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 (Enterouters) After inoculation, panels are read on the WalkAway® S/ System or equivalent (upgraded WalkAway® 40 or WalkAway® 96) according to the Package Insert.

This particular submission is for the antimicrobial Imipenem 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™ Cram-Negative MIC/Combo Panels are read on the WalkAway® S7 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 with a standardized suspension of the organism and incubated at 35℃ in the WalkAway® SI 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

Here's an analysis of the provided text regarding the acceptance criteria and study for the MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Imipenem:

1. Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (Implicit from FDA Guidance)	Reported Device Performance
Essential Agreement	> 90% (based on typical FDA guidance)	> 96%
Reproducibility	Acceptable (implied by "acceptable reproducibility and precision")	Acceptable
Quality Control Testing	Acceptable (implied by "acceptable results")	Acceptable

Note: The document explicitly states "overall Essential Agreement of greater than 96% for Imipenem when compared with the frozen Reference panel." While the specific numerical acceptance criteria (e.g., >90%) aren't explicitly stated in the provided text for all metrics, the "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices" dated March 8, 2000, which is referenced, would contain these. For Essential Agreement, >90% is a common benchmark for such devices.

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

Test Set Sample Size: Not explicitly stated. The document mentions "external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates/strains used is not provided.
Data Provenance: The document does not specify the country of origin. It indicates the data was collected through "external evaluation," implying it was not solely internal to the manufacturer. It also mentions "fresh and stock Efficacy isolates and stock Challenge strains," suggesting a mix of real-world isolates and controlled laboratory strains. The term "external evaluation" points to it being prospective data collection for the purpose of the submission.

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

This information is not provided in the document. The ground truth was established by an "NCCLS frozen Reference panel," which is a standardized method, not directly a human expert consensus.

4. Adjudication Method for the Test Set

This information is not applicable in the traditional sense, as the ground truth was an "NCCLS frozen Reference panel," which serves as the gold standard for comparison, rather than requiring human adjudication of discordant results.

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

No, an MRMC comparative effectiveness study was not done. This study focused on the performance of the device itself against a reference method, not on human reader improvement with or without AI assistance. The device is an automated system for reading susceptibility panels.

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

Yes, a standalone performance study was done. The goal was to demonstrate that the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel, read on the WalkAway® S7 System, could accurately determine antimicrobial susceptibility. This is an "algorithm only" performance because the device itself automates the reading and interpretation of the MIC panels.

7. Type of Ground Truth Used

The type of ground truth used was an "NCCLS frozen Reference Panel." NCCLS (now CLSI - Clinical and Laboratory Standards Institute) reference panels are standardized methods considered the gold standard for antimicrobial susceptibility testing.

8. Sample Size for the Training Set

This information is not provided in the document. The document describes the evaluation of the device, not the development or training of any underlying algorithms. Since the device is a microdilution system read by an instrument, it doesn't typically involve a "training set" in the machine learning sense for its core function, though instrument calibrations would require data.

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

This information is not provided as a "training set" in the AI/ML context is not mentioned. If referring to the development/calibration of the overall system, it would likely involve similar methods as the test set: comparison to NCCLS/CLSI reference methods and established microbiological standards.

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 consists of a stylized eagle or bird symbol, with its wings spread and head turned to the right. The bird is composed of three curved lines that suggest feathers or wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

Food and Drug Administration

AUG 3 0 2004

2098 Gaither Road Rockville MD 20850

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

Re: K020246 Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Imipenem (0.25, 1-32 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 February 6, 2002, regarding the trade This letter of 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 If your de roo is classified and 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/dsma/dsmamain.html.

Sincerely yours,

Freddie W. Poole for

Sally A. Hojvat, M.Sc., Ph 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): K020246

MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Imipenem Device Name: (0.25, 1 - 32 µg/ml)

Indications For Use:

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

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

Achromobacter spp Acinetobacter spp Aeromonas hydrophila Alcaligenes spp Citrobacter spp Escherichia coli Enterobacter spp Hafnia alvei Klebsiella spp Morganella morganii Pasteurella multocida Proteus vulgaris Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Serratia spp Shigellia spp Salmonella spp Yersinia 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)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of _ 1

510(k) 020246

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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 22, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® rapID/S plus™ Gram-Negative MIC/Combo panels
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	Antimicrobials: Imipenem
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 Imipenem.

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 plas™ Gram-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 greater than 96% for Imipenem 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 Imipenem.

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.”