(315 days)
Intended for the in vitro quantitative measurement of acetaminophen in serum, lithium heparin plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity.
The SEKURE Acetaminophen L3K assay is an enzymatic, spectrophotometric assay for the measurement of acetaminophen concentration in serum, lithium heparin plasma and sodium heparin plasma. The assay consists two working reagents, an enzyme reagent and a color reagent. The enzyme reagent contains acyl amidohydrolase, which cleaves the amide bond of the 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 605 nm which is directly proportional to the acetaminophen concentration in the sample. Testing is performed on open system clinical chemistry analyzers, such as the Hitachi 717 (K872494) in conjunction with a calibrator (510(k) exempt) which is included and controls which are provided separately.
The provided document is a 510(k) Pre-market Notification for a medical device called the "SEKURE Acetaminophen L3K Assay." This document describes the analytical studies conducted to demonstrate the device's performance and substantial equivalence to a predicate device, rather than a study involving human readers or AI assistance in image interpretation. Therefore, many of the requested points related to AI, human reader performance, expert consensus, and MRMC studies are not applicable to this type of device submission.
Here's an analysis based on the available information:
Device Type: In vitro diagnostic device (IVD) for quantitative measurement of acetaminophen in biological samples.
Focus of the Document: Analytical performance studies (precision, analytical sensitivity, linearity, interference, method comparison, matrix comparison) to demonstrate the assay's accuracy and reliability.
Information NOT Applicable to this Document Type:
- Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective) - Data provenance is typically not detailed for IVD analytical studies in this manner; samples are clinical specimens or prepared materials.
- Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience) - Ground truth for IVDs is established by reference methods or gravimetric preparation, not expert review of images.
- Adjudication method (e.g. 2+1, 3+1, none) for the test set - Not applicable for IVD analytical studies.
- 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 not an AI-assisted diagnostic imaging device.
- If a standalone (i.e. algorithm only without human-in-the-loop performance) was done - Not applicable; this is not an AI algorithm.
- The type of ground truth used (expert consensus, pathology, outcomes data, etc) - Ground truth is established by reference methods, gravimetric preparation, or theoretical values.
- The sample size for the training set - Not applicable; this device does not use an AI training set.
- How the ground truth for the training set was established - Not applicable.
Acceptance Criteria and Reported Device Performance
The device is an in vitro diagnostic assay, and its performance is evaluated through various analytical studies. The acceptance criteria are therefore analytical performance specifications, not clinical outcomes directly.
Here's a table summarizing the acceptance criteria and a selection of reported performance data from the document:
Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance (Example Data) | Pass/Fail |
|---|---|---|---|
| Precision (Within Laboratory %CV) | ≤ 4% CV (for Control 1, Lot 1 example) | Lot 1, Control 1: 3.8% (Acetaminophen 68 µmol/L) | Pass |
| Lot 1, Unaltered P1: 1.4% (Acetaminophen 170.3 µmol/L) | Pass | ||
| Limit of Blank (LoB) | Maximal value across three lots. Specific criteria not explicitly stated but implied by calculation. | 1.0 µmol/L (maximal value across 3 lots) | Pass |
| Limit of Detection (LoD) | Maximal value across three lots. Specific criteria not explicitly stated but implied by calculation. | 2.4 µmol/L (maximal value across 3 lots) | Pass |
| Limit of Quantitation (LoQ) | Lowest acetaminophen concentration at which %TE was ≤25% | 8 µmol/L (based on lowest concentration where Total Error (TE) for each lot was ≤25%, e.g., Lot 1 @ 8umol/L was 20.41% TE) | Pass |
| Linearity/Assay Reportable Range | Deviation ±10% from theoretical values | For 100 µmol/L (theoretical), Lot 1: -1.2% deviation; For 2500 µmol/L, Lot 1: 0.6% deviation. All reported deviations within ±10% across lots and concentrations. | Pass |
| Analytical Specificity (Interference) - Endogenous | Significant interference defined as percent difference > ±10% or 8 µmol/L from control | Hemoglobin: No significant interference up to 1000 mg/dL (155 µmol/L) at various acetaminophen levels. Conjugated Bilirubin: No significant interference up to 40 mg/dL. | Pass |
| Analytical Specificity (Interference) - Exogenous Drugs | Significant interference defined as percent difference > ±10% or 8 µmol/L from control | Theophylline: No significant interference at 222 µmol/L. Salicylate: No significant interference at 4.34 mmol/L. | Pass |
| Method Comparison (Slope) | 1.0 ± 0.1 (comparing to predicate device) | Lot A: 0.974 (Deming), 0.975 (Passing-Bablok); Lot B: 0.984 (Deming); Lot C: 1.009 (Deming). All within the target range. | Pass |
| Method Comparison (% Bias) | ± 5.0% (comparing to predicate device) | Lot A: -2.27%; Lot B: -1.38%; Lot C: 1.55%. All within the target range. | Pass |
| Method Comparison (Correlation Coefficient) | ≥ 0.975 (comparing to predicate device) | Lot A: 0.99999; Lot B: 0.99992; Lot C: 0.9998. All met the criterion. | Pass |
| Matrix Comparison (Slope vs. Serum) | 1.0 ± 0.1 | SST: 1.012; Lithium Heparin: 1.015; PST: 1.009; Sodium Heparin: 1.012; Barricor: 1.004. All met the criterion. | Pass |
| Matrix Comparison (% Bias vs. Serum) | ± 5.0% | SST: 1.1%; Lithium Heparin: 1.2%; PST: 0.8%; Sodium Heparin: 1.1%; Barricor: 0.2%. All met the criterion. | Pass |
| Matrix Comparison (Correlation Coefficient vs. Serum) | ≥ 0.975 | All tested tubes (SST, Lithium Heparin, PST, Sodium Heparin, Barricor) showed a correlation coefficient of 1.000. | Pass |
Study that Proves the Device Meets the Acceptance Criteria
The study that proves the device meets the acceptance criteria is a series of Non-Clinical Performance Data studies, as detailed in the "510(k) Summary" document. These are analytical studies, typically following CLSI (Clinical and Laboratory Standards Institute) guidelines, to characterize the performance of the in vitro diagnostic assay.
1. Sample Sized Used for the Test Set and Data Provenance:
- Precision: 80 measurements per sample/control per lot (assayed in duplicate twice a day for 20 days). This included two unaltered patient serum samples, two spiked patient serum samples, and three levels of controls. Data is likely from laboratory samples, not specified by country.
- Analytical Sensitivity (LoB/LoD): 60 measurements per lot (five blank samples and five low concentration samples in quadruplicate over three operating days).
- Analytical Sensitivity (LoQ): 40 replicates per low concentration sample per lot (five low concentration samples tested in 40 replicates over five runs across three operating days).
- Linearity/Assay Reportable Range: 4 replicates per sample per lot (nine internally prepared samples across the measuring range).
- Analytical Specificity (Interference): 5 replicates per interferent concentration per acetaminophen concentration (tested at 3-4 acetaminophen concentrations).
- Method Comparison: 105 patient specimens, tested in duplicate, over seven operating days. Samples were distributed evenly throughout the assay range.
- Matrix Comparison: 40 matched sets of patient specimens.
Data Provenance: The document does not explicitly state the country of origin for patient samples or whether they were retrospective or prospective. However, for analytical performance, samples are typically collected from a pool of patient samples or are internally prepared clinical matrix materials.
2. Number of Experts and Qualifications:
- Not applicable. This device is an analytical chemistry assay, not one that relies on human experts for interpretation or ground truth establishment. The performance is assessed against quantitative analytical standards and a predicate device.
3. Adjudication Method:
- None. Not applicable for analytical performance studies of an IVD assay.
4. MRMC Comparative Effectiveness Study:
- No. Not applicable as this is not an imaging device or an AI-assisted diagnostic device.
5. Standalone Performance:
- Yes (in the context of an IVD). The performance data presented (e.g., precision, analytical sensitivity, linearity, interference) represent the standalone performance of the SEKURE Acetaminophen L3K Assay itself, without a "human-in-the-loop" in the artificial intelligence sense. The assay quantitatively measures acetaminophen concentration.
6. Type of Ground Truth Used:
- Reference Methods / Gravimetric Preparation / Theoretical Values / Predicate Device Comparison.
- Precision: Relative to the mean of repeat measurements.
- Analytical Sensitivity: Derived statistically from blank and low-level samples.
- Linearity: Compared to theoretical concentrations of gravimetrically prepared standards.
- Interference: Compared to control samples without interferent.
- Method Comparison: Compared to measurements obtained using a legally marketed predicate device (SEKURE Acetaminophen L3K Assay, K081938). This is a common form of "ground truth" for demonstrating substantial equivalence for IVDs.
- Matrix Comparison: Compared to serum samples (considered the reference matrix).
7. Sample Size for the Training Set:
- Not applicable. This device is an in vitro diagnostic assay, not an AI algorithm that requires a training set.
8. How the Ground Truth for the Training Set Was Established:
- Not applicable. See above.
§ 862.3030 Acetaminophen test system.
(a)
Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of acetaminophen overdose.(b)
Classification. Class II.