(26 days)
The ARCHITECT Free T4 (FT4) assay is a Chemiluminescent Microparticle Immunoassay (CMIA) for the quantitative determination of free thyroxine (Free T4) in human serum and plasma. The ARCHITECT Free T4 assay is to be used as an aid in the assessment of thyroid status.
The ARCHITECT Free T4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of free thyroxine (Free T4) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.
The ARCHITECT Free T4 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of free thyroxine (Free T4) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.
The ARCHITECT Free T4 assay is a two-step immunoassay to determine the presence of free thyroxine (Free T4) in human serum and plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and anti-T4 coated paramagnetic microparticles are combined. Free T 4 (unbound) present in the sample binds to the anti-T4 coated microparticles. After washing. T3 acridinium labeled conjugate is added in the second step. Pre-Trigger and Trigger Solutions are then added to the reaction mixture; the resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of Free T4 in the sample and the RLUs detected by the ARCHITECT i optical system.
The calibrators are devices intended for medical purposes for use in the ARCHITECT Free T 4 assay test system to establish points of reference that are used in the quantitative determination of values in the measurement of substances in human specimens. Free T4 measurements are used as an aid in the assessment of thyroid status.
This is a 510(k) summary for a medical device modification, specifically for the Abbott ARCHITECT Free T4 assay. It describes the device, its intended use, and the modifications made. The document also lists the verification and validation studies performed to demonstrate the device's performance after the modification. However, the provided text does not contain explicit "acceptance criteria" for the device's overall performance, nor does it present a study that directly "proves" the device meets such criteria in the format requested.
Instead, the document focuses on demonstrating substantial equivalence to a predicate device after a modification (changing from a 2-point to a 6-point calibration). The studies listed are typical for verifying the analytical performance of an in vitro diagnostic (IVD) device after a change, ensuring that the modified device performs comparably or better and continues to be safe and effective for its intended use.
Here's an attempt to extract the requested information based on the provided text, acknowledging that many details are not explicitly stated in the typical format of acceptance criteria and performance results:
1. Table of Acceptance Criteria and Reported Device Performance
As the document is a 510(k) summary for a modification, it describes studies conducted to demonstrate that the modified device is substantially equivalent to the predicate. Explicit, consolidated acceptance criteria with directly corresponding performance results in a single table are not provided. Instead, the document lists specific studies (e.g., Accuracy by Correlation, Limits of Blank/Detection/Quantitation, Linearity, Precision) that would have had their own internal acceptance criteria for passing.
For instance, the "Limits of Blank/Detection/Quantitation (LoB/LoD/LoQ)" are presented as device specifications, which could imply internal acceptance criteria were met during their determination.
| Performance Metric | Acceptance Criteria (Inferred/Typical for IVD, Not Explicitly Stated) | Reported Device Performance (Modified Device) |
|---|---|---|
| Accuracy by Correlation | (Typically seeks good correlation with a reference method or predicate device, often R² > 0.95 or similar) | Study performed; specific results and criteria not detailed in this summary. |
| Accelerated Calibrator Stability | (Typically ensures calibrators remain stable for a specified period and conditions) | Study performed; specific results and criteria not detailed in this summary. |
| Real Time Calibrator Stability (In-Use) | (Typically ensures calibrators remain stable during usage life after opening) | Study performed; specific results and criteria not detailed in this summary. |
| Real Time Calibrator Stability (Intended Storage) | (Typically ensures calibrators remain stable for their shelf life under storage conditions) | Study performed; specific results and criteria not detailed in this summary. |
| Limit of Blank (LoB) | (Maximum blank measurement below which the analyte cannot be reliably detected) | 0.22 ng/dL |
| Limit of Detection (LoD) | (Lowest analyte concentration reliably detected) | 0.28 ng/dL |
| Limit of Quantitation (LoQ) | (Lowest analyte concentration reliably quantified with acceptable precision and accuracy) | 0.4 ng/dL |
| Linearity | (Typically demonstrates proportional response across the measuring interval) | Study performed; specific results and criteria not detailed in this summary. |
| 20-Day Precision (at Measuring Interval Limits) | (Typically assesses assay variability at low and high ends of the dynamic range) | Study performed; specific results and criteria not detailed in this summary. |
| 20-Day Precision (to Verify Product Requirements) | (Typically assesses overall assay variability for various concentrations) | Study performed; specific results and criteria not detailed in this summary. |
| 20-Day Precision (for Native Samples) | (Typically assesses assay variability using real patient samples) | Study performed; specific results and criteria not detailed in this summary. |
| Dynamic Range / Measuring Interval | (Range within which the assay can accurately measure the analyte) | 0.4–6.0 ng/dL |
| Analytical Sensitivity | (Lowest concentration of analyte the method can differentiate from zero with a high probability) | Replaced by LoQ (0.4 ng/dL) |
2. Sample Size Used for the Test Set and Data Provenance
The document lists various verification/validation studies, but does not specify the sample sizes used for these studies. It refers to human serum and plasma being used for the determination of Free T4, implying human samples. The provenance of the data (e.g., country of origin, retrospective or prospective) is not mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable or provided in this type of document. For an in vitro diagnostic assay like Free T4, the "ground truth" for the test set values is typically established by reference methods, gravimetric methods, or highly characterized reference materials, not by expert human graders or reviewers in the way an imaging AI algorithm might use. The calibrators described are matched to an "Abbott internal reference standard" manufactured by gravimetric methods, which serves as a form of ground truth for calibration.
4. Adjudication Method for the Test Set
This is not applicable for this type of IVD device and its verification studies. Adjudication methods (like 2+1, 3+1) are typically used in clinical trials or studies where human expert consensus is needed to determine the "correct" classification or diagnosis, often in imaging or pathology. For an analytical assay, the "correct" value is determined instrumentally or by reference methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI algorithms that assist human readers (e.g., radiologists interpreting images) to quantify the improvement in human performance with AI assistance. The ARCHITECT Free T4 assay is an automated in vitro diagnostic test system, not an AI-assisted human reading device.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The device itself is a standalone automated diagnostic assay. The listed studies (Accuracy, Limits, Linearity, Precision) are all demonstrations of the algorithm/system's standalone performance in determining Free T4 levels. There is no human-in-the-loop component for the measurement process itself, beyond operating the instrument and interpreting the numerical result.
7. The Type of Ground Truth Used
The ground truth for the device's calibration and analytical performance is established through:
- Abbott internal reference standard, which is manufactured by gravimetric methods based on Free Thyroxine calculation (FT4c) using L-Thyroxine, sodium salt pentahydrate (HPLC grade).
- For precision studies, "native samples" (real patient samples) are mentioned, which would presumably be analyzed against the established calibration curve.
- "Accuracy by Correlation" implies comparison to a reference method or the predicate device, which would serve as a comparative ground truth.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an AI algorithm. For an IVD assay, the system is "trained" by calibrators. The modified device uses a 6-point calibration (levels: 0.0, 0.5, 1.0, 2.0, 3.5, 6.0 ng/dL L-thyroxine in human serum). The number of runs or replicates used to establish the calibration curve from these 6 points is not specified.
9. How the Ground Truth for the Training Set Was Established
The "ground truth" for the calibrators (which serve as the "training set" for the instrument's measurement curve) is established by:
- Gravimetric methods using L-Thyroxine, sodium salt pentahydrate (HPLC grade) to prepare the calibrators at specific, known concentrations.
- These calibrators are further "matched to an Abbott internal reference standard," which itself is manufactured and characterized by gravimetric methods. This ensures traceability and accuracy of the calibrator values.
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.