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.

Device Description

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:

1. Candida albicans and/or Candida tropicalis,
1. Candida parapsilosis
1. 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.

AI/ML Overview

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.

Summary

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December 12, 2017

T2 Biosystems, Inc. Anne Whalen Sr. Director, Regulatory and Clinical Affairs 101 Hartwell Avenue Lexington, Massachusetts 02421

Re: K173536

Trade/Device Name: T2Candida 1.1 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: PII Dated: November 13, 2017 Received: November 15, 2017

Dear Anne Whalen:

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 (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. 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.

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 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/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

For

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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T2 Biosystems, Inc. T2Candida 1.1 Panel for use on the T2Dx® Instrument Special 510(k) Submission

	DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration	Form Approved: OMB No. 0910-0120Expiration Date: 06/30/2020See PRA Statement below.
	Indications for Use
510(k) Number (if known)
Device Name	T2Candida 1.1 Panel
Indications for Use (Describe)	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:1. Candida albicans and/or Candida tropicalis2. Candida parapsilosis3. Candida glabrata and/or Candida kruseiThe 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.
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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15.	510(k) SUMMARY
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Date of Summary	November 13, 2017
Product Name	T2Candida® 1.1 Panel
Sponsor	T2 Biosystems, Inc.101 Hartwell AvenueLexington, MA 02421
Correspondent	T2Biosystems, Inc.Anne Marie Whalen, PhDSr. Director, Regulatory and Clinical AffairsOffice: (781) 761-4647Mobile: (908) 581-3440Fax : (781) 357-3080awhalen@t2biosystems.com
Device Trade or Proprietary Name	T2Candida® 1.1 Panel
Regulation	21 CFR 866.3690
Common Name	Candida Species Nucleic Acid Detection System
Product Code	PII
Classification	Class II
Classification Panel	Microbiology (83)

Intended Use Statement

1. Candida albicans and/or Candida tropicalis,
1. Candida parapsilosis
1. 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

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T2 Biosystems, Inc.

T2Candida 1.1 Panel for use on the T2Dx® Instrument Special 510(k) Submission

Page 50 of 147

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.

Limitations:

For prescription use only. Please refer to the T2Bacteria Panel labeling for a more complete list of warnings, precautions, and contraindications.

Principles of Operation:

The fundamental scientific technology and principle of operation of the T2Candida 1.1 Panel on the T2Dx instrument is equivalent to that used in the original T2Candida Panel, as submitted and cleared (DEN140019, Summary Decision September, 2014). The T2Candida 1.1 Panel utilizes the same magnetic resonance-based detection (T2®MR technology) to qualitatively detect the same five species of Candida: Candida albicans and/or Candida tropicalis, Candida parapsilosis, Candida glabrata and/or Candida krusei, 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 at a limit of detection as low as 1 CFU/mL in approximately 3.5 hours. The test incorporates an Internal Control (IC) for monitoring test performance. The internal control for the T2Candida 1.1 Panel has not been changed from the original assay. 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.

In response to stability issues caused by the generation of inhibitory byproducts originating from two, foil-sealed tubes containing calcium hypochlorite ("bleach tubes") in the T2Candida Cartridge, a design change to remove the bleach tubes from the cartridge configuration and modify the software to remove the bleach transfer steps from the T2Dx workflow (collectively referred to the "the bleach steps") was made under design control. The bleach tubes were originally included as a precautionary element of post-testing decontamination, and are unrelated to the performance of the assay, and do not impact the fundamental scientific technology of the T2Candida Panel.

With the exception of the addition of an assay version to the T2Candida label (1.1), and the addition of a brand name for positive (T2Candida QCheck) and negative (T2Dx QCheck) External Controls, the intended use and fundamental scientific technology of these product remains unchanged. There are no changes except branding to the external controls.

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Page 51 of 147

Performance Data

The removal of the bleach steps does not impact the fundamental scientific technology associated with the T2Candida Panel intended use or operation. Two performance issues were addressed to validate the T2Candida 1.1 Panel, run in the absence of the bleach steps: the potential of higher cross-contamination in the absence of the bleach steps and recovery of stability in the absence of the bleach byproduct inhibitor.

1. To determine that the absence of bleach does not result in higher levels of cross-contamination/carryover (i.e. lower specificity) two specificity studies were conducted with human whole blood pooled from healthy donors triplespiked with either high titer (100 CFU or 1000 CFU) of C. albicans, C. parapsilosis and C. qlabrata (APG) or C. tropicalis and C. parapsilosis and C. krusei (TPK). Negative samples were human whole blood samples from the same pool without spiking. Samples were loaded such that Negative Samples and Positive APG or TPK were positioned in adjacent drawers. Results obtained with the T2Candida 1.1 Panel (with bleach tubes removed) were compared with original data submitted to FDA (DEN140019).

Channel	T2Candida Panel(DEN140019 Predicate)%Specificity (± 95% CI)	T2Candida 1.1 Panel%Specificity (± 95% CI)
A/T	99.5 (97.4-99.9)	100.0 (97.1-100.0)
P	100.0 (98.3-100.0)	99.2 (95.7-99.9)
K/G	99.5 (97.4-99.9)	99.2 (95.7-99.9)
Overall	99.7 (98.9-99.9)	99.5 (98.1-99.9)

The results verified that specificity for each target was statistically equivalent to the original claim.

1. Stability studies of the T2Candida 1.1 Cartridge demonstrated that the reduced stability originally observed in the presence of the bleach steps has been mitigated. Based on these studies, expiration dates can be set at 8 months, with studies ongoing to extend this product shelf-life.

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T2 Biosystems, Inc. T2Candida 1.1 Panel for use on the T2Dx® Instrument Special 510(k) Submission

0(k) Submission						Page 52 of 147
Time point	Negative Sample Equivalence Test			Positive Sample Equivalence Test
CartridgeStability Lot	Lot 1	Lot 2	Lot 3	Lot 1	Lot 2	Lot 3
	WO-05642	WO-05822	WO-05920	WO-05642	WO-05822	WO-05920
Three Months(T3)	Pass	Pass	Pass	Pass	Pass	Pass
Six Months (T6)	Pass	Pass	Pass	Pass	Pass	Pass
Nine Months (T9)	Pass	Pass	Pass	Pass	Pass	Pass

Elimination of the bleach steps required software revisions. This set of commands, which executed the bleach transfer from the bleach tubes to all spent reaction vessels in the cartridge assembly, were eliminated for T2Candida 1.1 Panel. The Assay Definition File and T2Dx instructions are the same in all other ways, including the task scheduler, timing of each task and safe-waiting limits. The removed software commands do not interact with other steps in the workflow and are executed after results are reported; therefore, results reporting are not affected.

Conclusion

The design change was implemented to address the issue of product stability by removal of two bleach tubes from the T2Candida 1.1 Cartridge and elimination of the bleach transfer steps. Removal of the bleach steps has allowed for an acceptable shelf-life for the T2Candida 1.1 Panel, can be implemented with no discernible impact on assay performance, with demonstrated equivalence to key validation criteria, and without changing the intended use or fundamental scientific technology of the original cleared test. Validation of the design change demonstrates equivalent performance to the original test, but with increased stability.

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Regulation Number and Section

§ 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.