BECKMAN COULTER IMMAGE IMMUNOCHEMISTRY SYSTEM LOW CONCENTRATION IMMUNOGLOBULIN M (IGMLC) REAGENT, BECKMAN COULTER CEREB

K993547 · Beckman Coulter, Inc. · CFN · Feb 1, 2000 · Immunology

Device Facts

• Record ID: K993547
• Device Name: BECKMAN COULTER IMMAGE IMMUNOCHEMISTRY SYSTEM LOW CONCENTRATION IMMUNOGLOBULIN M (IGMLC) REAGENT, BECKMAN COULTER CEREB
• Applicant: Beckman Coulter, Inc.
• Product Code: CFN · Immunology
• Decision Date: Feb 1, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5510
• Device Class: Class 2

Intended Use

The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent, when used in conjunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin M in serum and cerebrospinal fluid by rate nephelometry.

Device Story

The IMMAGE® Immunochemistry System uses rate nephelometry to quantify human IgM in serum and CSF samples. The system utilizes goat anti-human IgM antibodies to react with IgM in the sample; the resulting light scattering is measured to determine concentration. The device is intended for use in clinical laboratory settings by trained laboratory personnel. The system automates the analysis, providing quantitative results via a calibration curve, which replaces manual or semi-quantitative methods like immunofixation electrophoresis. Clinicians use these IgM concentration results to assess blood-CSF barrier integrity and identify intrathecal immunoglobulin synthesis, aiding in the diagnosis of CNS conditions such as meningitis or encephalitis.

Clinical Evidence

Bench testing only. Method comparison studies (N=55 for serum; N=51 for CSF) demonstrated high correlation with predicate methods (slope 0.977, r=0.988 for serum). CSF sensitivity was 100% and specificity ranged from 89.5% to 100%. Imprecision studies (N=80 per sample level) showed low CVs for both serum (1.7-3.5%) and CSF (2.0-6.0%) matrices.

Technological Characteristics

Rate nephelometry system; goat anti-human IgM antibody; liquid, azide-preserved calibrator (human urine base). Operates at a controlled 37°C. Quantitative output via calibration curve. Designed for use on the IMMAGE® Immunochemistry System.

Indications for Use

Indicated for the quantitative determination of human immunoglobulin M (IgM) in serum and cerebrospinal fluid (CSF) to assist in the diagnosis of Central Nervous System (CNS) diseases, including brain tumor, intracerebral hemorrhage, meningitis, encephalitis, and bacterial infections, by detecting increased blood-CSF barrier permeability and intrathecal immunoglobulin synthesis.

Regulatory Classification

Identification

An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Predicate Devices

• IMMAGE Immunochemistry Systems Immunoglobulin M (IGM) Reagent (K963868)
• Paragon® Immunofixation Electrophoresis Reagent (K823884)

Submission Summary (Full Text)

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K993547

Image /page/0/Picture/2 description: The image shows the logo for Beckman Coulter. The logo consists of a circular graphic on the left and the company name on the right. The graphic is a stylized image of two curved lines within a circle. The text "BECKMAN COULTER" is written in bold, sans-serif font.

Summary of Safety & Effectiveness Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

### 1.0 Submitted By:

Richard T. Ross Staff Regulatory Specialist, Product Submissions Beckman Coulter, Inc. 200 South Kraemer Blvd., W-104 Brea, California 92822-8000 Telephone: [phone] FAX: [phone]

### 2.0 Date Submitted: 01 October 1999

### 3.0 Device Name(s):

### 3.1 Proprietary Names

Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

#### 3.2 Classification Name

Method, Nephelometric, Immunoglobulins (G, A, M) (21 CFR §866.5510)

#### 4.0 Predicate Device(s):

| IMMAGE System | Serum Predicate | Manufacturer | Docket Number |
|------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|------------------------------|---------------|
| IMMAGE System<br>Low Concentration<br>Immunoglobulin M<br>(IGMLC) Reagent<br>Cerebrospinal Fluid<br>Protein Calibrator | IMMAGE<br>Immunochemistry<br>Systems<br>Immunoglobulin M<br>(IGM) Reagent | Beckman<br>Instruments, Inc. | K963868 |
| | CSF Predicate | Manufacturer | Docket Number |
| | Paragon®<br>Immunofixation<br>Electrophoresis Reagent | Beckman<br>Instruments, Inc. | K823884 |

#### 5.0 Description:

The IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent and Cerebrospinal Fluid Calibrator are designed for optimal performance on the IMMAGE® Immunochemistry Systems. It is intended for the quantitative determination of immunoglobulin M in serum and cerebrospinal fluid.

#### 6.0 Intended Use:

The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent, when used in coniunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin M in serum and cerebrospinal fluid by rate nephelometry.

Mailing Address: 200 S. Kraemer Boulevard P.O. Box 8000 Brea, CA 92822-8000

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#### 7.0 Comparison to Predicate(s):

The following tables show similarities and differences between the predicate identified in Section 4.0 of this summary.

## SIMILARITIES to the SERUM PREDICATE

| IMMAGE System | Aspect/Characteristic | Comments |
|-------------------------------------------|---------------------------------------------------------------|--------------------------------|
| IMMAGE System IGMLC Reagent | Intended use | Same as<br>Predicate<br>device |
| | Rate nephelometry method | |
| | Antibody is goat antihuman IgM | |
| Cerebrospinal Fluid Protein Calibrator | Single level calibrator | |
| SIMILARITIES to the CSF PREDICATE | | |
| IMMAGE System | Aspect/Characteristic | Comments |
| IMMAGE System IGMLC | Intended use | Same as predicate device |
| Reagent | Serum and CSF are acceptable sample types | |
| | Antibody is goat antihuman IgM | |
| Cerebrospinal Fluid Protein<br>Calibrator | Single level calibrator | N/A |
| | Protein is of human serum origin<br>added to human urine base | Predicate has<br>no calibrator |

# DIFFERENCES from the SERUM PREDICATE

| IMMAGE System | Aspect/Characteristic | Comments |
|--------------------------------|-------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|
| IMMAGE System<br>IGMLC Reagent | Serum or CSF as sample type | Predicate cleared for serum only |
| CSF CAL | CSF CAL Cerebrospinal Fluid<br>Calibrator is a single level,<br>human urine base, azide<br>preserved liquid | Predicate calibrator is a single<br>level, human serum based, azide<br>preserved liquid |

# DIFFERENCES from the CSF PREDICATE

| IMMAGE System | Aspect/Characteristic | Comments |
|--------------------------------|---------------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| IMMAGE System<br>IGMLC Reagent | IMMAGE System IGMLC is<br>a rate nephelometric reaction<br>at a controlled 37°C | Predicate is a gel immunofixation<br>electrophoresis at room<br>temperature |
| IMMAGE System<br>IGMLC Reagent | IMMAGE System provides<br>quantitative result based on<br>calibration curve | Qualitative result based on visual<br>comparison to known controls |
| IMMAGE System<br>IGMLC Reagent | Sample may be loaded<br>and/or run neat without pre-<br>analysis concentration | Sample concentration typically<br>required prior to IFE analysis |
| CSF CAL | Single level calibrator | Predicate has no calibrator |

Beckman Coulter, Inc. IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent Filename: igmlcSSE2.doc

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#### 8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison and imprecision experiments.

| Serum Study Results | | CSF Study Results | |
|-------------------------|-------|----------------------------------------------|----------|
| N | 55 | N | 51 51 |
| Slope | 0.977 | Test Positive | 51 45 |
| Intercept | 9.12 | Test Negative | 0 6 |
| Mean (IGMLC) mg/L | 1039 | False Positives | 6 0 |
| Mean (predicate) mg/L | 1054 | False Negative | 0 0 |
| Correlation Coefficient | 0.988 | Sensitivity % | 100 100 |
| | | Specificity % | 89.5 100 |
| | | % sensitivity = (N/(N + false negative))*100 | |
| | | % specificity = (N/(N + false positive))*100 | |

Method Comparisons

Estimated IMMAGE System IGMLC Reagent Imprecision (Serum)

| PRECISION | SAMPLE | N | MEAN (mg/L) | SD (mg/L) | % CV |
|------------|--------|----|-------------|-----------|------|
| Within-Run | Low | 80 | 173 | 5.4 | 3.2 |
| Within-Run | Mid | 80 | 869 | 14.6 | 1.7 |
| Within-Run | High | 80 | 1779 | 31.8 | 1.8 |
| Total | Low | 80 | 173 | 6.1 | 3.5 |
| Total | Mid | 80 | 869 | 21.8 | 2.5 |
| Total | High | 80 | 1779 | 35.5 | 2.0 |

Estimated IMMAGE System IGALC Reagent Imprecision (CSF)

| PRECISION | SAMPLE | N | MEAN (mg/L) | SD (mg/L) | % CV |
|------------|--------|----|-------------|-----------|------|
| Within-Run | Low | 80 | 0.536 | 0.0279 | 5.2 |
| Within-Run | Mid | 80 | 4.77 | 0.096 | 2.0 |
| Within-Run | High | 80 | 8.61 | 0.182 | 2.1 |
| Total | Low | 80 | 0.536 | 0.0320 | 6.0 |
| Total | Mid | 80 | 4.77 | 0.197 | 4.1 |
| Total | High | 80 | 8.61 | 0.299 | 3.5 |

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

Beckman Coulter, Inc. IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent Filename: igmlcSSE.doc

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FEB 1 2000 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Richard T. Ross Staff Regulatory Specialist Beckman Coulter, Inc. 200 S. Kraemer Boulevard, W-104 P.O. Box 8000 Brea, California 92622-8000

Re: K993547

> Trade Name: IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL) Regulatory Class: II Product Code: CFN Dated: December 20, 1999 Received: December 21, 1999

Dear Mr. Ross:

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 (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS 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 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" (21CFR 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 Radiological Health

Enclosure

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K993547

page _ of _

510(k) Number (if known): Not yot assigned

Device Name:

IMMAGE® Immunochemistry System

Low Concentration Immunoglobulin M (IGMLC) Reagent

Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

Indications for Use:

The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent, when used in conjunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin M in serum and cerebrospinal fluid by rate nephelometry.

Clinical Significance:

The concentration ratio of immunoglobulins in CSF and serum detects increased permeability of the blood-CSF barrier and intrathecal synthesis of immunoglobulins.

The permeability of the blood-CSF barrier to plasma increases due to brain tumor, intracerebral hemorrhage, meningitis, encephalitis, and bacterial infections. The intrathecal synthesis of immunoglobulins is important in the diagnosis of diseases of the Central Nervous Systems (CNS).

> Method, Nephelometric, Immunoglobulins (G, A, M) (21 CFR §866.5510)

(b) Classification. Class II.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices

| 510(k) Number | K993547 |
|---------------|---------|
|---------------|---------|

| Prescription Use (per 21 CFR 801.109) | <div style="text-align: center;">✓</div> | OR | Over-the-Counter Use |
|---------------------------------------|------------------------------------------|----|------------------------|
| | | | Optional Format 1-2-96 |