MICROSCAN MICROSTREP PLUS PANEL AZITHROMYCIN by DADE BEHRING, INC.

Intended Use: To determine bacterial antimicrobial agent susceptibility
Indications for Use: The MicroScan MICroSTREP plus® Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. Additionally, the panels may be incubated in and read by a MicroScan® WalkAway instrument.

This particular submission is for the addition of instrument read capability of the antimicrobial Azithromycin, at concentrations of 0.12 to 4 mcg/m1 on the MicroScan MICroSTREP plus® Panel.

The organisms which may be used for Azithromycin susceptibility testing in this panel are:

Streptococcus pneumoniae (including penicillin-resistant strains) Streptococcus pyogenes Streptococcus agalactiae Streptococci (Groups C, F, G) viridans group streptococci

Device Description

The MicroScan MICroSTREP plus® Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/-1 °C in a non-CO2 incubator, and read according to the Package Insert.

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test. Various antimicrobial agents are diluted in water, buffer or minute concentrations of broth to concentrations bridging the range of clinical interest. Panels are rehydrated with 115 µl Mueller-Hinton broth supplemented with 2-5% lysed horse blood (LHB) and buffered with 50 mM HEPES, after inoculation of the broth with a standardized suspension of the organism in saline. After incubation in a non-CO2 incubator for 20-24 hours, the minimum inhibitory concentration (MIC) for the test organism is manually read by observing the lowest antimicrobial concentration showing inhibition of growth. Additionally, the panels may be incubated in and read by a MicroScan® WalkAway instrument.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the MicroScan MICroSTREP plus® Panel with Azithromycin:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Essential Agreement)	Reported Device Performance
Overall Essential Agreement of ≥ 95%	95.7% (for Azithromycin instrument read results compared with the Expected Result)

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

Sample Size: The document mentions "stock and CDC Challenge strains" were used for the external evaluation, but it does not specify the exact number of strains or isolates used in the test set.
Data Provenance: The study involved an "external evaluation," which suggests the data was collected outside of the manufacturer's internal lab. The use of "stock and CDC Challenge strains" implies a mix of strains with known characteristics, likely derived from various sources. The document does not explicitly state the country of origin, but "CDC Challenge strains" suggests a U.S.-centric source for at least some of the strains. The study appears to be prospective in nature, as it was designed to confirm the acceptability of the proposed instrument read method.

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

The document states that the performance was compared with an "expected result generated on a CLSI 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 implies that the ground truth was established by adherence to a recognized standard (CLSI reference method) rather than by individual experts.

Number of Experts: Not applicable in the context of this ground truth method.
Qualifications of Experts: Not applicable. The ground truth relies on a standardized reference method.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method in the traditional sense of multiple human readers or experts resolving discrepancies. Instead, it refers to comparing the instrument read results against "Expected Results determined before the evaluation" which were generated using a CLSI frozen Reference Panel. This suggests a direct comparison to a standardized, pre-established reference.

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

No, a MRMC comparative effectiveness study was not done. The study's focus was on the performance of the instrument read method compared to a reference standard, not on comparing human readers with and without AI assistance. The device is an automated instrument reader, effectively a "standalone" algorithm for reading MIC results.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was done. The entire evaluation described is focused on the "proposed instrument read method" (i.e., the MicroScan® WalkAway instrument's automated reading capability) for the MICroSTREP plus® Panel. This is a standalone performance assessment of the instrument's ability to read MIC results.

7. Type of Ground Truth Used

Reference Standard / Expert Consensus (Indirectly): The ground truth was established by an "expected result generated on a CLSI 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'." This represents a widely accepted and standardized method for determining antimicrobial susceptibility, which is itself based on extensive expert consensus and validation within the microbiology community.

8. Sample Size for the Training Set

The document does not provide information on the sample size for a training set. This is a commercial device for determining antimicrobial susceptibility, and the "instrument read method" typically relies on an existing, validated algorithm. While the algorithm would have been trained at some point, the 510(k) summary focuses on the validation of the instrument's read capability for Azithromycin specifically, rather than the initial development and training of the core reading algorithm. Therefore, details about algorithm training data are not presented for this specific submission.

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

Not specified in this document. As mentioned above, the document does not detail the training set or the method for establishing its ground truth. For AST systems, the ground truth for training would typically involve either manual readings by trained microbiologists following CLSI guidelines, or comparisons to established reference methods (like macrobroth dilution).

Summary

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510(k) Summary Information:

SEP 1 9 2006

Device Manufacturer:	Dade Behring Inc.
Contact name:	Shannon Popson, Regulatory Affairs Manager
Phone/Fax:	916-374-3330/916-374-3144
Date prepared:	August 18, 2006
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan MICroSTREP plus® Panel
Intended Use:	To determine bacterial susceptibility to Azithromycin
Indication for Use:	For determining antimicrobic susceptibility with aerobic streptococci including Streptococcus pneumoniae
Predicate device:	MicroScan MICroSTREP plus® Panel (K021169)

510(k) Summary:

The proposed instrument read method for the MicroScan MICroSTREP plus® Panel demonstrated substantially equivalent performance with streptococcal isolates when compared with an expected result generated on a CLSI 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 Premarket Notification (510[k]) presents data in support of reading the MICroSTREP plus Panel with Azithromycin on the MicroScan® WalkAway instrument.

The external evaluation was conducted with stock and CDC Challenge strains. The external evaluations were designed to confirm the acceptability of the proposed instrument read method for

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the MICroSTREP plus® Panel by comparing its performance with Expected Results determined before the evaluation. The MICroSTREP plus® Panel demonstrated acceptable performance with an overall Essential Agreement of 95.7% for Azithromycin instrument read results compared with the Expected Result.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Azithromycin and the WalkAway® instrument.

Quality Control testing demonstrated acceptable results for Azithromycin.

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Image /page/2/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in a bold, sans-serif font. The text is black and the background is white. The text is centered in the image.

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Shannon Popson Regulatory Affairs Manager Dade Behring, Inc. 1584 Enterprise Boulevard West Sacramento, CA 95691-9972

SEP 1 9 2006

K062585 Re:

Trade/Device Name: MicroScan MICroSTREP plus® Panel Azithromycin (0.12-4 mcg/ml) Regulation Number: 21 CFR § 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: LRG, LTT Dated: August 18, 2006 Received: September 1, 2006

Dear Ms. Popson:

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 application (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 such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, atton

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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Indication for Use Statement

162585

To be assigned by FDA)

510(k) No .:

Device Name:

MicroScan MICroSTREP plus® Panel Azithromycin (0.12 - 4 mcg/ml)

Intended Use

To determine bacterial antimicrobial agent susceptibility

Indications for Use:

The MicroScan MICroSTREP plus® Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. Additionally, the panels may be incubated in and read by a MicroScan® WalkAway instrument.

This particular submission is for the addition of instrument read capability of the antimicrobial Azithromycin, at concentrations of 0.12 to 4 mcg/m1 on the MicroScan MICroSTREP plus® Panel.

The organisms which may be used for Azithromycin susceptibility testing in this panel are:

Streptococcus pneumoniae (including penicillin-resistant strains) Streptococcus pyogenes Streptococcus agalactiae Streptococci (Groups C, F, G) viridans group streptococci

Prescription Use X (Part 21 CFR 801 Subpart D)

Over-The-Counter Use AND/OR (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)

Freddie Poole
Division Sign-Off

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Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).