← Product Code [LDP](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/LDP) · K081938

# ACETAMINOPHEN L3K ASSAY, AND ACETAMINOPHEN L3K ASSAY, MODELS 506-10, 506-30 (K081938)

_Genzyme Diagnostics P.E.I., Inc. · LDP · May 1, 2009 · Clinical Toxicology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/LDP/K081938

## Device Facts

- **Applicant:** Genzyme Diagnostics P.E.I., Inc.
- **Product Code:** [LDP](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/LDP.md)
- **Decision Date:** May 1, 2009
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.3030
- **Device Class:** Class 2
- **Review Panel:** Clinical Toxicology

## Indications for Use

For the quantitative measurement of acetaminophen in serum and plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity. Excessive amounts of acetaminophen leads to hepatotoxicity and nephrotoxicity. In acute overdosage, acetaminophen can cause severe hepatic damage leading to hepatic failure if untreated.

## Device Story

The Acetaminophen L3K® Assay is an in vitro diagnostic reagent kit for the quantitative measurement of acetaminophen in human serum and plasma. The device utilizes an enzymatic colorimetric method involving aryl acylamidase to hydrolyze acetaminophen, followed by an oxidative coupling reaction with 2,5-dimethylphenol to produce a measurable color change. The intensity of the color is proportional to the concentration of acetaminophen in the sample. The assay is intended for use in clinical laboratory settings by trained personnel. Healthcare providers use the resulting quantitative values to assess the severity of acetaminophen overdose, monitor for potential hepatotoxicity and nephrotoxicity, and guide clinical treatment decisions. The assay provides a rapid diagnostic tool to identify patients at risk of severe hepatic damage or failure, facilitating timely medical intervention.

## Clinical Evidence

No clinical data. Performance established via bench testing on the Hitachi 717 analyzer. Precision studies (n=40 runs) showed total CV% between 0.6% and 2.9%. Linearity evaluated across 11 concentrations (slope 0.993). Method comparison against predicate (n=88 samples) yielded a correlation coefficient of 0.9998, slope 1.063, and y-intercept 7.0 μmol/L. Matrix comparison (n=25 matched serum/plasma sets) showed high correlation (r=0.9999). Analytical specificity testing confirmed no significant interference from common endogenous substances or therapeutic drugs.

## Technological Characteristics

Two-part liquid reagent system. R1: buffer (pH 8.6), MnCl2, aryl acylamidase, surfactant, preservatives. R2: sodium carbonate buffer (pH 12.2), 2,5-dimethylphenol, surfactant, preservatives. Principle: enzymatic hydrolysis followed by oxidative coupling colorimetry. Standalone diagnostic assay for use on clinical chemistry analyzers.

## Regulatory 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.

## Predicate Devices

- Genzyme Diagnostics P.E.I. Inc. ([K042330](/device/K042330.md))

## Submission Summary (Full Text)

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1

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

A. 510(k) Number:
k081938

B. Purpose for Submission:
New Device

C. Measurand:
Acetaminophen

D. Type of Test:
Quantitative Colorimetry

E. Applicant:
Genzyme Diagnostics P.E.I., Inc.

F. Proprietary and Established Names:
Acetaminophen L3K Assay

G. Regulatory Information:
1. Regulation section:
21 CFR Section 862.3030 - Acetaminophen test system
2. Classification:
Class II
3. Product code:
LDP – Acetaminophen, colorimetry
4. Panel:
Toxicology (91)

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H. Intended Use:

1. Intended use(s):

See indications for use below.

2. Indication(s) for use:

For the quantitative measurement of acetaminophen in serum and plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity. Excessive amounts of acetaminophen leads to hepatotoxicity and nephrotoxicity. In acute overdosage, acetaminophen can cause severe hepatic damage leading to hepatic failure if untreated.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

Performance characteristics were established using the Hitachi 717 analyzer.

I. Device Description:

This device contains three liquid ready-to-use components; a component that contains an acetaminophen enzyme reagent, an acetaminophen color reagent, and an acetaminophen standard.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Diagnostic Chemicals, Ltd. Acetaminophen-SL Assay

2. Predicate K number(s):

k042330

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Enzyme method | Aryl Acylamidase | Aryl Acylamidase  |
|  Sample type | Serum and Plasma | Serum and Plasma  |
|  Form | Liquid Ready to use | Liquid Ready to use  |
|  Reagent storage | 2 – 8°C | 2 – 8°C  |

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|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Chromophore used in the oxidative coupling reaction | 2,5 dimethylphenol | 8 hydroxyquinoline  |
|  Measuring range | 4-2500 μmol/L | 20-2500 μmol/L  |

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

CLSI Guidance EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods

# L. Test Principle:

The enzyme, acyl amidohydrolase, cleaves the amide bond of the acetaminophen molecule, leaving p-aminophenol and acetate. The p-aminophenol is coupled with 2,5-dimethylphenol in the presence of manganese ions to form a colored compound, 4-(4-iminophenol)-2,5-dimethylcyclohexadiene-1-one. The increased absorbance due to the formation of 4-(4-iminophenol)-2,5-dimethylcyclohexadiene-1-one is directly proportional to the acetaminophen in the sample.

# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility:

Total precision studies were performed on the Hitachi 717 in accordance CLSI guidance document EP5-A2. A total of 40 runs were performed on 20 different days. Each run consisted of 3 concentrations of serum controls each run in duplicate. Controls were run on the same instrument twice a day by one operator in Genzyme Diagnostics P.E.I. Inc. laboratories. Within run precision testing was performed by testing three serum controls 20 times each in one run. The results are summarized below.

|  Acetaminophen Concentration (μmol/L) | Total SD (μmol/L) | Total CV % | Acetaminophen Concentration (μmol/L) | Within SD (μmol/L) | Within CV %  |
| --- | --- | --- | --- | --- | --- |
|  67 | 1.9 | 2.9 | 67 | 1.0 | 1.5  |
|  243 | 3.1 | 1.3 | 240 | 1.9 | 0.8  |
|  743 | 9.9 | 1.3 | 729 | 4.6 | 0.6  |

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An additional precision study consisting of a total of 40 runs on 10 different days was performed. Each run consisted of 2 concentrations of serum controls run in duplicate. Within run and total precision were calculated and are summarized below.

|  Acetaminophen Concentration (μmol/L) | Total SD (μmol/L) | Total CV % | Acetaminophen Concentration (μmol/L) | Within SD (μmol/L) | Within CV %  |
| --- | --- | --- | --- | --- | --- |
|  1331 | 17.2 | 1.3 | 67 | 5.3 | 0.4  |
|  2120 | 30.6 | 1.4 | 240 | 10.89 | 0.5  |

b. Linearity/assay reportable range:

Linearity was evaluated on the Hitachi 717 by testing a spiked serum set that consisted of 11 concentrations of acetaminophen across the assay range. Each sample was tested four times and linearity was calculated. All samples tested were within $\pm 3.9\%$ of the expected value and the linear regression calculations resulted in a slope of 0.993 and an intercept of $1.6~\mu \mathrm{mol} / \mathrm{L}$. These results support the manufacture's claimed measurement range of 4-2500 umol/L.

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

The calibrator was previously cleared under k952949.

d. Detection limit:

The limit of quantitation (LoQ) was evaluated on the Hitachi 717 by performing serial dilutions of a commercial control, then testing each dilution $n = 40$ over 5 days. The sponsor defined the LoQ as the lowest concentration at which the CV% did not exceed $20\%$. The LoQ was calculated as $4\mu \mathrm{mol} / \mathrm{L}$, supporting the claimed lower limit of the assay.

e. Analytical specificity:

Interferences from hemolysis, icterus, lipemia, ascorbic acid, and N-acetylcysteine were evaluated on the Hitachi 717 by testing three concentrations of acetaminophen with multiple concentrations of each interferent. Significant interference was defined by the manufacturer as $>10\%$ or $\pm 8~\mu \mathrm{mol} / \mathrm{L}$ variance from control, whichever is greater. The highest concentrations of each substance that did not show significant interference with each acetaminophen concentration tested are shown below.

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|  Acetaminophen Concentration | Concentration without Significant Interference  |
| --- | --- |
|  μmol/L | Hemoglobin (mg/dL)  |
|  93 | 200  |
|  315 | 800  |
|  918 | 1000  |
|  μmol/L | Conjugated Bilirubin (mg/dL)  |
|  110 | 16  |
|  327 | 40  |
|  936 | 40  |
|  μmol/L | Unconjugated Bilirubin (mg/dL)  |
|  102 | 40  |
|  328 | 40  |
|  990 | 40  |
|  μmol/L | Intralipid (mg/dL)  |
|  101 | 200  |
|  341 | 1000  |
|  984 | 1000  |
|  μmol/L | Ascorbic Acid (μg/dL)  |
|  104 | 3000  |
|  313 | 3000  |
|  968 | 3000  |
|  μmol/L | N-Acetylcysteine (mg/L)  |
|  92 | 2000  |
|  322 | 2000  |
|  933 | 2000  |

Interferences from the following therapeutic drugs were tested as recommended in CLSI EP7-A2 Interference Testing in Clinical Chemistry at acetaminophen concentrations of 33 μmol/L and 199 μmol/L. Significant interference was defined as > 10% or ±8 μmol/L variance from control, whichever is greater. The following drugs did not show significant interference at the concentrations listed.

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|  Substance Tested | Concentration with no Significant Interference  |
| --- | --- |
|  Theophylline | 222 mmol/L  |
|  Phenylbutazone | 2.89 mmol/L  |
|  Ibuprofen | 2425 mmol/L  |
|  Imipramine | 2.5 mmol/L  |
|  Acetysalicylic Acid | 6.51 mmol/L  |
|  Levodopa | 25.3 mmol/L  |
|  Ampicillin | 152 mmol/L  |
|  Doxycycline | 67.5 mmol/L  |
|  Amitriptyline | 3.61 mmol/L  |
|  Metronidazole | 701 mmol/L  |
|  Cefoxitin | 1546 mmol/L  |
|  Cyclosporin | 10.0 mmol/L  |
|  Methyl-I-Dopa | 71 mmol/L  |
|  Rifampicin | 78.1 mmol/L  |
|  Salicylate | 4.34 mmol/L  |
|  Ascorbic Acid | 342 mmol/L  |

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study was performed on the Hitachi 717 by testing 88 patient samples in singlicate on the Acetaminophen L3K Assay and a previously cleared predicate device. The samples ranged in concentration from 38 to 2361 μmol/L. Linear regression was performed and resulted in a slope of 1.063 (95% confidence interval 1.058 to 1.068), a y-intercept of 7.0 μmol/L (95% confidence interval 3.2 to 11.2), and a correlation coefficient of 0.9998.

b. Matrix comparison:

A matrix comparison study was performed on the Hitachi 717 by testing 25 sets of matched serum and lithium heparin plasma samples with acetaminophen concentrations that spanned the full measuring range of the device. Linear regression analysis was performed and resulted in the following equation. y = 0.999x - 2.2. The correlation coefficient was 0.9999.

3. Clinical studies:

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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:

The package insert contains the following reference ranges cited from literature. (Tietz Textbook of Clinical Chemistry, Second Edition, pp 1168, 2212, W.B. Saunders Company, Philadelphia (1994))

Therapeutic concentration: < 199 μmol/L (30 μg/mL)

Toxic concentration: > 1324 μmol/L (200 μg/mL)

These values are suggested guidelines. It is recommended that each laboratory establish its own expected range.

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.

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**Source:** [https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/LDP/K081938](https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/LDP/K081938)

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