ELITech Clinical Systems CALCIUM ARSENAZO

K151113 · Elitechgroup · CJY · Jul 22, 2015 · Clinical Chemistry

Device Facts

• Record ID: K151113
• Device Name: ELITech Clinical Systems CALCIUM ARSENAZO
• Applicant: Elitechgroup
• Product Code: CJY · Clinical Chemistry
• Decision Date: Jul 22, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2

Indications for Use

ELITech Clinical Systems CALCIUM ARSENAZO is intended for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma and urine using ELITech Clinical Systems Selectra Pro Series Analyzers. It is not intended for use in Point of Care settings. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Device Story

In vitro diagnostic reagent kit for quantitative total calcium determination in human serum, plasma, and urine; utilizes Arsenazo III colorimetric method. Input: patient serum, plasma, or urine samples. Process: Arsenazo III forms a blue complex with calcium in a neutral medium; color intensity measured via ELITech Clinical Systems Selectra Pro Series Analyzers. Output: quantitative calcium concentration (mg/dL). Used in clinical laboratories by professional staff; not for point-of-care. Healthcare providers use results to diagnose/treat parathyroid, bone, and renal diseases, and tetany. Benefits: provides accurate, automated calcium monitoring to support clinical decision-making.

Clinical Evidence

No clinical data. Performance was established via bench testing, including precision (total %CV 0.8-1.7%), linearity (R² > 0.99), and method comparison against the predicate (serum R²=0.986, urine R²=0.995). Interference testing followed CLSI EP07-A2 protocols.

Technological Characteristics

Mono-reagent system: 100 mmol/L MES buffer (pH 6.50), 200 μmol/L Arsenazo III. Colorimetric dye-binding principle. Quantitative measurement via Selectra ProM Analyzer. Traceable to NIST SRM 956c. Software performs automated calculations and 1:5 sample dilution.

Indications for Use

Indicated for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma, and urine to aid in the diagnosis and treatment of parathyroid disease, bone diseases, chronic renal disease, and tetany. Not for Point of Care use.

Regulatory Classification

Identification

A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Predicate Devices

• Horiba ABX PENTRA Calcium (k123171)

Submission Summary (Full Text)

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

A. 510(k) Number:
k151113

B. Purpose for Submission:
New Device

C. Measurand:
Calcium

D. Type of Test:
Quantitative, colorimetric chemistry test

E. Applicant:
ELITech Clinical Systems

F. Proprietary and Established Names:
ELITech Clinical Systems CALCIUM ARSENAZO

G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CJY | Class II | 21 CFR § 862.1145 Calcium Test System | Clinical Chemistry (75) |

H. Intended Use:
1. Intended use(s):
See indications for use below
2. Indication(s) for use:

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ELITech Clinical Systems CALCIUM ARSENAZO is intended for the quantitative in vitro diagnostic determination of total calcium in human serum, plasma and urine using ELITech Clinical Systems Selectra Pro Series Analyzers. It is not intended for use in Point of Care settings.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

3. Special conditions for use statement(s):

For in vitro diagnostic use only

For prescription use only

4. Special instrument requirements:

Selectra ProM Analyzer

I. Device Description:

The ELITech Clinical Systems Calcium Arsenazo kit reagents are one reagent systems. The kit consists of a mono-reagent R whose composition is: 100 mmol/L MES buffer (pH 6.50), 200 μmol/L Arsenazo III.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Horiba ABX PENTRA Calcium

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

k123171

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3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Item | Candidate Device
Calcium Arsenazo | Predicate Device
ABX PENTRA Calcium |
| Intended Use | Same | The reagent is for the quantitative determination of calcium concentration. |
| Measurand | Same | Calcium |
| Assay Method | Same | Colormetric |
| Measuring Range | Serum, Plasma : 5.00 – 15.00 mg/dL
Urine: 1.50 – 18.00 mg/dL | Serum, Plasma : 4.00 – 18.05 mg/dL
Urine: 0.64 – 18.05 mg/dL |
| Matrix | Same | Serum, plasma and urine |
| Instrument platform | Selectra Pro M | ABX Pentra 400 |

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

- CLSI Guideline, EP5-A2 Evaluation of Precision Performance of Clinical Chemistry Devices – Second Edition
- CLSI Guideline, EP9-A2 Method Comparison and Bias Estimation Using Patient Samples – Second Edition
- CLSI Guideline, EP6-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- CLSI Guideline, EP7-A2 Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
- CLSI Guideline, EP17-A Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
- FR EN 13640:2002 Stability Testing of In Vitro Diagnostic Reagents
- CLSI Guideline, EP9-A2 Method Comparison and Bias estimation Using Patient Samples; Approved Guideline

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L. Test Principle:

The assay utilizes a dye binding procedure in which calcium forms a blue-purple complex with Arsenazo under acidic condition. Calcium reacts with Arsenazo in an acidic solution to form a blue-purple colored complex. The intensity of color produced is directly proportional to the calcium concentration in the sample.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within run and total precision studies were performed according to CLSI EP5. Studies were performed by conducting two runs per day, two measures per run, for 3 levels of serum and urine samples, on 2 Selectra ProM instruments for 20 operating days. Results are presented in the tables below.

| | N | Sample Mean (mg/dL) | Within Run %CV | Total %CV |
| --- | --- | --- | --- | --- |
| Serum (mg/dL) | 80 | 8.28 | 1.1 | 1.7 |
| | 80 | 10.32 | 0.5 | 1.4 |
| | 80 | 12.96 | 0.5 | 1.0 |
| | N | Sample Mean (mg/dL) | Within Run %CV | Total %CV |
| --- | --- | --- | --- | --- |
| Urine (mg/dL) | 80 | 4.53 | 1.3 | 1.8 |
| | 80 | 10.89 | 0.5 | 1.2 |
| | 80 | 17.51 | 0.3 | 0.8 |

b. Linearity/assay reportable range:

Serum:

Linearity was evaluated according to CLSI EP6-A by comparing observed versus expected values for 11 equally-spaced serum samples. Samples were prepared from high (15.35 mg/dL) and low (4.94 mg/dL) analyte concentration serum pools. Each sample was evaluated in triplicate on the Selectra ProM instrument.

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Urine:

Linearity was evaluated by mixing a high (18.60 mg/dL) and low (1.45 mg/dL) urine concentrations to obtain 11 levels. Each sample was evaluated in triplicate on the Selectra ProM instrument.

Linear regression results from these studies are found in the table below:

| | Slope | Intercept | R² | Standard Error | Concentration Ranges tested |
| --- | --- | --- | --- | --- | --- |
| Serum | 1.0173 | -0.2048 | 0.9976 | 0.19 | 4.94 to 15.35 mg/dL |
| Urine | 1.0003 | -0.1174 | 0.9983 | 0.25 | 1.45 to 18.60 mg/dL |

The linearity supports the sponsor’s claimed reportable range of 5.00 – 15.00 mg/dL for serum and 1.50 – 18.00 mg/dL for urine.

Automatic dilution of 1: 5 by the instrument is available for sample that has concentration greater than the measuring range.

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

ELITech Clinical Systems ELICAL 2 calibrator was cleared under k132399.

Traceability for calcium is to NIST SRM 956c materials.

d. Detection limit:

Limit of Blank (LoB), Limit of detection (LoD), and limit of quantification (LoQ) were determined according to CLSI EP17-A with the Selectra ProM. LoB was determined using a blank sample tested over multi-runs over multi-days. For LoD and LoQ, testing using serum samples and urine samples was conducted over multiple days, with one run across two instruments, and with two reagent lots. The LoB, LoD, and LoQ results are as follows:

| | Serum (mg/dL) | Urine (mg/dL) |
| --- | --- | --- |
| LoB | 0.04 | 0.09 |
| LoD | 0.04 | 0.15 |
| LoQ | 5.00 | 1.50 |

The sponsor claimed the following measuring ranges: 5.00 – 15.00 mg/dL for serum and 1.50 – 18.00 mg/dL for urine

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# e. Analytical specificity:

Interferences due to unconjugated bilirubin, conjugated bilirubin, triglycerides, ascorbic acid, acetylsalicylic acid and acetaminophen were investigated following the recommended sample levels in CLSI EP07-A2 protocol. Two serum sample pools at two different calcium concentrations (8.0 and $12.0\mathrm{mg / dL}$ ) and two urine pools at two different calcium concentrations (4.0 and $16.0\mathrm{mg / dL}$ ) were used for the study. Sponsor defines non-significant interference as bias of $< 10\%$ between the spiked and unspiked samples. The results of the highest concentration tested without significant interference are summarized in the table below.

Serum:

| Interferent | Test range |
| --- | --- |
| Unconjugated bilirubin | up to 30.0 mg/dL |
| Conjugated bilirubin | up to 29.5 mg/dL |
| Hemoglobin | up to 500 mg/dL |
| Triglycerides | up to 1726 mg/dL |
| Magnesium | up to 12.0 mg/dL |
| Ascorbic acid | up to 20 mg/dL |
| Acetylsalicylic Acid | up to 200 mg/dL |
| Acetaminophen | up to 30 mg/dL |

Urine:

| Interferent | Test range |
| --- | --- |
| Conjugated bilirubin | up to 29.5 mg/dL |
| Hemoglobin | up to 500 mg/dL |
| Ascorbic acid | up to 10 mg/dL |
| Urea | up to 5000 mg/dL |
| Uric Acid | up to 100 mg/dL |
| Magnesium | up to 10 mg/dL |
| pH | 2.5 to 6.0 |

Sponsor includes the following statement and references in the labeling:

"Other compounds may interfere. Users should refer to the following literature references"

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1. Berth, M. & Delanghe, J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of literature, Acta Clin Belg., (2004), 59, 263.
2. Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 2nd Ed., AACC Press, (1997).
3. Young, D. S., Effects of drugs on clinical laboratory tests, 4th Ed., AACC Press, (1995).

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

**Serum Method Comparison:**

Two sets of method comparison studies, serum and urine, were performed according to the CLSI EP9-A2 guideline. The serum study was completed with 106 human serum samples (5 spiked, 5 diluted and 96 unaltered samples) spanning the linear range of the assay. The urine study was completed with 52 native samples spanning the linear range of the assay. Each serum and urine sample was analyzed in singlet using the Selectra ProM analyzer (test method) and in duplicate on the predicate ABX Pentra Calcium AS CP reagent on an ABX Pentra analyzer. Comparison of individual test values versus mean predicate values yielded the following results:

| Matrix | Slope | Intercept | R² | Conc. Range Tested |
| --- | --- | --- | --- | --- |
| Serum | 0.949 | 0.41 | 0.986 | 5.07 – 14.79 mg/dL |
| Urine | 0.936 | 0.20 | 0.995 | 1.50 – 17.14 mg/dL |

b. Matrix comparison

73 paired serum and plasma patient specimens (in lithium heparin samples, ranging from 5.19 to 14.38 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer according to CLSI protocol EP09-A2. 10% of the samples were either diluted (5) or spiked (2) to achieve the full range for comparison.

Regression analysis: y = 0.976x + 0.26, R² = 0.993

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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:

Reference ranges are provided in the labeling from literature as follows:

Serum/ Plasma⁽¹⁾:
8.6 - 10.3 mg/dL

Urine⁽²⁾ (for a urinary volume of 1.5 L per day):
100 – 300 mg/24h*

1. Wu, A.H.B., Tietz Clinical Guide to Laboratory Test, 4th Ed., (W.B. Saunders Company), (2006), 66.
2. Endres, D.B., Rude, R.K., Disorders of Bone, Tietz Fundamentals of Clinical Chemistry, 6th Ed., Burtis, C.A., Ashwood, E.R., Bruns, D.E. (Saunders), (2008), 711.

Each laboratory should establish and maintain its own reference values. The values given are used as guidelines only.

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.