MICROSCAN SYNERGIES PLUS GRAM POSITIVE MIC/COMBO PANELS WITH TETRACYCLINE by DADE BEHRING, INC.

The MicroScan® Synergies plus™ Gram-Positive 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-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 – 18 hours at 35℃ +/- 1℃, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO2 incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.

This particular submission is for the addition of the antimicrobial tetracycline, at concentrations of 0.25 to 16 µg/ml (7-Dilution MIC Sequence), 0.5 – 8 µg/ml (5-Dilution BP Sequence), and 2 - 8 ug/ml (3-Dilution BP Dilution Sequence), for all Staphylococcus species and Enterococcus species to the test panel.

The Gram-positive organisms which may be used for tetracycline susceptibility testing in this panel are: Staphylococcus aureus, Streptococcus faecalis (Enterococcus faecalis)

Device Description

MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels, utilizing both the MicroScan® Rapid Fluorogenic Identification and Dried Overnight Antimicrobial Susceptibility Testing (AST) technologies, 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-positive enterococci and staphylococci.

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in water and dehydrated. 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 Synergies plus™ Pos Broth, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SI, or equivalent, for 4.5 - 18 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with Tetracycline, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Overall Essential Agreement (compared to a frozen Reference Panel and Expected Results)	94.8% (for the 7-Dilution Sequence)
Instrument reproducibility testing (for Tetracycline with Turbidity inoculum preparation method and WalkAway® SI System)	Demonstrated acceptable reproducibility and precision.
Quality Control testing	Demonstrated acceptable results.

Study Details

Sample size used for the test set and the data provenance:
- Test Set Sample Size: Not explicitly stated as a number, but the study used "fresh and stock Efficacy isolates" and "stock Challenge strains."
- Data Provenance: Not specified (e.g., country of origin). The study was an "external validation."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified. The reference standard was a "frozen Reference Panel" and "Expected Results," which implies a gold standard established by expert consensus or predefined criteria, but the specific individuals are not detailed.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Adjudication Method: Not specified. The comparison was directly between the MicroScan® panel's results and the "frozen Reference panel" and "Expected Results."
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, this was not an MRMC study. This device is an automated antimicrobial susceptibility testing (AST) system, not an AI-assisted diagnostic imaging tool with human interpretation.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Standalone Performance: Yes, the device's performance was evaluated independently against the reference standard. While the system can be read visually for AST, the primary evaluation detailed here is for the automated system ("read by the MicroScan® Instrumentation"). The "read by determining the lowest antimicrobial concentration showing inhibition of growth" implies an automated or semi-automated reading process for the MIC.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Ground Truth Type: "Frozen Reference Panel" and "Expected Results." This suggests a highly standardized and validated reference method for antimicrobial susceptibility testing, commonly considered a gold standard in microbiology, likely established by expert consensus guidelines and previous validation studies of the reference method itself.
The sample size for the training set:
- Training Set Sample Size: Not applicable. This device is a diagnostic test kit based on established biochemical principles and does not involve machine learning or a "training set" in the conventional AI sense.
How the ground truth for the training set was established:
- Ground Truth for Training Set: Not applicable, as there is no training set for this type of device.

Summary

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K071268

510(k) Summarv

510(k) Submission Information: JUN 2 6 2007 Device Manufacturer: Dade Behring Inc. Contact name: Robert Eusebio, Regulatory Affairs Manager Fax: 916-374-3144 Date prepared: May 4, 2007 Product Name: Microdilution Minimum Inhibitory Concentration (MIC) Panels Trade Name: MicroScan® Synergies plus" Gram-Positive MIC/Combo Panels Intended Use: To determine antimicrobial agent susceptibility 510(k) Notification: New antimicrobial agent - Tetracycline Predicate device: MicroScan" Synergies plus " Gram-Negative MIC/Combo Panels and MicroScan® Dried Gram-Positive Panels

510(k) Summary:

The proposed MicroScan® Synergies plus'" Gram-Positive MIC/Combo Panel demonstrated substantially equivalent performance when compared with a 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. The Premarket Notification (510[k]) presents data in support of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with tetracycline.

The external validation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. The external validations were designed to confirm the acceptability of the proposed Synergies plus" Gram-Positive Panel by comparing its performance with a frozen Reference punel. Challenge strains were compared to Expected Results determined prior to the evaluation. The Synergies plus" Gram-Positive Panel demonstrated acceptable performance with an overall Essential Agreement of 94.8%, for the 7-Dilution Sequence when compared with the frozen Reference panel and Expected Results. Te 510k.doc 5/4/2007

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Instrument reproducibility testing demonstrated acceptable reproducibility and precision for Tetracycline with Turbidity inoculum preparation method and the WalkAway® SI System or equivalent.

Quality Control testing demonstrated acceptable results for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with tetracycline.

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

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 6 2007

Mr. Robert Eusebio Regulatory Affairs Manager Dade Behring, Inc. 1584 Enterprise Boulevard West Sacramento, California 95691-9972

Re: K071268

Trade/Device Name: MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panels Tetracycline Regulation Number: 21 CFR 866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system Regulatory Class: Class II Product Code: LON, LRG, JWY, LTT Dated: May 4, 2007 Received: May 7, 2007

Dear Mr. Eusebio:

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) rms letter will and w yours ough finding of substantial equivalence of your device to a legally premative nedicate 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, rr you destre specific introlion and advertising of your device, please contact the Office of In of quotions on one price 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 Oinci general intormation of you. 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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Indications for Use

510(k) Number (if known): K0712 68

Device Name: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with tetracycline (0.25 - 16 ug/ml 7-Dilution MIC Sequence, 0.5 - 8 ug/ml 5-Dilution MIC Sequence and 2 - 8 ug/ml 3-Dilution Breakpoint Sequence)

Indications For Use:

The Gram-positive organisms which may be used for tetracycline susceptibility testing in this panel

AND/OR

are:

Staphylococcus aureus

Streptococcus faecalis (Enterococcus faecalis)
Prescription Use X (Part 21 CFR 801 Subpart D) 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)

Seath

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Te 510k.doc 5/4/2007

7126d

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.”