The MicroScan® Dried Gram Negative Panel is designed for use in the Confirmation of Extended-Spectrum Beta-Lactamase (ESBL) production in Escherichia coli, Klebsiella spp. and Proteus mirabilis.

After inoculation, panels are incubated for 16-20 hours at 35°C +/- 1°C in a non-CO2 incubator and read either visually or with MicroScan® instrumentation, according to the Package Insert.

This particular submission is for the use of cefotaxime (2, 16 µg/ml), cefotaxime/clavulanic acid (0.5/4, 4/4 µg/ml), ceftazidime (1, 8 µg/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 µg/ml) for ESBL confirmatory testing on MicroScan® Dried Gram Negative MIC/Combo Panels and the addition of automated read methods.

The Gram Negative organisms which may be used for confirmation of ESBL production in this panel are:

Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis

Device Description

MicroScan® Dried Gram Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility for Gram Negative organisms and screening for suspected ESBL production in E. coli, Klebsiella spp. and P. mirabilis.

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water, after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator at 35 °C for a minimum of 16 hours, the minimum inhibitory concentration (MIC) for the test organism is determined by observing the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

The provided 510(k) summary focuses on the MicroScan® Dried Gram Negative MIC/Combo Panels for confirming Extended-Spectrum Beta-Lactamase (ESBL) production. The study details are specific to this device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria (Implied)	Reported Device Performance
Overall Agreement with molecular characterization for ESBL and non-ESBL-producing strains > 90% (industry standard for IVD often ≥90%)	The dried Test panel with streamlined dilutions of the antimicrobial agents demonstrated an overall Agreement of > 93% with ESBL and non-ESBL-producing strains. This implies that the device accurately classified over 93% of the tested strains as either ESBL producers or non-ESBL producers when compared to the molecular characterization gold standard.
Acceptable reproducibility across different inoculation methods and read methods.	Inoculation method and instrument reproducibility testing demonstrated acceptable reproducibility with the specified antimicrobial agents (cefotaxime, cefotaxime/clavulanic acid, ceftazidime, and ceftazidime/clavulanic acid) regardless of the inoculation method (Turbidity) and read method (Manual, WalkAway®, and autoSCAN®-4 instruments). This indicates consistent results under varying operational conditions.
Acceptable Quality Control throughout the ESBL evaluation.	The MicroScan® Dried Gram Negative panel with the relevant antimicrobial agents demonstrated acceptable Quality Control throughout each phase of the ESBL evaluation. This ensures the reliability and consistency of the test system itself during the study.

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

Sample Size: The document does not explicitly state a precise numerical sample size for the "test set" (referred to as "stock challenge strains" within "Design Validation studies"). It mentions "ESBL and non-ESBL-producing strains." Without a specific number, it is impossible to definitively detail the sample size.
Data Provenance: The data appears to be prospective as it's generated from "Challenge studies" and "Design Validation studies" specifically conducted to confirm the acceptability of the streamlined dilutions. The country of origin of the data is not specified, but given the manufacturer (Dade Behring Inc.) and the FDA submission, it's likely primarily US-based or international data submitted to the FDA for US market clearance.

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

The ground truth for the test set was established by "molecular characterization." This implies laboratory-based genetic or biochemical testing, not human expert interpretation of images or clinical findings. Therefore, the concept of "number of experts" and their "qualifications" in the traditional sense (e.g., radiologists) is not applicable here. The ground truth relies on the accuracy and established validity of the molecular characterization methods themselves.

4. Adjudication Method for the Test Set:

Since the ground truth was established by "molecular characterization," the concept of an "adjudication method" involving multiple human readers (like 2+1, 3+1) is not applicable. The molecular characterization itself serves as the definitive reference, and the device's results are compared directly against it.

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

No, an MRMC comparative effectiveness study was not explicitly mentioned or performed in the context typically seen for diagnostic imaging tools involving human readers. This device is an in-vitro diagnostic (IVD) for bacterial susceptibility testing, where the "reader" can be manual or an automated instrument. The study did assess "reproducibility" across "manual, WalkAway® and autoSCAN®-4 instruments," which addresses variation in reading methods but not human diagnostic improvement with AI assistance.
Therefore, the effect size of human readers improving with AI vs without AI assistance is not applicable here because it's not an AI-assisted diagnostic task for visual interpretation by humans.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:

Yes, a standalone performance study was conducted. The "Overall Agreement of > 93% with ESBL and non-ESBL-producing strains" was determined by comparing the "panel confirmation result" (the device's output) directly against the "molecular characterization result" (the ground truth). This is a standalone assessment of the device's accuracy without human intervention influencing the final classification, other than the initial setup and reading of the panel, which can be automated.

7. Type of Ground Truth Used:

The ground truth used was molecular characterization (described as "molecular characterization result"). This refers to laboratory techniques (e.g., PCR, sequencing, enzyme assays) that identify the presence or absence of ESBL-producing genes or enzymes, providing a definitive biological determination.

8. Sample Size for the Training Set:

The document does not explicitly state a sample size for a "training set." This type of device (microdilution panels) is typically developed and validated based on established microbiological principles and chemical formulations rather than machine learning models that require distinct training and test sets. The studies described are validation and challenge studies, which assess the performance of the final device, not the iterative training of an algorithm.

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

As there's no mention of a "training set" in the context of machine learning, the question of how its ground truth was established is not applicable. The development of such panels relies on a priori chemical and biological knowledge, and subsequent validation against well-characterized reference strains and clinical isolates. The "molecular characterization" served as the gold standard for the validation/test set.

Summary

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510(k) Summary

K061687

JUL 21 2006

510(k) Submission Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	Maureen Mende, Regulatory Affairs Group Manager
Fax:	916-374-3144
Date prepared:	June 14, 2006
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® Dried Gram Negative MIC/Combo Panels
Intended Use:	To be used in the confirmation of Extended-SpectrumBeta-Lactamase production in Escherichia coli, Klebsiella spp. andProteus mirabilis.
510(k) Notification:	Modification to K020037- ESBL Confirmation
Predicate device:	MicroScan® Dried ESBL plus ESBL Confirmation Panel

510(k) Summary:

The antimicrobics: cefotaxime/clavulanic acid, ceftazidime and ceftazidime/clavulanic acid have been cleared for confirmation of suspected extended-spectrum beta-lactamases with E. coli, K. oxytoca and K. pneumoniae via Premarket Notification submission (K020037). Confirmation of suspected ESBL with P. mirabilis was submitted to the FDA and is pending clearance.

This Premarket Notification 510(k) presents data in support of a request for confirmatory testing of suspected extendedspectrum beta-lactamase producing E. coli, K. oxytoca, K. pneumoniae and P. mirabilis using streamlined dilutions of the antimicrobial agents recommended for confirmation testing described in the CLSI document M100-S16 for cefotaxime and ceftazidime, alone and in combination with clavulanic acid. In addition, this Premarket Notification 510(k) presents data for automated (WalkAway® and autoSCAN®-4 instruments) reads of the MicroScan® Dried Gram Negative panel with streamlined dilutions.

Challenge studies with the MicroScan® Dried Gram Negative panel with cefotaxime (2, 16 ug/ml), cefotaxime/clavulanic acid (0.5/4, 4/4 µg/ml), ceftazidime (1, 8 µg/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 µg/ml) were conducted using stock challenge strains. The Design Validation studies were designed to confirm the acceptability of streamlined dilutions of these antimicrobial agents for confirmation of suspected ESBLproducing organisms by comparing the panel confirmation result against the molecular characterization result. The dried Test panel with streamlined dilutions of the antimicrobial agents demonstrated an overall Agreement of > 93% with ESBL and non-ESBL-producing strains.

Inoculation method and instrument reproducibility testing demonstrated acceptable reproducibility with cefotaxime (2, 16 µg/ml), cefotaxime/clavulanic acid (0.5/4, 4/4 µg/ml), ceftazidime (1, 8 µg/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 µg/ml) regardless of which inoculation method (i.e. Turbidity and read mathod (Manual, WalkAway® and autoSCAN®-4 instruments) used.

The MicroScan® Dried Gram Negative panel with cefotaxime/clavulanic acid, ceflazidime and ceftazidime/clavulanic acid antimicrobial agents demonstrated acceptable Quality Control throughout each phase of the ESBL evaluation.

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Image /page/1/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES" written around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Maureen Mende Regulatory Affairs Group Manager Dade Behring Inc. 2040 Enterprise Blvd. West Sacramento, CA 95691

JUL 2 1 2006

Re: K061687

Trade/Device Name: MicroScan® Dried Gram Negative MIC/Combo Panels with cefotaxime (2, 16 µg/ml), cefotaxime/clavulanic acid (0.5/4, 4/4 µg/ml), ceftazidime (1, 8 µg/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 µg/ml)

Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Regulatory Class: Class II Product Code: JWY, LRG Dated: June 14, 2006 Received: June 15, 2006

Dear Ms. Mende:

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 Title 21. Code of Federal Regulations (CFR). Parts 800 to 895. 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 Paris 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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, permitts your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please one the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 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 tolli dic
(900) 638-0041 - 1981) 11-12-2557 - 1991) 11-12-275 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, attorn

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K 0411687

Device Name:

MicroScan® Dried Gram Negative MIC/Combo Panels with cefotaxime (2, 16 ug/ml), cefotaxime/clavulanic acid (0.5/4, 4/4 µg/ml), ceftazidime (1, 8 µg/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 ug/ml)

Indications For Use:

The MicroScan® Dried Gram Negative Panel is designed for use in the Confirmation of Extended-Spectrum Beta-Lactamasc (ESBL) production in Escherichia coli, Klebsiella spp. and Proteus mirabilis.

After inoculation, panels are incubated for 16-20 hours at 35°C +/- 1°C in a non-CO2 incubator and read either visually or with MicroScan® instrumentation, according to the Package Insert.

The Gram Negative organisms which may be used for confirmation of ESBL production in this panel arc:

Escherichiu coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use _ (21 CFR 807 Subpart C)

Fuddhih t. Patil.

Page 1 of __ 1 __

Vision Sign-Off

Office of In Vitre Diagnostic Device Evaluation and Saicty

510(k) K061687

viii

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Indications for Use

510(k) Number (if known): K061687

Device Name:

MicroScan® Dried Gram Negative MIC/Combo Panels with cefotaxime (2, 16 µg/m), cefotaxime/clavulanic acid (0.5/4, 4/4 ug/ml), ceftazidime (1, 8 ug/ml) and ceftazidime/clavulanic acid (0.25/4, 2/4 ug/ml)

Indications For Use:

The MicroScan® Dried Gram Negative Panel is designed for use in the Confirmation of Extended-Spectrum Beta-Lactamase (ESBL) production in Escherichia coli, Klebsiella spp. and Proteus mirabilis.

After inoculation, panels are incubated for 16-20 hours at 35°C +/- 1°C in a non-CO2 incubator and read either visually or with MicroScan® instrumentation, according to the Package Insert.

The Gram Negative organisms which may be used for confirmation of ESBL production in this panel are:

Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Advisor Sign-Off

Office of
Evaluation an

agnostic Device

Kiloliz

iii

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).