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

Device Description

The Sekisui Magnesium assay kit consists of the following: Magnesium Reagent: A solution containing buffer (pH 11.2 at 25°C), 0.14 mmol/L xylidy/ blue-1, 0.1 mmol/L EGTÅ, and a surfactant.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the Sekisui Magnesium Assay, based on the provided text:

Acceptance Criteria and Device Performance

Performance Characteristic	Acceptance Criteria (Implicit from Study Design)	Reported Device Performance (Sekisui Magnesium Assay)
Precision	Total CV%:
0.8 mg/dL (low)	N/A (evaluated per CLSI EP5-A2)	6.1%
2.0 mg/dL (mid)	N/A (evaluated per CLSI EP5-A2)	3.7%
4.7 mg/dL (high)	N/A (evaluated per CLSI EP5-A2)	3.2%
Within Run CV%:
0.9 mg/dL (low)	N/A (evaluated per CLSI EP5-A2)	7.0%
2.0 mg/dL (mid)	N/A (evaluated per CLSI EP5-A2)	2.2%
4.9 mg/dL (high)	N/A (evaluated per CLSI EP5-A2)	1.6%
Linearity / Reportable Range	Demonstrably linear over the specified range for a linear equation (Nonlinearity < allowable nonlinearity).	Linear from 0.2 mg/dL to 8.0 mg/dL. Reportable range confirmed as 0.3 - 8.0 mg/dL.
Limit of Detection (LoD)	Reliably detect the smallest amount of analyte (LoD) and quantify at a specified CV (LoQ).	LoD: 0.25 mg/L, LoQ: 0.30 mg/L
Analytical Specificity / Interference	No significant interference (within +/- 10% of control result) at specified concentrations of interfering substances.	No significant interference found for: - Hemoglobin up to 1000 mg/dL - Conjugated Bilirubin up to 40 mg/dL - Unconjugated Bilirubin up to 40 mg/dL - Ascorbic Acid up to 3000 µg/dL - Intralipid up to 1000 mg/dL (or 3000 mg/dL simulated triglycerides)
Method Comparison (vs. Predicate)	Substantially comparable with the predicate device.	Slope: 0.981, Intercept: 0.00 mg/dL, Correlation: 0.9848
Matrix Comparison (Serum vs. Plasma)	Substantially comparable between serum and Li Heparin plasma.	Slope: 1.009, Intercept: -0.12 mg/dL, Correlation: 0.9903
Expected Values / Reference Range	Literature reports of adult reference ranges for magnesium are supported by a study with no outliers.	Reference range supported by a study of 20 healthy donors with no outliers.

Study Details

Sample size used for the test set and the data provenance:
- Precision: Not explicitly stated as a test set size for a single study, but samples (serum pools and control materials) were tested twice per day in duplicate for 20 days.
- Linearity: 11 concentrations of magnesium (dilutions of a high concentration serum pool).
- Detection Limit: 60 replicates of a zero magnesium sample and 60 replicates of a low concentration serum control (total 120 replicates).
- Analytical Specificity: Three samples of human serum at different magnesium concentrations were tested in quadruplicate for each interfering substance.
- Method Comparison: 100 serum samples.
- Matrix Comparison: Not explicitly stated as a number, but refers to "fresh samples from non-fasting donors."
- Reference Range Validation: 20 serum samples from apparently healthy donors.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be retrospective as they use acquired samples.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This is an in vitro diagnostic device for quantitative chemical measurement. The "ground truth" for analytical performance tests (precision, linearity, detection limits, specificity, method comparison) relies on established reference methods, spiked samples, or known concentrations, rather than expert consensus on diagnostic images or interpretations.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is an in vitro diagnostic device for quantitative chemical measurement. Adjudication methods are typically used for qualitative or interpretive assessments (e.g., in imaging studies) where human disagreement needs resolution.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader, multi-case comparative effectiveness study was not done. This type of study is relevant for devices involving human interpretation (e.g., radiology AI), not for a quantitative chemical assay.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics described (precision, linearity, detection limit, analytical specificity) are standalone performance of the assay itself on an automated chemistry analyzer (Roche/Hitachi 717). The method comparison and matrix comparison also evaluate the device's performance against a predicate or different matrix, not human readers.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Precision: Internal controls and serum pools with target values.
- Linearity: Serially diluted samples from a high concentration pool, where relative concentrations are known.
- Detection Limit: Zero magnesium samples and low concentration serum control samples.
- Analytical Specificity: Spiked samples with known concentrations of interfering substances, compared to unspiked controls.
- Method Comparison: Comparison against the predicate device (Beckman Coulter Magnesium Reagent, K944407)
- Matrix Comparison: Comparison between the candidate device run on serum vs. plasma samples.
- Reference Range: Samples from "apparently healthy donors" (implying clinically normal magnesium levels).
The sample size for the training set:
- Not applicable. This device is a chemical reagent and does not involve machine learning or AI that requires a "training set" in the conventional sense. Its performance is based on chemical reactions and assay optimization.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" for this type of device.

Summary

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Kll915

DEC - 2 2011

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION

DECISION SUMMARY

DEVICE 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:

1. Requlation section:
  21 CFR 862.1495
1. Classification:
  Class I
1. Product code:
  JGJ

Panel:

Chemistry (75)

H. Intended Use:

1. Intended use(s):
  For the IN VITRO quantitative measurement of magnesium in serum and plasma.
1. Indication(s) for use:
  The Sekisui Magnesium Assay is for the quantitative determination of magnesium in human serum and plasma (Lithium Heparin) on automated chemistry analyzers. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia (abnormally low levels of magnesium) and hypermagnesemia (abnormally high levels of magnesium). This device is intended for professional use and IN VITRO diagnostic use only.
1. Special conditions for use statement(s):
  For prescription use only

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4. Special instrument requirements:

Clinical chemistry analyzers (testing was performed on the Roche/Hitachi® 717 Automated Analvzer).

I. Device Description:

The Sekisui Magnesium assay kit consists of the following:

Magnesium Reagent: A solution containing buffer (pH 11.2 at 25°C), 0.14 mmol/L xylidy/ blue-1, 0.1 mmol/L EGTÅ, and a surfactant.

J. Substantial Equivalence Information:

1. Predicate device name(s):
  Beckman Coulter Magnesium Reagent

Predicate 510(k) number(s):

K944407

3. Comparison with predicate:

(Similarities and Differences between the candidate device and the predicate device).

Parameter	Candidate Device	Predicate Device
	Sekisui DiagnosticsMagnesium Assay	Beckman CoulterMagnesium Reagent OSR6189
		K944407
Analyte	Magnesium	Magnesium
Intended Use	For the IN VITRO quantitativemeasurement of magnesium inserum and plasma.	System reagent for the quantitativedetermination of Magnesium inHuman serum, plasma and urine onBeckman Coulter AU analyzers.
Sample Matrix	Serum or LiHeparin Plasma	Serum or Heparinized Plasma orurine
Reportable Range	0.3 - 8.0 mg/dL	0.5 -8.0 mg/dL
Reference Interval	1.6-2.6 mg/dL	1.9-2.7 mg/dL
Technology /Methodology	Colorimetric endpoint methodusing xylidyl blue.	Colorimetric endpoint method usingxylidyl blue.
Format	Liquid	Liquid

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

CLSI EP5-A2, Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline

CLSI EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline

CLSI EP9-A2, Method Comparison and Bias Estimation Using Patient samples; Approved Guideline

CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

CLSI C28-A2, How to define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline

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L. Test Principle:

Xylidyl blue-1 + Mg** -> Mg-xylidyl blue complex (red)

Under the alkaline conditions of the Magnesium reagent, magnesium present in the sample, when mixed with 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:
- a. Precision/Reproducibility:

Precision testing was performed according to CLSI guideline EP5-A2. Samples, including serum pools and control materials, were tested twice per day in duplicate for 20 days. Results are summarized below:

Precision table for Sekisui Diagnostics Magnesium on Roche Hitachi 717 automated analyzer:

Concentration		Total SD		TotalCV %	Concentration		Within Run SD		WithinRunCV %
mg/dL	mmol/	mg/dL	mmol/L		mg/d	mmol/L	mg/d	mmol/L
0.8	0.33	0.05	0.021	6.1	0.9	0.37	0.06	0.024	7.0
2.0	0.82	0.07	0.029	3.7	2.0	0.82	0.04	0.016	2.2
4.7	1.93	0.15	0.062	3.2	4.9	2.01	0.08	0.033	1.6

b. Linearity/assay reportable range:

A linearity study was performed in accordance with CLSI protocol EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures, a Statistical Approach, and the Sekisui Diagnostics Magnesium method was demonstrated to be linear across the reportable range from 0.2 mg/dL (0.08 mmol/L) to 8.0 mg/dL (3.29 mmo//L). A high concentration serum pool was diluted with saline to produce 11 concentrations of magnesium. Samples were assayed in replicates of four. The results were used to generate best fit regression lines using a linear equation.

Nonlinearity is less than allowable nonlinearity.

Summary of Linear Fit

Slope 1.01

Intercept 0.013 mg/dL

N 11

The linearity testing confirmed a reportable range of 0.3 - 8.0 mg/dL (0.12 - 3.29 mmol/L).

c. Detection limit:
The determination of the method detection limits was performed according to the CLSI EP17-A Guideline, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline. Limit of Detection (LoD) is defined as the smallest amount of an analyte that the method can reliably detect to determine presence or absence of the analyte. LoD was

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determined by measuring 60 replicates of a zero magnesium sample and 60 replicates of the low concentration serum control sample.

The results were used following the EP17-A quidelines to calculate the Limit of Blank (LoB). Limit of Detection, and Limit of Quantitaion (LoQ). The Limit of Blank was determined as 0.15 mg/dL magnesium. The Pooled SD for the low values of the samples was determined as 0.06 mg/dL; therefore, the LoD is calculated to be 0.25 mg/L. The LoQ represents the magnesium concentration where the CV is less than or equal to 20%. The LoQ is therefore 0.30 mg/L.

d. Analytical specificity:
Interference studies on the effects of endogenous and exogenous substances were designed according to the CLSI EP7-A2 guideline. Potentially cross-reactive or interfering substances that were evaluated included five endogenous substances (unconjugated bilirubin, conjugated bilirubin, hemoglobin, lipemia, and ascorbic acid). Three samples of human serum with different concentrations of magnesium were tested with the potential interference substances and analyzed in quadruplicate on the Roche Hitachi 717 automated analyzer. No significant interference was defined to be within +/- 10% of the corresponding control result for the high magnesium sample.

Concentration ofAnalyte		Substance Tested	Concentration of Interferent whereInterference is Insignificant
mg/dL	mmol/L
2.1	0.86		1000 mg/dL	155 µmol/L
4.2	1.73	Hemoglobin	1000 mg/dL	155 µmol/L
7.9	3.25		1000 mg/dL	155 µmol/L
2.0	0.82		40 mg/dL	684 µmol/L
4.3	1.77	Conjugated Bilirubin	40 mg/dL	684 µmol/L
6.8	2.79		40 mg/dL	684 µmol/L
2.0	0.82		40 mg/dL	684 µmol/L
4.2	1.73	UnconjugatedBilirubin	40 mg/dL	684 µmol/L
6.8	2.79		40 mg/dL	684 µmol/L
2.3	0.95		3000 µg/dL	170 µmol/L
4.4	1.81	Ascorbic Acid	3000 µg/dL	170 µmol/L
6.8	2.79		3000 µg/dL	170 µmol/L
1.9	0.78		800 mg/dL	2400 mg/dL (27.1mmol/L) SimulatedTriglycerides
4.1	1.69	Intralipid	1000mg/dL	3000 mg/dL (33.9mmol/L) SimulatedTriglycerides
6.9	2.84		1000mg/dL	3000 mg/dL (33.9mmol/L) SimulatedTriglycerides

e. Assay cut-off:

Not applicable

1. Comparison studies:
- a. Method comparison with predicate device:

A method comparison study was performed based on the CLSI EP9-A2 guideline. Serum samples (n=100) were obtained for the study, of which 100 were determined to be within the reportable range of the candidate method and the Predicate method (sample recoveries ranged from 0.5 mg/dL to 7.3 mg/dL magnesium. The Beckman Coulter method on the AU640 was used to compare the results performed using the Sekisui Diagnostics Magnesium Assay on the Roche Hitachi 717 automated analyzer. The results demonstrate the Sekisui Diagnostics Magnesium test method on Roche Hitachi 717 is substantially comparable with the Beckman Coulter magnesium assay on AU640 analyzer. A summary of the regression statistics is provided below:

Samples, n= 100

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Slope: 0.981 Intercept: 0.00 mg/dL Correlation: 0.9848

b. Matrix comparison:

A matrix comparison study was conducted using fresh samples from non-fasting donors drawn as serum, and Li Heparin plasma. Sekisui Diagnostics Magnesium method with serum was used to compare the results obtained using the Sekisui Diagnostics Magnesium Assay with plasma on the Roche Hitachi 717 automated analyzer. The results demonstrate the Sekisui Diagnostics Magnesium test method with plasma is substantially comparable with the Sekisui Diagnostics Magnesium test method with serum on Roche Hitachi 717 analyzer. A summary of the regression statistics is provided below:

Samples, n= દ્વ

Slope: 1.009

Intercept: - 0.12 mg/dL

Correlation: 0.9903

1. 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
1. Clinical cut-off:
  Not applicable
1. Expected values/Reference range:
  Testing followed the CSLI C28-A guideline to validate the reference range using a study of 20 serum samples from apparently healthy donors. The reference range is validated if the samples result in no outliers. The testing did not result in outliers supporting the literature reports of adult reference ranges for magnesium. [Tietz, N.W., (Editor) Clinical Guide to Laboratory Tests, W.B. Saunders Company, Philadelphia (1983) p.338.].

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The information presented in the premarket notification demonstrates that the performance of the Sekisui Diagnostics Magnesium Reagent for use with human serum and lithium heparin plasma is substantially equivalent to the cleared predicate device.

Equivalence was demonstrated using patient samples with magnesium values that span the assay range.

The information presented in the premarket notification provides a reasonable assurance that the Sekisui Diagnostics Magnesium for use with human serum and lithium heparin plasma is safe and effective for the stated intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged around the perimeter. Inside the circle is a stylized image of a bird-like figure, possibly representing a human profile, with outstretched wings.

10903 New Hampshire Avenue Silver Spring, MD 20993

SEKISUI DIAGNOSTICS P.E.I. INC C/O Penny White 70 Watts Ave Charlottetown Prince Edward Island Canada C1E2B9

DEC - 2 2011

Re: K111915

Trade Name: MAGNESIUM ASSAY Regulation Number: 21 CFR §862.1495 Regulation Name: Magnesium test system Regulatory Class: Class I,reserved Product Codes: JGJ Dated: October 19, 2011 Received: October 24, 2011

Dear Ms. White

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm

Sincerely yours,

Countney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Form

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: ___ Magnesium Assay

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.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Signature

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) < 111915

Page 1 of 1

Regulation Number and Section

§ 862.1495 Magnesium test system.

(a)
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).(b)
Classification. Class I.