(61 days)
Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II assay is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.
The Elecsys® CA 125 II™ employs a sandwich test principle with monoclonal antibodies directed against CA 125 II and with streptavidin microparticles and electrochemiluminescence detection. Total duration of assay: 18 minutes.
- 1st Incubation: 40 ul of sample, a biotinylated monoclonal CA 125 IIspecific antibody and a monoclonal CA 125 II-specific antibody labeled with a ruthenium complex react to form a sandwich complex.
- 2nd Incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
- The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
- Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's an analysis of the acceptance criteria and study information for the Boehringer Mannheim Corporation Elecsys® CA 125II on Elecsys® 1010, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on demonstrating substantial equivalence of the Elecsys® CA 125II assay on the Elecsys 1010 to the same assay on the predicate device, Elecsys 2010. Therefore, the "acceptance criteria" are implicitly a demonstration of comparable performance to the predicate device. The table below outlines the performance characteristics presented for both systems. Specific predefined acceptance ranges or thresholds (e.g., "%CV must be less than X%") are not explicitly stated in the provided text as "acceptance criteria" but rather are presented as the device's performance achieved in the study.
| Feature | Acceptance Criteria (Implicitly, comparable to Elecsys 2010) | Elecsys 1010 Reported Performance | Elecsys 2010 Reported Performance (Predicate) |
|---|---|---|---|
| Precision | |||
| Within-Run %CV | Low values, comparable to predicate | 0.76 - 1.15% (Controls/Pools) | 1.41 - 3.29% (Controls/Pools) |
| 0.84 - 0.76% (Pools) | 2.14 - 2.06% (HS med/high) | ||
| Total %CV | Low values, comparable to predicate | 2.13 - 3.13% (Controls/Pools) | 2.48 - 4.19% (Controls/Pools) |
| 2.82 - 2.13% (Pools) | 3.05 - 2.48% (HS med/high) | ||
| Lower Detection Limit | Comparable to predicate | 0.222 U/mL | 0.5 U/mL |
| Linearity | 0.6 - 5,000 U/ml | 0.6 - 5,000 U/ml | 0.6 - 5,000 U/ml |
| Method Comparison | High correlation (r value close to 1) and slopes/intercepts indicative of agreement | Vs Elecsys 2010: | |
| Least Squares: y=0.9614x - 2.15, r=0.997 | |||
| Passing Bablock: y=0.9745x + 3.15, r=0.997 | Vs CENTOCOR CA 125 II RIA: | ||
| Least Squares: y=0.93x + 5.57, r=0.98 | |||
| Passing/Bablock: y=0.98x + 5.08, r=0.98 | |||
| Hook Effect | No Hook Effect (up to a specified concentration) | No Hook Effect up to 24,000 U/ml CA 125 | No Hook Effect up to 30,000 U/mL CA 125 |
2. Sample Size Used for the Test Set and Data Provenance
- Precision: For each of the "Control" and "Pool" samples tested across both Elecsys 1010 and Elecsys 2010, the sample size (N) was 60. It is not explicitly stated if these were prospective or retrospective samples, or their country of origin.
- Method Comparison (Elecsys 1010 vs Elecsys 2010): N = 93 samples.
- Method Comparison (Elecsys 2010 vs CENTOCOR CA 125 II RIA): N = 139 samples.
The data provenance (e.g., country of origin, retrospective/prospective nature) is not specified in the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This submission is for an in-vitro diagnostic (IVD) assay that measures a biomarker (CA 125II) in serum/plasma. As such, the "ground truth" for the test set is established by the reference measurement method (in this case, other CA 125II assays or a defined concentration of the analyte), not by expert human interpretation of images or clinical findings. Therefore, information regarding "number of experts" and their "qualifications" is not applicable in the context of this type of device and study.
4. Adjudication Method for the Test Set
Not applicable for this type of IVD device and study. The accuracy of measurements is determined by comparison to reference methods or known concentrations, not by adjudication of human interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC study is relevant for devices where human reader performance is a critical component, often in interpretation of medical images. This submission is for an automated immunoassay, and thus, an MRMC study was not performed.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented are for the standalone performance of the Elecsys® CA 125II assay on both the Elecsys 1010 and Elecsys 2010 automated immunoassay analyzers. There is no human-in-the-loop component for the measurement process itself.
7. The Type of Ground Truth Used
The "ground truth" for this IVD device is based on different levels:
- Precision: The ground truth is the inherent variability of the assay when measuring known control or pooled samples.
- Linearity: The ground truth is the expected linear relationship between the measured value and a series of diluted samples with known concentrations.
- Method Comparison: The ground truth is established by the results from a predicate device (Elecsys 2010) or another commercially available comparative assay (CENTOCOR CA 125 II RIA). This implies that these predicate/comparative assays are themselves accepted reference methods for CA 125II measurement.
8. The Sample Size for the Training Set
The provided text describes studies for performance characteristics (precision, linearity, method comparison, hook effect) which are typically part of a verification and validation phase for an IVD, demonstrating the device meets its design specifications. It does not explicitly mention a "training set" for an algorithm in the sense of machine learning. If the term "training set" refers to the samples used to establish a calibration curve or reagent stability, that information is not detailed in this summary beyond the mention of "2-point calibration and a master curve provided via the reagent bar code." The focus is on the performance of the assay itself once calibrated.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" with ground truth in the context of a machine learning algorithm is not detailed here. For the calibration mentioned ("2-point calibration and a master curve"), the ground truth would be established using reference materials or calibrators with accurately known concentrations of CA 125II, according to standard laboratory practices and manufacturers' protocols. The specific process for establishing these reference values is not provided in this summary.
§ 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.