Yumizen C1200 Calcium AS, Yumizen C1200 Creatinine Jaffe

K191396 · HORIBA ABX SAS · CJY · Jul 26, 2019 · Clinical Chemistry

Device Facts

• Record ID: K191396
• Device Name: Yumizen C1200 Calcium AS, Yumizen C1200 Creatinine Jaffe
• Applicant: HORIBA ABX SAS
• Product Code: CJY · Clinical Chemistry
• Decision Date: Jul 26, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1145
• Device Class: Class 2

Indications for Use

Yumizen C1200 Calcium AS reagent is a diagnostic reagent for quantitative in vitro determination of calcium in human serum, plasma and urine based on colorimetric method, using the clinical chemistry analyzer. Measurement of calcium is used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms). Yumizen C1200 Creatinine Jaffé reagent is a diagnostic reagent for quantitative in vitro determination of creatinine in human serum, plasma and urine based on a kinetic method using alkaline picrate (Jaffé method). Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Device Story

Yumizen C1200 Calcium AS and Creatinine Jaffé are in vitro diagnostic reagents for use on the Yumizen C1200 clinical chemistry analyzer. Calcium assay uses Arsenazo III dye to form a blue complex at neutral pH; 8-hydroxyquinoline-5-sulfonic acid eliminates magnesium interference. Creatinine assay uses kinetic Jaffé method with alkaline picrate to form an orange-red complex. Analyzers measure absorbance changes proportional to analyte concentration. Used in clinical laboratories by trained personnel. Results assist clinicians in diagnosing and monitoring renal, parathyroid, and bone disorders. Device supports automated onboard sample dilution for high-concentration specimens.

Clinical Evidence

Bench testing only. Performance validated via precision (CLSI EP05-A3), linearity (CLSI EP06-A), and limit of detection/quantitation (CLSI EP17-A2) studies. Method comparison against predicates using Passing-Bablok regression showed high correlation (R² ≥ 0.976 for calcium, R² ≥ 0.995 for creatinine). Interference studies confirmed bias ≤10% for common interferents.

Technological Characteristics

Photometric clinical chemistry assays. Calcium: Arsenazo III, phosphate buffer, 8-hydroxyquinoline-5-sulfonic acid. Creatinine: Sodium hydroxide, picric acid. Automated analyzer-based. Traceable to NIST SRM909c (Calcium) and NIST SRM967a (Creatinine).

Indications for Use

Indicated for quantitative in vitro determination of calcium and creatinine in human serum, plasma, and urine to aid in the diagnosis and treatment of parathyroid, bone, and renal diseases, and for monitoring renal dialysis.

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).

Predicate Devices

• ABX Pentra Calcium AS CP on ABX Pentra 400 / Pentra C400 (k123171)
• ABX Pentra Creatinine 120 CP on ABX Pentra 400/ Pentra C400 (k110530)

Submission Summary (Full Text)

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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

k191396

B Applicant

Horiba ABX SAS

C Proprietary and Established Names

Yumizen C1200 Calcium AS, Yumizen C1200 Creatinine Jaffe

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CJY | Class II | 21 CFR 862.1145 - Calcium Test System | CH - Clinical Chemistry |
| CGX | Class II | 21 CFR 862.1225 - Creatinine test system | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:

New devices

B Measurand:

Calcium (Ca)

Creatinine (Crea)

C Type of Test:

Quantitative, colorimetric methods

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## III Intended Use/Indications for Use:

### A Intended Use(s):

See Indications for Use below.

### B Indication(s) for Use:

Yumizen C1200 Calcium AS reagent is a diagnostic reagent for quantitative in vitro determination of calcium in human serum, plasma and urine based on colorimetric method, using the clinical chemistry analyzer. Measurement of calcium is used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Yumizen C1200 Creatinine Jaffé reagent is a diagnostic reagent for quantitative in vitro determination of creatinine in human serum, plasma and urine based on a kinetic method using alkaline picrate (Jaffé method). Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

### C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

Yumizen C1200 Calcium AS:

Do not use EDTA plasma: EDTA anticoagulant is unsuitable for analysis because this compounds chelates calcium, making it unavailable for reaction with the reagent.

### D Special Instrument Requirements:

Yumizen C1200

## IV Device/System Characteristics:

### A Device Description:

The Yumizen C1200 Calcium AS assay consists of the following reagents:
- 50 mmol/L Phosphate buffer (pH = 7.50)
- 5 mmol/L 8-Hydroxyquinoline-5-sulfonic acid
- 120 μmol/L Arsenazo III

The Yumizen C1200 Creatinine Jaffé assay consists of the following reagents:
- 0.2 mol/L Sodium hydroxide
- 20 mmol/L Picric acid

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# B Principle of Operation:

Yumizen C1200 Calcium AS test is a photometric test using Arsenazo III die. Calcium in the sample binds to Arsenazo III at neutral pH yielding a blue colored complex, whose intensity is proportional to the calcium concentration. Interference by magnesium is eliminated by addition of 8-hydroxyquinoline-5-sulfonic acid.

Yumizen C1200 Creatinine Jaffé is a kinetic test without deproteinization according to the Jaffé method. Creatinine from the sample forms a colored orange-red complex in an alkaline picrate solution. The difference in absorbance at fixed times during conversion is proportional to the concentration of creatinine in the sample.

# C Instrument Description Information:

| Modes of Operation | Yes | No |
| --- | --- | --- |
| Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? | ☐ | ☑ |
| Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? | ☐ | ☑ |
| Software | | |
| FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types. | ☐ | ☑ |

1. Instrument Name:

Yumizen C1200

# V Substantial Equivalence Information:

# A Predicate Device Name(s):

ABX Pentra Calcium AS CP on ABX Pentra 400 / Pentra C400
ABX Pentra Creatinine 120 CP on ABX Pentra 400/ Pentra C400

# B Predicate 510(k) Number(s):

k123171
k110530

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C Comparison with Predicate(s):

Calcium:

| Device & Predicate Device(s): | K191396 | K123171 |
| --- | --- | --- |
| Device Trade Name | Yumizen C1200 Calcium AS | ABX Pentra Calcium AS CP on ABX Pentra 400 / Pentra C400 |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For quantitative in vitro determination of calcium in human serum, plasma and urine based on colorimetric method, using the clinical chemistry analyzer. Measurement of calcium is used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms). | Same |
| Sample type | Serum, plasma, urine | Same |
| Method | Colorimetry | Same |
| Measuring Range | Serum, plasma: 4.0-18.5 mg/dL
Urine: 0.64-18.05 mg/dL | Same |
| Automatic post-dilution | Serum, plasma and urine: up to 54.15 mg/dL | Same |
| General Device Characteristic Differences | | |
| Instrument | Yumizen C1200 Clinical chemistry analyzer | ABX Pentra 400 / Pentra C400 |
| Sample volume | 1.0 μL/test | 5.0 μL/test |
| Packaging and number of tests | Serum, plasma: 6 x 290 tests
Urine: 6 x 290 tests | Serum, plasma: 285 tests
Urine: 285 tests |
| On board stability | 6 weeks | 70 days |
| Calibration stability | 24 hours | 3 days |

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Creatinine:

| Device & Predicate Device(s): | K191396 | K110530 |
| --- | --- | --- |
| Device Trade Name | Yumizen C1200 Creatinine Jaffé | ABX Pentra Creatinine 120 CP on ABX Pentra 400/ Pentra C400 |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For quantitative in vitro determination of creatinine in human serum, plasma and urine based on a kinetic method using alkaline picrate (Jaffé method). Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes. | Same |
| Sample type | Serum, plasma, urine | Same |
| Method | Colorimetry | Same |
| Automatic post-dilution | Serum, plasma: up to 54.24 mg/dL
Urine: up to 847.5 mg/dL | Same |
| General Device Characteristic Differences | | |
| Instrument | Yumizen C1200 Clinical chemistry analyzer | ABX Pentra 400 / Pentra C400 |
| Sample volume | 5.0 μL/test | 10.0 μL/test |
| Measuring Range | Serum, plasma: 0.23-18.08 mg/dL
Urine: 3.0-282.5 mg/dL | Serum, plasma: Same
Urine: 2.9-282.5 mg/dL |
| Packaging and number of tests | 6 x 315 tests | 120 tests |
| On board stability | 7 days | 19 days |
| Calibration stability | 24 hours | 3 days |

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VI Standards/Guidance Documents Referenced:

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Third Edition.

CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition.

CLSI C28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition.

CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic reagents; Approved Guideline.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Precision studies were performed in accordance with CLSI EP05-A3 guideline.

Yumizen C1200 Calcium AS:

A study to evaluate repeatability and within-laboratory precision was performed using 2 levels of control materials and 3 levels of serum specimen (or 5 levels of urine specimens). The data was collected using 3 instrument systems and 1 reagent lot, and the samples were tested in duplicate for 20 days, 2 runs per day. The results are given below:

Serum:

| Sample | N | Mean (mg/dL) | Within-run (%CV) | Between-Run (%CV) | Between-Day (%CV) | Between-Instrument (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control N | 240 | 8.91 | 0.6 | 0.8 | 1.0 | 0.0 | 1.5 |
| Control P | 240 | 12.21 | 0.5 | 0.7 | 1.1 | 1.4 | 1.4 |
| Sample 1 | 240 | 6.41 | 0.8 | 0.8 | 1.1 | 0.4 | 1.7 |
| Sample 2 | 240 | 9.70 | 0.6 | 1.2 | 0.6 | 0.4 | 1.6 |
| Sample 3 | 240 | 14.68 | 0.5 | 1.1 | 1.0 | 0.8 | 1.8 |

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Urine:

| Sample | N | Mean (mg/dL) | Within-run (%CV) | Between-Run (%CV) | Between-Day (%CV) | Between-Instrument (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control 1 | 240 | 7.62 | 0.7 | 1.4 | 3.4 | 0.5 | 3.8 |
| Control 2 | 240 | 11.23 | 0.5 | 1.4 | 3.6 | 0.0 | 3.9 |
| Sample 1 | 240 | 2.92 | 1.6 | 1.0 | 1.8 | 0.0 | 2.6 |
| Sample 2 | 240 | 6.12 | 0.8 | 1.3 | 1.4 | 0.0 | 2.1 |
| Sample 3 | 240 | 8.28 | 0.7 | 1.5 | 1.0 | 0.0 | 2.0 |
| Sample 4 | 240 | 14.40 | 0.6 | 1.0 | 1.1 | 0.4 | 1.7 |
| Sample 5 | 240 | 17.07 | 0.6 | 0.9 | 1.2 | 0.3 | 1.6 |

A study to evaluate lot-to-lot imprecision was performed using 2 levels of control materials and 4 levels of serum specimen (or 5 levels of urine specimens). The data was collected using 1 instrument systems and 3 reagent lots, and the samples were tested in triplicate for 5 days, two runs per day. The results are given below:

Serum:

| Sample | N | Mean (mg/dL) | Within-Day (%CV) | Between-Day (%CV) | Within-Lot (%CV) | Between-Lot (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control N | 90 | 8.25 | 1.0 | 0.8 | 1.3 | 0.9 | 1.5 |
| Control P | 90 | 11.32 | 1.0 | 0.8 | 1.3 | 0.8 | 1.5 |
| Sample 1 | 90 | 7.19 | 1.2 | 0.6 | 1.4 | 0.5 | 1.5 |
| Sample 2 | 90 | 9.74 | 1.2 | 0.9 | 1.5 | 0.7 | 1.6 |
| Sample 3 | 90 | 14.06 | 0.8 | 0.0 | 0.8 | 0.9 | 1.2 |
| Sample 4 | 90 | 15.86 | 0.9 | 0.2 | 0.9 | 1.2 | 1.5 |

Urine:

| Sample | N | Mean (mg/dL) | Within-Day (%CV) | Between-Day (%CV) | Within-Lot (%CV) | Between-Lot (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control 1 | 90 | 7.19 | 1.1 | 1.0 | 1.5 | 1.7 | 2.2 |
| Control 2 | 90 | 10.22 | 0.7 | 0.7 | 1.0 | 1.2 | 1.5 |
| Sample 1 | 90 | 2.53 | 2.5 | 1.4 | 2.9 | 4.6 | 5.5 |
| Sample 2 | 90 | 5.80 | 1.2 | 1.1 | 1.6 | 3.0 | 3.4 |
| Sample 3 | 90 | 10.53 | 1.0 | 0.8 | 1.3 | 2.4 | 2.7 |
| Sample 4 | 90 | 13.05 | 1.0 | 0.5 | 1.1 | 2.1 | 2.4 |
| Sample 5 | 90 | 16.11 | 3.2 | 2.1 | 3.8 | 0.0 | 3.8 |

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# Yumizen C1200 Creatinine Jaffé:

A study to evaluate repeatability and within-laboratory precision was performed using 2 levels of control materials and 5 levels of patient samples (for both serum and urine matrices). The data was collected using 3 instrument systems and 1 reagent lot, and the samples were tested in duplicate for 20 days, 2 runs per day. The results are given below:

Serum:

| Sample | N | Mean (mg/dL) | Within-run (%CV) | Between-Run (%CV) | Between-Day (%CV) | Between-Instrument (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control N | 240 | 1.81 | 0.6 | 1.6 | 1.3 | 0.0 | 2.1 |
| Control P | 240 | 5.23 | 0.5 | 1.6 | 1.1 | 0.1 | 2.1 |
| Sample 1 | 240 | 0.55 | 1.9 | 1.8 | 1.8 | 0.0 | 3.1 |
| Sample 2 | 240 | 1.56 | 1.5 | 1.5 | 1.9 | 0.0 | 2.9 |
| Sample 3 | 240 | 6.56 | 0.5 | 1.8 | 0.9 | 0.0 | 2.0 |
| Sample 4 | 240 | 11.38 | 0.4 | 1.5 | 1.0 | 0.0 | 1.9 |
| Sample 5 | 240 | 16.56 | 0.4 | 2.4 | 0.5 | 0.0 | 2.5 |

Urine:

| Sample | N | Mean (mg/dL) | Within-run (%CV) | Between-Run (%CV) | Between-Day (%CV) | Between-Instrument (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control 1 | 240 | 60.38 | 0.8 | 1.7 | 1.0 | 0.0 | 2.1 |
| Control 2 | 240 | 150.24 | 0.5 | 1.6 | 1.3 | 0.0 | 2.1 |
| Sample 1 | 240 | 5.56 | 3.4 | 3.5 | 3.6 | 1.3 | 6.2 |
| Sample 2 | 240 | 11.52 | 2.1 | 2.1 | 1.9 | 0.0 | 3.5 |
| Sample 3 | 240 | 92.91 | 0.8 | 1.8 | 0.0 | 0.3 | 2.0 |
| Sample 4 | 240 | 143.42 | 0.8 | 2.9 | 0.0 | 0.0 | 3.0 |

A study to evaluate lot-to-lot imprecision was performed using 2 levels of control materials and 5 levels of patient samples (for both serum and urine matrices). The data was collected using 1 instrument systems and 3 reagent lots, and the samples were tested in triplicate for 5 days, two runs per day. The results are given below:

Serum:

| Sample | N | Mean (mg/dL) | Within-Day (%CV) | Between-Day (%CV) | Within-Lot (%CV) | Between-Lot (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control N | 90 | 1.56 | 0.9 | 2.3 | 2.5 | 0.0 | 2.5 |
| Control P | 90 | 5.00 | 0.9 | 2.0 | 2.2 | 0.0 | 2.2 |
| Sample 1 | 90 | 0.46 | 1.7 | 2.5 | 3.1 | 0.0 | 3.1 |
| Sample 2 | 90 | 1.65 | 1.1 | 4.2 | 4.4 | 0.0 | 4.4 |
| Sample 3 | 90 | 6.78 | 0.8 | 2.6 | 2.7 | 0.0 | 2.7 |
| Sample 4 | 90 | 11.42 | 0.7 | 2.1 | 2.3 | 0.0 | 2.3 |
| Sample 5 | 90 | 16.67 | 0.6 | 1.7 | 1.8 | 0.0 | 1.8 |

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Urine:

| Sample | N | Mean (mg/dL) | Within-Day (%CV) | Between-Day (%CV) | Within-Lot (%CV) | Between-Lot (%CV) | Total (%CV) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Control 1 | 90 | 68.47 | 0.9 | 1.5 | 1.8 | 0.0 | 1.8 |
| Control 2 | 90 | 140.31 | 0.9 | 1.7 | 1.9 | 0.0 | 1.9 |
| Sample 1 | 90 | 5.67 | 3.4 | 5.0 | 6.1 | 0.0 | 6.1 |
| Sample 2 | 90 | 11.63 | 2.1 | 3.1 | 3.7 | 0.0 | 3.7 |
| Sample 3 | 90 | 89.03 | 1.6 | 2.1 | 2.6 | 0.0 | 2.6 |
| Sample 4 | 90 | 132.13 | 0.8 | 2.5 | 2.6 | 0.0 | 2.6 |
| Sample 5 | 90 | 218.30 | 0.7 | 1.7 | 1.8 | 0.0 | 1.8 |

2. Linearity:

Linearity studies were performed in accordance with CLSI EP06-A guideline.

For each analyte and sample type a series of 10 samples was prepared by combining various volumetric proportions of a low-level analyte sample to a high analyte concentration to produce samples with concentrations spanning the corresponding claimed measuring interval. Each level was measured in 4 replicates using 1 instrument and 1 lot of reagent.

Experimentally determined values were compared to expected values using linear regression analysis. The results of the linearity studies supported the claimed measuring ranges, as summarized below:

| Analyte | Sample type | Linear regression | Measuring Range | Concentrations tested |
| --- | --- | --- | --- | --- |
| Calcium (mg/dL) | Serum | y = 1.020 x - 0.065, R² = 0.9996 | 4.0 - 18.05 | 0.00 - 19.41 |
| | Urine | y = 1.002 x + 0.003, R² = 0.9995 | 0.64 - 18.05 | 0.00 - 20.65 |
| Creatinine (mg/dL) | Serum | y = 1.021 x + 0.003, R² = 0.9995 | 0.23 - 18.08 | 0.00 - 25.16 |
| | Urine | y = 0.968 x + 0.112, R² = 0.9995 | 3.0 - 282.5 | 0.00 -333.70 |

The sponsor also performed a study to evaluate the auto-dilute feature available for serum and urine calcium and creatinine measurements. The study protocol and acceptance criteria were reviewed and found to be acceptable. The results of the study supported the sponsor's claim that samples with calcium concentrations above $18.05\mathrm{mg / dL}$ can be diluted onboard the analyzer to obtain results up to $54.15\mathrm{mg / dL}$ for serum and urine. The results of the study also support the sponsor's claim that samples with creatinine concentrations above 18.08 mg/dL (serum) or $282.5\mathrm{mg / dL}$ (urine) can be diluted onboard the analyzer to obtain results up to $54.24\mathrm{mg / dL}$ for serum samples and up to $847.5\mathrm{mg / dL}$ for urine samples.

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3. Analytical Specificity/Interference:

Interference studies were performed in accordance to the CLSI EP07-A2 guideline.

Yumizen C1200 Calcium AS:

Various concentrations of interferents were spiked into pooled human serum or pooled human urine containing calcium at normal and high concentrations. All samples were tested in quadruplicate. Non-significant interference was defined by the sponsor as the highest interferent level tested with bias ≤10% of the control for both serum and urine samples. The results of the interference study are summarized below:

| Test Interferent | Highest concentration tested that showed no interference | |
| --- | --- | --- |
| | Serum | Urine |
| Hemoglobin | 500 mg/dL | 500 mg/dL |
| Triglycerides | 495 mg/dL | 454 mg/dL |
| Total Bilirubin | 32.9 mg/dL | N/A |
| Direct Bilirubin | 24.0 mg/dL | 19.2 mg/dL |
| Acetylsalicylic Acid | 65.16 mg/dL | N/A |
| Ascorbic Acid | 5.98 mg/dL | 5.98 mg/dL |
| Ibuprofen | 50.1 mg/dL | 50.1 mg/dL |
| Acetaminophen | 20.0 mg/dL | N/A |
| Glucose | N/A | 1463.4 mg/dL |

Yumizen C1200 Creatinine Jaffé:

Various concentrations of interferents were spiked into pooled human serum or pooled human urine containing creatinine at normal and high concentrations. All samples were tested in quadruplicate. Non-significant interference was defined by the sponsor as the highest interferent level tested with bias ≤10% of the control for both serum and urine samples. The results of the interference study are summarized below:

| Test Interferent | Highest Concentration tested that showed no interference | |
| --- | --- | --- |
| | Serum | Urine |
| Hemoglobin | 500 mg/dL | 500 mg/dL |
| Triglycerides | 507.50 mg/dL | 393.75 mg/dL |
| Total Bilirubin | 23.24 mg/dL | N/A |
| Direct Bilirubin | 37.15 mg/dL | 31.39 mg/dL |
| Acetylsalicylic Acid | 48.87 mg/dL | N/A |
| Ascorbic Acid | 4.49 mg/dL | 5.98 mg/dL |
| Ibuprofen | 50.1 mg/dL | N/A |
| Acetaminophen | 20.0 mg/dL | N/A |
| Glucose | 682 mg/dL | N/A |
| Total Protein | 36 to 101 g/L | N/A |

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4. Assay Reportable Range:

| Analyte | Sample type | Reportable Range |
| --- | --- | --- |
| Calcium | Serum | 4.0 – 18.05 mg/dL |
| | Urine | 0.64 – 18.05 mg/dL |
| Creatinine | Serum | 0.23 – 18.08 mg/dL |
| | Urine | 3.0 – 282.5 mg/dL |

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The calibrators are traceable to NIST reference materials for calcium and creatinine. The information on the traceability of the assays is provided below:

| Test | Traceability |
| --- | --- |
| Calcium | NIST SRM909c |
| Creatinine | NIST SRM967a |

6. Detection Limit:

The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) studies were performed according to the CLSI EP17-A2 guideline.

Yumizen C1200 Calcium AS:

Limit of blank (LoB) study was performed by testing 4 individual blank serum samples, using two reagent lots over 5 days on a single instrument (or 5 individual blank urine samples using two reagent lots over 4 days on a single instrument). Each day, for each reagent lot, 4 replicate measurements were recorded (80 results per reagent lot). Data was analyzed using non-parametric analysis.

Limit of detection (LoD) study was performed by testing 4 low level serum samples and 4 low level urine samples using two reagent lots over 4 days on a single instrument. Each day, for each reagent lot, 4 replicate measurements were recorded (64 results per reagent lot). Data was analyzed using non-parametric analysis.

Limit of quantitation (LoQ) study was performed by testing 5 low level serum samples (or 5 low level urine samples) using 2 reagent lots over 4 days on a single instrument. Each day, for each reagent lot, 4 replicate measurements were recorded (80 results per reagent lot). The LoQ for calcium met an imprecision ≤ 20% CV.

Yumizen C1200 Creatinine Jaffé:

Limit of blank (LoB) study was performed by testing 1 blank sample, using two reagent lots over 4 days on 3 instrument systems. Each day, for each reagent lot and each instrument, 5 replicate measurements were recorded (60 results per reagent lot). Data was analyzed using non-parametric analysis.

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Limit of detection (LoD) study was performed by testing 4 low level serum samples and 4 low level urine samples using two reagent lots over 4 days on a single instrument. Each day, for each reagent lot, 4 replicate measurements were recorded (64 per reagent lot). Data was analyzed using non-parametric analysis.

Limit of quantitation (LoQ) study was performed by testing 5 low level serum samples and 5 low level urine samples using 2 reagent lots over 4 days on a single instrument. Each day, for each reagent lot, 4 replicate measurements were recorded (80 results per reagent lot). The LoQ for creatinine met an imprecision ≤ 20% CV.

Below is a summary of the results:

| Analyte | LoB | | LoD | | LoQ | |
| --- | --- | --- | --- | --- | --- | --- |
| | Serum | Urine | Serum | Urine | Serum | Urine |
| Calcium (mg/dL) | 0.16 | 0.12 | 0.48 | 0.24 | 0.57 | 0.64 |
| Creatinine (mg/dL) | 0.00 | 0.35 | 0.04 | 0.93 | 0.23 | 2.66 |

The upper and lower limits of the measuring range for the calcium and creatinine assays are supported by the LoQ studies and the linearity studies.

7. Assay Cut-Off:

Not applicable.

B Comparison Studies:

1. Method Comparison with Predicate Devices:

Performance of the Yumizen C1200 Calcium AS reagent for serum and urine was compared with the predicate device, ABX Pentra Calcium AS CP reagent (k123171). A total of 166 native serum samples and a total of 105 native urine samples were assayed in duplicate over 5 days. Only the first replicate was used for data analysis, which was conducted using Passing-Bablok regression.

Performance of the Yumizen C1200 Creatinine Jaffé reagent for serum and urine was compared with the predicate device, ABX Pentra Creatinine 120 CP reagent (k110530). A total of 131 native serum samples and a total of 148 native urine samples with creatinine concentrations were assayed in duplicate over 5 days. Only the first replicate was used for data analysis, which was conducted using Passing-Bablok regression.

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The correlations between the predicate device and the candidate are summarized below.

| Analyte | Specimen Type | N | Slope | Intercept | R2 | Test Range |
| --- | --- | --- | --- | --- | --- | --- |
| Calcium (mg/dL) | Serum | 166 | 1.0000 | 0.2406 | 0.976 | 6.26 - 17.92 |
| | Urine | 105 | 0.9436 | 0.5537 | 0.995 | 1.08 - 17.24 |
| Creatinine (mg/dL) | Serum | 131 | 0.9633 | 0.1035 | 0.995 | 0.32 – 13.94 |
| | Urine | 148 | 0.9483 | -0.4678 | 0.997 | 4.93 – 258.30 |

The sponsor also performed a second method comparison study to evaluate the performance of the candidate device when using lithium heparin plasma samples. For calcium, 108 plasma samples were evaluated on Yumizen C1200 analyzer using Yumizen C1200 Calcium AS reagent and on the Horiba Pentra C400 analyzer using Horiba Pentra reagent (Predicate device). For creatinine, 69 plasma samples were evaluated on Yumizen C1200 analyzer using Yumizen C1200 Creatinine Jaffe reagent and on the Horiba Pentra C400 analyzer using Horiba Pentra reagent. Each sample was measured by the candidate device in duplicate. Only the first replicate was used for data analysis.

| Analyte | Specimen Type | N | Slope | Intercept | R2 | Test Range |
| --- | --- | --- | --- | --- | --- | --- |
| Calcium | Plasma | 108 | 0.9423 | 0.4646 | 0.997 | 4.33 – 16.8 mg/dL |
| Creatinine | Plasma | 69 | 1.087 | -0.0825 | 0.999 | 0.58 – 18.29 mg/dL |

2. Matrix Comparison:

The performance of the device with serum and lithium heparin plasma samples was evaluated in the method comparison section above. The study results support the sponsor's claims that serum and heparin-lithium plasma specimens are acceptable sample types to be used with the Yumizen C1200 Calcium AS and Yumizen 1200 Creatinine Jaffe assays.

C Clinical Studies:

1. Clinical Sensitivity:

Not applicable.

2. Clinical Specificity:

Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Not applicable.

D Clinical Cut-Off:

Not applicable.

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# E Expected Values/Reference Range:

A reference range study for the Calcium AS and Creatinine Jaffé assays was conducted according to CLSI EP28-A3 to verify serum values cited from the literature. Serum samples were collected from healthy adults (n=40 for Calcium AS and 35 (men) + 25 (women) for Creatinine Jaffé). Each sample was assayed in duplicate. Results of the verification study support the serum reference ranges which were established through literature. Reference ranges for urine samples are cited from the literature.

## Calcium:

Serum/Plasma¹:
Adults: 8.6 – 10.2 mg/dL.

Urine²:
Women < 250 mg/24 h
Men < 300 mg/24 h

## Creatinine Jaffé:

Serum/Plasma³:
Women: 5-9 mg/dL
Men: 7-12 mg/dL

Urine¹:
Women: 10-20 mg/kg/day
Men: 14-26 mg/kg/day

## References:

1. Roberts WL, McMillin GA, Burtis CA, Bruns DE. Reference Information for the Clinical Laboratory, TIETZ Textbook of Clinical Chemistry and Molecular Diagnostics. 4th Ed; Burtis CA, Ashwood ER, Bruns DE, (Elsevier Saunders eds. St Louis, USA), (2006): 2258.
2. Thomas L. Clinical Laboratory Diagnostics. 1st ed. Frankfurt: TH-Books Verlagsgesellschaft; 1998. p. 231–241.
3. Mazzachi BC, Peake MJ, Ehrhard V. Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clin. Lab. (2000) 46: 53-55.

# F Other Supportive Instrument Performance Characteristics Data:

Not applicable.

# VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

# IX Conclusion:

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