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The FREND™ Free T4 Test System is a rapid indirect competitive immunoassay for the quantitation of free thyroxine (FT4) in human serum and lithium heparinized plasma specimens using the FREND™ Free T4 system. Measurements of free thyroxine (FT4) are used in the diagnosis of thyroid disorders. The FREND™ Free T4 Test System is intended for use in clinical laboratories. For in vitro diagnostic use only. The test is not intended for point-of-care facilities.

The FREND™ Free T4 is a rapid fluorescence immunoassay that measures Free T4 in human serum and in lithium heparinized plasma using the FREND™ Free T4 Test System. The FREND™ Free T4 is a single use fluorescence immunoassay designed to quantify the concentration of free thyroxine in serum and lithium heparinized plasma samples, The FREND™ Free T4 test is a two-step competitive immunoassay with gold nanoparticles labeled with T4-specific monoclonal anti-T4- antibody (mouse), T3-BSA labeled with fluorescent nanoparticles, and fluorescence detection by the FREND™ System. The FREND™ Free T4 Test utilizes microfluidic technology and detects immunecomplexes bound to Free T4. A 70ul Sample is first incubated during Step 1 for five minutes at 37 degrees C in the Free T4 Gold AB Tube with monoclonal anti-T4 antibody conjugated with gold nanoparticles. In Step 2, 35 ul of the mixture from Step 1 is manually loaded into the inlet of the cartridge, where it hydrates a T3-BSA fluorescent bead conjugate and migrates along the test strip. During migration the bound Free T4 in the sample and the fluorescent bead conjugates of T3-BSA compete to form antigenantibody complex in the test zone. Unbound T3-BSA fluorescent conjugates flow through and bind to the anti-T4 antibody that is fixed on the surface in the reference zone. Step 2 takes approximately four minutes after which the fluorescent signals in the test and reference zones are measured. Free T4 quantification is based upon the ratio of the intensity of the test and reference zones. A lower ratio of fluorescence is indicative of a higher Free T4 concentration, in other words, the maqnitude of the fluorescence ratio is inversely proportional to the amount of Free T4 in the sample. The free T4 detection range of the FREND™ Free T4 Test System is 0.4 to 6.0 ng/dL. Results are determined via a lot-specific calibration curve which is generated by the manufacturer using a six-point calibration determined from values averaged from five replicates at each level. The established curve is uploaded to the FREND™ System via the Free T4 Code-chip and is valid until the lot expiration date. The established curve is saved in the code-chip and valid until the expiration date of the test cartridge lot. The FREND™ Free T4 Test cartridge is a disposable plastic device that houses the reagents and contains a port or opening (inlet) where the sample is applied. Once the sample is applied, it will mix with the reagents and travel towards the detection area via capillary action. The FREND™ System is a portable, automated FREND™ cartridge reader. The FREND™ System is based on quantitative immunoassay technology capable of quantifying single or multiple analytes by measuring laser-induced fluorescence in a single-use disposable reagent cartridge. The FREND™ cartridge utilizes micro-fluidics lateral flow technology where the analyte of interest in the sample forms immune complexes while moving through the fluidics pathway in the cartridge. The concentration of the analyte of interest in an unknown sample is calculated using the ratio of the fluorescent intensity of the test zone and the reference zone. The FREND™ System is a bench top fluorescence reader containing a touch screen user interface. The System has a slot that accepts the FREND™ Free T4 Test Cartridge (which contains the reagents and sample), and is programmed to analyze the Test when the sample has fully reacted with the on-board in-cartridge reagents. Results of the test are displayed on the screen and can be printed on an optional printer. The FREND™ System software controls the graphical user interface, communication with hardware, database manaqement and data analysis. The software also controls the functions of the mechanical components including the motor, laser, printer control and acquisition of data from the sensor. The user can set the time and date and enter patient ID through the graphic user interface. The user cannot make any changes to the software.

Here's a summary of the acceptance criteria and study details for the FREND™ Free T4 Test System, based on the provided 510(k) submission:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as pass/fail values in many sections, but rather implied by the statistical analyses meeting CLSI guidelines and demonstrating comparability to the predicate device. The performance data is presented against these implicit standards.

2. Sample Size Used for the Test Set and Data Provenance

• Precision Study: 3 serum pools
• Linearity Study: 1 serum base pool diluted to 11 levels
• Interference Studies: Two levels of free T4 for various endogenous substances and pharmaceuticals.
• Cross-Reactivity Study: Two concentrations for various cross-reactants.
• Method Comparison: 358 samples
• Matrix Comparison: 48 paired serum and lithium heparin samples
• Expected Values/Reference Range: 196 normal, apparently healthy adult individuals

The specific country of origin for the test set data is not explicitly stated, but the precision, linearity, interference, and matrix comparison studies were performed at the NanoEnTek laboratory. The method comparison study was performed at a CLIA-certified laboratory testing facility. The clinical samples for the method comparison were evaluated at that CLIA laboratory. The reference range study used samples from 196 normal, apparently healthy adult individuals. The nature of "clinical samples" for the method comparison implies they would be patient samples, and "normal, apparently healthy adult individuals" for the reference range are also patient-like samples. The studies appear to be prospective in nature, as they involve testing the device with specific protocols (e.g., CLSI guidelines).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• None stated for the analytical performance studies. The ground truth for analytical studies (precision, linearity, LoD, LoQ, interference, cross-reactivity) is generally based on the inherent properties of the samples and the performance of established reference methods or spiked concentrations.
• For Method Comparison: The ground truth was established by a predicate device, the Abbott ARCHITECT Free T4 Assay. The number of human experts involved in interpreting results from either the predicate device or the FREND™ Free T4 Test System is not specified, as this is a quantitative immunoassay where results are read by a machine.

4. Adjudication Method for the Test Set

Not applicable for this type of quantitative immunoassay performance study. Ground truth is established by reference methods or defined concentrations, not human adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a quantitative immunoassay, not an imaging device requiring human interpretation, so MRMC studies are not relevant.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies described are standalone performance studies for the FREND™ Free T4 Test System. The device is intended for use in clinical laboratories, and the results are quantitatively measured by the FREND™ System directly. There is no human-in-the-loop performance evaluation described beyond standard laboratory procedures for operating the instrument and handling samples.

7. The Type of Ground Truth Used

• Analytical Performance:
  • Precision, Linearity, LoD, LoQ, Interference, Cross-reactivity: Ground truth was established by prepared samples with known concentrations, spiking experiments, and measurements against established laboratory protocols and standards (CLSI guidelines).
• Method Comparison: Ground truth was established by the predicate device, the Abbott ARCHITECT Free T4 Assay (K123379). This is a comparison against an existing, legally marketed device.
• Matrix Comparison: Ground truth (or comparative standard) derived from measuring the same analyte in different matrices (serum vs. plasma), with the expectation of comparable results.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/machine learning algorithm. For this immunoassay, the system's "training" involves the manufacturer-generated lot-specific calibration curve (six-point calibration determined from values averaged from five replicates at each level), which is then uploaded to the FREND™ System via a Code-chip.

9. How the Ground Truth for the Training Set Was Established

As described above, the "ground truth" for the device's operational curve (its calibration) is established by:

• Internal standards prepared according to CLSI C45-A Measurement of Free Thyroid Hormones.
• Gravimetric methods based on L-Thyroxine (Sigma T1775, Cell culture grade).
• Confirmation of calibrator Free T4 levels by measurement on the ARCHITECT i free T4 assay (K123379).

This process ensures that the device's internal calibration accurately reflects known Free T4 concentrations.

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