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510(k) Data Aggregation
(57 days)
NCW
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.
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(455 days)
NCW
The Bayer Immuno 1™ Her-2/neu Assay is an in vitro, diagnostic device intended for use in the quantitative determination of HER-2/neu in human serum. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer. 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 serum measurement of HER-2/neu as a prognostic indicator for early detection of recurrence and in the management of patients on immunotherapy regimens has not been fully established.
The Bayer Immuno I™ HER-2/neu Assay utilizes a well-established immunoassay technology in which one monoclonal HER-2/neu antibody (NB-3) is conjugated to fluorescein (designated Reagent 1, or R1) and the Fab' fragment of another monoclonal HER-2/neu antibody (TA-1) is conjugated to alkaline phosphatase (Reagent 2, or R2). The R1 and R2 conjugates are reacted with patient sample, calibrator, or control and are incubated at 37℃ on the system. Immuno 1 Magnetic Particles coated with an antifluorescein antibody (mIMP™ Reagent) are then added and a second incubation occurs during which the antibody complex is bound. The magnetic particles complexed with the immunological sandwich are then washed to separate unbound molecules, and a colorimetric substrate is added. The rate of conversion of substrate to a compound with absorbance at 405 and 450 nm is measured is proportional to the concentration of HER-2/neu in the sample. A cubic-through-zero curve-fitting algorithm is used to generate standard curves.
The assay has a range of zero to 250 ng/mL. The Bayer SETpoint™ HER-2/neu Calibrators consist of a set of six calibrator levels at 0, 10, 25, 60, 125, and 250 ng/mL. The Bayer TESTpoint™ HER-2/neu Controls consist of a set of three control levels at approximately 15, 50 and 100 ng/mL.
The provided document describes the Bayer Immuno 1™ HER-2/neu Assay, an in vitro diagnostic device for the quantitative determination of HER-2/neu in human serum for monitoring metastatic breast cancer patients.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Specificity: Interference | No significant interfering effects on HER-2/neu recovery were demonstrated from various potential endogenous (triglycerides, hemoglobin, immunoglobulin, bilirubin, albumin, cholesterol) or exogenous (chemotherapeutic drugs, OTC drugs, vitamins, HERCEPTIN®) interferents. |
| Cross-Reactivity | Maximum effect seen with Human Epidermal Growth Factor as a cross-reactant was not significant ( |
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(298 days)
NCW
The OSDI HER-2/neu Assay is an in vitro, diagnostic device intended for use in the quantitative determination of serum HER-2/neu in women with metastatic breast cancer who have an initial value of 15 ng/ml or greater. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer. 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 serum measurement of HER-2/neu as a prognostic indicator for early recurrence and in the management of patients on immunotherapy regiments has not been fully established.
The HER-2/neu ELISA is a sandwich enzyme immunoassay, which utilizes two monoclonal antibodies to quantitate the extracellular domain (ECD) of the HER-2/neu protein in serum. The capture antibody (NB-3) has been immobilized on the interior surface of the microtiter plate wells. To perform the assay, an appropriate volume of serum is incubated in the coated well to allow binding of the antigen by the capture antibody. The captured HER-2/neu ECD is then reacted with a different anti-HER-2/neu antibody designated TA-1. The TA-1 antibody is biotinylated. The detection of the ECD of HER-2/neu is with a streptavidin horseradish peroxidase conjugate, which then catalyzes the conversion of the chromogenic substrate o-phenylenediamine into a colored product. The colored reaction product is quantitated by spectrophotometry (read absorbance at 490 mm) and is related to the amount of the HER-2/neu ECD in the serum sample. Six prepared HER-2/neu standards (0, 2.5, 7.5, 15, 25 and 35 ng/ml) allow construction of a standard curve for subsequent quantification of HER-2/neu in serum samples. Also available from OSDI is a set of HER-2/neu controls (10-CVX) designed to be used in conjunction with the ELISA for quality monitoring of assay performance. This control set consists of three (3) control levels at 2.9, 9.1 and 24.0 ng/mL HER-2/neu protein.
The Oncogene Science Diagnostics, Inc. (OSDI) Manual HER-2/neu Microtiter ELISA is an in vitro diagnostic assay intended for the quantitative measurement of the extracellular domain of HER-2/neu protein in human serum. It is used in the follow-up and monitoring of patients with metastatic breast cancer whose initial serum level of HER-2/neu is 15 ng/mL or greater, in conjunction with other clinical and diagnostic procedures.
Here's an analysis of the acceptance criteria and the study proving the device meets those criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in a quantitative table within the document but can be inferred from the performance metrics described for various aspects of the assay. The "reported device performance" are the results from the non-clinical and clinical studies.
| Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|
| Specificity: Interference | "None of the potential endogenous or exogenous interferents demonstrated any significant interfering effects on HER-2/neu recovery." (Page 6) |
| Specificity: Cross-Reactivity | "The maximum effect seen with [Human Epidermal Growth Factor Receptor (HER-1)] cross-reactant was not significant (≤1%)... no cross-reactivity with HER-3." (Page 7) |
| Specificity: Heterophilic Antibodies and HAMA Interference | "HAMA and rheumatoid factors do not cause false negative or false positive results in the present assay format" when detector diluent contained Normal Mouse Serum (NMS). (Page 7) |
| Linearity | "When observed HER-2/neu concentration was plotted versus expected concentration, the slope and correlation coefficient of each data set were close to the optimum of 1, indicating linearity within the dynamic range of the assay." (Page 7) |
| Spike and Recovery (Matrix Effect) | "The total average percent recovery of all spiked serum samples in all three kit lots was 103%, indicating no effect of matrix on the ability of the ELISA to accurately measure HER-2/neu protein in serum." (Page 8) |
| Hook Effect (Antigen Excess) | "Separation of sample and reagent addition by washes prevents high-dose hook effect in this device." (Page 8) |
| Parallelism (Dilution Studies) | "Recoveries were evaluated at each of the dilution points for mean and standard deviation and were comparable for all three ELISA kit lots. Serum samples diluted in kit Sample Diluent result in accurate recovery of analyte at a range of concentrations in human samples." (Page 8) |
| End-to-End Variation (Robustness to timing) | "The expected variance in timing during normal use by skilled individuals should fall well short of these extended times tested and recoveries should be unaffected." (Page 9 - small increase/decrease (15%) observed only when times extended well beyond normal usage) |
| Plate Coating Variations | "Serum sample recovery, and therefore antibody coating, is consistent throughout plates and kit lots with 4.7-7.6 % CV." (Page 9) |
| Reproducibility (Intra- and Inter-assay) | OSDI Site, All Microtiter ELISA Lots Combined (Table 4.3-1): |
- Control 1 (24.2 ng/mL): Within Run %CV 3.8, Total %CV 7.8
- Control 2 (9.5 ng/mL): Within Run %CV 4.7, Total %CV 9.1
- Control 3 (2.9 ng/mL): Within Run %CV 7.8, Total %CV 10.6
- Control 4 (9.2 ng/mL): Within Run %CV 4.5, Total %CV 8.3
Three Sites and Three Kit Lots Combined (Table 4.3-2): - Control 1 (24.5 ng/mL): Within Run %CV 6.0, Total %CV 10.7
- Control 2 (9.8 ng/mL): Within Run %CV 7.0, Total %CV 10.4
- Control 3 (3.3 ng/mL): Within Run %CV 10.2, Total %CV 17.7
- Control 4 (9.5 ng/mL): Within Run %CV 6.9, Total %CV 10.8
"Within run CV's of 6-7% and total CV's of 10-11% for clinically relevant controls... well within acceptable limits for an assay of this type and for its intended use." (Page 9) |
| Sensitivity (Detection Limit) | "An MDD of 1.5 ng/mL was observed when assaying 232 replicates of Sample Diluent alone in three HER-2/neu ELISA kit lots. This MDD is acceptable for the intended use of this assay, where the lowest normal patient was 4.23 ng/ml and the cutoff determined in this study for elevated HER-2/neu values was 1.5 ng/ml." (Page 10) |
| Clinical Utility (Correspondence between HER-2/neu changes and clinical course) | Table 4.4-1: Correspondence of Metastatic Breast Cancer Patient Disease Status with Changes in Serum HER-2/neu: Visit-by-Visit - Change in HER-2/neu ≥20% ↑: 52 cases of Progression, 33 cases of No Progression (Total 85)
- Change in HER-2/neu
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