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 of Cefotaxime to Pasco panels at concentrations of 4-0.03 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 the study details for the Pasco MIC and MIC/ID Panels for Cefotaxime, based on the provided text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance (Cefotaxime)
Essential Agreement (EA) for S. pneumoniae	99.4% on initial testing, 99.4% on retesting
Category Agreement (CA) for S. pneumoniae	99.4%
Percentage of Major (M), Very Major (VM) or Minor Errors for S. pneumoniae	1 minor error on initial testing (not considered resolved as reference MIC didn't change); 16 random minor errors for CA.
Essential Agreement (EA) for 130 non-pneumococcal strains	100%
Percentage of Major (M), Very Major (VM) or Minor Errors for 130 non-pneumococcal strains	0 major, 0 very major, 0 minor errors
Category Agreement (CA) for 130 non-pneumococcal strains	100%
QC Endpoints for S. pneumoniae ATCC 49619	Within recommended NCCLS acceptable range
Reproducibility (within acceptable plus or minus 1 dilution)	100% for 9 organisms with on-scale endpoints (out of 12 tested)

Note: The document refers to "acceptable" agreement levels without explicitly stating quantitative thresholds for these (e.g., "EA must be >90%"). However, the reported performance levels are presented as meeting these implicit criteria.

Study Details

Sample size used for the test set and the data provenance:
- Test Set Size:
  - 101 S. pneumoniae strains
  - 130 non-pneumococcal strains
  - 12 organisms for reproducibility testing
  - Unspecified number of CDC challenge strains (included within the 101 S. pneumoniae and 130 non-pneumococcal strains)
- Data Provenance: The study was "performed at two sites using CDC challenge strains and clinical isolates." This indicates a combination of retrospective (CDC challenge strains) and prospective (clinical isolates) data. The country of origin for the clinical isolates is not specified, but Pasco is a US-based company, suggesting US clinical isolates.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number or qualifications of experts used. The ground truth ("reference panel") is likely established by a standardized method (e.g., broth microdilution) rather than expert consensus on individual results.
Adjudication method for the test set:
- The document does not explicitly state an adjudication method. It mentions that one minor error in S. pneumoniae testing was "not considered resolved since the reference method MIC results did not change," implying that the reference method was the ultimate arbiter, rather than a separate adjudication process.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This study evaluates the performance of an Antimicrobial Susceptibility Test (AST) panel – essentially a laboratory diagnostic device. It does not involve AI or human readers in the context of image interpretation or other diagnostic tasks typically associated with MRMC studies. The device itself (the panel) is the "reader" in this context.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The Pasco MIC and MIC/ID Panels are designed to provide quantitative or qualitative susceptibility results. While human observation is required to interpret visible growth or color changes, the "device performance" in terms of MIC determination is evaluated as a standalone entity compared to a reference method, not intertwined with human diagnostic variability. It's an in vitro diagnostic test, not an AI algorithm.
The type of ground truth used:
- The ground truth was established using a "reference panel" (also referred to as the "reference method"). This implies a gold standard laboratory method for determining antimicrobial susceptibility, such as a broth microdilution method, which is the established gold standard for MIC determination.
The sample size for the training set:
- The document does not explicitly state a separate "training set" size. The "test panels" were "prepared in-house at Pasco using routine manufacturing procedures." Antimicrobial susceptibility panels are typically subject to quality control during manufacturing and then evaluated in comparative studies like this, rather than going through a machine learning-style training/testing split. The data mentioned (101 S. pneumoniae strains, 130 non-pneumococcal strains) are used for the comparative testing, not for training an algorithm.
How the ground truth for the training set was established:
- As there is no explicitly mentioned "training set" in the context of machine learning, this question is not directly applicable. If interpreting "training set" broadly as data used for developing the panel or its manufacturing process, the ground truth would still be established by standard microbiological reference methods and quality control procedures to ensure the accuracy of the antimicrobial agent concentrations and their performance.

Summary

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1999 OCT 1:44

K992568

(3)

510(k) SUMMARY (page 1 of 2)

DATE:	July 29, 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: Minocvcline; 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 Cefotaxime at concentrations ranging from 4-0.03 mcg/ml were prepared inhouse 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% on initial testing and an EA of 99.4% on retesting. One minor error was observed upon initial testing. Although retest results were acceptable, this error was not considered resolved since the reference method MIC results did not change. Category agreement (CA) was 99.4% with 16 random minor errors noted. Test results of the 130 non-pneumococcal strains demonstrated acceptable Essential Agreement (EA) of 100%. No major (M), very major (VM) or minor errors were observed. Category Agreement (CA) was 100% with no random minor errors noted.

QC endpoints for the QC 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 seal of the U.S. Department of Health & Human Services. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the top half of the circle. Inside the circle is a stylized image of three abstract shapes that resemble birds in flight.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 1 4 1999

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

Re: K992568 Trade Name: PASCO MIC and MIC/ID Panels (Cefotaxime) Regulatory Class: II Product Code: JTN Dated: July 29, 1999 Received: August 2, 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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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Device Name:

PASCO MIC and MIC/ID Panels; Inclusion of Cefotaxime

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

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K992568

Prescription Use (Per 21 CFR 801.109) OR

Over-The Counter Use

(Optional Format 1-2-96)

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).