DIMENSION VISTA CARCINOEMBRYONIC ANTIGEN FLEX REAGENT CARTRIDGE (CEA)

K071603 · Dade Behring, Inc. · DHX · Jun 25, 2008 · Immunology

Device Facts

• Record ID: K071603
• Device Name: DIMENSION VISTA CARCINOEMBRYONIC ANTIGEN FLEX REAGENT CARTRIDGE (CEA)
• Applicant: Dade Behring, Inc.
• Product Code: DHX · Immunology
• Decision Date: Jun 25, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

The CEA method is an in vitro diagnostic test for the quantitative measurement of carcinoembryonic antigen in human serum and sodium or lithium heparinized plasma on the Dimension Vista System. Measurements of carcinoembryonic antigen are used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed. For the calibration of the Carcinoembryonic Antigen (CEA) method on the Dimension Vista® System.

Device Story

In vitro diagnostic test for quantitative measurement of carcinoembryonic antigen (CEA) in human serum or plasma. Uses LOCI™ homogeneous sandwich chemiluminescence immunoassay technology. Input: patient serum/plasma sample, biotinylated anti-CEA monoclonal antibody, and two synthetic bead reagents (Chemibeads with anti-CEA antibody/chemiluminescent dye; Sensibeads with streptavidin/photosensitizer). Process: sample incubation forms bead-CEA-biotinylated antibody sandwiches; Sensibeads bind to biotin; illumination at 680 nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, inducing chemiluminescence measured at 612 nm. Signal intensity is directly proportional to CEA concentration. Operated by laboratory personnel on the Dimension Vista® System. Output: quantitative CEA concentration (ng/mL). Clinicians use serial measurements to monitor cancer patient status; significant changes are determined using Reference Change Value (RCV) calculations to assess disease progression or response.

Clinical Evidence

Clinical evaluation of 74 colorectal cancer patients (retrospective serial serum samples, n=217 pairs). Performance compared to predicate using Reference Change Value (RCV) to identify disease progression. Dimension Vista CEA sensitivity 55.2% (95% CI: 41.5-68.3%), specificity 83.6% (95% CI: 77.0-89.0%). Overall agreement with predicate was 94.5%. Efficacy confirmed by sum of sensitivity and specificity > 1.0.

Technological Characteristics

LOCI (Luminescent Oxygen Channeling Immunoassay) technology. Reagents: synthetic Chemibeads (anti-CEA antibody, chemiluminescent dye) and Sensibeads (streptavidin, photosensitizer dye). Energy source: 680 nm illumination. Measurement: 612 nm chemiluminescence. Sample volume: 2 uL. System: Dimension Vista. Software: Automated calculation of CEA concentration via stored calibration curve.

Indications for Use

Indicated for the quantitative measurement of carcinoembryonic antigen (CEA) in human serum and sodium or lithium heparinized plasma to aid in the management of cancer patients by monitoring changing CEA concentrations. Prescription use only.

Regulatory Classification

Identification

A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.

Special Controls

*Classification.* Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Predicate Devices

• Beckman Access® CEA Reagents with Calibrators on the Access® Immunoassay System (k031270)

Submission Summary (Full Text)

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# 510{k} Summary for Dimension Vista® CEA Flex® reagent cartridge Dimension® Vista LOCI 5 Calibrator

JUN 2 5 2008

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K071603

| 1. | Manufacturer's Name, Address, Telephone, and Contact Person, Date of<br>Preparation: | |
|----|--------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Manufacturer: | Siemens Healthcare Diagnostics<br>P.O. Box 6101<br>Newark, Delaware 19714 |
| | Contact Information: | Siemens Healthcare Diagnostics<br>P.O. Box 6101<br>Newark, Delaware 19714-6101<br>Attn: Kathleen Dray-Lyons<br>Tel: [phone]<br>Fax: [phone] |
| | Preparation date: | June 2, 2008 |
| 2. | Device Name: | Dimension Vista® CEA Flex® reagent cartridge<br>Dimension Vista® LOCI 5 Calibrator |
| | Classification: | Class II; Class II |
| | Product Code: | DHX; JIX |
| | Panel: | Immunology (82) and Clinical Chemistry (75) |

### Identification of the Legally Marketed Devices: 3.

Beckman Access® CEA Reagents on the Access® Immunoassay System - K031270

#### Device Descriptions: 4.

## Dimension Vista® CEA Flex® reagent cartridge

The CEA method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI™ technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated anti-CEA monoclonal antibody fragment. The first bead reagent (Chemibeads) is coated with an anti-CEA monoclonal antibody and contains chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-CEA-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Ulumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the CEA concentration in the sample.

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## Dimension Vista® LOCI 5 Calibrator

LOCI 5 CAL is a liquid, multi-analyte, bovine serum albumin based product containing CEA from human tissue culture.

### 5. Device Intended Uses:

# Dimension Vista® CEA Flex® reagent cartridge:

The CEA method is an in vitro diagnostic test for the quantitative measurement of carcinoembryonic antigen in human serum and sodium or lithium heparinized plasma on the Dimension Vista System. Measurements of carcinoembryonic antigen are used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.

## Dimension Vista® LOCI 5 Calibrator:

For the calibration of the Carcinoembryonic Antigen (CEA) method on the Dimension Vista® System.

### 6. Medical device to which equivalence is claimed and comparison information:

The Dimension Vista® CEA Flex® reagent cartridge and Dimension Vista® LOCI 5 Calibrator are substantially equivalent to the Beckman Access® CEA Reagents on the Access Immunoassay System (K031270). The Dimension Vista CEA assay, like Beckman Access® CEA method is an in vitro diagnostic test for the quantitative measurement of CEA in human serum.

| Similarities | | |
|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate |
| Intended Use | The CEA method is an in vitro<br>diagnostic test for the quantitative<br>measurement of carcinoembryonic<br>antigen in human serum and<br>sodium or lithium heparinized<br>plasma on the Dimension Vista®<br>System.<br>Measurements of carcinoembryonic<br>antigen are used as an aid in the<br>management of cancer patients in<br>whom changing CEA<br>concentrations have been<br>observed. | The Access CEA assay is a paramagnetic<br>particle, chemiluminescent immunoassay<br>for the quantitative determination of<br>Carcinoembryonic Antigen (CEA) levels in<br>human serum, using the Access<br>Immunoassay System. CEA measured by<br>the Access Immunoassay System is used<br>as an aid in the management of cancer<br>patients. |
| Measuring<br>Range | 0.2- 1000.0 ng/mL | 0.1- 1000.0 ng/mL |
| Measurement<br>method | Chemiluminescent:<br>homogenous, sandwich<br>chemiluminescent immunoassay<br>based on LOCI® technology. | Chemiluminescent:<br>paramagnetic particle, chemiluminescent<br>immunoassay |

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| Differences | | |
|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate |
| Principles of<br>Procedure | The CEA method is a homogenous,<br>sandwich chemiluminescent<br>immunoassay based on LOCI®<br>technology. The LOCI® reagents<br>include two synthetic bead reagents<br>and a biotinylated anti-CEA<br>monoclonal antibody fragment. The<br>first bead reagent (Chemibeads) is<br>coated with an anti-CEA monoclonal<br>antibody and contains<br>chemiluminescent dye. The second<br>bead reagent (Sensibeads) is<br>coated with streptavidin and<br>contains a photosensitizer dye.<br>Sample is incubated with<br>biotinylated antibody and<br>Chemibeads to form bead-CEA-<br>biotinylated antibody sandwiches.<br>Sensibeads are added and bind to<br>the biotin to form bead-pair<br>immunocomplexes. Illumination of<br>the complex at 680 nm generates<br>singlet oxygen from Sensibeads<br>which diffuses into the Chemibeads,<br>triggering a chemiluminescent<br>reaction. | The Access CEA assay is a two-site<br>immunoenzymatic "sandwich" assay<br>using two mouse monoclonal anti-CEA<br>antibodies (MAb) which react with<br>different epitopes of CEA. A sample is<br>added to a reaction vessel, along with the<br>first anti-CEA MAb-alkaline phosphatase<br>conjugate and the second anti-CEA MAb<br>bound to paramagnetic particles. The<br>incubation is followed by a magnetic<br>separation and washing. A<br>chemiluminescent substrate, Lumi-Phos*<br>530, is added to the reaction vessel and<br>light generated by the reaction is<br>measured with a luminometer. The light<br>production is proportional to the<br>concentration of CEA in the sample. The<br>amount of analyte in the sample is<br>determined by means of a stored, multi-<br>point calibrator curve. |
| Sample<br>Types | Serum and Plasma | Serum |
| Sample Size | 2 uL | 10 uL |
| Precision | Repeatability: 1.3 - 2.9 %CV<br>Within Lab:<br>2.1 - 3.6 %CV | Within Run: 3.01 – 3.97 %CV<br>Total:<br>3.80 - 4.51 %CV |

### 7. Device Performance Characteristics:

## Method Comparison

# Regression Statisticsª

| Comparative<br>Method | Slope | Intercept<br>ng/mL [µg/L] | Correlation<br>Coefficient | n |
|-----------------------|-------|---------------------------|----------------------------|------|
| ACCESS® CEA | 1.01 | 9.01 | 0.989 | 141b |
| ACCESS® CEA | 1.04 | 0.44 | 0.970 | 46c |

ACCESS® Immunoassay System is a registered trademark of Beckman Coulter, Inc. a. CLSI/NCCLS EP9-A2 was used. The method used to fit the linear regression line was ordinary least squares.

b. The range of 141 values in the correlation study was 0.8 - 974 ng/mL [µg/L].

c. The range of 46 values in the correlation study was 0.8 -17.1 ng/mL [ug/L].

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| Precision | | | |
|-------------------------------------------|---------------------|--------------------------|------------|
| Material | Mean<br>ng/mL[µg/L] | Standard Deviation (%CV) | |
| | | Repeatability | Within-Lab |
| Liquichek™<br>Immunoassay Plus<br>Control | | | |
| Level 1 | 2.1 | 0.1 (2.9) | 0.1 (3.4) |
| Level 2 | 26.2 | 0.6 (2.2) | 0.8 (2.9) |
| Serum pool 1 | 0.9 | 0.02 (2.3) | 0.02 (2.6) |
| Serum pool 2 | 12.8 | 0.3 (2.6) | 0.4 (3.1) |
| Serum pool 3 | 67.5 | 1.3 (1.9) | 1.6 (2.4) |
| Serum pool 4 | 478.0 | 6.2 (1.3) | 10.1 (2.1) |
| Serum pool 5 | 756.4 | 13.6 (1.8) | 24.9 (3.3) |
| Plasma pool | 239.7 | 5.2 (2.2) | 8.6 (3.6) |

CLSI/NCCLS EP5-A2 was used. During each day of testing, two separate runs, with two test samples, for each test material, were analyzed for 20 days.

### 8. Conclusion:

These studies demonstrate correlation and equivalent precision performance between the Beckman Access® CEA Reagents on the Access® Immunoassay System and the Dimension Vista® CEA assay.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three stripes extending from its back, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the perimeter of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# JUN 2 5 2008

Dade Behring, Inc. c/o Ms. Kathleen Dray-Lyons Manager, Regulatory Affairs and Compliance Glasgow Site P.O. Box 6101 Newark, DE 19714-6101

Re: k071603

Trade/Device Name: Dimension Vista® CEA Flex® reagent cartridge Dimension Vista® LOCI 5 Calibrator Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: DHX, JIX Dated: June 2, 2008 Reccived: June 3, 2008

Dear Ms. Dray-Lyons:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to

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Pagc 2 -

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation catitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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,

ia m chan

Maria M. Chan, Ph.D. Acting Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications For Use Statement

# 510(k) Number (if known):

Device Name:

Dimension Vista® CEA Flex® reagent cartridge

## Indications for Use:

The CEA method is an in vitro diagnostic test for the quantitative measurement of carcinoembryonic antigen in human serum and sodium or lithium heparin plasma on the Dimension Vista® System. Measurements of carcinoembryonic antigen are used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.

Prescription Use (Per 21 CFR 801 Subpart D) AND/OR

Over-the-counter Use (21 CFR 801 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)

Maria M Chan
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K07160

000012

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# Indications For Use Statement

Device Name:

K071603

Dimension Vista® LOCI 5 Calibrator

Indications for Use:

For the calibration of the Carcinoembryonic Antigen (CEA) method on the Dimension Vista® System.

Prescription Use (Per 21 CFR 801 Subpart D) AND/OR

Over-the-counter Use (21 CFR 801 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)

Mana M Chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)_Ko71603

000046