(57 days)
For in vitro diagnostic use in the quantitative determination of the HER-2/neu protein in human serum or using the ADVIA Centaur System. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer whose initial serum HER-2/neu level is greater than 15 ng/mL. HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures in the management of breast cancer. The clinical utility of the measurement of HER-2/neu in serum as a prognostic indicator for early recurrence and in the management of patients on immunotherapy has not been fully established. This test should be used by or under the order of a physician. This assay is not intended for use on any other system.
The ADVIA Centaur HER-2/neu assay is a fully automated, two-site sandwich immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of the monoclonal mouse antibody, TA-1 labeled with acridinium ester. The Fluorescein Conjugate Reagent is composed of the monoclonal mouse antibody, NB-3, labeled with fluorescein. The two monoclonal antibodies are specific for unique epitopes on the extracellular domain of HER-2/neu. The Solid Phase is composed of purified monoclonal mouse capture antibody, which is covalently coupled to paramagnetic particles. The sample is incubated with Fluorescein Conjugate Reagent and Lite Reagent simultaneously for 5.5 minutes. After this incubation, the Solid Phase is added and the mixture is incubated for an additional 2.75 minutes. After this final incubation, the immuno-complex formed is washed. The measured chemiluminescence is directly proportional to the quantity of HER-2/neu antigen in the sample.
The provided text describes the ADVIA Centaur HER-2/neu Immunoassay and its substantial equivalence to a predicate device, the Bayer Immuno-1 HER-2/neu kit. The primary study presented focuses on demonstrating this equivalence rather than establishing new acceptance criteria against a clinical ground truth.
Here's an analysis based on the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implicit for Substantial Equivalence) | Reported Device Performance |
|---|---|
| Correlation Coefficient (r) | 0.99 |
| Linear Regression Equation | ADVIA Centaur HER-2/neu = 0.97 (Immuno 1) + 0.56 ng/mL |
| Assay Range Tested | 0.2 - 250 ng/mL |
| Substantial Equivalence to Predicate Device | Demonstrated as an adjunctive test for management (monitoring) of metastatic breast cancer patients. |
Note: The document directly states that the "data demonstrate substantial equivalence." The acceptance criteria here are implicitly the thresholds for correlation and agreement that the FDA and the manufacturer consider sufficient to declare substantial equivalence to the predicate.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 196 samples
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). However, the study involved comparing the new device's results to those of the predicate device on these 196 samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. The study's purpose was to demonstrate substantial equivalence to a predicate device, not to establish a new ground truth based on expert consensus for the 196 samples. The "ground truth" in this context is the results obtained from the predicate device.
4. Adjudication Method for the Test Set
Not applicable. The study involved a direct comparison between two assays: the new ADVIA Centaur HER-2/neu assay and the predicate Bayer Immuno-1 HER-2/neu assay. There was no expert adjudication process for discordant results as the goal was method comparison.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This was a direct comparison study between two in vitro diagnostic (IVD) assays, not a study evaluating human reader performance with or without AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes. The study assessed the performance of the ADVIA Centaur HER-2/neu assay as a standalone device by comparing its results to those of another standalone IVD, the Bayer Immuno-1 HER-2/neu assay. Human interpretation of the raw chemiluminescence signal is not part of the device's functional mechanism; the device provides a quantitative result directly.
7. The Type of Ground Truth Used
The "ground truth" for this study was the results obtained from the predicate device (Bayer Immuno-1 HER-2/neu assay). The study aimed to show that the new device produced comparable results to an already FDA-cleared device.
8. The Sample Size for the Training Set
Not applicable. This device is an immunoassay kit, not an AI/machine learning algorithm that requires a training set in the conventional sense. The development of such an assay involves reagent optimization and calibration, but not an "AI training set."
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an immunoassay kit in the same way there would be for an AI algorithm. The development of the assay's reagents and calibration would be based on established biochemical and immunological principles, likely utilizing reference materials and internal validation processes.
§ 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.