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

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

Escherichia coli Enterobacter spp. Klebsiella spp. (except Klebsiella oxytoca) Proteus spp. (except Proteus mirabilis) Providencia rettgeri Pseudomonas spp Serratia spp Shigella spp Salmonella spp. Yersinia spp.

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

Acinetobacter spp. Citrobacter spp. Klebsiella oxytoca Morganella morganii Proteus mirabilis

Device Description

MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels are designed for use in acterming quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid nedia of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. The MicroScan® rapIDS play™ (171 growing aeroon and faculture and 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 to the may The andilited in Mueller-Hinton Broth to concentrations bridging the range of clinical interest and are becal unded in micro-titer wells in dried form. rapID/S plus™ panels are inoculated with a presented in inicio-nier wells in and incubated at 35°C in the WalkAway® S7 System or equivalent standardized suspension of the organism and interest organism is determined by the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided document:

Acceptance Criteria and Device Performance

The document doesn't explicitly state a table of "acceptance criteria" with numerical targets for Essential Agreement (EA) or Category Agreement (CA) prior to presenting results, which is common in more recent FDA submissions. Instead, it states that the external evaluation was designed to "confirm the acceptability of the proposed rapID/S plus™ Gram-Negative MIC/Combo Panel with Piperacillin standards of the Panel, as defined in the FDA DRAFT document 'Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices'". The specific numerical criteria from this draft guidance are not provided in this document.

However, the reported device performance is:

Metric	Reported Performance (Piperacillin)
Overall Essential Agreement (EA)	94.4%

Note: The document refers to "Essential Agreement" but does not explicitly mention "Category Agreement." It implies that achieving an acceptable EA percentage is the primary measure of performance from this summary.

Study Information

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

Test Set Organisms: The external evaluation used "fresh and stock Efficacy isolates and stock Challenge strains."
- The "Efficacy isolates" are likely the clinical isolates, and the "Challenge strains" are likely isolates with known resistance mechanisms or difficult-to-test characteristics.
Sample Size: The document does not specify the exact number of isolates (sample size) used in the test set.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the use of "fresh and stock Efficacy isolates" suggests a mix, and "stock Challenge strains" are typically laboratory-maintained. It doesn't indicate if these were prospectively collected patient samples or geographically diverse.

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

The ground truth for the test set was established by an "NCCLS frozen Reference panel." This implies a standardized reference method rather than individual human experts.
Therefore, information on the number or qualifications of experts for establishing ground truth is not applicable in the traditional sense, as it relies on a reference method.

4. Adjudication method for the test set:

Not applicable. The ground truth was established by comparison to an "NCCLS frozen Reference panel," which is a standardized method, not a human consensus process.

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

No. This is an in vitro diagnostic device for antimicrobial susceptibility testing, which directly measures bacterial responses to antibiotics. It is not an imaging device or a decision support AI system meant to assist human readers, so an MRMC comparative effectiveness study is not applicable.

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

Yes, this is essentially a standalone performance study. The device itself (MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels read by the WalkAway® System) generates the susceptibility results based on its internal processes and measurements. The "Overall Essential Agreement 94.4%... when compared with the frozen Reference panel" directly reflects this standalone performance against a gold standard.

7. The type of ground truth used:

Reference Method (NCCLS frozen Reference panel). This is a highly standardized and accepted method for determining antimicrobial susceptibility, serving as the gold standard for comparison in these types of studies.

8. The sample size for the training set:

Not explicitly stated in the provided text. The document describes the external evaluation (test set) but does not mention a distinct "training set" or its size for the development of the device or its interpretive algorithms. For this type of in vitro diagnostic device, the "training" often involves extensive empirical testing and optimization during development, rather than a separate, formally delineated training set as understood in current machine learning paradigms.

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

Not explicitly stated in the provided text. As a "training set" is not mentioned, the method for establishing its ground truth is also not detailed. Device development typically involves internal testing against reference methods to refine specifications and performance, but specific details on a formal training set and its ground truth establishment are absent.

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

Re: K020397 Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Piperacillin (4- 256 ug/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 22, 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,

Freddie Poole for

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): K020397

MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Piperacillin Device Name: (4 - 256 µg/ml)

Indications For Use:

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

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

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

Acinetobacter spp. Citrobacter spp. Klebsiella oxytoca Morganella morganii Proteus mirabilis

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)

Luddi M. Poole

ivision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of _ 1

510(k) 02039.7

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K020397

APR 2 2 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:	February 4, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® rapID/S plus™ Gram-Negative MIC/Combo panel
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	Antimicrobials: Piperacillin
Predicate device:	MicroScan Dried Gram Negative MIC/Combo Panels

510(k) Summary:

The proposed MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel demonstration sites TDA The proposed MicroSean® Taptible of Start Comments of the Panel, as defined in the FDA DRAFT document "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", DRATT Gotument "Outdance on Review estitication (510[k]) presents data in support of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel with Piperacillin.

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 "Man-The catelian Changers were use with an NCCLS frozen Reference panel. Challenge strains Negative Faller of Venificant getermined prior to the evaluation. The rapID/S plus ™ Gram-Negative were computed to Laportu Tibers as with an overall Essential Agreement 94.4% for Piperacillin when compared with the frozen Reference panel.

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

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.”