ELITECH CLINICAL SYSTEMS CREATININE PAP SL, ELICAL 2, ELITROL I AND ELITROL II, URINE CONTROL BI-LEVEL

K132399 · Elitechgroup · JFY · Jan 3, 2014 · Clinical Chemistry

Device Facts

• Record ID: K132399
• Device Name: ELITECH CLINICAL SYSTEMS CREATININE PAP SL, ELICAL 2, ELITROL I AND ELITROL II, URINE CONTROL BI-LEVEL
• Applicant: Elitechgroup
• Product Code: JFY · Clinical Chemistry
• Decision Date: Jan 3, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Indications for Use

ELITech Clinical Systems CREATININE PAP SL is intended for the quantitative in vitro diagnostic determination of creatinine in human serum, plasma and urine on ELITech Clinical Systems Selectra Pro Series Analyzers. It is not intended for use in Point of Care settings. 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. ELITech Clinical Systems ELICAL 2 is a multi-parametric calibrator for in vitro diagnostic use in the calibration of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers. ELITech Clinical Systems ELITROL I and ELITROL II are multi-parametric control sera for in vitro diagnostic use in quality control of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers. ELITech Clinical Systems URINE CONTROL BI-LEVEL is a set of 2 levels of urine controls used for in vitro diagnostic in the quality control of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers.

Device Story

Enzymatic colorimetric assay for quantitative creatinine determination in human serum, plasma, and urine; utilizes Selectra ProM analyzer. Principle: Creatininase hydrolyzes creatinine to creatine; creatine hydrolyzed to sarcosine and urea; sarcosine oxidized to H2O2; H2O2 reacts with 4-amino-antipyrine and EHSPT via peroxidase to form colored quinoneimine. Absorbance measured at 546 nm; proportional to creatinine concentration. Used in clinical laboratories; operated by trained laboratory personnel. Output provides creatinine concentration values for clinical decision-making regarding renal function and dialysis monitoring.

Clinical Evidence

Bench testing only. Precision study (n=80 per pool) showed total CV% 1.5-2.9%. Linearity confirmed 0.1-30 mg/dL (serum) and 5-450 mg/dL (urine). Method comparison (n=100 serum, n=54 urine) against Roche Creatinine plus v2 showed high correlation (r=1.000). Interference testing performed per CLSI EP-7A. No clinical data.

Technological Characteristics

Enzymatic colorimetric assay. Reagents: MOPS buffer, creatinase, sarcosine oxidase, ascorbate oxidase, 4-aminoantipyrine, peroxidase, EHSPT. Form factor: Kit for automated clinical chemistry analyzers (Selectra Pro Series). Calibration: Multi-parametric, traceable to ID-MS. Controls: Lyophilized human serum or liquid urine. Connectivity: Integrated with Selectra Pro Series Analyzers.

Indications for Use

Indicated for quantitative in vitro diagnostic determination of creatinine in human serum, plasma, and urine to aid in diagnosis/treatment of renal diseases and monitoring renal dialysis. Not for Point of Care settings. 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.

Predicate Devices

• Roche Diagnostics Creatinine plus ver. 2 (k024098)
• Roche Calibrator for Automated Systems (C.f.a.s.) (k033501)
• Roche Precinorm and Precipath (k041227)
• Biorad Liquichek Urine Chemistry Control Level 1 and Level 2 (k020817)

Submission Summary (Full Text)

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

A. 510(k) Number:
k132399

B. Purpose for Submission:
New device

C. Measurand:
Creatinine

D. Type of Test:
Enzymatic, colorimetric, quantitative

E. Applicant:
ELITechGroup, Inc.

F. Proprietary and Established Names:
ELITech Clinical Systems CREATININE PAP SL
ELITech Clinical Systems ELICAL 2
ELITech Clinical Systems ELITROL I and ELITROL II
ELITech Clinical Systems URINE CONTROL BI-LEVEL

G. Regulatory Information:

| Regulation | Classification | Product Code | Panel |
| --- | --- | --- | --- |
| 21 CFR 862.1225
Creatinine Test system | Class II | JFY | Chemistry (75) |
| 21 CFR 862.1150
Calibrator | Class II | JIX | Chemistry (75) |
| 21 CFR 862.1660 Quality Control material (assayed and unassayed) | Class I, reserved | JJY | Chemistry (75) |

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H. Intended Use:

1. Intended use(s):

See indications for use below

2. Indication(s) for use:

ELITech Clinical Systems CREATININE PAP SL is intended for the quantitative in vitro diagnostic determination of creatinine in human serum, plasma and urine on ELITech Clinical Systems Selectra Pro Series Analyzers. It is not intended for use in Point of Care settings.

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.

ELITech Clinical Systems ELICAL 2 is a multi-parametric calibrator for in vitro diagnostic use in the calibration of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers.

ELITech Clinical Systems ELITROL I & ELITROL II are multi-parametric control sera for in vitro diagnostic use in quality control of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers.

ELITech Clinical Systems URINE CONTROL BI- LEVEL is a set of 2 levels of urine controls used for in vitro diagnostic in the quality control of quantitative ELITech Clinical Systems methods on ELITech Clinical Systems Selectra Pro Series Analyzers.

3. Special conditions for use statement(s):

In vitro diagnostic use only

The test system is not for use in Point of Care settings

4. Special instrument requirements:

ELITech Clinical Systems Selectra ProM Analyzer

I. Device Description:

ELITech Clinical Systems CREATININE PAP SL is available as kit only. It consists of a bi-reagent reagent 1 (R1) and reagent 2 (R2). R1 consists of; MOPS buffer (pH 7.50), EHSPT (N-Ethyl-N-(2-Hydroxy-3-Sulfopropyl)-m-Toluidine), creatinase, sarcosine oxidase, and ascorbate oxidase. R2 consists of: MOPS buffer (pH 7.50), 4-Aminoantipyrine, creatininase, peroxidase, and sodium azide.

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ELITech Clinical Systems ELICAL2 is a lyophilized calibrator based on human serum containing constituents to ensure optimal calibration. ELICAL 2 is prepared from the blood of donors tested individually and found to be negative for HbsAg and to the antibodies to HCV and HIV according to FDA-approved methods.

ELITech Clinical Systems ELITROL I and ELITROL II are two levels of quality control products consisting of a lyophilized human serum containing constituents at desired levels. ELITROL I and ELITROL II are prepared from the blood of donors tested individually and found to be negative for HbsAg and to antibodies to HCV and HIV according to FDA-approved methods.

ELITech Clinical Systems URINE CONTROL BI-LEVEL is a liquid solution prepared from human urine supplemented with constituents of human and animal origin, chemicals, preservatives and stabilizers. Human sera corresponding to the URINE CONTROL BI-LEVEL were tested for each urine donor and found to be negative for HbsAg and antibodies to HCV and HIV-1/HIV-2 according to FDA-approved methods.

## J. Substantial Equivalence Information:

1. Predicate device name(s):

k024098 – Roche Diagnostics Creatinine plus ver. 2
k033501 – Roche Calibrator for Automated Systems (C.f.a.s.)
k041227 – Roche Precinorm and Precipath
k020817 – Biorad Liquichek Urine Chemistry Control Level 1 and Level 2

3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Items | Candidate Device | Predicate Device k024098 |
| | ELITECH Clinical Systems CREATININE PAP SL | Roche Diagnostics Creatinine plus ver. 2 |
| Intended use/Indication for use | Same | For the quantitative determination of the creatinine concentration in serum, plasma, and urine |
| Test method | Same | Enzymatic colorimetric |
| Sample type | Serum, plasma (lithium heparin), and urine | Serum, plasma (lithium heparin, Potassium EDTA), and urine |
| Measuring range | Serum/plasma: 0.10 – 30 mg/dL
Urine: 5 – 450 mg/dL | Serum/plasma: 0.06 – 30.5 mg/dL
Urine: 1.1 – 452 mg/dL |

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| Similarities and Differences | | |
| --- | --- | --- |
| Items | Candidate Device | Predicate Device k033501 |
| | ELITECH Clinical Systems ELICAL 2 | Roche Calibrator for Automated Systems (C.f.a.s.) |
| Intended use/Indication for use | Same | For use in the calibration of quantitative methods on clinical chemistry analyzers |
| Matrix | Same | Lyophilized serum |
| Level(s) | Same | Single level |
| Number of analytes | 21 | 30 |
| Stability | Same | Lyophilized: To store at 2-8°C and protected from light until the expiry date After reconstitution, the stabilities are : - 8 hours between 15-25 °C. - 2 days between 2-8 °C. - 4 weeks between -25 and -15 °C (when frozen once) |
| Similarities and Differences | | |
| --- | --- | --- |
| Items | Candidate Device | Predicate Device k041227 |
| | ELITECH Clinical Systems ELITROL I and ELITROL II | Roche Diagnostics Precinorm U and Precipath U |
| Intended use/Indication for use | Same | For use in quality control by monitoring accuracy and precision for quantitative methods |
| Matrix | Same | Lyophilized serum |
| Levels | Same | 2 |
| Stability | Same | Lyophilized: To store at 2-8°C and protected from light until the expiry date After reconstitution, the stabilities are : - 12 hours between 15-25 °C. - 5 days between 2-8 °C. - 4 weeks between -25 and -15 °C (when frozen once) |

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| Similarities and Differences | | |
| --- | --- | --- |
| Items | Candidate Device | Predicate Device k020817 |
| | ELITECH Clinical Systems URINE CONTROL BI - LEVEL | Biorad Liquichek Urine Chemistry Control Level 1 and Level 2 |
| Intended use/Indication for use | Same | For quality control in quantitative methods on clinical chemistry analyzers |
| Matrix | Same | Urine |
| Levels | Same | 2 |

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

Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline—Second Edition. CLSI document EP05-A2, Vol 24, No. 25, August 2004.

Protocols for Determination of Limits of Detection and Limits of Quantification; Approved Guideline. CLSI document EP17-A, vol 24, No. 34, October 2004.

Method Comparison and Bias estimation Using Patient Samples; Approved Guideline—Second Edition. CLSI document EP09-A2-IR, Vol 30, No. 17, July 2010.

Use of Symbols on Labels and in Labeling of In Vitro Diagnostic Devices Intended for Professional Use: Guidance for Industry and FDA Staff, November 2004.

Interference Testing in Clinical Chemistry; Approved Guideline—Second Edition. CLSI document EP07-A2, Vol 25, No. 27, November 2005.

Evaluation of the Linearity of the Measurement of Quantitative Procedures: a Statistical Approach; Approved Guideline. CLSI document EP06-A, Vol 23, No. 16, April 2003.

## L. Test Principle:

Creatininase hydrolyzes creatinine in sample to creatine. Creatine is hydrolyzed by creatinase to sarcosine and urea. Sarcosine is then oxidized by sarcosine oxidase to produce hydrogen peroxide $(\mathrm{H}_2\mathrm{O}_2)$. $\mathrm{H}_2\mathrm{O}_2$ reacts with 4-amino-antipyrine (4-AAP) and EHSPT (N-Ethyl-N-2(-Hydroxy-3-Sulfopropyl)-m-Toluidine) under the catalytic action of peroxidase to form a colored quinoneimine. The absorbance of the quinoneimine at $546~\mathrm{nm}$ is proportional to the concentration of creatinine in the sample.

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A precision study was performed by assaying three serum pools at 3 concentrations over 20 operating days, on two Selectra PROM analyzers and with two lots of reagent. Assay runs were performed twice per day and each sample was tested in duplicate. Calibration was performed for each run. The results are summarized below:

Serum

| Samples | n | Mean (mg/dL) | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | CV(%) | SD | CV(%) |
| pool 1 | 80 | 0.76 | 0.01 | 1.2 | 0.01 | 1.9 |
| pool 2 | 80 | 1.52 | 0.01 | 0.6 | 0.03 | 1.7 |
| pool 3 | 80 | 5.52 | 0.03 | 0.5 | 0.08 | 1.5 |

Urine

| Samples | n | Mean (mg/dL) | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | CV(%) | SD | CV(%) |
| pool 1 | 80 | 83 | 1 | 0.8 | 2 | 2.2 |
| pool 2 | 80 | 159 | 1 | 0.7 | 4 | 2.3 |
| pool 3 | 80 | 308 | 6 | 1.9 | 9 | 2.9 |

b. Linearity/assay reportable range:

A linearity study across the claimed assay range was performed by preparing samples from patient serum pools at a low creatinine concentration and a high concentration. The low pool contained serum diluted with albumin/NaCl (6 g/dL/0.9%). Eleven samples in all were assayed in triplicate

The expected values were plotted against the observed values and a linear regression line was fitted with the following regression equation:

Serum

| Level | Expected value | Mean value |
| --- | --- | --- |
| 1 | 0.18 | 0.10 |
| 2 | 3.20 | 3.23 |
| 3 | 6.22 | 6.21 |
| 4 | 9.24 | 9.20 |
| 5 | 12.26 | 12.22 |
| 6 | 15.28 | 15.31 |
| 7 | 18.30 | 18.43 |

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| 8 | 21.32 | 21.46 |
| --- | --- | --- |
| 9 | 24.34 | 24.41 |
| 10 | 27.36 | 27.27 |
| 11 | 30.38 | 30.25 |

$\mathrm{y} = 0.9893\mathrm{x} + 0.08,\mathrm{r} = 1.0000$

Based on these results, the sponsor claims that the assay is linear from $0.10 - 30\mathrm{mg / dL}$ .

Urine

| Level | Expected value | Mean value |
| --- | --- | --- |
| 1 | 5 | 5 |
| 2 | 50 | 50 |
| 3 | 95 | 96 |
| 4 | 140 | 138 |
| 5 | 185 | 185 |
| 6 | 230 | 228 |
| 7 | 276 | 281 |
| 8 | 321 | 322 |
| 9 | 366 | 364 |
| 10 | 411 | 407 |
| 11 | 456 | 457 |

$\mathrm{y} = 1.0195\mathrm{x} - 3,\mathrm{r} = 0.9999$

Based on these results, the sponsor claims that the assay is linear from $5 - 450\mathrm{mg / dL}$ .

The sponsor has also provided data to support that post auto dilution the extended range claim is $30 - 150.00\mathrm{mg / dL}$ for serum

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

Stability

Real-time testing was conducted. The stability study protocol and the acceptance criteria have been reviewed and found to be acceptable. The study results support the following stability claims in the labeling:

| Item | Storage Conditions | | Claimed Stability |
| --- | --- | --- | --- |
| Reagent Packs | Closed-vial | 2 – 8 °C | 20 months |
| | Open-vial | On board | 28 days |
| Calibrator | Closed-vial | 2 – 8 °C | 11 months |
| | Open-vial | 15 – 25 °C | 8 hours |
| | | 2 – 8 °C | 2 days |

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| | | -25 to -15 °C
(frozen once) | 4 weeks |
| --- | --- | --- | --- |
| Serum Controls | Closed-vial | 2 – 8 °C | 30 months |
| | Open-vial | 15 – 25 °C | 12 hours |
| | | 2 – 8 °C | 5 days |
| | | -25 to -15 °C
(frozen once) | 4 weeks |
| Urine Controls | Closed-vial | 2 – 8 °C | 24 months |
| | Open-vial | 2 – 8 °C | 30 days |

The creatinine in ELICAL 2 is traceable to ID-MS (Isotope dilution-Mass Spectrometry) and was previously cleared under k103376

The serum control materials ELITROL I and ELITROL II were previously cleared under k103376

URINE CONTROL BI – LEVEL

## Value Assignment

The target value is determined by the median of 80 results from 2 Selectra ProM analyzers. The median is acceptable to the sponsor when percentage deviation is less than 10%.

## Calibration frequency

Stability across a 14-day calibration interval was assessed by calculating the percentage bias of 2 urine control specimens on each day from the result obtained on day 0. The results support the calibration interval claims of 14 days. The sponsor also noted in the labeling that a recalibration is recommended when reagent lots change, and when quality control results fall outside the range established, and after a maintenance operation.

## d. Detection limit:

Limit of Blank (LoB) and Limit of Detection (LoD) were determined following CLSI guideline EP17-A. For LoB determination, albumin/NaCl (6 g/dL/0.9%) was used as the zero sample and assayed 60 times on 2 selectra ProM analyzers. For LoD determination, 4 diluted serum or urine samples with creatinine concentrations between LoB and 4 * LoB were assayed 15 times for each sample (N = 60).

For LoQ determination, 4 low concentration samples were prepared by saline dilution and were assayed 15 times each (N = 60). The CV% and the SD at each tested concentration were calculated. The sponsor’s acceptable total error for the determination Limit of Quantification is ≤ 0.02 and 4 mg/dL for serum and urine, respectively. If the confidence interval is within the acceptable total error limits, then the Limit of Quantification is acceptable.

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# Summary:

Based on the limit of quantitation determined in this study (see result in the below table) and the result from the linearity study in M1.b., the sponsor's labeling claims a measuring range of 0.1 to $30\mathrm{mg / dL}$ for serum and 5 to $450\mathrm{mg / dL}$ for urine..

| | LoB | LoD | LoQ |
| --- | --- | --- | --- |
| Serum | 0.01 | 0.02 | 0.08 |
| Urine | 0.2 | 0.5 | 2.0 |

# e. Analytical specificity:

Testing for interfering substances was based on CLSI EP-7A. Testing was performed on a minimum of six concentrations for each interfering substance. Two different clinically relevant concentrations of creatinine (1.50 and $5.00\mathrm{mg / dL}$ ) were used for evaluation. Samples with increasing amounts of potential interferents were tested in triplicate and compared to a control sample without the interferent.

The sponsor defined non-significant interference as the highest level tested that does not cause $\geq \pm 10\%$ change between the tested samples and the control sample.

Serum

| Analyte | Highest concentration tested with no significant interference (mg/dL) (≤10%) |
| --- | --- |
| Triglyceride | 3000 |
| Unconjugated Bilirubin | 30.0 |
| Conjugated Bilirubin | 14.8 |
| Hemoglobin | 500 |
| Glucose | 500 |
| Creatinine | 5.0 |
| Uric acid | 20 |
| Ascorbic Acid | 20.0 |

Calcium dobesilate, Methyl-dopa and L-dopa cause falsely low results at therapeutic concentrations.

Urine

| Analyte | Highest concentration tested with no significant interference (mg/dL) (≤10%) |
| --- | --- |
| Conjugated Bilirubin | 29.5 |
| Hemoglobin | 500 |
| Ascorbic Acid | 20.0 |
| Methyl dopa | 10 |
| Calcium dobesilate | 50.0 |

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| Glucose | 5000 |
| --- | --- |
| pH | 2.5 – 12 |

A summary of these results and interferences is found in the labeling.

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Serum

The performance of the Creatinine PAP SL reagent on the Selectra ProM analyzer was compared with the Roche Creatinine plus v2 reagent on the cobas c111 analyzer. Study performed according to CLSI protocol EP9-A2 using 100 serum samples covering the measuring range with values from 0.10 to 30.1 mg/dL. The linear regression results are summarized below:

| | Regression parameters | Confidence Interval, 95% | |
| --- | --- | --- | --- |
| | | Lower 95% | Upper 95% |
| slope | 0.979 | 0.977 | 0.981 |
| Intercept | 0.05 | 0.03 | 0.07 |
| r | 1.000 | | |

Urine

The performance of the Creatinine PAP SL reagent on the Selectra ProM analyzer was compared with the Roche Creatinine plus v2 reagent on the cobas c111 analyzer. Study performed according to CLSI protocol EP9-A2 using 54 urine samples covering the measuring range with values from 5 – 413 mg/dL. The linear regression results are summarized below:

| | Regression parameters | Confidence Interval, 95% | |
| --- | --- | --- | --- |
| | | Lower 95% | Upper 95% |
| slope | 1.063 | 1.055 | 1.070 |
| Intercept | 2 | 1 | 3 |
| r | 1.000 | | |

b. Matrix comparison:

To demonstrate comparable performance between serum, and lithium heparin, 40 matched samples were compared with the Creatinine PAP SL reagent on the Selectra ProM analyzer. Study performed according to CLSI protocol EP9-A2 covering the measuring

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range with values from 0.11 to 29.49 mg/dL. The linear regression results are summarized below:

| | Regression parameters | Confidence Interval, 95% | |
| --- | --- | --- | --- |
| | | Lower 95% | Upper 95% |
| slope | 0.994 | 0.990 | 0.997 |
| Intercept | 0.00 | -0.03 | 0.03 |
| r | 1.000 | | |

# 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):

None

# 4. Clinical cut-off:

Not applicable

# 5. Expected values/Reference range:

| Matrix | Men | Women |
| --- | --- | --- |
| Serum, mg/dL | 0.72 - 1.18 | 0.55 – 1.02 |
| Serum, μmol /L | 64 – 104 | 49 – 90 |
| | | |
| Urine, mg/kg/24h | 14 – 26 | 11 – 20 |
| Urine, μmol/kg/24h | 124 – 230 | 97 – 177 |

Newman, D.J., Price C.P., Tietz Fundamentals of Clinical Chemistry, 5th Ed., Burtis, C.A. & Ashwood, E.R. (W.B. Saunders eds. Philadelphia USA), (2001), 414.

Ceriotti, F., Reference Intervals for Serum Creatinine Concentrations: Assessment of Available Data for Global Application. Clin. Chem., (2008), 54, 559.

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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