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® SI System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments).

This particular submission is for the antimicrobials Ofloxacin, Norfloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin on the Synergies plus" Gram-Negative MIC/Combo Panels.

The Gram-Negative organisms which may be used for Ofloxacin (Ofl), Norfloxacin (Nxn), Levofloxacin (Lvx), Lomefloxacin (Lmf), Sparfloxacin (Sfx), and Ciprofloxacin (Cp) susceptibility testing in this panel are listed in the attached table.

Device Description

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. The rapID/S plus™ panels are inoculated with a standardized suspension of the organism and incubated at 35℃ in the WalkAway® SI 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

Acceptance Criteria and Study for MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels

This document describes the acceptance criteria and study details for the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels for determining antimicrobial agent susceptibility, specifically for Ofloxacin, Norfloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are derived from the "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", dated March 8, 2000, and are presented below alongside the device's reported performance.

Antimicrobial Agent	Acceptance Criteria (Essential Agreement)	Reported Device Performance (Essential Agreement)	Acceptance Criteria (Categorical Agreement)	Reported Device Performance (Categorical Agreement)
Ciprofloxacin	N/A (implied high agreement)	98.3% (640/651)	N/A (implied high agreement)	92.8% (604/651)
Levofloxacin	N/A (implied high agreement)	98.2% (639/651)	N/A (implied high agreement)	94.3% (614/651)
Lomefloxacin	N/A (implied high agreement)	98.6% (642/651)	N/A (implied high agreement)	94.9% (618/651)
Norfloxacin	N/A (implied high agreement)	97.4% (634/651)	N/A (implied high agreement)	93.5% (609/651)
Ofloxacin	N/A (implied high agreement)	98.3% (640/651)	N/A (implied high agreement)	93.5% (609/651)
Sparfloxacin	N/A (implied high agreement)	98.6% (561/569)	N/A (implied high agreement)	96.3% (548/569)

Note on Acceptance Criteria: The provided text explicitly states that the device "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." While specific numerical thresholds for "Essential Agreement" and "Categorical Agreement" for acceptance are not explicitly listed in the provided summary, the reported percentages are presented as successful outcomes in meeting these criteria. The phrase "acceptable performance" is used, implying the reported values met the established thresholds.

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

Test Set Sample Sizes:
- Ciprofloxacin, Levofloxacin, Lomefloxacin, Norfloxacin, Ofloxacin: 651 isolates each.
- Sparfloxacin: 569 isolates.
Data Provenance: The external evaluation was conducted with a mix of:
- "fresh and stock Efficacy isolates": These likely represent clinical isolates.
- "stock Challenge strains": These are likely well-characterized strains used for quality control and validation.
  The country of origin is not explicitly stated, but the evaluation compared performance against an "NCCLS frozen Reference Panel," suggesting a standardization against US-based clinical microbiology guidelines. The study appears to be prospective in nature for the efficacy isolates and challenge strains as they were evaluated against a reference method.

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

The submission does not specify the number or qualifications of experts used to establish the ground truth. The ground truth was established by an NCCLS frozen Reference Panel. This implies a standardized laboratory method, likely performed by trained laboratory professionals, rather than a subjective expert consensus scenario often seen in image-based diagnostics.

4. Adjudication Method for the Test Set

The adjudication method is not explicitly described. However, the study involved comparing the device's results to an "NCCLS frozen Reference panel." This typically means that any discrepancies between the device and the reference method would be analyzed, but a formal "adjudication" process with multiple human readers resolving disagreements is not applicable in this context. The reference panel itself serves as the "gold standard."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for diagnostic imaging devices where human reader performance is a key metric. This submission concerns an in vitro diagnostic device for antimicrobial susceptibility testing, where the focus is on the agreement with a reference laboratory method rather than human interpretation of complex images.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone performance study was done. The study evaluated the performance of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels when read on the WalkAway® SI System or equivalent. This automated reading by the instrument constitutes the "standalone" or "algorithm only" performance, comparing its output directly to the reference standard.

7. The Type of Ground Truth Used

The type of ground truth used was comparison to an NCCLS frozen Reference Panel. This method effectively serves as the "gold standard" for determining Minimum Inhibitory Concentrations (MICs) in antimicrobial susceptibility testing, representing a highly standardized and accepted laboratory procedure.

8. The Sample Size for the Training Set

The submission does not explicitly state the sample size used for the training set. The descriptions focus on the external evaluation (test set) and reproducibility/quality control testing. As an in vitro diagnostic device, the "training set" might refer to internal development and validation data, which is not detailed in this 510(k) summary.

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

Similar to the training set sample size, the document does not explicitly describe how the ground truth for a potential training set was established. However, given the nature of the device (MIC panels), it is highly probable that any internal development or training would also rely on comparisons to established reference methods, such as those defined by NCCLS guidelines, or characterized microbiological strains with known susceptibility profiles.

Summary

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K020142

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 15, 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: Ofloxacin, Norfloxacin, Levofloxacin, Lomefloxacin Sparfloxacin, and Ciprofloxacin
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 Ofloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin.

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 Expected Results determined prior to the evaluation. The rapID/S plus™ Gram-Negative Panel demonstrated acceptable performance with an overall Essential Agreement of 98.3% for Offloxacin, 97.4% for Nortloxacin, 98.2% for Levofloxacin, 98.6% for Lomefloxacin, 98.6% for Sparfloxacin and 98.3% for Ciprofloxacin when compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Offloxacin, Norfloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin 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 Ofloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin.

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Section 1. LABELING SUMMARY

Labeling Changes Requiring FDA Clearance Prior to Implementation

Clearance is requested for an MIC range which allows MicroScan the ability to select . any number of antimicrobic for inclusion on future panels. The combination of dily halls chosen will be verified for acceptable performance, as defined in the DRAFT FDA guidance document titled "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", dated March 8, 2000, prior to release. The dilutions requested, for use with gram-negative are indicated below:

Antimicrobial	Panel Type	Abbreviation	MIC DilutionsRequested
Ciprofloxacin	gram-negative	Cp	0.25 – 8 µg/ml
Levofloxacin	gram-negative	Lvx	0.5 - 16 µg/ml
Lomefloxacin	gram-negative	Lmf	1.0 - 16 µg/ml
Norfloxacin	gram-negative	Nxn	0.12 - 32 µg/ml
Ofloxacin	gram-negative	Ofx	0.12 - 16 µg/ml
Sparfloxacin	gram-negative	Sfx	0.5 - 8 µg/ml

The following FDA Interpretive Breakpoints will be added to the MicroScan® rapID/S plus™ Procedural Manuals:

Interpretive Breakpoints1	Antimicrobial Agents	Susceptible	Intermediate
Ciprofloxacin	≤1	2	≥4
Levofloxacin2	≤2	4	≥8
Lomefloxacin3	≤2	4	≥8
Norfloxacin3	≤4	8	≥16
Ofloxacin3	≤2	4	≥8
Sparfloxacin4	≤1	2	≥4

Based on Interpretive Breakpoints as indicated in NCCLS Document M100-S11. There are antimicrobials included on the rapID/S plus™ panels that are not proven to be effective for treating clinical infections for all organisms that may be tested. For interpreting and reporting of antimicrobial results which have shown to be active against organism groups, tooth in chiro and in clinical infections, refer to NCCLS M100 Performance Standard Table1 or the pharmaceutical antibiotic labeling.

antiblotic laboling.
2. Interpretive criteria for urinary tract infections are only for P.aeruginosa and Other Non-Enterobacteriaceae,

Interpretive criteria applies to urinary tract infections only.
Interpretive criteria applies to Enterobacteriaceae only.

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The following Performance Characteristics claims will be added to the Procedural . Manual:

Antimicrobial Agent	Essential Agreement (%)	Categorical Agreement (%)
Ciprofloxacin	640/651(98.3)	604/651 (92.8)
Levofloxacin	639/651 (98.2)	614/651 (94.3)
Lomefloxacin	642/651 (98.6)	618/651 (94.9)
Norfloxacin	634/651 (97.4)	609/651 (93.5)
Ofloxacin	640/651 (98.3)	609/651 (93.5)
Sparfloxacin	561/569 (98.6)	548/569 (96.3)

Percent Agreement to Reference Method

The following QC ranges will be added to the Quality Control Manual: .

AntimicrobialAgent	Abbreviation	E. coliATCC 25922Range1	P. aeruginosaATCC 27853Range1
Ciprofloxacin	Cp	<= 0.25	<= 0.25-1
Levofloxacin	Lvx	<= 0.5	<=0.5-4
Lomefloxacin	Lmf	<= 1.0	<=1-4
Norfloxacin	Nxn	<= 0.12	1-4
Ofloxacin	Ofl	<= 0.12	1-82
Sparfloxacin	Sfx	<= 0.5	<=0.5-23

Range = Expected value (µg/ml) 1.

Out-of-range results may require extended incubation and reporting may range from 16-20 hours. 2.

Organism intended for Quality Control Testing only. 3.

The following limitations will be added to the Limitations Section of the MicroScan® . rapID/S plus™ Gram-Negative Procedural Manual:
- For Ofloxacin confirm and report Pseudomonas aeruginosa results at 16-20 hours . incubation.

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MicroScan rapID/S plus" Gram - Negative Procedural Manual

Oflox Norflox Levo Lomeflox Sparflox Cipro labeling summary.doc.doc

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and three wavy lines below it. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 1 4 2004

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

Re: K020142

Trade/Device Name: MicroScan® Synergies Plus Gram Negative MIC/Combo Panels with Ofloxacin, (0.12-16 ug/ml), Norfloxacin (0.12-32 ug/ml), Levofloxacin (0.5-16 µg/ml), Lomefloxacin (1.0-16 µg/ml), Sparfloxacin (0.5-8 µg/ml), Ciprofloxacin (0.25-8 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 Dated: February 13, 2002 Received: February 15, 2002

Dear Mr. Eusebio:

This letter corrects our substantially equivalent letter of March 14, 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,

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): K020142

Device Name: MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Offloxacin, (0.12 -- 16 µg/ml), Norfloxacin (0.12 - 32 µg/ml), Levofloxacin (0.5 - 16 µg/ml), Lomefloxacin (1.0 - 16 ug/ml), Sparfloxacin (0.5 - 8 ug/ml), Ciprofloxacin (0.25 - 8 ug/ml)

Indications For Use:

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® S/ System or equivalent (upgraded WalkAway® 40 or WalkAway® 96) according to the Package Insert.

This particular submission is for the antimicrobials Ofloxacin, Norfloxacin, Levofloxacin, Lomefloxacin, Sparfloxacin, and Ciprofloxacin on the Synergies plus" Gram-Negative MIC/Combo Panels.

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)

Page 1 of 1

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INDICATIONS FOR USE STATEMENT

Page 2 of 3 .

510(k) Number (if known): K_

Device Name:

MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels with Ofloxacin, (0.12 - 16 ug/ml), Norfloxacin (0.12 - 32 µg/ml), Levofloxacin (0.5 - 16 µg/ml), Lomefloxacin

(1.0-16 ug/ml), Sparfloxacin (0.5 - 8 µg/ml), Ciprofloxacin (0.25 - 8 µg/ml

Indications For Use:

Organism	Cp	Lvx	Lmf	Nxn	Ofn	Sfx
Acinetobacter baumanii		X				X
Acinetobacter calcoaceticus		X		X	X
Acinetobacter Iwoffi	X	X				X
Aeromonas caviae	X				X
Aeromonas hydrophila	X		X		X
Aeromonas spp				X
Alcaligenes spp				X
Citrobacter koseri (diversus)	X	X		X	X	X
Citrobacter freundii	X	X	X	X	X
Edwardsiella tarda	X			X
Escherichia coli	X	X	X	X	X
Enterobacter aerogenes		X	X	X	X	X
Enterobacter agglomerans		X	X
Enterobacter cloacae	X	X	X	X	X	X
Enterobacter sakazakii		X
Flavobacterium spp				X
Hafnia alvei			X	X
Klebsiella oxytoca	X	X	X	X	X	X
Klebsiella ozaenae			X
Klebsiella pneumoniae	X	X	X	X	X	X
Klebsiella rhinoscleromatis				X
Morganella morganii	X	X	X	X	X	X
Pasteurella multocida	X
Proteus mirabilis	X	X	X	X	X	X
Proteus vulgaris	X	X	X	X	X	X

ORGANISMS INTENDED FOR TESTING

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use_ (Per 21 CFR 801.109) Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

OR (Optional Format 1-2-96)

Oflox Norflox Levo Lomeflox Sparflox Cipro 510k rev1a.doc.

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INDICATIONS FOR USE STATEMENT

Page _ 3_of_ 3_

510(k) Number (if known): K_ MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels with Ofloxacin, (0.12 - 16 Device Name: ug/ml), Norfloxacin (0.12 - 32 µg/ml), Levofloxacin (0.5 - 16 µg/ml), Lomefloxacin

(1.0 - 16 µg/ml), Sparfloxacin (0.5 - 8 µg/ml), Ciprofloxacin (0.25 - 8 µg/ml)

Indications For Use:

Organism	Cp	Lvx	Lmf	Nxn	Ofl
Providencia alcalifaciens			X	X
Providencia rettgeri	X	X	X	X	X
Providencia stuartii	X	X	X	X	X
Pseudomonas aeruginosa	X	X	X	X	X
Pseudomonas fluorescens		X
Serratia liquefaciens			X
Serratia marcescens	X	X	X	X	X
Shigella boydii	X
Shigella dysenteriae	X
Shigella flexneri	X
Shigella sonnei	X
Shigella spp				X
Salmonella enteriditis	X
Salmonella spp				X
Salmonella typhi	X
Yersinia enterocolitica	X			X
Vibrio cholerae	X			X
Vibrio parahaemolyticus	X	X		X	X
Vibrio vulnificus	X

ORGANISMS INTENDED FOR TESING (cont.)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use_X (Per 21 CFR 801.109) Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

OR (Optional Format 1-2-96)

Oflox Norflox Levo Lomeflox Sparflox Cipro 510k rev1a.doc.

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.”