RANDOX ETHANOL ASSAY

K092273 · Randox Laboratories, Ltd. · DIC · Nov 1, 2010 · Clinical Toxicology

Device Facts

• Record ID: K092273
• Device Name: RANDOX ETHANOL ASSAY
• Applicant: Randox Laboratories, Ltd.
• Product Code: DIC · Clinical Toxicology
• Decision Date: Nov 1, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3040
• Device Class: Class 2

Intended Use

The Randox Ethanol Assay is an in vitro diagnostic test for the quantitative analysis of Ethanol in human urine and serum on the forme analysers, which includes the JX day to na™ and the Amota™ analysers. The measurement of ethanol is used for the diagnosis and treatment of alcohol intoxication and poisoning. This is an in vitro diagnostic device intended for prescription use only. The Randox Ethanol Calibrator Set is intended for the Randox Ethanol assay, which is used for the quantitative analysis of ethanol in human urine and serum on the December analysers which includes the X day to na™ and the 121mona™. The Randox Ethanol Control Set is intended for the quality control of the Randox Ethanol assay, which is used for the quantitative analysis of ethanol in human urine and serum on the forme analysers which includes the Aday to na™ and the Mimola™ This is an in vitro diagnostic device intended for prescription use only.

Device Story

The Randox Ethanol Assay is an in vitro diagnostic reagent system for the quantitative measurement of ethanol in human urine and serum samples. It is designed for use on automated clinical chemistry analyzers (e.g., Daytona, Monaco). The assay utilizes enzymatic chemistry to determine ethanol concentration; the resulting absorbance change is measured photometrically by the analyzer. The device provides quantitative results to clinicians to assist in the diagnosis and management of alcohol intoxication and poisoning. It is intended for professional use in clinical laboratory settings.

Clinical Evidence

No clinical studies were performed. Substantial equivalence is supported by analytical performance data including precision/reproducibility (80 runs per concentration), linearity (r > 0.99), limit of detection/quantitation, and interference testing. Method comparison studies against the predicate device using clinical serum and urine samples showed high correlation (r > 0.99).

Technological Characteristics

Ready-to-use liquid reagents: Ethanol Buffer (tris, sodium azide) and Ethanol Enzyme Reagent (alcohol dehydrogenase, NAD, sodium azide, stabilizers). Kinetic spectrophotometric measurement at 340 nm. Calibrators/controls are human urine-based. Complies with CLSI guidelines EP5-A2, EP6-A, EP7-A2, EP17-A, and EP9-A2.

Indications for Use

Indicated for the quantitative analysis of ethanol in human urine and serum for the diagnosis and treatment of alcohol intoxication and poisoning. Intended for prescription use.

Regulatory Classification

Identification

An alcohol test system is a device intented to measure alcohol (e.g., ethanol, methanol, isopropanol, etc.) in human body fluids (e.g., serum, whole blood, and urine). Measurements obtained by this device are used in the diagnosis and treatment of alcohol intoxication and poisoning.

Predicate Devices

• Randox Ethanol Assay (K092273)

Submission Summary (Full Text)

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

A. 510(k) Number:
k092273

B. Purpose for Submission:
New device

C. Measurand:
Ethanol (Ethyl Alcohol)

D. Type of Test:
Quantitative, enzymatic Alcohol Dehydrogenase

E. Applicant:
Randox Laboratories

F. Proprietary and Established Names:
Randox Ethanol Assay
Randox Ethanol Calibrator/Control Set

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DIC | Class II | 21 CFR 862.3040, Alcohol test system | 91-Toxicology |
| DLJ | Class II | 21 CFR 862.3200, Clinical toxicology calibrators | 91-Toxicology |
| LAS | Class I, reserved | 21 CFR 862.3280, Clinical toxicology control material | 91-Toxicology |

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H. Intended Use:

1. Intended use(s):

See indications for use below

2. Indication(s) for use:

Randox Ethanol Assay

The Randox Ethanol Assay is an in vitro diagnostic test for the quantitative analysis of Ethanol in human urine and serum on the Xseries analyzers, which includes the Xdaytona and the Ximola analyzers.

The measurement of ethanol is used for the diagnosis and treatment of alcohol intoxication and poisoning.

This is an in vitro diagnostic device intended for prescription use only.

Randox Ethanol Calibrator

The Randox Ethanol Calibrator is intended for the calibration of the Randox Ethanol assay, which is used for the quantitative analysis of ethanol in human urine and serum on the Xseries analyzers, which includes the Xdaytona and the Ximola analyzers.

Randox Ethanol Control

The Randox Ethanol Control Set is intended for the quality control of the Randox Ethanol assay, which is used for the quantitative analysis of ethanol in human urine and serum on the Xseries analyzers, which includes the Xdaytona and the Ximola analyzers.

This is an in vitro diagnostic device intended for prescription use only.

3. Special conditions for use statement(s):

This assay is for prescription use

4. Special instrument requirements:

The sponsor provided data for the RX Daytona and RX Imola analyzers

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I. Device Description:

This assay consists of ready-to-use liquid reagents. Reagent 1 is an Ethanol Buffer which contains tris and sodium azide. Reagent 2 is an Ethanol Enzyme Reagent containing alcohol dehydrogenase, NAD, Sodium azide and stabilizers.

The calibrators and controls are ready-to-use human urine-based liquid and are sold separately.

J. Substantial Equivalence Information:

1. Predicate device name(s):

DRI MULTIGENT Ethanol Assay

DRI MULTIGENT Alcohol Calibrators and Controls

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

K923783 and k924733 respectively

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicates |
| Intended Use | For the quantitative analysis of ethanol.
Calibrator Set is intended for the calibration of the Ethanol assay
Control Set is intended for the quality control of the Ethanol assay | Same |
| Principle of Procedure | Kinetic assay | Same |
| Setting of Use | For prescription use only | Same |
| Calibrator/Control format | Liquid Ready to Use Control Low 50 mg/dL, Control high 300 mg/dL, Level 0 calibrator 0 mg/dL and Level 1 calibrator 100 mg/dL | Same |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay Range | Rx Daytona, Serum 8-500 mg/dl
Rx Daytona, Urine 20-500 mg/dl
Rx Imola, Serum 3-500 mg/dL
Rx Imola, Urine 3-500 mg/dL | 10 – 600 mg/dL |
| Matrix | Urine and Serum | Urine, Serum and Plasma |
| Calibrator/Control size | 1 x 10 mL | 1 x 5 mL |

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

CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition (2004)

CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures, A Statistical Approach: Approved Guideline (2003)

CLSI EP7-A2: Interference Testing in Clinical Chemistry; Approved Guideline (2002)

CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline (2004)

CLSI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (2002)

## L. Test Principle:

The RANDOX ethanol assay is a ready-to-use liquid reagent. The assay is based on the oxidation of ethyl alcohol to acetaldehyde by alcohol dehydrogenase (ADH) and NAD to NADH, resulting in an absorbance change measured spectrophotometrically at 340 nm. The concentration of ethanol alcohol is directly proportional to the ADH activity, measured at 340 nm wavelength.

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

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Reproducibility studies were conducted by spiking serum or urine to the following concentrations; 20 mg/dL, 50 mg/dL, 150 mg/dL, 300 mg/dL and 475 mg/dL. Testing was performed over 20 non-consecutive, two runs/day and two replicates /run, 2 operators and 5 calibrations on the Imola and 6 on the Daytona instruments for a total of 80 runs/concentration. The results are in the table below:

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Rx Daytona

| Sample Description (Concentration mg/dL) | Sample Type | N | Mean | SD | CV | SD | CV |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 20 | Serum | 80 | 18.76 | 1.07 | 5.7 | 3.10 | 16.6 |
| | Urine | 80 | 18.82 | 1.64 | 8.7 | 3.58 | 19.0 |
| 50 | Serum | 80 | 47.67 | 1.62 | 3.4 | 3.31 | 6.9 |
| | Urine | 79 | 46.04 | 1.62 | 3.5 | 3.16 | 6.9 |
| 150 | Serum | 79 | 147.21 | 3.31 | 2.2 | 5.39 | 3.7 |
| | Urine | 80 | 144.56 | 1.87 | 1.3 | 4.81 | 3.3 |
| 300 | Serum | 80 | 296.16 | 3.99 | 1.3 | 9.06 | 3.1 |
| | Urine | 80 | 299.62 | 3.82 | 1.3 | 9.58 | 3.3 |
| 475 | Serum | 79 | 478.01 | 3.91 | 0.8 | 13.86 | 2.9 |
| | Urine | 79 | 487.96 | 5.44 | 1.1 | 13.52 | 2.8 |

Rx Imola

| Sample Description (Concentration ng/mL) | Sample Type | N | Mean | SD | CV | SD | CV |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 20 | Serum | 79 | 19.52 | 0.88 | 4.5 | 1.15 | 5.9 |
| | Urine | 80 | 19.15 | 0.78 | 4.1 | 1.04 | 5.4 |
| 50 | Serum | 79 | 47.77 | 2.00 | 4.2 | 2.09 | 4.4 |
| | Urine | 80 | 45.97 | 1.96 | 4.3 | 1.96 | 4.3 |
| 150 | Serum | 80 | 147.01 | 7.13 | 4.9 | 7.31 | 5.0 |
| | Urine | 80 | 144.40 | 3.71 | 2.6 | 4.49 | 3.1 |
| 300 | Serum | 79 | 295.88 | 13.28 | 4.5 | 13.30 | 4.5 |
| | Urine | 80 | 298.50 | 7.59 | 2.5 | 9.34 | 3.1 |
| 475 | Serum | 80 | 472.68 | 20.85 | 4.4 | 20.85 | 4.4 |
| | Urine | 80 | 482.48 | 3.16 | 0.7 | 11.67 | 2.4 |

# b. Linearity/assay reportable range:

Linearity samples for serum and urine were prepared from two pools of each sample type with ethanol concentrations near the extremes of the assay range (low pool and high pool). The two pools were mixed to create 9 additional pools of intermediate concentrations. Five determinations of each pool were tested on each instrument and a linear regression analysis was performed by the method of least squares. The data provided in the tables below supports the claimed measuring range for Imola serum and urine $3 - 500\mathrm{mg / dL}$ and Daytona serum $8 - 500\mathrm{mg / dL}$ and urine $20 - 500\mathrm{mg / dL}$ .

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| | Imola Urine | | Daytona Urine | |
| --- | --- | --- | --- | --- |
| Sample | Expected ETOH mg/dL | Observed ETOH mg/dL | Expected ETOH mg/dL | Observed ETOH mg/dL |
| 1 | 3 | 2.94 | 69 | 73.71 |
| 2 | 62.7 | 60.26 | 1.28 | 134.74 |
| 3 | 122.4 | 133.53 | 187 | 200.63 |
| 4 | 182.1 | 181.96 | 246 | 254.26 |
| 5 | 241.8 | 251.04 | 305 | 306.91 |
| 6 | 301.5 | 304.43 | 364 | 368.99 |
| 7 | 361.2 | 392.56 | 423 | 420.54 |
| 8 | 420.9 | 426.85 | 482 | 471.24 |
| 9 | 480.6 | 486.69 | | |
| Slope | 1.03 | | 0.96 | |
| Intercept | 0.82 | | 13.75 | |
| r | 0.997 | | 0.999 | |
| | Imola Serum | | Daytona Serum | |
| --- | --- | --- | --- | --- |
| Sample | Expected ETOH mg/dL | Observed ETOH mg/dL | Expected ETOH mg/dL | Observed ETOH mg/dL |
| 1 | 3 | 2.93 | 8 | 8.32 |
| 2 | 62.7 | 60.04 | 67.2 | 72.43 |
| 3 | 122.4 | 128.18 | 126.4 | 136.88 |
| 4 | 182.1 | 187.53 | 185.6 | 190.33 |
| 5 | 241.8 | 250.37 | 244.8 | 254.49 |
| 6 | 301.5 | 291.44 | 304 | 310.35 |
| 7 | 361.2 | 361.72 | 363.2 | 363.56 |
| 8 | 420.9 | 414.50 | 422.4 | 423.48 |
| 9 | 480.6 | 457.25 | 481.6 | 467.85 |
| Slope | 0.96 | | 0.98 | |
| Intercept | 6.27 | | 8.74 | |
| r | 0.999 | | 0.999 | |

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

Calibrator and controls are prepared by spiking ethanol (supplied by Sigma-Aldrich) into inorganic buffer. Value assignment is performed by testing new lots of calibrator and control against the master lot.

Stability of the calibrators and controls was demonstrated by real-time stability studies. Calibrators and controls come ready to use. The calibrator is stable up to the expiry date (12 months) when capped and the open vial is stable for 27 days stored at 2-8° C.

d. Detection limit:

The method to determine detection limit is based upon the CLSI document EP17-A3. The study assayed 60 replicates of blank and 6 low positives samples on both instruments for the LoB and LoD. The LoQ was determined by assaying 200 replicates of each of 4 additional low positive samples on both instruments. The results are presented in the Table below.

| | Limit of Blank | | Limit of Detection | | Limit of Quantitation | |
| --- | --- | --- | --- | --- | --- | --- |
| | Serum | Urine | Serum | Urine | Serum | Urine |
| | mg/dL | | mg/dL | | mg/dL | |
| RX Daytona | 1.17 | 1.92 | 3.34 | 4.75 | 8.00 | 20.00 |
| RX Imola | 1.35 | 0.59 | 1.79 | 1.19 | 3.00 | 3.00 |

e. Analytical specificity:

The Randox ethanol assay was evaluated for interference. The interfernet was spiked into serum and urine samples having ethyl alcohol concentrations of 10 and 100 mg/dL. The following substances at the tested concentration demonstrated no significant bias (defined as < 10%).

| | RX Daytona | | RX Imola | |
| --- | --- | --- | --- | --- |
| Serum ethyl alcohol concentration | 10 mg/dL | 100 mg/dL | 10 mg/dL | 100 mg/dL |
| Interferent | Tested Concentration (mg/dL) | | Tested Concentration (mg/dL) | |
| Hemoglobin | 62.5 | 1000 | 125 | 1000 |
| Triglycerides | 500 | 500 | 250 | 500 |
| Intralipid | 187.5 | 750 | 40 | 375 |
| Total Bilirubin | 60 | 80 | 20 | 80 |
| Direct Bilirubin | 60 | 80 | 20 | 80 |
| Acetaminophen | 20 | 20 | 20 | 20 |

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| | RX Daytona | | RX Imola | |
| --- | --- | --- | --- | --- |
| Amikacin | 8 | 8 | 8 | 8 |
| Ampicillin | 5.3 | 5.3 | 5.3 | 5.3 |
| Ascorbic Acid | 6 | 6 | 6 | 6 |
| Caffeine | 6 | 6 | 6 | 6 |
| Cardamezepine | 3 | 3 | 3 | 3 |
| Cloramphenicol | 5 | 5 | 5 | 5 |
| Clordiazepoxide | 1 | 1 | 1 | 1 |
| Chlorpromazine | 0.2 | 0.2 | 0.2 | 0.2 |
| Cholesterol | 30 | 503 | 251.5 | 503 |
| Cimetidine | 2 | 2 | 2 | 2 |
| Creatinine | 30 | 30 | 30 | 30 |
| Dextran | 6000 | 6000 | 6000 | 6000 |
| Diazepam | 0.51 | 0.51 | 0.51 | 0.51 |
| Digoxin | 6.1 | 6.1 | 6.1 | 6.1 |
| Erythromycin | 6 | 6 | 6 | 6 |
| Ethosuximide | 25 | 25 | 25 | 25 |
| Furosemide | 6 | 6 | 6 | 6 |
| Gentamicin | 1 | 1 | 1 | 1 |
| Heparin | 3 U/mL | 3 U/mL | 3 U/mL | 3 U/mL |
| Ibuprofen | 50 | 50 | 50 | 50 |
| Immunoglobulin | 5000 | 5000 | 5000 | 5000 |
| LDH | 237,500 U/mL | 237,500 U/mL | 237,500 U/mL | 237,500 U/mL |
| Lactate | 901 | 901 | 901 | 901 |
| Lidocaine | 1.2 | 1.2 | 1.2 | 1.2 |
| Lithium | 2.2 | 2.2 | 2.2 | 2.2 |
| Mannitol | 500 | 500 | 500 | 500 |
| Nicotine | 0.1 | 0.1 | 0.1 | 0.1 |
| Penicillin | 25 u/mL | 25 U/mL | 25 U/mL | 25 U/mL |
| Pentobarbital | 8 | 8 | 8 | 8 |
| Phenobarbital | 10 | 10 | 10 | 10 |
| Phenytoin | 5 | 5 | 5 | 5 |
| Primidone | 4 | 4 | 4 | 4 |
| Propoxyphene | 0.16 | 0.16 | 0.16 | 0.16 |
| H.S.A. | 37.5 | 1250 | 100 | 1500 |
| Protein-total | 50 | 1500 | 100 | 1500 |
| Salicylic acid | 60 | 60 | 60 | 60 |
| Theophylline | 4 | 4 | 4 | 4 |
| Urea | 500 | 500 | 500 | 500 |
| Uric acid | 20 | 20 | 20 | 20 |
| Valproic acid | 50 | 50 | 50 | 50 |

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| | RX Daytona | RX Imola | |
| --- | --- | --- | --- |
| Urine ethyl alcohol concentration | 100 mg/dL | 10 mg/dL | 100 mg/dL |
| Interferent | Tested Concentration (mg/dL) | Tested Concentration (mg/dL) | |
| Total Bilirubin | 15 | 15 | 15 |
| Direct Bilirubin | 5 | 5 | 5 |
| Hemoglobin | 115 | 68.75 | 115 |
| Creatinine | 30 | 30 | 30 |
| Urea | 285 | 285 | 285 |
| Glucose | 2000 | 2000 | 2000 |
| H.S.A. | 500 | 500 | 500 |
| Ascorbic acid | 1000 | 1000 | 1000 |
| Gamma globulin | 500 | 500 | 500 |
| Oxalic acid | 100 | 100 | 100 |
| Riboflavin | 7.5 | 7.5 | 7.5 |
| Sodium Chloride | 6000 | 6000 | 6000 |
| Boric acid | 1000 | 1000 | 1000 |
| Sodium azide | 1000 | 1000 | 1000 |
| Sodium Fluoride | 1000 | 1000 | 1000 |

Cross-reactivity of structurally related compounds

| Serum and Urine ethyl alcohol concentration 10 mg/dL | RX Daytona | | RX Imola | | |
| --- | --- | --- | --- | --- | --- |
| | | % cross-reactivity | | % cross-reactivity | |
| Compound | Conc. Tested (mg/dL) | Serum | Urine | Serum | Urine |
| 1-Propanol | 3000 | 7.18 | 7.39 | 6.74 | 7.15 |
| 1,2-Propandiol | 3000 | -0.02 | 0.01 | 0.00 | -0.01 |
| 1-Butanol | 3000 | 1.40 | 1.64 | 1.44 | 1.37 |
| Acetaldehyde | 3000 | -0.20 | -0.16 | -0.15 | -0.22 |
| Acetone | 3000 | 0.01 | -0.01 | -0.01 | -0.01 |
| Ethylene glycol | 3000 | 0.05 | 0.05 | 0.05 | 0.04 |
| Isopropanol | 3000 | 0.25 | 0.24 | 0.22 | 0.23 |
| Methanol | 3000 | 0.01 | -0.01 | 0.00 | 0.00 |

f. Assay cut-off:

Not applicable

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2. Comparison studies:

a. Method comparison with predicate device:
Unaltered clinical 50 serum and 60 urine samples were used in the method comparison study. All the samples were measured in singlet and only one specimen per patient was obtained. Samples within the measurement range were used in the data analysis. The correlation study between the device and the predicate for urine and serum yielded the following results.

RX Daytona
| Matrix | n | Slope | Intercept | r | Device range (mg/dL) | Predicate range (mg/dL) |
| --- | --- | --- | --- | --- | --- | --- |
| Serum | 45 | 0.922 | 0.94 | 0.995 | 8-500 | 10-600 |
| Urine | 42 | 1.001 | -2.44 | 0.995 | 20-500 | 10-600 |

RX Imola
| Matrix | n | Slope | Intercept | r | Device range (mg/dL) | Predicate range (mg/dL) |
| --- | --- | --- | --- | --- | --- | --- |
| Serum | 48 | 0.951 | 0.01 | 0.999 | 3-500 | 10-600 |
| Urine | 53 | 0.954 | -2.01 | 0.998 | 3-500 | 10-600 |

b. Matrix comparison:
Assay is for serum and urine samples only

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

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5. Expected values/Reference range:

Ethyl alcohol is not present in detectable concentrations in healthy adults who have not consumed ethanol.

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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