S TEST REAGENT CARTRIDGE BUN AND S TEST REAGENT CARTRIDGE CRE

K132462 · Hitachi Chemical Diagnostics, Inc. · CDN · Oct 28, 2013 · Clinical Chemistry

Device Facts

• Record ID: K132462
• Device Name: S TEST REAGENT CARTRIDGE BUN AND S TEST REAGENT CARTRIDGE CRE
• Applicant: Hitachi Chemical Diagnostics, Inc.
• Product Code: CDN · Clinical Chemistry
• Decision Date: Oct 28, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1770
• Device Class: Class 2

Indications for Use

The S TEST Reagent Cartridge Blood Urea Nitrogen (BUN) is intended for the quantitative measurement of BUN in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. BUN measurements are used in the diagnosis and treatment of certain renal and metabolic diseases. The S TEST reagent cartridge Creatinine (CRE) is intended for the quantitative measurement of creatinine in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. 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

Ready-to-use reagent cartridges for Hitachi Clinical Analyzer E40; input: human serum or plasma samples. BUN assay uses kinetic UV rate method with urease and glutamate dehydrogenase; Creatinine assay uses enzymatic method with creatinase, sarcosine oxidase, and peroxidase to form quinone pigment. 2D barcode on cartridge provides lot-specific calibration data to analyzer; no user calibration required. System measures absorbance changes to determine analyte concentration. Used in clinical labs or physician offices by trained personnel. Output: quantitative concentration values (mg/dL) displayed on analyzer. Results assist clinicians in diagnosing/treating renal and metabolic diseases and monitoring dialysis.

Clinical Evidence

Clinical performance evaluated at three external physician office laboratory (POL) sites. Precision study (n=30 replicates per sample per site) showed total %CVs ranging from 0.6% to 6.8% for BUN and CRE. Method comparison studies (n=75 for BUN, n=45 for CRE) against reference laboratory methods demonstrated high correlation (r=0.999) and linear regression slopes between 0.94 and 0.98, confirming accuracy in the intended use environment.

Technological Characteristics

Ready-to-use reagent cartridges with 2D barcode identification. BUN reagents: urease, glutamate dehydrogenase, NADPH, alpha-ketoglutaric acid. Creatinine reagents: creatinase, sarcosine oxidase, catalase, creatininase, peroxidase, TODB, 4-aminoantipyrine. Kinetic UV rate (BUN) and enzymatic colorimetric (CRE) detection. Analyzed on Hitachi Clinical Analyzer E40. Traceable to ReCCS JCCRM 521 standard. No user calibration required.

Indications for Use

Indicated for quantitative measurement of BUN and creatinine in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma. Used for diagnosis/treatment of renal and metabolic diseases and monitoring renal dialysis. Intended for clinical laboratories or physician office laboratories. Prescription use only.

Regulatory Classification

Identification

A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.

Predicate Devices

• Roche cobas c systems (k100853)

Submission Summary (Full Text)

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

A. 510(k) Number:
k132462

B. Purpose for Submission:
New Device

C. Measurand:
Blood Urea Nitrogen
Creatinine

D. Type of Test:
Blood Urea Nitrogen: Quantitative, Kinetic
Creatinine: Quantitative, Enzymatic

E. Applicant:
Hitachi Chemical Diagnostics, Inc

F. Proprietary and Established Names:
Hitachi S TEST Reagent Cartridge Blood Urea Nitrogen (BUN)
Hitachi S TEST Reagent Cartridge Creatinine (CRE)

G. Regulatory Information:
1. Regulation section:
21 CFR 862.1770, Blood urea nitrogen (BUN) test system
21 CFR 862.1225, Creatinine (CRE) test system
2. Classification:
Class II

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3. Product code:
CDN, CGX

4. Panel:
Clinical Chemistry (75)

H. Intended Use:

1. Intended use(s):
See indications for use below.

2. Indication(s) for use:
The S TEST Reagent Cartridge Blood Urea Nitrogen (BUN) is intended for the quantitative measurement of BUN in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. BUN measurements are used in the diagnosis and treatment of certain renal and metabolic diseases.

The S TEST reagent cartridge Creatinine (CRE) is intended for the quantitative measurement of creatinine in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. 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 prescription use only

4. Special instrument requirements:
Hitachi Clinical Analyzer E40 (k111753)

I. Device Description:
The S TEST Reagent Cartridge BUN is provided ready-to-use. The 2D code label on the front of each cartridge automatically identifies the reagent to the system. It consists of the following reagents:
BUN Reagent (1):
Glutamate dehydrogenase (E.coli)
Nicotinamide adenine dinucleotide phosphate (reduced form)
$\alpha$-Ketoglutaric acid
2-Amino-2-hydroxymethyl-1,3-propanediol Buffer (pH 9.1)

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BUN Reagent (2):
Urease (Jack bean)
$\alpha$-Ketoglutaric acid
2-Amino-2-hydroxymethyl-1,3-propanediol Buffer (pH 7.3)

The S TEST Reagent Cartridge CRE is provided ready-to-use. The 2D code label on the front of each cartridge automatically identifies the reagent to the system. It consists of the following reagents:

CRE Reagent (1):
Sarcosine oxidase (E. coli)
N,N-Bis(4-sulfobutyl)-3-methylaniline disodium salt
Creatinase (E. coli)
Catalase (Micrococcus lysodeikticus)
Good's buffer (pH 7.8)

CRE Reagent (2):
Creatininase (E. coli)
4-Aminoantipyrine
Peroxidase (Horseradish)
Good's buffer (pH 8.2)

## J. Substantial Equivalence Information:

1. Predicate device name(s):
Roche cobas c systems

2. Predicate 510(k) number(s):
k100853

3. Comparison with predicate:

| Similarities and Differences Blood Urea Nitrogen (BUN) | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate Device |
| Intended Use | For in vitro quantitative measurement of BUN | Same |
| Testing Environment | Physician office or clinical lab | Clinical lab |
| Test Principle | Kinetic test (UV rate) with urease and glutamate dehydrogenase | Kinetic test with urease and glutamate dehydrogenase |
| Specimen Type | Human serum or plasma | Human serum, plasma, or urine |
| Reportable Range | 1.5 to 80 mg/dL | 1.4 to 112 mg/dL |
| Detection Wavelength | 546/340 nm | 700/340 nm |
| Detection Limit | 0.8 mg/dL | 1.4 mg/dL |
| Linearity | 0.9 to 110 mg/dL | 1.4 to 112 mg/dL |
| Instrument platform | Hitachi Clinical Analyzer E40 | Roche cobas c systems |

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| Similarities and Differences Creatinine (CRE) | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate Device |
| Intended Use | For in vitro quantitative measurement of CRE | Same |
| Testing Environment | Physician office or clinical lab | Clinical lab- cobas |
| Test Principle | Enzymatic with creatinase and formation of quinone pigment | Kinetic colorimetric assay based on Jaffe method |
| Specimen Type | Human serum or plasma | Human serum, plasma, or urine |
| Reportable Range | 0.1 to 25.0 mg/dL | 0.2 to 24.9 mg/dL |
| Detection Wavelength | 546/700 nm | 570/505 nm |
| Detection Limit | 0.1 mg/dL | 0.2 mg/dL |
| Linearity | 0.1 to 31.3 mg/dL | 0.2 to 24.9 mg/dL |
| Instrument platform | Hitachi Clinical Analyzer E40 | Roche cobas c systems |

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

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

CLSI-EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures, A statistical Approach; Approved Guideline

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

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

# L. Test Principle:

Blood Urea Nitrogen: Urea is degraded by urease into ammonia. When glutamate dehydrogenase (GLD) reacts with ammonia and alfa-ketoglutaric acid to produce glutamic acid, NADPH is converted into NADP with a decrease of absorbance at $340~\mathrm{nm}$ . The concentration of urea nitrogen can be determined by measuring the amount of change in absorbance.

Creatinine: As the first reaction, creatine in samples is decomposed into water and oxygen by the action of creatinase, sarcosine oxidase, and catalase. Subsequently, as the second reaction, creatinine in samples is converted into creatine by the action of creatininase, and then sarcosine is formed by creatinase. After that, the quinone pigment is formed by oxidation condensation between N,N-Bis (4-sulfobutyl)-3-methylaniline disodium salt (TODB) and 4-aminoantipyrine in the presence of peroxidase (POD) and hydrogen peroxide is formed by sarcosine oxidase. The concentration of creatinine can be determined by measuring the absorbance of the resulting quinone pigment (purple-red).

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision studies for the S TEST Reagent Cartridge BUN were performed following CLSI EP5-A2 with three levels of analytes (low, middle and high) and one instrument. Serum samples were tested in duplicate, twice a day, for 20 days for a total of 80 results per level. The samples were neat serum samples. Results for BUN precision are summarized below:

| Analyte | Sample | Mean (mg/dL) | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV |
| BUN | Low | 7.24 | 0.22 | 3.0 | 0.36 | 5.0 |
| | Middle | 14.07 | 0.23 | 1.6 | 0.38 | 2.7 |
| | High | 49.05 | 0.58 | 1.2 | 1.13 | 2.3 |

Precision studies for the S TEST Reagent Cartridge CRE were performed following CLSI EP5-A2 with four levels of analytes (low, middle, high and very high) and one instrument. Serum samples were tested in duplicate, twice a day, for 20 days for a total of 80 results per level. The samples were archived (stored frozen) patient serum samples. Results for creatinine precision are summarized below:

| Analyte | Sample | Mean (mg/dL) | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV |
| CRE | Low | 0.59 | 0.04 | 6.8 | 0.05 | 8.5 |
| | Middle | 1.75 | 0.04 | 2.3 | 1.75 | 3.4 |
| | High | 6.55 | 0.08 | 1.2 | 0.19 | 2.9 |
| | Very High | 20.34 | 0.18 | 0.9 | 0.29 | 1.4 |

Precision was evaluated at three POL sites. BUN was evaluated using 6 lots of reagent and Creatinine was evaluated using 3 lots. Each site received three blinded serum samples (A, B, C) that were chosen to represent low, intermediate, and high concentrations of the analytes. Each sample was assayed six times per day for 5 days resulting in 30 results per level. The BUN samples were a combination of neat and spiked specimens. The Creatinine samples were commercial controls. The results are listed below:

Physician Office Precision: BUN

| Sample | Site | Mean (mg/dL) | Within run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| A | 1 | 12.04 | 0.13 | 1.1 | 0.22 | 1.8 |
| | 2 | 10.92 | 0.26 | 2.3 | 0.39 | 3.6 |
| | 3 | 11.68 | 0.24 | 2.0 | 0.23 | 2.0 |
| | 1 | 46.94 | 0.37 | 0.8 | 0.69 | 1.5 |

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| B | 2 | 45.40 | 0.48 | 1.1 | 0.65 | 1.4 |
| --- | --- | --- | --- | --- | --- | --- |
| | 3 | 46.40 | 0.48 | 1.0 | 0.66 | 1.4 |
| C | 1 | 75.68 | 0.71 | 0.9 | 0.69 | 0.9 |
| | 2 | 74.29 | 0.60 | 0.8 | 0.85 | 1.2 |
| | 3 | 75.23 | 0.41 | 0.5 | 0.47 | 0.6 |

Physician Office Precision: Creatinine

| Sample | Site | Mean (mg/dL) | Within run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| A | 1 | 0.58 | 0.03 | 5.0 | 0.04 | 6.8 |
| | 2 | 0.60 | 0.00 | 0.0 | 0.00 | 0.0 |
| | 3 | 0.51 | 0.03 | 6.7 | 0.03 | 6.7 |
| B | 1 | 1.80 | 0.03 | 1.8 | 0.07 | 3.8 |
| | 2 | 1.80 | 0.03 | 1.8 | 0.07 | 3.8 |
| | 3 | 1.61 | 0.03 | 2.0 | 0.07 | 4.4 |
| C | 1 | 6.52 | 0.05 | 0.7 | 0.13 | 2.1 |
| | 2 | 6.38 | 0.05 | 0.8 | 0.08 | 1.2 |
| | 3 | 5.95 | 0.07 | 1.2 | 0.31 | 5.2 |

# b. Linearity/assay reportable range:

The claimed measuring range for BUN is $1.5 - 80\mathrm{mg / dL}$ . The linearity of the BUN assay was assessed following CLSI EP6-A with commercially available linearity sets which include 7 samples (0.9 to $110.0\mathrm{mg / dL}$ ). All samples were tested in duplicate on one Hitachi Clinical Analyzer E40. Recoveries were within $\pm 10\%$ or $2.5\mathrm{mg / dL}$ . The summary of the linear regression analysis of the data is below:

$$
y = 0. 9 5 4 8 x + 0. 6 1 6 8; R ^ {2} = 0. 9 9 7 7
$$

The BUN assay data demonstrates linearity between $0.9\mathrm{mg / dL}$ and $110\mathrm{mg / dL}$ and support the sponsor's claimed measuring range of 1.5 to $80\mathrm{mg / dL}$ .

The claimed measuring range for Creatinine is $0.1 - 25\mathrm{mg / dL}$ . The linearity of the creatinine assay was assessed following CLSI EP6-A with commercially available linearity sets which include 11 samples (0.1 to $31.3\mathrm{mg / dL}$ ). All samples were tested in duplicate on one Hitachi Clinical Analyzer E40. Recoveries were within $\pm 10\%$ or $0.2\mathrm{mg / dL}$ . The summary of the linear regression analysis of the data is below:

$$
y = 1. 0 2 0 1 x + 0. 0 4 5 7; R ^ {2} = 0. 9 9 9 1
$$

The creatinine assay data demonstrates linearity between $0.1\mathrm{mg / dL}$ and $31.3\mathrm{mg / dL}$ and support the sponsor's claimed measuring range of 0.1 to $25\mathrm{mg / dL}$ .

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

Traceability:

Each lot of the S TEST Reagent Cartridge Blood Urea Nitrogen (BUN) is calibrated by the manufacturer prior to shipment using material traceable to Reference Material Institute for Clinical Chemistry Standards (ReCCS) Standard Serum JCCRM 521. The 2D code printed on each cartridge provides the analyzer with lot-specific calibration data. BUN concentration is directly determined by multiplying the change in absorbance of the unknown samples by the calibrator factor on the barcode. No calibration is needed by the user.

Each lot of S TEST Reagent Cartridge Creatinine (CRE) is calibrated by the manufacturer prior to shipment using material traceable to ReCCS standard serum JCCRM 521; this standard is traceable to IDMS. The 2D code printed on each cartridge provides the analyzer with lot-specific calibration data. CRE concentration is directly determined by multiplying the change in absorbance of the unknown samples by the calibrator factor on the barcode. No calibration is needed by the user.

Commercially available controls are required and users should follow Federal, state, and local requirements.

Stability:

Real-time shelf-life studies for the BUN reagent cartridge were performed. A two-level control set was tested in replicates of five with three lots of cartridges across six analyzers. The protocols for stability and acceptance criteria were reviewed and are acceptable and support a stability claim of 12 months when stored at 2-8°C.

Real-time shelf-life studies for the Creatinine reagent cartridge were performed. A two-level control set was tested in replicates of five with three lots of cartridges across six analyzers. The protocols for stability and acceptance criteria were reviewed and are acceptable and support a stability claim of 18 months when stored at 2-8°C.

d. Detection limit:

The limit of blank (LoB) and limit of detection (LoD) studies for the S TEST Reagent Cartridge BUN and Reagent Cartridge CRE were performed in accordance to CLSI EP17-A. The analytical sensitivity was defined as the limit of detection, and the LoD was calculated from the LoB. LoB was determined using a blank sample assayed 20 times per day for three days for a total of 60 replicates. The LoB was estimated as the mean of the 57th and 58th highest values for the true blanks. LoD was determined using five low samples assayed four times per day for three days, for a total of 60 replicate results. The LoD was calculated as the LoB + 1.645 x SD of the low samples.

LoQ for the S TEST Reagent Cartridge BUN and CRE was assessed by preparing several low samples to cover the lower limit of the analyte range. Each sample was assayed in replicates of six. The mean, standard deviation and percent coefficient of variation were calculated for the six replicates at each sample and a plot (expected

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values (X) against $\% \mathrm{CV}$ (Y)) was generated. LoQ was defined at the value of sample where the interassay precision is $< 20\%$ CV.

The LoQ study supported performance with low level BUN specimens ( $\sim 4\mathrm{mg / dL}$ ) but the low end of the reportable range was defined by a functional sensitivity study. Six samples between $0.5\mathrm{mg / dL}$ and $10\mathrm{mg / dL}$ were tested. Each sample was assayed in replicates of six. The mean, standard deviation and percent $\% \mathrm{CVs}$ were calculated for the six replicates. A plot of expected (X) against actual (Y) concentrations and a plot of expected values (X) against $\% \mathrm{CV}$ (Y) was generated. The data support an LoQ of $0.8\mathrm{mg / dL}$ and the low end of the measuring range is claimed to be $1.5\mathrm{mg / dL}$ .

The LoQ study supported performance with low level Creatinine specimens ( $\sim 0.3$ mg/dL) but the low end of the reportable range was defined by a functional sensitivity study. Six samples between $0.05\mathrm{mg / dL}$ and $0.5\mathrm{mg / dL}$ . Each sample was assayed in replicates of six. The mean, standard deviation and percent $\% \mathrm{CVs}$ were calculated for the six replicates. A plot of expected (X) against actual (Y) concentrations and a plot of expected values (X) against $\% \mathrm{CV}$ (Y) was generated. The data support an LoQ of $0.1\mathrm{mg / dL}$ and the low end of the measuring range is claimed to be $0.1\mathrm{mg / dL}$ .

The LoB, LoD and LoQ for Blood Urea Nitrogen and Creatinine are tabulated below:

| Analyte | LoB (g/dL) | LoD (g/dL) | LoQ (g/dL) |
| --- | --- | --- | --- |
| Blood Urea Nitrogen (BUN) | 0.52 | 0.8 | 0.8 |
| Creatinine (CRE) | 0.03 | 0.06 | 0.1 |

The sponsor's claimed measuring range of BUN is 1.5 to $80\mathrm{mg / dL}$ and Creatinine is 0.1 to $25\mathrm{mg / dL}$ .

# e. Analytical specificity:

An interference study was performed in accordance with CLSI EP7-A. Two levels of commercial control sera containing approximately $12\mathrm{mg / dL}$ and $30\mathrm{mg / dL}$ BUN and $1.5\mathrm{mg / dL}$ and $5.7\mathrm{mg / dL}$ creatinine were spiked to six levels with each interferent (ascorbic acid, unconjugated bilirubin, hemoglobin and lipemia) and all seven samples were tested in replicates of three by the Hitachi Clinical Analyzer E40. The spiked sample results mean was compared to its neat control mean result and recoveries were calculated. The sponsor defines non-interference as the mean results from the testing of the spiked samples within $10\%$ of the mean of the neat samples. Recoveries were between $90\%$ and $110\%$ of the neat value. The highest level tested with non significant interference is listed below.

| Substance | Blood Urea Nitrogen (BUN) | Creatinine (CRE) |
| --- | --- | --- |
| | Highest level tested with no interference | Highest level tested with no interference |
| Ascorbic acid | 50 mg/dL | 25 mg/dL |
| Bilirubin (unconjugated) | 50 mg/dL | 25 mg/dL |
| Hemoglobin | 1000 mg/dL | 250 mg/dL |
| Lipemia (Intralipid) | 1000 mg/dL | 1000 mg/dL |

The sponsor states in the labeling that hemolyzed specimens should not be used for creatinine.

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f. Assay cut-off:

Not applicable

## 2. Comparison studies:

a. Method comparison with predicate device:

A total of 162 (for BUN) and 100 (for creatinine) serum specimens, spanning the dynamic range were assayed in singleton using the Hitachi system and the predicate device. The BUN study set included four diluted and four spiked samples and the creatinine study set included four spiked samples to ensure the dynamic range was fully evaluated. Results obtained were analyzed by Deming regression and summarized in the following table:

| Analyte | Comparative Methods | N | Range of Samples mg/dL | Deming Regression | | r |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | Slope (95% CI) | y-Intercept (95% CI) | |
| Blood Urea Nitrogen (BUN) | Hitachi vs. Roche | 162 | 2.4 – 78.5 | 0.96 (0.95 to 0.97) | -0.3 (-0.64 to 0.10) | 0.997 |
| Creatinine (CRE) | Hitachi vs. Roche | 100 | 0.5 – 24.7 | 0.99 (0.98 to 1.00) | -0.1 (-0.18 to -0.07) | 0.999 |

## Physician office accuracy (Method Comparison): BUN

Method comparison was performed at three POL sites on the Hitachi E40 Analyzer vs. the predicate device at the central laboratory. Each site and the central laboratory tested approximately 75 blinded neat serum samples (ranging from 5.7 to 73.6 mg/dL) that were chosen to represent a full range of BUN concentrations. The data was analyzed by Deming regression and is summarized below.

| Site | N | Range of Samples mg/dL | Deming Regression | | r |
| --- | --- | --- | --- | --- | --- |
| | | | Slope (95% CI) | y-Intercept (95% CI) | |
| 1 | 75 | 6.0 to 73.6 | 0.98 (0.96 to 0.99) | -0.23 (-0.59 to 0.13) | 0.999 |
| 2 | 74 | 5.7 to 69.3 | 0.94 (0.93 to 0.95) | -0.24 (-0.50 to 0.01) | 0.999 |
| 3 | 73 | 5.7 to 70.8 | 0.95 (0.93 to 0.96) | -0.04 (-0.41 to 0.32) | 0.999 |

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Physician office accuracy (Method Comparison): Creatinine

Method comparison was performed at three POL sites on the Hitachi E40 Analyzer vs. the predicate device at the central laboratory. Each site and the central laboratory tested approximately 45 blinded serum samples (ranging from 0.6 to $24.1\mathrm{mg / dL}$ , a combination of neat serum specimens and 4 spiked samples) that were chosen to represent a full range of creatinine concentrations. The data was analyzed by Deming regression and is summarized below.

| Site | N | Range of Samples mg/dL | Deming Regression | | r |
| --- | --- | --- | --- | --- | --- |
| | | | Slope (95% CI) | y-Intercept (95% CI) | |
| 1 | 45 | 0.6 to 23.5 | 0.97 (0.96 to 0.98) | -0.06 (-0.13 to 0.02) | 0.999 |
| 2 | 44 | 0.6 to 24.1 | 0.98 (0.96 to 0.99) | -0.09 (-0.19 to 0.02) | 0.999 |
| 3 | 47 | 0.6 to 22.8 | 0.96 (0.95 to 0.96) | -0.04 (-0.10 to 0.02) | 0.999 |

# b. Matrix comparison:

Lithium heparinized plasma, EDTA plasma and sodium citrate plasma was analyzed as a secondary sample matrix to serum. Thirty-six (36 matched clinical specimens (serum and each plasma type) with BUN concentrations spanning the dynamic range (including 2 diluted and 4 spiked samples) were assayed in singleton and in a blinded fashion on one analyzer and S TEST Reagent Cartridge BUN. Thirty-nine (39) matched clinical specimens (serum and each plasma type) with creatinine concentrations spanning the dynamic range (including 6 diluted samples) were assayed in singleton and in a blinded fashion on one analyzer and S TEST Reagent Cartridge CRE. The results were analyzed by least-squares linear regression and are summarized below:

| Analyte | Comparative Matrices | Serum Range (mg/dL) | N | Least-Squares Linear Regression | | r |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | Slope (95% CI) | y-Intercept (95% CI) | |
| Blood Urea Nitrogen (BUN) | Serum (x) vs. Heparinized Plasma (y) | 2.4–75.3 | 36 | 1.01 (1.00 to 1.03) | -0.56 (-0.84 to -0.28) | 0.999 |
| | Serum (x) vs. EDTA Plasma (y) | | 36 | 1.01 (1.00 to 1.03) | -0.61 (-0.94 to 0.27) | 0.999 |
| | Serum (x) vs. Na Citrate Plasma (y) | | 36 | 0.99 (0.97 to 1.01) | -0.98 (-1.42 to -0.54) | 0.998 |

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11

| Creatinine (CRE) | Serum (x) vs. Heparinized Plasma (y) | 0.1–24.5 | 39 | 0.99
(0.98 to 1.00) | -0.02
(-0.08 to 0.05) | 0.999 |
| --- | --- | --- | --- | --- | --- | --- |
| | Serum (x) vs. EDTA Plasma (y) | | 39 | 1.01
(1.00 to 1.02) | -0.06
(-0.15 to 0.03) | 0.999 |
| | Serum (x) vs. Na Citrate Plasma (y) | | 39 | 1.00
(0.99 to 1.02) | -0.05
(-0.14 to 0.05) | 0.999 |

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 range:
The expected values are stated within the labeling based on the literature. The manufacturer recommends each laboratory determine the expected values for its particular population.

Blood Urea Nitrogen Reference range: 6 – 20 mg/dL¹
Creatinine Reference range: Males: 0.62 – 1.10 mg/dL; Females: 0.45 – 0.75 mg/dL¹

1. Tietz, Fundamentals of Clinical Chemistry, 6th Edition, WB Saunders Company, 2008.

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.