For in vitro diagnostic use with the IMMULITE 2000 Analyzer – for the quantitative measurement of tobramycin in serum or plasma, as an aid in monitoring the therapeutic administration of this aminoglycoside.

Device Description

IMMULITE® 2000 Tobramycin is a solid-phase, chemiluminescent enzyme immunoassay for use with the IMMULITE® 2000 Automated Analyzer.

AI/ML Overview

Here's an analysis of the provided text regarding the IMMULITE® 2000 Tobramycin device, structured to address your specific questions:

Acceptance Criteria and Study Details for IMMULITE® 2000 Tobramycin

The provided document describes the performance equivalence of the IMMULITE® 2000 Tobramycin device to a predicate device, Abbott AxSYM® Tobramycin, through a method comparison study. The primary acceptance criteria appear to be based on the statistical results of this comparison, demonstrating substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets in the provided text. Instead, the document implies acceptance based on the statistical outcomes of the method comparison demonstrating substantial equivalence to the predicate device.

Acceptance Criteria (Implied)	Reported Device Performance
Preamble: Substantial equivalence to Abbott AxSYM® Tobramycin	Demonstrated through method comparison and linear regression analysis.
Strong linear correlation (r value)	r = 0.981
Agreement in measured concentration ranges	IMMULITE 2000 Mean: 3.76 µg/mL Abbott AxSYM® Mean: 4.10 µg/mL
Linear regression equation indicating proportionality	(IMMULITE 2000) = 0.96 (Abbott AxSYM® Tobramycin) - 0.18 µg/mL

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

Sample Size for Test Set: 41 patient samples.
Data Provenance: The document does not specify the country of origin. It indicates it was a comparison between the IMMULITE 2000 Tobramycin procedure and a "commercially available assay," suggesting clinical samples. The study is retrospective in the sense that the samples were collected and then analyzed by both methods for comparison.

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

Not applicable. This was a method comparison study between two quantitative diagnostic devices. The "ground truth" for the test set was established by the measurements obtained from the predicate device (Abbott AxSYM® Tobramycin) rather than human expert interpretation or a separate gold standard.

4. Adjudication Method for the Test Set

Not applicable. As this is a quantitative method comparison between two devices, there was no adjudication method involving human experts. The comparison relies solely on the numerical output of each analyzer.

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

No. A MRMC comparative effectiveness study was not done. This device is a quantitative immunoassay with an automated analyzer, not an imaging device requiring human interpretation alongside AI assistance. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-loop Performance)

Yes. The study presented is effectively a standalone performance study. It evaluates the IMMULITE® 2000 system's ability to measure tobramycin concentrations on its own, with its results directly compared to another standalone device (Abbott AxSYM® Tobramycin). There is no human intervention or "in-the-loop" component discussed for the measurement process itself.

7. Type of Ground Truth Used

The "ground truth" in this context is the measurements obtained from the legally marketed predicate device (Abbott AxSYM® Tobramycin). This is a common approach for demonstrating substantial equivalence for quantitative diagnostic assays.

8. Sample Size for the Training Set

The document does not provide information regarding a separate training set or its sample size. The description focuses on the method comparison study using 41 patient samples. For immunoassay development, calibration and validation are typically performed using standards, controls, and characterized samples, but explicit "training set" details as might be described for AI/ML algorithms are not presented.

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

As no training set is explicitly mentioned or detailed in the provided text, the method for establishing its "ground truth" is not available. Immunoassays like this are developed using established reference materials and chemical standards for calibration rather than a "ground truth" derived from expert consensus on complex data.

Summary

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510 (k) Summary Safety and Effectiveness

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Par1 807.92.

Name:	Diagnostic Products Corporation
Address:	5700 West 96th StreetLos Angeles, CA 90045
Telephone Number:	(310) 645-8200
Facsimile Number:	(310) 645-9999
Contact Person:	Edward M. Levine, Ph DDirector of Clinical Affairs
Date of Preparation:	July 20, 2001
Device Name:Trade:	IMMULITE® 2000 Tobramycin
Catalog Number:	L2KTC2 (200 tests), L2KTC6 (600 tests)
CFR:	A tobramycin test system is a device intended to measuretobramycin, an aminoglycoside antibiotic drug, in plasmaand serum. Measurements obtained by this device are usedin the diagnosis and treatment of tobramycin overdose andin monitoring levels of tobramycin to ensure appropriatetherapy.
Common:	Reagent system for the determination of tobramycin inplasma and serum.
Classification:	Class II device, KLB (21 CFR 862.3900)
Panel:	Toxicology
CLIA ComplexityCategory:	We believe the category to be moderate, based on previousclassification of analogous tests

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Manufacturer:	Diagnostic Products Corporation (DPC)5700 West 96th StreetLos Angeles, CA 90045-5597
EstablishmentRegistration #:	DPC's establishment Registration No. is 2017183
Substantially EquivalentPredicate Device:	Abbott AxSYM® Tobramycin (K941614)
Description of Device:	IMMULITE® 2000 Tobramycin is a solid-phase,chemiluminescent enzyme immunoassay for use with theIMMULITE® 2000 Automated Analyzer.
Intended Use of theDevice:	IMMULITE® 2000 Tobramycin is for in vitro diagnosticuse with the IMMULITE® 2000 Analyzer - for thequantitative measurement of tobramycin in serum orplasma, as an aid in monitoring the therapeuticadministration of this aminoglycoside.

Technology:

This section does not contain any new information for a reviewer who is familiar with the DPC IMMULITE® 2000 System based upon the review of previous IMMULITE® 2000 assay submissions.

IMMULITE 2000 Tobramycin is a solid-phase, chemiluminescent competitive immunoassay. The solid-phase, a polystyrene bead, is coated with a polyclonal rabbit antibody specific for tobramycin.

The patient sample and alkaline phosphatase-labeled tobramycin are simultaneously introduced into the Reaction Tube and incubated for approximately 30 minutes at 37 ℃ with intermittent agitation. During this time, tobramycin in the samples competes with wize me-labeled tobramycin for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Reaction Tube is incubated for an additional 5 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex and thus also the photon output, as measured by the luminometer - is inversely proportional to the concentration of tobramycin in the sample.

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Abbott AxSYM® Tobramycin utilizes fluorescence polarization immunoassay technology in a competitive ligand format. The unlabeled antibiotic (antigen being measured) competes with the fluorescent-labeled antigen for the antibody binding sites. With increasing concentration of unlabeled antigen, more fluorescent-labeled antigen becomes unbound. Therefore, the fluorescent polarization signal decreases as the drug concentration increases, as measured by the fluorometer. Concentrations are determined from a stored standard curve

Performance Equivalence:

Diagnostic Products Corporation asserts that the IMMULITE 2000 Tobramycin produces substantially equivalent results to other commercially marketed Tobramycin assays, such as Abbott AxSYM® Tobramycin. The assay, Abbott AxSYM® Tobramycin utilizes fluorescence polarization technology. Each product is designed for the quantitative measurement of tobramycin in serum or plasma. Each product is intended strictly for in vitro diagnostic use as an aid in monitoring the therapeutic administration of this drug.

Method Comparison:

The IMMULITE 2000 Tobramycin procedure was compared to a commercially available assay (Abbott AxSYM® Tobramycin) on 41 patient samples, with tobramycin concentrations ranging from approximately 1.1 to 11.0 µg/mL. Linear regression analysis yielded the following statistics.

(IMMULITE 2000) = 0.96 (Abbott AxSYM® Tobramycin) - 0.18 µg/mL

r = 0.981

3.76 ug/mL (IMMULITE 2000) Means: 4.10 ug/mL (Abbott AxSYM(8)

Conclusion:

The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® 2000 Tobramycin.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, resembling a bird-like shape.

AUG 2 0 2001

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597

510(k) Number: K012312 Re: Trade/Device Name: IMMULITE®2000 Tobramycin Regulation Number: 862.3900 Regulatory Class: II Product Code: KLB Dated: July 20, 2001 Received: July 23, 2001

Dear Dr. Levine:

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 to 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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 regulations.

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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 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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,

Steven Autman

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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510(k) Number (if known): _HQ12312 Device Name: IMMULITE®2000 Tobramycin

Indications For Use:

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Kesia Alexander for John Cooper

(Division Sign- Division of C 510(k) Number

510(k) Number

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Formal 1-2-96)

Regulation Number and Section

§ 862.3900 Tobramycin test system.

(a)
Identification. A tobramycin test system is a device intended to measure tobramycin, an aminoglycoside antibiotic drug, in plasma and serum. Measurements obtained by this device are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to ensure appropriate therapy.(b)
Classification. Class II.