DRIED GRAM-NEGATIVE AND GRAM-POSITIVE MIC/COMBO PANELS

• K Number: K983922
• Device Name: DRIED GRAM-NEGATIVE AND GRAM-POSITIVE MIC/COMBO PANELS
• Manufacturer: DADE MICROSCAN, INC.
• Date Cleared: 1999-06-17 ( 225 days)
• Product Code: JWY
• Regulation Number: 866.1640
• Type: Traditional
• Panel: Microbiology
• Reference & Predicate Devices: N/A
• Predicate For: N/A

Intended Use

To determine gram-negative and gram-positive bacterial susceptibility against the antimicrobial agent Cefdinir.

Organisms with indications for testing* include:
Gram-Negative Bacteria: None**
Gram-Positive Bacteria: Staphylococcus aureus *** (Including methicillin-susceptible, β-lactamase producing strains), Streptococcus pyogenes

*As taken from the indications and Usage section of the manufacturer's package insert (Issued: March 1998).
**No gram-negative organisms for which Microscan is seeking clearance are indicated for testing in the Indications and Usage section of the manufacturer's package insert.
***Cefdinir is inactive against methicillin-resistant Staphylococcus

The following secondary organisms included for the testing of MicroScan® panels with Cefdinir have in vitro data but the safety and effectiveness in treating clinical infections have not been established: Citrobacter (diversus) koseri, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus epidermidis (methicillin-susceptible), Streptococcus agalactiae

Device Description

Microdilution Minimum Inhibitory Concentration (MIC) Panels, specifically MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Cefdinir.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Cefdinir:

The document describes the regulatory submission (510(k)) for a new antimicrobial agent, Cefdinir, to be used with MicroScan MIC (Minimum Inhibitory Concentration) panels. The study aims to demonstrate that the performance of these new panels is substantially equivalent to a legally marketed predicate device, the NCCLS Frozen Cefdinir Reference Panels.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria for Essential Agreement (Based on FDA DRAFT document "Review Criteria for Assessment of Antimicrobial Susceptibility Devices" dated May 31, 1991): While the exact numerical acceptance criteria are not explicitly stated within this document fragment, it is implied that an "acceptable performance" is defined by Essential Agreement. Based on similar FDA guidances for antimicrobial susceptibility testing devices, an Essential Agreement (EA) of ≥ 90% and/or ≥ 95% is typically required for new antimicrobial-device combinations. Given the reported performance, the presumed acceptance criterion for Essential Agreement would be in this range.

Metric	Acceptance Criteria (Implied)	Reported Device Performance (Gram-Negative)	Reported Device Performance (Gram-Positive)
Essential Agreement	Acceptable Performance (e.g., ≥ 90-95%)	97.9%	94.0%
Reproducibility	Acceptable Reproducibility	Acceptable	Acceptable
Precision	Acceptable Precision	Acceptable	Acceptable
Quality Control	Acceptable Performance	Acceptable	Acceptable

Notes on Essential Agreement: Essential Agreement refers to agreement between the MIC values of the test device and the reference method within a specified range (typically ±1 doubling dilution).

2. Sample Size and Data Provenance

• Test Set Sample Size: The exact number of isolates (sample size) for the external evaluations is not explicitly stated in the provided text. It mentions "fresh and stock Efficacy isolates and stock Challenge strains" were used.
• Data Provenance: The studies were described as "external evaluations," implying they were conducted at sites outside the manufacturer's primary facility. The country of origin is not specified, but given the manufacturer (Dade MicroScan Inc., located in West Sacramento, CA) and the FDA submission, it is highly likely the evaluations were conducted in the United States. The data is prospective, as it was generated specifically for this 510(k) submission to compare the new device against a reference.

3. Number of Experts and Qualifications for Ground Truth

• The document does not explicitly mention the number of experts or their specific qualifications (e.g., years of experience) used to establish the ground truth for the test set.
• The ground truth was established by the NCCLS Frozen Cefdinir Reference Panel. This implies that the 'experts' would be the individuals or laboratories meticulously performing and interpreting the reference method according to NCCLS (now CLSI) guidelines, which are established by consensus among microbiologists and clinicians.

4. Adjudication Method for the Test Set

• The document does not specify an explicit adjudication method (e.g., 2+1, 3+1). The comparison is described as a direct performance comparison (Essential Agreement) between the MicroScan device and the NCCLS reference panel. Any discrepancies would typically be resolved by retesting or further analysis in accordance with standard microbiology practices for AST performance studies, though this is not detailed.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed or described for this device. This type of study is more common in imaging diagnostics where human interpretation is a primary component of the diagnostic workflow. For automated microbiology susceptibility testing panels, the focus is on the agreement of the device's output (MIC values) with a gold standard, rather than how human readers' performance is affected by the device.

6. Standalone Performance Study

• Yes, a standalone performance study was done. The reported Essential Agreement (97.9% for gram-negative and 94.0% for gram-positive) directly reflects the algorithm-only/device-only performance of the MicroScan panels when compared to the NCCLS reference method. There is no mention of a human-in-the-loop component for interpreting the raw results beyond what is standard for any AST device (e.g., technician reading a panel, entering data, etc.). The study evaluated the device's ability to accurately determine MIC values on its own.

7. Type of Ground Truth Used

• The ground truth used was expert consensus / reference method. Specifically, the "NCCLS Frozen Cefdinir Reference Panel" served as the gold standard. NCCLS (National Committee for Clinical Laboratory Standards, now CLSI) methods are widely regarded as the gold standard for antimicrobial susceptibility testing, representing a consensus of expert microbiological and clinical knowledge.

8. Sample Size for the Training Set

• The document does not provide any information regarding a "training set" or its sample size. This is typical for a device like this, which likely uses a pre-defined algorithm and interpretive rules for MIC determination rather than a machine learning model that requires a dedicated training phase with labeled data. The development of the panel itself (e.g., concentrations of antimicrobials) would be based on extensive prior knowledge and calibration, but not in the sense of a machine learning "training set."

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

• As no training set is described or implied for a machine learning context, the method for establishing its ground truth is not applicable here. The overall "training" for such a device relies on established microbiological principles, extensive historical data on drug-bug interactions, and adherence to reference methods (like those from NCCLS/CLSI) during its development and validation.

Summary

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JUN 17 1999

Attachment G

510(k) Summary

510(k) Submission Information:

Device Manufacturer:	Dade MicroScan Inc.
Contact name:	Cynthia Van Duker, Sr. Regulatory Affairs Specialist
Fax:	916-374-3144
Date prepared:	November 3, 1998
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	New antimicrobial - Cefdinir
Predicate device:	NCCLS Frozen Cefdinir Reference Panels

510(k) Summarv:

The proposed MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panel with Cefdinir demonstrated substantially equivalent performance when compared with an NCCLS frozen Cefdinir Reference Panel, as defined in the FDA DRAFT document "Review Criteria for Assessment of Antimicrobial Susceptibility Devices" (dated May 31, 1991).

The Premarket Notification (510[k]) presents data in support of the new antimicrobial, Cefdinir, for the MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels.

Both the gram-negative and gram-positive 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 Cefdinir panels by comparing their performance with an NCCLS frozen Cefdinir Reference panel.

The Dried gram-negative Cefdinir panel demonstrated acceptable performance with an overall Essential Agreement of 97.9% when compared with the frozen Cefdinir Reference panel. The Dried gram-positive Cefdinir panel demonstrated acceptable performance with an overall Essential Agreement of 94.0% when compared with the frozen Cefdinir Reference panel.

Inoculum and instrument reproducibility testing was conducted; both the gram-negative and the gram-positive Dried Cefdinir panels demonstrated acceptable reproducibility and precision, regardless of which inoculum method (i.e., Turbidity and Prompt), or instrument (autoScan-4® and WalkAway®) was used.

Quality Control performance was acceptable for both the gram-negative and the grampositive Dried Cefdinir panels.

The following limitations will be added to the labeling for Cefdinir:

. .

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"Do Not Report" with S. pneumoniae and viridans streptococci (MIC and Breakpoint dilutions).

"Do Not Report" with methicillin-resistant, coagulase-negative staphylococci (MIC and Breakpoint dilutions).

"Use Alternate Method" with Providencia spp. (MIC and Breakpoint dilutions).

"The performance of Cefdinir has not been established with Stationary and Log Inoculum methods."

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle or bird with three stylized lines representing its wings or feathers.

Public Health Service

JUN 17 1999

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Sharon K. Cullen Director RA/Compliance Dade MicroScan. Inc. 1584 Enterprise Boulevard West Sacramento. CA 95691

Re: K983922

Trade Name: MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels/Cefdinir Regulatory Class: II Product Code: JWY Dated: May 21, 1999 Received: May 24, 1999

Dear Ms. Cullen:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Attachment F

Indications for Use Statement

510(k) No.:	K983922
Device Name:	MicroScan® Dried Gram-Negative and Gram-PositiveMIC/Combo Panels with Cefdinir (0.015 - 8 mcg/ml on thegram-negative and gram-positive panels)
Indications for Use:	To determine gram-negative and gram-positive bacterial susceptibility against the antimicrobial agent Cefdinir.
	Organisms with indications for testing* include:
	Gram-Negative Bacteria	Gram-Positive Bacteria
	None**	Staphylococcus aureus ***(Including methicillin-susceptible, β-lactamaseproducing strains)
		Streptococcus pyogenes
	*As taken from the indications and Usage section of themanufacturer's package insert (Issued: March 1998).
	**No gram-negative organisms for which Microscan is seekingclearance are indicated for testing in the Indications and Usagesection of the manufacturer's package insert.
	***Cefdinir is inactive against methicillin-resistant Staphylococcus
	The following secondary organisms included for the testing ofMicroScan® panels with Cefdinir have in vitro data but the safetyand effectiveness in treating clinical infections have not beenestablished: Citrobacter (diversus) koseri, Escherichia coli,Klebsiella pneumoniae, Proteus mirabilis, Staphylococcusepidermidis (methicillin-susceptible), Streptococcus agalactiae

:

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The MicroScan® Dried Gram-Negative and Gram-Positive The MicroScall - Dried Crain 1105 --------------------------------------------------------------------------------------------------------------------------------------------MIC/Combo I and viridans streptococci.

Woody Dubois

Division of Clinical Laboratory Devices 510(k) Number_K 98 3922

PRESCRIPTION USE X

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).