(52 days)
The ACS:180 and ADVIA Centaur Intact PTH Immunoassay is intended for the quantitative determination of intact parathyroid hormone in human EDTA plasma on the automated ACS:180 and ADVIA Centaur analyzers marketed by Bayer Corporation. Intact PTH levels can be used to aide in the differential diagnosis of hyperparathyroidism, hypoparathyroidism, or hypercalcemia of malignancy.
The ACS:180 Intact PTH assay is a two-site "sandwich" immunoassay using direct, chemiluminometric technology, which uses two affinity purified goat polyclonal antibodies specific for the PTH molecules. The first antibody is directed toward the N-terminal (1-34) antigenic PTH domain and is labeled with acridinium ester (AE). The second antibody is directed toward the C-terminal (39-84) antigenic domain and is labeled with biotin. Patient sample (calibrator or control material) is incubated, for 5 minutes at 37°C with the Lite Reagent (LR) material that contains both the capture and tracer antibody conjugates. An immuno-complex is formed between the intact PTH in the sample and the two antibody conjugates. Subsequently, Solid Phase (SP) reagent is added and incubated for 2.5 minutes at 37°C. The immuno-complex molecule is captured by the streptavidim coated paramagnetic particles in the SP. Following incubation the unbound antibody conjugates are washed away. The chemiluminescent of the immuno-complex signal is measured in a luminometer. A sample with low intact PTH will have a minimum amount of bound AE label, while samples containing high levels of intact PTH will have maximum label complex bound. Thus, a direct relationship exists between the amount of intact PTH present in the sample and the amount of relative light units (RLUs) detected by the system.
The provided text describes the Bayer Diagnostics ACS:180 and ADVIA Centaur Intact PTH Immunoassay, focusing on its comparison to a predicate device to establish substantial equivalence for FDA clearance.
Here's the breakdown of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the FDA's "substantial equivalence" determination, which typically relies on demonstrating comparable performance to an already cleared predicate device. The performance metrics reported are primarily correlation and agreement with the predicate device.
| Acceptance Criterion (Implied) | Reported Device Performance |
|---|---|
| ACS:180 vs. Predicate Device (Nichols IRMA Intact PTH) | |
| Correlation with predicate device | r = 0.985 (for 100 EDTA plasma samples) |
| Linear Regression Intercept (ACS:180 vs. Nichols IRMA) | y = 0.976x - 17 pg/mL |
| Standard Error of Estimate (Sy.x) | 66 |
| ADVIA Centaur vs. ACS:180 | |
| Correlation with ACS:180 | r = 0.994 (for 252 EDTA plasma samples) |
| Linear Regression Intercept (ADVIA Centaur vs. ACS:180) | ADVIA Centaur iPTH = 1.03 (ACS:180 iPTH) + 3.36 pg/mL |
| Standard Error of Estimate (Sy) | 31 |
2. Sample Size Used for the Test Set and Data Provenance
- ACS:180 vs. Predicate Device:
- Sample Size: 100 EDTA plasma samples.
- Data Provenance: Not explicitly stated (e.g., country of origin, specific population). The study is described as a "method comparison" which implies a prospective collection for this testing, but it's not explicitly stated as retrospective or prospective.
- ADVIA Centaur vs. ACS:180:
- Sample Size: This comparison used transference for 268 EDTA plasma samples, with results reported for 252 samples.
- Data Provenance: Not explicitly stated (e.g., country of origin, specific population). The use of "transference" implies a process of validating reference intervals from one system to another, likely using a new set of samples, but doesn't explicitly state retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This document describes an immunoassay device, which measures a specific analyte concentration (Intact PTH) in a sample. The "ground truth" for such devices is typically the result obtained from a gold- standard or predicate assay. Therefore, there are no "experts" in the sense of human readers interpreting images, but rather the established accuracy of the predicate device's measurements.
4. Adjudication Method for the Test Set
Not applicable. This is an immunoassay device, not one requiring human adjudication of results. The comparison is quantitative between two analytical methods.
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
Not applicable. This is an immunoassay device, not an imaging or diagnostic device that involves human readers interpreting cases, with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are standalone performance studies of the ACS:180 and ADVIA Centaur Intact PTH immunoassays. They function as automated laboratory tests without human interpretation affecting the quantitative result. The comparison is between the new device and a predicate device (also an automated or manual assay).
7. The Type of Ground Truth Used
The ground truth for the device's performance was established using the measurements from the predicate device, the Nichols Institute Diagnostics Intact Parathyroid Hormone (PTH) kit (K954418). The assumption is that the predicate device's results are sufficiently accurate and are the benchmark for "truth" in this context.
8. The Sample Size for the Training Set
The document does not explicitly state a "training set" size. For laboratory assays, "training" often refers to the development phase (e.g., reagent formulation, assay parameters) and initial validation studies, rather than a distinct, labeled dataset for algorithm training as seen in AI/ML products. The reported data pertains to the validation of the final product.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" in the context of an AI/ML device is not explicitly described, the method for establishing its ground truth is not detailed. For the validation studies, as mentioned in point 7, the predicate device results served as the ground truth. The development of an immunoassay itself involves extensive research, optimization, and calibration using characterized samples and reference materials, but these are not typically described as "training set" and "ground truth establishment" in the same way as for AI.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.