(27 days)
T2Candida 1.1 Panel and T2Dx Instrument is a qualitative T2 Magnetic Resonance (T2MR) assay for the direct detection of Candida species in K2EDTA human whole blood specimens from patients with symptoms of, or medical conditions predisposing the patient to, invasive fungal infections. The T2Candida 1.1 Panel identifies five species of Candida and categorizes them into the following three species groups:
- Candida albicans and/or Candida tropicalis
- Candida parapsilosis
- Candida glabrata and/or Candida krusei
The T2Candida 1.1 Panel is indicated for the presumptive diagnosis of candidemia. The T2Candida 1.1 Panel is performed independent of blood culture. Concomitant blood cultures are necessary to recover organisms for susceptibility testing or further identification. The T2Candida QCheck Positive and T2Dx QCheck Negative External Controls are intended to be used as quality control samples with the T2Candida 1.1 Panel when run on the T2Dx Instrument. These controls are not intended for use with other assays or systems.
The T2Candida 1.1 Panel run on the T2Dx® Instrument is a qualitative T2 Magnetic Resonance (T2MR®) assay for the direct detection of Candida species in EDTA human whole blood specimens from patients with symptoms of, or medical conditions predisposing the patient to, invasive fungal infections. The T2Candida Panel identifies five species of Candida and categorizes them into the following three groups:
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- Candida albicans and/or Candida tropicalis,
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- Candida parapsilosis
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- Candida qlabrata and/or Candida krusei
The T2Candida 1.1 Panel does not distinguish between C. albicans and C. tropicalis. The T2Candida 1.1 Panel does not distinguish between C. glabrata and C. krusei. The T2Candida Panel is indicated for the presumptive diagnosis of candidemia. The T2Candida Panel is performed independent of blood culture. Concomitant blood cultures are necessary to recover organisms for susceptibility testing or further identification. The T2Candida positive (T2Candida QCheck) and negative External Controls (T2Dx QCheck) are intended to be used as quality control samples with the T2Candida 1.1 Panel when run on the T2Dx Instrument. These controls are not intended for use with other assays or systems. The T2Candida 1.1 Panel utilizes magnetic resonance-based detection (T2®MR technology) to qualitatively detect the same five species of Candida direct from K2EDTA-treated human whole blood. The T2Candida 1.1 Panel, run on the T2Dx instrument, performs sample concentration and Candida target DNA amplification for direct detection of species-specific amplicon. The test incorporates an Internal Control (IC) for monitoring test performance. The workflow for T2Candida 1.1 Panel is the same as the original cleared test and can only be performed on the T2Dx instrument, a bench-top, automated sample-to-result system, which performs all steps in the test after specimen loading. A design change was made to remove two foil-sealed tubes containing calcium hypochlorite ("bleach tubes") from the T2Candida Cartridge configuration and modify the software to remove the bleach transfer steps from the T2Dx workflow.
- Candida qlabrata and/or Candida krusei
Here's an analysis of the acceptance criteria and study findings for the T2Candida 1.1 Panel, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
| Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|
| Maintain Specificity (non-inferiority to predicate) | T2Candida 1.1 Panel % Specificity (95% CI): |
- A/T Channel: 100.0 (97.1-100.0)
- P Channel: 99.2 (95.7-99.9)
- K/G Channel: 99.2 (95.7-99.9)
- Overall: 99.5 (98.1-99.9)
Compared favorably to the predicate (T2Candida Panel DEN140019) specificity. |
| Improved Product Stability (ability to achieve acceptable shelf-life) | Product shelf-life demonstrated at 8 months, with studies ongoing to extend it. Stability issues observed with the predicate panel due to bleach byproducts were mitigated. |
2. Sample Size and Data Provenance
- Test Set Sample Size: Not explicitly stated as a single number. Two specificity studies were conducted, each involving:
- Human whole blood pooled from healthy donors.
- Samples triple-spiked with high titer (100 CFU or 1000 CFU) of Candida species (C. albicans, C. parapsilosis, C. glabrata or C. tropicalis, C. parapsilosis, C. krusei).
- Negative samples were human whole blood from the same pool without spiking.
- Samples were loaded such that Negative Samples and Positive APG or TPK were positioned in adjacent drawers.
- Data Provenance: The studies appear to be conducted internally by the manufacturer (T2 Biosystems, Inc.) in a controlled laboratory setting. The origin of the healthy donor whole blood is not specified (e.g., country of origin). The studies are retrospective modifications to an existing device, validating the changes.
3. Number of Experts and Qualifications
This information is not provided in the text. The study focuses on laboratory performance metrics (specificity, stability) rather than human interpretation or expert-adjudicated ground truth.
4. Adjudication Method
This information is not applicable/provided in the text. The device is a qualitative diagnostic assay, and the study evaluates its direct detection performance against known spiked concentrations. There's no mention of human adjudication of results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was done. The device is a standalone diagnostic panel, not one designed for human-in-the-loop assistance. The study focuses on the device's technical performance.
6. Standalone Performance
- Yes, a standalone performance study was done. The specificity studies described directly evaluate the T2Candida 1.1 Panel's ability to accurately detect Candida species (or their absence) in blood samples, without human intervention in the diagnostic process beyond sample loading and result interpretation.
7. Type of Ground Truth Used
- Known Spiked Samples: The ground truth for the specificity studies was established by preparing blood samples with known concentrations (high titer: 100 CFU or 1000 CFU) of specific Candida species or known negative (unspiked) blood samples. This is a form of controlled laboratory spiking to simulate infection.
8. Sample Size for Training Set
- Not explicitly provided. The document describes a Special 510(k) submission for a modified version (1.1) of an already cleared device. It states the fundamental scientific technology and principle of operation are equivalent to the original T2Candida Panel (cleared as DEN140019). Information regarding the training set for the original algorithm or the 1.1 update is not presented in this document.
9. How Ground Truth for Training Set Was Established
- Not explicitly provided. As with the training set size, this document focuses on the validation of the modified device. Details on how the ground truth was established for the original algorithm's development (training) are not included.
§ 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.