Magnesium
Device Facts
| Record ID | K181748 |
|---|---|
| Device Name | Magnesium |
| Applicant | Abbott Laboratories |
| Product Code | JGJ · Clinical Chemistry |
| Decision Date | Sep 12, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1495 |
| Device Class | Class 1 |
Indications for Use
The Magnesium assay is used for the quantitation of magnesium in human serum, plasma, or urine on the ARCHITECT c8000 System. 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). For in vitro diagnostic use only. For prescription use only.
Device Story
The Magnesium assay is an in vitro diagnostic reagent kit for use on the ARCHITECT c8000 System. It utilizes an enzymatic rate-up methodology where magnesium in the sample acts as a cofactor for isocitrate dehydrogenase. The reaction produces NADPH, causing an increase in absorbance at 340 nm that is directly proportional to the magnesium concentration. The device is intended for use in clinical laboratory settings by trained personnel. Results are provided to healthcare providers to assist in diagnosing and managing magnesium-related metabolic disorders. The assay supports automated and manual dilution protocols for samples exceeding the measuring interval.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP05-A2 (n=80 per sample, CVs 1.2-2.4%). Linearity evaluated per CLSI EP06-A (r=1.00, range 1.81-26.35 mg/dL). Detection limits (LoB 0.04, LoD 0.09, LoQ 0.75 mg/dL) established per CLSI EP17-A2. Interference testing per CLSI EP07-A2 identified hemoglobin as a potential interferent. Method comparison against predicate (n=118) showed high correlation (r=1.00) across various acidification conditions.
Technological Characteristics
Enzymatic rate-up assay; reagents include isocitrate dehydrogenase, D-isocitrate potassium salt, and NADP. Designed for use on the ARCHITECT c8000 System. Analytical measuring interval: 1.81 to 26.35 mg/dL. Aqueous analysis medium. Requires calibration and controls.
Indications for Use
Indicated for the quantitation of magnesium in human serum, plasma, or urine 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
- Roche Magnesium Gen.2 (k983416)
Related Devices
- K173294 — Magnesium · Abbott Laboratories · May 18, 2018
- K981791 — MG · Abbott Laboratories · Oct 23, 1998
- K030010 — ATAC PAK MAGNESIUM REAGENT · Elan Diagnostics · Mar 10, 2003
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k181748
B. Purpose for Submission:
Addition of a new matrix (urine) to a previously cleared assay.
C. Measurand:
Magnesium
D. Type of Test:
Quantitative, enzymatic assay
E. Applicant:
Abbott Laboratories
F. Proprietary and Established Names:
Magnesium
G. Regulatory Information:
1. Regulation section:
CFR 862.1495, Magnesium test system
2. Classification:
Class I, reserved
3. Product code:
JGJ
4. Panel:
Chemistry (75)
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H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:
The Magnesium assay is used for the quantitation of magnesium in human serum, plasma, or urine on the ARCHITECT c8000 System.
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).
3. Special conditions for use statement(s):
For *in vitro* diagnostic use only.
For prescription use only.
4. Special instrument requirements:
ARCHITECT c8000 Analyzer
I. Device Description:
The magnesium assay consists of 2 ready to use reagent solutions (R1 and R2). The R1 reagent contains isocitrate dehydrogenase at a concentration of $2.2\mathrm{U/mL}$ and D-isocitrate potassium salt with a concentration of $1.47\mathrm{mg/mL}$. The R2 reagent contains NADP with a concentration of $8.37\mathrm{mg/mL}$.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Roche Magnesium Gen.2
2. Predicate $510(k)$ number(s):
k983416
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3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device Magnesium LN 3P68 (k181748) | Predicate Device Roche Magnesium Gen. 2 (k983416) |
| Intended Use | For the quantitation of magnesium in serum, plasma, or urine. | Same |
| Analysis Medium | Aqueous solution | Same |
| Used on Automated Chemistry Analyzers? | Yes | Same |
| Reference Range - Urine | 24-hour 72.9 to 121.5 mg/day | Same |
| Sample types | Serum, plasma, or urine | Same |
| Calibrators | Two levels | Same |
| Differences | | |
| --- | --- | --- |
| Item | Candidate Device Magnesium LN 3P68 (k181748) | Predicate Device Roche Magnesium Gen. 2 (k983416) |
| Device Technology | Enzymatic quantitative method | Colorimetric photometric method |
| Assay Range (urine) | 1.81 to 26.35 mg/dL (0.74 to 10.85 mmol/L) | 1.36 to 26.7 mg/dL (0.56 11.0 mmol/L) |
| Traceability | NIST SRM 956 | AAS method |
| Controls | Two levels | Four levels |
K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline—Second Edition
- CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- CLSI EP05-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline—Second Edition
- CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition
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L. Test Principle:
Magnesium present in the sample is a cofactor in an enzymatic reaction with isocitrate dehydrogenase. The rate of increase in absorbance at 340 nm, due to the formation of NADPH, is directly proportional to the magnesium concentration.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
Analytical performance for serum and plasma was cleared under k173294. Analytical performance for urine is presented below.
a. Precision/Reproducibility:
Precision was evaluated according to the CLSI EP05-A2 guideline. Precision testing included 2 commercially available urine-based controls (Control 1 and 2) and 3 contrived urine pools (A, B, and C). Each sample was tested in 2 replicates per run, 2 runs per day for 20 days for a total of 80 replicates per sample. The results from the precision study are summarized in the table that follows:
| Sample | n | Mean (mg/dL) | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV |
| Control 1 | 80 | 4.54 | 0.055 | 1.2 | 0.058 | 1.3% |
| Control 2 | 80 | 11.17 | 0.114 | 1.0 | 0.149 | 1.3% |
| Urine Pool A | 80 | 1.89 | 0.036 | 1.9 | 0.045 | 2.4% |
| Urine Pool B | 80 | 5.7 | 0.096 | 1.7 | 0.102 | 1.8% |
| Urine Pool C | 80 | 22.51 | 0.394 | 1.7 | 0.394 | 1.8% |
b. Linearity/assay reportable range:
Linearity was evaluated according to CLSI EP06-A guideline. The linearity of the Magnesium assay was evaluated by preparing a series of 12 sample pools with analyte concentrations of 0.98, 1.47, 1.97, 3.09, 5.12, 9.27, 13.60, 18.04, 22.51, 27.02, 31.95 and 36.34 mg/dL. Samples were tested in four replicates with 2 reagent lots on 1 ARCHITECT c8000 System. The linear regression results of a representative sample set are as follows:
$$
y = 1.03 x - 0.20, r = 1.00
$$
The results of the linearity study supports the claimed analytical measuring interval of 1.81 to 26.35 mg/dL.
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Automatic dilution:
The sponsor evaluated the automatic dilution (auto-dilution) protocol using a 1:3 dilution factor. Two urine pools were prepared to magnesium concentrations above $26.35\mathrm{mg / dL}$ and evaluated in replicates of 12 using the on board auto-dilution on the ARCHITECT c8000 System. Results obtained using auto-dilution were found to be less than $10\%$ difference from the expected values. The results of this study support the sponsor's labeling claims that, using the Automated Dilution Protocol, samples with magnesium concentrations above $26.35\mathrm{mg / dL}$ may be auto-diluted 1:3 on board the analyzer.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:
The assigned values for Magnesium are traceable to NIST SRM 956 reference material.
d. Detection limit:
Detection limit studies were carried out in accordance with the CLSI EP17-A2 guideline.
The limit of blank (LoB) was determined by running 4 blank samples in 10 replicates per run and 2 runs per day for 3 days using 2 reagent lots on one ARCHITECT c8000 System. The $95^{\text{th}}$ percentile of the zero-analyte sample concentration was calculated and considered to the estimated LoB.
The limit of detection (LoD) was determined by running ten low level samples in 10 replicates per run and 2 runs per day for 3 days using 2 reagent lots on one ARCHITECT c8000 System. LoD was calculated based on the following equation: $\mathrm{LoD} = \mathrm{LoB} + \mathrm{Cp} \times \mathrm{SD}_{\mathrm{L}}$ , where $\mathrm{Cp}$ is multiplier to give the $95^{\text{th}}$ percentile of a normal distribution and $\mathrm{SD}_{\mathrm{L}}$ is the pooled SD).
The limit of quantitation (LoQ) was determined by running ten low level samples in 10 replicates per run and 2 runs per day for 3 days using 2 reagent lots on one ARCHITECT c8000 System. LoQ was defined as the lowest concentration that yielded an estimated total error less than or equal to the total allowable error of $22.0\%$ .
The results for the urine application of the assay (new claim) are summarized in the table below:
| | mg/dL |
| --- | --- |
| LoB | 0.04 |
| LoD | 0.09 |
| LoQ | 0.75 |
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The detection limit study supports the claimed measuring range of 1.81 mg/dL to 26.35 mg/dL.
e. Analytical specificity:
An interference study was performed based on the CLSI EP07-A2 guideline. Interference effects were assessed by dose response and paired difference methods. For each potentially interfering substance, 2 base pools were prepared using human urine and magnesium chloride at magnesium levels of approximately 5 mg/dL and 14 mg/dL. Bias is defined as the difference in the results between the control sample (without interference) and the test sample (contains interferent) expressed in percent. Difference exceeding 10% is considered significant interference by the sponsor.
The highest concentration of substance tested that did not cause significant interference for magnesium samples is summarized in the table below.
| Substance | Highest concentration tested that did not show significant interference |
| --- | --- |
| Albumin | 64 mg/dL |
| Ascorbic acid | 200 mg/dL |
| Bilirubin (conjugated) | 59.5 mg/dL |
| Calcium | 26 mg/dL |
| Glucose | 1220 mg/dL |
| Hemoglobin | 1200 mg/dL |
| Phosphorus | 307 mg/dL |
| Boric Acid | 1000 mg/dL |
| Hydrochloric Acid | 3.0 mL/dL |
| Copper | 21.6 μg/dL |
| Zinc | 3504 μg/dL |
| Iron | 0.6 mg/dL |
The following statements have been included in the Limitations of the Procedure section of the package insert:
- The Magnesium assay is susceptible to interference from hemoglobin.
- Do not use acetic acid, nitric acid, and sodium fluoride as urine preservatives.
- Do not use more than 2.5 mL 6N HCl per 100 mL of urine. Excess hydrochloric acid may cause elevated results with this methodology.
- Do not exceed 10 g/L boric acid.
f. Assay cut-off:
Not applicable.
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# 2. Comparison studies:
## a. Method comparison with predicate device:
A method comparison study was conducted by testing a total of 118 patient urine samples (106 native and 12 spiked urine samples) with magnesium concentrations from $1.82 - 23.25\mathrm{mg / dL}$, as determined on the predicate device. Three aliquots from each sample were prepared to characterize bias under different testing conditions: (a) without acidification to represent random urine samples with no preservative added, (b) with acidification to $\mathrm{pH} < 2$ ($\mathrm{pH}1.8 - 1.9$) using 6N HCl to represent samples with added preservative, or (c) with acidification to $\mathrm{pH} \sim 1$ ($\mathrm{pH}0.9 - 1.1$) using 6N HCl, as per predicate device instructions. Results obtained for each aliquot (a), (b), and (c) on the candidate device were compared to results obtained for aliquot (c) using the predicate device (Roche Magnesium Gen.2).
The results of the regression analyses are summarized in the tables below:
No acidification
| N | Concentration Range Tested | Slope | Intercept | R |
| --- | --- | --- | --- | --- |
| 118 | 1.82-23.25 mg/dL (predicate) | 1.04 | -0.10 | 1.00 |
pH < 2
| N | Concentration Range Tested | Slope | Intercept | R |
| --- | --- | --- | --- | --- |
| 118 | 1.82-23.25 mg/dL (predicate) | 1.08 | -0.14 | 1.00 |
pH ~ 1
| N | Concentration Range Tested | Slope | Intercept | R |
| --- | --- | --- | --- | --- |
| 118 | 1.82-23.25 mg/dL (predicate) | 1.05 | -0.13 | 1.00 |
## b. Matrix comparison:
Serum, plasma, and urine samples are acceptable to be used with this assay. Serum and plasma were previously cleared under k173294. Please refer to the method comparison studies in M.2. a. above for urine.
# 3. Clinical studies:
## a. Clinical Sensitivity:
Not applicable
## b. Clinical specificity:
Not applicable.
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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 intervals are based on literature¹ (see table below). The sponsor recommends that each laboratory should determine its own reference range based upon its locale and population characteristics.
Urine
| | Range (mg/day) |
| --- | --- |
| 24 Hour | 72.9 to 121.5 |
¹Wu AHB. Tietz Clinical Guide to Laboratory Tests. 4th ed. Philadelphia, P.A: WB
Sauders; 2006: 706 -708.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
