(85 days)
The ARCHITECT HE4 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of HE4 antigen in human serum. The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer.
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
The ARCHITECT HE4 assay is a two-step immunoassay for the quantitative determination of HE4 antigen in human serum using CMIA technology with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and 2H5 anti-HE4 coated paramagnetic microparticles are combined. HE4 antigen present in the sample binds to the anti-HE4 coated microparticles. After washing, 3D8 anti-HE4 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs).
A direct relationship exists between the amount of HE4 antigen in the sample and the RLUs detected by the ARCHITECT i System optics.
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Here's a summary of the acceptance criteria and the studies that demonstrate the ARCHITECT HE4 Assay meets those criteria, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison (vs. commercially available HE4 EIA) | Slope: 1.0 ± 0.1 | Slope: 0.96 (95% CI: 0.93 to 1.00) |
| Correlation Coefficient (r): ≥ 0.90 | Correlation Coefficient: 0.97 | |
| Precision | Imprecision (Total CV): ≤ 10% | (Specific values for CV not explicitly given, but stated to meet the design, and testing followed NCCLS EP5-A2 guidance.) |
| Linearity | Linear across measurement range: 20.0 to 1500.0 pmol/L | Demonstrated linearity from 20.0 to 1500.0 pmol/L |
| Sensitivity - Limit of Detection (LoD) | LoD: ≤ 15 pmol/L | LoD: 0.2 pmol/L |
| Sensitivity - Limit of Quantitation (LoQ) | LoQ: ≤ 20 pmol/L | LoQ: 0.2 pmol/L |
| Specificity (Cross-reactivity with other tumor markers) | Reactivities > 15 pmol/L HE4 (LoD) not observed | Reactivities > 15 pmol/L HE4 (LoD) not observed for tested markers (CA 125, CA 15-3, CA 19-9, CEA, AFP) |
| Interference (Therapeutic Agents & Endogenous Substances) | Individual Recovery: 100 ± 15% | Range: 96-113% (across all tested agents/substances) |
| Mean Recovery: 100 ± 10% | Range: 98-108% (across all tested agents/substances) | |
| Interference (Clinical Conditions - HAMA, RF) | (Implicitly, no significant interference, similar to recovery criteria) | HAMA: Mean % Recovery 102% (Range 91-108%) |
| RF: Mean % Recovery 103% (Range 98-111%) | ||
| Monitoring Disease Status (using 14% HE4 increase threshold) | Implicitly, to demonstrate clinical utility in monitoring recurrence/progression | 54% sensitivity (53/99 progressive pairs showed ≥14% increase) |
| 79% specificity (261/331 non-progressive pairs showed |
§ 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.