MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Netilmicin (0.12 - 32 ug/ml) 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 bac!II (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 Netilmicin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

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

Acintobacter spp Citrobacter koseri (diversus) Citrobacter freundii Escherichia coli Enterobacter spp Klebsiella pneumoniae Proteus vulgaris Pseudomonas aeruginosa Serratia spp Shigella spp Salmonella spp

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

Proteus mirabilis

Device Description

MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels are designed for use in determing 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 ® Cramgrowing aeroon and racullanter and on the WalkAway Sy System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments).

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have I le allumic oblar susceptions broth to concentrations bridging the range of clinical interest and are occar unders in Macher Innoin arout form. rapID/S plus™ panels are inoculated with a standardized suspension of the organism and incubated at 35°C in the WalkAway® SY System or equivalent Standardized Suspension of the organism and ancentration (MIC) for the test organism is determined by the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

The provided text describes the MicroScan® Synergies plus™ (initially rapID/S plus™) Gram-Negative MIC/Combo Panels with Netilmicin for determining antimicrobial agent susceptibility. Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document references "FDA criteria for Assessment of Antimicrobial Susceptibility Devices," dated March 8, 2000. While the specific numerical acceptance criteria for Essential Agreement and Category Agreement are not explicitly stated as distinct acceptance criteria in the provided text, the performance is reported against this standard.

Performance Metric	Acceptance Criteria (Implied by reference to FDA Guidance)	Reported Device Performance
Essential Agreement (EA)	Not explicitly stated, but typically ≥ 90%	95.1% (for Netilmicin compared with frozen Reference panel)
Category Agreement (CA)	Not explicitly stated, but typically ≥ 90%	(Not explicitly reported in the provided text)
Reproducibility	Acceptable reproducibility	Demonstrated acceptable reproducibility and precision
Quality Control	Acceptable results	Demonstrated acceptable results for Netilmicin

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

Sample Size:
- The test set consisted of "fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates or strains used is not specified in the provided text.
Data Provenance:
- The evaluation was conducted as an "external evaluation." The country of origin of the data is not specified.
- The study utilized both "fresh and stock Efficacy isolates and stock Challenge strains," indicating a mix of retrospective (stock strains) and potentially prospective (fresh isolates) data collection, though the specifics are not detailed.

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

The ground truth was established by comparing the device's performance to an "NCCLS frozen Reference Panel" and "Expected Results" for challenge strains. This implies a standardized reference method rather than direct expert interpretation of each case for ground truth. Therefore:

Number of experts: Not applicable in the context of individual case reads. The NCCLS panel and "Expected Results" define the ground truth based on established methods.
Qualifications of experts: Not applicable.

4. Adjudication method for the test set

The text describes a comparison against an "NCCLS frozen Reference Panel" and "Expected Results" for challenge strains. This is a reference method comparison, not an adjudication process involving multiple human readers. Therefore, an adjudication method (like 2+1, 3+1) is not applicable here.

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

MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility testing panel, not a diagnostic imaging AI system designed to assist human readers.
Effect size of human reader improvement: Not applicable.

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

Yes, a standalone performance evaluation was done. The device (MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Netilmicin read on the WalkAway® SI System or equivalent) functions as an automated system to determine Minimum Inhibitory Concentration (MIC) without direct human interpretation for each individual result once inoculated. The performance reported (95.1% Essential Agreement) is a standalone performance metric of the combined device and automated reading system against a reference standard.

7. The type of ground truth used

The ground truth used was:

Reference Standard Comparison: Performance was compared to an "NCCLS frozen Reference Panel."
Expected Results: For challenge strains, performance was compared to "Expected Results determined prior to the evaluation."

This represents a laboratory reference method ground truth, not expert consensus, pathology, or outcomes data.

8. The sample size for the training set

The provided text does not specify a separate training set or its sample size. The description focuses on the evaluation/test set. For an in-vitro diagnostic device of this nature, the "training" aspect is more about the scientific and engineering development and optimization of the panel and reading system, rather than a distinct machine learning training set with labeled data as seen in AI algorithms.

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

Since a distinct training set with established ground truth as commonly understood in AI/ML contexts is not mentioned, this information is not applicable based on the provided text. The development of the device itself would have relied on established microbiological principles, reference methods, and quality control procedures to ensure its performance characteristics.

Summary

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AUG 3 0 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

Re: K020182 Trade/Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Netilmicin (0.12-32 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 February 6, 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,

fu. Paolo
Aldington

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): K020182

Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Netilmicin

(0.12 - 32 ug/ml)

media of rapidly growing aerobic and facultative anaerobic Gram-Negative bac!II (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 Netilmicin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

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

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

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)

Division Sign-Off

on Sign-Off
Office of In Vitro Diagnostic Device
Evaluation and Seitro Diagnost
valuation and Safety
510(k) 020182

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K020182

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 17, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panel
Trade Name:	MicroScan® rapID/S plus™ Gram-Negative MIC/Combo panel
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	Antimicrobials: Netilmicin
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 The proposed thinklobano rapon's prosvith an NCCLS frozen Reference Panel, as defined in the FDA equivalent performance when 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 Netilmicin.

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-The extential evaluations were designed to ver with an NCCLS frozen Reference panel. Challenge strains were compared to Expected Results determined prior to the evaluation. The rapID/S plus "Foram-Negative Were compared acceptable performance with an overall Essential Agreement of 95.1% for Netilmicin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Turbidity inculum preparation method and the WalkAway® System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments).

Quality Control testing demonstrated acceptable results for Netilmicin.

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.”