(58 days)
The ADVIA Centaur® BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum and plasma (EDTA) using the ADVIA Centaur XP, and ADVIA Centaur XPT systems. The test is intended for use as an aid in monitoring patients previously treated for Stage III breast cancer. Serial testing for CA 27.29 in the serum and plasma of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.
The ADVIA Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve with the reagent bar code. The ADVIA Centaur BR assay is intended for use on the ADVIA Centaur family of analyzers. The ADVIA Centaur Calibrator G is a set of 2 level calibrators for the assay. Siemens recommends the use of commercially available quality control materials with at least two levels (low and high).
The ADVIA Centaur BR reagent kit contains the following:
- ADVIA Centaur BR ReadyPack primary reagent pack contains Lite Reagent and Solid Phase ● Reagent.
- Materials Required but Not provided:
- ADVIA Centaur Calibrator G: consists of 2 levels (low and high) of CA 27.29 calibrators in equine serum with sodium azide (0.1%) and preservatives; lyophilized.
- ADVIA Centaur BR Pretreatment Reagent: consists of sodium hydroxide (0.24 N) Optional Reagents:
- ADVIA Centaur Multi-Diluent 1: consists of equine serum with sodium azide (0.1%) and preservatives.
- . ADVIA Centaur BR Master Curve Material: consists of a set of 7 levels of CA 27.29 (MCM1-7) spiked in lyophilized equine serum with sodium azide (0.1% after reconstitution) and preservatives.
The Siemens Healthcare Diagnostics Inc. ADVIA Centaur BR assay, with updated claims for plasma (EDTA) sample and detection capability (LoB, LoD, and LoQ), was determined to be substantially equivalent to the predicate device (K982680). The purpose of this submission was to add the plasma (EDTA) sample claim and update the detection capability claims.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Predicate) | Reported Device Performance (New Claims) |
|---|---|---|
| Detection Capability (LoB) | Analytical Sensitivity: 3.5 U/mL (Serum) | 3.5 U/mL (Serum and Plasma) |
| Detection Capability (LoD) | Not explicitly stated as LoD | 7.0 U/mL (Serum and Plasma) |
| Detection Capability (LoQ) | Not explicitly stated as LoQ | 9.0 U/mL (Serum and Plasma) |
| Assay Range (Serum) | 3.5 - 450 U/mL | 9.0 - 450 U/mL |
| Assay Range (Plasma) | Not applicable (Serum only) | 9.0 - 450 U/mL |
| Sample Type | Serum | Serum, Plasma (EDTA) |
| Measurement | Quantitative | Quantitative |
| Operating Principle | Competitive immunoassay | Competitive immunoassay |
| Technology | Direct chemiluminescent | Direct chemiluminescent |
| Sample Volume | 20 µL (serum) | 20 µL (serum and plasma) |
| Traceability/Standardization | Traceable to internal standard | Same |
| Calibration | 2-point | Same |
| Calibrator/Levels | Calibrator G/2 levels | Same |
| Controls/Levels | Commercial Controls/2 levels | Same |
| Master Curve Materials | Seven levels (MCM1-7) | Same |
| Detection Antibody | Monoclonal mouse anti-CA 27.29 antibody (~1.2 µg/mL) labeled with acridinium ester | Same |
| Capture Antibody | Human CA 27.29 (~0.72 U/mL) covalently coupled to paramagnetic particles | Same |
Comparisons of Candidate and Predicate Device for Specimen Equivalence (Dipotassium EDTA Plasma vs. Serum):
| Measurement | N | Sample Interval | Slope (95% CI) | Intercept (95% CI) | Correlation Coefficient (r) |
|---|---|---|---|---|---|
| Performance | 101 | 10.80 - 444.42 U/mL | 0.97 (0.955 – 0.993) | 2.21 U/mL (1.376 – 3.040) | 1.00 |
Interference Testing (Dipotassium EDTA):
| Interferent | Interferent Concentration | Analyte Concentration (U/mL) | Bias (%) |
|---|---|---|---|
| Dipotassium EDTA | 5.4 mg/mL | 20.46 | 1.8 |
| 318.39 | 3.7 |
2. Sample Size Used for the Test Set and Data Provenance
-
Specimen Equivalence by Method Comparison:
- Sample Size: 101 samples (N=101)
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The study used patient samples.
-
Detection Capability (LoB, LoD, LoQ): The specific sample sizes for LoB, LoD, and LoQ determination are not provided in this summary, but the determination was performed in accordance with CLSI Document EP17-A2.
-
Interferences: EDTA: The specific number of samples tested for interference is not provided, but tests were performed at two analyte concentrations.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay (measuring tumor-associated antigen CA 27.29) does not typically involve expert review of images or clinical data for establishing ground truth in the same way imaging devices do. The ground truth for analytical performance studies is established by the known concentration of the analyte in the samples, or by comparison to a reference method, rather than through expert consensus.
4. Adjudication Method for the Test Set
Not applicable for this type of analytical performance study. Adjudication methods (e.g., 2+1) are typically used in studies involving subjective interpretation of data, such as medical images, where discrepancies between readers need to be resolved. This study involves quantitative measurements.
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
No MRMC comparative effectiveness study was conducted as this device is an in vitro diagnostic test for quantitative serial determination of a cancer antigen, not an AI-based imaging or diagnostic tool requiring human reader interpretation in that context.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This is a standalone in vitro diagnostic assay. Its performance is evaluated based on its ability to accurately measure the target analyte (CA 27.29) in patient samples. Human intervention is limited to sample handling, loading, and interpreting the quantitative results per clinical guidelines, not in generating the test result itself.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the performance characteristics was established by:
- Detection Capability: Defined statistically based on measured values from blank and low-concentration samples (in accordance with CLSI EP17-A2).
- Specimen Equivalence: Comparison of results from plasma (EDTA) samples to serum samples using Deming linear regression, implying serum results (from the predicate device/established method) serve as the reference.
- Interferences: Known concentrations of interferents and analyte spiked into samples.
8. The Sample Size for the Training Set
No training set information is provided in the summary. Immunoassays are generally optimized and validated during development, and the performance studies presented reflect the validation of the finalized assay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as no training set information is provided as per point 8.
§ 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.