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

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

Acinetobacter calcoaceticus Escherichia coli Enterobacter spp. (except Enterobacter cloacae) Klebsiella pneumoniae Klebsiella oxytoca Morganella morganii Proteus mirabilis Providencia spp. Pseudomonas aeruginosa Serratia marcescens Shigella spp. Salmonella spp.

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

Citrobacter son Enterobacter cloacae Proteus vulgaris

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 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

This document describes the 510(k) premarket notification for the MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Ceftriaxone. It details the device's intended use and provides a summary of the performance study conducted.

Here is an analysis based on your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state "acceptance criteria" in a tabulated format with specific pass/fail thresholds. However, it does report performance metrics that imply the criteria met for substantial equivalence.

Performance Metric	Reported Device Performance (Ceftriaxone)	Implicit Acceptance Criteria (based on "acceptable performance")
Overall Essential Agreement	95.9%	Likely ≥ 90% or 95% (common for microdilution susceptibility)
Overall Categorical Agreement (breakpoint dilutions)	89.6%	Likely ≥ 90% (common for microdilution susceptibility)
Instrument Reproducibility (Turbidity inoculum)	Acceptable	Implies meeting pre-defined precision/variability standards
Quality Control Testing	Acceptable	Implies meeting pre-defined QC ranges

2. Sample size used for the test set and the data provenance

Sample Size for Test Set: The document mentions "external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates/samples used in the test set is not specified.
Data Provenance: The document does not explicitly state the country of origin. It indicates it was an "external evaluation," and given the FDA approval, it's reasonable to assume the study was conducted to meet US regulatory requirements. The study appears to be retrospective, using "fresh and stock Efficacy isolates and stock Challenge strains."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document. The ground truth was established by an "NCCLS frozen Reference Panel." The document doesn't detail how this reference panel's results were determined or if expert consensus was involved in its creation.

4. Adjudication method for the test set

This information is not provided in the document.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC study was done. This device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic tool involving human readers interpreting results. It determines MIC values autonomously.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance study was done. The device (MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels read on the WalkAway® System) was compared against an "NCCLS frozen Reference Panel" without human intervention in the result interpretation from the device itself. The "human-in-the-loop" aspect for this type of device typically involves preparing the inoculum and loading the panels, but the reading and interpretation of MICs are automated.

7. The type of ground truth used

The ground truth used was an NCCLS frozen Reference Panel. This type of reference standard is typically established through a standardized, highly controlled laboratory method (e.g., broth microdilution or agar dilution) performed by experienced microbiologists, potentially following guidelines set by organizations like the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS).

8. The sample size for the training set

The document does not specify a training set size. For an antimicrobial susceptibility device, the "training" aspect is more about assay development and optimization rather than machine learning algorithm training with distinct datasets. The performance evaluation focuses on the test set of isolates.

9. How the ground truth for the training set was established

As a training set is not explicitly mentioned in the context of typical machine learning, this question is not directly applicable. If "training" refers to the development of the device's reading algorithms, the ground truth for establishing those algorithms would have been based on established phenotypic antimicrobial susceptibility testing methods. However, the document does not detail this developmental process.

Summary

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Image /page/0/Picture/2 description: The image shows a partial view of a document with a logo and some text. On the left side, there's a circular logo with the words "DEPARTMENT OF HEALTH & HUMAN" arranged around it. To the right of the logo, there's a word that appears to be a heading or title, but the full word is not visible in the image. The overall impression is that this is a formal document, possibly from a government or health-related organization.

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

K020506 Re: Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Ceftriaxone (0.5, 2- 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 April 17, 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/dsma/dsmamain.html.

Sincerely yours,

Luddite Code fo

ly 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): K020506

Device Name: MicroScan® Synergies plus" Gram-Negative MIC/Combo Panels with Ceftriaxone (0.5 , 2 - 128 ug/ml)

Indications For Use:

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

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

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

Citrobacter son Enterobacter cloacae Proteus vulgaris

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)

Leddute. Pody

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of __ 1

510(k) 020506

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APR 1 7 2002

K020506

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:	February 13, 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: Ceftriaxone
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 Ceftriaxone.

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™ Gram-Negative Panel by comparing its performance with an NCCLS frozen Reference panel. Challenge strains were compared to Frozen Results determined prior to the evaluation. The rapID/S plus™ Gram-Negative Panel demonstrated acceptable performance with an overall Essential Agreement of 95.9% for Ceftriaxone long dilutions and 89.6% Categorical Agreement for breakpoint dilutions when compared with the frozen Reference panel.

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

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.”