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 and heparinized plasma. 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 sample and alkaline phosphatase-conjugated polyclonal antibody are incubated for approximately 30 minutes at 37 ℃ 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 centrifugal 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

The provided document describes the IMMULITE® Myoglobin device and a study demonstrating its substantial equivalence to a predicate device. Here's an analysis of the requested information based on the provided text:

Acceptance Criteria and Reported Device Performance

The core of the "acceptance criteria" here is that the IMMULITE® Myoglobin device's performance should be "substantially equivalent" to the predicate device, the ACS:180 Myoglobin. The study aims to show a strong correlation and agreement between the measurements from both devices.

Acceptance Criteria (Implied by Substantial Equivalence Goal)	Reported Device Performance (IMMULITE® Myoglobin vs. ACS:180 Myoglobin)
Strong linear relationship between device and predicate measurements.	Linear Regression Analysis:
	(IMMULITE®) = 0.87 (ACS: 180) + 5.7 ng/mL
High correlation coefficient (r) indicating good agreement.	Correlation Coefficient (r): 0.981
Mean values of measurements should be comparable.	Means:
	61 ng/mL (IMMULITE®)
	76 ng/mL (ACS:180)

Study Details

Sample Size used for the test set and the data provenance:
- Sample Size: 172 patient samples.
- Data Provenance: Not explicitly stated whether the samples were retrospective or prospective, nor the country of origin. It only mentions "patient samples."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. The study compares the new device to an existing commercially available immunoassay (ACS:180), not directly to a ground truth established by experts.
Adjudication method for the test set:
- None explicitly mentioned. The comparison is a direct reading of values from two automated systems.
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 study is for a diagnostic assay, an automated immunoassay for myoglobin, not an AI-assisted diagnostic imaging system that would involve human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes. The study describes the performance of the IMMULITE® Myoglobin assay itself, which is an automated system without human-in-the-loop performance in terms of result generation. It compares the results of this automated system to another automated system.
The type of ground truth used:
- The "ground truth" for this study is implicitly the measurements from the predicate device (ACS:180 Myoglobin). The study aimed to show substantial equivalence to this already marketed device, rather than an independent gold standard like pathology or clinical outcomes for myoglobin itself.
The sample size for the training set:
- Not applicable / not provided. As an immunoassay, the device itself doesn't typically have a "training set" in the machine learning sense. The development of the assay (e.g., antibody selection, chemiluminescent reaction parameters) would involve internal R&D and validation, but not a distinct "training set" as understood in AI/ML validation.
How the ground truth for the training set was established:
- Not applicable / not provided for the reasons stated above.

Summary

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4/27/99

K991277

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:Address:	Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597
Telephone Number:Facsimile Number:	(310) 645-8200(310) 645-9999
Contact Person:	Edward M. Levine, Ph.D.Director of Clinical Affairs
Date of Preparation:	April 13, 1999
Device Name:Trade:	IMMULITE® Myoglobin
Catalog Number:	LKMY1 (100 tests), LKMY5 (500 tests)
Common:	Reagent system for the determination of myoglobinin serum and heparinized plasma.
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 usewith the IMMULITE® Automated ImmunoassayAnalyzer.

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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 0.5-2 hours after chest pain onset and peak within 5-12 hours. The kidneys rapidly eliminate the 17.8 kDa protein from the system, restoring normal circulating concentrations within 16-36 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 sample and alkaline phosphatase-conjugated polyclonal antibody are incubated for approximately 30 minutes at 37 ℃ 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 centrifugal 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 antimyoglobin 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 >
Dispenses 300 µL 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

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K991277

Technology Comparison (continued):

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.

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 vielded the following statistics:

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

Means:

61 ng/mL (IMMULITE®) 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 M. Lewis

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

4/13/55
Date

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Image /page/4/Picture/1 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is a stylized image of a bird with three wing-like shapes, representing health and human services.

Public Health Service

APR 2 7 1999

Food and Drug Administration 9200 Corporate Boulevard 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: K991277 Trade Name: IMMULITE® Myoglobin Regulatory Class: II Product Code: DDR Dated: April 13, 1999 Received: April 14, 1999

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 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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Page 2

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 (770)488-7655.

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

Sincerely yours,

Steven Butman

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):_ Device Name: IMMULITE® Myoglobin

Indications For Use:

Dean Conger
Division Sign-Off

Division of Clinical Laboratory Devices Vog12 510(k) Number.

(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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Prescription U: (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-

ત્ત્વ)

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).