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 Cefuroxime on the Synergies plus™ Gram-Negative MIC/Combo Panels.

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

Citrobacter spp Escherichia coli Klebsiella oxytoca Morganella morganii Proteus mirabilis Providencia rettgeri Shigella spp Salmonella spp

The MicroScan® Synergies plus" Gram-Negative with Cefuroxime is not intended for use with:

Enterobacter sop Klebsiella pneumoniae

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® 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® 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

This document describes the acceptance criteria and study proving the device meets those criteria, based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (FDA DRAFT Guidance, March 8, 2000)	Reported Device Performance (Cefuroxime)
Essential Agreement (Overall)	Not explicitly stated in the document, but contextually implied to be high for substantial equivalence	97% (with parenteral and oral breakpoints)
Reproducibility and Precision	Acceptable	Acceptable
Quality Control Testing	Acceptable	Acceptable

2. Sample Size and Data Provenance

Test Set Sample Size: The document mentions "external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains." However, specific numerical sample sizes for these isolates and strains are not provided.
Data Provenance: The evaluation involved "fresh and stock Efficacy isolates" and "stock Challenge strains." This suggests a mix of retrospective (stock strains) and potentially prospective (fresh isolates) data. The origin of these isolates and strains (e.g., country of origin) is not specified.

3. Number of Experts and Qualifications for Ground Truth

The document states that "Challenge strains were compared to Expected Results determined prior to the evaluation." This implies that experts were involved in establishing the "Expected Results" for the Challenge strains, which served as part of the ground truth. However:

The number of experts is not specified.
The qualifications of these experts are not specified.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for the test set. The comparison was primarily against an "NCCLS frozen Reference Panel" for efficacy isolates and "Expected Results" for challenge strains. This suggests a direct comparison method rather than an independent adjudication process involving multiple readers resolving discrepancies.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not mentioned in the provided text. The study focuses on comparing the device's performance to a reference standard, not on human reader performance with and without AI assistance.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was conducted. The "external evaluation" and comparison to the "NCCLS frozen Reference Panel" and "Expected Results" for challenge strains represents the performance of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel with Cefuroxime itself (the algorithm/device).

7. Type of Ground Truth Used

The ground truth used for the test set consists of two main components:

Reference Standard (NCCLS frozen Reference Panel): For efficacy isolates, the device's performance was compared against an NCCLS (National Committee for Clinical Laboratory Standards) frozen Reference Panel. This is a recognized standard in antimicrobial susceptibility testing.
Expert-Determined Expected Results: For challenge strains, the ground truth was "Expected Results determined prior to the evaluation." This implies a form of expert consensus or established reference values for these specific strains.

8. Sample Size for the Training Set

The document does not provide any information regarding a distinct training set sample size or how the device was trained. The focus is solely on the external evaluation (testing) phase.

9. How Ground Truth for Training Set Was Established

Since no training set is mentioned, information on how its ground truth was established is not provided.

Summary

{0}------------------------------------------------

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 a bird or eagle in flight, composed of three curved lines that suggest the wings and body. 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 0 2004

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

K020328 Re: Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Cefuroxime (1-64 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 19, 2004, 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 ecommerce prave 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.

{1}------------------------------------------------

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 L. Pade 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

{2}------------------------------------------------

Indications for Use Statement

510(k) Number (if known): K020328

MicroScan® Synergies plus" Gram-Negative MIC/Combo Panels with Cefuroxime Device Name: (1 - 64 µg/ml)

Indications For Use:

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

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

Citrobacter spp Escherichia coli Klebsiella oxytoca Morganella morganii Proteus mirabilis Providencia rettgeri Shigella spp Salmonella spp

The MicroScan® Synergies plus" Gram-Negative with Cefuroxime is not intended for use with:

Enterobacter sop Klebsiella pneumoniae

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)

Fredahtu Paul

Division Sign-Off

Page 1 of __ l

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) 020328

{3}------------------------------------------------

FEB 1 9 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 29, 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: Cefuroxime
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 Cefuroxime.

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 p/us™ 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 97% for Cefuroxime, with parenteral and oral breakpoints, when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Cefuroxime 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 Cefuroxime.

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.”