MicroScan® Synergies plus™ Gram-Negative 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-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 Ampicillin on the Synergies plus" Gram-Negative MIC/Combo Panels.

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

Escherichia coli Salmonella spp.

The MicroScan® Synergies plus™ Gram-Negative with Ampicillin is not intended for use with:

Citrobacter spp. Enterobacter spp. Klebsiella spp. Providencia spp. Proteus mirabilis Proteus vulgaris Shigella spp.

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°C in the WalkAway® SV 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 document describes the performance of the MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Ampicillin for determining antimicrobial susceptibility.

1. Acceptance Criteria and Reported Device Performance

The study compares the performance of the MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panel with Ampicillin against an NCCLS frozen Reference Panel.

Acceptance Criteria (Stated Goal in "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices")	Reported Device Performance (MicroScan® Synergies plus™ Gram-Negative with Ampicillin)
Overall Essential Agreement (EA) with reference method	97.6% EA
Reproducibility and Precision	Acceptable for Turbidity inoculum prep method and WalkAway SI System
Quality Control results	Acceptable for Ampicillin

Note: The specific numeric acceptance criteria for Essential Agreement, Reproducibility, and Quality Control are not explicitly stated in the provided text but are implied to have been met by the device's reported performance.

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

Sample Size for Test Set: The document mentions that the external evaluation was conducted with "fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates or strains used for the test set is not specified in the provided text.
Data Provenance: The data provenance is not explicitly stated in terms of country of origin. The evaluation was an "external evaluation," implying it was conducted outside the manufacturer's internal testing. It appears to be a prospective evaluation comparing the new device against a reference method.

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

This information is not provided in the document. The ground truth was established by an "NCCLS frozen Reference Panel" and "Expected Results determined prior to the evaluation" for challenge strains, but details on human experts involved or their qualifications are absent.

4. Adjudication Method for the Test Set

The adjudication method is not explicitly stated. The comparison was made against an "NCCLS frozen Reference Panel" and "Expected Results" for challenge strains. It's likely that the reference panel itself serves as the 'ground truth' rather than a human adjudication process in the traditional sense for image interpretation.

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 done. This study is focused on the standalone performance of the automated antimicrobial susceptibility testing device compared to a reference method, not on human reader performance with or without AI assistance.

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

Yes, a standalone performance study was done. The report describes the evaluation of the MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panel with Ampicillin (an automated device that determines MIC) against an "NCCLS frozen Reference Panel." This evaluation assesses the device's ability to accurately determine antimicrobial susceptibility concentrations without human intervention in the interpretation of the results.

7. The Type of Ground Truth Used

The ground truth used was primarily an NCCLS frozen Reference Panel. For challenge strains, "Expected Results" determined prior to the evaluation were used. These methods are considered established laboratory reference standards for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not provide any information about a separate training set or its sample size. This type of device evaluation typically focuses on validation against a reference method rather than a machine learning training paradigm.

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

As no training set is mentioned, this information is not available.

Summary

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 3 0 2004

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

K020398 Re: Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Ampicillin (0.25- 128 µg/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Devices Regulatory Class: Class II Product Code: LON Dated: July 30, 2004 Received: August 3, 2004

Dear Mr. Eusebio:

This letter corrects our substantially equivalent letter of May 16, 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). 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 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 forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to continue 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 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 Manufacturers, 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/dsmadsmamain.html.

Sincerely yours,

Freddi tu. Pode
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): K020398

Device Name: MicroScan® Synergies plus" Gram-Negative MIC/Combo Panels with Ampicillin (0.25 - 128 ug/ml)

Indications For Use:

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

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

Escherichia coli Salmonella spp.

The MicroScan® Synergies plus™ Gram-Negative with Ampicillin is not intended for use with:

Citrobacter spp. Enterobacter spp. Klebsiella spp. Providencia spp. Proteus mirabilis Proteus vulgaris Shigella spp.

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)

Ludwita. Pool

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of _ 1

510(k) 020398

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K020398

MAY 1 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:	May 14, 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: Ampicillin
Predicate device:	MicroScan Dried Gram Negative MIC/Combo Panels

510(k) Summary:

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 with Ampicillin.

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 plus™ Cram-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 97.6% for Ampicillin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Turbidity inoculum preparation method and the WalkAway S7 System or equivalent (upgraded WalkAway 40 or WalkAway® 96 instruments).

Quality Control testing demonstrated acceptable results for Ampicillin.

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.”