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°C +/- 1°C, 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 Ampicillin, at concentrations of 0.12 to 64 ug/ml for the Long Dilution Sequence and 2 - 8 µg/ml for the Breakpoint Dilution Sequence, to the test panel.

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

Enterococcus species

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® SI 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 summary of the acceptance criteria and study information for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Ampicillin, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Stated or Implied)	Reported Device Performance
Overall Essential Agreement (EA)	Greater than 97% (as defined in "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated February 5, 2003)	">97% for Ampicillin when compared with the frozen Reference panel." The submission also notes "Overnight Instrument and Manual read method(s) Essential Agreement & Categorical Agreement percentages were of equal, or greater, values than the Rapid read method."
Reproducibility & Precision	Acceptable reproducibility and precision for Ampicillin.	"Instrument reproducibility testing demonstrated acceptable reproducibility and precision for Ampicillin, with Turbidity inoculum preparation method and the WalkAway® SI System or equivalent."
Quality Control (QC)	Acceptable results for Ampicillin.	"Quality Control testing demonstrated acceptable results for Ampicillin."

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

Sample Size:
- Efficacy Isolates: 293 isolates
- Challenge Strains: 72 isolates
- Note: 16 isolates (13 efficacy, 3 challenge) were excluded due to read times >16 hours.
Data Provenance: The document does not specify the country of origin. It indicates that the evaluation was "external," meaning outside of the manufacturer's internal development testing. The data appears to be prospective as it's an evaluation of the panel's performance against a reference standard to demonstrate substantial equivalence.

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

The document does not explicitly state the number of experts or their qualifications for establishing the ground truth for the test set. However, the ground truth for the challenge strains was "Expected Results determined prior to the evaluation," and the comparison for efficacy isolates was against a "frozen Reference panel" which implies a highly standardized and validated method, likely established by expert consensus or a reference laboratory.

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method. The comparison was primarily against a "frozen Reference Panel" and "Expected Results," which serve as the standard. Discrepancies between the device and the reference would be analyzed, but a specific user-based adjudication process (like 2+1) is not described.

5. If a Multi-Reader, Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not conducted. This study focuses on the standalone performance of the automated system compared to a reference standard, not on human reader performance with or without AI assistance.

6. If a Standalone Study Was Done

Yes, a standalone study (algorithm only, without human-in-the-loop performance) was performed. The entire evaluation compares the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Ampicillin, read by the WalkAway® SI System, directly against a frozen Reference Panel and expected results.

7. The Type of Ground Truth Used

The ground truth used was:

Reference Standard: A "frozen Reference Panel" for the efficacy isolates. These panels are typically highly standardized and validated MIC determinations, often established by a reference laboratory following CLSI (Clinical and Laboratory Standards Institute) guidelines.
Expected Results: For the "Challenge strains." These are likely strains with known antimicrobial susceptibility profiles, serving as a form of "expert consensus" or established standard.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size for a training set. This submission is for the addition of a new antimicrobial (Ampicillin) to an existing, previously cleared system. It's likely that the core technology and algorithm for reading the panels were trained and validated in prior submissions. The current submission focuses on validating the performance of Ampicillin within that established framework.

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

Since information about a specific training set or its size is not provided for this submission, there is no information on how its ground truth was established. For AST systems, the ground truth would typically be established using validated methods such as macrobroth or microbroth dilution reference methods performed by expert microbiologists or reference laboratories.

Summary

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K060088

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:	April 25, 2005
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 - Ampicillin
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 two hundred and ninety three (293) isolates and Challenge total equaled seventy two (72). Results for sixteen (16) isolates, thirteen (13) in Efficacy and three (3) in Challenge, 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 support of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with Ampicillin.

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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 Ampicillin when compared with the frozen Reference panel.

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

Quality Control testing demonstrated acceptable results for Ampicillin.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the department's name around the perimeter. Inside the circle is an abstract image of an eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 3 2006

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

Re: K060088

Trade/Device Name: MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panels Ampicillin (0.12 - 64 µg/ml Long Dilution) (2 - 8 µg/ml Breakpoint Dilution) 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: January 11, 2006 Received: January 12, 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)276-0484. 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 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/industry/support/index.html

Sincerely yours,

Sale, a Hon

Sally A. Hojvat, M.Sc., Ph.D. I)irector 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 Ampicillin (0.12 - 64 ug/ml - Long Dilution) (2 - 8 µg/ml Breakpoint Dilution)

Indications For Use:

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

Enterococcus species �

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)

Liedditi Carlie

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Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Am 510k.doc 1/1/2006

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		A proposa production and consistence and children and children and children and children and consistence and on any

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.”