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 staphylococci and enterococci. 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-CO, 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 vancomycin, at concentrations of 0.25 to 64 µg/ml, to the test panel.

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

Enterococcus spp. (e.g., Enterococcus faecalis)
Staphylococcus spp.
Staphylococcus aureus (including methicillin-resistant strains)
Staphylococcus epidermidis (including methicillin-resistant strains)

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 staphylococci and enterococci.

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® SJ 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 a breakdown of the acceptance criteria and study details for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with vancomycin:

Description of the Acceptance Criteria and Study to Prove Device Meets Acceptance Criteria

The MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with vancomycin are designed to determine the antimicrobial agent susceptibility of gram-positive staphylococci and enterococci using a microdilution minimum inhibitory concentration (MIC) method. The device's performance was evaluated against a frozen Reference Panel, as per FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems."

1. Table of Acceptance Criteria and the Reported Device Performance

Acceptance Criteria Category	Specific Metric	Acceptance Criterion	Reported Device Performance
Overall Performance	Essential Agreement	>97%	>97% for vancomycin
Reproducibility	Reproducibility & Precision	Acceptable	Acceptable
Quality Control	QC Results	Acceptable	Acceptable

Note: The document explicitly states the overall Essential Agreement, reproducibility, and quality control. Specific numerical thresholds for "acceptable" reproducibility and QC are not provided in this summary but are generally defined in the referenced FDA guidance document.

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

Test Set Sample Size for Efficacy (Rapid Read Method): 507 isolates.
Provenance: The study used "fresh and stock Efficacy isolates and stock Challenge strains." The specific country of origin is not specified but it's an "external evaluation," implying data collected outside of the manufacturing site, most likely within the US given the FDA submission. The nature of "fresh" and "stock" isolates indicates a mix of prospectively collected and potentially retrospectively stored (stock) samples.

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

This information is not provided in the summary. For AST panels, the "ground truth" is typically established by comparative testing against a recognized reference method (e.g., broth microdilution or agar dilution as per CLSI guidelines), often performed by trained microbiologists. The "Expected Results" for challenge strains would have been determined using such reference methods.

4. Adjudication Method for the Test Set

This information is not provided. In AST studies, direct adjudication of results in the traditional sense (like in image reading) is less common. Instead, the comparison is directly between the device's MIC determination and the reference method's MIC, and agreements/disagreements are categorized based on defined criteria (Essential Agreement, Categorical Agreement).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance.

No. This type of study (MRMC, AI assistance) is not applicable to this device. This device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic imaging or interpretation tool for human readers.

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

Yes, indirectly. The "Rapid read method" describes the automated instrumental reading of the panels. The performance claims are based on this automated rapid read. While human involvement is required for initial inoculum preparation and loading, the reading and interpretation for performance claims are automated. The summary also notes that "Overnight Instrument and Manual read method(s) Essential Agreement & Categorical Agreement percentages were of equal, or greater, values than the Rapid read method," indicating other reading methods were also assessed, but the primary claims are based on the automated rapid read.

7. The Type of Ground Truth Used

Reference Panel: The ground truth was established using a frozen Reference Panel. This reference panel serves as the gold standard for comparison, with results typically derived from established reference methods for antimicrobial susceptibility testing (e.g., broth microdilution methods conforming to CLSI standards). For "Challenge strains," the ground truth was "Expected Results determined prior to the evaluation," which would have been established by similar reference methods.

8. The Sample Size for the Training Set

This information is not provided in the summary. For AST devices, there isn't typically a "training set" in the machine learning sense, as the device operates based on predefined biochemical reactions and algorithms rather than learning from data in a training phase. The "efficacy isolates" and "challenge strains" are primarily for validation/testing.

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

As a "training set" in the machine learning context is not applicable, the method for establishing ground truth for a training set is not relevant here. The ground truth for the evaluation was established using a frozen Reference Panel and pre-determined expected results for challenge strains, which are standard reference methods for AST.

Summary

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MAR 2 3 2006

K060312

510(k) Summary

510(k) Submission Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	Robert Eusebio, Regulatory Affairs Manager
Fax:	916-374-3144
Date prepared:	January 24, 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 - Vancomycin
Predicate device:	MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panelsand MicroScan® Dried Gram-Positive Panels

510(k) Summary:

Note: Efficacy total for the Rapid read method equaled five hundred and seven (507) isolates. Results for forty-two (42) isolates were not reported due to read times ≥16 hours. Performance claims are based on the Rapid read method. Overnight Instrument and Manual read method(s) Essential Agreement & Categorical Agreement percentages were of equal, or greater, values than the Rapid read method.

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

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support of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with vancomycin.

The external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. The external evaluations 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-Positive Panel demonstrated acceptable performance with an overall Essential Agreement of >97% for vancomycin when compared with the frozen Reference panel.

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

Quality Control testing demonstrated acceptable results for vancomycin.

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DEPARTMENT OF HEAL TH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The caduceus is depicted with three lines forming the wings and a stylized staff. The text is in all caps and is evenly spaced around the circle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 3 2006

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

K060312 Re:

Trade/Device Name: MicroScan® Synergies plus TM Gram-Positive MIC/Combo Panels Vancomycin (0.25 - 64 µg/ml)

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: February 6, 2006 Received: February 8, 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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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) rins letter will and my you to organization of substantial equivalence of your device to a legally prematics notification " "I 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)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I ou may octurity 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/industry/support/index.html

Sincerely yours,

Sale, a Form

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): 长060312-

Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Vancomycin (0.25 - 64 ug/ml)

Indications For Use:

This particular submission is for the addition of the antimicrobial vancomycin, at concentrations of 0.25 to 64 µg/ml, to the test panel.

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

Enterococcus spp. (e.g., Enterococcus faecalis) �
Staphylococcus spp. .
Staphylococcus aureus (including methicillin-resistant strains) .
Staphylococcus epidermidis (including methicillin-resistant strains) .

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)
Division Sign-Off

Va 510k.doc	Office of In Vitro Diagnostic Device Evaluation and Safety	Page 1 of 1
2/6/2006	510(k) K060512

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.”