EON CALCIUM REGENT

K120626 · Vital Diagnostics (Manufacturing) Ptyltd · CJY · Aug 22, 2012 · Clinical Chemistry

Device Facts

• Record ID: K120626
• Device Name: EON CALCIUM REGENT
• Applicant: Vital Diagnostics (Manufacturing) Ptyltd
• Product Code: CJY · Clinical Chemistry
• Decision Date: Aug 22, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2

Indications for Use

Vital Diagnostics Eon Calcium Reagent is a device intended to measure the total calcium level in serum or plasma on an Eon 100 Analyzer. 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

Eon Calcium Reagent is an in vitro diagnostic reagent used with the Eon 100 Analyzer to quantify total calcium levels in human serum and plasma samples. The system is intended for use by healthcare professionals in clinical laboratory settings. The reagent facilitates the measurement of calcium, which aids clinicians in diagnosing and monitoring conditions such as parathyroid disease, bone disorders, chronic renal disease, and tetany. The device provides quantitative results that inform clinical decision-making regarding patient metabolic and endocrine health.

Clinical Evidence

Bench testing only. Precision evaluated over 21 days (42 runs) with total CVs ranging from 1.2% to 1.7%. Linearity confirmed across 1.3–16.0 mg/dL (r²=0.9990). LoB=0.1 mg/dL, LoD=0.3 mg/dL. Interference testing showed no significant impact (<10%) from hemoglobin (1000 mg/dL), lipemia (500 mg/dL), bilirubin (30 mg/dL), ascorbic acid, acetylsalicylic acid, or acetaminophen. Method comparison (n=62) against predicate yielded a slope of 1.054 and R²=0.9787. Matrix comparison (n=49) confirmed Lithium Heparin plasma is equivalent to serum.

Technological Characteristics

Quantitative photometric assay; Arsenazo III colorimetric method; absorbance measured at 630 nm. Reagent contains >0.13mmol/L arsenazo III, buffer, surfactants, and sodium azide. Single-part liquid configuration. Designed for use on the Eon 100 clinical chemistry analyzer. Traceable to NIST SRM 915b.

Indications for Use

Indicated for the quantitative determination of total calcium in serum or plasma to aid in the diagnosis and treatment of parathyroid disease, bone diseases, chronic renal disease, and tetany.

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

• Roche Calcium (Ca) Reagent (k871811)

Submission Summary (Full Text)

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

A. 510(k) Number:
k120626

B. Purpose for Submission:
New device

C. Measurand:
Calcium

D. Type of Test:
Quantitative photometric method

E. Applicant:
Vital Diagnostics

F. Proprietary and Established Names:
Eon Calcium Reagent

G. Regulatory Information:

| Measurand | Regulation Section | Classification | Product Code | Panel |
| --- | --- | --- | --- | --- |
| Calcium | 21CFR862.1145 | Class II | CJY | (75) Clinical Chemistry |

H. Intended Use:

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

2. Indication(s) for use:
Vital Diagnostics Eon Calcium Reagent is a device intended to measure the total calcium level in serum or plasma on an Eon 100 Analyzer. 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):
Prescription use only

4. Special instrument requirements:

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Eon 100 clinical chemistry analyzer.

I. Device Description:
The Eon Calcium Reagent kit includes 4 x 22 mL bottles of Eon Calcium Reagent. The Reagent contains &gt; 0.13mmol/L arsenazo III, buffer, surfactants, sodium azide and other non-active ingredients.

J. Substantial Equivalence Information:

1. Predicate Device Name(s):
Roche Calcium (Ca) Reagent

2. Predicate 510(k) number(s):
k871811

3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Item | Eon Calcium Reagent Candidate Device (k120626) | Roche Calcium (Ca) Reagent Predicate Device (k871811) |
| Intended Use/Indications for Use | Same | In vitro test for the quantitative determination of calcium |
| Specimen Type | Serum and Plasma | Serum, Plasma, and Urine |
| Instrument | Eon 100 clinical chemistry analyzer | Roche automated clinical chemistry analyzers |
| Expected values in Serum | 8.6 -10.2 mg/dL | 8.4 - 10.2 mg/dL |
| Measuring range (Serum /Plasma) | 1.3 - 1.6 mg/dL | 0.2-16 mg/dL |
| Reagent Configuration | Single part liquid | Two part liquid |
| Reagent Stability | Unopened: 2-8°C until expiration date
On board stability: 28 days | Unopened: 2-8°C until expiration date
On board stability: 42 days Reagent 1
90 days Reagent 2 |
| Calibration Stability | 28 days | 3 days |

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K. Standard/Guidance Document Referenced (if applicable):
- CLSI Guideline, EP5-A2 Evaluation of Precision Performance of Clinical Chemistry Devices – Second Edition
- CLSI Guideline, EP6-A2 Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach
- CLSI Guideline, EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation
- CLSI Guideline, EP9-A2 Method Comparison and Bias Estimation Using Patient Samples; Approved Guidelines - Second Revision (Interim Revision)

L. Test Principle:
The Eon Calcium reagent employs a colorimetric method which is based on the binding of calcium by arsenazo III to form a blue complex that absorbs at 630 nm. This absorbance change is proportional to the calcium concentration of the sample.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:
All the performance studies were conducted using the Eon 100 clinical chemistry analyzer.

a. Precision/Reproducibility:
Precision was evaluated according to the CLSI Document EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods. Studies were carried out over a period of 21 days (42 runs) using three levels of control serum. Two runs per day were carried out on a single reagent lot on one Eon 100 analyzer. The following Precision data (Within Run and Total) were obtained.

| | Total Precision | | | | Within Run | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | N | Mean (mg/dL) | SD | % CV | N | Mean (mg/dL) | SD | % CV |
| Level 1 | 84 | 8.33 | 0.14 | 1.7 | 84 | 8.33 | 0.10 | 1.2 |
| Level 2 | 84 | 11.11 | 0.14 | 1.2 | 84 | 11.11 | 0.10 | 0.9 |
| Level 3 | 84 | 15.07 | 0.21 | 1.4 | 84 | 15.07 | 0.12 | 0.8 |

b. Linearity/assay reportable range:
The measuring range of the assay for serum is 1.3 – 16.0 mg/dL (0.325 – 4.00 mmol/L). Ten dilutions of a stock standard were prepared to exceed the target linearity claim (16 mg/dL) using commercially available materials. Calcium levels were measured in duplicates. The measured vs. expected linear regression analysis resulted in a following linear regression parameters:

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| Lowest and the highest concentration tested | Intercept | Slope | r2 |
| --- | --- | --- | --- |
| 1.3 – 20.7 mg/dL | - 0.936 | 1.058 | 0.9990 |

Based on the linearity study results, the sponsor claimed that the assay’s measuring range is 1.3 to 16.0 mg/dL.

c. Traceability, Stability, Expected values (controls, calibrators, or methods): Vital Serum Calibrator has an assigned calcium value traceable to NIST Standard Reference Material (SRM) 915b.

Eon Calibrators were cleared in k110394

Eon Serum Controls were cleared in k111063

The sponsor performed reagent stability studies and protocol and acceptance criteria were reviewed and found to be adequate. Accelerated stability studies were performed to simulate 24 months stability of the reagent when stored at 2°C to 8°C. Real time stability studies are on-going.

d. Detection limit:

Studies were carried out in accordance with CLSI Guidance Document EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation. The detection of Limit of the Blank (LoB) and Limit of Detection (LoD) were performed using 60 blank and 60 low level samples. The samples were measured using two reagent lots on two Eon 100 analyzers. LoB and LoD were calculated using the following equations:

Limit of Blank (LoB) = Mean blank + 1.645 x (SD blank)

Limit of Detection (LoD) = LoB + 1.645 x (SD low level sample)

For the purposes of determining LoB, the mean blank result was a negative value (-0.189) and was rounded up to zero

Based on results of this study, the following claims for LoB and LoD are made:

LoB = 0.1 mg/dL

LoD = 0.3 mg/dL.

The sponsor’s claimed measuring range is 1.3 to 16.0 mg/dL.

e. Analytical specificity:

The sponsor performed studies to evaluate effect of endogenous interferences for icterus (conjugated and unconjugated bilirubin), hemolysis (hemoglobin), lipemia (intralipids), and exogenous compounds on the performance of the Eon Calcium Reagent assay, following CLSI EP7-A2, Interference Testing in

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Clinical Chemistry; Approved Guideline.

Testing was performed with serum samples in the presence of two levels of Calcium and different concentrations of the endogenous and exogenous compounds. Percent recovery was calculated relative to control samples containing Calcium without spiked compounds. The sponsor defines non-significant interference as &lt;10% difference between the spiked and the non-spiked samples. Based on the results, the sponsor concludes no significant interference for the following endogenous substances:

Hemoglobin up to 1000 mg/dL (10 g/L)

Lipemia (Intralipid® measured as Triglycerides) up to 500 mg/dL

Bilirubin up to 30 mg/dL (513 µmol/L)

Exogenous substances listed below were tested at 2 concentrations (low and high) and the sponsor concludes no significant interference (± 10%) in calcium recovery in the presence of:

Ascorbic Acid up to 4 mg/dL (227 µmol/L)

Acetylsalicyclic Acid up to 60 mg/dL (3.3 mmol/L)

Acetaminophen up to 25 mg/dL (1.6 mmol/L)

In addition the sponsor cites literature in the labeling regarding other potential drug interference¹

1. Young S. Effects of drugs on clinical laboratory tests. 5th Ed. Washington DC: AACC press; 2000

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

The sponsor performed studies to compare the performance of the Eon Calcium assay (y) with a predicate method on Roche Hitachi 911 (x) based on CLSI EP9-A2 guidelines. A total of 62 human serum samples from which 3 samples were spiked and 8 diluted were assayed in the range from 2.2 to 15.1 mg/dL. The comparison by Deming regression resulted in a slope of 1.054 (95%CI = 1.015 to 1.094), an intercept of -0.265 (95%CI = -0.638 to 0.109), correlation coefficient of R² = 0.9787, and a std. error of 0.328.

b. Matrix comparison:

The sponsor performed a matrix study to compare the performance of the

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assay when different sample types/tubes (serum vs. Lithium Heparin plasma) were tested. Parallel drawn (matched) serum and plasma (Lithium Heparin) samples from 49 individuals were assayed and the results compared by regular and Deming regression. A total of 49 samples contained 4 diluted and 4 spiked samples. Duplicate samples were tested in the range of 1.4 to 14.2 mg/dL. Samples were analyzed on one Eon 100 analyzer and using one Eon Calcium Reagent. Each plasma sample was compared to the respective serum sample. Results of regression analysis are summarized below:

| Regression analysis | n | Range (mg/dL) | Regression Equation | Correlation Coefficient (R2) | Standard Error | Confidence Interval Slope | Confidence Interval Intercept |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Regular | 49 | 1.4 to 14.2 | y =1.026 x - 0.405 | 0.9761 | 0.336 | 0.978 to 1.073 | - 0.867 to - 0.058 |
| Deming | 49 | 1.4 to 14.2 | y = 1.038x - 0.529 | 0.9761 | 0.337 | 0.991 to 1.086 | - 0.993 to - 0.065 |

The sponsor claims that Lithium heparin is an acceptable anticoagulant to be used with the Eon Calcium assay.

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:

8.6 – 10.2 mg/dL (2.15 – 2.55 mmol/L)

The quoted range should serve as a guide only. It is recommended that each laboratory verifies this range or establishes a reference interval for the population that it services.

1. Wachtel M, Paulson R, Plese C. Creation and verification of reference

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intervals. Lab Med 1995; 26: 593-7.

**N. Proposed Labeling:**

The labeling is sufficient and does satisfy 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.

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