(133 days)
Not Found
No
The description focuses on the T2MR technology, nucleic acid amplification, and automated sample processing. There is no mention of AI or ML being used for data analysis or interpretation. The results are interpreted by the T2Dx applications software as valid/invalid and positive/negative/indeterminate based on the generated signal, which appears to be a rule-based or threshold-based system, not AI/ML.
No
Explanation: The device is a diagnostic test intended to aid in the diagnosis of bacteremia by detecting bacterial species. It explicitly states that "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," which indicates it is not used for therapy.
Yes
The device is explicitly stated to be "indicated as an aid in the diagnosis of bacteremia." It detects bacterial species directly from whole blood specimens, providing information that contributes to the diagnostic process, even if results are not solely used for diagnosis, treatment, or patient management decisions.
No
The device description explicitly states that the assay is performed on the "proprietary T2Dx platform" and involves loading a "single use self-contained unit that contains all of the reagents and disposables required to run a single test" onto the instrument. This indicates the device includes significant hardware components (the T2Dx instrument and the cartridge) in addition to software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "direct detection of bacterial species in K2EDTA human whole blood specimens with suspected bacteremia" and is indicated as "an aid in the diagnosis of bacteremia." This clearly describes a test performed on a biological sample (whole blood) to provide information for medical diagnosis.
- Device Description: The description details a test that analyzes a human biological specimen (whole blood) using laboratory techniques (nucleic acid amplification, T2MR detection) to identify specific analytes (bacterial DNA).
- Performance Studies: The document includes extensive performance studies (Analytical Reactivity, Analytical Specificity, Interfering Substances, Competitive Inhibition, Clinical Performance) which are standard for demonstrating the performance of an IVD.
- Key Metrics: The document provides key metrics like Sensitivity, Specificity, and False Positive percentages, which are used to evaluate the performance of diagnostic tests.
- Predicate Device: The mention of a predicate device (K172708; T2Bacteria Panel) indicates that this device is being compared to a previously cleared IVD.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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.
Product codes
QBX, NSU
Device Description
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A multicenter reproducibility study was performed to determine the run to run, reagent lot, day to day and site to site reproducibility. Testing was performed at three sites (two external with a panel of five target species, each tested in triplicate at two concentrations (1-2X LoD and 3-4X LoD) using two reagent lots. Testing was performed for six non-consecutive days with at least two operators per site for a total of 36 replicates per sample per site.
The reproducibility panel was comprised of each target spiked in fresh human whole blood specimens in triple-spiked samples (A. baumannii / K. pneumoniae / S. aureus or E. coli / P. aeruginosa / E. faecium). Bacterial levels were confirmed by colony count testing of the original suspension used for spiking. A total of 108 negative blood samples were included in reproducibility panel.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Summary of Analytical Performance (Acinetobacter baumannii)
- Limit of Detection (LoD): The LoD was established by testing a minimum of twenty replicates each of two strains of A. baumannii. at multiple concentrations. The LoD established for A. baumannii. in the T2Bacteria Panel is 3 CFU/mL.
- Reproducibility: A multicenter reproducibility study was performed at three sites. Total of 108 negative blood samples included.
- A. baumannii, S. aureus and K. pneumoniae Spike (1-2 x LoD): N Pos / N Total 108/108, % Accurate 100, 95% CI 96.6-100
- A. baumannii, S. aureus and K. pneumoniae Spike (3-4 x LoD): N Pos / N Total 108/108, % Accurate 100, 95% CI 96.6-100
- E. coli, P. aeruginosa, and E. faecium Spike (1-2 x LoD): N Pos / N Total 1/108, % Accurate 99.1, 95% CI 94.9-100
- E. coli, P. aeruginosa, and E. faecium Spike (3-4 x LoD): N Pos / N Total 0/108, % Accurate 100, 95% CI 96.6-100
- Negatives: N Neg / N Total 108/108, % Accurate 100, 95% CI 96.6-100
- Analytical Reactivity (Inclusivity): A total of 14 organisms were evaluated for inclusivity of A. baumannii. Testing was performed in triplicate, with retesting of 20 replicates if false negative. All 14 isolates tested Pass.
- Analytical Specificity (Exclusivity): Analytical exclusivity testing included 128 different organisms. The test results establish the specificity of A. baumannii on the T2Bacteria Panel in the presence of all organisms tested at 1,000 units / mL.
- Interfering Substances: Studies evaluated the impact of potential endogenous interfering substances on A. baumannii detection. Feraheme (Ferumoxytol) at concentrations ≥ 21 µg/mL interfered; other substances did not.
- Competitive Inhibition: No competitive effects were observed in samples containing competing species at ≤1,000 CFU/mL for A. baumannii on the T2Bacteria Panel when co-infected with other panel targets or non-panel organisms.
Summary of Clinical Performance (Acinetobacter baumannii)
- Study Design: Evaluated at eleven sites in the US, compared to blood culture. 1,427 subjects prospectively, plus 50 contrived specimens and 300 additional blood samples not spiked with A. baumannii.
- Overall Performance (Prospective and Contrived Arms):
- Sensitivity (PPA): 97.5% (39/40), 95% CI 87.1% - 99.6%
- Specificity (NPA): 99.2% (1713/1727), 95% CI 98.6% - 99.5%
- Prospective Arm:
- Sensitivity (PPA): --- (0/0), 95% CI --- (cannot be calculated as no positive specimens identified by blood culture)
- Specificity (NPA): 99.1% (1414/1427), 95% CI 98.4 - 99.5%
- Contrived Arm PPA based on LoD:
- ≥ LoD: 97.5% (39/40), 95% CI 87.1 - 99.6%
§ 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.
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Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo, which features a stylized caduceus. To the right is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
February 8, 2024
T2 Biosystems, Inc. Rachel Gilbert Manager, Regulatory Affairs 101 Hartwell Avenue Lexington, Massachusetts 02421
Re: K233184
Trade/Device Name: T2Bacteria Panel Regulation Number: 21 CFR 866.3960 Regulation Name: Nucleic Acid-Based Device For The Amplification, And Identification Of Microbial Pathogens Directly From Whole Blood Specimens Regulatory Class: Class II Product Code: QBX, NSU Dated: September 28, 2023 Received: September 28, 2023
Dear Rachel Gilbert:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K233184
Device Name T2Bacteria Panel
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
| Date of Summary | February 5, 2024 |
|---|---|
| Product Name | T2Bacteria® Panel |
| Sponsor | T2Biosystems, Inc. |
| 101 Hartwell Avenue | |
| Lexington, MA 02421 | |
| Correspondent | Rachel Gilbert |
| Associate Director, Regulatory Affairs | |
| 781-226-2767, 1970 | |
| rgilbert@t2biosystems.com | |
| Device Trade or Proprietary Name | T2Bacteria® Panel |
| Regulation | 21 CFR 866.3960 |
| Common Name | Nucleic acid-based device for the amplification, detection and |
| identification of microbial pathogens directly from whole blood | |
| specimens | |
| Product Code | QBX, NSU |
| Classification | Class II |
The purpose of this pre-market 510(k) submission is to amend the T2Bacteria Panel initially cleared under K172708. The following changes to the Panel are addressed within the submission:
- Addition of Acinetobacter baumannii to the device intended use/indications for use .
- . Removal of the warnings related to false positives for E. coli and P. aeruginosa from the panel labeling
No changes have been made to the device components or technology since the initial clearance of the T2Bacteria Panel.
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Intended Use
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 from patients with suspected bacteremia. The T2Bacteria Panel identifies six species of bacteria: Acinetobacter baumannii, Enterococcus faecium, 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 the sole basis for diagnosis, treatment, or other patient management decisions in patients with suspected bacteremia.
Limitations
For prescription use only.
Please refer to the T2Bacteria Panel labeling for a more complete list of warnings, precautions, and contraindications.
Methodology
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
5
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.
Summary of Analytical Performance (Acinetobacter baumannii)
Limit of Detection (LoD)
The limit of detection (LoD) for was determined by spiking whole blood specimens with A. baumannii. The LoD is defined as the lowest concentration (CFU/mL) of A. baumannii. that can be detected at a rate ≥ 95%. The LoD was established by testing a minimum of twenty replicates each of two strains of A. baumannii. at multiple concentrations. The LoD established for A. baumannii. in the T2Bacteria Panel is shown in Table 1.
Table 1: T2Bacteria Confirmed Limit of Detection - Acinetobacter baumannii
| Species | Strain 1 LoD | Strain 2 LoD | Final Confirmed LoD |
|---|---|---|---|
| Acinetobacter baumannii | 3 CFU/mL | 3 CFU/mL | 3 CFU/mL |
Reproducibility
A multicenter reproducibility study was performed to determine the run to run, reagent lot, day to day and site to site reproducibility. Testing was performed at three sites (two external with a panel of five target species, each tested in triplicate at two concentrations (1-2X LoD and 3-4X LoD) using two reagent lots. Testing was performed for six non-consecutive days with at least two operators per site for a total of 36 replicates per sample per site.
The reproducibility panel was comprised of each target spiked in fresh human whole blood specimens in triple-spiked samples (A. baumannii / K. pneumoniae / S. aureus or E. coli / P. aeruginosa / E. faecium). Bacterial levels were confirmed by colony count testing of the original suspension used for spiking. A total of 108 negative blood samples were included in reproducibility panel.
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| Sample Type | Concentration | Ab |
|---|---|---|
| A. baumannii, S. aureus and | ||
| K. pneumoniae Spike | 1-2 x LoD | N Pos / N Total 108/108 |
| % Accurate 100 | ||
| 95% CI 96.6-100 | ||
| 3-4 x LoD | N Pos / N Total 108/108 | |
| % Accurate 100 | ||
| 95% CI 96.6-100 | ||
| E. coli, P. aeruginosa, and E. | ||
| faecium Spike | 1-2 x LoD | N Pos / N Total 1/108 |
| % Accurate 99.1 | ||
| 95% CI 94.9-100 | ||
| 3-4 x LoD | N Pos / N Total 0/108 | |
| % Accurate 100 | ||
| 95% CI 96.6-100 | ||
| Negatives | N/A | N Neg / N Total 108/ |
| 108 | ||
| % Accurate 100 | ||
| 95% CI 96.6-100 |
Table 2: Summary of Reproducibility Results – Acinetobacter baumannii
Analytical Reactivity (Inclusivity)
Analytical reactivity testing was conducted to ensure that the T2Bacteria Panel is capable of detecting multiple strains of A. baumannii. Clinical isolates were chosen based on resistance, phylogenetic, temporal, and geographic diversity and spiked into whole blood at 2-3x the established LoD.
A total of 14 organisms were evaluated for inclusivity of A. baumannii on the T2Bacteria Panel. Testing was performed in triplicate. In the event of a false negative result, testing was repeated with 20 replicates and 19/20 replicates had to generate a positive result to be considered passing. Test results summarized in Table 3 demonstrate that the T2Bacteria Panel is able to detect multiple strains of A. baumannii.
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| Isolate ID | N=3 | N=20 | Study Pass/Fail |
|---|---|---|---|
| 17961 | 3/3 | NT | Pass |
| BAA-2093 | 3/3 | NT | Pass |
| BAA-1878 | 3/3 | NT | Pass |
| BAA-747 | 2/3 | 20/20 | Pass |
| BAA-1797 | 3/3 | NT | Pass |
| 51432 | 3/3 | NT | Pass |
| 17904 | 3/3 | NT | Pass |
| BAA-1605 | 3/3 | NT | Pass |
| 13421 | 3/3 | NT | Pass |
| LMG 10542 | 3/3 | NT | Pass |
| LMG 10551 | 3/3 | NT | Pass |
| LMG 1157 | 3/3 | NT | Pass |
| LMG 22454 | 3/3 | NT | Pass |
| CCUG 6644 | 3/3 | NT | Pass |
Table 3: Results Summary for T2Bacteria Reactivity (Inclusivity) Testing – Acinetobacter baumannii
Analytical Specificity (Exclusivity)
Analytical exclusivity testing of the T2Bacteria Panel was conducted to assess the cross-reactivity of A. baumannii to non-panel species at 1,000 units/mL concentrations (CFU, TCID-so, or copies /mL where applicable) of pathogenically, phylogenetically, or environmentally relevant organisms in whole blood. Species that were shown to be potentially cross-reactive at the initial test concentration were further evaluated at lower target concentrations using a pre-defined titration scheme (100, 33, and 10 units/mL). Analytical testing of the T2Bacteria Panel included 128 different organisms comprised of the T2Bacteria Panel members themselves, viruses, and pathogenically, or environmentally relevant bacterial and fungal species. The test results establish the specificity of A. boumannii on the T2Bacteria Panel in the presence of all organisms tested at 1,000 units / mL.
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Table 4: Bacteria Species for which no reactivity was detected at 1,000 CFU/mL – Acinetobacter baumannii
| Non-Reactive Bacteria Species | ||
|---|---|---|
| Acinetobacter calcoaceticus | Escherichia fergusonii | Raoultella ornithinolytica |
| Acinetobacter Iwoffi | Finegoldia magna | Raoultella planticola |
| Acinetobacter nosocomialis | Fusobacterium necrophorum | Salmonella enterica Enteritidis |
| Acinetobacter pittii | Fusobacterium nucleatum | Salmonella enterica Typhimurium |
| Acinetobacter radioresistans | Klebsiella oxytoca | Serratia marcescens |
| Actinomyces israelii | Klebsiella variicola | Shewanella putrefaciens |
| Aeromonas hydrophila | Lactobacillus acidophilus | Shigella boydii |
| Bacteroides fragilis | Lactococcus lactis | Shigella dysenteriae |
| Burkholderia cepacia | Leptotrichia trevisanii | Shigella flexneri |
| Chryseobacterium indologenes | Leuconostoc mesenteroides | Shigella sonnei |
| Citrobacter koseri | Listeria monocytogenes | Staphylococcus auricularis |
| Clostridium sphenoides | Moraxella catarrhalis | Staphylococcus capitis |
| Corynebacterium jeikeium | Morganella morganii | Staphylococcus epidermidis |
| Cupriavidus pauculus | Myroides odoratus | Staphylococcus haemolyticus |
| Enterobacter aerogenes | Ochrobactrum anthropi | Staphylococcus hominis |
| Enterobacter cloacae | Oligella urethralis | Staphylococcus lugdunensis |
| Enterobacter hormaechei | Pantoea agglomerans | Staphylococcus saprophyticus |
| Enterococcus avium | Parvimonas micra | Staphylococcus warneri |
| Enterococcus caccae | Pediococcus pentosaceus | Staphylococcus xylosus |
| Enterococcus casseliflavus | Peptostreptococcus anaerobius | Stenotrophomonas maltophilia |
| Enterococcus cecorum | Peptoniphilus harei | Streptococcus agalactiae |
| Enterococcus dispar | Plesiomonas shigelloides | Streptococcus anginosus |
| Enterococcus durans | Propionibacterium acnes | Streptococcus bovis |
| Enterococcus faecalis | Proteus mirabilis | Streptococcus constellatus |
| Enterococcus gallinarum | Proteus vulgaris | Streptococcus dysgalactiae |
| Enterococcus gilvus | Providencia stuartii | Streptococcus oralis |
| Enterococcus hirae | Pseudomonas alcaligenes | Streptococcus mutans |
| Enterococcus italicus | Pseudomonas fluorescens | Streptococcus pneumoniae |
| Enterococcus malodoratus | Pseudomonas luteola | Streptococcus pyogenes |
| Enterococcus mundtii | Pseudomonas oryzihabitans | Streptococcus salivarius |
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| 510(k) Summary | Page 7 of 14 | ||
|---|---|---|---|
| Non-Reactive Bacteria Species | |||
| Enterococcus pallens | Pseudomonas pseudoalcaligenes | ||
| (oleovorans) | Weeksella virosa | ||
| Enterococcus pseudoavium | Pseudomonas putida | Yersinia pseudotuberculosis | |
| Enterococcus raffinosus | Pseudomonas stutzeri | ||
| Escherichia albertii | Ralstonia pickettii |
Table 5: Fungal Species for which no reactivity was detected at 1,000 CFU/mL – Acinetobacter baumannii
| Non-Reactive Fungal Species | ||
|---|---|---|
| Aspergillus fumigatus | Candida parapsilosis | Fusarium oxysporum |
| Aspergillus niger | Candida tropicalis | Rhizomucor miehei |
| Candida albicans | Cryptococcus albidus | Rhizopus microsporus |
| Candida glabrata | Cryptococcus neoformans | Rhizopus oryzae |
| Candida krusei | Fusarium moniliforme | Rhodotorula glutinis |
Table 6: Viral Species for which no reactivity was detected at 1,000 units – Acinetobacter baumannii
| Non-Reactive Viral Species | ||
|---|---|---|
| Adenovirus1 | Epstein-Barr Virus2 | Herpes Simplex Virus 11 |
| Cytomegalovirus1 | Hepatitis A Virus2 | Herpes Simplex Virus 21 |
| Enterovirus Type 681 | Hepatitis B Virus1 | Varicella-Zoster Virus2 |
4Units = TCID50/mL; 2Units= Copies/mL
Interfering Substances
Studies were conducted to evaluate the impact of potential endogenous interfering substances on the performance of A. baumannii on the T2Bacteria Panel. These substances were added to negative whole blood samples or to whole blood samples multi-spiked with either A. baumannii at 2-3x LoD. Three replicate samples were run for each interfering substance tested.
All of the substances were tested in excess of standard reference or physiological levels and did not interfere with the performance of A. baumannii with the exception of Feraheme). Initially, Ferumoxytol was tested at 618 µg/ml, which is threefold higher than its tmax of 206 µg/mL, but was found to be inhibitory to the performance of A. baumannii on the T2Bacteria Panel. Dilutions of Ferumoxytol
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were performed and it was determined that concentrations ≥ 21 µg/mL interfere with the performance of A. baumannii on the T2Bacteria Panel.
| Endogenous Substances &
Concentrations | Exogenous Substances &
Concentrations |
|----------------------------------------------------|---------------------------------------------------------|
| Albumin 60 g/L | Amphotericin B Trihydrate 240 µg/mL |
| ALT 120 U/liter | Ampicillin 152 µmol/L |
| AST 144 U/liter | Azithromycin 15.3 µmol/L |
| Bilirubin (conjugated) 342 µmol/L | Caspofungin 52.8 µg/mL |
| Bilirubin (unconjugated) 342 µmol/L | Cefepime Hydrochloride 492 µg/mL |
| Creatinine 50 mg/L | Cefazolin Sodium Salt 2.643 mmol/L |
| Gamma Globulin 60 g/L | Cefoxitin Sodium Salt 180 µg/mL |
| Hemoglobin 22.8 - 23.9 g/dL | Ceftazidime Pentahydrate 487 µg/mL |
| Human DNA 2.2 µg/mL | Ciprofloxacin 30.2 µmol/L |
| Intralipid (to mimic triglycerides) 3270 mg/dL | Clindamycin HCl 89.1 µmol/L |
| Lactoferrin 7.5 µmol/L | Cytarabine 32.4 µg/mL |
| Urea 42.9 mmol/L | Dexamethasone 1.53 µg/mL |
| White Blood Cells 2.08 x 107 - 2.48 x 107 cells/mL | EDTA 5.4 mg/mL |
| | Fluconazole 245 µmol/L |
| | Gentamicin sulfate 21 µmol/L |
| | Heparin 3,000 U/L |
| | Isovue 370 180 µL per 4mL vacutainer |
| | Linezolid 55.8 µg/mL |
| | Lisinopril 0.74 µmol/L |
| | Magnevist (gadopentetate dimeglumine) 1.5 mM |
| | Meropenem trihydrate 186 µg/mL |
| | Metronidazole 701 µmol/L |
| | Micafungin 90 mg/L |
| | Piperacillin/Pipril 117 µg/mL |
| | Primaxin, 50:50 ratio of Imipenem: Cilastatin 528 µg/mL |
| | Tazobactam (Tazobac) 18.9 µg/mL |
| | Vancomycin 103 µg/mL |
Table 7: Substances Tested for Interference with the T2Bacteria Panel: No Interference Observed – Acinetobacter baumannii
Competitive Inhibition
A Competitive Inhibition Study was conducted on the T2Bacteria Panel to evaluate A. baumannii performance in the presence of other Panel bacterial target species at high and low concentrations as well as selected bacterial and fungal non-Panel target organisms. The conditions tested included: co-infection with A. baumannii and an additional Panel target species both at or near the LoD; co-infection with A. baumannii and an additional Panel target species where one species is at high titer (1,000 CFU/mL) and the other is at or near the LoD; and co-infection with A. baumannii at or near the LoD and a non-Panel
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species at high titer (1,000 CFU/mL). Four replicates were tested and if any false negative results were generated, the test was repeated with 20 replicates.
No competitive effects were observed in samples containing competing species at ≤1,000 CFU/mL for A. baumannii on the T2Bacteria Panel.
Summary of Clinical Performance (Acinetobacter baumannii)
The performance of A. baumannii on the T2Bacteria Panel was evaluated at eleven sites within the US and compared to the reference method of blood culture. Patients were enrolled prospectively and two paired sample collections, one for blood culture and one for testing by the T2Bacteria Panel were drawn from each subject. The blood culture systems used in the study were BD Bactec™ FX, bioMerieux BacT/ALERT™, and Thermo Fisher VersaTREK®. Species identification was performed on all positive bacteria cultures and methods included Gram stain, bioMerieux Vitek® 2, bioMerieux or Bruker MALDI TOF, and PCR. The T2Bacteria Panel A. baumannii result was compared against results from these blood culture systems for Positive Percent Agreement (PPA) and Negative Percent (NPA). A total of 1,427 subjects were tested prospectively. Due to the low prevalence of the organisms contained in the Panel, an additional 50 contrived specimens were evaluated at three sites. Contrived specimens were prepared by spiking A. baumannii at defined concentrations (CFU/mL) into healthy donor whole blood. Further, an additional 300 blood samples not spiked with A. baumannii members were also evaluated as part of the contrived arm of the study. 250 of these blood samples were spiked with the additional 5 bacterial species available on the T2Bacteria Panel (50 each).
Table 8 summarizes the overall PPA (sensitivity) and NPA (specificity) of A. baumannii from the prospective and contrived arms of the study.
| Species | Sensitivity (PPA) | Specificity (NPA) | ||
|---|---|---|---|---|
| PPA | ||||
| (TP / (TP + FN)) | 95% Cl | NPA | ||
| (TN / (FP + TN)) | 95% Cl | |||
| A. baumannii | 97.5% (39/40) | 87.1% - 99.6% | 99.2% (1713/1727) | 98.6% - 99.5% |
| Table 8: Overall Performance of the T2Bacteria Panel in the Clinical | |
|---|---|
| Study – Acinetobacter baumannii |
• Sensitivity (PPA) calculated against samples with titer levels at or above limit of detection (LoD) in Contrived Arm and blood culture positives in Prospective Arm
• Specificity (NPA) calculated from all samples (including below LoD and unspiked negative samples) as the total number of negative channels divided by total number of non-spiked channels in Contrived Arm and blood culture negatives in Prospective Arm.
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Prospective Arm: T2Bacteria Panel Performance vs. Blood Culture
In the prospective arm of the specificity (NPA) of A. baumannii on the T2Bacteria Panel against blood culture from all included subjects was evaluated. The sensitivity (PPA) could not be calculated for A. baumannii as there were no positive specimens identified by blood culture.
Table 9: T2Bacteria Panel Performance Characteristics for the Prospective Arm of the Clinical Study – Acinetobacter baumannii
| Target Species | PPA | NPA | ||
|---|---|---|---|---|
| Sensitivity | 95% CI | Specificity | 95% CI | |
| A. baumannii | --- (0/0) | --- | 99.1% | |
| (1414/1427) | 98.4 - 99.5% |
Table 10: T2Bacteria Panel vs. Blood Culture Contingency table, All Included Subjects – Acinetobacter baumannii
| Ab | ||||
|---|---|---|---|---|
| Blood culture | ||||
| + | - | |||
| T2 | + | 0 | 13 | 13 |
| - | 0 | 1414 | 1414 | |
| 0 | 1427 | 1427 | ||
| Value - 95% CI + 95% Cl | ||||
| PPA | --- | --- | --- | |
| NPA | 99.1% | 98.4% | 99.5% |
Contrived Arm
Results for the Contrived arm were further analyzed based on A. baumannii concentration (either above or below the LoD).
Table 11: PPA for Contrived Specimens Above and Below the LoD – Acinetobacter baumannii
| Target Species | LoD
(CFU/mL) | ≥ LoD | | A. baumannii | 3 | 97.5% (39/40) | 87.1 - 99.6% | 40.0% (4/10) | 16.8 - 68.7% |
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Evaluation of False Positive Results
Overall, in the prospective study, there were 13 T2+/BC- potential false positive results. consisting of 35 T2+/BC+ concordant results and 155 T2+/BC- potential false positive results. Of the 13 potential false positive results, 1 represented a result for which an additional blood specimen (drawn at the same time as the original positive T2 specimen) was positive by an amplification and gene sequencing method.
| Species | T2(+)/
BC(-)
total | Other
Blood
Culture
positive1 | Sequencing
positive2 | T2(+) / BC(-)
associated with
strong evidence
of infection3 | T2(+) / BC(-)
associated with
other evidence of
infection Non-Blood
Matrices Culture
Positive4 | T2(+) / BC(-)
associated with
no evidence of
infection |
|---------------------|--------------------------|----------------------------------------|-------------------------|----------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------|
| A. baumannii | 13 | 0 | 1 | 7.7% (1/13) | 0.0% (0/13) | 92.3% (12/13) |
Table 12: Summary of T2 (+)/BC (-) Results in Prospective Arm -Acinetobacter baumannii
4 Blood cultures positive for the T2 species identified other than the paired blood culture and processed within ± 14 days of collection of the T2 sample.
2 Sequencing from blood samples drawn at the as collection of the T2 sample and positive for the T2 species identified, where this sequencing assay was only run on subjects without positive evidence from other sample sources (footnote 1 and 4).
3 Strong evidence defined as a T2 positive result associated with a blood culture positive from a different draw than T2 draw or a sequencing positive result from a blood sample drawn concurrently with the T2 draw.
Evaluation of A. baumannii, E. coli, and P. aeruginosa Detection in Negative Blood Samples
Following manufacturing process and facility improvements undertaken by T2 Biosystems to improve the cleanliness of the reagents in the T2Bacteria Panel, data from the testing for ten (10) different lots of T2Bacteria Panel reagents with negative human whole blood was retrospectively pulled and evaluated for percent false positivity. A total of 980 valid samples were evaluated, 98 replicates for each reagent lot. Testing demonstrated A. baumannii had an overall fall positive percentage of 0.2%, E. coli had an overall false positive percentage of 0.5%, and P. aeruginosa had an overall false positive percentage of 0.4%.
A. baumannii
Testing negative whole blood with ten different lots of T2Bacteria Panel reagents resulted in two (2) lots that contained a single A. boumannii false positive each. Across the different lots the NPA ranged from 99% to 100%. Overall results from testing 980 samples demonstrated a 99.8% NPA and a false positive percentage of 0.2%.
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E. coli
Testing negative whole blood with ten different lots of T2Bacteria Panel reagents resulted in single false positive detection of E. coli in 5 different lots. Across the different lots the NPA ranged from 99% to 100%. Overall results from testing 980 samples demonstrated a 99.5% NPA and a false positive percentage of 0.5%.
P. aeruginosa
Testing negative whole blood with ten different lots of T2Bacteria Panel reagents resulted in three (3) lots that contained false positives for P. aeruginosa. Across the NPA ranged from 98% to 100%. Overall results from testing 980 samples demonstrated a 99.6% NPA and a false positive percentage of 0.4%.
| Channel | % False Positive | 95% CI |
|---|---|---|
| A. baumannii | 0.2% | 0.1% - 0.7% |
| E. coli | 0.5% | 0.2% - 1.2% |
| P. aeruginosa | 0.4% | 0.2% - 0.4% |
Table 13: Percent False Positive – A. baumannii, E. coli, P. aeruginosa
Additional Testing of A. baumannii Contrived Samples
Testing was completed on thirty-three unique strains of Acinetobacter baumannii that were spiked individually into human whole blood at 2-3x LoD (6-9 CFU/mL). Testing was conducted across four (4) different T2Dx devices, utilized two (2) lots of cartridges, two (2) lots of reagents and blood from five (5) unique donors over 9 testing days. Testing demonstrated positive detection of all strains except for one (32/33).
Table 14: PPA for A. baumannii
| A. baumannii
Concentration
Tested | PPA
(TP/(TP+FN)) | 95% Cl |
|-----------------------------------------|---------------------|--------------|
| 6-9 CFU/mL | 97.0% (32/33) | 84.7 - 99.5% |
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Predicate Comparison
Table 15: Comparison Between T2Bacteria Panel and Predicate Device
| Characteristic | T2Bacteria Panel
(New Device) | T2Bacteria Panel (K172708)
(Predicate Device) |
|---------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| FDA Product Code | QBX, NSU | Same |
| Regulatory Classification | Class II | Same |
| Regulation Number | 21 CFR 866.3960 | Same |
| Intended Use/Indications for Use | 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 from patients with suspected bacteremia. The T2Bacteria Panel identifies six species of bacteria: Acinetobacter baumannii, Enterococcus faecium, 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 the sole basis for diagnosis, treatment, or other patient management decisions in patients with suspected bacteremia. | 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 from patients with suspected bacteremia. The T2Bacteria Panel identifies five species of bacteria: Enterococcus faecium, 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 the sole basis for diagnosis, treatment, or other patient management decisions in patients with suspected bacteremia. |
| Sample Type | 4 ml whole blood collected in a blood collection tube with K₂EDTA anticoagulant | Same |
| Test Platform | T2Dx Instrument | Same |
| Reagent Trays | T2Bacteria Test Reagents for detection of bacteria | Same |
| Test Cartridge Format | T2Bacteria Test Cartridge and disposables | Same |
| Test Principle | Nucleic acid amplification followed by T2 magnetic resonance detection | Same |
| Differences | | |
| Characteristic | T2Bacteria Panel (New Device) | T2Bacteria Panel (K172708) (Predicate Device) |
| Targets | Six (6) different species of bacteria commonly implicated in bacteremia: Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus | Five (5) different species of bacteria commonly implicated in bacteremia: Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus |
| Warnings Statements – False-Positives | None | During prospective clinical studies, false positive results were observed for E. coli and P. aeruginosa in prospectively collected specimens. Users should be aware of the possibility of occurrence of false positive results, especially for E. coli and P. aeruginosa and should closely monitor QCheck negative control results for any trends and determine the need for action. |
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