PASCO MIC AND MIC/ID PANELS are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement or category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.

This 510(k) notification is for the addition Ofloxacin to Pasco panels at concentrations of 0.5 to 16 mcg/ml for use in determining the susceptibility of S. pneumoniae and non-pneumococcal streptococci.

Device Description

Varying concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco panels and the panels are then frozen. Panels are thawed prior to use, inoculated with the test organisms, incubated the traditional 16-24 hours and panels are then observed for visible growth or color changes as described in the package insert. The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Changes in pH and production of specific metabolites from growth in biochemical substrates are interpreted as described in the package insert for conventional tubed media.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Pasco MIC and MIC/ID Panels for Ofloxacin, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Criterion	Acceptance Criteria	Reported Device Performance (S. pneumoniae)	Reported Device Performance (Non-pneumococcal streptococci)
Essential Agreement (EA)	Not explicitly stated as a number, but implied to be high; "acceptable Essential Agreement"	99.4% (initial testing, with 1 minor error) and 100% (retesting, no minor errors)	100%
Major (M) Errors	None	None observed	None observed
Very Major (VM) Errors	None	None observed	None observed
Category Agreement (CA)	Not explicitly stated as a number, but implied to be high; "acceptable"	100% (no additional minor errors)	100% (17 random minor errors, all within EA)
QC Endpoints (S. pneumoniae ATCC 49619)	Within recommended NCCLS acceptable range	Within recommended NCCLS acceptable range (both reference and Pasco panels)	N/A (specific to S. pneumoniae QC organism)
Reproducibility	Not explicitly stated as a number, but implied to be high; "+/- 1 dilution"	100% within acceptable plus or minus 1 dilution for 9 out of 12 on-scale organisms	N/A

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

Sample Sizes:
- S. pneumoniae: 101 strains
- Non-pneumococcal streptococci: 130 strains
- Reproducibility: 12 organisms at each of the two sites.
Data Provenance: The study used both CDC challenge strains and clinical isolates. This suggests a mix of standardized laboratory strains and real-world patient samples. No country of origin is specified, but given the FDA review, it is implied to be within the scope of U.S. regulatory standards (likely U.S.-sourced or compliant with U.S. clinical study requirements at the time). The study is prospective as it involved preparing panels and performing comparative testing specifically for this submission.

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

The document does not specify the number or qualifications of experts used to establish the ground truth. It states that comparative testing was performed against a "reference panel" and mentions "CDC challenge strains," which implies an established gold standard for antimicrobial susceptibility testing, likely based on recognized laboratory methods and expert consensus within microbiology.

4. Adjudication Method

The document does not explicitly describe an adjudication method (like 2+1, 3+1). The "retesting" for S. pneumoniae suggests a method for resolving discrepancies when initial results were not 100%, but the specific process isn't detailed.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a MRMC comparative effectiveness study was not done. This study focuses on the performance of the device itself (Pasco panels) against a reference method, not on how human readers' performance might improve with or without AI assistance. The device is an in vitro diagnostic for antimicrobial susceptibility, not an AI-assisted diagnostic tool for human interpretation.

6. Standalone (Algorithm Only) Performance Study

Yes, this was a standalone performance study of the Pasco MIC and MIC/ID Panels. The device itself performs the susceptibility testing and provides the results. There's no human-in-the-loop performance being evaluated in terms of interpreting the device's output. The performance metrics (EA, CA, error rates) directly reflect the device's ability to accurately determine MICs and category results compared to a reference method.

7. Type of Ground Truth Used

The ground truth was established by a reference panel and CDC challenge strains. This indicates an established, recognized method for determining antimicrobial susceptibility, likely involving standard laboratory procedures (e.g., broth microdilution, agar dilution) performed by qualified personnel, which serves as the "gold standard" for accuracy in microbiology.

8. Sample Size for the Training Set

The document does not explicitly state a "training set" sample size. This is a traditional in vitro diagnostic (IVD) device, not an AI/machine learning device that typically requires a separate training set. The "Test panels" mentioned were prepared in-house, but this refers to the manufactured product, not a dataset used to train an algorithm. The 101 S. pneumoniae and 130 non-pneumococcal streptococci strains represent the test set used to validate the device's performance.

9. How Ground Truth for the Training Set Was Established

As there's no explicitly defined "training set" in the context of an AI algorithm, this question isn't directly applicable. The device's underlying principles are based on established microbiological methods for detecting bacterial growth inhibition by antimicrobial agents. The development and calibration of the panels (if one were to loosely consider that a form of "training") would rely on decades of microbiological science and standard susceptibility testing guidelines, with the "ground truth" derived from validated reference methods.

Summary

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K992077)

SEP ! 3 1999

510(k) SUMMARY (page I of 2)

DATE:	June 9, 1999
CONTACT PERSON:	Linda K. DillonChuck Lakel
TRADE NAME OF DEVICE:	Pasco MIC and MIC/ID Panels
COMMON NAME:	Antimicrobial Susceptibility Test
CLASSIFICATION NAME:	Class II Antimicrobial Susceptibility Test Microbiology Panel#83

SUBSTANTIAL EQUIVALENCE:

In review of previous 510(k) notifications for the Pasco MIC and MIC/ID panels (most recently: K982235, July 30, 1998 RE: Minocycline; K982156, July 29, 1998 RE: Cefdinir; K980955 May 18, 1998 RE: Trovafloxacin: K974362, February 12, 1998 RE: Cefepime; K973317, November 14, 1997 RE: Cefpodoxime; K973695, November 5, 1997 RE: Meropenem; K972567, August 20,1997 RE: Sparfloxacin; K971951, August 15, 1997 RE: Levofloxacin; and K946126, January 17, 1995 RE: Detection of resistant pneumococci), the FDA has determined the Pasco panels to be substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments.

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.

DESCRIPTION OF THE DEVICE:

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The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Changes in pH and production of specific metabolites from growth in biochemical substrates are interpreted as described in the package insert for conventional tubed media.

INTENDED USE FOR THE PASCO MIC AND MIC/ID PANELS:

SUMMARY/CONCLUSION OF SUBSTANTIAL EQUIVALENCE TESTING:

Test panels containing Ofloxacin at concentrations ranging from 16 to 0.5 mcg/ml were prepared in-house at Pasco using routine manufacturing procedures. Comparative testing of the Pasco test panel to a reference panel was performed at two sites using CDC challenge strains and clinical isolates.

Test results of the 101 S. pneumoniae strains demonstrated acceptable Essential Agreement (EA) of 99.4% with 1 minor error upon initial testing and an EA of 100% and no minor errors on retesting. No major (M) or very major (VM) errors were observed. Category agreement (CA) was 100% with no additional minor errors noted. Test results of the 130 non-pneumococcal streptococci strains demonstrated acceptable Essential Agreement (EA) of 100% on initial testing. No Major (M) or Very Major (VM) errors were observed. Category Agreement (CA) was 100% with 17 random minor errors noted (all of which were within EA).

QC endpoints for the OC organism S. pneumoniae ATCC 49619 from both the reference and Pasco panels throughout testing were within the recommended NCCLS acceptable range.

Reproducibility testing of 12 organisms at each site provided 9 organisms with on-scale endpoints. Overall reproducibility data demonstrated 100% within the acceptable plus or minus 1 dilution.

The results of the clinical testing, reproducibility testing and QC performance testing supports Substantial Equivalence as outlined in the FDA draft document "Review Criteria For Assessment Of Antimicrobial Susceptibility Devices" (May 1991).

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with three wavy lines instead of snakes.

SEP 3 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Linda K. Dillon Technical Manager Pasco Laboratories, Inc. 12750 West Forty-Second Avenue Wheat Ridge, Colorado 80033

Re: K992077 Trade Name: PASCO MIC and MIC/ID Panels Regulatory Class: II Product Code: JTN Dated: June 9, 1999 Received: June 21, 1999

Dear Ms. Dillon:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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 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"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Sutman

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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Device Name:

PASCO MIC and MIC/ID Panels; Inclusion of Ofloxacin

Indication For Use:

Pasco MIC and MIC/ID panels are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement of category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.

Woody Dubois

vision of Clinical Laboratory Devices K 99 510(k) Number_

PRESCRIPTION USE X

Regulation Number and Section

§ 866.1620 Antimicrobial susceptibility test disc.

(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).