MICROSCAN MICROSTREP PLUS PANEL-CLARITHROMYCIN by DADE BEHRING, INC.

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℃ +/- 1℃ 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 Clarithromycin, at concentrations of 0.06 - 2 mcg/ml on the MicroScan MICroSTREP plus® Panel.

The organisms which may be used for Clarithromycin susceptibility testing on this panel are:

Streptococcus pneumoniae
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 ℃ 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 regarding the acceptance criteria and the study that proves the device meets those criteria:

Device: MicroScan MICroSTREP plus® Panel with Clarithromycin (0.06 – 2 mcg/ml)
Intended Use: To determine bacterial antimicrobial agent susceptibility, specifically for Clarithromycin against aerobic streptococci, including Streptococcus pneumoniae. This submission focuses on adding instrument-read capability using the MicroScan® WalkAway instrument.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred from "acceptable performance")	Reported Device Performance (Clarithromycin, instrument read vs. Expected Result)
Overall Essential Agreement (EA)	98.6%
Reproducibility and Precision	Acceptable
Quality Control (QC)	Acceptable

Note: The document explicitly states "acceptable performance with an overall Essential Agreement of 98.6%". The "acceptable" for reproducibility, precision, and QC implies these were also acceptance criteria, though no numerical thresholds are given in the provided text.

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

Sample Size (Test Set): Not explicitly stated. The document mentions "external evaluation was conducted with stock and CDC Challenge strains," but the specific number of strains or isolates tested is not provided.
Data Provenance: The study was an "external evaluation." While the specific country is not mentioned, the manufacturer (Dade Behring Inc.) is based in the USA, and the FDA submission is to the US regulatory body, suggesting the evaluation would align with US standards and likely involve US-based laboratories or strains. The data appears to be prospective in nature, as it was designed to "confirm the acceptability of the proposed instrument read method" by comparing it to "Expected Results determined before the evaluation."

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

This information is not provided in the given text. The "Expected Result" is mentioned as the comparator, and it was "generated on a CLSI frozen Reference Panel," but the human involvement in establishing these "Expected Results" or "ground truth" is not detailed.

4. Adjudication Method for the Test Set

This information is not provided in the given text. While an "Expected Result" was used, the method by which this ground truth was confirmed or adjudicated (e.g., beyond the CLSI reference panel itself) is not described.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is focused on the performance of the instrument-read method for antimicrobial susceptibility testing, comparing it to an "expected result" from a reference method, not on human reader performance with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance study was done. The entire premise of the submission is to demonstrate the performance of the MicroScan® WalkAway instrument (an automated system, essentially an algorithm/device only) in reading the MICroSTREP plus® Panel with Clarithromycin. It compares the "instrument read results" to a predefined "Expected Result," implying an algorithm-only evaluation. The primary comparison is the instrument reading versus the CLSI frozen Reference Panel, which serves as the independent standard. The original method was "manually read by observing the lowest antimicrobial concentration showing inhibition of growth," but the study explicitly focuses on the "addition of instrument read capability."

7. The Type of Ground Truth Used

The ground truth used was based on an "Expected Result generated on a CLSI frozen Reference Panel." This indicates a well-established, standardized reference method, likely involving expert consensus and adherence to Clinical and Laboratory Standards Institute (CLSI) guidelines, which are recognized standards for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not provide information regarding a distinct "training set." The study described is an "external evaluation" conducted to confirm acceptability, implying a validation or test set. For an AST system, the "training" analogous to machine learning often happens during the initial development and optimization of the instrument's reading algorithms, using various characterized strains and concentration ranges. This information is typically proprietary and not part of the 510(k) summary for a post-development validation.

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

As no specific training set is mentioned in the context of this 510(k) summary, the method for establishing its ground truth is not described. If "training" implicitly refers to the initial development of the instrument's reading capabilities, it would have involved a similar process as the ground truth for the test set, likely using CLSI reference methods and expert interpretation to teach the instrument to accurately "read" MIC values.

Summary

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K063299

NOV 2 7 200E

510(k) Summary Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	May Morishima, Regulatory Affairs Administrator
Phone/Fax:	916-374-2006/916-374-3144
Date prepared:	October 11, 2006
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan MICroSTREP plus® Panel
Intended Use:	To determine bacterial susceptibility to Clarithromycin
Indication for Use:	For determining antimicrobic susceptibility with aerobic streptococciincluding Streptococcus pneumoniae.
Predicate device:	MicroScan® MICroSTREP plus® Panel

510(k) Summary:

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 ℃ in a non-CO2 incubator, and read according to the Package Insert.

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 Clarithromycin 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 the MICroSTREP plus® Panel by comparing its performance with Expected Results determined before the evaluation.

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The MICroSTREP plus® Panel demonstrated acceptable performance with an overall Essential Agrecment of 98.6% for Clarithromycin instrument read results compared with the Expected Result.

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

Quality Control testing demonstrated acceptable results for Clarithromycin.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with its wings spread, and three horizontal lines below the eagle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circle around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 27 2006

Ms. May Morishima Dade Behring Inc. Microscan 2040 Enterprise Blvd West Sacramento, CA 95691

Re: K063299

Trade/Device Name: MicroScan MICroSTREP plus® Panel Clarithromycin (0.06 – 2 mcg/ml) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: LRG, LTT Dated: October 11, 2006 Received: November 1, 2006

Dear Ms. Morishima:

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 FFA may publish further announcements concerning your device in the Federal Degister.

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. Your 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 10gally marketed predicate device results in a classification for your device and thus, perror to 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 tollified non ber (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely vours.

Sally, artm

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

510(k) No.:

K063299 (To be assigned by FDA)

MicroScan MICroSTREP plus® Panel Clarithromycin (0.06 -- 2 mcg/ml)

Intended Use

Device Name:

To determine bacterial antimicrobial agent susceptibility

Indications for Use:

This particular submission is for the addition of instrument read capability of the antimicrobial Clarithromycin, at concentrations of 0.06 - 2 mcg/ml on the MicroScan MICroSTREP plus® Panel.

The organisms which may be used for Clarithromycin susceptibility testing on this panel are:

Streptococcus pneumoniae Streptococcus pyogenes Streptococcus agalactiae Streptococci (Groups C, F, G) viridans group streptococci

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)

Freddi tu. Poole

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety Page 1 of 1

KD6329fi

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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).