MAGNESIUM ASSAY

K111915 · Sekisui Diagnostics P.E.I., Inc. · JGJ · Dec 2, 2011 · Clinical Chemistry

Device Facts

• Record ID: K111915
• Device Name: MAGNESIUM ASSAY
• Applicant: Sekisui Diagnostics P.E.I., Inc.
• Product Code: JGJ · Clinical Chemistry
• Decision Date: Dec 2, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1495
• Device Class: Class 1

Indications for Use

The Sekisui Magnesium Assay is intended for the quantitative measurement of magnesium in human serum and plasma (Lithium Heparin) on automated clinical chemistry analyzers. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia and hypermagnesemia. This device is intended for professional use and IN VITRO diagnostic use only.

Device Story

The Sekisui Magnesium Assay is a liquid, colorimetric reagent kit for the quantitative measurement of magnesium in human serum and lithium heparin plasma. It is designed for use on automated clinical chemistry analyzers by healthcare professionals in clinical laboratory settings. The assay utilizes xylidyl blue-1, which forms a red complex with magnesium under alkaline conditions. The concentration of magnesium is determined spectrophotometrically by measuring the decrease in absorbance at 660 nm, which is directly proportional to the amount of magnesium-xylidyl blue complex formed. Results are used by clinicians to diagnose and manage magnesium-related metabolic disorders, specifically hypomagnesemia and hypermagnesemia.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (Total CV 3.2-6.1%). Linearity confirmed from 0.3 to 8.0 mg/dL (y=1.01x+0.013). LoQ established at 0.3 mg/dL. Interference testing per CLSI EP7-A2 showed no significant interference (<10%) for hemoglobin (1000 mg/dL), conjugated/unconjugated bilirubin (40 mg/dL), and ascorbic acid (3 mg/dL). Method comparison with predicate (n=100) yielded Deming regression slope 0.981, r=0.98. Matrix comparison (serum vs LiHeparin plasma, n=54) showed r=0.99.

Technological Characteristics

Liquid ready-to-use reagent containing buffer (pH 11.2), xylidyl blue-1, EGTA, and surfactant. Principle: Colorimetric spectrophotometry (660 nm). Measuring range: 0.3–8.0 mg/dL. Designed for automated clinical chemistry analyzers. Complies with CLSI guidelines EP5-A2, EP6-A2, EP7-A2, EP9-A2, EP17-A2, and C28-A.

Indications for Use

Indicated for the quantitative measurement of magnesium in human serum and Lithium Heparin plasma to aid in the diagnosis and treatment of hypomagnesemia and hypermagnesemia in professional clinical laboratory settings.

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

• Olympus Magnesium Reagent (k944407)

Submission Summary (Full Text)

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

A. 510(k) Number:
k111915

B. Purpose for Submission:
New device

C. Measurand:
Magnesium

D. Type of Test:
Quantitative photometric method

E. Applicant:
Sekisui Diagnostics P.E.I. Inc.

F. Proprietary and Established Names:
Magnesium Assay

G. Regulatory Information:

| Measurand | Regulation Section | Classification | Product Code | Panel |
| --- | --- | --- | --- | --- |
| Magnesium | 21CFR862.1495 | Class I, reserved | JGJ-Photometric | (75) Clinical Chemistry |

H. Intended Use:

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

2. Indication(s) for use:
The Sekisui Magnesium Assay is intended for the quantitative measurement of magnesium in human serum and plasma (Lithium Heparin) on automated clinical chemistry analyzers. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia and hypermagnesemia. This device is intended for professional use and IN VITRO diagnostic use only.

3. Special conditions for use statement(s):
Prescription use only

4. Special instrument requirements:
All performance studies were conducted on the Hitachi 717 analyzer.

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I. Device Description:

The Sekisui Magnesium Assay kit consists of the following: Magnesium Reagent: A solution containing buffer (pH 11.2 at 25°C), 0.014 mmol/L xylidyl blue – 1, 0.1 EGTA and a surfactant. This Reagent is in ready-for use liquid form.

J. Substantial Equivalence Information:

1. Predicate Device Name(s): Olympus Magnesium Reagent
2. Predicate 510(k) number(s): k944407
3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Item | Candidate Device
Magnesium Assay | Predicate Device (k944407) Olympus Magnesium Reagent |
| Intended Use | For the In Vitro quantitative measurement of magnesium in serum and plasma (Lithium heparin) | Same |
| Specimen Type | Serum and LiHeparin plasma | Serum and LiHeparin plasma and urine |
| Reagent Type | Liquid ready-for-use | Same |
| Assay Principle | Colorimetric-xylidyl blue | Same |
| Measuring Range | 0.3 – 8 mg/dL | 0.5 – 8 mg/dL |

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, EP7-A2 Interference Testing in Clinical Chemistry
- CLSI Guideline, EP9-A2 Method Comparison and Bias Estimation Using Patient Samples – Second Edition
- CLSI Guideline, EP17-A2 Protocols for Determination of Limits of Detection

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and Limits of Quantitation

- CLSI Guideline, C28-A How to Define and Determine Reference Interval in the Clinical Laboratory

## L. Test Principle:

Under the alkaline conditions of the Magnesium reagent, magnesium present in the sample, when mixed with the reagent, forms a red complex with the diazonium salt of xylidyl blue. The concentration of magnesium in the sample is directly proportional to the amount of xylidyl blue – magnesium complex formed and can be measured spectrophotometrically by the decrease in absorbance measured at 660 nm.

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

### 1. Analytical performance:

All the performance studies were conducted using the Hitachi 717 analyzer.

#### a. Precision/Reproducibility:

Precision was evaluated according to the CLSI Document EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods. Total precision and within-run precision were established by assaying human serum pool materials, twice a day for 20 days using two reagent lots at one site.

| | N | Mean (mg/dL) | Total | | Within Run | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV |
| Sample 1 | 40 | 0.8 | 0.05 | 6.1 | 0.04 | 5.2 |
| Sample 2 | 40 | 2.0 | 0.07 | 3.7 | 0.04 | 2.2 |
| Sample 3 | 40 | 4.7 | 0.15 | 3.2 | 0.08 | 1.6 |

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

The measuring range of the assay is 0.3 to 8.0 mg/dL. Linearity was evaluated according to the CLSI Document EP6-A2, Evaluation of the Linearity of quantitative Measurement Procedures: A Statistical Approach. A high concentration sample obtained by spiking magnesium chloride in serum was diluted to produce eleven concentrations across the measuring range. Each sample was assayed in quadruplicate. The resulting mean concentrations of each sample were compared to predicted concentrations and yielded a linear regression of $y = 1.01x + 0.013$. Recovery was from 90% to 100%. Results of the study support the sponsor's claim that the assay is linear from 0.3 to 8.0 mg/dL.

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

Calibrators and controls were cleared under k882258 and k874772 and are sold separately.

The sponsor performed reagent stability studies and protocol and acceptance criteria and found them 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 still on-going.

d. Detection limit:

The Limit of the Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were established following the CLSI guideline EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation. The LoB was determined to be 0.15 mg/dL based on 60 determinations of 5 blank samples. The LoD was determined to be 0.25 mg/dL based on 60 determinations of 5 low level samples. Limit of Quantitation (LoQ) is the lowest concentration of Mg that can be measured with CV≤20%. The observed LoQ of the Mg assay is 0.3 mg/dL.

The Mg assay has a measuring range of 0.3 to 8.0 mg/dL.

e. Analytical specificity:

The sponsor performed studies to evaluate effect of different compounds (such as ascorbic acid, hemoglobin, intralipid, unconjugated and conjugated bilirubin) on the performance of the Magnesium assay, following CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. Testing was done in the presence of three levels of Magnesium (~2 mg/dL, 4.2 mg/dL and ~7.2 mg/dL) and different concentrations of the listed compounds. Percent recovery was calculated relative to control samples containing Magnesium without spiked compounds. The table below lists all substances tested at concentrations with non-significant interference (defined by the sponsor as &lt; 10%):

| Concentration of Mg | Substance Tested | Concentration with <10% interference (mg/dL) |
| --- | --- | --- |
| Level 1 | Hemoglobin | 1000 mg/dL |
| Level 2 | | 1000 mg/dL |
| Level 3 | | 1000 mg/dL |
| Level 1 | Conjugated Bilirubin | 40 mg/dL |
| Level 2 | | 40 mg/dL |
| Level 3 | | 40 mg/dL |
| Level 1 | Unconjugated Bilirubin | 40 mg/dL |
| Level 2 | | 40 mg/dL |
| Level 3 | | 40 mg/dL |
| Level 1 | Ascorbic Acid | 3 mg/dL |

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# 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 Magnesium assay with the performance of the predicate assay (k9444076) following CLSI EP9-A2 Method Comparison and Bias Estimation Using Patient Samples. A total of 100 specimens in the range of 0.5 to $7.3\mathrm{mg / dL}$ , were used in this comparison. A small number of the samples $(5\%)$ were altered (spiked) in order to span the measuring range. Regression analysis was based on single measurements of the candidate device and the average of duplicates for the predicate device. Results of regression analysis are summarized below:

Deming Regression:

| x axis | y axis | n | r | Slope | Intercept |
| --- | --- | --- | --- | --- | --- |
| Predicate | Candidate | 100 | 0.98 | 0.981 (CI:0.947,1.016) | 0.00 (CI:-0.09, 0.09) |

Linear regression:

# b. Matrix comparison:

The sponsor performed a matrix study to compare the performance of the assay when different sample types (serum vs. LiHeparin plasma) were tested. The study was completed with human plasma (LiHeparin) and serum samples spanning the linear range of the assay and following the CLSI EP9-A2 Method Comparison and Bias Estimation Using Patient Samples guidance. A total of 54 unaltered patient samples were tested in the range of 0.5 to 5.4 mg/dL. One single set of plasma samples was used as test samples, while duplicate serum samples were used as references. Results of regression analysis are summarized below:

| x axis | y axis | n | r | Slope | Intercept |
| --- | --- | --- | --- | --- | --- |
| Serum samples | Plasma samples | 54 | 0.99 | 1.009 (CI:0.941,0.971) | -0.12 (CI:-0.07,0.01) |

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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 range of 1.6 – 2.6 mg/dL is provided in the labeling from the following literature:
Tietz, N.W. Clinical Guide to Laboratory Tests, W.B. Saunders Company, p. 338; 1983

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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