OLYMPUS URIC ACID REAGENT, MODEL OSR6X98

K062862 · Olympus America, Inc. · KNK · Apr 6, 2007 · Clinical Chemistry

Device Facts

• Record ID: K062862
• Device Name: OLYMPUS URIC ACID REAGENT, MODEL OSR6X98
• Applicant: Olympus America, Inc.
• Product Code: KNK · Clinical Chemistry
• Decision Date: Apr 6, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1775
• Device Class: Class 1

Indications for Use

System reagent for the quantitative determination of Uric Acid in human serum, heparinized plasma and urine on OLYMPUS analyzers Measurements of Uric Acid are used in the diagnosis and treatment of numerous renal and metabolic disorders, including renal failure, gout, leukemia, psoriasis, starvation or other wasting conditions, and of patients receiving cytotoxic drugs.

Device Story

Olympus Uric Acid Reagent is an in vitro diagnostic reagent used on Olympus clinical chemistry analyzers. It enables quantitative measurement of uric acid levels in human serum, heparinized plasma, and urine samples. The device is intended for use by clinical laboratory professionals to assist in the diagnosis and management of renal and metabolic conditions, including gout and renal failure, and to monitor patients undergoing cytotoxic therapy. The reagent facilitates automated biochemical analysis within a clinical laboratory setting, providing quantitative data that informs clinical decision-making regarding patient metabolic status and treatment efficacy.

Clinical Evidence

No clinical data provided; bench testing only.

Technological Characteristics

In vitro diagnostic reagent for quantitative uric acid determination. Designed for use on Olympus automated clinical chemistry analyzers. Principle of operation involves enzymatic or chemical reaction for uric acid quantification in serum, plasma, or urine.

Indications for Use

Indicated for quantitative determination of uric acid in human serum, heparinized plasma, and urine to aid in diagnosis/treatment of renal and metabolic disorders (e.g., renal failure, gout, leukemia, psoriasis, wasting conditions) and monitoring patients on cytotoxic drugs.

Regulatory Classification

Identification

A uric acid test system is a device intended to measure uric acid in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of numerous renal and metabolic disorders, including renal failure, gout, leukemia, psoriasis, starvation or other wasting conditions, and of patients receiving cytotoxic drugs.

Submission Summary (Full Text)

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

A. 510(k) Number:
k062862

B. Purpose for Submission
New device

C. Measurand:
Uric acid

D. Type of Test:
Quantitative, enzymatic, colorimetric assay

E. Applicant:
Olympus America Inc.

F. Proprietary and Established Names:
Olympus Uric Acid Reagent

G. Regulatory Information:
1. Regulation Section
21 CFR §862.1775, uric acid test system
2. Classification:
Class I, Reserved
3. Product Code:
KNK
4. Panel
Clinical Chemistry (75)

H. Intended Use:
1. Intended use(s)
See Indications for use below.
2. Indication(s) for use:
Olympus Uric Acid Reagent is for the quantitative determination of Uric Acid in human serum, heparinized plasma and urine on OLYMPUS analyzers.

Measurements of Uric Acid are used in the diagnosis and treatment of numerous renal and metabolic disorders, including renal failure, gout, leukemia, psoriasis, starvation or other wasting conditions, and of patients receiving cytotoxic drugs.

3. Special conditions for use statement(s):
For Prescription Use only
4. Special instrument requirements:
AU400/400°, AU600/640/640°, AU2700/5400 system

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I. Device Description:

This *in vitro* diagnostic reagent is packaged as two reagents, R1 and R2. The final concentrations of the reactive ingredients are presented in the table below:

Phosphate buffer (pH 7.5) 42 mmol/L
Peroxidase ≥ 5.9 kU/L
MADB 0.15 mmol/L
4-Aminophenazone 0.30 mmol/L
EDTA 0.44 mmol/L
Uricase ≥ 250 U/L
Preservatives

J. SUBSTANTIAL EQUIVALENCE INFORMATION

1. Predicate device name(s):
Olympus Uric Acid Reagents

2. Predicate 510(k) number(s):
k961274

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Method Principle | This Olympus Uric Acid procedure is a modification of the Fossati method. Uric acid is converted by uricase to allantoin and hydrogen peroxide. Hydrogen peroxide reacts with 4-aminoantipyrine (4-AAP) in the presence of N,N-bis(4-sulfobutyl)-3,5-dimethylaniline, disodium salt (MADB) to produce a chromophore which is read bichromatically at 660/800 nm. The amount of dye formed is proportional to the uric acid concentration in the sample. | This Olympus Uric Acid procedure is a modification of the Fossati method. Uric acid is converted by uricase to allantoin and hydrogen peroxide. Hydrogen peroxide reacts with 4-aminoantipyrine (4-AAP) in the presence of N,N-bis(4-sulfobutyl)-3,5-dimethylaniline, disodium salt (MADB) to produce a chromophore which is read bichromatically at 660/800 nm. The amount of dye formed is proportional to the uric acid concentration in the sample. |
| Calibrator Traceability | National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 909b | National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 909b |
| On-board stability | 30 days | 30 days |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | System reagent is for the quantitative determination of Uric Acid in human serum, heparinized plasma and urine on OLYMPUS analyzers. | System reagent is for the quantitative determination of Uric Acid in human serum, and urine on OLYMPUS analyzers. |
| Specimen | Serum, plasma, & urine | Serum, & urine |

# K. STANDARD/GUIDANCE DOCUMENT REFERENCED (IF APPLICABLE)

CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; CLSI EP7-A2: Interference Testing in Clinical Chemistry; Approved Guideline.

# L. Test Principle

This Olympus Uric Acid procedure is a modification of the Fossati method. Uric acid is converted by uricase to allantoin and hydrogen peroxide. Hydrogen peroxide reacts with 4-aminoantipyrine (4-AAP) in the presence of N,N-bis(4-sulfobutyl)-3,5-dimethylaniline, disodium salt (MADB) to produce a chromophore which is read bichromatically at 660/800 nm. The amount of dye formed is proportional to the uric acid concentration in the sample.

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

1. Analytical Performance:

a. Precision /Reproducibility:

Precision was performed by testing four sample pools two-fold twice a day for twenty days. The within-run and total CVs were calculated according to CLSI EP5-A protocol. The within run precision for serum samples is less than 2% and total precision is less than 3% on the AU400/400e, AU600/640/640e, and AU2700/5400 instruments. The within run precision for urine samples is less than 3% and total precision is less than 5% on the AU400/400e, AU600/640/640e, and AU2700/5400 instruments. The results are shown in the table below:

AU400/400ᵉ Serum

| N = 80 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 3.9 | 0.02 | 0.53 | 0.05 | 1.31 |
| 7.3 | 0.05 | 0.64 | 0.07 | 0.98 |
| 9.8 | 0.06 | 0.59 | 0.12 | 1.17 |

AU600/640/640ᵉ Serum

| N = 80 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 3.8 | 0.01 | 0.38 | 0.03 | 0.80 |
| 7.2 | 0.03 | 0.43 | 0.06 | 0.89 |
| 9.7 | 0.05 | 0.53 | 0.08 | 0.85 |

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AU2700/5400 Serum

| N = 80 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 3.8 | 0.02 | 0.48 | 0.06 | 1.49 |
| 7.3 | 0.02 | 0.34 | 0.11 | 1.52 |
| 9.8 | 0.05 | 0.50 | 0.16 | 1.60 |

$\mathrm{AU400 / 400^{e}}$ Urine

| N = 80 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 21.5 | 0.23 | 1.09 | 0.36 | 1.66 |
| 58.0 | 1.06 | 1.84 | 1.37 | 2.36 |
| 88.4 | 1.80 | 2.03 | 1.91 | 2.16 |

AU600/640/640e Urine

| N = 100 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 21.8 | 0.24 | 1.12 | 0.35 | 1.61 |
| 58.4 | 0.95 | 1.63 | 1.33 | 2.28 |
| 89.3 | 1.78 | 2.00 | 2.01 | 2.25 |

AU2700/5400 Urine

| N = 80 | Within run | | Total | |
| --- | --- | --- | --- | --- |
| Mean, mg/dL | SD | CV% | SD | CV% |
| 21.5 | 0.25 | 1.17 | 0.37 | 1.73 |
| 58.2 | 0.76 | 1.31 | 1.27 | 2.19 |
| 88.8 | 1.71 | 1.93 | 1.98 | 2.23 |

b. Linearity/ Assay reportable range.

A linearity study was conducted on the Olympus Uric Acid reagent using prepared standard solutions. Samples were prepared by diluting a high pool containing 33.49 mg/dL with a 0 mg/dL sample and assayed. The linearity was established for serum as 1.5 to 30 mg/dL. For urine linearity, samples were prepared by diluting a high pool containing 123 mg/dL with a 0 mg/dL sample. The linearity was established for urine as 0.7 to 100 mg/dL.

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

The frequency of calibration is every 30 days. Calibration of the Olympus Uric Acid reagent is accomplished by use of the Olympus Chemistry Calibrator (Cat # DR0070 or DR0071), which is traceable to the National Institute of Standard and Technology (NIST) Standard Reference Material (SRM) 909b for serum and plasma specimens. For urine specimens the calibration is established using the Olympus Urine Calibrator (Cat # DR0090).

A stability study was conducted on the Olympus Uric Acid reagent whereby both fresh reagent and reagent at the end of its on-board stability (30 days) were assayed for uric acid recovery on prepared control material and to confirm that the linearity of the reagent was maintained after 30 days on-board,

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The manufacturer recommends in the labeling that during operation of the Olympus analyzer at least two levels of an appropriate quality control material should be tested a minimum of once a day. In addition, these controls should be performed after calibration, with each new lot of reagent, and after specific maintenance or troubleshooting steps described in the appropriate Olympus User's Guide. Quality control testing should be performed in accordance with regulatory requirements and each laboratory's standard procedure.

## d. Detection Limit

The lowest detectable level represents the lowest measurable level of uric acid that can be distinguished from zero. It is calculated as the absolute mean plus three standard deviations of 20 replicates of an analyte free sample.

The lowest detectable level using serum settings was estimated as follows:

| Analyzer | Lowest Detectable Level (mg/dL) |
| --- | --- |
| AU600/640/640^{e} | 0.02 |
| AU400/400^{e} | 0.02 |
| AU2700/5400 | 0.02 |

## Functional Sensitivity:

### Serum:

Precision results (40-fold determination) for a level <0.8 mg/dL are shown below with a CV of <20% for each application.

| Analyzer | Mean Concentration (mg/dL) | SD | CV% |
| --- | --- | --- | --- |
| AU600/640/640^{e} | 0.24 | 0.013 | 5.5 |
| AU2700/5400 | 0.24 | 0.015 | 6.2 |
| AU400/400^{e} | 0.23 | 0.012 | 5.4 |

### Urine:

Precision results (40-fold determination) for a level <3 mg/dL are shown below with a CV of <20% for each application.

| Analyzer | Mean Concentration (mg/dL) | SD | CV% |
| --- | --- | --- | --- |
| AU600/640/640^{e} | 0.64 | 0.058 | 9.0 |
| AU2700/5400 | 0.64 | 0.038 | 5.9 |
| AU400/400^{e} | 0.63 | 0.053 | 8.5 |

## e. Analytical Specificity

A study of common interfering substances was conducted. The results of the study were evaluated following the recommendations of CLSI EP7-A on the AU400/400e, AU600/640/640e, and AU2700/5400. The following substances interfere with this uric acid method:

### AU400/400e

Ascorbic Acid: Interference less than 5% up to 20 mg/dL Ascorbate

Bilirubin: Interference less than 5% up to 40 mg/dL Bilirubin

Hemolysis: Interference less than 5% up to 500 mg/dL Hemolysate

Lipemia: Interference less than 5% up to 1000 mg/dL Intralipid

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AU600/640/640

Ascorbic Acid: Interference less than 5% up to 20 mg/dL Ascorbate
Bilirubin: Interference less than 5% up to 40 mg/dL Bilirubin
Hemolysis: Interference less than 5% up to 500 mg/dL Hemolysate
Lipemia: Interference less than 5% up to 1000 mg/dL Intralipid

AU2700/5400

Ascorbic Acid: Interference less than 5% up to 20 mg/dL Ascorbate
Bilirubin: Interference less than 5% up to 40 mg/dL Bilirubin
Hemolysis: Interference less than 5% up to 500 mg/dL Hemolysate
Lipemia: Interference less than 5% up to 1000 mg/dL Intralipid

f. Assay Cut-off

Not applicable

2. Comparison Studies:

a. Method comparison with predicate device:

Serum

Patient samples were used to compare the Olympus Uric Acid on the AU600 to another Olympus analyzer Uric Acid method (Method 2). Further studies were conducted as outlined below:

| Y Method | AU600/640/640^{e} | AU400/400^{e} | AU2700/5400 |
| --- | --- | --- | --- |
| X Method | Method 2 | AU600/640/640^{e} | AU600/640/640^{e} |
| Slope | 1.014 | 0.973 | 0.980 |
| Intercept | -0.226 | 0.250 | 0.253 |
| Correlation Coeff. (r) | 1.000 | 1.000 | 1.000 |
| No. of Samples (n) | 122 | 122 | 122 |
| Range (mg/dL) | 1.9 – 29.4 | 1.7 - 29.4 | 1.7-29.4 |

Urine

Urine samples were used to compare this Olympus Uric Acid on the AU640 to another Olympus analyzer Uric Acid method (Method 2). Further studies were conducted as outlined below:

| Y Method | AU600/640/640^{e} | AU400/400^{e} | AU2700/5400 |
| --- | --- | --- | --- |
| X Method | Method 2 | AU600/640/640^{e} | AU600/640/640^{e} |
| Slope | 0.981 | 1.034 | 1.014 |
| Intercept | 0.496 | -0.199 | -0.195 |
| Correlation Coeff. (r) | 0.998 | 0.999 | 0.999 |
| No. of Samples (n) | 159 | 159 | 159 |
| Range (mg/dL) | 0.9 – 98.6 | 0.8 - 96.7 | 0.8 – 96.7 |

b. Matrix comparison

Matched serum and heparinized plasma samples were assayed on the AU640 Olympus analyzer to demonstrate that no matrix effect exists for this Olympus Uric acid reagent, between serum and heparinized plasma samples.

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| Slope | 1.018 |
| --- | --- |
| Intercept | -0.241 |
| Correlation Coeff. (r) | 1.000 |
| No. of Samples (n) | 47 |
| Range (mg/dL) | 1.51 – 29.1 |

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 Ranges: In the labeling the expected values are provided from Teitz, Guide to Laboratory Tests, 4th Edition, Saunders, 2006 as follows:

Serum: Adults:
Female: 2.3 - 6.6 mg/dL
Male: 4.4 - 7.6 mg/dL
Urine:
Female: 250 – 750 mg/24 hours
Male: 250 – 800 mg/24 hours

Excretion may decrease by 20 to 25% on a purine-free diet to less than 400 mg/24 hours. Expected values may vary with age, sex, diet and geographical location. Each laboratory should determine its own expected values as dictated by good laboratory practice.

N. Proposed Labeling:

The labeling is sufficient to and 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.