(210 days)
For the quantitative measurement of alpha-fetoprotein (AFP) concentrations in human serum using the VITROS 5600 Integrated system to aid in the management of patients with non-seminomatous testicular cancer.
The VITROS Immunodiagnostic Products AFP Reagent Pack is performed using the VITROS Immunodiagnostic Products AFP Reagent Pack and the VITROS AFP Calibrators on the VITROS 5600 System. VITROS Immunodiagnostic Products AFP Reagent Pack contains: 1 reagent pack containing: 100 coated wells (antibody, sheep anti-AFP, binds>25 IU AFP/well); 20.6 mL conjugate reagent (HRP-mouse monoclonal anti-AFP, binds ≥156 IU AFP/ mL) in buffer with bovine serum and antimicrobial agent; 15.8 mL assay reagent (buffer containing bovine serum albumin and antimicrobial agent). VITROS Immunodiagnostic Products AFP Calibrator contains: 1 set of VITROS AFP Calibrators 1, 2 and 3 (human cord serum/plasma derived AFP in human plasma with antimicrobial agent, 2 mL); nominal values 2; 22 and 220 IU/mL (1st International Reference Preparation 72/225) (2.42; 26.6 and 266 ng/mL); Lot calibration card; Protocol card; 24 calibrator bar code labels (8 for each calibrator).
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the VITROS Immunodiagnostic Products AFP Reagent Pack:
Device Name: VITROS® Immunodiagnostic Products AFP Reagent Pack
Intended Use: For the quantitative measurement of alpha-fetoprotein (AFP) concentrations in human serum using the VITROS 5600 Integrated system to aid in the management of patients with non-seminomatous testicular cancer.
1. Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (VITROS 5600 System) |
|---|---|
| Precision/Reproducibility | |
| Repeatability (Within-run precision) | Mean AFP Conc. (IU/mL) |
| 2.92 | |
| 11.9 | |
| 77.0 | |
| 236 | |
| 395 | |
| Within-Lab Precision | Mean AFP Conc. (IU/mL) |
| 2.92 | |
| 11.9 | |
| 77.0 | |
| 236 | |
| 395 | |
| Linearity/Measuring Range | 0.800–500 IU/mL |
| Detection Limits | |
| Limit of Blank (LoB) | 0.229 IU/mL |
| Limit of Detection (LoD) | 0.476 IU/mL |
| Limit of Quantitation (LoQ) | 0.800 IU/mL (at 20% CV) |
| Analytical Specificity (Known Interferences) | No interference (bias >10%) found for a list of tested compounds at approximately 4.80 IU/mL and 19.2 IU/mL AFP concentrations. |
| Cross-Reactivity | No detectable cross-reactivity with human α-1-acid glycoprotein, α-1-antitrypsin, ceruloplasmin, chorionic gonadotrophin, IgG, placental lactogen, serum albumin, transferrin, and prolactin (concentration below measuring interval of 0.800 to 500 IU/mL). |
| Method Comparison with Predicate Device (Accuracy) | N=150 |
| Intercept 95% CI: -0.029 to 0.066 | |
| Dilution Recovery | Able to dilute samples up to 4000-fold manually and up to 1:400 automatically. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility: Patient pools were used.
- For each mean AFP concentration value, 80 observations were made over 20 days.
- Provenance: Not explicitly stated (e.g., country of origin). The use of "patient pools" implies human samples, likely retrospective, created by combining individual patient samples.
- Linearity: Not specified as a separate "test set" with a specific sample size, but established using the CLSI protocol EP06, which involves creating dilution series.
- Detection Limits (LoB, LoD, LoQ): Not specified as a distinct "test set" sample size. Determined consistent with CLSI document EP17.
- Analytical Specificity/Known Interferences: Not specified as a distinct "test set" sample size. Tested at two AFP concentrations (4.80 IU/mL and 19.2 IU/mL) with various interfering substances.
- Cross-Reactivity: Not specified as a distinct "test set" sample size. Evaluated by adding specific substances to an AFP-free sample.
- Method Comparison with Predicate Device:
- Sample Size: 150 patient serum samples.
- Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The samples were "patient (serum) samples."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This device is an in vitro diagnostic (IVD) immunoassay for quantitative measurement of alpha-fetoprotein. The "ground truth" for such devices is typically established through reference methods and certified reference materials traceable to international standards, rather than expert consensus on individual cases.
- Traceability: Calibration is traceable to in-house reference calibrators, which are calibrated against the First International Reference Preparation 72/225. This indicates a high-level, international standard for AFP measurement, providing the "ground truth" reference for the assays.
- There were no experts used in the sense of clinical specialists establishing a diagnosis or outcome for the test data, as the study focuses on the analytical performance of the assay.
4. Adjudication Method for the Test Set
Not applicable. As an IVD device measuring a biomarker concentration, the "judgement" is determined by the analytical results against established reference materials and comparison to a predicate device, not by multi-expert review of clinical cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is typically relevant for interpretative diagnostic devices (e.g., imaging AI) where human readers make a diagnosis or assessment, and the AI assists or replaces that human interpretation. For a quantitative immunoassay like this AFP reagent pack, the performance is assessed analytically and by method comparison, not by reader performance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies presented are standalone performance evaluations of the VITROS Immunodiagnostic Products AFP Reagent Pack and the VITROS 5600 Integrated system. The reported precision, linearity, detection limits, analytical specificity, cross-reactivity, and method comparison are all characteristics of the assay system itself, without human intervention in the result generation or interpretation beyond the standard operation of the instrument.
7. Type of Ground Truth Used
The ground truth for the analytical performance of this immunoassay is based on:
- Reference Materials and International Standards: Calibration is traceable to the First International Reference Preparation 72/225. This is a highly characterized and internationally recognized standard for AFP.
- Predicate Device Comparison: For accuracy, the device's performance was compared against a legally marketed predicate device (VITROS Immunodiagnostic Products AFP Reagent Pack K983031), which itself would have been validated against reference standards.
8. Sample Size for the Training Set
The document does not specify a "training set" in the context of a machine learning or AI algorithm. This device is a traditional immunoassay, not an AI/ML-based diagnostic. Therefore, the concept of a "training set" for an algorithm is not applicable here. Performance characteristics are established through analytical validation studies using various types of samples (patient pools, spiked samples, etc.).
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" is not applicable for this traditional immunoassay device. The analytical "ground truth" is established using traceable reference materials and comparison to a predicate device, as described in point 7.
§ 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.