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The Acetaminophen assay is an enzymatic, spectrophotometric assay for the measurement of acetaminophen concentration in human serum and plasma. The assay consists two working reagents, an enzyme reagent and a color reagent.

The enzyme reagent contains aryl acylamidase, which cleaves the amide bond of acetaminophen, forming p-aminophenol which then reacts with the 2,5-dimethylphenol (contained the color reagent) in the presence of manganese. The product of that reaction causes increased absorbance at 660 nm which is directly proportional to the acetaminophen concentration in the sample.

Testing is performed on the ARCHITECT c8000 clinical chemistry analyzers in conjunction with a calibrator (510(k) exempt) which is provided separately.

AI/ML Overview

The provided text describes a 510(k) premarket notification for an Acetaminophen assay (K202644). The document details various performance studies conducted to demonstrate the device's substantial equivalence to a legally marketed predicate device.

Here's an analysis of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Stated or Implied)	Reported Device Performance
Precision (Within-Run %CV)	Not explicitly stated as acceptance criteria, but typically within acceptable laboratory limits for clinical assays. For example, for Control Level 1, %CV (0.9) is excellent; for Panel A, %CV (5.6) is higher but likely acceptable for low concentrations.	Control Level 1: Mean 15 µg/mL, SD 0.1, %CV 0.9Control Level 2: Mean 73 µg/mL, SD 0.5, %CV 0.6Control Level 3: Mean 227 µg/mL, SD 0.8, %CV 0.3Panel A: Mean 5 µg/mL, SD 0.3, %CV 5.6Panel B: Mean 51 µg/mL, SD 0.3, %CV 0.6Panel C: Mean 84 µg/mL, SD 0.4, %CV 0.4Panel D: Mean 278 µg/mL, SD 1.0, %CV 0.4Panel E: Mean 362 µg/mL, SD 1.6, %CV 0.4
Precision (Within-Laboratory %CV)	Not explicitly stated as acceptance criteria, but typically within acceptable laboratory limits.	Control Level 1: SD 0.2, %CV 1.3Control Level 2: SD 0.6, %CV 0.8Control Level 3: SD 1.3, %CV 0.6Panel A: SD 0.5, %CV 9.1Panel B: SD 0.4, %CV 0.7Panel C: SD 0.6, %CV 0.7Panel D: SD 2.0, %CV 0.7Panel E: SD 2.6, %CV 0.7
Reproducibility (%CV)	Not explicitly stated as acceptance criteria, but typically within acceptable laboratory limits.	Control 1: Mean 14 µg/mL, SD 0.5, %CV 3.2Control 2: Mean 68 µg/mL, SD 0.6, %CV 0.9Control 3: Mean 208 µg/mL, SD 1.6, %CV 0.8Panel: Mean 163 µg/mL, SD 1.2, %CV 0.7
Limit of Blank (LoB)	Not explicitly stated, but should ideally be very low.	0 µg/mL (0 µmol/L)
Limit of Detection (LoD)	The sponsor chose to use 1 µg/mL (7 µmol/L) for reporting purposes.	Scientific LoD: 0.2 µg/mL (1.3 µmol/L)Reporting LoD: 1 µg/mL (7 µmol/L)
Limit of Quantitation (LoQ)	The sponsor chose to use 3 µg/mL (20 µmol/L) for reporting purposes. This is the lower end of the analytical measuring interval.	Scientific LoQ: 1.9 µg/mL (12.6 µmol/L)Reporting LoQ (lower end of AMI): 3 µg/mL (20 µmol/L)
Linearity/Assay Range	Device demonstrated linearity across the range of 0 to 386 µg/mL, which spans the analytical measuring interval of 3 to 377 µg/mL. Implicit acceptance is that the assay is linear across its claimed analytical measuring interval.	Linear across 0 to 386 µg/mL. Analytical Measuring Interval: 3 to 377 µg/mL (20 to 2496 µmol/L).
Analytical Specificity (Interference)	Interference within ± 7.5% for acetaminophen samples > 20 µg/mL, ORwithin ± 1.50 µg/mL for acetaminophen samples < 20 µg/mL.	Specific endogenous and exogenous substances (e.g., conjugated bilirubin ≤ 14 mg/dL, hemoglobin ≤ 570 mg/dL, N-Acetylcysteine ≤ 1663 mg/L) tested and demonstrated to meet the acceptance criteria at the specified interferent levels.
Method Comparison (Correlation)	Not explicitly stated, but the predicate device has a strong correlation (0.9993) with the candidate. Implicit acceptance would be a high correlation coefficient (e.g., >0.975 or >0.98), slope close to 1, and intercept close to 0.	Correlation Coefficient: 0.9993Slope: 1.042Intercept: -0.034(Comparing 3.50 - 356.26 µg/mL (predicate) to 3.58 - 375.28 µg/mL (candidate))
Matrix Comparison	Recovered within ± 7.5% for values ≥ 20 µg/mL, ORwithin ± 1.50 µg/mL for values < 20 µg/mL.	Serum, lithium heparin, lithium heparin mechanical separator, lithium heparin (separator tube), serum (separator tube), and sodium heparin tube types were found suitable for analysis.
Automated/Manual Dilution	Not explicitly stated, but results showed % difference of 1.5% to 5.3%, implying these met specific internal criteria for analytical accuracy of diluted samples. The range of 1.5% to 5.3% is generally considered excellent for dilution recovery.	Demonstrated % difference results of 1.5% to 5.3% when measuring samples above the analytical measuring interval by 1:10 autodilution vs. manual dilution methods.

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

Precision: 5 human serum panels and 3 control levels. Each assayed in a minimum of 2 replicates, twice per day on 20 days. N=120 for controls and panels.
Reproducibility: 1 human serum panel and 3 control levels. Each assayed in a minimum of 3 replicates at 2 separate times per day on 5 different days. N=146-150 for controls and panel.
Analytical Sensitivity (LoB, LoD, LoQ): Zero analyte samples and low analyte samples tested in replicates of 10.
Linearity/Assay Reportable Range: One unique sample set, 13 sample levels, tested in a minimum of 2 replicates.
Analytical Specificity (Interference): Test and reference samples tested in a minimum of 12 replicates.
Method Comparison: 119 patient specimens (114 unaltered native samples, 5 contrived).
Matrix Comparison: 78 matched specimen sets.
Automated/Manual Dilution: 5 samples with high acetaminophen concentrations, tested in replicates of 42.

Data Provenance: The document does not explicitly state the country of origin of the data. The studies appear to be prospective as they were specifically designed and executed to evaluate the performance of the device for this submission (e.g., "A study was performed based on guidance...", "Testing was conducted according to CLSI EP05-A3...").

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

This type of information (number and qualifications of experts) is typically associated with studies involving subjective interpretation, such as imaging or pathology studies. For an in vitro diagnostic (IVD) like this Acetaminophen assay, the "ground truth" is generally established using reference methods or gravimetric preparation of standards, rather than expert consensus on patient data.

For Value Assignment: The Acetaminophen Calibrator is prepared gravimetrically from USP grade reference acetaminophen material to a specific concentration, and verified against a master calibrator (internal reference standard). This is the analytical "ground truth" for calibration.
For Method Comparison: The predicate device is considered the "reference" for comparison, not a "ground truth" established by experts.

Therefore, the concept of "experts establishing ground truth" as you've defined it (e.g., radiologists) is not applicable to this type of IVD device performance study.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where multiple readers or experts provide independent assessments, and discrepancies need to be resolved. Since this is an IVD device measuring an analyte quantitatively, and the "ground truth" is established analytically (gravimetric, reference methods, or predicate device results), an adjudication method in the traditional sense is not applicable. The studies involve quantitative measurements from instruments and comparisons to established analytical standards or 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

No, an MRMC comparative effectiveness study was not done. This is an in vitro diagnostic (IVD) device, specifically an assay for measuring acetaminophen levels, not an imaging or AI-assisted diagnostic tool that involves human readers. Therefore, the concept of "human readers improving with AI vs. without AI assistance" is not applicable.

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

The device itself (the Acetaminophen assay on the ARCHITECT c Systems) is a standalone system for quantitative measurement. The performance studies detailed (precision, linearity, method comparison, etc.) represent the standalone performance of the algorithm/reagent system as it processes samples on the automated platform without human intervention beyond sample loading and system operation. There is no "human-in-the-loop" component for interpretation of results in the direct sense; the device provides a quantitative number.

7. The Type of Ground Truth Used

The ground truth for the performance studies is established via:

Gravimetric Preparation/Reference Standards: For analytical performance characteristics like calibrator value assignment, LoB, LoD, LoQ, and linearity. For example, calibrators are "prepared gravimetrically from USP grade reference acetaminophen material."
Predicate Device Results: For the method comparison study, the results from the legally marketed predicate device (SEKURE Acetaminophen L3K Assay on Hitachi 717) serve as the comparative "reference" or "ground truth" against which the new device's performance is measured.
Controlled Samples: For interference studies, samples with known concentrations of acetaminophen and specific interferents are used.

8. The Sample Size for the Training Set

The document does not mention a training set because this is not a machine learning or artificial intelligence (AI) device that requires extensive supervised learning. This is an enzymatic spectrophotometric assay, which relies on chemical reactions and optical measurement principles, not statistical pattern recognition trained on a dataset.

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

As there is no training set for this type of IVD device, this question is not applicable.

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