The MicroScan® Dried 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 bacteria. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.

This particular submission is for the addition of the antimicrobial Tigecycline at concentrations of 0.12 - 8 mcg/ml to the test panel. MicroScan® Dried Gram-Positive Tigecycline is a qualitative test.

Tigecycline has been shown to be active against the organisms listed below according to the FDA label for the antimicrobial.

Active in vitro and in clinical infections:

Enterococcus faecalis (vancomycin-susceptible isolates) Staphylococcus aureus (methicillin-susceptible and -resistant isolates)

Active in vitro but clinical significance unknown: Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates)

Device Description

MicroScan Dried Gram-Positive 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-positive bacteria.

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 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

The MicroScan® Dried Gram-Positive MIC/Combo Panels with Tigecycline (0.12-8 mcg/ml) is a medical device designed to determine antimicrobial agent susceptibility. The device's performance was evaluated against a CLSI frozen Reference Panel to demonstrate substantial equivalence, as defined in the FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA."

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (from FDA Guidance Document)	Reported Device Performance (for Tigecycline)
Overall Categorical Agreement	Not explicitly stated in the provided text, but generally expected to be very high for AST systems. Commonly >90% or >95% for substantial equivalence.	99.4% (when compared with the frozen Reference panel)
Inoculum Reproducibility	Acceptable reproducibility and precision	Acceptable reproducibility and precision
Instrument Reproducibility	Acceptable reproducibility and precision	Acceptable reproducibility and precision
Quality Control Testing	Acceptable results	Acceptable results

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

Test Set Sample Size: The document mentions "fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates/strains used in the external evaluation (test set) is not explicitly stated in the provided text.
Data Provenance: The data was collected during an "external evaluation" designed to confirm acceptability. The specific country of origin is not mentioned, but it can be inferred that it aligns with FDA submission requirements, likely involving clinical or reference laboratories within the United States or equivalent international standards. The study appears to be retrospective in the sense that stock isolates and challenge strains were used, although fresh isolates were also included.

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

The document states the device's performance was compared to a "CLSI frozen Reference panel" and "Expected Results determined prior to the evaluation" for challenge strains. This implies that the ground truth for antimicrobial susceptibility was established through a standardized, well-defined method (likely CLSI M7 guidelines for broth microdilution) rather than relying on individual expert consensus.

Number of Experts: Not applicable in the traditional sense of a consensus panel, as a CLSI frozen Reference Panel and pre-determined "Expected Results" were used as the gold standard.
Qualifications of Experts: The CLSI (Clinical and Laboratory Standards Institute) methods themselves are developed by panels of experts in microbiology, infectious diseases, and laboratory medicine. However, the document does not specify individual experts for establishing the ground truth for this particular study.

4. Adjudication Method for the Test Set

The establishment of ground truth was based on comparison to a "CLSI frozen Reference panel" and "Expected Results" for challenge strains. This suggests a direct comparison method rather than an adjudication process among human readers.

Adjudication method: None in the context of human reader disagreement, as the ground truth was a standardized reference method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size

MRMC Study: No, a multi-reader multi-case comparative effectiveness study was not done. This study focuses on the performance of an automated/semi-automated AST system against a reference method, not on the improvement of human readers with AI assistance.
Effect Size: Not applicable, as no MRMC study was conducted.

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

Standalone Study: Yes, the evaluation conducted was a standalone study of the device. The MicroScan Dried Gram-Positive MIC/Combo Panel, either read visually or with MicroScan instrumentation (autoSCAN®-4 and WalkAway®), operates as an algorithm/system to determine MIC values and categorical interpretations. Its performance was compared directly to a "CLSI frozen Reference panel" and "Expected Results," which represents its standalone capability without direct human interpretation being part of the primary performance metric for substantial equivalence (though human reading is an option for panel interpretation).

7. The Type of Ground Truth Used

Ground Truth Type: The ground truth used was established by a CLSI frozen Reference Panel and pre-determined expected results for challenge strains. This is a highly standardized and well-accepted method for determining antimicrobial susceptibility, considered the gold standard in microbiology. It is essentially a form of reference standard data based on established protocol outcomes.

8. The Sample Size for the Training Set

The provided text does not contain any information about a specific training set or its sample size. This type of device (Microdilution MIC Panels) is typically developed based on established microbiological principles and validated against reference methods, rather than being a machine learning model that requires a discrete training set in the modern sense. The "development" would involve optimizing panel concentrations and reading algorithms.

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

Since no specific training set is mentioned as part of a machine learning paradigm, the establishment of ground truth for a "training set" is not applicable as described in the provided text. The overall design and optimization of such panels are based on extensive antimicrobial susceptibility testing literature, CLSI guidelines, and internal research and development following established microbiological practices.

Summary

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K/3/275

510(k) Summary

NOV 08 2013

510(k) Submission Information:

Device Manufacturer:	Siemens Healthcare Diagnostics
Contact name:	Elisabeth Warriner, Regulatory Technical Specialist
Phone:	916-374-3244
Fax:	916-372-6418
Date prepared:	August 27, 2013
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® Dried Gram-Positive MIC/Combo Panels with Tigecycline (0.12-8mcg/ml)
Intended Use:	To determine antimicrobial agent susceptibility
Classification:	Class II
Product Code:	LTT
510(k) Notification:	New antimicrobial - Tigecycline
Predicate device:	MicroScan Dried Gram-Positive MIC/Combo Panels - Linezolid (K003619)

510(k) Summary:

The proposed MicroScan Dried Gram-Positive MIC/Combo Panel with Tigecvcline demonstrated substantially equivalent performance when compared with an 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 August 28, 2009. The Premarket Notification (510|k|) presents data in support of the MicroScan Dried Gram-Positive MIC/Combo Panel with Tigecycline. MicroScan Dried Gram-Positive Tigecycline is a qualitative test.

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 Dried Gram-Positive Panel by comparing its performance with a CLSI frozen Reference panel. Challenge strains were compared to Expected Results determined prior to the evaluation. The Dried Gram-Positive Panel demonstrated acceptable performance with an overall Categorical Agreement of 99.4% for Tigecycline when compared with the frozen Reference panel.

Inoculum and instrument reproducibility testing demonstrated acceptable reproducibility and precision with Tigecycline, regardless of which inoculum method (i.e., Turbidity and Prompt™). or instrument (autoSCAN®-4 and WalkAway®) was used.

Quality Control testing demonstrated acceptable results for Tigecycline.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Homoshim Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

SIEMENS HEALTHCARE DIAGNOSTICS, INC. ELISABETH WARRINER REGULATORY TECHNICAL SPECIALIST 1584 ENTERPRISE BLVD. WEST SACRAMENTO CA 95691

November 8. 2013

Re: K131275

Trade/Device Name: MicroScan Dried Gram-Positive MIC/Combo Panels with Tigecycline (0.12 - 8mcg/ml) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: LTT, JWY, LRG, LTW Dated: September 27, 2013 Received: September 30, 2013

Dear Ms. Warriner:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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.

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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.

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Page 2-Ms. Warriner

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometries/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Uwe Scherf -Sior

Sally Hojvat, M.Sc., PhD. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):__K131275

Device Name: _ MicroScan® Dried Gram-Positive MIC/Combo Panels with Tigecycline (0.12 - 8 mcg/ml)

Indications For Use:

Tigecycline has been shown to be active against the organisms listed below according to the FDA label for the antimicrobial.

Active in vitro and in clinical infections:

Enterococcus faecalis (vancomycin-susceptible isolates) Staphylococcus aureus (methicillin-susceptible and -resistant isolates)

Active in vitro but clinical significance unknown: Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates)

Prescription Use V (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 Diagnostics and Radiological Health (OIR)

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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).