RAICHEM CALCIUM (OCPC) LIQUID REAGENT

K041009 · Hemagen Diagnostics, Inc. · CIC · Jun 25, 2004 · Clinical Chemistry

Device Facts

• Record ID: K041009
• Device Name: RAICHEM CALCIUM (OCPC) LIQUID REAGENT
• Applicant: Hemagen Diagnostics, Inc.
• Product Code: CIC · Clinical Chemistry
• Decision Date: Jun 25, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

This reagent is intended for the quantitative determination of Calcium in serum, heparinized plasma, or urine. For in vitro diagnostic use only. This 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.

Device Story

The Calcium (oCPC) test system is an in vitro diagnostic reagent used to measure total calcium levels in serum, heparinized plasma, or urine. The device utilizes the o-cresolphthalein complexone (oCPC) colorimetric method. In this chemical reaction, calcium ions react with oCPC in an alkaline medium to form a purple-colored complex. The intensity of the color produced is directly proportional to the calcium concentration in the sample. The test is performed in a clinical laboratory setting by trained laboratory personnel using automated or semi-automated clinical chemistry analyzers. The healthcare provider uses the resulting quantitative calcium concentration to assist in the diagnosis and management of metabolic disorders, including parathyroid, bone, and renal diseases. The device provides objective data to support clinical decision-making regarding patient treatment and monitoring.

Clinical Evidence

No clinical data provided; bench testing only.

Technological Characteristics

Quantitative colorimetric assay. Reagents: ethanolamine, o-cresolphtalein (oCPC), 8-quinolinol, buffers, stabilizers. Form factor: two-part liquid reagent system. Instrument: Roche COBAS Mira Chemistry System. Standards: NCCLS EP9-A (method comparison), EP5-A (precision), EP6-A (linearity), EP7-A (interference).

Indications for Use

Indicated for quantitative determination of calcium in serum, heparinized plasma, or urine for diagnosis and treatment of parathyroid disease, bone diseases, chronic renal disease, and tetany. Patient population includes adult, pediatric, and neonatal.

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).

Submission Summary (Full Text)

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

A. 510(k) Number:
k041009

B. Purpose for Submission:
New product

C. Analyte:
Calcium

D. Type of Test:
Quantitative colorimetric assay

E. Applicant:
Hemagen Diagnostics Inc.

F. Proprietary and Established Names:
Raichem Calcium (oCPC) Reagent (liquid); Calcium Reagent

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1145: Calcium test system
2. Classification:
Class II
3. Product Code:
CIC
4. Panel:
Chemistry (75)

H. Intended Use:
1. Intended use/Indication(s) for use:
"This reagent is intended for the quantitative determination of Calcium in serum, heparinized plasma, or urine. For in vitro diagnostic use only.

This 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). The intended patient population may be adult, pediatric, and neonatal."

2. Special condition for use statement(s):
This product is for prescription use only.

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3. Special instrument Requirements:
Roche COBAS Mira Chemistry System

I. Device Description:
The device consists of two liquid reagents. Reagent 1 contains ethanolamine, buffers, stabilizers, and fillers while Reagent 2 contains o-cresolphtalein (oCPC), 8-quinolinol, buffers, stabilizers, and fillers. The reagents are ready for use.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Raichem Calcium (oCPC) Powder Reagent

2. Predicate K number(s):
k843353

3. Comparison with predicate:
Raichem Calcium Liquid Reagent is similar, or identical, to the listed predicate in the following ways: both products have the same intended use, utilize the enzymatic reactions on the same instrument, have the same analytic range, use the matrices, and have the same stability. The proposed product has been modified from a dry powder to a format consisting of two liquid components, optimized for stability.

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

| Area of Study | Reference Procedure | Procedure Title |
| --- | --- | --- |
| Method Comparison/Anticoagulant Studies | NCCLS EP9-A | User Comparison of Quantitative Clinical Laboratory Methods Using Patient Samples |
| Precision | NCCLS EP5-A | User Evaluation of Precision Performance of Clinical Chemistry Devices |
| Linearity | NCCLS EP6-A | Evaluation of the Linearity of Quantitative Methods |
| Interferences/Cross-Reactivity | NCCLS EP7-A | Interference Testing in Clinical Chemistry |
| Guidance | FDA (Draft) | “Data for commercialization of original equipment manufacturer, secondary, and generic reagents for automated analyzers, 10 June 1996” |

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L. Test Principle:
The test is based on the production of a colored complex when calcium reacts with oCPC. The color intensity of the solution of the dye is proportional to the concentration of calcium in serum.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:
Precision studies to support the serum claim were performed according to NCCLS EP5-A guidelines; two studies tested two levels of controls 20 times in one day, and a separate study was performed over 20 days, two runs per day, with two levels of Raichem quality controls tested in duplicate. Only within-run precision was measured for urine since the performance during the within-run testing was very similar to the performance of serum during both with-in tests. The sponsor set acceptance criteria as ≤0.3 SD for both matrices.

Precision of Raichem Calcium Liquid Reagent with Serum

| | Assay Values | | Mean (mg/dL) | Within Run* | | Total Imprecision | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Level | Min | Max | | Std Dev | % CV | Std Dev | % CV |
| Normal | 8.40 | 9.20 | 8.78 | 0.09 | 1.0 | 0.19 | 2.1 |
| Abnormal | 12.0 | 12.9 | 12.50 | 0.12 | 1.0 | 0.23 | 1.8 |

* Within run data shown here is compiled from the Total Imprecision testing. These results are comparable to the results obtained in both separate within run tests described above.

Precision of Raichem Calcium Liquid Reagent with Urine

| | Assay Values | | Mean (mg/dL) | Within Run | |
| --- | --- | --- | --- | --- | --- |
| Level | Min | Max | | Std Dev | % CV |
| Normal | 4.3 | 4.6 | 4.5 | 0.10 | 2.2 |
| Abnormal | 13.4 | 14.0 | 12.5 | 0.13 | 0.9 |

The sponsor tested accuracy by assaying two levels of control material in duplicate. Acceptance criteria were based on whether the results were within the specified range of the controls.

Control Recovery (mg/dL) by Raichem Calcium Reagent

| | Range | Mean Results |
| --- | --- | --- |
| Assayed Serum Control 1 | 8.1 – 10.1 mg/dL | 9.0 mg/dL |
| Assayed Serum Control 2 | 11.2 – 13.6 mg/dL | 12.3 mg/dL |

b. Linearity/assay reportable range:
NCCLS EP6-A guidelines were used to design this study. To support the serum claim, five pre-diluted commercially supplied linearity levels were read four times. To support the urine claim, dilutions of

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spiked urine were read four times. Recovery was calculated from the assay mean; all recoveries were within the manufacturer's specification of 95% to 105% of the assigned value of the diluted sample (serum, y=0.991x + 0.090, r² = 0.997: urine, y=1.015x + 0.012, r² = 0.999). The data supports the claim of linearity to 15 mg/dL.

c. Traceability (controls, calibrators, or method): None provided.

d. Detection limit: Water was assayed twenty times in a single analytical run. The detection limit is calculated as the mean (or zero if the mean is less than zero) plus two standard deviations of the results. The observed mean and standard deviation was 0.02 and 0.04 mg/dL respectively. Therefore, the detection limit of the assay is 0.08 mg/dL calcium.

e. Analytical specificity: Clear, unhemolyzed serum, heparinized plasma, and urine are acceptable matrices; do not use plasma prepared using EDTA, oxalate, or citrate, which function by removing calcium.

Interference effects of several substances, including some endogenous compounds, were tested on the Cobas Mira. Results are presented as percent variance sample of the highest concentration tested from an unaltered serum.

Interferent's Effect on Raichem Calcium (o-CPC) Assay

| Interferent | Concentration Tested | % Variance |
| --- | --- | --- |
| Bilirubin (Free) | 60 mg/dL | -17.1 |
| Bilirubin (Conjugated) | 60 mg/dL | -2.4 |
| Omniscan (gadodiamide) | 2.5 mg/dL | -27.3 |
| Hemoglobin | 1000 mg/dL | -5.3 |
| Intralipid | 1000 mg/dL | -14.9 |
| Magnesium (low conc) | 5.3 mg/dL | 0 |
| Magnesium (hi conc) | 20 mg/dL | 2.4 |
| Magnesium (hi serum conc) | 20 mg/dL | 0 |

f. Assay cut-off: Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

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Method comparison studies were based on NCCLS 9A. The sponsor tested 131 serum samples ranging from 0.45 to 14.5 mg/dL in duplicate using Roche Calcium (Arsenazo III) Reagent and the proposed Raichem Calcium reagent on a Cobas MIRA analyzer.

Urine samples (n=54) ranging from 0.29 to 30.5 mg/dL were compared by using values obtained from the predicate method (oOPC) tested on a Hitachi 717 analyzer and the proposed Raichem reagent tested on a Cobas MIRA analyzer. Samples above the assay range were auto-diluted and retested. Regression statistics are shown below; all are within the manufacturer's specifications.

## Comparison of Raichem Calcium Reagent and Predicates

| Value | Serum | Urine |
| --- | --- | --- |
| Method | Arsenazo III v. oOPC | oOPC v. oOPC |
| Slope | 1.017 | 1.008 |
| Intercept | 0.013 mg/dL | 0.00 mg/dL |
| R² value | 0.981 | 0.998 |
| N | 131 | 54 |
| Range | 0.45 – 14.5 mg/d | 0.29 – 30.5 mg/dL |

b. Matrix comparison: Not applicable.

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: Tietz reports a normal reference range of 8.5 – 10.5 mg/dL serum calcium (Fundamentals of Clinical Chemistry).

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