SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH LINEZOLID 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 linezolid, at concentrations of 0.5 to 16 ug/ml Long Dilution Sequence and 0.5 - 4 ug/ml 4-Dilution Breakpoint Sequence, for enterococci and staphylococci, to the test panel.

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

Enterococcus faecium (vancomycin-resistant) Staphylococcus aureus (methicillin-susceptible and methicillin-resistant)

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 anaerobic 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, System, 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

Here's an analysis of the provided text regarding the acceptance criteria and study for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with linezolid:

1. Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (Implicit from Guidance)	Reported Device Performance (Linezolid)
Overall Essential Agreement (EA)	Not explicitly stated but expected to demonstrate "acceptable performance" as per FDA guidance for AST systems.	Demonstrated "acceptable performance with an overall Essential Agreement (EA) and 4-Dilution Agreement of 76.0% with the Long Dilution Sequence and 76.0% with the 4-Dilution Breakpoint Sequence"
Reproducibility	Acceptable reproducibility	Demonstrated "acceptable reproducibility"
Quality Control Testing	Acceptable results for linezolid	Demonstrated "acceptable results for linezolid"

Note: The document refers to the FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA" dated February 5, 2003. This document would contain the explicit, quantitative acceptance criteria for Essential Agreement, Category Agreement, and reproducibility that the device must meet. The provided summary only states that the device "demonstrated acceptable performance" and met the criteria.

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

Sample Size: The document does not explicitly state the total number of isolates (fresh, stock efficacy, and stock challenge strains combined) used for the external validation.
- It mentions that "external validation was conducted with fresh and stock Efficacy isolates and stock Challenge strains."
- For the reported performance of linezolid, it states "Essential Agreement (EA) and 4-Dilution Agreement of 76.0%," which implies a certain number of comparisons were made, but the exact count is not given.
Data Provenance: The text does not specify the country of origin. The study was an "external validation." It involved both retrospective (stock isolates) and potentially prospective (fresh isolates) data, though the exact proportion is not mentioned.

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

The document does not provide information on the number or qualifications of experts used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method used for the test set. The ground truth appears to be established by comparison to a "frozen Reference Panel" and "Expected Results determined prior to the evaluation" for challenge strains, rather than expert consensus on individual cases.

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

No, an MRMC comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility test system, not a diagnostic imaging device that typically involves human readers interpreting results.

6. Standalone Performance Study

Yes, a standalone study was done. The study specifically compared the performance of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with linezolid against a "frozen Reference Panel" and "Expected Results" for challenge strains. This evaluates the algorithm's (or system's) performance purely in terms of its output (MIC values and agreement) without direct human intervention in the interpretation phase beyond setting up the test and reading the final MIC.

7. Type of Ground Truth Used

The ground truth was established by:

Comparison to a frozen Reference Panel for efficacy isolates. This suggests a pre-established, highly reliable method for determining antimicrobial susceptibility.
"Expected Results determined prior to the evaluation" for stock Challenge strains. These are typically well-characterized strains with known susceptibility profiles.

8. Sample Size for the Training Set

The document does not provide any information about a discreet training set used for developing the device. This is typical for a microbiology susceptibility panel, where the "training" (if it can be called that) often comes from years of established methodology and the development of the panel's design, rather than a machine learning training phase on a specific dataset.

9. How Ground Truth for the Training Set Was Established

Since no explicit training set is mentioned, the method for establishing its ground truth is not applicable/not provided. The device's design and expected performance would be based on well-established microbiological principles and previous generations of AST systems, rather than a separate "training phase" and associated ground truth process as seen in AI algorithms.

Summary

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K062705

OCT 20 2006

510(k) Summary

510(k) Submission Information: Device Manufacturer: D Dade Behring Inc. Contact name: Robert Eusebio, Regulatory Affairs Manager 916-374-3144 Fax: Date prepared: August 21, 2006 Product Name: Microdilution Minimum Inhibitory Concentration (MIC) Panels MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels Trade Name: To determine antimicrobial agent susceptibility Intended Use: New antimicrobial - linezolid 510(k) Notification: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Predicate device: 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 linezolid.

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

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Expected Results determined prior to the evaluation. The Synergies plus" Gram-Expected Results determined proprable performance with an overall Essential I ostire I and demonstrator association Sequence and 4-Dilution Agteencer of 76.070, 10, 10, 10, 10, 10, 10, 2019 - 10:15
Breakpoint Sequence, for Linezolid when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and mstrainent reproductive with Turbidity inoculum preparation method and the WalkAway® SI System or equivalent.

Quality Control testing demonstrated acceptable results for linezolid.

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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

OCT 2 0 2006

Re: K062705 Trade/Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels Linezolid (0.5-16 µg/ml Long Dilution Sequence and 0.5 – 4 µg/ml 4 - Dilution Breakpoint 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: September 7, 2006 Received: September 20, 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 indicons for use stated in the enclosure) to legally marketed predicated devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical In microa in microsities 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, intiling 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 O intor gonetar in the 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

510(k) Number (if known):

Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Linezolid (0.5 - 16 ug/ml Long Dilution Sequence and 0.5 - 4 ug/ml 4-Dilution Breakpoint Sequence)

Indications For Use:

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

Enterococcus faecium (vancomycin-resistant) Staphylococcus aureus (methicillin-susceptible and methicillin-resistant)

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)

Luddi W. Poole
Division Sign-Off

sion Sign-C

Lzd 510k.doc 10/11/2006

Office of In Vitro Diagnostic Device Evaluation and Safety

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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.”