(133 days)
The T2Bacteria Panel run on the T2Dx Instrument is a qualitative T2 Magnetic Resonance (T2MR) test for the direct detection of bacterial species in K2EDTA human whole blood specimens with suspected bacteremia. The T2Bacteria Panel identifies six species of bacter baumannii, Enterococus faccium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus.
The T2Bacteria Panel is indicated as an aid in the diagnosis of bacteremia and results should be used in conjunction with other clinical and laboratory data. Concomitant blood cultures are necessary to recover organisms for susceptibility testing or further identification and for organisms not detected by the T2Bacteria Panel.
Results from the T2Bacteria Panel are not intended to be used as for diagnosis, treatment, or other patient management decisions in patients with suspected bacteremia.
The T2Bacteria Panel detects and identifies six bacterial target species directly from whole blood specimens and independent of blood culture using nucleic acid amplification and proprietary T2MR detection technology. The assay is performed on the proprietary T2Dx platform. The whole blood specimen, drawn into a blood collection tube containing K₂EDTA is used for the test. The blood collection tube containing a minimum of 3 mL of blood is loaded directly onto the T2Dx instrument as part of the assembled Cartridge, a single use self-contained unit that contains all of the reagents and disposables required to run a single test. Fully automated on the T2Dx, the blood specimen is mixed with the Lysis Reagent to lyse the red blood cells and the bacterial cells are concentrated by centrifygation. The Internal Control is added to the concentrated bacterial cells, which then undergo a bead beating step to lyse the bacteria cells. The supernatant containing the DNA from the lysed bacterial cells and the Internal Control are amplified with the target and Internal Control specific primers. The generated amplicon is then aliquoted into individual tubes containing target specific conjugated particles for Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and the Internal Control. These individual tubes are read in the MR reader and a signal is generated.
Up to seven specimens can be loaded onto the T2Dx Instrument in parallel. When running a single specimen, the first result is reported in 3.5 hours from the specimen is loaded onto the instrument. The results are interpreted using the T2Dx applications software as valid or invalid, and if valid, target specific results are reported as Positive or Target not Detected. For one target, the Escherichia coli channel, results are reported as Positive, Indeterminate, or Target not Detected. An Indeterminate result is a valid result, but the presence or absence of Escherichia coli cannot be definitively assessed, and the indeterminate status applies only to the Escherichia coli channel. Results are displayed on the T2Dx touchscreen and can be printed. Raw T2MR data are not available to the end user.
Here's a summary of the acceptance criteria and study details for the T2Bacteria Panel, specifically concerning the addition of Acinetobacter baumannii detection:
Acceptance Criteria and Device Performance for Acinetobacter baumannii
| Criteria Category | Acceptance Criteria (Targeted) | Reported Device Performance for Acinetobacter baumannii |
|---|---|---|
| Limit of Detection (LoD) | Lowest concentration (CFU/mL) detected at ≥ 95% | 3 CFU/mL (for both tested strains) |
| Reproducibility | High accuracy/concordance across sites, lots, days, operators. | 1-2x LoD: 100% Accurate (108/108), 95% CI 96.6-100 |
| 3-4x LoD: 100% Accurate (108/108), 95% CI 96.6-100 | ||
| Negatives: 100% Accurate (108/108), 95% CI 96.6-100 | ||
| Analytical Reactivity (Inclusivity) | Detection of multiple strains at 2-3x LoD. If false negative, must pass with 19/20 replicates. | Passed for all 14 evaluated strains. One strain (BAA-747) initially showed 2/3 detection but passed with 20/20 replicates upon retesting. |
| Analytical Specificity (Exclusivity) | No cross-reactivity with non-panel species at 1,000 units/mL. | No reactivity detected for 90 non-reactive bacteria species, 11 fungal species, and 9 viral species at 1,000 CFU/mL (or TCID50/mL, Copies/mL for viruses). |
| Interfering Substances | No interference from common endogenous/exogenous substances. | No interference observed from 13 endogenous and 22 exogenous substances at tested concentrations, with the exception of Ferumoxytol (Feraheme). Ferumoxytol at concentrations ≥ 21 µg/mL interferes with performance. |
| Competitive Inhibition | No competitive effects in co-infection scenarios. | No competitive effects observed in samples containing competing species (panel targets or non-panel organisms) at ≤1,000 CFU/mL. |
| Clinical Performance (Overall PPA) | Calculated against samples with titer ≥ LoD (contrived) and blood culture positives (prospective). | 97.5% (39/40), 95% CI 87.1% - 99.6% |
| Clinical Performance (Overall NPA) | Calculated from all samples (including |
§ 866.3960 Nucleic acid-based device for the amplification, detection, and identification of microbial pathogens directly from whole blood specimens.
(a)
Identification. A nucleic acid-based device for the amplification, detection, and identification of microbial pathogens directly from whole blood specimens is a qualitative in vitro device intended for the amplification, detection, and identification of microbial-associated nucleic acid sequences from patients with suspected bloodstream infections. This device is intended to aid in the diagnosis of bloodstream infection when used in conjunction with clinical signs and symptoms and other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.
(6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(7) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.
(8) As part of the risk management activities performed as part of your 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.