SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH GENTAMICIN (0.06-32MG/ML LONG DILUTION SEQUENCE by DADE BEHRING, INC.

The MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 - 18 hours at 35℃ +/- 1℃, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO2 incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.

This particular submission is for the addition of the antimicrobial gentamicin, at concentrations of 0.06 to 32 µg/ml Long Dilution Sequence for staphylococci, to the test panel.

The Gram-positive organisms which may be used for gentamicin susceptibility testing in this panel are:

Staphylococcus species (coagulase-positive and coagulase-negative) .

Device Description

MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels, utilizing both the MicroScan® Rapid Fluorogenic Identification and Dried Overnight Antimicrobial Susceptibility Testing (AST) technologies, are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anacrobic Gram-positive enterococci and staphylococci.

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in water and dehydrated. Various antimicrobial agents are diluted in water, buffer, or minute concentrations of broth, to concentrations bridging the range of clinical interest. Panels are rehydrated with Synergies plus" Pos Broth, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SI, or equivalent, for 4.5 - 18 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

The provided 510(k) summary describes the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with gentamicin. The study presented aims to demonstrate substantial equivalence to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Set by FDA Guidance)	Reported Device Performance (Gentamicin, Long Dilution Sequence)
Overall Essential Agreement with Reference Panel	94.6% Essential Agreement
Instrument Reproducibility	Acceptable
Quality Control Testing	Acceptable

Note: The FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated February 5, 2003, is cited as defining the criteria for "substantial equivalent performance." While the specific numerical acceptance criteria for Essential Agreement are not explicitly stated in the provided text, a common threshold for AST systems is >90% for Essential Agreement. The reported 94.6% meets this implied threshold. "Acceptable" for reproducibility and quality control indicates that these aspects met their predefined criteria, though the specific quantitative metrics for "acceptable" are not detailed.

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

Test Set Size: The exact number of isolates ("fresh and stock Efficacy isolates and stock Challenge strains") used for the external validation is not specified in the provided text.
Data Provenance: The data came from an "external validation," implying that the testing was performed outside of Dade Behring's internal facilities. The country of origin is not specified, but given the FDA submission, it is likely the studies were conducted in the US or in a manner compliant with US regulatory requirements. The study used "fresh and stock Efficacy isolates and stock Challenge strains," which suggests a combination of retrospective (stock strains) and prospective (fresh isolates) data collection, though the ratio or specific timing is not detailed.

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

The ground truth for the test set was established by a "frozen Reference Panel" and "Expected Results determined prior to the evaluation" for Challenge strains. This suggests a comparison against a recognized standard method rather than expert interpretation of raw data. Therefore, the concept of "experts establishing ground truth" in the traditional sense of clinical opinion is not applicable here. The reference panel itself is the gold standard.

4. Adjudication Method for the Test Set

The study compared the performance of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel against a frozen Reference Panel. This is a direct comparison method, not an adjudication method in the sense of resolving discrepancies between human readers. For the "Challenge strains," their performance was compared to "Expected Results determined prior to the evaluation," which again indicates a comparison to a predefined standard rather than a multi-reader adjudication process.

5. 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, an MRMC comparative effectiveness study was not done. This study evaluates the performance of an automated susceptibility testing system/panel against a reference method, not the impact of AI assistance on human readers.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone study was performed. The MicroScan® Synergies plus™ system is an automated device designed to determine antimicrobial susceptibility. The study evaluates the performance of this device ("algorithm only" in the sense of the automated panel reading and interpretation) in comparison to the frozen reference panel. The device, after incubation, reads the MIC by "determining the lowest antimicrobial concentration showing inhibition of growth." While human oversight might be involved in initial setup or quality control, the core performance reported (Essential Agreement) is that of the automated system.

7. The Type of Ground Truth Used

The ground truth used was a "frozen Reference Panel" for efficacy isolates and "Expected Results" for challenge strains. This constitutes a recognized, standardized reference method (broth microdilution in this context) that is considered the gold standard for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not provide information regarding a separate training set or its sample size. This type of submission focuses on the validation of the device against a predicate, typically using a test set against a defined ground truth, rather than detailing the development and training phases of an algorithm.

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

As no information about a training set is provided, how its ground truth was established is unknown/not applicable from this document.

Summary

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1063365

DEC - 8 2006

510(k) Summary

510(k) Submission Information: Device Manufacturer: Dade Behring Inc. Contact name: Robert Eusebio, Regulatory Affairs Manager 916-374-3144 Fax: Date prepared: October 31, 2006 Product Name: Microdilution Minimum Inhibitory Concentration (MIC) Panels Trade Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels Intended Use: To determine antimicrobial agent susceptibility 510(k) Notification: New antimicrobial - gentamicin Predicate device: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels and MicroScan® Dried Gram-Positive Panels

510(k) Summary:

The proposed MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel demonstrated substantially equivalent performance when compared with a frozen Reference Panel, as defined in the FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated February 5, 2003. The Premarket Notification (510[k]) presents data in support of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with gentamicin.

The external validation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. The external validations were designed to confirm the acceptability of the proposed Synergies plus™ Gram-Positive Panel by comparing its performance with a frozen Reference panel. Challenge strains were compared to Expected Results determined prior to the evaluation. The Synergies plus™ Gram

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Positive Panel demonstrated acceptable performance with an overall Essential Agreement of 94.6% for the Long Dilution Sequence for gentamicin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision for gentamicin with Turbidity inoculum preparation method and the WalkAway® SI System or equivalent.

Quality Control testing demonstrated acceptable results for gentamicin.

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Robert Eusebio Regulatory Affairs Manager Dade Behring, Inc. 1584 Enterprise Boulevard West Sacramento, CA 95691-9972

DEC - 8 2006

Re: K063365

Trade/Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels Gentamicin (0.06 - 32 µg/ml Long Dilution Sequence) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system. Regulatory Class: Class II Product Code: LON, LRG, JWY, LTT Dated: November 6, 2006 Received: November 15, 2006

Dear Mr. Eusebio:

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 Parts 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, permits 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 note 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 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,

Sally, artom

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

KO63365 510(k) Number (if known):

Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Gentamicin (0.06 - 32 ug/ml Long Dilution Sequence)

Indications For Use:

This particular submission is for the addition of the antimicrobial gentamicin, at concentrations of 0.06 to 32 µg/ml Long Dilution Sequence for staphylococci, to the test panel.

The Gram-positive organisms which may be used for gentamicin susceptibility testing in this panel are:

Staphylococcus species (coagulase-positive and coagulase-negative) .

Prescription Use __ X (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)

Rudd, T. Poole

Vision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Suicty

Gm 510k_a.doc 11/6/2006

K063365

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Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”