POLY-CHEM CREATININE

K061944 · Polymedco, Inc. · JFY · Nov 3, 2006 · Clinical Chemistry

Device Facts

• Record ID: K061944
• Device Name: POLY-CHEM CREATININE
• Applicant: Polymedco, Inc.
• Product Code: JFY · Clinical Chemistry
• Decision Date: Nov 3, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Indications for Use

The Poly-Chem Creatinine test is 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.

Device Story

Poly-Chem Creatinine is an in vitro diagnostic test system for quantitative measurement of creatinine in plasma and urine. Used in clinical laboratory settings by trained personnel. Provides creatinine concentration values to assist clinicians in diagnosing renal disease, managing dialysis patients, and normalizing other urine analyte measurements. Operates via standard chemical assay principles for creatinine detection.

Clinical Evidence

No clinical data provided in the document; substantial equivalence is based on regulatory classification and intended use.

Technological Characteristics

In vitro diagnostic test system for creatinine measurement. Class II device. Product code JFY. Regulation 21 CFR 862.1225.

Indications for Use

Indicated for patients requiring creatinine measurement in serum and urine for diagnosis and treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes. For prescription 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.

Submission Summary (Full Text)

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

A. 510(k) Number:
k061944

B. Purpose for Submission:
New device

C. Measurand:
Creatinine

D. Type of Test:
Quantitative, Enzymatic Colorimetric

E. Applicant:
Polymedco Inc.

F. Proprietary and Established Names:
Poly-Chem Creatinine

G. Regulatory Information:
1. Regulation section:
Creatinine test system- 21CFR §862.1225
2. Classification:
Class II
3. Product code:
JFY
4. Panel:
75 (Chemistry)

H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:
The Poly-Chem Creatinine is intended to measure the creatinine levels in serum and urine. Creatinine measurements are used in the diagnosis and treatment of renal

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diseases, in monitoring renal dialysis and as a calculation basis for measuring other urine analytes.

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

4 Special instrument requirements:
Poly-Chem Chemistry Analyzer

I. Device Description:

The Poly-Chem Creatinine test has two reagents, R1 and R2. R1 contains 27 mL of the following ingredients: Good's buffer 30 mM, Creatinase 9 U/mL, Sarcosine oxidase 4 U/mL, Catalase 100 U/mL, Ascorbate oxidase 1 U/mL, and N-Ethyl-N-(2-hydroxy-3sulfopropyl)-3-methylaniline 1.4 mM. R2 contains 33 mL of the following ingredients: Good's buffer 30 mM, Creatininase 40 U/mL, Peroxidase 4 U/mL, and 4-AA 5.9 mM.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Arkray SpotChem II Creatinine and Ortho-Clinical VITROS Creatinine

2. Predicate 510(k) number(s):
k050652 and k001769

3. Comparison with predicate:

| Similarities and Differences for Creatinine | | | |
| --- | --- | --- | --- |
| | Poly-Chem Creatinine test (New device) | Arkray SpotChem II Creatinine (Predicate device) | Ortho-Clinical VITROS Creatinine (Predicate device) |
| Indications for use | To measure the creatinine levels in serum 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. | To measure the creatinine levels in serum/plasma and whole blood. 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. | For in vitro diagnostic use only. VITROS CREA slides quantitatively measure creatinine concentration in serum, plasma, and urine. |
| Methodology | Enzymatic colorimetric | Colorimetric | Colorimetric |
| Reagent storage temperature | 2-8°C | 2-8°C | 2-8°C |
| Sample types | Serum and Urine | Serum/Plasma, Whole | Serum, plasma, and |

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| Detection limits | Serum: 0.46mg/dL
Urine: 11 mg/dL | Blood | urine |
| --- | --- | --- | --- |
| Detection limits | Serum: 0.46mg/dL
Urine: 11 mg/dL | Serum: 0.66 mg/dL | Serum: 0.05mg/dL
Urine: 1.05 mg/dL |
| Measuring range | Serum: 0.46- 34.2 mg/dL
Urine: 11- 1300 mg/dL | Serum: 0.66-37.9 mg/dL | Serum: 0.05-14.0 mg/dL
Urine: 1.05-346.5 mg/dL |
| Expected range | **Serum:**
Male: 0.7–1.3 mg/dL (62-115μmol/L)
Female: 0.6–1.1 mg/dL (53-97 μmol/L)

**Urine:**
Male: 14-26(mg/d)/kg [124-230 (μmol/d)/kg]
Female: 11-20(mg/d)/kg [97-177 (μmol/d)/kg] | **Serum:**
Male: 0.7–1.3 mg/dL (62-115μmol/L)
Female: 0.6–1.1 mg/dL (53-97 μmol/L) | **Serum:**
Male: 0.8–1.5 mg/dL (72-113μmol/L)
Female: 0.7–1.2 mg/dL (62-106 μmol/L)

**Urine:**
24 hrs: 800-2800 mg/day |

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

Application of Kinetic Models and Arrhenius Methods to Product Stability Evaluation, MD&DI, April 1984.

## L. Test Principle:

Creatinine in serum or urine sample is hydrolyzed to creatine, which is then hydrolyzed to sarcosine and urea. Sarcosine is oxidized to formaldehyde, glycine, and hydrogen peroxide. Finally, a peroxidise-catalyzed reaction produces a dye that can be measured by the instrument. The intensity of the dye, when read at 546 nm, is proportional to the amount of creatinine in the patient sample.

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

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Intra-assay precision was determined by analyzing three control samples for both serum and urine controls twenty times in one run. The results are presented in the tables below:

| Poly-Chem Creatinine | Serum Level 1 | Serum Level 2 | Serum Level 3 |
| --- | --- | --- | --- |
| Mean (mg/dL) | 0.922 | 2.546 | 6.521 |
| SD | 0.042 | 0.104 | 0.115 |
| CV (%) | 4.5 | 4.1 | 1.8 |
| N | 20 | 20 | 20 |

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| | Urine Level 1 | Urine Level 2 | Urine Level 3 |
| --- | --- | --- | --- |
| Mean (mg/dL) | 17.66 | 64.68 | 155.70 |
| SD | 0.790 | 2.721 | 2.867 |
| CV (%) | 4.5 | 4.2 | 1.8 |
| N | 20 | 20 | 20 |

Inter-assay precision was determined by analyzing duplicates of three different samples in different runs over 5 days. The acceptance criteria are CV of $\leq 10\%$ . The results are presented in the tables below:

| Poly-Chem Creatinine | Serum Level 1 | Serum Level 2 | Serum Level 3 |
| --- | --- | --- | --- |
| Mean (mg/dL) | 0.957 | 2.600 | 6.624 |
| SD | 0.073 | 0.081 | 0.182 |
| CV (%) | 7.6 | 3.1 | 2.8 |
| N | 20 | 20 | 20 |
| | Urine Level 1 | Urine Level 2 | Urine Level 3 |
| Mean (mg/dL) | 39.94 | 206.58 | 322.76 |
| SD | 1.972 | 7.233 | 13.752 |
| CV (%) | 4.9 | 3.5 | 4.3 |
| N | 20 | 20 | 20 |

# b. Linearity/assay reportable range:

The linearity was determined by assaying serial dilutions using a pool that spanned the linear range of the test. The results at each level were averaged and the linear fit was calculated. The sponsor's acceptance criteria are deviation of $\leq 5\%$ at the two highest analyte concentrations. This test is linear up to $34.2\mathrm{mg / dL}$ with serum and $1300\mathrm{mg / dL}$ with urine. The results of the linearity study were shown in the tables below:

Table 1: Summary of the Serum Creatinine Linearity Study, lower concentrations. Means in mg/dL.

| Theoretical Level | Mean Actual Level | Standard Deviation | %CV | Deviation from Theoretical | % Deviation | % Recovery |
| --- | --- | --- | --- | --- | --- | --- |
| 0.59 | 0.60 | 0.05 | 8.8 | 0.01 | 2.4 | 102.4 |
| 1.17 | 1.14 | 0.04 | 3.2 | -0.03 | -2.7 | 97.3 |
| 1.76 | 1.72 | 0.06 | 3.2 | -0.03 | -1.9 | 98.1 |
| 2.34 | 2.30 | 0.03 | 1.4 | -0.04 | -1.7 | 98.3 |
| 2.93 | 2.88 | 0.02 | 0.6 | -0.05 | -1.7 | 98.3 |
| 3.51 | 3.55 | 0.08 | 2.2 | 0.04 | 1.0 | 101.0 |
| 4.10 | 4.09 | 0.07 | 1.8 | -0.01 | -0.2 | 99.8 |
| 4.69 | 4.70 | 0.06 | 1.2 | 0.02 | 0.4 | 100.4 |

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Table 2: Summary of the Serum Creatinine Linearity Study, higher concentrations. Means in mg/dL.

| Theoretical Level | Mean Actual Level | Standard Deviation | %CV | Deviation from Theoretical | % Deviation | % Recovery |
| --- | --- | --- | --- | --- | --- | --- |
| 3.42 | 3.28 | 0.11 | 3.2 | -0.15 | -4.3 | 95.7 |
| 6.85 | 6.73 | 0.12 | 1.8 | -0.12 | -1.7 | 98.3 |
| 10.27 | 9.98 | 0.08 | 0.8 | -0.29 | -2.8 | 97.2 |
| 13.69 | 13.56 | 0.11 | 0.8 | -0.13 | -1.0 | 99.0 |
| 17.12 | 16.90 | 0.17 | 1.0 | -0.21 | -1.2 | 98.8 |
| 20.54 | 20.52 | 0.35 | 1.7 | -0.02 | -0.1 | 99.9 |
| 23.96 | 24.25 | 0.09 | 0.4 | 0.29 | 1.2 | 101.2 |
| 27.38 | 27.46 | 0.15 | 0.5 | 0.08 | 0.3 | 100.3 |
| 30.81 | 31.11 | 0.17 | 0.5 | 0.30 | 1.0 | 101.0 |
| 34.23 | 34.23 | 0.33 | 1.0 | 0.00 | 0.0 | 100.0 |

Linear Fit Parameters
Slope: 1.013
Intercept: -0.275
r: 0.9999

Table 3: Summary of the Urine Creatinine Linearity Study with urine samples. Means in mg/dL.

| Theoretical Level | Mean Actual Level | Standard Deviation | %CV | Deviation from Theoretical | % Deviation | % Recovery |
| --- | --- | --- | --- | --- | --- | --- |
| 66.7 | 69.50 | 4.00 | 5.8 | 2.80 | 4.2 | 104.2 |
| 133.4 | 129.17 | 5.69 | 4.4 | -4.23 | -3.2 | 96.8 |
| 266.8 | 258.83 | 7.57 | 2.9 | -7.97 | -3.0 | 97.0 |
| 400.2 | 399.17 | 4.80 | 1.2 | -1.03 | -0.3 | 99.7 |
| 533.6 | 522.50 | 13.03 | 2.5 | -11.10 | -2.1 | 97.9 |
| 667.0 | 667.00 | 11.14 | 1.7 | 0.00 | 0.0 | 100.0 |
| 800.4 | 791.50 | 16.30 | 2.1 | -8.90 | -1.1 | 98.9 |
| 933.8 | 944.33 | 5.62 | 0.6 | 10.53 | 1.1 | 101.1 |
| 1067.2 | 1057.50 | 6.06 | 0.6 | -9.70 | -0.9 | 99.1 |
| 1200.6 | 1175.50 | 4.77 | 0.4 | -25.10 | -2.1 | 97.9 |
| 1334.0 | 1299.83 | 9.00 | 0.7 | -34.17 | -2.6 | 97.4 |
| | | | Linear Fit Parameters | | | |
| | | | Slope: | | 0.983 | |

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

The Poly-Chem Creatinine test was standardized to NIST SRM 909b. The calibration set points are fixed by the manufacturer and are unique with each calibrator lot. The stability of the recommended calibrators on the Poly-Chem instrument is 4 days. The calibrators can be stored at $2 - 8^{\circ}\mathrm{C}$ until expiration date. A calibration is recommended at least once every 4 days, with each reagent lot or bottle change, or as indicated by quality control.

The recommended control and calibrator materials were $510(\mathrm{k})$ cleared previously and are sold separately from the creatinine reagents.

d. Detection limit:

Functional sensitivity was determined by diluting a pool sample to 10 different concentrations below the lower limit of the normal test range for the analyte. Each dilution was assayed in replicates of ten. The mean, standard deviation and percent coefficient of variation were calculated for the ten replicates of each dilution. The functional sensitivity of the test was defined at the value of the dilution where the CV is approximately $20\%$ (taking into consideration that the actual mean was within $\pm 10\%$ of the expected target). The manufacturer determined that functional sensitivity was $0.46\mathrm{mg / dL}$ with a CV of $12.5\%$ for serum creatinine and $11.0\mathrm{mg / dL}$ with a CV of $7.6\%$ for urine creatinine.

e. Analytical specificity:

Studies were performed to determine common or known substances that could interfere with the method. The interfering substances were evaluated in serum pools that had creatinine concentrations of approximately 1.0, 3.3, and 6.6 mg/dL. The acceptable established criteria are that the analyte recovery should not vary from the base recovery by $\pm 10\%$. The summary of the results of the recovery studies is provided in the table below:

| Substances | Highest Level Tested with No Interference |
| --- | --- |
| Hemoglobin | 150 mg/dL |
| Bilirubin | 9.84 mg/dL |
| Triglycerides | 302.5 mg/dL |

Urine interference studies were performed on samples with creatinine concentrations of approximately $63.9\mathrm{mg / dL}$. The summary of the results of the recovery studies is provided in the table below:

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| Substances | Highest Level Tested with No Interference |
| --- | --- |
| Glucose | 5 g/L |
| Citric acid | 500 mg/dL |
| Tartaric acid | 500 mg/dL |
| Oxalic acid | 500 mg/dL |
| Uric acid | 140 mg/dL |
| Ascorbic acid | 500 mg/dL |
| Human serum albumin | 1 g/dL |
| Creatine | 100 mg/dL |
| Calcium | 500 mg/dL |

Urine samples with creatinine concentrations of approximately 76.7 mg/dL were tested from pH 2 to 11 and no interference was observed.

The labeling includes a literature source for the statement “Known drug interferences include levodopa, methyldopa, and nitrofuran derivatives, which may cause falsely elevated urine creatinine levels.”

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

A method correlation study was performed comparing the Poly-Chem creatinine and SpotChem II creatinine results using serum samples. The 60 serum samples tested spanned from 0.65 mg/dL to 18.9 mg/dL. The regression equation was y = 1.082x - 0.061 and r = 0.9977. (y = Poly-Chem creatinine and x = SpotChem II creatinine)

Another method correlation study was performed comparing the Poly-Chem creatinine and Ortho-Clinical VITROS creatinine results using urine samples. The 49 urine samples tested spanned from 11.0 mg/dL to 1127.2 mg/dL. The regression equation was y = 1.038 x + 3.737 and r = 0.9941. (y = Poly-Chem creatinine and x = Ortho-Clinical VITROS creatinine)

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

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b. Clinical specificity:

Not applicable

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

None

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

The sponsor cites reference range from "Tietz, N.W. Textbook of Clinical Chemistry," Second Edition, W.B Saunders Company, 1994

Serum: Male: 0.7–1.3 mg/dL (62–115 μmol/L)
Female: 0.6–1.1 mg/dL (53–97 μmol/L)

Urine: Male: 14–26 (mg/d)/kg [124–230 (μmol/d)/kg]
Female: 11–20 (mg/d)/kg [97–177 (μmol/d)/kg]

The sponsor recommends in the labeling that each laboratory establish its own reference range to reflect the age, sex, diet and geographical location of the population.

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.