The 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. After inoculation, panels are incubated for 4.5 - 18 hours at 35°C +/- 1°C, 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 AST portions can be read visually, according to the Package Insert.

This particular submission is for the addition of the antimicrobial Nitrofurantoin, at concentrations of 1 to 256 ug/ml, to the test panel.

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

Escherichia coli Citrobacter amalonaticus Citrobacter freundii Citrobacter koseri (diversus) Klebsiella oxytoca Klebsiella ozaenae Klebsiella spp. * Enterobacter spp. *

Some strains of Klebsiella species and Enterobacter species are resistant to Nitrofurantoin.

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 antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in Mueller-Hinton Broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SJ 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

The provided text describes the 510(k) submission for the MicroScan® Synergies Plus Gram-Negative MIC/Combo Panels with Nitrofurantoin. The device is an antimicrobial susceptibility test system.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Overall Essential Agreement (EA) with NCCLS frozen Reference Panel	>99% Essential Agreement for Nitrofurantoin
Reproducibility for Nitrofurantoin	Acceptable reproducibility and precision
Quality Control results for Nitrofurantoin	Acceptable results

Explanation of "Implied" Acceptance Criteria: The document mentions that the device "demonstrated substantially equivalent performance when compared with an NCCLS 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." This FDA guidance document would contain the specific acceptance criteria (e.g., percentage for Essential Agreement, Categorical Agreement, etc.). While the exact numerical criteria from the guidance are not explicitly stated in this document, the reported performance of ">99% Essential Agreement" is presented as meeting those criteria.

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

Test Set Description: The external evaluation was conducted with "fresh and stock Efficacy isolates and stock Challenge strains."
Sample Size: The exact number of isolates/strains used for the test set is not explicitly stated in the provided text.
Data Provenance: The text does not specify the country of origin of the data. It indicates the evaluation was "external," meaning performed outside the manufacturer's internal labs, but doesn't detail the location. The study involves "Efficacy isolates" and "Challenge strains," suggesting a mix of clinical relevance and specific strains designed to test performance limits. It is a prospective comparison against a reference method.

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

The ground truth for the test set was established by comparing the device's performance against an NCCLS frozen Reference Panel.
The NCCLS (National Committee for Clinical Laboratory Standards, now CLSI) sets standards for antimicrobial susceptibility testing. The "Expected Results" for the "Challenge strains" were "determined prior to the evaluation," implying expert consensus in establishing these reference values.
The document does not specify the number or qualifications of experts directly involved in establishing the NCCLS frozen Reference Panel or the "Expected Results" for the challenge strains. However, an NCCLS reference panel inherently represents a consensus of experts in the field of clinical microbiology.

4. Adjudication Method for the Test Set

The adjudication method described is a direct comparison of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel with Nitrofurantoin against an NCCLS frozen Reference Panel and against "Expected Results" for challenge strains. This is a point-by-point comparison rather than a human reader adjudication method. Therefore, no multi-reader adjudication method (like 2+1 or 3+1) is applicable here.

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

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not performed or described. This device is an automated antimicrobial susceptibility testing system, and its performance is evaluated against a reference standard, not in the context of human reader improvement.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone performance study was performed. The device's performance (ability to determine MICs) was directly compared against the NCCLS frozen Reference Panel and Expected Results for challenge strains, without human intervention affecting the interpretive results of the MicroScan system itself. The text states: "...the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth" by the MicroScan® system.

7. Type of Ground Truth Used

The ground truth used was based on NCCLS frozen Reference Panel results and pre-determined "Expected Results" for stock Challenge strains. This is a reference standard method widely accepted in microbiology for establishing the accuracy of antimicrobial susceptibility tests.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its sample size. This type of device's development typically involves extensive internal testing and refinement (which could be considered analogous to training), but the document specifically focuses on the external validation study using "fresh and stock Efficacy isolates and stock Challenge strains" as the evaluation set. It's possible the 'training' or development phase used a different set of isolates not detailed here, or the system's design is based on established biochemical/microbiological principles rather than a machine learning training paradigm requiring a distinct, large 'training set' in the modern AI sense.

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

As a training set is not explicitly described, the method for establishing its ground truth is not provided. If an internal 'training' process occurred, it would likely also rely on comparison to established reference methods or expert interpretation similar to the NCCLS reference standard.

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 representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol.

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

K031602 Re: Trade/Device Name: MicroScan® Synergies Plus Gram Negative MIC/Combo Panels with Nitrofurantoin (1 - 256 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, JWY Dated: July 30, 2004 Received: August 3, 2004

Dear Mr. Eusebio:

This letter corrects our substantially equivalent letter of July 31, 2003, 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/dsma/dsmamain.html.

Sincerely vours.

Luddu tu. Poole
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): K031602

MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Nitrofurantoin Device Name: (1 - 256 ug/ml)

Indications For Use:

This particular submission is for the addition of the antimicrobial Nitrofurantoin, at concentrations of 1 to 256 ug/ml, to the test panel.

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

Escherichia coli Citrobacter amalonaticus Citrobacter freundii Citrobacter koseri (diversus) Klebsiella oxytoca Klebsiella ozaenae Klebsiella spp. * Enterobacter spp. *

Some strains of Klebsiella species and Enterobacter species are resistant to Nitrofurantoin.

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)

Lieddute. Pook
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of _ 1

510(k)_031602

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K03/602

JUL 3 1 2003

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:	May 15, 2003
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:	New antimicrobial - Nitrofurantoin
Predicate device:	MicroScan® rapID/S plus™ 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 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® rapID/S plus™ Gram-Negative MIC/Combo Panel with Nitrofuranton.

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" (fram-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 >99% for Nitrofurantoin when compared with the frozen NCCLS Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Nitrofurantoin.

Quality Control testing demonstrated acceptable results for Nitrofurantoin.

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.”