(77 days)
Immunoassay for the in vitro quantitative determination of α₁-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys immunoassay analyzers.
The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes. 1st incubation: 15 µl of sample, a biotinylated monoclonal AFP-specific antibody and a monoclonal AFP-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 a breakdown of the acceptance criteria and study information for the Elecsys AFP device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text for K973351 primarily describes the device and its comparison to a predicate device, but it does not explicitly state specific numerical acceptance criteria for each performance characteristic. Instead, it lists the types of studies performed to demonstrate substantial equivalence.
However, based on the types of studies listed, we can infer the aspects of performance that were evaluated and for which the device was considered acceptable. The "Reported Device Performance" below reflects what the submission claims to have demonstrated.
| Performance Characteristic | Acceptance Criteria (Inferred from Study Type) | Reported Device Performance (Summary from Submission) |
|---|---|---|
| Precision | To meet NCCLS recommendations | Evaluated according to NCCLS recommendations. (Details not provided in the summary, but implies acceptable precision.) |
| Lower Detection Limit | To be accurately determinable | Determined. (Specific value not provided, but implies acceptable sensitivity for clinical use.) |
| Linearity | To demonstrate linear response across range | Demonstrated. (Implies a reliable and proportional measurement across its intended assay range.) |
| Correlation with Predicate | To show substantial equivalence | Correlated with the predicate device (Enzymun-Test® AFP). (Implies comparable results to the reference method.) This was further supported by comparisons with samples from serially monitored patients diagnosed and treated for testicular cancer. |
| Interference (Endogenous) | No significant interference in results | Evaluated for the effect of various endogenous substances (hemoglobin, biotin, triglyceride, lipemia, and rheumatoid factor). (Implies no significant interference found, or interference within acceptable limits.) |
| Interference (Pharmaceutical) | No significant interference in results | Evaluated for the effect of commonly used pharmaceutical compounds. (Implies no significant interference found, or interference within acceptable limits.) |
| Sample Matrix Equivalence | Serum and plasma results to be comparable | Serum and plasma sample comparisons performed. (Implies comparable performance between serum and plasma samples.) |
| Hook Effect | To be determined (and generally absent/managed) | Determination of hook effect. (Implies the device handles very high concentrations without false low readings, or that the effect is understood and managed if present.) |
| Stability | To ensure reliable performance over time | Stability studies performed. (Implies the device maintains its performance characteristics over its stated shelf-life and in-use periods.) |
| Clinical Performance | Aid in patient management (comparable to predicate) | Comparisons of the Elecsys AFP and the predicate device were performed with samples from serially monitored patients diagnosed and treated for testicular cancer. (This surrogate for clinical utility demonstrates that the new device performs similarly in a real-world clinical context to the approved predicate, thus reasonably aiding in patient management.) |
2. Sample Size Used for the Test Set and Data Provenance
The submission does not explicitly state the numerical sample sizes used for the various tests mentioned (precision, linearity, interference, etc.). It only describes the types of studies performed.
The data provenance is not explicitly mentioned (e.g., country of origin). The studies appear to be retrospective in nature, as they involve comparisons with an existing predicate device and samples from "serially monitored patients diagnosed and treated for testicular cancer," suggesting pre-collected samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the submission. For an in vitro diagnostic (IVD) like the Elecsys AFP, the "ground truth" for performance studies typically comes from reference methods (like the predicate device) or known concentrations/spiked samples, rather than human expert interpretation of images or clinical data. However, the diagnosis of "testicular cancer" in the patient samples would have been established by medical professionals, but the details of who and how many are not discussed in relation to the device's technical validation.
4. Adjudication Method for the Test Set
This is not applicable and therefore not mentioned for this type of IVD device. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human readers or interpretation of complex medical data (e.g., imaging studies) where there might be inter-reader variability in establishing ground truth. For an automated immunoassay, the "ground truth" is established through analytical methods and reference standards.
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, an MRMC comparative effectiveness study was not conducted and is not applicable for this type of IVD device. This device is an automated immunoassay, not an AI-powered diagnostic image analysis tool that assists human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are standalone performance evaluations of the Elecsys AFP immunoassay. The device itself is an automated system for quantitative determination of AFP; there is no human-in-the-loop in the assay run or measurement process. Results are then interpreted by clinicians, but the device's performance characteristics (precision, linearity, correlation, etc.) are inherent to the algorithm and instrument.
7. The Type of Ground Truth Used
The ground truth used for various aspects of the study includes:
- Reference materials/standards: For linearity, lower detection limit, and potentially stability, calibrated reference materials or spiked samples of known concentrations would be used.
- Predicate device: The Enzymun-Test® AFP served as the primary "ground truth" or reference for comparative performance (correlation).
- Known clinical status: For the patient sample comparisons, the "serially monitored patients diagnosed and treated for testicular cancer" represent samples with a known clinical diagnosis, allowing for comparison of the new device's performance in a clinically relevant population against the predicate.
8. The Sample Size for the Training Set
This information is not applicable and therefore not provided. The Elecsys AFP is a chemistry immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The "calibration curve" is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code; this is a form of calibration, not model training.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, there is no "training set" in the context of machine learning for this device. The closest equivalent would be the calibration process. The ground truth for this would be:
- Calibrators with known, traceable concentrations: Used to establish the device's response curve. The master curve is provided via the reagent bar code, implying that the manufacturer pre-established the curve characteristics using highly controlled and validated calibrators.
- 2-point calibration: This periodic user calibration adjusts the master curve to account for minor variations in reagents or instrument performance, using calibrators with known values.
§ 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.