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 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). 2. The VITROS ECi Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. 3. Common reagents used by the VITROS System in each assay.

AI/ML Overview

Acceptance Criteria and Device Performance for VITROS® Immunodiagnostic Products CEA Assay

This report describes the acceptance criteria and the study that demonstrates the VITROS® Immunodiagnostic Products CEA assay meets those criteria.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the VITROS® Immunodiagnostic Products CEA assay are primarily based on demonstrating substantial equivalence to a legally marketed predicate device, the Abbott AxSYM CEA Assay. This equivalence is established through various analytical characteristic comparisons and clinical performance evaluations.

Acceptance Criterion	Reported Device Performance
Substantial Equivalence (Overall)	The VITROS CEA assay performs substantially equivalent to the approved predicate device (Abbott AxSYM CEA Assay). Equivalence was demonstrated using commercially available reagents and patient specimens.
Correlation with Predicate Device	VITROS CEA assay = 1.06 x [Abbott AxSYM CEA assay] + 0.124 (ng/mL) with a correlation coefficient of 0.977.
Analytical Sensitivity	0.3 ng/mL (Predicate device: 0.5 ng/mL). The VITROS CEA assay demonstrates slightly better analytical sensitivity.
Calibration Range (Reportable Range)	0 - 400 ng/mL (Predicate device: 0.5 - 500 ng/mL). This range is comparable.
Clinical Performance (Patient Distributions)	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. This indicates appropriate clinical utility across different patient populations.
Serial Monitoring Study	The serial monitoring study demonstrated that the VITROS CEA assay is substantially equivalent to the predicate device in patients previously treated for colorectal cancer. This confirms its utility for monitoring disease progression/recurrence.
Other Analytical Characteristics	Tests were performed to obtain specificity, precision, and dilution validation results. (Specific numerical details for these are not provided in the summary but are referenced to the package insert). These characteristics are implicitly accepted as meeting a standard comparable to or better than the predicate device for substantial equivalence.
Intended Use	The device demonstrated performance suitable for its intended use: quantitative measurement of 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. The performed studies align with this intended use (e.g., studies in cancer patients, serial monitoring).

2. Sample Size and Data Provenance

Test Set Sample Size: The document does not explicitly state the exact sample size for the test set used in the correlation and clinical performance studies. It mentions "samples from a variety of clinical categories" and "patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation."
Data Provenance: The document does not specify the country of origin of the data. It indicates that the studies involved "patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation" and "patients previously treated for colorectal cancer," suggesting retrospective or prospective clinical samples were used, likely drawn from a clinical laboratory or hospital setting.

3. Number of Experts and Qualifications for Ground Truth

This device is an in vitro diagnostic assay that provides quantitative numerical results (CEA concentration). The "ground truth" for such devices is typically established by comparing the device's output to a reference method or a legally marketed predicate device's output.
Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists interpreting images) is not directly applicable here. The "experts" would be the clinical laboratory professionals who performed the reference measurements and interpreted the data for analysis. Their qualifications would involve expertise in in vitro diagnostic testing and laboratory medicine. The document does not specify the number of such professionals.

4. Adjudication Method

Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretations (e.g., image reading).
For an in vitro diagnostic quantitative assay, adjudication is not usually performed in this manner. The comparison is between the numerical output of the new device and the numerical output of the predicate device/reference method. Any discrepancies would be analyzed statistically, not through panel review.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not performed. This type of study is relevant for diagnostic devices where human readers interpret outputs (e.g., medical images) and the AI aims to improve their performance.
This device is an automated in vitro diagnostic test that provides a direct numerical result, not an interpretation for human readers to act upon or be "assisted" by.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire submission details the performance of the VITROS CEA assay as a standalone algorithm/device in generating quantitative CEA measurements.
The comparison studies directly pitted the VITROS CEA assay against the predicate device to establish its direct performance, not its performance in assisting a human. The correlation coefficient, analytical sensitivity, and clinical distribution data all represent the standalone performance of the VITROS CEA assay.

7. Type of Ground Truth Used

The primary ground truth used for performance evaluation was:

Predicate Device Measurements: The results obtained from the Abbott AxSYM CEA Assay (P830066) served as the direct comparator and primary "ground truth" for demonstrating substantial equivalence.
Expected Clinical Distributions: For the clinical performance, the "expected distributions" for CEA levels in apparently healthy individuals, patients with malignant disease, and patients with non-malignant diseases served as the ground truth. This is based on established medical knowledge and clinical guidelines for CEA interpretation.

8. Sample Size for the Training Set

This document describes a 510(k) premarket notification for a traditional in vitro diagnostic assay, not a machine learning or AI-based device that typically requires a large "training set" for model development.
Therefore, the concept of a separate "training set" with a distinct sample size for algorithm development is not applicable in the context of this device. The development and validation of such assays involve rigorous analytical studies (precision, linearity, interference, etc.) using various characterized samples and clinical studies for performance comparison against established methods.

9. How the Ground Truth for the Training Set Was Established

As concluded in point 8, the concept of a "training set" for an AI algorithm is not applicable here.
The "ground truth" or reference values for the development and testing of this type of in vitro diagnostic assay are established through reference methods, certified reference materials, and established clinical measurements from predicate devices or other validated assays. These are subject to strict quality control and laboratory standards.

Summary

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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 (716) 453-3790

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 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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1. 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).
1. 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

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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DeviceCharacteristic	VITROS CEA assay	PredicateDevice
Calibration range(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-CEA in biotinylatedantibody reagent2) mouse monoclonal anti-CEA in conjugate reagent	1) mouse monoclonal anti-CEA coated Microparticles2) mouse monoclonal anti-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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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 (770) 488-7655.

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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or (301) 443-6597, 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

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

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)

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

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
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.(b)
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.