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-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 Rifampin, at concentrations of 0.25 to 8 ug/ml, to the test panel.

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

Staphylococcus aureus (including methicillin-resistant strains/MRSA) Staphylococcus epidermidis

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™ Post Broth, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SZ 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 acceptance criteria and study details from the provided 510(k) summary (K051478):

Acceptance Criteria and Device Performance

The core acceptance criterion for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Rifampin, as stated, is based on a comparison to a frozen Reference Panel.

Context: The FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated February 5, 2003, defines the performance standards for such devices. While the exact numerical acceptance criteria for each metric (Essential Agreement, Category Agreement, etc.) are not explicitly detailed in the provided text, the summary indicates that the device met these criteria.

Acceptance Criteria Category	Reported Device Performance	Comments
Essential Agreement (EA)	>98% for Rifampin	Performance against a frozen Reference Panel. Essential Agreement is a measure of how closely the MIC results (within ±1 dilution) compare between the test device and the reference method.
Reproducibility	Acceptable	Confirmed for both filled panels and inoculum preparation methods, using the WalkAway® SI System or equivalent.
Precision	Acceptable	Similar to reproducibility, ensures consistent results under repeated testing.
Quality Control (QC)	Acceptable results	For Rifampin. Ensures the system performs as expected with known controls.

Study Details

The provided text describes an "external evaluation" that served as the primary study to demonstrate substantial equivalence.

A table of acceptance criteria and the reported device performance:
(See table above)
Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated as a number of isolates. The summary mentions "fresh and stock Efficacy isolates and stock Challenge strains" were used for the external evaluation. Without a specific count, the exact sample size cannot be determined from this text.
- Data Provenance: The origin of the isolates (e.g., country of origin, specific hospitals) is not specified. It refers to "external evaluation," implying the testing was conducted outside of the manufacturer's primary lab, but the specific location is not given. The isolates are categorized as retrospective given they are "stock Efficacy isolates" and "stock Challenge strains," and "fresh isolates" which suggests some prospective collection, but no further details are provided on the "fresh" isolates.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- Not applicable/Not explicitly stated. For AST devices, the "ground truth" or reference method is typically another well-established AST method (e.g., broth microdilution) rather than human expert interpretation of an image or clinical observation. The study compared the device's results to a "frozen Reference Panel," which implicitly serves as the ground truth. There is no mention of human experts directly establishing ground truth for individual cases.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies where human readers interpret complex data (e.g., medical images) and need to reach consensus. For AST, the comparison is directly between the result from the test device and the result from the reference method. Discrepancies are analyzed, but not subjected to a human adjudication process in the same way.
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:
- Not applicable. This device is an automated in vitro diagnostic antimicrobial susceptibility test system, not an AI-assisted diagnostic tool that directly aids human readers in interpreting complex data. Therefore, an MRMC study comparing human reader performance with and without AI assistance is not relevant to this device.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, effectively. The performance described (Essential Agreement >98%) is the standalone performance of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel system compared to the reference method. While human involvement is required for initial panel inoculation and system operation, the MIC determination and interpretation of that result are automated by the "MicroScan® Instrumentation" (WalkAway® SZ System or equivalent). The exception is that AST portions can be read visually, but the primary claims for the automated system would be based on its automated readings.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Reference Method/Frozen Reference Panel: The ground truth was established by a "frozen Reference Panel." This likely refers to a panel tested using a recognized reference method for antimicrobial susceptibility testing, such as a broth microdilution or agar dilution method, which is considered the gold standard for MIC determination. The "Expected Results determined prior to the evaluation" for Challenge strains also fall under this category.
The sample size for the training set:
- The document does not explicitly mention a separate "training set" or its sample size. For traditional AST devices, the development process generally involves extensive internal testing and refinement (which could be considered analogous to training) using a wide array of isolates, but this is distinct from the formal "external evaluation" or validation study. The 510(k) summary focuses on the validation study that demonstrates the device's performance against a reference.
How the ground truth for the training set was established:
- As no specific training set is mentioned in the provided text, the method for establishing its ground truth is also not detailed. In the context of AST device development, internal testing would generally involve comparison to a recognized reference method, similar to the validation study.

Summary

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K051478

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 - Rifampin
Predicate device:	MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panelsand 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 Rifampin.

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

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demonstrated acceptable performance with an overall Essential Agreement of >98% for Rifampin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision filled and reproduction inoculum preparation method and the WalkAway® SI System or equivalent.

Quality Control testing demonstrated acceptable results for Rifampin.

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized representation of a human figure, with three abstract shapes forming the body and head.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 27 2005

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

K051478 Re: Trade/Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels Rifampin (0.25-8 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: June 1, 2005 Received: June 29, 2005

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 for use stated in the encreated of the enactment date of the Medical Device Amendments, or to conniner or prior to 1125 20, 2017 11:11 accordance with the provisions of the Federal Food, Drug, de nees mat have been require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, mercere, mains of the Act include requirements for annual registration, listing of general controls pro risevring 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 it may of cacions 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 I loase oc advised that I DT brosantes over device complies with other requirements of the Act that I Dri has made a astad regulations administered by other Federal agencies. You must or any I cacal statutes and regaraments, 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) I mis leter will anon you wo ought finding of substantial equivalence of your device to a legally premaired notification: ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 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 va may overnit ones generational 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,

Sales, 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): 4051478

Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Rifampin (0.25 - 8 µg/ml)

Indications For Use:

This particular submission is for the addition of the antimicrobial Rifampin, at concentrations of 0.25 to 8 ug/ml, to the test panel.

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

Staphylococcus aureus (including methicillin-resistant strains/MRSA) Staphylococcus epidermidis

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)

	Hall doty
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	Division Sign-Off
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KO 51478

510(k)

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.”