PICCOLO MAGNESIUM TEST SYSTEM

K040115 · Abaxis, Inc. · JGJ · Jan 30, 2004 · Clinical Chemistry

Device Facts

• Record ID: K040115
• Device Name: PICCOLO MAGNESIUM TEST SYSTEM
• Applicant: Abaxis, Inc.
• Product Code: JGJ · Clinical Chemistry
• Decision Date: Jan 30, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1495
• Device Class: Class 1

Indications for Use

The Piccolo Magnesium test system is intended to be used for the in vitro quantitative determination of magnesium in heparinized whole blood, heparinized plasma, or serum in a clinical laboratory setting or point of care location. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia and hypermagnesemia.

Device Story

The Piccolo Magnesium Test System is a diagnostic reagent disc used with the Piccolo Point-of-Care Chemistry Analyzer. It processes heparinized whole blood, heparinized plasma, or serum samples. The disc separates blood cells from plasma, meters the sample and diluent, and delivers the mixture to reaction cuvettes. Inside the disc, the sample reacts with dry reagent beads via an enzymatic rate reaction. The analyzer monitors these chemical reactions at 37°C. The system provides quantitative magnesium results to clinicians in point-of-care or laboratory settings. Results assist in diagnosing and managing magnesium-related disorders (hypomagnesemia/hypermagnesemia). Calibration is handled via a bar code on the disc containing factory-calibrated, lot-specific data.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP5-A (n=80 per level, CV 1.0-3.4%). Linearity confirmed (R²=0.998) across 0.1–8.0 mg/dL. Method comparison with predicate (n=67) showed strong correlation (Linear regression y=1.002x+0.01, R²=0.993). Matrix comparison (n=10) confirmed equivalency between whole blood, plasma, and serum. Interference testing per NCCLS EP7-P established thresholds for hemoglobin, bilirubin, and triglycerides.

Technological Characteristics

System uses dry test-specific reagent beads on a reagent disc. Sensing principle is enzymatic rate reaction monitored at 37°C. Assay range: 0.1 - 8.0 mg/dL. Sensitivity: 0.1 mg/dL. Sample volume: ~100 µL. Calibration via bar code with factory-calibrated lot-specific data. Designed for professional use in point-of-care or laboratory environments.

Indications for Use

Indicated for the quantitative determination of magnesium in heparinized whole blood, heparinized plasma, or serum to aid in the diagnosis and treatment of hypomagnesemia and hypermagnesemia.

Regulatory Classification

Identification

A magnesium test system is a device intended to measure magnesium levels in serum and plasma. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia (abnormally low plasma levels of magnesium) and hypermagnesemia (abnormally high plasma levels of magnesium).

Predicate Devices

• Magnesium slides on the Vitros 950 Chemistry System, Johnson and Johnson Clinical Diagnostics (K861386)

Submission Summary (Full Text)

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

A. 510(k) Number:
k040115

B. Analyte:
Magnesium

C. Type of Test:
Quantitative enzymatic assay

D. Applicant:
Abaxis, Inc.

E. Proprietary and Established Names:
Piccolo® Magnesium test system

F. Regulatory Information:
1. Regulation section:
21 CFR § 862.1495, Magnesium test system
2. Classification:
Class I, reserved
3. Product Code:
JGJ Photometric method, magnesium
4. Panel:
Clinical Chemistry (75)

G. Intended Use:

1. Indication(s) for use:
The Piccolo Magnesium test system is intended to be used for the in vitro quantitative determination of magnesium in heparinized whole blood, heparinized plasma, or serum in a clinical laboratory setting or point of care location.

Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia and hypermagnesemia.

2. Special condition for use statement(s):
For professional use only

3. Special instrument Requirements:
Piccolo Point-of-Care Chemistry Analyzer

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# H. Device Description:

The Piccolo® Magnesium assay is contained within the Renal Function panel plus Reagent Disk. The disk is an 8 cm diameter single-use device that contains chambers for reagents along the outer edge of the disk and chambers for the sample and dilution of sample. Sample is placed in the disk, the disk is placed into the analyzer, and the sample assay is automatic.

# I. Substantial Equivalence Information:

1. Predicate device name(s): Magnesium slides on the Vitros 950 Chemistry System, Johnson and Johnson Clinical Diagnostics
2. Predicate K number(s): K861386
3. Comparison with predicate: The device and its predicate share the same intended use and are both for professional use only.

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Sensitivity | 0.1 mg/dL | 0.2 mg/dL |
| Reaction Temperature | 37°C | 37°C |
| Assay Range | 0.1 – 8.0 mg/dL | 0.2 – 10.0 mg/dL |
| Differences | | |
| Item | Device | Predicate |
| Sample Type | Heparinized whole blood, heparinized plasma, and serum | Heparinized plasma, serum, and urine |
| Reagents | Dry test-specific reagent beads | Dry multi-layered, analytical element coated on a polyester support. Contains 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (Ca2+chelator) and 1,5-bis(2-hydroxy-3,5-dichlorophenyl)-3-cyano-formazan (dye). |
| Calibration | Each disk is bar coded with factory-calibrated lot-specific data | Calibrated periodically using vendor-supplied calibrators |
| Sample Size | Approximately 100 μL | 10 μL |

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

- In Vitro Diagnostic Devices: Guidance for the Preparation of $510(\mathrm{k})$ Submissions

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- NCCLS Guideline EP9-A – Method Comparison and bias estimation using patient samples
- NCCLS Guideline EP5-A – Evaluation of precision performance of clinical chemistry devices
- NCCLS Guideline EP18-P – Quality management for unit-use testing
- NCCLS Guideline EP6-P – Evaluation of the linearity of quantitative analytical methods
- NCCLS Guideline EP7-P – Interference testing in clinical chemistry
- NCCLS Guideline C28-A2 – How to define and determine reference intervals in the clinical laboratory

## K. Test Principle:

Appropriate sample types are heparinized whole blood, heparinized plasma, or serum. If whole blood is used, the device is designed to separate the blood cells from the plasma. The plasma is then diluted and introduced into the sample cuvette which contains lyophilized reagents. Magnesium concentration is measured by a hexokinase (HK) activation method. The reaction proceeds as follows (G-6-P = Glucose-6-Phosphate, G-6-PDH = Glucose-6-Phosphate Dehydrogenase):

$$
\begin{array}{c c c}
& \mathrm{HK} \\
\mathrm{G l u c o s e + A T P} & \xrightarrow[\mathrm{M g}^{2+}]{\mathrm{M g}^{2+}} & \mathrm{G - 6 - P + A D P}
\end{array}
$$

$$
\mathrm{G - 6 - P + N A D P^{+}} \xrightarrow{\mathrm{G - 6 - P D H}} \mathrm{6 - P h o s p h o g l u c o n a t e + N A D P H + H^{+}}
$$

The hexokinase reaction is rate limiting, therefore the rate of NADPH production is proportional to the concentration of magnesium in the sample. NADPH concentration is measured spectrophotometrically at $340~\mathrm{nm}$ and $405~\mathrm{nm}$.

## L. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Precision was evaluated per NCCLS EP5-A using two commercially available human serum-based controls. Samples were run in duplicate on two instruments twice per day for 5 days at each of two sites. Data from both sites were combined to yield $n = 80$ per control level. Results are summarized below (units = mg/dL).

| | Within Run | | | Total | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | % CV | Mean | SD | % CV |
| Control 1 | 1.9 | 0.03 | 1.7 % | 1.9 | 0.06 | 3.4 % |
| Control 2 | 3.9 | 0.04 | 1.0 % | 3.9 | 0.10 | 2.6 % |

#### b. Linearity/assay reportable range:

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Human serum was spiked with magnesium and diluted with magnesium-free serum for a total of 5 samples ranging from 0 to 7.9 mg/dL. Each sample was assayed in quadruplicate on four different analyzers. Results are summarized below.

$$
\begin{array}{l}
\text{Observed} = 0.992(\text{Expected}) - 0.05 \\
R^2 = 0.998 \\
r = 0.999
\end{array}
$$

The assay's reportable range is 0.1 – 8.0 mg/dL.

c. Traceability (controls, calibrators, or method):

The reagent disks are calibrated at the manufacturer using human serum based pools that are spiked with magnesium to 6 levels covering the reportable range of the assay. The pools are verified against a NIST standard reference material (No. 909b, Human Serum) using a commercially available magnesium assay. The pools are then analyzed on the Piccolo analyzer to determine the enzymatic rate at each level, and a calibration curve is generated from that data. The calibration information is bar-encoded on each reagent disk. No user calibration is required.

Quality control beads (for both stability and chemistry) are included on each reagent disk and automatically run with each assay. The information from this quality control analysis is stored with the test results and can be printed by the user. In addition, users can run commercially available control materials or pseudospecimens to verify assay performance.

d. Detection limit:

Analytical sensitivity was determined by assaying 20 replicates of magnesium-free serum across 20 analyzers. The sensitivity was determined as two standard deviations above the 0 mg/dL sample. The analytical sensitivity is 0.1 mg/dL.

e. Analytical specificity:

Serum pools (at least 4 test pools containing different levels of the potential endogenous interferents and a control pool) were prepared according to NCCLS EP7-P. Five replicates of each pool were assayed and compared to the control pool. Below are shown the levels of the endogenous substance that exhibit <10% interference. Samples with values above these levels will be reported as "HEM", "LIP", or "ICT" on the result card.

| Substance | Level with <10% interference (mg/dL) |
| --- | --- |
| Hemoglobin | 1000 |
| Bilirubin | 50 |
| Triglycerides | 1500 |

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Interference from exogenous substances was examined as for endogenous substances above. Concentrations of the 35 substances tested that did not induce &gt;10% interference are presented in the package insert.

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Serum samples were collected from patients and assayed within 30 minutes by both the device and the predicate. Four frozen samples were also used to provide additional abnormal values to cover the range yielding 67 total samples. Each sample was tested in duplicate on the predicate and on one of four Piccolo analyzers. Both linear and Deming regression analysis was performed for comparison. Summary data is as follows (Piccolo range = 0.9 – 7.7 mg/dL, Predicate range = 0.9 – 7.7 mg/dL).

Linear Regression: y = 1.002x + 0.01
R² = 0.993
r = 0.996

Deming Regression: y = 1.003x + 0.01
R² = 0.993
r = 0.996

b. Matrix comparison:

Whole blood (heparinized), plasma (processed from the whole blood samples), and serum samples were collected for 10 individuals and tested in replicates of 8. The results were compared using descriptive statistics, plots, correlation analysis, and non-parametric tests of association. There is a statistically significant correlation among all sample types, indicating equivalency.

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):

Although this is a POC analyzer, POC studies were not needed to support this 510(k), as the procedures followed to analyze magnesium are not different from those previously evaluated in POC studies.

4. Clinical cut-off:
Not applicable

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# 5. Expected values/Reference range:

The sponsor assayed 61 samples from healthy individuals to verify the reference range published in the predicate device labeling (method correlation $y = 1.002x + 0.01$ ). Below are the results from this analysis as well as the predicate's reference range. Because the ranges are similar and the two devices show good correlation, the sponsor reports the predicate range in the labeling for this device.

| Method | Reference interval |
| --- | --- |
| Predicate | 1.6 – 2.3 mg/dL |
| Piccolo | 1.7 – 2.2 mg/dL |

# M. Conclusion:

I recommend that the Piccolo® Magnesium test system is substantially equivalent to the legally marketed predicate device.