(111 days)
The Access® CEA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic antigen (CEA) in human serum using the ACCESS Immunoassay System. CEA measured by the Access CEA Immunoassay, is used as an aid in the management of cancer patients.
The ACCESS CEA Immunoassay Reagents and the ACCESS Immunoassay Analyzer comprise the ACCESS Immunoassay System for the quantitative determination of CEA in human serum.
The provided text describes a 510(k) submission for the ACCESS® CEA Assay, a device intended for the quantitative determination of carcinoembryonic antigen (CEA) in human serum to aid in the management of cancer patients. The submission focuses on demonstrating substantial equivalence to a predicate device, the Abbott IMx CEA Microparticle Enzyme Immunoassay.
Here's an analysis based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for the ACCESS CEA Immunoassay in numerical thresholds. Instead, it presents summaries of studies demonstrating its performance in comparison to the predicate device and in various analytical tests. The underlying acceptance logic for substantial equivalence would be that the performance of the new device is comparable to or better than the predicate.
| Performance Characteristic | Acceptance Criteria (Implied by Comparison/Analytical Limits) | Reported Device Performance |
|---|---|---|
| Correlation with Predicate Device (Abbott IMx CEA) | Strong correlation (e.g., r > 0.95 and slope ~1, intercept ~0) | 146 samples (0-1000 ng/ml). r = 0.97; y = 1.02x + 1.76. |
| Expected Range (Healthy Population) | Low CEA values for apparently healthy individuals. | 98.7% of 234 healthy individuals had CEA ≤ 5.0 ng/ml; 1.3% had 5.1-10.0 ng/ml. |
| Monitoring Data (Longitudinal Samples) | High concordance with predicate device and clinical assessments for monitoring cancer patients. | ACCESS CEA results were "highly concordant to both the IMx CEA results and the concurrent clinical assessments." |
| Recovery (Linearity) | Average recovery close to 100%, within an acceptable range (e.g., 90-110%). | Average recovery of 99.9% (range 91.1-109.1%) for diluted samples. Average recovery of 103.0% (range 99.0-106.2%) for spiked samples. |
| Precision (Imprecision) | Imprecision (CV) generally low, usually <10% or <5% for critical ranges. | Within-run, between-run, and total imprecision were less than 5% at concentrations between 5.0 and 500 ng/ml. |
| Specificity (Interference) | No significant interference from CEA-like antigens, potential sample contaminants, or therapeutic agents. | No significant interference observed from NCA, NCA-2, NCA-50, NFA-1, albumin, bilirubin, HAMA, hemoglobin, lipemia, rheumatoid factor, or a list of therapeutic agents. |
| Hook Effect | No hook effect observed at high concentrations. | No hook effect observed at CEA concentrations up to 100,000 ng/ml. |
| Analytical Sensitivity (LOD) | Low limit of detection, distinguishable from zero with high confidence. | 0.1 ng/ml (distinguishable from zero with 95% confidence). |
2. Sample Size Used for the Test Set and Data Providence
- Correlation: 146 samples, ranging from 0 to 1000 ng/ml.
- Expected Range: 234 apparently healthy males and females.
- Monitoring Data: "Longitudinal serum samples from previously diagnosed cancer patients." The exact number of patients or samples is not specified.
- Recovery, Precision, Specificity, Hook Effect, Analytical Sensitivity: Specific sample sizes for these analytical studies are not detailed beyond "human serum samples" or "spiked into serum samples."
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be quantitative laboratory analyses of human serum samples. The context of a US 510(k) submission generally implies that at least some data would be relevant to the US population, but this is not guaranteed for all sample types. The data is retrospective in the sense that the samples were analyzed after collection, but the studies themselves were conducted prospectively to evaluate the device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Ground Truth for Correlation, Recovery, Precision, Hook Effect, Analytical Sensitivity: The "ground truth" for these analytical studies is based on the quantitative measurements derived from the reference methods or the expected values of spiked/diluted samples. No human experts are explicitly mentioned for establishing ground truth in these specific analytical performance tests for the test set.
- Ground Truth for Monitoring Data: The "monitoring data" relies on "concurrent clinical assessments." This implies that clinicians or medical professionals were involved in evaluating the patient's condition over time. The number and qualifications of these experts are not explicitly stated, but they would typically include oncologists or other physicians managing cancer patients.
- Ground Truth for Expected Range: This involves classifying individuals as "apparently healthy." This classification is typically done by medical professionals, but details about the number and qualifications are not provided.
4. Adjudication Method for the Test Set
- The document does not describe a formal "adjudication method" in the context of multiple human readers or reviewers for the quantitative analytical studies (correlation, precision, etc.). These are objective quantitative measurements.
- For the "monitoring data" and "clinical assessments," while multiple clinicians might be involved in patient management, a specific adjudication process (like 2+1 or 3+1 consensus) for establishing a definitive ground truth across different clinicians is not described in the summary.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. This type of study typically involves human readers interpreting cases (e.g., medical images) with and without AI assistance to measure reader performance improvement. The ACCESS CEA Immunoassay is a diagnostic assay measuring a biomarker, not an imaging interpretation device. The "monitoring data" involved comparing the assay results with clinical assessments, which is a form of clinical utility assessment, but not an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are primarily standalone performance assessments of the ACCESS CEA Immunoassay. The device itself is an automated immunoassay system (ACCESS Immunoassay Analyzer and ACCESS CEA Immunoassay Reagents). The results it produces (CEA values) are quantitative outputs. The comparisons to the predicate device and the analytical performance tests (precision, recovery, specificity, etc.) evaluate the device's performance inherently in a standalone manner, without human intervention in the generation of the CEA value. While clinicians use these results, the performance evaluation in this 510(k) focuses on the analytical accuracy and reliability of the device's output.
7. The Type of Ground Truth Used
- Correlation: The ground truth is the measurement obtained from the predicate device, the Abbott IMx CEA Immunoassay.
- Expected Range: The ground truth is established by clinical assessment identifying "apparently healthy" individuals, and the measured CEA values in that population.
- Monitoring Data: The ground truth is "concurrent clinical assessments" of cancer patients, implying a physician's overall evaluation of the patient's condition and disease progression.
- Recovery: The ground truth is the known concentration of CEA in diluted or spiked samples.
- Precision, Specificity, Hook Effect, Analytical Sensitivity: The ground truth largely relies on the inherent properties of the samples (e.g., known concentrations, presence/absence of interferents) and accepted laboratory standards for analytical performance.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of developing a machine learning algorithm. This device is an immunoassay, which functions based on chemical and immunological reactions, not a machine learning model that requires a discrete training phase. Therefore, the concept of a training set as understood in AI/ML is not applicable here. The development and validation of the assay would have involved various internal optimization and verification studies, but these would not typically be called a "training set" in this context.
9. How the Ground Truth for the Training Set Was Established
As explained above, the concept of a "training set" for an immunoassay device is not applicable in the same way it is for an AI/ML device. The ground truth for developing and optimizing such an assay would involve using characterized samples with known CEA concentrations, spiked samples, and samples from well-defined patient populations, as well as adherence to established analytical chemistry and immunology principles.
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K 981985
510(k) Summary of Safety and Effectiveness
1. General Information
Device Generic Name:
Device Trade Name:
Applicant's Name and Address:
Carcinoembryonic Antigen (CEA) Immunological Test System for Management of Cancers
ACCESS® CEA Assay
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
Date:
June 4, 1998
2. Predicate Device
Abbott IMx CEA Microparticle Enzyme Immunoassay Abbott Laboratories One Abbott Park Road Abbott Park, IL 60064-3500
PMA Number: P830066
3. Device Description
The ACCESS CEA Immunoassay Reagents and the ACCESS Immunoassay Analyzer comprise the ACCESS Immunoassay System for the quantitative determination of CEA in human serum.
4. Indications for Use
The ACCESS CEA Immunoassay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of carcinoembryonic antigen (CEA) in human serum using the ACCESS Immunoassay System. CEA, measured by the ACCESS CEA Immunoassay, is intended for use as an aid in the management of cancer patients.
5. Comparison of Technological Characteristics
Both the ACCESS CEA Immunoassay and the Abbott IMx CEA assay quantitatively measure serum CEA by means of simultaneous immunoassays utilizing the binding of CEA to monoclonal antibodies specific to epitopes on the CEA molecule. Both systems utilize liquid multi-point calibrators.
The ACCESS CEA Immunoassay Reagents are designed for use on the ACCESS Immunoassay Analyzer, a fully automated random access system, with up to 24 different reagents on board. The Abbott IMx Immunoanalyzer is an automated batch mode system in which a single analyte is assaved at one time. The ACCESS Immunoassay Analyzer uses magnetic particle solid phase enzyme immunoassays with chemiluminescent measurement, while the Abbott IMx CEA Immunoassay uses a glass-fiber matrix as the solid phase with a fluorescent detection method.
6. Summary of Studies
Correlation: A comparison of CEA values from 146 samples, ranging from 0 to 1000 ng/ml, run with both the ACCESS CEA Immunoassay and the Abbott IMx CEA Immunoassay demonstrated very good agreement with the following statistical data: r = 0.97; y = 1.02x + 1.76.
Expected Range: In a population of 234 apparently healthy males and females, 98.7% had CEA values of 5.0 ng/ml or less, with the remaining 1.3% having values in the 5.1 to 10.0 nq/ml range.
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Monitoring Data: Longitudinal serum samples from previously diagnosed cancer patients were compared using the ACCESS CEA and IMx CEA assays. The monitoring patient data demonstrate that the Access CEA results are highly concordant to both the IMx CEA results and the concurrent clinical assessments.
Recovery: Linearity studies performed by diluting human serum samples with ACCESS CEA Sample Diluent provided an average recovery of 99.9%, with sample mean recoveries ranging from 91.1 to 109.1%. Recovery of exogenous CEA spiked into serum samples resulted in an overall mean recovery of 103.0%, with mean recoveries ranging from 99.0 to 106.2%.
Precision: Within-run, between-run and total imprecision of the Access CEA immunoassay were less than 5% when tested at concentrations between 5.0 and 500 ng/ml.
Specificity: There was no significant interference from CEA-like antigens (NCA, NCA-2. NCA-50 and NFA-1), potential sample contaminants (albumin, bilirubin, HAMA, hemoglobin, lipemia and rheumatoid factor), and therapeutic agents (bleomycin-, cisplatin, cyclophosphamide, doxorubicin, fluorouracil, leucovorin, methotrexate, mitomycin, tamoxifen, vinblastine, and vincristine).
Hook Effect: There was no hook effect observed at CEA concentrations up to 100,000 ng/ml.
Analytical Sensitivity: The lowest level of detection of CEA distinguishable from zero (ACCESS CEA Calibrator S0) with 95% confidence is 0.1 ng/ml.
7. Conclusion
The ACCESS CEA Immunoassay Reagents, when used in conjunction with the ACCESS Immunoassay Analyzer, are substantially equivalent to the Abbott IMx CEA Immunoassay. The ACCESS CEA Immunoassay is appropriate for monitoring patients with cancer.
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SEP 2 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Ellen Voss Regulatory Affairs Beckman Coulter 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084
Re: K981985/S1 Trade Name: ACCESS® CEA Assay Regulatory Class: II Product Code: DHX Dated: July 31, 1998 Received: July 31, 1998
Dear Ms. Voss : .......
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 reqistration, listing of devices, good manufacturing practice, labeling, and prohibitions aqainst misbranding and adulteration.
the country of the same
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 Requlations, 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 themact = " for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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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 leqally 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 "ram address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Gutman
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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Page _________________________________________________________________________________________________________________________________________________________________________ 1 of of 1
510(k) Number (if known):
Device Name: ACCESS® CEA
Indications For Use:
The Access® CEA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic antigen (CEA) in human serum using the ACCESS Immunoassay System. CEA measured by the Access CEA Immunoassay, is used as an aid in the management of cancer patients.
(PLEASE DO NOT WRITE BELOW THIS LINE--CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Peter E. Malm
(Division Sign Division of Clinical Laboratory De 510(k) Number
Prescription Use (Per 21 CFR 801.109)
OR
Over-The Counter Use _________________________________________________________________________________________________________________________________________________________
(Optional Format 1-2-96)
§ 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.