacturer Postal | 84108 |
| Manufacturer Phone | 8017366354 |
| Manufacturer G1 | BIOFIRE DIAGNOSTICS, LLC |
| Manufacturer Street | 515 COLOROW DRIVE |
| Manufacturer City | SALT LAKE CITY UT 84108 |
| Manufacturer Country | US |
| Manufacturer Postal Code | 84108 |
| Single Use | 3 |
| Previous Use Code | 3 |
| Event Type | 3 |
| Type of Report | 3 |
| Brand Name | FILMARRAY? MENINGITIS/ENCEPHALITIS (ME) PANEL |
| Generic Name | FILMARRAY? MENINGITIS/ENCEPHALITIS (ME) PANEL |
| Product Code | PLO |
| Date Received | 2019-02-15 |
| Model Number | RFIT-ASY-0119 |
| Catalog Number | RFIT-ASY-0119 |
| Lot Number | 695118 |
| Operator | HEALTH PROFESSIONAL |
| Device Availability | N |
| Device Eval'ed by Mfgr | Y |
| Device Sequence No | 1 |
| Device Event Key | 0 |
| Manufacturer | BIOFIRE DIAGNOSTICS, LLC |
| Manufacturer Address | 515 COLOROW DRIVE SALT LAKE CITY UT 84108 US 84108 |
| Patient Number | Treatment | Outcome | Date |
|---|---|---|---|
| 1 | 0 | 1. Death | 2019-02-15 |