WAKO L-TYPE CREATININE-M TEST, AND WAKO CREATININE CALIBRATOR

K061775 · Wako Chemicals USA, Inc. · JFY · Feb 23, 2007 · Clinical Chemistry

Device Facts

• Record ID: K061775
• Device Name: WAKO L-TYPE CREATININE-M TEST, AND WAKO CREATININE CALIBRATOR
• Applicant: Wako Chemicals USA, Inc.
• Product Code: JFY · Clinical Chemistry
• Decision Date: Feb 23, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Indications for Use

The L-Type Creatinine-M is an in-vitro assay for the quantitative determination of creatinine in serum, plasma, and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Device Story

Wako L-Type Creatinine-M Test is a two-reagent enzymatic colorimetric assay for automated analyzers (e.g., Hitachi 917). Input: serum, plasma, or urine samples. Principle: creatinine reacts with creatininase, creatinase, sarcosine oxidase, and HMMPS to produce a blue pigment; absorbance of pigment measured to determine creatinine concentration. Output: quantitative creatinine concentration. Used in clinical laboratories by professional staff. Results assist clinicians in diagnosing/treating renal disease and monitoring dialysis. Calibrated using NIST SRM914a-traceable calibrator.

Clinical Evidence

Bench testing only. Precision evaluated via within-run (n=21) and total precision (21 days) studies. Linearity confirmed across 0.2-100 mg/dL (serum/plasma) and 1.0-200 mg/dL (urine). Method comparison against predicate using 60 serum and 60 urine samples showed correlation coefficients of 0.999. Interference testing performed for common endogenous and exogenous compounds. No clinical studies performed.

Technological Characteristics

Enzymatic colorimetric assay; two-reagent system. Reagents contain enzymes, buffers, and stabilizers. Calibrator matrix includes pH, viscosity, and specific gravity adjustors. Traceable to NIST SRM914a. Designed for automated clinical chemistry analyzers (e.g., Hitachi 917).

Indications for Use

Indicated for the quantitative determination of creatinine in serum, plasma, and urine for patients requiring diagnosis and treatment of renal diseases or monitoring of renal dialysis. For professional use only.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• Wako Creatinine HA (k842847)
• Roche Diagnostics Creatinine Plus (k003261)

Submission Summary (Full Text)

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

A. 510(k) Number:
k061775

B. Purpose for Submission:
New device

C. Measurand:
Creatinine

D. Type of Test:
Enzymatic colorimetric

E. Applicant:
Wako Chemicals USA, inc.

F. Proprietary and Established Names:
Wako L-Type Creatinine-M Test
Wako Creatinine Calibrator

G. Regulatory Information:
1. Regulation section:
Creatinine Test: section 862.1225
Calibrator: section 862.1150
2. Classification:
Class II
3. Product code:
Enzymatic Method, Creatinine (JFY)

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Calibrator, secondary (JIT)

4. Panel:
Clinical Chemistry (75)

H. Intended Use:

1. Intended use(s):
See indication(s) for use.

2. Indication(s) for use:
The L-Type Creatinine-M is an in-vitro assay for the quantitative determination of creatinine in serum, plasma, and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

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

4. Special instrument requirements:
Hitachi 917

I. Device Description:
The Wako L-Type Creatinine-M Test is a two reagent system for use on an automated analyzer such as the Hitachi 917. Both reagents contain enzymes with stabilizers and/or buffers. The test is calibrated by using a calibrator with values determined by using enzymatic reagents and SRM914a (NIST) creatinine standard material as the primary standard. The calibrator matrix is an aqueous solution containing pH, viscosity, and specific gravity adjustors.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Wako Creatinine HA and Creatinine Standard Solution
Roche Diagnostics Creatinine Plus

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

k842847, k003261

3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Item | Wako L-Type Creatinine-M | Wako Creatinine HA k842847 |
| Method | HMMPS-method, end point assay | Jaff'e Method, rate assay |
| Storage | Store at 2-10°C | Store at 2-25°C |
| Linearity | 0.2-100 mg/dL in serum/plasma
1.0-200 mg/dL in urine | 0-24 mg/dL |
| LLD | 0.06 mg/dL in urine and 0.03 mg/dL in serum/plasma | 0.0 mg/dL |
| Calibrator | Creatinine Calibrator | Creatinine Standard Solution |
| Sample type | Serum, plasma, urine | Serum |

The device is similar to the Roche Creatinine Plus assay in intended use and matrices measured.

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

CLSI EP5-A: Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline

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

## L. Test Principle:

Creatinine present in samples is acted upon by creatininase, creatinase, sarcosine oxidase, and HMMPS to form a blue pigment. The creatinine concentration is obtained by measuring the absorbance of the blue pigment.

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

### 1. Analytical performance:

a. Precision/Reproducibility:

Within run precision was evaluated by testing 3 serum and 3 urine samples in one run 21 times. The results are summarized below.

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| Sample# | Replicates | Mean(mg/dL) | CV(%) |
| --- | --- | --- | --- |
| Serum1 | 21 | 0.84 | 2.38 |
| Serum2 | 21 | 7.16 | 0.42 |
| Serum3 | 21 | 96.58 | 0.43 |
| Urine1 | 21 | 23.74 | 0.51 |
| Urine2 | 21 | 102.49 | 0.42 |
| Urine3 | 21 | 180.67 | 0.68 |

Total Precision was evaluated following CLSI EP-5A by performing two runs per day, with each run testing 3 serum and 3 urine samples in duplicate for 21 days. The results are summarized below.

| Sample# | Replicates | Mean(mg/dL) | CV(%) |
| --- | --- | --- | --- |
| Serum4 | 21 | 1.26 | 1.59 |
| Serum5 | 21 | 7.22 | 0.88 |
| Serum6 | 21 | 95.14 | 0.40 |
| Urine4 | 21 | 24.13 | 0.50 |
| Urine5 | 21 | 104.36 | 0.37 |
| Urine6 | 21 | 184.45 | 0.42 |

# b. Linearity/assay reportable range:

High level creatinine samples were created by spiking creatinine into pooled serum and urine samples at concentrations $10\%$ to $20\%$ above the upper end of the measuring ranges. These samples were then sequentially diluted with low level serum and urine samples, respectively. Both the serum and urine samples had measured results within $\pm 10\%$ of the expected values. A slope close to 1 and correlation coefficient of 0.99 was calculated for both the serum and urine linearity samples. These results demonstrated that with this assay the measurement of creatinine is linear in the range of $0.2\mathrm{mg / dL}$ to $100\mathrm{mg / dL}$ in serum or plasma and $1.0\mathrm{mg / dL}$ to $200\mathrm{mg / dL}$ in urine.

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

The creatinine calibrator value is traceable to NIST SRM914a. The assigned value of the calibrator is determined by enzymatic methods.

The calibrators are stable until the expiration date when stored at $2 - 10^{\circ}\mathrm{C}$ . Once opened the calibrator is stable for 3 months when tightly recapped and stored in the original container at $2 - 10^{\circ}\mathrm{C}$ .

# d. Detection limit:

The limit of detection was determined at outlined in CLSI EP-17A. The limit of detection was determined to be $0.06\mathrm{mg / dL}$ in urine and $0.03\mathrm{mg / dL}$ in serum/plasma.

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e. Analytical specificity:

Interfering compounds were evaluated by spiking various concentrations of the interferants into a creatinine sample and comparing the results of the interferent spiked samples with an unspiked creatinine reference sample. Non-interference was defined as a recovery of 90% - 110% of the unspiked reference sample. The highest concentration of each compound that did not interfere is shown below.

| Interfering compound | Maximum concentration tested |
| --- | --- |
| Hemoglobin | 500 mg/dL |
| Bilirubin | 50 mg/dL |
| Conjugated Bilirubin | 40 mg/dL |
| Intralipid | 5% |
| Ascorbic Acid | 50 mg/dL |
| Creatine | 50 mg/dL |
| EDTA | 0.5% |
| Sodium Citrate | 2.0% |
| Ammonium Oxalate | 0.8% |
| Sodium Fluoride | 2.0% |
| Heparin Sodium | 0.5% |

f. Assay cut-off:

Not Applicable

2. Comparison studies:

a. Method comparison with predicate device:

The sponsor compared 60 serum samples ranging from 0.60 to 99.32 mg/dL creatinine to the predicate device. Linear regression produced a slope of 1.05, a y-intercept of -0.35, and a correlation coefficient of 0.999.

The sponsor also compared 60 urine samples ranging from 30.44 to 197.01 mg/dL creatinine to the predicate device. Linear regression produced a slope of 0.99, a y-intercept of 1.24, and a correlation coefficient of 0.999.

b. Matrix comparison:

A method comparison was performed using the L-Type creatinine method with 60 matched serum-plasma samples ranging in concentration from 0.48 to 98.51 mg/dL creatinine (in serum). Linear regression produced a slope of 1.00, a y-intercept of -0.04, and a correlation coefficient of 0.999.

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 sponsor cites the following reference ranges for serum from DG Klinische Chemie (1995) Volume 29, 205-224:

Adult Male: 0.62 - 1.09 mg/dL

Adult Female: 0.45 - 0.75 mg/dL

The sponsor cites the following reference ranges for urine from Ann Clin Biochem 1992, Volume 29, 525-528:

Adult Male: 1070 - 2150 mg/day

Adult Female: 764 -1200 mg/day

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.