The MicroScan Dried Gram-Negative 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-negative bacilli. 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 reformulated antimicrobial imipenem at concentrations of 0.25 to 8 ug/ml to the test panel.

The gram-negative organisms which may be used for imipenem susceptibility testing in this panel are:

Acinetobacter spp. Citrobacter spp. Escherichia coli, Klebsiella spp. Morganella morganii, Proteus vulgaris, Providencia rettgeri, and Pseudomonas aeruginosa

Device Description

MicroScan Dried Gram-Negative 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-neqative bacilli.

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

This document is a 510(k) premarket notification for a medical device: the MicroScan Dried Gram-Negative MIC/Combo Panels with Imipenem. This type of document is filed with the FDA to demonstrate that a device is substantially equivalent to a legally marketed predicate device, rather than requiring full PMA approval. Therefore, the "study" described herein is a validation study comparing the new device to a reference method, rather than a clinical trial assessing a new drug or treatment.

Here's an analysis of the provided text to extract the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (from "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated August 28, 2009)	Reported Device Performance (MicroScan Dried Gram-Negative MIC/Combo Panel with Imipenem)
Overall Essential Agreement (compared to CLSI frozen Reference Panel)	Not explicitly stated in the provided text as a numerical acceptance criterion, but the context implies "acceptable performance" as defined by the guidance document.	95.5%
Inoculum and Instrument Reproducibility	Not explicitly stated as a numerical acceptance criterion in the provided text, but the context implies "acceptable reproducibility and precision."	Demonstrated acceptable reproducibility and precision.
Quality Control (QC) Testing	Not explicitly stated as a numerical acceptance criterion in the provided text, but the context implies "acceptable results."	Demonstrated acceptable results.

Explanation of "Essential Agreement": In antimicrobial susceptibility testing, Essential Agreement (EA) typically means that the MIC (Minimum Inhibitory Concentration) results from the test device are within +/- one doubling dilution of the reference method's MIC.

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

Test Set Sample Size: The document does not explicitly state the total number of isolates (samples) used in the "external evaluations." It mentions "fresh and stock Efficacy isolates and stock Challenge strains."
Data Provenance: Not explicitly stated (e.g., country of origin). The study involved "external evaluations," which could imply multi-center or independent lab testing, but no specific locations are mentioned. The data is retrospective, as it uses "stock" isolates and challenge strains.

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

This information is not provided in the document. The ground truth for susceptibility testing is established by the CLSI (Clinical and Laboratory Standards Institute) frozen Reference Panel, which represents a standardized and accepted method, not typically by human expert consensus in the same way a diagnostic imaging study would be.

4. Adjudication Method for the Test Set

This is not applicable in the context of antimicrobial susceptibility testing where the "ground truth" is determined by a reference laboratory method (CLSI frozen Reference Panel), rather than human interpretation requiring adjudication.

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

No, an MRMC study was not done. This type of study is relevant for diagnostic imaging interpretation where human readers interpret images. For an AST device, the comparison is against a reference laboratory method.
Effect Size of Human Readers Improvement: Not applicable as no MRMC study was conducted. However, the document does imply human involvement in reading results (visually or with MicroScan instrumentation) after incubation. The study validated the device's performance in generating the MIC, not the human interpretation of that MIC.

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

Yes, effectively. While the device can be read visually, the core validation is of the device's ability to produce an accurate MIC result when compared to the CLSI reference method. The "MicroScan instrumentation" option for reading implies algorithmic interpretation. The study evaluates the panel's performance as a standalone system for determining antimicrobial susceptibility, regardless of the reading method. The reproducibility testing confirms the device's consistent performance.

7. The Type of Ground Truth Used

The ground truth used was the CLSI frozen Reference Panel. This is a recognized standard method for antimicrobial susceptibility testing, providing a highly reliable and standardized reference for MIC values. It's akin to a "gold standard" laboratory method.

8. The Sample Size for the Training Set

This information is not provided in the document. For a 510(k) for an AST device, the "training set" doesn't typically refer to a machine learning training dataset. Instead, it would refer to the development and internal validation data used during the device's creation. The provided document focuses on the final validation study for regulatory submission.

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

This information is not provided in the document. As noted above, the concept of a "training set" with ground truth in the machine learning sense is likely not applicable here in the way it would be for an AI/ML-based diagnostic device. The development of an AST panel involves optimizing the concentrations and formulation to ensure accurate results, which would rely on established microbiological methods and internal testing, analogous to how the final validation ground truth (CLSI reference) is established.

Summary

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

March 21, 2017

BECKMAN COULTER, INC. SHANNON POPSON STAFF REGULATORY AFFAIRS 1584 ENTERPRISE BLVD WEST SACRAMENTO CA 95691

Re: K162740

Trade/Device Name: MicroScan Dried Gram-Negative MIC/Combo Panels With Imipenem (0.25 - 8 ug/ml) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: LTT, JWY, LRG, LTW Dated: March 13, 2017 Received: March 15, 2017

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. 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 (OS) 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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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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" (21 CFR 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/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education 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,

Ribhi Shawar -A

For Uwe Scherf, M.Sc., Ph.D. 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) K162740

Device Name

MicroScan Dried Gram-Negative MIC/Combo Panels with Imipenem (0.25 - 8 µg/ml)

Indications for Use (Describe)

This particular submission is for the addition of the reformulated antimicrobial imipenem at concentrations of 0.25 to 8 ug/ml to the test panel.

The gram-negative organisms which may be used for imipenem susceptibility testing in this panel are:

Acinetobacter spp. Citrobacter spp. Escherichia coli, Klebsiella spp. Morganella morganii, Proteus vulgaris, Providencia rettgeri, and Pseudomonas aeruginosa

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	☒
Over-The-Counter Use (21 CFR 801 Subpart C)	☐

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510(k) Summary

510(k) Submission Information:

Device Manufacturer:	Beckman Coulter
Contact name:	Shannon Popson, Staff Regulatory Affairs
Phone:	916-374-3330
Fax:	916-374-2119
Date prepared:	September 25, 2016
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan Dried Gram-Negative MIC/Combo Panels with Imipenem (0.25 – 8 µg/mL)
Intended Use:	To determine antimicrobial agent susceptibility
Classification:	Class II
Product Code:	LTT
510(k) Notification:	Reformulated antimicrobial - Imipenem
Predicate device:	MicroScan Dried Gram-Negative MIC/Combo Panels - Tigecycline (K083262)

510(k) Summary:

The proposed MicroScan Dried Gram-Negative MIC/Combo Panel 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-Negative MIC/Combo Panel with imipenem.

The external evaluations were 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-Negative Panel by comparing its performance with a CLSI frozen Reference panel. The Dried Gram-Negative Panel demonstrated acceptable performance with an overall Essential Agreement of 95.5% for imipenem when compared with the frozen Reference panel.

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

Quality Control testing demonstrated acceptable results for imipenem.

Beckman Coulter, the stylized logo, MicroScan, and WalkAway are trademarks of Beckman Coulter and the stylized logo are registered with the USPTO.

Prompt™ is a trademark of 3M Company, St. Paul, MN USA

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).