The BACTEC® MGIT™ 960 PZA Kit is used as a rapid qualitative procedure for susceptibility testing of Mycobacterium tuberculosis, from culture, to pyrazinamide (PZA). The BACTEC® MGIT™ 960 PZA kit is used with the BACTEC® MGIT™ 960 System.

Device Description

The BACTEC® MGIT™ 960 PZA susceptibility test kit is used with the BACTEC® MGIT™ PZA Medium and performed on the BACTEC® MGIT™ 960 System. The PZA Medium tube is supplemented with BACTEC® MGIT™ 960 PZA Supplement and prepared with the appropriate dilution of pyrazinamide as the mechanism for performing the susceptibility test.

The BACTEC® MGIT™ 960 PZA susceptibility test utilizes a four to twenty-one day testing protocol. A standardized suspension of Mycobacterium tuberculosis growth is prepared from either solid or liquid culture media. An appropriate dilution is made of this suspension and 0.5 mL is inoculated into a Growth Control tube (drug-free) and a tube containing pyrazinamide (both tubes are 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 tube.

At the completion of the PZA susceptibility testing protocol. the instrument reports a susceptible or resistant result for the Mycobacterium tuberculosis isolate being tested.

AI/ML Overview

The BACTEC® MGIT™ 960 PZA Kit is a medical device used for the rapid qualitative susceptibility testing of Mycobacterium tuberculosis to pyrazinamide (PZA) from culture. The device is used with the BACTEC® MGIT™ 960 System.

Acceptance Criteria and Device Performance

The acceptance criteria are implied through the comparison with a predicate device (BACTEC® 460TB PZA) and the achievement of high agreement percentages in various studies. The primary measure of performance is the "category agreement" with the reference method (BACTEC® 460TB PZA).

Acceptance Criteria (Implied)	Reported Device Performance (BACTEC® MGIT™ 960 PZA)
Overall reproducibility	96.8% (Analytical Study)
CDC Challenge Panel Agreement	98.7% (Analytical Study)
Clinical Reproducibility	94% (Range 86-100%)
Clinical CDC Panel Agreement	91.7%
Category Agreement (Liquid Source)	98.2% (vs. BACTEC® 460TB PZA)
Category Agreement (Solid Source)	95.6% (vs. BACTEC® 460TB PZA)
Overall Performance vs. Predicate Device	Substantially Equivalent

Study Details

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

Analytical Study (Reproducibility): 26 qualified Mycobacterium tuberculosis strains (including 3 ATCC® strains).
Analytical Study (CDC Challenge Panel): A panel of challenge strains from the Centers for Disease Control and Prevention (CDC).
Clinical Studies (Reproducibility): A panel of five qualified strains.
Clinical Studies (CDC Challenge Panel): A panel of challenge strains from the Centers for Disease Control and Prevention (CDC).
Clinical Isolate Testing: A total of 118 clinical strains of Mycobacterium tuberculosis. This generated 228 PZA test results. The testing included fresh clinical and subculture isolates from both liquid and solid source cultures.
Data Provenance: The clinical studies were conducted at four geographically diverse clinical sites, comprising regional reference centers and university-based laboratories. This suggests a prospective collection of data from various real-world clinical settings within the US (given the involvement of the CDC).

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
The document does not explicitly state the "number of experts" or their specific qualifications for establishing the ground truth. However, for the clinical isolate testing, the BACTEC® 460TB PZA test was used as the reference method. This implies that the results from the BACTEC® 460TB PZA, a legally marketed and established device, served as the ground truth. The CDC provides "expected results" for their challenge panels, indicating that their consensus or established laboratory findings were used as ground truth for those specific panels.

4. Adjudication Method for the Test Set:
The document does not describe a formal adjudication method (e.g., 2+1, 3+1). Instead, the performance of the BACTEC® MGIT™ 960 PZA was compared directly to the results obtained from either the "expected results" (for reproducibility and CDC challenge panels) or the "reference method" (BACTEC® 460TB PZA) for clinical isolate testing. Discrepancy resolution is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, an MRMC comparative effectiveness study involving human readers improving with or without AI assistance was not performed. This device is an automated in vitro diagnostic test, not an AI-assisted diagnostic tool that would involve human interpretation of images or data.

6. If a Standalone Study (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies described are standalone performance evaluations of the BACTEC® MGIT™ 960 PZA Kit and system. The device automatically interprets results ("the instrument reports a susceptible or resistant result," "data are automatically interpreted by the instrument software"). While human operators are involved in preparing the samples and loading them into the instrument, the interpretation of the susceptibility result itself is automated by the device, making this a standalone performance assessment.

7. The Type of Ground Truth Used:

Expected Results: For reproducibility testing (analytical and clinical) and CDC challenge panel testing (analytical and clinical), the "expected results" or "CDC expected results" were used as ground truth. These are likely established reference values for known strains.
Reference Method: For the clinical isolate testing, the BACTEC® 460TB PZA test served as the reference method (ground truth). This implies that the results from an established and legally marketed predicate device were considered the correct outcome for comparison.

8. The Sample Size for the Training Set:
The document does not explicitly specify a "training set" size. The reported studies evaluate the performance of the device, implying that the algorithm and methodology were already developed. In vitro diagnostic devices like this typically undergo extensive development and internal testing, which would involve data, but it's not generally referred to as a "training set" in the context of reporting clinical validation for regulatory submission, as is common for AI/ML-based devices.

9. How the Ground Truth for the Training Set Was Established:
Since a "training set" is not explicitly mentioned in the context of this regulatory submission, how its ground truth might have been established is not described. The focus is on the validation of the final device against established methods and reference panels.

Summary

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KO21582

JUL 1 3 2002

510(k) SUMMARY

SUBMITTED BY:	Becton Dickinson and Company7 Loveton CircleSparks, MD 21152Phone: 410-316-4778Fax: 410-316-4499
CONTACT NAME:	Michelle Bandy, Regulatory Affairs Specialist
DATE PREPARED:	May 9, 2002
DEVICE TRADE NAME:	BACTEC® MGIT™ 960 PZA Kit
DEVICE COMMON NAME:	Antimicrobial susceptibility test powder
DEVICE CLASSIFICATION:	21 CFR§866.1640
PREDICATE DEVICE:	BACTEC® 460TB PZA Kit

INTENDED USE:

DEVICE DESCRIPTION:

At the completion of the PZA susceptibility testing protocol. the instrument reports a susceptible or resistant result for the Mycobacterium tuberculosis isolate being tested.

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DEVICE COMPARISON:

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

Both methods test drug susceptibility of Mycobacterium tuberculosis culture . isolates.
Both methods use the antimycobacterial drug pyrazinamide. .
Both methods compare organism growth in drug-free medium to organism . growth in medium that contains the drug to obtain a susceptibility result.
. Both methods provide susceptibility results - susceptible (S) or resistant (R).
. Both methods utilize a four to twenty-one day protocol.
Both methods test PZA using a drug concentration of 100 ug/mL. .
Both methods use Modified Middlebrook 7H9 Broth with a reduced pH. ●
Both methods may use Mvcobacterium tuberculosis isolates recovered from . either solid or liquid source cultures.

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

The BACTEC® MGIT™ 960 PZA susceptibility test does not require user . manipulation of the PZA test vials once entered into the instrument while the BACTEC® 460TB PZA susceptibility test requires off-line incubation and a daily manipulation of the PZA test bottles into the instrument for monitoring.
The BACTEC® MGIT™ 960 PZA susceptibility test is continually monitored by . the instrument while the BACTEC® 460TB PZA susceptibility test is monitored once daily.
The BACTEC® MGIT™ 960 PZA susceptibility test uses an oxygen sensitive . fluorescent sensor to monitor organism growth while the BACTEC® 460TB PZA susceptibility test uses radioactive labeled carbon dioxide ("CO2) to monitor organism growth.
The BACTEC® MGIT™ 960 PZA susceptibility test data are automatically . interpreted by the instrument software while the BACTEC® 460TB PZA susceptibility test data are manually calculated for result interpretation.
The BACTEC® MGIT™ 960 PZA susceptibility test is performed using . organism suspensions prepared directly from solid or liquid source while the BACTEC® 460TB PZA susceptibility test requires the solid or liquid source isolate to be subcultured into a BACTEC® 460TB 12B medium vial prior to performing the PZA susceptibility test.

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SUMMARY OF SUBSTANTIAL EQUIVALENCE TESTING DATA:

Analytical Studies:

Reproducibility Testing

Reproducibility of the BACTEC® MGIT™ 960 PZA susceptibility test was evaluated using twenty-six qualified Mycobacterium tuberculosis strains (including three ATCC® strains). Three different lots of the reagents required to conduct the BACTEC® MGIT™ 960 PZA susceptibility test were evaluated. Observed results were compared to the expected results. The overall reproducibility was 96.8%.

CDC Challenge Panel Testing

The performance of the BACTEC® MGIT™ 960 PZA susceptibility test was evaluated using a panel of challenge strains obtained from the Centers for Disease Control and Prevention (CDC). Observed results were compared to the CDC expected results. The percent agreement was 98.7% to the CDC expected results.

Clinical Studies:

The BACTEC® MGIT™ 960 PZA susceptibility test was evaluated at four geographically diverse clinical sites, composed of regional reference centers and university-based laboratories.

Reproducibility Testing

The reproducibility of the BACTEC® MGIT™ 960 PZA Kit was evaluated at the clinical sites using a panel of five qualified strains. Observed results were compared to expected results. Overall reproducibility was 94%, with a range across sites of 86-100%.

CDC Challenge Panel Testing

The performance of the BACTEC® MGIT™ 960 PZA Kit was evaluated using a panel of challenge strains obtained from the Centers for Disease Control and Prevention (CDC). Observed results were compared to the CDC expected results. The percent agreement was 91.7% to the CDC expected results.

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Clinical Isolate Testing

A total of 118 clinical strains of Mycobacterium tuberculosis were evaluated with the BACTEC® MGIT™ 960 PZA susceptibility test and the BACTEC® 460TB PZA test (reference method). This testing included fresh clinical and subculture isolates from both liquid and solid source cultures. A total of 228 PZA test results were generated and analyzed.

Category agreement was calculated for the isolates tested from both liquid and solid source cultures. The BACTEC® MGIT™ 960 PZA susceptibility test demonstrated a category agreement for liguid source culture of 98.2% and a category agreement of 95.6% for solid source culture.

The overall performance data demonstrate that the BACTEC® MGIT™ 960 PZA THE STORIE ponomianos attact actIACTEC® MGIT™ 960 System, is substantially equivalent to the BACTEC® 460TB PZA susceptibility test (K895362).

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 premarket 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 U.S. Patent Laws or their application by the courts.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three curved lines representing its wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

JUL 1 3 2002

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Michelle B. Bandy Regulatory Affairs Specialist BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

Re: K021582

Trade/Device Name: BACTEC® MGIT™ 960 PZA Kit Pyrazinamide Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: MJA Dated: May 13, 2002 Received: May 14, 2002

Dear Ms. Bandy:

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/cdrb/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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510(k) Number (if known): K021582

Page _1

Device Name: _________________________________________________________________________________________________________________________________________________________________

Indications for Use:

The BACTEC® MGIT™ 960 PZA Kit is a rapid qualitative procedure for susceptibility testing of Mycobacterium tuberculosis, from culture, to pyrazinamide (PZA).

The BACTEC® MGIT™ 960 PZA Kit is used with the BACTEC® MGIT™ 960 System. The BACTEC® MGIT™ 960 PZA Kit final test concentration is 100 µg/mL for pyrazinamide.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Ludoli In. Poole

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K021582

*For Prescription Use

(Optional Format 3-10-98)

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).