(76 days)
For in vitro diagnostic use in the quantitative measurement of carcinoembryonic antigen (CEA) in serum and plasma (EDTA and lithium heparin) to aid in the management of cancer patients in whom changing concentrations of CEA are observed using the ADVIA Centaur® XP and ADVIA Centaur® XPT systems.
The assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur CEA Lite Reagent and Solid Phase ADVIA Centaur CEA Master Curve card (500 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur CEA Lite Reagent and Solid Phase ADVIA Centaur CEA Master Curve card (100 Tests)
The ReadyPack consists of the following:
ADVIA Centaur® CEA ReadyPack® primary reagent pack; Lite Reagent: 5.0 mL/reagent pack polyclonal rabbit anti-CEA antibody (~400 ng/mL) labeled with acridinium ester in phosphate buffered saline with protein stabilizers, sodium azide (0.12%), and preservatives
ADVIA Centaur® CEA ReadyPack® primary reagent pack; Solid Phase Reagent: 25.0 mL/reagent pack monoclonal mouse anti-CEA antibody (~120 µg/mL) covalently coupled to paramagnetic particles in phosphate buffered saline with protein stabilizers, sodium azide (0.11%), and preservatives
ADVIA Centaur® CEA ReadyPack® ancillary reagent pack; CEA Diluent: 5.0 mL/reagent pack bicine buffer, gelatin, and BSA with preservatives and sodium azide (0.1%)
ADVIA Centaur® CEA Diluent: 10.0 mL/reagent vial bicine buffer, gelatin, and BSA with preservatives and sodium azide (0.1%)
This document describes the acceptance criteria and the study proving that the ADVIA Centaur® CEA assay meets these criteria, specifically for the addition of plasma (EDTA and lithium heparin) sample claims.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the reported performance characteristics, especially for specimen equivalence and interference, as the submission focuses on demonstrating equivalence to a previously cleared device.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance (Candidate Device) |
|---|---|---|
| Detection Capability | LoB: 0.50 ng/mL (µg/L) | |
| LoD: 1.00 ng/mL (µg/L) | ||
| LoQ: 2.00 ng/mL (µg/L) | ||
| Accuracy / Method Comparison | Correlation (r) close to 1.00; Slope (ADVIA Centaur CEA vs ACS:180 CEA) close to 1.00; Intercept close to 0.00 | Correlation (r) = 1.00; Slope = 0.97; Intercept = 0.11 ng/mL |
| Specimen Equivalence | Slope (alternate tube types vs serum) = 0.90–1.10 | Dipotassium EDTA plasma vs Serum: |
| Slope = 0.95, Intercept = 0.20 ng/mL (µg/L), r = 1.00 | ||
| Lithium Heparin plasma vs Serum: | ||
| Slope = 0.99, Intercept = 0.19 ng/mL (µg/L), r = 1.00 | ||
| Interferences | Bias due to interferents within acceptable limits (not explicitly stated, but implied by data presentation) | Dipotassium EDTA (9.0 mg/mL): |
| 5.78 ng/mL: -0.3% Bias | ||
| 55.62 ng/mL: 4.6% Bias | ||
| Heparin (75 U/mL): | ||
| 5.83 ng/mL: -0.6% Bias | ||
| 61.23 ng/mL: 0.9% Bias |
2. Sample Sizes Used for the Test Set and Data Provenance
- Accuracy/Method Comparison: 201 samples (range of 2.00 to 78.93 ng/mL).
- Specimen Equivalence:
- Dipotassium EDTA plasma vs. Serum: 64 samples (range of 2.08-97.10 ng/mL).
- Lithium Heparin plasma vs. Serum: 46 samples (range of 2.11-97.10 ng/mL).
- Interferences: Analyte concentrations were tested at 5-6 ng/mL and 55-61 ng/mL for each interferent (Dipotassium EDTA and Heparin). The exact number of samples per concentration is not specified, but it implies a controlled experimental setup.
The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective. However, given the context of a 510(k) submission for a diagnostic device, the data would typically be derived from controlled, prospective studies conducted in a clinical or laboratory setting.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable. The device measures a quantitative analyte (CEA) in blood samples. The "ground truth" for the test set is established by the reference method (ACS:180 CEA assay for accuracy/method comparison, or the serum sample itself for specimen equivalence) and the intrinsic concentration of the analyte, rather than expert consensus on interpretive tasks.
4. Adjudication Method (for the test set)
Not applicable, as the "ground truth" is based on quantitative measurements by a reference method or direct comparison, not subjective interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was done. This type of study is typical for imaging or interpretive AI devices comparing human performance with and without AI assistance. The ADVIA Centaur® CEA assay is an in vitro diagnostic device for quantitative chemical measurement, not an AI-powered interpretive tool.
6. Standalone Performance
Yes, a standalone performance study was done. The document reports the detection capability (LoB, LoD, LoQ), method comparison, specimen equivalence, and interference studies of the ADVIA Centaur® CEA assay as a standalone device. These studies evaluate the assay's characteristics directly without a human-in-the-loop component for interpretation.
7. Type of Ground Truth Used
- Accuracy/Method Comparison: The ground truth was established by comparison to a legally marketed predicate device, the ACS:180 CEA assay. This essentially uses the measurements from an established, accepted method as the reference.
- Specimen Equivalence: The ground truth was the CEA concentration measured in serum samples, against which plasma samples (EDTA and lithium heparin) were compared.
- Detection Capability and Interferences: The ground truth for these studies would be based on known concentrations of CEA and interferents in control samples, which are objectively measurable.
8. Sample Size for the Training Set
No information is provided regarding a separate "training set" for the assay itself. For in vitro diagnostic devices like this, the development process involves extensive calibration, reagent optimization, and verification using various samples, but these are generally considered part of development and verification, not a distinct "training set" in the machine learning sense. The clinical studies described (method comparison, specimen equivalence) serve as external validation of the device's performance.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no explicitly defined "training set" in the context of machine learning for this in vitro diagnostic assay. The device's performance is driven by the biochemical interactions of the reagents, not by a learned model from a training set. The calibration and standardization of the assay are traceable to an internal standard manufactured using highly purified material, as stated in the "Standardization" section of Table 1.
§ 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.