IMMULITE MYOGLOBIN, MODEL LKMY1 AND LKMY5

K983970 · Diagnostic Products Corp. · DDR · Nov 25, 1998 · Immunology

Device Facts

• Record ID: K983970
• Device Name: IMMULITE MYOGLOBIN, MODEL LKMY1 AND LKMY5
• Applicant: Diagnostic Products Corp.
• Product Code: DDR · Immunology
• Decision Date: Nov 25, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5680
• Device Class: Class 2

Intended Use

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 Story

IMMULITE® Myoglobin is an in vitro diagnostic assay used with the IMMULITE Automated Analyzer to measure myoglobin in patient serum. The device utilizes a solid-phase, two-site chemiluminescent enzyme immunometric assay. A polystyrene bead coated with monoclonal anti-myoglobin antibody captures myoglobin from the sample, forming an antibody-sandwich complex with an alkaline phosphatase-conjugated polyclonal antibody. Following incubation and washing, a phosphate ester substrate is added; hydrolysis by alkaline phosphatase produces an unstable intermediate that emits light. The luminometer measures photon output, which is directly proportional to myoglobin concentration. Results are used by clinicians to aid in the diagnosis of acute myocardial infarction (AMI), assess reperfusion after thrombolytic treatment, and monitor for reinfarction. The test provides early detection of AMI due to rapid myoglobin diffusion following cardiac cell membrane disruption.

Clinical Evidence

Method comparison study performed on 172 patient samples with myoglobin concentrations ranging from 13 to 831 ng/mL. Linear regression analysis comparing IMMULITE® Myoglobin to the ACS:180 predicate yielded a correlation coefficient (r) of 0.981. Mean values were 61 ng/mL for IMMULITE® and 76 ng/mL for the predicate.

Technological Characteristics

Solid-phase, two-site chemiluminescent enzyme immunometric assay. Solid phase: polystyrene bead coated with monoclonal anti-myoglobin antibody. Detection: alkaline phosphatase-conjugated polyclonal antibody; phosphate ester of adamantyl dioxetane substrate. Energy source: automated analyzer luminometer. Connectivity: integrated with IMMULITE Automated Analyzer. Software: automated assay processing and signal quantification.

Indications for Use

Indicated for the quantitative measurement of myoglobin in serum as an aid in the diagnosis of acute myocardial infarction (AMI).

Regulatory Classification

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.

Predicate Devices

• ACS:180 Myoglobin (K974325)

Submission Summary (Full Text)

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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 Street<br>Los Angeles, California 90045-5597 |
| Telephone Number: | [phone] |
| Facsimile Number: | [phone] |
| Contact Person: | Edward M. Levine, Ph.D.<br>Director of Clinical Affairs |
| Date of Preparation: | November 5, 1998 |
| Device Name:<br>Trade: | IMMULITE® Myoglobin |
| Catalog Number: | LKMY1 (100 tests), LKMY5 (500 tests) |
| Common: | Reagent system for the determination of myoglobin in<br>serum. |
| Classification: | Class II device, 75-DDR (21CFR 866.5680) |
| Manufacturer: | Diagnostic Products Corporation<br>5700 West 96th Street<br>Los Angeles, California 90045-5597 |
| Sole U.S. Importer: | Diagnostic Products Corporation<br>5700 West 96th Street<br>Los Angeles, California 90045-5597 |
| Establishment Registration<br>Number | DPC's Registration Number is 2017183 |
| Substantially Equivalent<br>Predicate Device: | ACS:180 Myoglobin (K974325)<br>Manufactured by Chiron Diagnostics |
| Description of Device: | IMMULITE® Myoglobin is a clinical device for use with<br>the IMMULITE® Automated Immunoassay Analyzer. |

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# Intended Use of the Device:

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).

#### 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 [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 [phone], 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:

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).

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

for k Mon famang
(Division Sign-Off)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number A983970

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Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use

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