The Access CEA assay is a paramagnetic particle, chemiluminescent immunossay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay System. CEA measured by the Access Immunoassay System is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.

Device Description

The Access® CEA reagents consist of reagent packs, calibrators, bi-level controls, substrate, and wash buffer.

. The Access® CEA reagent packs consist of paramagnetic particles coated with monoclonal (mouse) anti-human CEA antibodies in Tris buffered saline, sample diluent, monoclonal anti-human CEA-alkaline phosphatase conjugate in phosphate buffered saline, bovine serum albumin (BSA) and preservatives.
. The Access® CEA calibrators consist of multi-point calibrators for use with the Access CEA assay. The calibrator vials contain zero and approximately 1, 10, 100, 500, and 1000 ng/ml purified CEA, respectively, in a phosphate buffered BSA matrix with preservatives.
. The Access® CEA QC controls consist of approximately 3 ng/ml and 300 ng/ml of human CEA in a phosphate buffered BSA matrix with preservatives.
. The Access® substrate, Lumi-Phos* 530, is a dioxetane-based chemiluminescent substrate.
. The Access® wash buffer consists of Tris buffered saline containing surfactant and preservatives.

AI/ML Overview

The provided text describes the Access® CEA Assay, a two-site immunoenzymatic "sandwich" assay, and its modification for improved correlation around a critical decision point of 5.0 ng/ml. However, the document does not contain specific acceptance criteria or a detailed study proving the device meets those criteria, as typically found in clinical validation reports.

The provided text focuses on the device description, principles of the procedure, indications for use, and a modification to the calibrator mass to improve correlation with an existing device. It also includes an FDA 510(k) clearance letter.

Therefore, many of the requested details cannot be extracted from the given information.

Here's a breakdown of what can and cannot be answered:

1. A table of acceptance criteria and the reported device performance

Cannot be provided. The document does not specify quantitative acceptance criteria (e.g., sensitivity, specificity, accuracy thresholds) or present a table of reported device performance metrics against such criteria.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

Cannot be provided. The document states that "Insert changes have been made to reflect results from completed validation studies," but it does not detail these validation studies, including sample size, data provenance, or study design.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

Not applicable. This device is an in-vitro diagnostic (IVD) immunoassay measuring a biomarker (CEA). Ground truth for such devices is typically established through reference methods or clinical outcomes, not expert consensus on images or interpretations. The document does not describe how ground truth was established for any validation.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable/Cannot be provided. Adjudication methods are typically used in studies involving human interpretation (e.g., imaging studies) where expert consensus resolves discrepancies. This is an immunoassay, not an interpretation-based device. No information on any "test set" and its adjudication is available.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an automated immunoassay device, not an AI-assisted diagnostic tool requiring human readers. Therefore, an MRMC study and effects on human reader performance are not relevant to this device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, implicitly. As an automated immunoassay, the device performs "standalone" by producing a quantitative result. The study of its performance (which is alluded to as "validation studies" but not detailed) would inherently be a standalone study of the algorithm/assay's ability to measure CEA.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

Implicitly, reference methods or clinical diagnosis related to cancer management. For an immunoassay like CEA, ground truth would typically be established by using a reference method for CEA measurement, or by correlating CEA levels with clinical diagnosis, disease progression, or treatment response in cancer patients, as it's used as "an aid in the management of cancer patients." However, the specific method is not detailed in the provided text.

8. The sample size for the training set

Cannot be provided. This document describes a modification to an existing device (re-calibration) and refers to "validation studies" for this modification. It does not mention a "training set" in the context of device development or machine learning, which is not applicable to a traditional immunoassay.

9. How the ground truth for the training set was established

Cannot be provided. As a training set is not mentioned and is not typically relevant for this type of device, this question cannot be answered.

Summary based on available information:

Information Type	Details
1. Acceptance Criteria & Reported Performance	Cannot be provided. Document does not specify quantitative acceptance criteria or present performance data against them. It only mentions calibration improvement around 5.0 ng/ml for better correlation with another device.
2. Test Set Sample Size & Data Provenance	Cannot be provided. "Validation studies" are mentioned, but their details (sample size, retrospective/prospective, country of origin) are absent.
3. Number & Qualifications of Experts for Ground Truth (Test Set)	Not applicable. This is an immunoassay, not an interpretation-based device. Ground truth is typically clinical or by reference methods, not expert consensus on interpretations.
4. Adjudication Method (Test Set)	Not applicable. No details provided, as adjudication is typically for subjective interpretations, not automated quantitative measurements from an immunoassay.
5. MRMC Comparative Effectiveness Study (AI vs. without AI)	Not applicable. This is an automated immunoassay, not an AI-assisted diagnostic tool involving human readers.
6. Standalone Performance Study (Algorithm Only)	Implicitly Yes. As an automated immunoassay, any performance study would inherently be a standalone evaluation of the device's measurement capabilities. The document alludes to "validation studies."
7. Type of Ground Truth Used	Implicitly by reference methods or clinical outcomes. For CEA, ground truth is typically established by comparing results to reference CEA assays or correlating with patient clinical status, disease progression, or treatment response consistent with its "aid in the management of cancer patients" indication. Specifics are not provided.
8. Training Set Sample Size	Cannot be provided. No mention of a "training set" as this is a traditional immunoassay, not a machine learning model. The modification involved re-calibration based on existing data, not training an AI model.
9. Ground Truth Establishment for Training Set	Cannot be provided. As a training set is not described, the method for establishing its ground truth is also not mentioned. The re-calibration was explicitly to "improve correlation with another commercially available device," suggesting cross-validation against an established product rather than creation of a de novo training set with new ground truth.

Summary

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Access®CEA Assay

Section 1 D: SUMMARY OF SAFETY AND EFFECTIVENESS FOR THE ACCESS® CEA ASSAY

General Information 1.0

Device Generic Name:	Carcinoembryonic Antigen (CEA) ImmunologicalTest System for Management of Cancers
Device Trade Name:	Access® CEA Reagents for use on theAccess® Immunoassay Analyzer
Device Class:	Class II
Applicant's Name and Address:	Beckman Coulter, Inc.Immunodiagnostics Development Center1000 Lake Hazeltine DriveChaska, MN 55318
Date:	May 18, 1999

Date:

2.0

Legally Marketed Device

The Modified Access® CEA Immunoassay claims substantial equivalence to the Access® CEA Immunoassay currently in commercial distribution.

FDA 510(k) Number K981985

3.0 Device Description

The Access® CEA reagents consist of reagent packs, calibrators, bi-level controls, substrate, and wash buffer.

. The Access® CEA reagent packs consist of paramagnetic particles coated with monoclonal (mouse) anti-human CEA antibodies in Tris buffered saline, sample diluent, monoclonal anti-human CEA-alkaline phosphatase conjugate in phosphate buffered saline, bovine serum albumin (BSA) and preservatives.
. The Access® CEA calibrators consist of multi-point calibrators for use with the Access CEA assay. The calibrator vials contain zero and approximately 1, 10, 100, 500, and 1000 ng/ml purified CEA, respectively, in a phosphate buffered BSA matrix with preservatives.
. The Access® CEA QC controls consist of approximately 3 ng/ml and 300 ng/ml of human CEA in a phosphate buffered BSA matrix with preservatives.
. The Access® substrate, Lumi-Phos* 530, is a dioxetane-based chemiluminescent substrate.
. The Access® wash buffer consists of Tris buffered saline containing surfactant and preservatives.

Page 9

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4.0 Principles of the Procedure

The Access® CEA assay is a two-site immunoenzymatic "sandwich" assay using two mouse monoclonal anti-CEA antibodies (MAb) which react with different epitopes of CEA. A sample is added to a reaction vessel, along with the first anti-CEA MAb-alkallne phosphatase conjugate and the second anti-CEA MAb bound to paramagnetic particles. The incubation is followed by a magnetic separation and washing. A chemiluminescent substrate, Lumi-Phos* 530, is added to the reaction vessel and light generated by the reaction is measured with a luminometer. The light production is proportional to the concentration of CEA in the sample. The amount of analyte in the sample is determined by means of a stored, multi-point calibrator curve.

Indications for Use 5.0

The Access CEA assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay System. CEA measured by the Access Immunoassay System is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.

Description of the Modification to the Legally Marketed Device 6.0

The Access CEA assay has been re-calibrated in order to improve correlation with another commercially available device around the critical decision point of 5.0 ng/ml. There has been no change to the formulation or function of the product. The design change involves a reduction in calibrator mass with no change in labeled calibrator values. Insert changes have been made to reflect results from completed validation studies.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

DEPARTMENT OF HEALTH & HUMAN SERVICES USA

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Angela Byland Requlatory Specialist BECKMAN COULTER, INC. 1000 Lake Hazeltine Drive Chaska, MN 55318

Re: K991707 Trade Name: Access® CEA Reagents for use on the Access® Immunoassay Analyzer Regulatory Class: II Product Code: DHX May 18, 1999 Dated: May 19, 1999 Received:

Dear Ms. Byland:

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 (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 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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Beckman Coulter, Inc.

Special 510(k): Device Modification Confidential

Section 1 C:

INDICATIONS FOR USE STATEMENT

Page 1 of 1

510(k) Number: K984885 K991707

Dovice Name: Access® CEA Reagents for use on the Access® Immunoassay Analyzer

Indications for Use:

The Access CEA assay is a paramagnetic particle, chemiluminescent immunossay for the The Access CEA assay is a paramagnetic particle (CEA) levels in human setem, using the super les and quantitative determination of Cardidentifyone Antigen Cerca in Naman Sales (1 and 18 and Access Immunoassay System. CEA measured by the Acouse Minores of Submitten observed.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Peter E. Mahar

(Divisior: S. Divisidi 510(x) Number

Prescription Use
(Per 21 CFR 801.109)

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Over-The Counter Use_

(Optional Format 1-2-96)

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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.