IMMULITE® Myoglobin is a solid-phase, two-site chemiluminescent enzyme immunometric assay for use with the IMMULITE Automated Analyzer and designed for the quantitative measurement of myoglobin in serum. It is intended strictly for in vitro use as an aid in the diagnosis of acute myocardial infarction (AMI).

Device Description

IMMULITE® Myoglobin is a clinical device for use with the IMMULITE® Automated Immunoassay Analyzer. IMMULITE® Myoglobin is a solid-phase, two-site chemiluminescent immunometric assay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for myoglobin. While the patient serum sample and alkaline phosphatase-conjugated polyclonal antibody are incubated for approximately 30 minutes at 37 "C in the Test Unit with intermittent agitation, myoglobin in the sample is bound to form an antibody sandwich complex. Unbound conjugate is then removed by a centrifygal wash, after which substrate is added and the Test Unit is incubated for a further 10 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 proportional to the concentration of myoglobin in the sample.

AI/ML Overview

Here's a summary of the acceptance criteria and study information for the IMMULITE® Myoglobin device, based on the provided text:

Acceptance Criteria and Device Performance

The core of the acceptance criteria for this device appears to be demonstrating substantial equivalence to a legally marketed predicate device. The primary performance metric reported is a method comparison using linear regression analysis.

Acceptance Criteria	Reported Device Performance
Substantial equivalence to predicate device (ACS:180 Myoglobin) in measuring myoglobin in serum for AMI diagnosis.	Linear Regression (IMMULITE® vs. ACS:180):(IMMULITE®) = 0.87 (ACS: 180) + 5.7 ng/mLCorrelation Coefficient (r) = 0.981Mean Concentration Comparison:IMMULITE® Mean = 61 ng/mLACS:180 Mean = 76 ng/mL

Study Details

The provided document describes a method comparison study.

Sample size used for the test set and the data provenance:
- Sample Size: 172 patient samples.
- Data Provenance: Not explicitly stated, but based on the date of preparation (November 5, 1998) and the context of a 510(k) submission, this would be considered retrospective clinical data used for device validation. The country of origin is not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable to this type of device and study. The "ground truth" for a quantitative diagnostic assay is typically established by comparison to a reference method or a predicate device, rather than expert consensus on individual cases.
Adjudication method for the test set:
- Not applicable. This was a direct method comparison, not a study involving human adjudication of 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:
- No. This is a study comparing an automated immunoassay device to another automated immunoassay device, not an AI-powered diagnostic tool involving human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this was a standalone performance evaluation of the IMMULITE® Myoglobin device. It measures myoglobin quantitatively from serum samples without direct human intervention in the result generation process beyond operating the analyzer. Its performance was compared against another standalone device.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" or reference standard for this study was the results obtained from the predicate device (ACS:180 Myoglobin), a commercially available solid-phase immunoassay.
The sample size for the training set:
- Not applicable. This document describes a validation study for a device, not the development or training of an algorithm in the sense of machine learning. The device itself (IMMULITE® Myoglobin) is a specific immunoassay technology, not an AI/ML model that requires a distinct training set.
How the ground truth for the training set was established:
- Not applicable, as there is no training set in the context of an AI/ML model for this device. The development of the immunoassay itself would involve standard laboratory development and validation procedures to establish its analytical characteristics (e.g., sensitivity, specificity, linearity, precision), but these are distinct from the concept of a "ground truth" for a training set in an AI study.

Summary

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NOV 2 5 1998

K983970

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 Part 807.92.

Name:	Diagnostic Products Corporation
Address:	5700 West 96th StreetLos Angeles, California 90045-5597
Telephone Number:	(310) 645-8200
Facsimile Number:	(310) 645-9999
Contact Person:	Edward M. Levine, Ph.D.Director of Clinical Affairs
Date of Preparation:	November 5, 1998
Device Name:Trade:	IMMULITE® Myoglobin
Catalog Number:	LKMY1 (100 tests), LKMY5 (500 tests)
Common:	Reagent system for the determination of myoglobin inserum.
Classification:	Class II device, 75-DDR (21CFR 866.5680)
Manufacturer:	Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597
Sole U.S. Importer:	Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597
Establishment RegistrationNumber	DPC's Registration Number is 2017183
Substantially EquivalentPredicate Device:	ACS:180 Myoglobin (K974325)Manufactured by Chiron Diagnostics
Description of Device:	IMMULITE® Myoglobin is a clinical device for use withthe IMMULITE® Automated Immunoassay Analyzer.

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Intended Use of the Device:

Performance Equivalence:

Diagnostic Products Corporation (DPC) asserts that the IMMULITE® Myoglobin produces substantially equivalent results to other commercially marketed myoglobin assays, such as the ACS:180 Myoglobin. Each product is intended strictly for in vitro diagnostic use to aid in the clinical diagnosis of acute myocardial infarction.

Summary and Explanation of the Test:

Acute myocardial infarction (AMI) disrupts cardiac cell membranes, releasing intracellular cardiac proteins into the vascular system. Some of the proteins, including myoglobin, creatine kinase-MB (CK-MB), lactate dehydrogenase type 1 (LD1), and cardiac troponin subunits I and T, have proven useful in diagnosing AMI. The optimal clinical utility of each marker depends on specific protein characteristics. Myoglobin, the smallest of the markers, diffuses rapidly throughout the vascular system and provides the earliest indication of AMI. Myoglobin levels become elevated 2-3 hours after chest pain onset and peak within 6-9 hours. Other markers reach peak levels 12-19 hours after pain onset. The kidneys rapidly eliminate the 17.8 kDa protein from the system, restoring normal circulating concentrations within 24 hours. Since the protein rapidly clears from the system, myoglobin concentrations can reliably indicate reinfarction. Additionally, myoglobin measurements can preclude AMI: two consecutive low measurements, the first upon patient admission and the second 1-2 hours later, negatively predict AMI in nearly all cases. Myoglobin measurements provide early detection of reperfusion after thrombolytic treatment as well. Some unrelated patients conditions produce high myoglobin levels, decreasing test specificity. Myoglobin participates in aerobic metabolism in both skeletal and cardiac muscle cells, and high levels accompany various muscle traumas. Renal failure and other kidney problems produce high myoglobin levels as well. Most of the complications have distinct clinical symptoms that allow reliable differential diagnosis.

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Technology Comparison:

Provided for the reviewer is a comparison of DPC's IMMULITE® Myoglobin technology vs. the ACS: 180 Myoglobin technology: This section does not contain any new information for a reviewer who is familiar with the DPC IMMULITE® System based upon the review of previous IMMULITE® assay submissions.

IMMULITE® Myoglobin is a solid-phase, two-site chemiluminescent immunometric assay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for myoglobin. While the patient serum sample and alkaline phosphatase-conjugated polyclonal antibody are incubated for approximately 30 minutes at 37 "C in the Test Unit with intermittent agitation, myoglobin in the sample is bound to form an antibody sandwich complex. Unbound conjugate is then removed by a centrifygal wash, after which substrate is added and the Test Unit is incubated for a further 10 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 proportional to the concentration of myoglobin in the sample.

The ACS:180 Myoglobin is a two-site sandwich immunoassay using direct chemiluminescent technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a polyclonal goat anti-myoglobin antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-myoglobin antibody covalently coupled to paramagnetic particles.

The system automatically performs the following steps:

Dispenses 10 uL of sample into a cuvette .
Dispenses 100 uL of Lite Reagent and incubates the reagents for 2.5 minutes at 37 °C .
. Dispenses 200 uL of Solid Phase and incubates the reagents for 5.0 minutes at 37 °C
Separates, aspirates, and washed the cuvettes with reagent water
o Dispenses 300 uL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent reaction
. Reports results according to the selected option, as described in the system operating instructions or in the online help system

A direct relationship exists between the amount of myoglobin present in the patient sample and the amount of relative light units (RLUs) detected by the system.

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Method Comparison:

The IMMULITE® Myoglobin procedure was compared to a commercially available solid phase immunoassay for myoglobin (ACS:180) on 172 patient samples, with myoglobin concentrations ranging from approximately 13 to 831 ng/mL. Linear regression analysis yielded the following statistics:

(IMMULITE®) = 0.87 (ACS: 180) = 5.7 ng/mL r = 0.981

61 ng/mL (IMMULITE®) Means 76 ng/mL (ACS:180)

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® Myoglobin.

Edward Heenan

Edward M. Levine, Ph.D. Director of Clinical Affairs

11/6/98
Date

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Image /page/4/Picture/2 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized caduceus with three intertwined snakes and a bowl. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the seal's perimeter. The seal is black and white.

NOV 2 5 1998

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

Re: K983970 Trade Name: IMMULITE® Myoglobin Regulatory Class: II Product Code: 82 DDR November 05, 1998 Dated: November 09, 1998 Received:

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 (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 In addition, FDA may publish further regulatory action. announcements concerning your device in the Federal Reqister. 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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Page 2

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 (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" (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 (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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

Enclosure

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49:39 510(k) Number (if known): Device Name: IMMULITE® Myoglobin

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Division of Clinical Laboratory Devices
510(k) Number A983970

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Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

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Regulation Number and Section

§ 866.5680 Myoglobin immunological test system.

(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).