MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on sold media of rapidly growing aerobic and facultative anaerobic Gram-Negative bacilli (Enterobacteriaceae, glucose non-fermenters, and non-Enterobacteriaceae glucose fermenters. After inoculation, panels are read on the WalkAway® SI System or equivalent (upgraded WalkAway® 40 or WalkAway® 96) according to the Package Insert. This particular submission is for the antimicrobial Tobramycin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

Device Description

MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels 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-negative bacilli. The MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels are read on the WalkAway® SI System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments). The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in Mueller-Hinton Broth to concentrations bridging the range of clinical interest and are presented in micro-titer wells in dried form. rapID/S plus™ panels are inoculated and rehydrated with a standardized suspension of the organism and incubated at 35℃ in the WalkAway® SY System or equivalent for 4.5 - 18 hours. The minimum inhibitory concentration (MIC) for the test organism is determined by the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

The provided text describes the MicroScan® Synergies Plus Gram-Negative MIC/Combo Panels with Tobramycin, a device used for antimicrobial agent susceptibility testing. The original submission was for the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo panel, and the name was later changed.

Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (or equivalent)	Reported Device Performance (Tobramycin)
Essential Agreement	Not explicitly stated as a numerical criterion in the provided text, but implied as "acceptable performance" as defined in the FDA DRAFT document "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices".	96.6% (when compared with the NCCLS frozen Reference panel)
Reproducibility	"acceptable reproducibility and precision"	Demonstrated acceptable reproducibility and precision.
Quality Control	"acceptable results"	Demonstrated acceptable results.

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

The text states that the external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. However, the exact sample size (number of isolates/strains) used for the test set is not explicitly provided in the given document.

The data provenance is described as an "external evaluation." While the country of origin isn't specified, the reference to "FDA DRAFT document 'Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices'" suggests a U.S. regulatory context. Given the nature of susceptibility testing, it would typically be prospective, as the device is being tested against these isolates to determine its performance.

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

The document does not specify the number of experts used or their qualifications to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set. The comparison was primarily against an "NCCLS frozen Reference Panel" and "Expected Results" for challenge strains, which suggests a direct comparison method rather than expert adjudication of discrepancies.

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

No, an MRMC comparative effectiveness study was not done. This type of study would typically involve human readers interpreting results with and without AI assistance to quantify performance improvement. This device (MicroScan® Synergies Plus) is an automated system for determining antimicrobial susceptibility, not an AI-assisted diagnostic tool that aids human interpretation in the same way an imaging AI might. Therefore, the concept of "improving human readers with AI vs without AI assistance" does not directly apply here.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the study described is a standalone performance study. The MicroScan® Synergies Plus system, read on the WalkAway® SI System, is designed to provide results without human interpretation of the raw susceptibility data beyond loading the panel and retrieving the processed results. The stated "Essential Agreement of 96.6% for Tobramycin when compared with the frozen Reference panel" reflects the algorithm's performance in determining MIC values.

7. The Type of Ground Truth Used

The ground truth for the test set was established using:

NCCLS frozen Reference Panel: This is a standardized method for antimicrobial susceptibility testing, considered the gold standard for comparison in many such studies.
Expected Results: For "Challenge strains," their susceptibility profiles were pre-determined and used as the "Expected Results" for comparison. This implies either expert consensus, prior laboratory reference methods, or established databases for known challenge strains.

8. The Sample Size for the Training Set

The document does not provide information about a separate "training set" or its sample size. This type of device's development typically involves establishing methodologies and validating them against known standards rather than training a machine learning model on a distinct dataset in the way a modern AI algorithm might be.

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

Since a dedicated "training set" is not mentioned, the method for establishing its ground truth is not applicable/provided in this document. The development of the MicroScan® system would have relied on established microbiological principles and validated reference methods.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines forming its body and wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" arranged in a circular fashion around the emblem.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 3 1 2004

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

K020168 Trade/Device Name: MicroScan® Synergies Plus Gram Negative MIC/Combo Panels with Tobramycin (0.12 - 32 µg/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: II Product Code: LON Dated: July 30, 2004 Received: August 3, 2004

Dear Mr. Eusebio:

Re:

This letter corrects our substantially equivalent letter of February 6, 2002, regarding the trade name which was changed to MicroScan® Synergies Plus to better reflect the intended use of the device.

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 (PMA). Vou 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 additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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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 Part 801); good manufacturing practice requirements as set premainet 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally Part 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-3084. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufactures, International and Consumer Assistance at their toll free number (800) 638-2041 or at (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

fucddite. Rocke for

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 Statement

510(k) Number (if known): K020168

MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Tobramycin Device Name: (0.12 - 32 ug/ml)

Indications For Use:

This particular submission is for the antimicrobial Tobramycin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

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

Citrobacter amalonaticus Citrobacter koseri (diversus) Citrobacter freundit Citrobacter spp Escherichia coli Enterobacter aerogenes Enterobacter agglomerans Enterobacter cloacae Enterobacter sakazakii Enterobacter spp Klebsiella oxytoca Klebsiella ozaenae

Klebsiella pneumoniae Klebsiella rhinoscleromatis Klebsiella spp Morganella morganii Proteus mirabilis Proteus vulgaris Proteus spp Providencia alcalifaciens Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Serratia spp Serratia marcescens

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)

Lueddin L. Poole

Division Sign Off

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of _ 1

510(k) 22-0168

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K020168

FEB 0 6 2002

510(k) Summary

510(k) Submission Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	Maureen Mende, Group Manager Regulatory Affairs
Fax:	916-374-3144
Date prepared:	January 15, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panel
Trade Name:	MicroScan® rapID/S plus™ Gram-Negative MIC/Combo panel
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	Antimicrobials: Tobramycin
Predicate device:	MicroScan Dried Gram Negative MIC/Combo Panels

510(k) Summary:

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in Mueller-Hinton Broth to concentrations bridging the range of clinical interest and are presented in micro-titer wells in dried form. rapID/S plus™ panels are inoculated and rehydrated with a standardized suspension of the organism and incubated at 35℃ in the WalkAway® SY System or equivalent for 4.5 - 18 hours. The minimum inhibitory concentration (MIC) for the test organism is determined by the lowest antimicrobial concentration showing inhibition of growth.

The proposed MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel demonstrated substantially equivalent performance when compared with an NCCLS frozen Reference Panel, as defined in the FDA DRAFT document "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", dated March 8, 2000. The Premarket Notification (510[k]) presents data in support of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel Tobramycin.

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 rapID/S plasm-Negative Panel by comparing its performance with an NCCLS frozen Reference panel. Challenge strains were compared to Expected Results determined prior to the evaluation. The rapID/S plus™ Gram-Negative Panel demonstrated acceptable performance with an overall Essential Agreement of 96.6% for Tobranycin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Tobramycin with Turbidity inoculum preparation method and the WalkAway® SI System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments).

Quality Control testing demonstrated acceptable results for Tobramycin.

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.”