PARAGON CZE 2000 URINE PROTEIN ELECTROPHORESIS KIT AND URINE IMMUNOFIXATION BY SUBTRACTION KIT

K050119 · Beckman Coulter, Inc. · JKM · May 6, 2005 · Immunology

Device Facts

• Record ID: K050119
• Device Name: PARAGON CZE 2000 URINE PROTEIN ELECTROPHORESIS KIT AND URINE IMMUNOFIXATION BY SUBTRACTION KIT
• Applicant: Beckman Coulter, Inc.
• Product Code: JKM · Immunology
• Decision Date: May 6, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5150
• Device Class: Class 2

Intended Use

The PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the electrophoretic separation of proteins in human urine. The PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the immunologic identification of monoclonal components in human urine.

Device Story

The PARAGON CZE 2000 UPE and U-IFE/s kits are reagents used with the Paragon CZE 2000 Capillary Electrophoresis System. The system processes human urine samples; samples undergo desalting prior to analysis. The UPE kit performs electrophoretic separation of proteins; the U-IFE/s kit performs immunologic identification of monoclonal components via subtraction. The system uses capillary electrophoresis technology to detect proteins by absorbance at 214 nm. Results are presented as electropherograms, which are visually inspected by laboratory personnel to identify monoclonal components or Bence-Jones proteins. This information assists clinicians in diagnosing and monitoring monoclonal gammopathies. The device is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Method comparison studies were conducted against predicate gel electrophoresis kits. UPE kit showed 95% agreement (n=100). U-IFE/s kit showed 92.7% agreement (n=82). Precision and reproducibility studies were performed, including within-run and total imprecision metrics; CVs for albumin and Bence-Jones proteins (BJP) ranged from 2.0% to 12.7%. Visual inspection of electropherograms confirmed morphology and subtraction performance met the 80% agreement specification.

Technological Characteristics

Capillary electrophoresis system; utilizes desalting columns and segment packages for sample processing. Detection via absorbance at 214 nm. Reagents include desalting reagents. System is designed for automated electrophoretic separation and immunologic identification. Operates at 2-30°C. Connectivity and software details not specified beyond system integration.

Indications for Use

Indicated for the electrophoretic separation of proteins and immunologic identification of monoclonal components in human urine to aid in the detection of Bence-Jones proteins and other monoclonal components.

Regulatory Classification

Identification

A Bence-Jones proteins immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the Bence-Jones proteins in urine and plasma. Immunoglobulin molecules normally consist of pairs of polypeptide chains (subunits) of unequal size (light chains and heavy chains) bound together by several disulfide bridges. In some cancerous conditions, there is a proliferation of one plasma cell (antibody-producing cell) with excess production of light chains of one specific kind (monoclonal light chains). These free homogeneous light chains not associated with an immunoglobulin molecule can be found in urine and plasma, and have been called Bence-Jones proteins. Measurement of Bence-Jones proteins and determination that they are monoclonal aid in the diagnosis of multiple myeloma (malignant proliferation of plasma cells), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins by spleen and bone marrow cells), leukemia (cancer of the blood-forming organs), and lymphoma (cancer of the lymphoid tissue).

Predicate Devices

• PARAGON SPE Kit (K802592)
• PARAGON IFE Kit (K823884)

Submission Summary (Full Text)

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Ko50119

## MAY - 6 21:5

### 510(k) Summary Beckman Coulter PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation By Subtraction (U-IFE/s) Kit

#### Submitted By: 1.0

Kim Walker Requlatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-515 Brea, California 92822-8000 Telephone: [phone] FAX: [phone]

#### 2.0 Date Submitted:

January 14, 2005

#### 3.0 Device Name(s):

.

#### Proprietary Names 3.1

PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit

PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit

#### 3.2 Classification Name

UPE & U-IFE/s - Bence-Jones proteins immunological test (21 CFR \$ 866.5150)

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#### Predicate Devices: 4.0

| Candidate | Predicate | Manufacturer | Docket<br>Number |
|---------------------------------|-----------------|--------------------------|------------------|
| PARAGON CZE<br>2000 UPE Kit | PARAGON SPE Kit | Beckman<br>Coulter, Inc. | K802592 |
| PARAGON CZE<br>2000 U-IFE/s Kit | PARAGON IFE Kit | Beckman<br>Coulter, Inc. | K823884 |

#### 5.0 Description:

The PARAGON CZE® 2000 UPE and U-IFE/s kits are designed for optimal performance on the PARAGON CZE® 2000. The UPE kits contain one Segment package containing 20 Segments, five Desalting Column packages with 4 columns per package, and four 500 mL Desalting Reagent bottles. The U-IFE/s kits contain two Segment packages containing 10 Segments, one Desalting Column package with 4 columns per package, and one 500 mL Desalting Reagent bottle.

#### 6.0 Intended Use:

The PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the electrophoretic separation of proteins in human urine.

The PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the immunologic identification of monoclonal components in human urine.

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

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

| Kit | Aspect/Characteristic | Comments |
|-------------|---------------------------------------------------------------------|------------------------------------|
| UPE Kit | Basic Technology (Electrophoretic Migration) | Same as Beckman<br>Paragon SPE Kit |
| | Urine Sample Type | |
| | Shelf Life Stability | |
| | Specificity | |
| | Qualitative Results | |
| U-IFE/s Kit | Basic Technology (Electrophoretic Migration<br>with Immunofixation) | Same as Beckman<br>Paragon IFE Kit |
| | Urine Sample Type | |
| | Qualitative Results | |
| | Shelf Life Stability | |
| | Antisera Storage | |
| | Antisera Specificity | |

Similarities to the Predicate

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# Differences From The Predicate

| Kit | Aspect/<br>Characteristic | Comments |
|----------------|-----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| UPE Kit | Intended Use | The Paragon CZE 2000 Urine Protein Electrophoresis<br>(UPE) Kit is intended for use with the Paragon CZE<br>2000 Capillary Electrophoresis System for the<br>electrophoretic separation of proteins in human urine.<br><br>The Paragon Serum Protein Electrophoresis (SPE) Kit<br>is intended for the electrophoretic separation of<br>proteins in human serum, cerebrospinal fluid, and urine. |
| | Sample Preparation | UPE - No concentration required for urine samples<br>with a total protein of 20-4800 mg/dL. Must desalt<br>before running sample on CZE. Any samples <20<br>mg/dL must be concentrated and >4800 mg/dL must<br>be diluted.<br><br>SPE - Concentration required for all urine samples<br><700 mg/dL total protein. |
| | Interferences | UPE- Any materials that would absorb at 214 nm and<br>not removed by desalting. Hemoglobin co-migrates<br>with transferrin.<br><br>SPE - Lipemic and hemolyzed samples. |
| | Lowest Detectible<br>Limit | UPE - 0.5-2.0 mg/dL of Kappa and Lambda Bence<br>Jones Proteins were visible when no other co-<br>migrating proteins were present.<br><br>SPE - No claims made. |
| | Methodology | UPE - Capillary Electrophoresis<br>SPE - Gel Electrophoresis |
| | Sample Size | UPE - 0.5 mL Desalted Urine<br>SPE - 3-5 uL Concentrated or Neat Urine |
| | Storage<br>Temperature | UPE-2-30°C<br>SPE - 18 - 26°C |
| | Analytic Range | UPE - Single Protein Component 0.5 - 2.0 mg/dL to<br>4600 mg/dL & Total Protein 0.02 - 4.80 g/dL<br>SPE - Total Protein >700 mg/dL |
| Kit | Aspect/<br>Characteristic | Comments |
| U-IFE/s<br>Kit | Intended Use | The Paragon CZE 2000 Urine Immunofixation by<br>Subtraction (U-IFE/s) Electrophoresis Kit is intended<br>for use with the Paragon CZE 2000 Capillary<br>Electrophoresis System for the immunologic<br>identification of monoclonal components in human<br>urine.<br><br>The Paragon Immunofixation Electrophoresis (IFE) Kit<br>is for the immunologic identification of proteins in<br>human serum, cerebrospinal fluid, and urine. |
| | Sample Preparation | U-IFE/s - No concentration required for urine samples<br>w/ monoclonal components of 5 - 300 mg/dL. Must<br>desalt before running sample on CZE. Any samples<br><5 mg/dL of monoclonal components or <2.5 - 10.0<br>mg/dL of monoclonal components must be<br>concentrated & >300 mg/dL of monoclonal<br>components must be diluted.<br>IFE - Concentration required for all urine samples<br><100 mg/dL total protein for the detection of Bence-<br>Jones Proteins. Concentration up to 800 - 1000<br>mg/dL should be conducted on all urine samples for<br>the detection of immunoglobulins. |
| | Interferences | U-IFE/s- Any materials that would absorb at 214 nm<br>and not removed by desalting. Hemoglobin co-<br>migrates w/ transferrin.<br>IFE - Fibrinogen containing, IgM Immune complex<br>containing & hemolyzed samples. |
| | Lowest Detectible<br>Limit | U-IFE/s – 2.5-5.0 mg/dL of Lambda & 5.0-10.0 mg/dL<br>of Kappa Bence-Jones proteins were visible when no<br>other co-migrating proteins were present.<br>IFE - No claims made. |
| | Methodology | U-IFE/s - Capillary Electrophoresis<br>IFE - Gel Electrophoresis |
| | Sample Size | U-IFE/s – 300-700 μL Desalted Urine depending on<br>the dilution used<br>IFE - 3-5 uL Concentrated or Neat Urine |
| | Storage<br>Temperature other<br>than Antisera | U-IFE/s – 2 - 30°C<br>IFE – 18 - 26°C |
| | Analytic Range | U-IFE/s – 2.5 - 5.0 mg/dL to 300 mg/dL Lambda & 5.0<br>- 10.0 mg/dL to 300 mg/dL Kappa<br>IFE - Total Protein >100 mg/dL for detection of Bence-<br>Jones Proteins. Total Protein >800-1000 mg/dL for<br>detection of immunoglobulins. |

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.

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#### Summary of Performance Data: 8.0

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, stability, linearity/sensitivity, and precision/ reproducibility experiments.

| Instrument | Agreement | Partial<br>Agreement | Disagreement | n | Comparison<br>Method |
|----------------------------------|-----------|----------------------|--------------|-----|---------------------------------------------|
| PARAGON<br>CZE 2000<br>– UPE Kit | 95 | 4 | 1 | 100 | PARAGON Gel<br>Electrophoresis –<br>SPE Kit |

### Method Comparison Study Results

| Instrument | Full Agreement | Disagreement | n | Comparison Method |
|-----------------------------------------|----------------|--------------|----|---------------------------------------------|
| PARAGON<br>CZE 2000<br>– U-IFE/s<br>Kit | 76<br>(92.7%) | 6<br>(7.3%) | 82 | PARAGON Gel<br>Electrophoresis – IFE<br>Kit |

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| Type of<br>Imprecision | Sample | Fraction | Mean<br>(Relative %) | S.D.<br>(Relative %) | %<br>C.V. | N |
|------------------------------|------------------|----------|----------------------|----------------------|-----------|----|
| Within-Run Imprecision | | | | | | |
| System<br>Reproducibility | Urine<br>Pool | Albumin | 55.1 | 1.38 | 2.5 | 21 |
| | | BJP | 13.2 | 0.93 | 7.1 | 21 |
| Desalting<br>Reproducibility | Urine<br>Pool | Albumin | 54.8 | 1.65 | 3.0 | 21 |
| | | BJP | 13.5 | 0.71 | 5.3 | 21 |
| Total Imprecision | | | | | | |
| Total<br>(EP 10-A) | Urine<br>Level 1 | Albumin | 28.8 | 0.7 | 2.5 | 15 |
| | | BJP | 13.4 | 0.8 | 5.9 | 15 |
| | Urine<br>Level 2 | Albumin | 60.8 | 1.3 | 2.2 | 15 |
| | | BJP | 6.5 | 0.8 | 12.7 | 15 |
| | Urine<br>Level 3 | Albumin | 9.2 | 0.8 | 9.2 | 15 |
| | | BJP | 72.1 | 1.5 | 2.0 | 15 |

### UPE Imprecision Results

### U-IFE/s Reproducibility Results

The electropherograms were visually inspected to ensure that at least 80% were within agreement. No observable difference in morphology or subtraction was seen between the segments for each of the samples BJP subtraction with kappa and lambda was as expected. tested. Reproducibility meets the 80% specification for visual agreement for the replicate segments.

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.

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Image /page/7/Figure/0 description: The image is a flowchart outlining the process for determining substantial equivalence under Section 510(k) of the FDA regulations. The flowchart starts with the question of whether the new device is compared to a marketed device. The flowchart then proceeds through a series of questions about the device's indications, intended use, technological characteristics, and the availability of performance data. The flowchart ends with a determination of whether the device is substantially equivalent or not.

CZE_UPE & UIFES 510K_Section1, January 2005

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized eagle with three lines forming its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

MAY - 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kim Walker, RAC Regulatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Boulevard M/S W-515 Brea, California 92822-8000

Re: k050119

Trade/Device Name: PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation by Subtraction (U-IFE/s) Kit Regulation Number: 21 CFR § 866.5150 Regulation Name: Bence-Jones proteins immunological test Regulatory Class: II Product Code: JKM, CFF, DFH, DEH Dated: March 30, 2005 Received: March 31, 2005

### Dear Ms Walker:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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Page 2 –

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., MD, PK.D Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

Koro 119

510(k) Number (if known):

Device Name:

PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation By Subtraction (U-IFE/s) Kit

Indications for Use:

The PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the electrophoretic separation of proteins in human urine.

The PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the immunologic identification of monoclonal components in human urine.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Sunshine Burutta

Division Sign

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050119

Beckman Coulter, Inc., Section 510(k) Notification PARAGON CZE® 2000 UPE & U-IFE/s Kits CZE_UPE & UIFEs 510K_Section1 Final.doc, January 2005 Page 1 of ____________________________________________________________________________________________________________________________________________________________________