VITROS IMMUNODIAGNOSTIC PRODUCTS CEA CALIBRATORS, VITROS IMMUNODIAGNOSTIC PRODUCTS CEA REAGENT PACK

K990943 · Ortho-Clinical Diagnostics, Inc. · DHX · Jun 1, 1999 · Immunology

Device Facts

• Record ID: K990943
• Device Name: VITROS IMMUNODIAGNOSTIC PRODUCTS CEA CALIBRATORS, VITROS IMMUNODIAGNOSTIC PRODUCTS CEA REAGENT PACK
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: DHX · Immunology
• Decision Date: Jun 1, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

The Vitros® CEA is an in vitro assay intended for the quantitative measurement of carcinoembyronic antigen (CEA) in human serum and plasma (EDTA or heparin) to aid in the prognosis and management of cancer patients in whom changing concentrations of CEA are observed.

Device Story

The VITROS CEA assay is an in vitro diagnostic test for the quantitative measurement of carcinoembryonic antigen (CEA) in human serum or plasma. The device utilizes the VITROS ECi Immunodiagnostic System, which employs a solid-phase immunoassay principle using coated microwells. The system automates the immunoassay process, using luminescence as the signal for detection. The device requires 20 µL of patient sample. It is intended for use by clinical laboratory professionals to assist in the prognosis and management of cancer patients by monitoring CEA levels over time. The system provides quantitative results that help healthcare providers assess disease progression or response to therapy.

Clinical Evidence

Clinical evidence includes comparative studies against the predicate device using patient specimens from healthy individuals, patients with malignant disease, and patients with non-malignant diseases. A serial monitoring study was conducted in patients previously treated for colorectal cancer. Correlation between the VITROS CEA assay and the predicate device was established using Passing and Bablok regression (r=0.977). Analytical performance metrics including analytical sensitivity (0.3 ng/mL), precision, and dilution linearity were evaluated.

Technological Characteristics

Solid-phase immunoassay using coated microwells. Employs mouse monoclonal anti-CEA antibodies in biotinylated and conjugate reagents. Detection via luminescence on the VITROS ECi Immunodiagnostic System. Sample volume: 20 µL. Reportable range: 0-400 ng/mL. Analytical sensitivity: 0.3 ng/mL. System is automated and uses common reagents (Signal Reagent, Universal Wash Reagent).

Indications for Use

Indicated for the quantitative measurement of carcinoembryonic antigen (CEA) in human serum and plasma (EDTA or heparin) to aid in the prognosis and management of cancer patients experiencing changing CEA concentrations.

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

• Abbott AxSYM CEA Assay (P830066)

Reference Devices

• VITROS Immunodiagnostic Products Total T3 (K964310)
• VITROS ECi Immunodiagnostic System (K962919)

Submission Summary (Full Text)

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#### ADMINISTRATIVE 1

#### 510(k) Summary 1.1

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: 1990943

# 1. Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 [phone]

Contact Person: Anne Zavertnik

Date 510(k) prepared: March 19, 1999

### 2. Device Name

Trade or Proprietary Name: VITROS® Immunodiagnostic Products CEA Calibrators

VITROS® Immunodiagnostic Products CEA Reagent Pack

#### Common Name: CEA assay

Classification Name: test for the in vitro quantitative determination of carcinoembyronic antigen in serum or plasma.

### 3. Predicate Device

The VITROS Immunodiagnostic Products CEA assay is substantially equivalent to the Abbott AxSYM CEA Assay (P830066).

### 4. Device Description

The VITROS ECi Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma or urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

- 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products CEA Reagent Pack, VITROS Immunodiagnostic Products CEA Calibrators, which are combined by the VITROS ECi System to perform the VITROS CEA assay).

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- 2. The VITROS ECi Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS ECi System was cleared for market by a separate 510(k) pre-market notification (K962919).
- 3. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K964310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

### 5. Device Intended Use

The Vitros® CEA is an in vitro assay intended for the quantitative measurement of carcinoembyronic antigen (CEA) in human serum and plasma (EDTA or heparin) to aid in the prognosis and management of cancer patients in whom changing concentrations of CEA are observed.

#### 6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products CEA assay is substantially equivalent to Abbott AxSYM CEA Assay (predicate device), which was approved by FDA (P830066) for IVD use.

The relationship between the VITROS CEA assay and the predicate device, determined by Passing and Bablok, is:

VITROS CEA assay = 1.06 x [Abbott AxSYM CEA assay] + 0.124 (ng/mL), with a correlation coefficient of 0.977.

Comparisons of the VITROS CEA assay and the predicate device were performed with samples from a variety of clinical categories.

In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS CEA assay package insert for VITROS CEA assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS CEA assay with the predicate device:

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| Device<br>Characteristic | VITROS CEA assay | Predicate<br>Device |
|-----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------|
| Calibration range<br>(reportable range) | 0 - 400 ng/mL | 0.5 - 500ng/mL |
| Basic principle | Solid phase immunoassay | Solid phase immunoassay |
| Sample type | Serum, plasma (heparin or EDTA) | Serum, plasma (heparin or EDTA) |
| Antibody | 1) mouse monoclonal anti-<br>CEA in biotinylated<br>antibody reagent<br><br>2) mouse monoclonal anti-<br>CEA in conjugate reagent | 1) mouse monoclonal anti-<br>CEA coated Microparticles<br><br>2) mouse monoclonal anti-<br>CEA in conjugate reagent |
| Sample volume | 20 µL | 150 µL |
| Analytical sensitivity | 0.3 ng/mL | 0.5 ng/mL |

Table 1 List of the assay characteristics

### 7. Conclusions

The data presented in the premarket notification demonstrate that the VITROS CEA assay performs substantially equivalent to the approved predicate device.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation. In clinical studies of apparently healthy individuals, patients with malignant disease and patients with a variety of non-malignant diseases, the VITROS CEA assay exhibited distribution results that parallel expected distributions for these patient types.

The serial monitoring study demonstrated that the VITROS CEA assay is substantial equivalent to the predicate device in patients previously treated for colorectal cancer.

The data presented in the premarket notification provide a reasonable assurance that the VITROS CEA assay is safe and effective for the stated intended use.

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The logo is black and white.

DEPARTMENT OF HEALTH & HUMAN SERVICES

JUN 1 1099 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Anne Zavertnik Regulatory Affairs Associate ORTHO-CLINICAL DIAGNOSTICS, INC. 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: K990943 Trade Name: VITROS® Immunodiagnostic Products CEA Calibrators VITROS® Immunodiagnostic Products CEA Reagent Pack Regulatory Class: II Product Code: DHX Dated: March 19, 1999 March 22, 1999 Received:

Dear Ms. Zavertnik:

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 [phone].

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 vours.

Steven Sutman

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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# 1.2 Indications For Use Statement

## Page 1 of 1

510(k) Number (if known): K990943

Device Name: VITROS Immunodiagnostic Products CEA Reagent Pack
VITROS Immunodiagnostic Products CEA Calibrators

Indications for Use: The Vitros® CEA is an *in vitro* assay intended for the
quantitative measurement of carcinoembryonic antigen (CEA) in
human serum and plasma (EDTA or heparin) to aid in the
prognosis and management of cancer patients in whom changing

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concentrations of CEA are observed.

Concurrence of CDRH, Office of Device Evaluation (ODE)

| (Division Sign-Off) | |
|-----------------------------------------|---------|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K990943 |

| Prescription Use | |
|----------------------|--|
| (Per 21 CFR 801.109) | |

OR

| Over-The-Counter Use | |
|--------------------------|--|
| (Optional Format 1-2-96) | |