The BACTEC® MGIT™ 960 SIRE Kit is a rapid qualitative procedure for susceptibility testing of Mycobacterium tuberculosis, from culture, to streptomycin (STR), isoniazid (INH), rifampin (RIF) and ethambutol (EMB). The BACTEC® MGIT™ 960 STR 4.0 Kit and the BACTEC® MGIT™ 960 INH 0.4 Kit are for testing at higher drug concentrations. The BACTEC® MGIT™ 960 SIRE kits are used with the BACTEC® MGIT™ 960 System. The BACTEC® MGIT™ 960 SIRE Kit final test concentrations are 1.0 µg/mL for streptomycin, 0.1 µg/mL for isoniazid, 1.0 µg/mL for rifampin and 5.0 µg/mL for ethambutol. The BACTEC® MGIT™ 960 STR 4.0 Kit final test concentration is 4.0 µg/mL for streptomycin and the BACTEC® MGIT™ 960 INH 0.4 Kit final test concentration is 0.4 µg/mL for isoniazid.

Device Description

The BACTEC® MGIT™ 960 SIRE susceptibility test kit is used with the BBL® Mycobacteria Growth Indicator Tube (MGIT™)-7mL on the BACTEC® MGIT™ 960 System. The tube is supplemented with BACTEC® MGIT™ 960 SIRE Supplement enrichment and prepared with the appropriate dilutions of streptomycin, isoniazid, rifampin and ethambutol as the mechanism for performing the susceptibility test. The BACTEC® MGIT™ 960 SIRE test utilizes a four to thirteen day testing protocol. A standardized suspension of Mycobacterium tuberculosis growth, from either solid or broth culture media, is prepared. An appropriate dilution is made of this suspension and 0.5 mL is inoculated into a Growth Control tube (drug-free) and tubes containing streptomycin, isoniazid, rifampin and ethambutol (this is referred to as an AST Set). The test interpretation is based on growth of the Mycobacterium tuberculosis isolate in the Growth Control tube compared to the growth in the drug-containing tubes. At the completion of the susceptibility testing protocol, the instrument reports a susceptible or resistant result for each drug at the concentration(s) being tested.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the BACTEC® MGIT™ 960 SIRE Kits, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state quantitative acceptance criteria in the typical pass/fail threshold sense. Instead, it presents the "observed results" or "overall agreement" as the performance metrics achieved during the studies. The standard for acceptance implicitly appears to be "substantial equivalence" to the predicate method.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance (Ethambutol)
Lot Reproducibility	N/A (Substantial Equivalence)	100%
CDC Challenge Panel Agreement (Analytical)	N/A (Substantial Equivalence)	100%
Clinical Reproducibility	N/A (Substantial Equivalence)	97.5%
CDC Challenge Panel Agreement (Clinical)	N/A (Substantial Equivalence)	93.3%
Clinical Isolate Agreement (Liquid Source - Susceptible)	N/A (Substantial Equivalence)	97%
Clinical Isolate Agreement (Liquid Source - Resistant)	N/A (Substantial Equivalence)	85%
Clinical Isolate Agreement (Solid Source - Susceptible)	N/A (Substantial Equivalence)	99%
Clinical Isolate Agreement (Solid Source - Resistant)	N/A (Substantial Equivalence)	80.0%

2. Sample Size Used for the Test Set and Data Provenance

Lot Reproducibility: 25 M. tuberculosis strains (including five ATCC strains).
CDC Challenge Panels: 30 challenge strains obtained from the Centers for Disease Control and Prevention (CDC), GA, USA.
Clinical Reproducibility: A panel of ten qualified strains.
Clinical Isolate Testing: A total of 106 clinical isolates of M. tuberculosis. This generated a total of 223 test results for ethambutol at the critical concentration (likely due to testing both liquid and solid culture sources).
Data Provenance: The document explicitly mentions "one foreign site" in the clinical evaluation, indicating international data. It also states "fresh clinical and stock isolates from both liquid and solid culture sources," implying both retrospective (stock isolates) and prospective (fresh clinical isolates) data. The CDC data is from the USA.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not specify the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with x years of experience).

For the clinical isolate testing, the ground truth appears to be established by comparison to the Method of Proportion (MOP) susceptibility test, which is the predicate device. For discordant results, MOP testing at two independent sites was performed.

For CDC Challenge Panels, the ground truth was the CDC expected results. The method by which CDC establishes these expected results is not detailed in this document.

4. Adjudication Method for the Test Set

For the clinical isolate testing, when discordant results occurred between the BACTEC® MGIT™ 960 SIRE ethambutol test and the MOP test, a form of adjudication was used: "All isolates with discordant BACTEC® MGIT™ 960 EMB 5.0 results were tested by MOP at two independent sites." The outcome of this re-testing presumably informed the final ground truth or understanding of the discrepancy. This can be considered a 2-site re-testing adjudication method for discordant cases.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not mentioned. This device is an automated in vitro diagnostic system for susceptibility testing, not an AI-powered image analysis tool where human reader performance would be a primary metric. Its comparison is against another laboratory testing method (MOP).

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, this is essentially a standalone performance study. The BACTEC® MGIT™ 960 SIRE system is an automated instrument that "automatically interprets" results. The performance data presented (reproducibility, agreement with CDC expected results, and comparison to MOP) reflects the performance of the device without human intervention in the interpretation of the primary growth signal. Human involvement would likely be limited to preparing samples and loading the instrument.

7. The Type of Ground Truth Used

Reference Method/Predicate Device: The primary ground truth for clinical isolates was the Method of Proportion (MOP) susceptibility test.
Established Reference Materials: For the CDC Challenge Panels, the ground truth was the CDC expected results.
Reproducibility: For reproducibility studies, the ground truth was "expected results" for the strains used, likely based on prior characterization or a consensus of reference methods.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" or its size. This is common for this type of IVD (in vitro diagnostic) device, where the underlying "algorithm" or system logic is based on established biological principles of microbial growth and drug inhibition rather than a machine learning model that requires a distinct training phase on clinical data. The development process would involve internal optimization and verification rather than a classic "training set" in the AI sense.

9. How the Ground Truth for the Training Set Was Established

As a "training set" is not explicitly mentioned, the method for establishing its ground truth is also not described. If one were to consider the initial development and optimization of the BACTEC® MGIT™ 960 SIRE system, the ground truth would have been established through a combination of traditional microbiology methods, laboratory testing, and potentially comparison to predicate devices, similar to how the current validation studies are performed.

Summary

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APR 1 9 2002

K014123

510(k) SUMMARY

Becton, Dickinson and Company SUBMITTED BY: 7 Loveton Circle Sparks, MD 21152
CONTACT: Jody Hoffmann, Regulatory Affairs Specialist (410) 316-4192 TELEPHONE:
PREPARED: April 12, 2002

BACTEC® MGIT™ 960 SIRE Kits DEVICE NAME:

PREDICATE

Method of Proportion agar plates DEVICES: BACTEC® 460TB SIRE Kit

The BACTEC® MGIT™ 960 SIRE Kit is a rapid qualitative INTENDED USE: brocedure for susceptibility testing of Mycobacterium tuberculosis, from culture, to streptomycin (STR), isoniazid (INH), rifampin (RIF) and ethambutol (EMB). The BACTEC® MGIT™ 960 STR 4.0 Kit and the BACTEC® MGIT™ 960 INH 0.4 Kit are for testing at higher drug concentrations.
The BACTEC® MGIT™ 960 SIRE kits are used with the BACTEC® MGIT™ 960 System.

DEVICE DESCRIPTION:

The BACTEC® MGIT™ 960 SIRE test utilizes a four to thirteen day testing protocol. A standardized suspension of Mycobacterium tuberculosis growth, from either solid or broth culture media, is prepared. An appropriate dilution is made of this suspension and 0.5 mL is inoculated into a Growth Control tube (drug-free) and tubes containing streptomycin, isoniazid, rifampin and ethambutol (this is referred to as an AST Set). The test interpretation is based on growth of the Mycobacterium tuberculosis isolate in the Growth Control tube compared to the growth in the drug-containing tubes.

At the completion of the susceptibility testing protocol, the instrument reports a susceptible or resistant result for each drug at the concentration(s) being tested.

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DEVICE COMPARISON:

The BACTEC® MGIT™ 960 SIRE susceptibility test is similar to the Method of Proportion (MOP) susceptibility test method in that:

Both methods test drug susceptibility of Mycobacterium tuberculosis culture . isolates.
Both methods use the same culture source, either liquid or solid culture . medium, for preparation of organism inoculum.
Both methods use the antimycobacterial drug ethambutol. .
Both methods compare organism growth in a control to organism growth in . the presence of the drug to obtain the susceptibility result.
. Both methods report test results as susceptible (S) or resistant (R).

The BACTEC® MGIT™ 960 SIRE susceptibility test differs from the MOP susceptibility test method in that:

The BACTEC® MGIT™ 960 SIRE kits use a modified Middlebrook 7H9 broth . as the growth medium while the MOP method uses Middlebrook 7H10 agar as the growth medium.
The BACTEC® MGIT™ 960 SIRE test utilizes a four to thirteen day testing . protocol while the MOP method requires a three week (21 day) testing protocol.
The BACTEC® MGIT™ 960 SIRE test is automatically monitored by the . instrument to detect organism growth using an oxygen sensitive fluorescent sensor while the MOP method requires manual monitoring of the plates to visually detect growth.
The BACTEC® MGIT™ 960 SIRE test data are automatically interpreted by . the instrument software while the MOP susceptibility test data are manually calculated for result interpretation.

The BACTEC® MGIT™ 960 SIRE susceptibility test is similar to the BACTEC® 460TB SIRE susceptibility test method in that:

Both methods test drug susceptibility of Mycobacterium tuberculosis culture . isolates.
Both methods use the same culture source, either liquid or solid culture . medium, for preparation of organism inoculum.
Both methods use modified Middlebrook 7H9 broth as the growth medium. .
Both methods use the antimycobacterial drug ethambutol. .
. Both methods compare organism growth in a control to organism growth in the presence of the drug to obtain the susceptibility result.
Both methods report test results as susceptible (S) or resistant (R). .

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The BACTEC® MGIT™ 960 SIRE susceptibility test differs from the BACTEC® 460TB SIRE susceptibility test method in that:

The BACTEC® MGIT™ 960 SIRE test utilizes a four to thirteen day testing . The BACTEC "MOT" - 000 SIRE method utilizes a four to twelve day testing protocol.
The BACTEC® MGIT™ 960 SIRE test is automatically monitored by the . instrument to detect organism growth using an oxygen sensitive fluorescent Instrument to delect organism growth acing an experies manual testing of sensor while the BAOTEO - 400 FB Off LE mon using a radioactive labeled end product.
The BACTEC® MGIT™ 960 SIRE test data are automatically interpreted by . The BACTEC "MOT" - 000 ORE 150 and are are are are are susceptibility test data are manually calculated for result interpretation.

SUMMARY OF PERFORMANCE DATA:

Analytical studies:

Lot Reproducibility

Reproducibility of the BACTEC® MGIT™ 960 SIRE ethambutol susceptibility test Reproducibility of the DAOTES - M. tuberculosis strains (to include five ATCCC
was evaluated using twenty-five M. tuberculosis strains (to include five ATCCC . was evaluated using twenty five in: taberouless on and to the 960 ethambutton Strains). Each Strain was toested tion. Observed results were compared to the test at the childed drug consembrility for the BACTEC® MGIT™ 960 ethambutol test at the critical concentration is 100%.

CDC Challenge Panel Testing

The performance of the BACTEC® MGIT™ 960 SIRE ethambutol susceptibility The performance of the Drie first in the right of thirty challenge strains obtained from the test was evaluated abing a panel brevention (CDC), GA, USA. Observed results Oenters for Diodoo Ochiler and the CDC expected results. The overall agreement of the were compared to the moutol test at the critical concentration with CDC expected results is 100%.

Clinical Evaluation

The BACTEC® MGIT™ 960 SIRE ethambutol susceptibility test was evaluated at f ne DAO read inical sites composed of regional reference centers and university hospital-based laboratories, including one foreign site.

Reproducibility Testing

The reproducibility of the BACTEC® MGIT™ 960 SIRE ethambutol test was rne reproducibility of all sites using a panel of ten qualified strains. Observed

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results were compared to the expected results. Overall reproducibility for the BACTEC® MGIT™ 960 ethambutol test at the critical concentration is 97.5%.

CDC Challenge Panel Testing

The performance of the BACTEC® MGIT™ 960 SIRE ethambutol susceptibility test was evaluated using a panel of thirty challenge strains obtained from the Centers for Disease Control and Prevention (CDC), GA, USA. Observed results were compared to the CDC expected results. The overall agreement of the BACTEC® MGIT™ 960 ethambutol test at the critical concentration with CDC expected results is 93.3%

Clinical Isolate Testing

A total of 106 clinical isolates of M. tuberculosis were tested with the BACTEC® MGIT™ 960 SIRE ethambutol susceptibility test and the MOP susceptibility test. This included testing of both fresh clinical and stock isolates from both liquid and solid culture sources. This generated a total of 223 test results for the ethambutol test at the critical concentration.

Category agreement was calculated for isolates from both liquid and solid source cultures tested at EMB 5.0. The agreement for liquid source susceptible strains is 97% and for resistant strains is 85%. The agreement for solid source susceptible strains is 99% and for resistant strains is 80.0%.

All isolates with discordant BACTEC® MGIT™ 960 EMB 5.0 results were tested by MOP at two independent sites. Of the four discordant EMB resistant (R-960, S-MOP) isolates, one had resistant results from both sites and three had susceptible results from both sites. Of the eight discordant EMB susceptible (S-960, R-MOP) isolates, six had susceptible results from both sites and two had resistant results from one site and susceptible results from the other site.

The overall performance data demonstrate that the BACTEC® MGIT™ 960 SIRE ethambutol susceptibility test, used with the BACTEC® MGIT™ 960 System, is substantially equivalent to the Method of Proportion susceptibility test that was in use prior to May 28, 1976.

1 The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

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Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with three heads, representing the department's focus on health, human services, and science. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The seal is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 1 9 2002

Ms. Jody J. Hoffman Regulatory Affairs Specialist BD Diagnostic Systems 7 Loveton Circle Sparks, MD 21152-0999

K014123 Re:

Trade/Device Name: BACTEC® MGIT™ 960 SIRE Kits - Ethambutol at 5µg/ml Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: MJA Dated: March 11, 2002 Received: March 12, 2002

Dear Ms. Hoffman:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number (if known):

BACTEC® MGIT™ 960 SIRE Kits Device Name: _________________________________________________________________________________________________________________________________________________________________

Indications for Use:

The BACTEC® MGIT™ 960 SIRE Kit is a rapid qualitative procedure for The BAOTEO Thion of Mycobacterium tuberculosis, from culture, to streptomycin Susceptibling tooling of my on my on (RIF) and ethambutol (EMB). The BACTEC® (STY), Isomazid (INT), mampin (Fill ) and Stranic 2000 INH 0.4 Kit are for testing at higher drug concentrations.

The BACTEC® MGIT™ 960 SIRE kits are used with the BACTEC® MGIT™ 960 System. The BACTEC® MGIT™ 960 SIRE Kit final test concentrations are 1.0 µg/mL for streptomycin, 0.1 µg/mL for isoniazid, 1.0 µg/mL for rifampin and r.o pg/mL for ethambutol. The BACTEC® MGIT™ 960 STR 4.0 Kit final test 0.0 pg/mL for Sthambutor. The streptomycin and the BACTEC® MGIT™ 960 INH 0.4 Kit final test concentration is 0.4 µg/mL for isoniazid.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Freddie L. Poole

Division Sian-Off) Division of Clinical Laboratory Devices

510(k) Number KD14123

(Optional Format 3-10-98)

*Prescription Use Only

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).