(273 days)
For in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in serum using the ADVIA Centaur, ADVIA Centaur XP and ADVIA Centaur XPT systems. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.
The ADVIA Centaur TSH assay is a two-site sandwich immunoassay using direct chemiluminometric technology. It utilizes a ReadyPack Primary Reagent Pack containing both Solid Phase (Polyclonal sheep anti-TSH antibody covalently coupled to paramagnetic particles) and Lite Reagent (Monoclonal mouse anti-TSH antibody labeled with acridinium ester) in separate wells. The assay is performed on the ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems.
This document is a 510(k) premarket notification for the ADVIA Centaur TSH assay, specifically focusing on its use with the new ADVIA Centaur XPT system. The notification seeks to demonstrate substantial equivalence to the previously cleared ADVIA Centaur TSH assay used with the ADVIA Centaur XP system.
It's important to note that this document does not describe a study proving a device meets acceptance criteria in the traditional sense of a clinical trial for a new diagnostic device. Instead, it focuses on demonstrating that modifications to an existing assay (ADVIA Centaur TSH assay) and a new instrument platform (ADVIA Centaur XPT) do not negatively impact the performance, safety, or effectiveness of the assay, and thus maintain substantial equivalence to the predicate device.
The "acceptance criteria" here are essentially the performance characteristics established for the predicate ADVIA Centaur TSH assay on the ADVIA Centaur XP system. The "study" refers to verification testing done to ensure the modified system (ADVIA Centaur TSH assay on ADVIA Centaur XPT) performs equivalently.
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of acceptance criteria and reported performance in a single section. Instead, it describes changes and states that verification testing met pre-determined acceptance criteria. The key change discussed that directly relates to performance is the Lower Limit of Detection (LoD).
| Performance Metric | Acceptance Criteria (Predicate Device on XP) | Reported Device Performance (Modified Device on XPT) |
|---|---|---|
| Lower Limit of Detection | 0.01 µIU/mL (Based on Analytical Sensitivity) | 0.05 µIU/mL (Based on Limit of Quantitation) |
| Analytical Measuring Range | 0.01-150 µIU/mL | 0.05-150 µIU/mL |
Note: The document states that "All verification testing met pre-determined acceptance criteria." and that the "performance of the ADVIA Centaur TSH assay on the ADVIA Centaur XPT system is substantially equivalent to the ADVIA Centaur TSH assay running on the currently-marketed predicate ADVIA Centaur XP system." This implies that other performance characteristics (e.g., precision, linearity, interference) were evaluated and found to be acceptable, even though specific numerical acceptance criteria and results are not detailed in this summary.
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify the sample size used for the verification testing.
It also does not specify the data provenance (e.g., country of origin, retrospective or prospective). The testing would typically be performed internally by the manufacturer during the development and verification phases of the new instrument and its compatibility with the assay.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Since this is a submission for an in vitro diagnostic (IVD) device assessing a biomarker (TSH), the "ground truth" for individual sample values is generally established by the device itself or a reference method. It's not a scenario where human experts (like radiologists) establish a ground truth from images. Therefore, this information is not applicable in the context of this document.
4. Adjudication Method for the Test Set
As this is an IVD device measuring a biomarker, the concept of an adjudication method (like 2+1, 3+1 for expert review) for a test set is not applicable. The instrument directly provides quantitative results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Its Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for medical image analysis where human readers interpret cases, and AI assistance might impact their performance. For an automated in vitro diagnostic assay, this type of study is not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself, the ADVIA Centaur TSH assay on the ADVIA Centaur XPT system, operates in a standalone manner. It is an automated in vitro diagnostic test that provides quantitative TSH values. There is no "human-in-the-loop" component in the direct generation of results from the instrument. The results are then used by healthcare professionals for diagnosis.
7. The Type of Ground Truth Used
For a quantitative in vitro diagnostic device like a TSH assay, the "ground truth" for accuracy often refers to:
- Reference methods or highly characterized reference materials for accuracy and calibration.
- Agreement with the predicate device for substantial equivalence demonstrations.
The document implicitly uses agreement with the predicate device (ADVIA Centaur XP system) as the primary "ground truth" for demonstrating substantial equivalence of the modified device (ADVIA Centaur XPT system) performance. The performance of the predicate device itself would have been established against reference methods or clinical outcomes during its initial clearance.
8. The Sample Size for the Training Set
The document does not specify a sample size for a training set. This is because the ADVIA Centaur TSH assay is a reagent-based immunoassay run on an automated instrument, not an AI/ML-based algorithm that typically requires a large training dataset for model development. The "training" for such a system involves calibrating the instrument and assay using specific calibrator materials.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, there isn't a "training set" in the sense of AI/ML. The "calibration" of the assay utilizes specific calibrator materials. The document states:
- Calibration: "2-point calibration using Calibrator B"
- Calibrators: "Calibrators checked with barcode; Calibrator lot numbers stored and displayed"
The ground truth for these calibrators would have been established by the manufacturer through rigorous testing, potentially against reference methods and with traceability to international standards, to ensure their assigned TSH values are accurate.
§ 862.1690 Thyroid stimulating hormone test system.
(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.