MICROSCAN MICROSTREP PLUS PANEL CEFUROXIME (0.12-8 MCG/ML) by DADE BEHRING, INC.

To determine bacterial antimicrobial agent susceptibility. 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 Cefuroxime, at concentrations of 0.12 to 8 mcg/ml on the MicroScan MICroSTREP plus® Panel. The organisms which may be used for Cefuroxime susceptibility testing in this panel are: Streptococcus pneumoniae.

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℃ +/-1ºC 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 ul 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 information regarding the MicroScan MICroSTREP plus® Panel's acceptance criteria and the study proving its performance:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Overall Essential Agreement for Cefuroxime instrument read results compared with Expected Result	98.1%
Reproducibility and Precision for Vancomycin and WalkAway instrument	Demonstrated acceptable reproducibility and precision
Quality Control Testing for Cefuroxime	Demonstrated acceptable results

Study Details

Sample Size used for the test set and data provenance:
- The document mentions "external evaluations" conducted with "stock and CDC Challenge strains." However, the exact sample size for the test set (number of unique isolates) is not explicitly stated.
- The data provenance is from in vitro testing using laboratory strains ("stock and CDC Challenge strains"), implying a controlled, laboratory-based study. The country of origin is not specified but given the FDA submission, it's likely primarily US-based or compliant with US standards. The study appears to be prospective for the device's performance evaluation against the established "Expected Result."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document implies that the ground truth, referred to as the "Expected Result," was generated on a CLSI frozen Reference Panel. This suggests the ground truth was established by a standardized, validated method (CLSI reference method), rather than by individual human experts per se. It doesn't specify the number or qualifications of experts involved in the initial CLSI reference panel validation or the generation of the "Expected Result" for this specific study.
Adjudication method for the test set:
- The document states that the "external evaluations were designed to confirm the acceptability of the proposed instrument read method... by comparing its performance with Expected Results determined before the evaluation." This indicates a direct comparison to a pre-defined reference standard. There is no mention of an adjudication method as typically understood for human reader discrepancies (e.g., 2+1 or 3+1). The "Expected Result" serves as the single, authoritative ground truth.
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:
- No, an MRMC comparative effectiveness study was not done. This study focuses on the standalone performance of an instrument-read method for antimicrobial susceptibility testing, comparing it to a reference method. It does not involve human readers or AI assistance in the context of an MRMC study.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, a standalone study was done. The study evaluates the "proposed instrument read method" (MicroScan® WalkAway instrument) for the MICroSTREP plus® Panel. This is a standalone evaluation of the device without human intervention in the reading process, comparing it to an "expected result."
The type of ground truth used:
- The ground truth used was based on an "expected result generated on a CLSI frozen Reference Panel." This is a highly standardized, reference method ground truth (broth dilution method as miniaturized for the panels) which is widely accepted in microbiology for antimicrobial susceptibility testing.
The sample size for the training set:
- The document pertains to the evaluation of an instrument-read method for an existing panel. There is no mention of a separate "training set" for an algorithm in the traditional machine learning sense. The "MicroScan MICroSTREP plus® Panel" itself is a product; the evaluation is about adding "instrument read capability" for a specific antimicrobial (Cefuroxime). If the WalkAway instrument's reading mechanism involved an algorithm that required training, those details are not provided in this 510(k) summary. The study is an evaluation of the instrument's performance, not the development of a new algorithm.
How the ground truth for the training set was established:
- Since there's no explicit training set mentioned in the context of algorithm development, the method for establishing its ground truth is not applicable or detailed here. The "Expected Results" for the test set were established using the CLSI frozen Reference Panel.

Summary

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K063053

OCT 26 2006

510(k) Summary Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	Shannon Popson, Regulatory Affairs Manager
Phone/Fax:	916-374-3330/916-374-3144
Date prepared:	September 20, 2006
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan MICroSTREP plus® Panel
Intended Use:	To determine bacterial susceptibility to Cefuroxime
Indication for Use:	For determining antimicrobic susceptibility with aerobic streptococciincluding Streptococcus pneumoniae
Predicate device:	MicroScan MICroSTREP plus® Panel (K020820)

510(k) Summary:

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 ul 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.

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 Cefuroxime 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 98.1% for Cefuroxime instrument read results compared with the Expected Result.

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

Quality Control testing demonstrated acceptable results for Cefuroxime.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS) in the United States. The logo features the department's name in a circular arrangement around a stylized emblem. The emblem consists of an abstract representation of an eagle or bird-like figure, with three curved lines forming its body and wings.

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

Re: K063053

Trade/Device Name: MicroScan MICroSTREP plus® Panel Cefuroxime (0.12 - 8 mcg/ml) Regulation Number: 21 CFR § 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: LRG, LTT Dated: September 20, 2006 Received: October 4, 2006

Dear Ms. Poposon:

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.

OCT 26 2006

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, anton

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

163053

MicroScan MICroSTREP plus® Panel

Cefuroxime (0.12 - 8 mcg/ml)

(To be assigned by FDA

510(k) No.:

Device Name:

Intended Use

To determine bacterial antimicrobial agent susceptibility

Indications for Use:

This particular submission is for the addition of instrument read capability of the antimicrobial Cefuroxime, at concentrations of 0.12 to 8 mcg/ml on the MicroScan MICroSTREP plus® Panel.

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

Streptococcus pneumoniae

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)

Lunddite Pauly

Division Sign-Off

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

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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).