← Product Code [DKB](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DKB) · K141928

# COBAS C ACETAMINOPHEN GEN.2 ASSAY, ACET2 CALIBRATOR (K141928)

_Roche Diagnostics Operations (Rdo) · DKB · Nov 25, 2014 · Clinical Toxicology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKB/K141928

## Device Facts

- **Applicant:** Roche Diagnostics Operations (Rdo)
- **Product Code:** [DKB](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DKB.md)
- **Decision Date:** Nov 25, 2014
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.3200
- **Device Class:** Class 2
- **Review Panel:** Clinical Toxicology

## Indications for Use

The cobas c Acetaminophen Gen.2 assay is an in vitro diagnostic test for the quantitative determination of acetaminophen of acetaminophen overdose in serum and plasma on Roche/Hitachi cobas c systems. The ACET2 calibrator is for use in the calibration of the Acetaminophen Gen.2 Roche assay.

## Device Story

The cobas c Acetaminophen Gen.2 assay is a homogeneous enzyme immunoassay for quantitative analysis of acetaminophen in human serum and plasma. It uses a competitive binding principle: drug in the sample competes with enzyme-labeled drug (bacterial G6PDH) for anti-acetaminophen antibody binding sites. Enzyme activity is inversely proportional to drug concentration; activity is measured spectrophotometrically via absorbance change of NADH. The ACET2 calibrator is a liquid, ready-to-use reagent containing a known quantity of acetaminophen; the analyzer performs on-board dilution with NaCl to create a six-level calibration set. The device is used in clinical laboratories on Roche/Hitachi cobas c 501 analyzers. Healthcare providers use the quantitative results to assess overdose severity and guide clinical decision-making, potentially preventing liver/kidney damage.

## Clinical Evidence

Bench testing only. Precision (CLSI EP5-A2) showed CVs 2.2-3.5%. Linearity (CLSI EP6-A) confirmed 5-200 µg/mL range. Method comparison (n=105) against predicate yielded Deming regression y = 1.02x - 0.699 (r=0.997). LoB/LoD/LoQ established at 1.5/3/5 µg/mL respectively. Interference testing confirmed no significant interference from endogenous substances (hemoglobin, lipids, bilirubin) or 24 common drugs.

## Technological Characteristics

Quantitative enzyme immunoassay. Reagents: sheep polyclonal anti-acetaminophen antibody, G6PDH-labeled acetaminophen, NAD, glucose-6-phosphate. Energy source: spectrophotometric (340/415 nm). Form factor: cassette-based reagents for cobas c 501 analyzer. Connectivity: integrated with analyzer software. Standards: CLSI EP05-A2, EP06-A2, EP17-A2, EP09-A2.

## Regulatory Identification

A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)

## Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

## Predicate Devices

- Siemens Emit® tox™ Acetaminophen Assay (k002974)
- Siemens Emit® tox™ Acetaminophen Calibrators (k002974)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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1

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k141928

B. Purpose for Submission:
New Device

C. Measurand:
Acetaminophen

D. Type of Test:
Quantitative enzyme immunoassay

E. Applicant:
Roche Diagnostics

F. Proprietary and Established Names:
cobas C Acetaminophen Gen.2 assay
ACET2 Calibrator

G. Regulatory Information:
1. Regulation section:
21 CFR Sec. 862.3030-Acetaminophen test system
21 CFR Sec. 862.3200-Clinical toxicology calibrator
2. Classification:
Class II
3. Product code:
LDP-Colorimetry, Acetaminophen
DKB-Calibrators, Drug Mixture
4. Panel:
Toxicology (91)

H. Intended Use:
1. Intended use(s):
See Indications for use below.
2. Indication(s) for use:

{1}

The cobas c Acetaminophen Gen.2 assay is an in vitro diagnostic test for the quantitative determination of acetaminophen of acetaminophen overdose in serum and plasma on Roche/Hitachi cobas c systems.

The ACET2 calibrator is for use in the calibration of the Acetaminophen Gen.2 Roche assay.

3. Special conditions for use statement(s):
For prescription use only

4. Special instrument requirements:
Roche Hitachi cobas c 501 clinical chemistry analyzer

I. Device Description:

The cobas c Acetaminophen Gen.2 assay consists of reagents packaged in a cassette labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2).

- R1 contains anti-acetaminophen antibody (sheep polyclonal), Glucose-6-phosphate, Nicotinamide adenine dinucleotide (NAD), bovine serum albumin, preservatives (Proclin), and stabilizers (pepstatin and aprotinin).
- R2 contains acetaminophen labeled with bacterial Glucose-6-phosphate dehydrogenase, Tris buffer, preservatives (Sodium Azide and 2-methyl-2H-isothiazol-3-one (MIT)) bovine serum albumin, and stabilizers (pepstatin and aprotinin).

The ACET2 calibrator contains a known quantity of acetaminophen (~200 µg/mL), sodium phosphate, sodium EDTA, sodium chloride (NaCl), and preservatives (Proclin and MIT). The cobas c 501 analyzer dilutes the ACET2 calibrator on-board the analyzer with NaCl diluent, in order to create five concentration levels (level 2, 3, 4, 5, and 6) containing 10, 30.2, 75.0, 100, and 200 µg/mL of acetaminophen, respectively. Level 1 contains no acetaminophen.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Emit® tox™ Acetaminophen Assay
Emit® tox™ Acetaminophen Calibrators

2. Predicate 510(k) number(s):
K002974

3. Comparison with predicate:

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|  Assay Comparison - Similarities and Differences  |   |   |
| --- | --- | --- |
|  Feature | Predicate Device: Emit® tox™ Acetaminophen Assay | Candidate Device: Acetaminophen Gen.2  |
|  Intended Use | The Emit® tox™ Acetaminophen Assay is a homogeneous enzyme immunoassay intended for in vitro diagnostic use in the quantitative analysis of acetaminophen in human serum or plasma. | Same  |
|  Test Principle | Homogeneous enzyme immunoassay | Same  |
|  Measuring Range | Up to 200 μg/mL (1324 μmol/L) | 5–200 μg/mL (33.1–1324 μmol/L)  |
|  Traceability | This method has been standardized against USP reference standards. | Same  |
|  Sample Types | Serum and EDTA, heparin, citrate and oxalate/fluoride plasma | Serum and K2- or K3-EDTA, or lithium heparinized plasma  |
|  Calibrator Comparison - Similarities and Differences  |   |   |
| --- | --- | --- |
|  Feature | Predicate Device: Emit® tox™ Acetaminophen Calibrators | Candidate Device: ACET2 Calibrator  |
|  Intended Use | The Emit® tox™ Acetaminophen Calibrators are intended for use with the Emit® tox™ Acetaminophen Assay. | ACET2 calibrator is for use in the calibration of the Acetaminophen Gen.2 Roche assay.  |
|  Format | Liquid ready-to-use | Same  |
|  Analyte | Acetaminophen | Same  |
|  Storage Conditions | 2-8°C | Same  |

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|  Storage and Stability | When stored refrigerated at 2–8°C, the Emit® tox™ Acetaminophen Calibrators are stable until the expiration date printed on the dropper vial label. | Same  |
| --- | --- | --- |
|  Quantity | Emit® tox™ Acetaminophen Calibrators are a six-level set that contain the following acetaminophen concentrations: 0, 10, 25, 50, 100, 200 μg/mL. | The ACET2 calibrator has a nominal value of 200 μg/mL of acetaminophen. The analyzer dilutes the ACET2 calibrator on-board with NaCl diluent, in order to create five concentration levels. This results in a six- level calibrator set: 0.0, 10.0, 30.2, 75.0, 100, 200 μg/mL.  |

K. Standard/Guidance Document Referenced (if applicable):

- Standard Title CLSI EP05-A2- Evaluation of Precision Performance of Quantitative Measurement Methods
- Standard Title CLSI EP06-A2- Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach
- Standard Title CLSI EP17-A2- Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
- Standard Title CLSI EP09-A2- Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Second Edition

L. Test Principle:

The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of acetaminophen in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phoshate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically (at 415 nm and 340 nm).

M. Performance Characteristics (if/when applicable):

All performance studies were conducted with the Roche Hitachi cobas c 501 clinical chemistry analyzer.

1. Analytical performance:

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# a. Precision/Reproducibility:

Precision of the Acetaminophen Gen.2 assay was evaluated with a 21-day precision study according to CLSI EP05-A2, using control material as well as pooled human sera samples (from patients taking acetaminophen). The acetaminophen concentrations of all tested samples are noted in the table below. All samples were tested using 3 reagent kit lots, with 2 replicates per run and 2 runs per day. Data from all lots tested were similar. Data from a representative lot is presented below.

|  Test Specimen | Mean Acetaminophen Concentration (μg/mL) | Within-Run (Repeatability) |   | Between-Run |   | Total Precision (within lab precision)  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  | SD (μg/mL) | % CV | SD (μg/mL) | % CV | SD (μg/mL) | % CV  |
|  Human Sample 1 | 7.6 | 0.224 | 3.0 | 0.107 | 1.4 | 0.258 | 3.4  |
|  Human Sample 2 | 73 | 1.66 | 2.3 | 0.314 | 0.4 | 1.95 | 2.7  |
|  Human Sample 3 | 130 | 2.90 | 2.2 | 0 | 0 | 3.32 | 2.5  |
|  Human Sample 4 | 169 | 3.69 | 2.2 | 0.377 | 0.2 | 4.66 | 2.8  |
|  Human Sample 5 | 184 | 4.25 | 2.3 | 0 | 0 | 5.31 | 2.9  |
|  Control 1 | 15.3 | 0.385 | 2.5 | 0.193 | 1.3 | 0.455 | 3.0  |
|  Control 2 | 35.3 | 0.637 | 1.8 | 0.470 | 1.3 | 0.791 | 2.2  |
|  Control 3 | 107 | 2.18 | 2.0 | 0.641 | 0.6 | 2.71 | 2.5  |

# b. Linearity/assay reportable range:

Linearity was assessed in a study using serum and Li-Heparin plasma samples containing acetaminophen concentrations across the measuring range of the assay (5-200  $\mu$ g/mL acetaminophen). Samples were prepared by 13 dilutions of a high concentration sample with an acetaminophen free sample. Expected concentrations were determined based on the known value of the commercially available standard material values and the dilution factors. Samples were analyzed in triplicate. Percent recoveries relative to the expected concentrations are shown below for serum and Li-Heparin plasma. Results support linearity across the measuring range.

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Serum

|  Sample | Expected (μg/mL) | C501 mean (μg/mL) (μg/mL) | Absolute deviation (μg/mL) | % recovery of mean values  |
| --- | --- | --- | --- | --- |
|  1 | 0 | 0.00 | 0.0 | -  |
|  2 | 3 | 2.40 | -0.6 | -  |
|  3 | 6 | 5.40 | -0.6 | 90  |
|  4 | 24 | 23.1 | - | 96  |
|  5 | 48 | 45.7 | - | 95  |
|  6 | 72 | 68.4 | - | 95  |
|  7 | 96 | 92.1 | - | 96  |
|  8 | 12 | 113 | - | 94  |
|  9 | 14 | 139 | - | 97  |
|  10 | 168 | 160 | - | 95  |
|  11 | 192 | 188 | - | 98  |
|  12 | 216 | 206 | - | 95  |
|  13 | 240 | 232 | - | 97  |

Li-Heparin plasma

|  Sample | Expected (μg/mL) | c 501 mean (μg/mL) | Absolute deviation (μg/mL) | % recovery of mean values  |
| --- | --- | --- | --- | --- |
|  1 | 0 | 0 | 0 | -  |
|  2 | 3 | 2.4 | -0.6 | -  |
|  3 | 6 | 5.1 | -0.9 | 85  |
|  4 | 24 | 21.7 | - | 90  |
|  5 | 48 | 44.3 | - | 92  |
|  6 | 72 | 65.4 | - | 91  |
|  7 | 96 | 89.0 | - | 93  |
|  8 | 120 | 110 | - | 92  |
|  9 | 144 | 132 | - | 92  |
|  10 | 168 | 155 | - | 92  |
|  11 | 192 | 180 | - | 94  |
|  12 | 216 | 194 | - | 90  |
|  13 | 240 | 228 | - | 95  |

Dilution Accuracy:

The sponsor provided data supporting dilution accuracy (re-run function) by comparing manually diluted serum and Li-heparin plasma samples to expected values (5-fold dilution). Each sample was diluted with NaCl. Data is provided in the table below.

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|  Sample type | Replicate | Expected acetaminophen concentration (μg/mL) | Auto rerun acetaminophen concentration (μg/mL) | Mean Expected value | Mean autorerun value | % Recovery  |
| --- | --- | --- | --- | --- | --- | --- |
|  Serum | 1 | 234 | 232.0 | 224.7 | 230.7 | 102.7  |
|   |  2 | 224 | 226.7  |   |   |   |
|   |  3 | 216 | 233.4  |   |   |   |
|  Serum | 1 | 510 | 566.8 | 535.7 | 561.3 | 104.8  |
|   |  2 | 551 | 560.1  |   |   |   |
|   |  3 | 546 | 557.0  |   |   |   |
|  Serum | 1 | 839 | 871.3 | 839.0 | 887.1 | 105.7  |
|   |  2 | 817 | 907.4  |   |   |   |
|   |  3 | 861 | 882.5  |   |   |   |
|  Plasma | 1 | 201 | 209.7 | 206.7 | 212.0 | 102.6  |
|   |  2 | 213 | 213.7  |   |   |   |
|   |  3 | 206 | 212.6  |   |   |   |
|  Plasma | 1 | 614 | 629.2 | 611.7 | 625.7 | 102.3  |
|   |  2 | 615 | 614.2  |   |   |   |
|   |  3 | 606 | 633.7  |   |   |   |
|  Plasma | 1 | 773 | 852.9 | 794.3 | 854.7 | 107.6  |
|   |  2 | 785 | 873.2  |   |   |   |
|   |  3 | 825 | 838.1  |   |   |   |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The cobas c Acetaminophen Gen.2 assay is calibrated using a calibrator that was previously cleared under k002974. The Roche ACET2 calibrator is prepared gravimetrically from commercially available purified materials. See k002974 for traceability and stability information.

d. Detection limit:

LoB, LoD, and LoQ studies were performed based upon CLSI EP17-A2.

**LoB Protocol**

One analyte-free sample was measured in replicates of 5 for 2 runs on 2 analyzers for 3 days for each of 3 reagent lots (for total n=60 per lot). The LoB was determined to be 1.5 μg/mL.

**LoD Protocol**

Five low-analyte samples spiked with acetaminophen were measured with 1 determination per run (2 runs) on two analyzers with 3 reagent lots for six runs per day across three days. This study yielded a LoD of 3 μg/mL.

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8

# LoQ Protocol

A set of six low-level samples was measured in two aliquots using 3 lots over at least 6 days (n=12 for each low-level sample). The total number of measurements made for each lot was 72.

Bias was determined by the difference between average and target values. The target values were determined by a chromatography system. Standard deviations were determined over all replicates for each lot. The following results were observed.

|  Lot | Mean value (ug/mL) (C501) | SD (ug/mL) | Absolute bias compared to target value (ug/mL)  |
| --- | --- | --- | --- |
|  1 | 4.73 | 0.123 | 0.367  |
|  2 | 4.63 | 0.129 | 0.475  |
|  3 | 4.88 | 0.221 | 0.217  |

The LoQ was determined to be 5 µg/mL.

## e. Analytical specificity:

### i. Interference from endogenous substances/cross reactants

Cross reactivity with compounds of similar structure were evaluated by using serum sample pools, with two acetaminophen target concentrations (~5.0 and ~30.0 µg/mL). Test samples included the acetaminophen plus potential cross-reactant (at the concentrations shown below). Control samples contained corresponding concentrations of acetaminophen without potential interferents. The table below provides the % cross reactivity for each of the compounds tested.

|  Compound | Compound Concentration (µg/mL) | Acetaminophen (µg/mL) | % cross reactivity  |
| --- | --- | --- | --- |
|  Acetaminophen cysteine | 100 | 6.1 | 0.5  |
|  Acetaminophen glucuronide | 1000 | 5.2 | n.d.*  |
|  Acetaminophen mercapturate | 300 | 5.4 | 0.2  |
|  Acetaminophen sulfate | 200 | 6.1 | n.d.*  |
|  Phenacitin | 500 | 6.7 | 0.5  |
|  Acetaminophen cysteine | 100 | 29.2 | -0.3  |
|  Acetaminophen glucuronide | 1000 | 25.4 | -0.1  |

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The n.d.* stands for 'not detectable'.

The assay was also evaluated with hemoglobin (hemolysis), lipids (lipemia), and bilirubin (Icterus) for potential interferences with the measurement of acetaminophen using serum sample pools. Evaluation of interference included normal levels of bilirubin and lipids (triglycerides). Recoveries of acetaminophen were within the sponsor's acceptance criteria of  $\pm 10\%$ . No interference was noted when tested up to the concentrations shown in the table below. The H and I index values in the table are equivalent to  $\sim 1\mathrm{mg / dL}$ .

|   | Conc. Of Acetaminophen (μg/mL) | No interference up to  |
| --- | --- | --- |
|  Lipemia Level 1 | 6.3 | 1100 mg/dL  |
|  Lipemia Level 2 | 29.7 | 997 mg/dL  |
|  Lipemia Level 3 | 52.7 | 810 mg/dL  |
|  Lipemia Level 4 | 104 | 698 mg/dL  |
|  Lipemia Level 5 | 149 | 682 mg/dL  |
|  Lipemia Level 6 | 178 | 678 mg/dL  |
|  Hemolysis Level 1 | 5.8 | 926 H index  |
|  Hemolysis Level 2 | 28.2 | 936 H index  |
|  Hemolysis Level 3 | 46.1 | 1009 H index  |
|  Hemolysis Level 4 | 91.8 | 1008 H index  |
|  Hemolysis Level 5 | 135 | 1016 H index  |
|  Hemolysis Level 6 | 174 | 817 H index  |
|  Unconjugated bilirubin Level 1 | 6.2 | 47 I index  |
|  Unconjugated bilirubin Level 2 | 30.2 | 45 I index  |
|  Unconjugated bilirubin Level 3 | 51.1 | 63 I index  |
|  Unconjugated bilirubin Level 4 | 99.1 | 63 I index  |
|  Unconjugated bilirubin Level 5 | 150 | 63 I index  |
|  Unconjugated bilirubin Level 6 | 178 | 63 I index  |
|  Conjugated bilirubin Level 1 | 6.5 | 45 I index  |
|  Conjugated bilirubin | 30.3 | 46 I index  |

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# ii. Interference from common drugs

Interference from common drugs was also examined. A total of 24 commonly used drugs were examined for potential interferences. Testing was performed with serum sample pools at two levels of acetaminophen ( $\sim 7$  and  $\sim 30~\mu \mathrm{g / mL}$ ). Recoveries of acetaminophen were within the sponsor's acceptance criteria of  $\pm 10\%$ . The highest concentrations of common drugs shown not to interfere with the assay are provided in the table below.

|  Drug | Highest Concentration Shown Not to Interfere with ACET2  |
| --- | --- |
|  Acetylcysteine | 1663 μg/mL  |
|  Acetylsalicylic acid | 1000 mg/L  |
|  Ampicillin-sodium | 1000 mg/L  |
|  Ascorbic acid | 300 mg/L  |
|  Cefoxitin | 2500 mg/L  |
|  Cyclosporine | 5 mg/L  |
|  Doxycycline | 50 mg/L  |
|  Phenylbutazone | 400 mg/L  |
|  Rifampicin | 64 mg/L  |
|  Theophylline | 100 mg/L  |
|  Amitriptyline | 277 μg/mL  |
|  Caffeine | 1000 μg/mL  |
|  Codeine | 1.6 μg/mL  |
|  Diazepam | 5.1 μg/mL  |
|  Heparin | 5000 U/mL  |
|  Ibuprofen | 500 mg/L  |
|  Levodopa | 20 mg/L  |
|  Methyldopa | 20 mg/L  |
|  Metronidazole | 200 mg/L  |
|  Methionine | 1000 μg/mL  |
|  Phenylephrine | 20 μg/mL  |
|  Propoxyphene | 20 μg/mL  |
|  Salicylate | 1000 μg/mL  |

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|  Secobarbital | 22 μg/mL  |
| --- | --- |
|  Imipramine | 280 μg/mL  |
|  Cysteine | 1300 μg/mL  |

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison test was performed on the Roche/Hitachi cobas c 501 analyzer by testing 117 human serum samples in singlicate on the Acetaminophen Gen.2 assay and the predicate device. The samples ranged in concentration from 5.2 to 198  $\mu \mathrm{g} / \mathrm{mL}$ . An additional set of eleven native serum samples from individual patients taking acetaminophen were spiked with a stock solution of  $4\mathrm{mg / mL}$  acetaminophen in NaCl so concentrations were above the measuring range of the assay. These samples were spiked with a minimal volume of the stock solution, so that dilution effects were minimized. Deming regression analysis resulted in a slope of 1.02, a y-intercept of -0.699, and a correlation coefficient of 0.997. Ninety-five percent confidence intervals for the y-intercept and slope were -0.981 to -0.417 and 1.005 to 1.030, respectively.

b. Matrix comparison:

Matrix comparison studies were performed for Li-Heparin plasma vs serum,  $\mathrm{K}_2$ -EDTA plasma vs serum, and  $\mathrm{K}_3$ -EDTA plasma vs. serum. A total of 50 tubes were collected per anticoagulant and percent recovery was determined. All percent recoveries were within  $\pm 10\%$ .

|  anticoagulants | Sample concentration range tested (μg/mL) | Claimed Measuring Range (μg/mL)  |
| --- | --- | --- |
|  Li-Heparin | 2.6 - 187 | 5 – 200  |
|  K2-EDTA (full) | 2.6 - 187  |   |
|  K3-EDTA (full) | 2.6 - 187  |   |

In addition, the following linear regression statistics were obtained (Passing/Bablok):

|  Matrix | slope | y-intercept | r value  |
| --- | --- | --- | --- |
|  Lithium-heparin vs serum | 0.989 | 0.0891 | 0.998  |
|  K2-EDTA vs serum | 1.000 | 0.000 | 0.998  |
|  K3-EDTA vs serum | 0.992 | -0.163 | 0.998  |

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12

3. Clinical studies:

a. Clinical Sensitivity:
Not applicable.

b. Clinical specificity:
Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable.

4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:

Normal therapeutic doses of acetaminophen result in serum concentrations of 10-30 µg/mL (66-199 µmol/L) in healthy adults. (From Jacobs DS, DeMott WR, Grad HI, et al. Laboratory Test Handbook 5th ed. Stow, Ohio: Lexi Comp Inc 2001;768).

Toxic manifestations have been observed at serum concentrations > 100 µg/mL, however the toxic range is generally reported at > 200 µg/mL. Toxic concentrations can be more effectively related to post dose interval; > 200, > 100, and > 50 µg/mL serum concentrations at 4, 8, and 12 hours post dose, respectively. (Rumack BH. Acetaminophen overdose. Arch Intern Med 1981;141:380)

Each laboratory should investigate the transferability of the expected values of its own patient population and if necessary determine its own reference ranges.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

---

**Source:** [https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKB/K141928](https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKB/K141928)

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