Comprehensive Metabolic Panel, skyla Clinical Chemistry Analyzer, Minicare C300 Clinical Chemistry Analyzer
Device Facts
| Record ID | K171971 |
|---|---|
| Device Name | Comprehensive Metabolic Panel, skyla Clinical Chemistry Analyzer, Minicare C300 Clinical Chemistry Analyzer |
| Applicant | Lite-On Technology Corp. H.S.P.B. |
| Product Code | CJE · Clinical Chemistry |
| Decision Date | Jan 25, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1050 |
| Device Class | Class 2 |
Indications for Use
The Comprehensive Metabolic Panel is intended to be used for the quantitative determination of Alkaline Phosphate (ALP), Alanine Aminotransferase (ALP/GPT), Aspartate Aminotransferase (AST/GOT), Blood Urea Nitrogen (BUN) and Creatinine (CREA) in concentrations in lithium-heparinized venous whole blood, heparinized plasma, or serum in a clinical laboratory setting or point-of-care location. Alkaline phosphatase or its isoenzymes measurements are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases. Aspartate aminotransferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease. Blood urea nitrogen measurements are used in the diagnosis and treatment of certain types of renal and metabolic diseases. 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. The skyla Clinical Chemistry Analyzer is an in-vitro diagnostic device for the quantitative determination of clinical chemistry analytes in lithium-heparinized venous whole blood, heparinized plasma, or serum. It is for clinical laboratory and point-of-care use. The Minicare C300 Clinical Chemistry Analyzer is an in-vitro diagnostic device for the quantitative determination of clinical chemistry analytes in lithium-heparinized venous whole blood, heparinized plasma, or serum. It is for clinical laboratory and point-of-care use.
Device Story
System comprises portable analyzer and single-use disposable reagent panel discs; used in clinical labs or point-of-care settings. Input: lithium-heparinized venous whole blood, plasma, or serum. Operation: disc separates sample into plasma/cells; meters plasma and diluent; mixes with reagent beads; analyzer uses photometric measurement (absorbance change) to determine analyte concentration. Output: quantitative concentration values for ALP, ALT, AST, BUN, and CREA. Healthcare providers use results for diagnosis and treatment of liver, bone, parathyroid, intestinal, heart, and renal diseases. Benefits include rapid, automated point-of-care testing.
Clinical Evidence
Bench testing only. Analytical performance established via CLSI guidelines (EP05-A3, EP06-A, EP07-A2, EP09-A3, EP17-A2). Precision studies (N=80) showed total CVs generally <10%. Linearity confirmed across claimed ranges (R2 > 0.99). Method comparison against Beckman Coulter AU2700 (N=120-221 samples) showed high correlation (r > 0.99). Matrix comparison confirmed equivalence between serum, plasma, and whole blood.
Technological Characteristics
Portable analyzer using LED light source and photodiode detector. Employs centrifugal liquid handling and colorimetric (absorbance) measurement. Operates at 37°C. Connectivity includes bar-coded reagent discs for calibration. Electrical safety/EMC per IEC 60601-1-2. Software includes internal quality control beads for fluidics, spectrophotometer, and temperature monitoring.
Indications for Use
Indicated for quantitative determination of ALP, ALT, AST, BUN, and CREA in lithium-heparinized venous whole blood, heparinized plasma, or serum. Used in clinical labs or point-of-care settings for diagnosis/treatment of liver, bone, parathyroid, intestinal, heart, renal, and metabolic diseases.
Regulatory Classification
Identification
An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
Predicate Devices
Related Devices
- K022312 — PICCOLO PHOSPHORUS TEST SYSTEM · Abaxis, Inc. · Sep 5, 2002
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number:
k171971
B. Purpose for Submission:
New Device
C. Measurand:
Alkaline phosphate (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Blood urea nitrogen (BUN) and Creatinine (CREA)
D. Type of Test:
Quantitative, photometric/colorimetric
E. Applicant:
Lite-On Technology Corp.
F. Proprietary and Established Names:
Comprehensive Metabolic Panel
skyla Clinical Chemistry Analyzer
Minicare C300 Clinical Chemistry Analyzer
G. Regulatory Information:
| Regulation description | Product Code | Device Class | Regulation Number | Panel |
| --- | --- | --- | --- | --- |
| Alkaline Phosphatase test system | CJE | Class II | 862.1050 | Clinical Chemistry (75) |
| Blood Urea Nitrogen test system | CDN | Class II | 862.1770 | |
| Creatinine test system | CGX | Class II | 862.1225 | |
| Aspartate aminotransferase (AST/SGOT) test system | CIT | Class II | 862.1100 | |
| Alanine amino transferase (ALT/SGPT) test system | CKA | Class I | 862.1030 | |
| Analyzer, chemistry, centrifugal, for clinical use | JJG | Class I | 862.2160 | |
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H. Intended Use:
1. Intended use(s):
See Indications for use below
2. Indication(s) for use:
The Comprehensive Metabolic Panel is intended to be used for the quantitative determination of Alkaline Phosphate (ALP), Alanine Aminotransferase (ALP/GPT), Aspartate Aminotransferase (AST/GOT), Blood Urea Nitrogen (BUN) and Creatinine (CREA) in concentrations in lithium-heparinized venous whole blood, heparinized plasma, or serum in a clinical laboratory setting or point-of-care location.
Alkaline phosphatase or its isoenzymes measurements are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.
Aspartate aminotransferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease.
Blood urea nitrogen measurements are used in the diagnosis and treatment of certain types of renal and metabolic diseases.
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.
The skyla Clinical Chemistry Analyzer is an in-vitro diagnostic device for the quantitative determination of clinical chemistry analytes in lithium-heparinized venous whole blood, heparinized plasma, or serum. It is for clinical laboratory and point-of-care use.
The Minicare C300 Clinical Chemistry Analyzer is an in-vitro diagnostic device for the quantitative determination of clinical chemistry analytes in lithium-heparinized venous whole blood, heparinized plasma, or serum. It is for clinical laboratory and point-of-care use.
3. Special conditions for use statement(s):
For prescription use only at point-of-care (POC) and clinical laboratory settings.
4. Special instrument requirements:
skyla Clinical Chemistry Analyzer or Minicare C300 Clinical Chemistry Analyzer
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I. Device Description:
The Comprehensive Metabolic Panel contains a set of dried reagents that are used in the quantitative testing of various substances in the blood sample. The Comprehensive Metabolic Panel reagent discs are designed to separate a heparinized venous whole blood sample into plasma and blood cells, quantity the amount of plasma and diluent through the metering function of disc, mix both of plasma and diluent, and deliver the mixture to each reaction wells where the dried reagent are present to initiate the chemical reactions that are then measured by analyzer. Alternately, the disc may also be used with heparinized plasma only and serum sample.
The skyla Clinical Chemistry System consists of a portable analyzer and single-use disposable reagent panel discs. The analyzers utilize precision photometric measurement technology, combined with the use of specific reagent panel disc, to measure the amount of substance in blood. The analyzer measures absorbance change of each reaction well in reagent panel disc and covert it to a concentration value for each analyte included on the panel.
The analyzer contains the following features and components:
- Compatibility with lithium-heparinized venous whole blood samples without the need for sample dilution.
- Operation by a colored touchscreen panel
- Fully automated system for simple operation
- Rapid analysis, reporting test results in approximately 15 minutes
- Power-on self-test capability, ensuring instrument stability
- Internal quality control functionality, ensuring reliable test results
- Built-in thermal printer for immediate printing of the test results
The Minicare C300 Clinical Chemistry Analyzer has the identical design and specifications of skyla Clinical Chemistry Analyzer, except the appearance and 2 additional USB ports.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Abaxis Piccolo
Abaxis Piccolo Primary Health Panel Reagent Rotor
2. Predicate 510(k) number(s):
k942782
k950164
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3. Comparison with predicate:
Assay
| Similarities / Differences | | |
| --- | --- | --- |
| Item | Candidate Device
Comprehensive Metabolic Panel
k171971 | Predicate Device
Abaxis Piccolo Primary
Health Panel Reagent Rotor
k950164 |
| Intended Use | Quantitative determination of alkaline phosphate, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine concentrations in lithium-heparinized venous whole blood, heparinized plasma, or serum in a clinical laboratory setting or point-of-care location. | Same |
| Intended users | Clinical laboratories or point-of-care (POC) settings | Same |
| Specimen Type | Serum and lithium-heparinized venous whole blood or plasma | Same |
| Reportable range | ALT: 20 – 500 U/L
ALP: 41 – 1500 U/L
AST: 20 – 1000 U/L
BUN: 2 – 120 mg/dL
CREA: 0.6 – 20 mg/dL | ALT: 5 - 2000 U/L
ALP: 5 - 2400 U/L
AST: 5 – 2000 U/L
BUN: 2 – 180 mg/dL
CREA: 0.2 - 20 mg/dL |
| Detection Wavelength | ALT: 340 nm
ALP: 405 nm
AST: 340 nm
BUN: 340 nm
CREA: 546 nm | ALT: 340 - 405 nm
ALP: 405 - 500 nm
AST: 340 – 405 nm
BUN: 340 - 405 nm
CREA: 550 - 600 nm |
| Calibration | Bar-encode on each reagent disc with factory calibrated lot specific data | Same |
| Quality control | Internal quality control function for each reagent disc | Same |
| Reagent storage | 2-8 °C (36-45 °F) | Same |
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Analyzers
| Similarities / Differences | | |
| --- | --- | --- |
| Item | Candidate Device
Skyla Clinical Chemistry Analyzer,
Minicare C300 Clinical Chemistry Analyzer
k171971 | Predicate Device
Abaxis Piccolo
k942782 |
| Intended Use | An in-vitro diagnostic device for the quantitative determination of clinical chemistry analytes in lithium-heparinized venous whole blood, heparinized plasma, or serum. It is for clinical laboratory and point-of-care use. | Same |
| Detector | Photodiode | Same |
| Method of measurement | Colorimetry (Absorbance) | Same |
| Blood separation function | Centrifugation technology integrated into the instrument | Same |
| Assay temperature | 37 °C (98.6 °F) | Same |
| Test time | 15 minutes | 12 minutes |
| Light Source | LEDs | Xenon arc stroboscopic lamp |
| Power requirements | 100-240 volts AC; 50-60 Hz; or 12 volts DC, 5.0A | 100-240 volts AC; 50-60 Hz; or 15 volts DC, 5.0 A |
| Operating temperature | 10-32 °C (50-90 °F) | 15-32 °C (59-90 °F) |
| Sample volume | 200 μL | 100 μL |
## K. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures
CLSI EP06-A Evaluation of Linearity of Quantitative Measurement Procedures
CLSI EP07-A2 Interference Testing in Clinical Chemistry
CLSI EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples
CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents
IEC 60601-1-2 Medical Electrical Equipment-Part 1-2: General Requirements for Basic Safety and Essential Performance
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L. Test Principle:
ALP activity is enzymatically determined. $p$-Nitrophenyl phosphate that is hydrolyzed by ALP into a yellow colored product $p$-Nitrophenol which has an absorbance at a wavelength of $405~\mathrm{nm}$. The rate of the reaction is directly proportional to the enzyme activity.
$$
p\text{-Nitrophenyl Phosphate} \xrightarrow{\text{ALP}} p\text{-Nitrophenol} + \text{Phosphate}
$$
ALT activity is enzymatically determined. ALT catalyzes the reaction of alanine with $\alpha$-ketoglutarate, converting them into glutamate and pyruvate. In the presence of NADH, lactate dehydrogenase converts pyruvate into lactate. In the course of the reaction NADH is oxidized to $\mathrm{NAD^{+}}$. The decrease of NADH absorbance is measured at a wavelength of 340 nm and is proportional to ALT activity.
$$
\text{L-Alanine} + \alpha\text{-ketoglutarate} \xrightarrow{\text{ALT}} \text{Pyruvate} + \text{L-Glutamate}
$$
$$
\text{Pyruvate} + \text{NADH} + \text{H}^{+} \xrightarrow{\text{LDH}} \text{L-Lactate} + \text{NAD}^{+} + \text{H}_2\text{O}
$$
AST activity is enzymatically determined. When the test sample reacts with the substrate-enzyme reagent, AST converts L-Aspartic acid and $\alpha$-ketoglutarate into monosodium glutamate and amide acetate. amide acetate is subsequently converted into malate by malate dehydrogenase while NADH undergoes oxidation to $\mathrm{NAD^{+}}$. The decrease of NADH absorbance is measured at a wavelength of $340~\mathrm{nm}$ and is proportional to AST activity.
$$
\text{L-asparate} + \alpha\text{-ketoglutarate} \xrightarrow{\text{AST}} \text{oxaloactate} + \text{L-glutamate} \xrightarrow{\text{MDH}} \text{oxaloactate} + \text{NADH} \xrightarrow{\text{malate}} + \text{NAD}^{+}
$$
BUN is enzymatically determined. Urea undergoes a urease catalyzed hydrolysis, thus producing ammonia and carbon dioxide. In a glutamate dehydrogenase (GLDH) catalyzed reaction ammonia reacts with 2-oxoglutarate yielding L-glutamate. In the process of this reaction, NADH is oxidized to $\mathrm{NAD^{+}}$ which in turn undergoes a color reaction. The rate of change of absorbance at wavelength of $340~\mathrm{nm}$ is measured and proportional to the BUN concentration.
$$
\text{Urea} + \text{H}_2\text{O} \xrightarrow{\text/Urease}} 2\text{NH}_3 + \text{CO}_2
$$
$$
\text{NH}_3 + 2\text{-Oxoglutarate} + \text{NADH} \xrightarrow{\text{GLDH}} \text{L-Glutamate} + \text{H}_2\text{O} + \text{NAD}^{+}
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CREA is determined through the endpoint enzymatic reaction approach. Creatinine amidohydrolase hydrolyzes CREA to creatine. Then creatine is converted into sarcosine through catalysis of creatine amidinohydrolase. Furthermore, sarcosine oxidase oxidizes sarcosine, yielding glycine, formaldehyde and peroxide (H2O2) in the process. The enzyme peroxidase processes hydrogen peroxide, 2,4,6-3 hydroxy-benzoic acid (TBHBA) and 4-amine triazolam alternate pyrazol (4-AAP), forming a quinoneimine dye as a product. The dye formation is measured at wavelength of 546 nm and is proportional to the amount of creatinine in the sample.
Creatinine amidohyrolase
Creatinine + H2O → Creatine
Creatine amidohyrolase
Creatine + H2O → Sarcosine + Urea
Estimated Glomerular Filtration Rate (eGFR)
eGFR is the kidney filtrate per minute, which is calculated from creatinine results. It is used to assess renal function. Calculation of the eGFR is performed by the skyla Clinical Chemistry Analyzer using the patient's age, gender and race. The equation is shown below. For African American, multiply the eGFR value by 1.212.
$$
\mathrm{eGFR} = 175 \times (\mathrm{Scr}) - 1.154 \times (\mathrm{Age}) - 0.203 \times (0.742 \text{ if female})
$$
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
Analytical performance was established using the skyla Clinical Chemistry Analyzer; performance is also representative of the Minicare C300 Clinical Chemistry Analyzer.
### a. Internal Precision/Reproducibility:
Internal precision was conducted using CLSI EP5-A3 guideline. The study was performed using three levels (low, middle, high) of patient serum samples. Each level was tested on 3 skyla Clinical Chemistry Analyzers and 1 lot of Comprehensive Metabolic Panel disc in duplicates with 2 runs per day over 20 days. The results of the within-run and total precision for one representative analyzer are summarized below:
| Test System | N | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| ALP (U/L) | 80 | 1 | 71.9 | 1.8 | 2.5 | 1.8 | 2.5 |
| | | 2 | 788.8 | 33.9 | 4.3 | 33.9 | 4.3 |
| | | 3 | 1403.1 | 23.4 | 1.7 | 24.2 | 1.7 |
| ALT (U/L) | 80 | 1 | 39.9 | 2.7 | 6.7 | 2.7 | 6.8 |
| | | 2 | 194.6 | 6.1 | 3.1 | 6.3 | 3.2 |
| | | 3 | 478.0 | 14.5 | 3.0 | 14.8 | 3.1 |
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| Test System | N | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| AST (U/L) | 80 | 1 | 36.9 | 3.0 | 8.1 | 3.6 | 9.7 |
| | | 2 | 282.4 | 6.2 | 2.2 | 6.3 | 2.2 |
| | | 3 | 839.7 | 18.4 | 2.2 | 18.9 | 2.3 |
| BUN (mg/dL) | 80 | 1 | 14.46 | 0.52 | 3.6 | 0.55 | 4.5 |
| | | 2 | 23.29 | 0.73 | 3.1 | 0.79 | 3.4 |
| | | 3 | 106.86 | 2.77 | 2.6 | 3.26 | 3.0 |
| Crea (mg/dL) | 80 | 1 | 1.17 | 0.09 | 8.1 | 0.10 | 8.5 |
| | | 2 | 7.52 | 0.32 | 4.3 | 0.32 | 4.3 |
| | | 3 | 15.65 | 0.37 | 2.4 | 0.40 | 2.6 |
## b. External Precision studies (serum)
Precision at external POC sites was evaluated as described in CLSI EP5-A3 guideline. The study was performed at 3 point of care settings in 3 outpatient clinics. Each site used 2 analyzers and a total of 9 POC operators. Three levels of human serum were prepared (low, middle, high). The samples were tested by POC operators on the skyla Clinical Chemistry Analyzers in 2 replicates per run, 2 runs per day for 20 days (N=80). The within run, total SD, and percent CVs were calculated. The results for the three POC sites are summarized in the tables below:
| Test System | Site | Level | Mean (U/L) | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| Serum ALP | POC 1 | Serum 1 | 71.9 | 2.3 | 3.2 | 2.4 | 3.4 |
| | | Serum 2 | 785.6 | 31.7 | 4.0 | 32.4 | 4.1 |
| | | Serum 3 | 1407.3 | 38.9 | 2.8 | 42.3 | 3.0 |
| | POC 2 | Serum 1 | 72.2 | 2.1 | 2.9 | 2.1 | 2.9 |
| | | Serum 2 | 787 | 28.1 | 3.6 | 30.1 | 3.8 |
| | | Serum 3 | 1405.1 | 20.5 | 1.5 | 25.9 | 1.8 |
| | POC 3 | Serum 1 | 71.9 | 1.7 | 2.3 | 1.7 | 2.3 |
| | | Serum 2 | 784.1 | 27.1 | 3.5 | 32.8 | 4.2 |
| | | Serum 3 | 1405.9 | 36.8 | 2.6 | 37.5 | 2.7 |
| | Combined | Serum 1 | 72.0 | | | 1.8 | 2.56 |
| | | Serum 2 | 785.5 | | | 29.3 | 3.73 |
| | | Serum 3 | 1406.0 | | | 33.3 | 2.36 |
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| Test System | Site | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| Serum ALT | POC 1 | Serum 1 | 40.5 | 2.3 | 5.7 | 2.4 | 5.8 |
| | | Serum 2 | 193.9 | 5.6 | 2.9 | 5.6 | 2.9 |
| | | Serum 3 | 474.5 | 11.9 | 2.5 | 12.6 | 2.7 |
| | POC 2 | Serum 1 | 40.7 | 2.3 | 5.6 | 2.3 | 5.6 |
| | | Serum 2 | 192.3 | 5.0 | 2.6 | 5.4 | 2.8 |
| | | Serum 3 | 477.2 | 9.8 | 2.0 | 10.8 | 2.3 |
| | POC 3 | Serum 1 | 40.6 | 2.0 | 5.0 | 2.2 | 5.3 |
| | | Serum 2 | 194.8 | 5.9 | 3.0 | 6.7 | 3.4 |
| | | Serum 3 | 478.2 | 14.8 | 3.1 | 14.8 | 3.1 |
| | Combined | Serum 1 | 40.6 | | | 2.0 | 5.0 |
| | | Serum 2 | 193.6 | | | 5.8 | 3.0 |
| | | Serum 3 | 476.7 | | | 12.3 | 206 |
| Test System | Site | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| Serum AST | POC 1 | Serum 1 | 40.3 | 2.9 | 7.3 | 3.1 | 7.65 |
| | | Serum 2 | 283.5 | 4.7 | 1.6 | 5.0 | 1.8 |
| | | Serum 3 | 842.5 | 13.8 | 1.6 | 13.9 | 1.6 |
| | POC 2 | Serum 1 | 40.1 | 3.3 | 8.2 | 3.4 | 8.6 |
| | | Serum 2 | 279.7 | 5.6 | 2.0 | 5.8 | 2.1 |
| | | Serum 3 | 839.6 | 10.0 | 1.2 | 11.7 | 1.4 |
| | POC 3 | Serum 1 | 40.0 | 2.93 | 7.3 | 3.4 | 8.4 |
| | | Serum 2 | 286.0 | 5.5 | 1.9 | 7.2 | 2.5 |
| | | Serum 3 | 843.3 | 16.3 | 1.9 | 16.5 | 2.0 |
| | Combined | Serum 1 | 40 | | | 2.9 | 7.3 |
| | | Serum 2 | 283 | | | 6.2 | 2.2 |
| | | Serum 3 | 841 | | | 14.3 | 1.7 |
| Test System | Site | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| Serum BUN | POC 1 | Serum 1 | 14.43 | 0.48 | 3.3 | 0.50 | 3.5 |
| | | Serum 2 | 2.43 | 0.78 | 3.3 | 0.78 | 3.3 |
| | | Serum 3 | 106.67 | 3.14 | 2.9 | 3.57 | 3.4 |
| | POC 2 | Serum 1 | 14.59 | 0.43 | 3.0 | 0.49 | 3.4 |
| | | Serum 2 | 23.36 | 0.88 | 3.8 | 0.94 | 4.0 |
| | | Serum 3 | 106.35 | 2.53 | 2.4 | 3.37 | 3.2 |
| | POC 3 | Serum 1 | 14.52 | 0.46 | 3.1 | 0.49 | 3.4 |
| | | Serum 2 | 23.40 | 0.86 | 3.7 | 0.94 | 4.0 |
| | | Serum 3 | 105.82 | 3.12 | 2.9 | 3.40 | 3.25 |
| | Combined | Serum 1 | 14.51 | | | 0.48 | 3.3 |
| | | Serum 2 | 23.40 | | | 0.81 | 3.5 |
| | | Serum 3 | 106.28 | | | 3.29 | 3.1 |
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| Test System | Site | Level | Mean | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | CV (%) | SD | CV (%) |
| Serum CREA | POC 1 | Serum 1 | 0.97 | 0.06 | 5.8 | 0.07 | 7.0 |
| | | Serum 2 | 7.36 | 0.25 | 3.3 | 0.25 | 3.4 |
| | | Serum 3 | 15.75 | 0.35 | 2.2 | 0.36 | 2.3 |
| | POC 2 | Serum 1 | 1.28 | 0.08 | 6.4 | 0.09 | 6.8 |
| | | Serum 2 | 7.62 | 0.22 | 2.9 | 0.25 | 3.2 |
| | | Serum 3 | 15.62 | 0.45 | 2.9 | 0.48 | 3.1 |
| | POC 3 | Serum 1 | 1.07 | 0.07 | 6.7 | 0.07 | 6.8 |
| | | Serum 2 | 7.36 | 0.27 | 3.7 | 0.30 | 4.0 |
| | | Serum 3 | 15.45 | 0.41 | 2.7 | 0.46 | 3.0 |
| | Combined | Serum 1 | 1.11 | | | 0.08 | 7.0 |
| | | Serum 2 | 7.45 | | | 0.27 | 3.7 |
| | | Serum 3 | 15.6 | | | 0.43 | 2.8 |
c. External precision studies (whole blood)
Whole blood precision was performed at 3 point of care settings in 3 outpatient clinics. Three levels of whole blood samples were tested in ten replicates by 3 POC (total 9 operators) using twelve analyzers in one day. The results are summarized in the following table:
| | | | ALP (U/L) | | | ALT (U/L) | | | AST(g/dL) | | | BUN (mg/dL) | | | CREA (mg/dL) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Site | OP | Level | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% |
| 1 | 1 | Low | 56.9 | 2.51 | 4.4 | 28 | 2.7 | 9.7 | 32 | 2.7 | 8.6 | 11.0 | 0.24 | 2.2 | 0.9 | 0.05 | 5.5 |
| | 2 | Low | 61.5 | 3.57 | 5.8 | 30 | 2.2 | 7.5 | 29 | 1.9 | 6.4 | 10.9 | 0.21 | 2.0 | 0.9 | 0.07 | 7.4 |
| | 3 | Low | 61.9 | 2.69 | 4.3 | 31 | 2.5 | 8.1 | 31 | 2.9 | 9.3 | 10.5 | 0.36 | 3.5 | 0.9 | 0.07 | 7.3 |
| | 1 | Med | 744.9 | 12.06 | 1.6 | 294 | 4.1 | 1.4 | 459 | 6.4 | 1.4 | 30.9 | 0.72 | 2.3 | 7.7 | 0.17 | 2.2 |
| | 2 | Med | 749.9 | 15.79 | 2.1 | 294 | 3.4 | 1.2 | 459 | 5.4 | 1.2 | 31.1 | 0.88 | 2.8 | 7.6 | 0.27 | 3.5 |
| | 3 | Med | 757.7 | 13.57 | 1.8 | 298 | 6.5 | 2.2 | 31.6 | 2.7 | 8.6 | 30.6 | 1.18 | 3.9 | 7.6 | 0.45 | 5.9 |
| | 1 | High | 1341.0 | 10.84 | 0.8 | 402 | 6.6 | 1.6 | 29.3 | 1.9 | 6.4 | 93.7 | 3.06 | 3.3 | 16.5 | 0.6 | 3.6 |
| | 2 | High | 1322.5 | 11.33 | 0.9 | 397 | 12.9 | 3.2 | 30.9 | 2.9 | 9.3 | 92.3 | 2.96 | 3.2 | 16.6 | 0.62 | 3.8 |
| | 3 | High | 1315.1 | 17.22 | 1.3 | 401 | 9.8 | 2.4 | 458.6 | 6.4 | 1.4 | 93.8 | 2.77 | 3.0 | 16.6 | 1.05 | 6.3 |
| 2 | 1 | Low | 75.9 | 2.64 | 3.5 | 37 | 1.0 | 2.8 | 458.6 | 5.4 | 1.2 | 10.7 | 0.33 | 3.1 | 0.8 | 0.05 | 6.8 |
| | 2 | Low | 68.5 | 2.84 | 4.1 | 37 | 1.3 | 3.6 | 455.6 | 13.1 | 2.9 | 10.5 | 0.32 | 3.0 | 0.7 | 0.04 | 5.9 |
| | 3 | Low | 66.0 | 3.97 | 6.0 | 37 | 1.1 | 2.9 | 814.1 | 3.2 | 0.4 | 10.3 | 0.20 | 1.9 | 0.8 | 0.05 | 6.3 |
| | 1 | Med | 781.6 | 12.69 | 1.6 | 228 | 3.2 | 1.4 | 800.6 | 1.6 | 0.2 | 16.1 | 0.45 | 2.8 | 3.6 | 0.17 | 4.8 |
| | 2 | Med | 766.5 | 10.83 | 1.4 | 230 | 4.5 | 2.0 | 798.0 | 3.6 | 0.5 | 16.2 | 0.42 | 2.6 | 3.7 | 0.16 | 4.4 |
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| | | | ALP (U/L) | | | ALT (U/L) | | | AST(g/dL) | | | BUN (mg/dL) | | | CREA (mg/dL) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Site | OP | Level | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% | Mean | SD | CV% |
| | 3 | Med | 767.7 | 13.32 | 1.7 | 230 | 7.9 | 3.4 | 32.4 | 2.2 | 6.7 | 16.1 | 0.65 | 4.0 | 3.9 | 0.27 | 6.9 |
| | 1 | High | 1312.6 | 13.13 | 1.0 | 397 | 9.8 | 2.5 | 28.3 | 2.2 | 7.8 | 111.0 | 2.98 | 2.7 | 16.4 | 0.63 | 3.8 |
| | 2 | High | 1311.5 | 18.92 | 1.4 | 401 | 9.6 | 2.4 | 32.5 | 2.6 | 8.1 | 110.5 | 4.78 | 4.3 | 15.8 | 0.56 | 3.5 |
| | 3 | High | 1330.0 | 16.05 | 1.2 | 408 | 10.8 | 2.6 | 105.5 | 6.5 | 6.2 | 110.1 | 4.11 | 3.7 | 16.1 | 0.68 | 4.2 |
| 3 | 1 | Low | 99.4 | 2.91 | 2.9 | 41 | 3.3 | 8.1 | 102.6 | 6.4 | 6.2 | 7.4 | 0.33 | 4.5 | 0.8 | 0.05 | 7.0 |
| | 2 | Low | 101.0 | 2.54 | 2.5 | 39 | 1.2 | 3.0 | 104.4 | 7.9 | 7.6 | 7.4 | 0.29 | 3.9 | 0.7 | 0.05 | 7.0 |
| | 3 | Low | 106.5 | 3.50 | 3.3 | 41 | 3.9 | 9.4 | 817.9 | 15.8 | 1.9 | 7.4 | 0.23 | 3.1 | 0.7 | 0.04 | 5.9 |
| | 1 | Med | 677.9 | 8.88 | 1.3 | 219 | 9.5 | 4.3 | 833.3 | 15.8 | 1.9 | 29.0 | 1.03 | 3.6 | 4.7 | 0.14 | 3.0 |
| | 2 | Med | 665.0 | 10.02 | 1.5 | 224 | 5.3 | 2.3 | 841.1 | 11.2 | 1.3 | 29.1 | 0.68 | 2.3 | 4.6 | 0.22 | 4.7 |
| | 3 | Med | 682.0 | 4.67 | 0.7 | 225 | 5.6 | 2.5 | 40.7 | 2.1 | 5.1 | 28.2 | 1.05 | 3.7 | 4.8 | 0.33 | 6.8 |
| | 1 | High | 1405.8 | 18.27 | 1.3 | 476 | 8.9 | 1.9 | 37.8 | 2.9 | 7.8 | 91.4 | 3.98 | 4.4 | 14 | 0.75 | 5.3 |
| | 2 | High | 1419.3 | 9.87 | 0.7 | 480 | 14.9 | 3.1 | 40.4 | 1.4 | 3.5 | 93.8 | 3.30 | 3.5 | 14.1 | 0.62 | 4.4 |
| | 3 | High | 1398.4 | 19.68 | 1.4 | 481 | 9.1 | 1.9 | 264.7 | 8.3 | 3.1 | 94.7 | 4.02 | 4.2 | 14.4 | 0.93 | 6.5 |
# d. Linearity/assay reportable range:
The linearity studies of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen and creatinine were conducted in accordance to CLSI EP6-A guideline. A high and a low human serum pool sample were proportionally mixed to create 9 intermediate dilutions that span the claimed measuring range of each analyte test. The observed values were plotted against the expected values and linear regression analysis was performed. The summary results are provided in the table below.
| Analyte | Concentration Tested | R2 | Slope | Intercept | Claimed Measuring Range |
| --- | --- | --- | --- | --- | --- |
| ALP (U/L) | 30 – 2083 | 0.9967 | 1.0417 | 10.329 | 41 – 1500 |
| ALT (U/L) | 17 – 535 | 0.9999 | 0.9985 | 0.4839 | 20 – 500 |
| AST (U/L) | 16 – 1021.3 | 0.9984 | 1.0006 | 0.0405 | 20 – 1000 |
| BUN (mg/dL) | 1.8 – 126.9 | 0.9979 | 0.9588 | 0.7389 | 2 – 120 |
| CREA (mg/dL) | 0.48 – 21.48 | 0.9993 | 0.9988 | -0.0015 | 0.6 – 20 |
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The results of the linearity study support the sponsor's claimed measuring ranges (as described in the table above).
e. Traceability, Stability, Expected values (controls, calibrators, or methods):
# Traceability
The calibrators are traceable to Siemens ADVIA Chemistry analyzer method calibration to below reference material or method. The calibration parameters of each test system were established internally, and are unique with each reagent lot. The calibration information is bar-encoded on each reagent disc.
| Assay | Reference material / method |
| --- | --- |
| ALT | The ADVIA ALT method is traceable to the IFCC reference method via patient sample correlation. |
| ALP | The ADVIA ALP method is traceable to the IFCC reference method via patient sample correlation. |
| AST | The ADVIA AST method is traceable to the IFCC reference method via patient sample correlation. |
| BUN | The ADVIA BUN method is traceable to the CDC reference method, which uses reference materials from the National Institute of Standards and Technology (NIST). via patient sample correlation. |
| CREA | The ADVIA CREA_2 method is traceable to the IDMS Reference Method via correlation of patient samples and reference material SRM967 from the National Institute of Standards and Technology (NIST). |
# f. Detection limit:
The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined according to CLSI EP17-A2 guideline. Human serum samples were diluted with BSA to obtain the blank for the LoB studies and low concentration samples for LoD and LoQ studies. LoB was determined by running three blank samples in triplicate on two skyla Clinical Chemistry Analyzers with two reagent disc lots per day for ten days $(N = 60)$ . LoD and LoQ were performed using serum samples containing very low concentrations of the analyte tested in triplicate using 2 lots of reagents disc for ten days $(N = 60)$ .
The LoB is the 95th percentile value from 60 measurements of a near zero of sample over 10 days.
The LoD was calculated using the following formula: $\mathrm{LoD} = \mathrm{LoB} + \mathrm{c}\beta^{*}\mathrm{SD}_{\mathrm{S}}$ . In the equation, $\mathrm{c}\beta = 1.645 / (1 - (1 / (4^{*}\mathrm{f}))$ , where $\mathrm{f}$ is the degrees of freedom, and $\mathrm{SD}_{\mathrm{S}}$ is the standard deviation of the low concentration sample.
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LoQ is defined as the concentration at which measured total error is less than the predefined total error of $\pm 30\%$ .
The results of LoB, LoD and LoQ are summarized below table.
| Analyte | LoB | LoD | LoQ | Claimed Measuring Range |
| --- | --- | --- | --- | --- |
| ALP (U/L) | 2.350 | 4.405 | 4.405 | 41 – 1500 |
| ALT (U/L) | 2.701 | 5.228 | 5.228 | 20 – 500 |
| AST (U/L) | 6.695 | 12.089 | 11.690 | 20 – 1000 |
| BUN (mg/dL) | 0.795 | 1.526 | 1.526 | 2 – 120 |
| CREA (mg/dL) | 0.108 | 0.262 | 0.262 | 0.6 – 20 |
# g. Analytical specificity:
To determine the effects of potential endogenous and exogenous interference, the sponsor conducted an analytical specificity study according to CLSI EP07-A2 guideline. Different known concentrations of the interferent were tested in triplicate on two concentration of each analyte: level 1 (within normal range) and level 2 (high level at abnormal range). Samples were tested using the skyla Clinical Chemistry Analyzer with the Comprehensive Metabolic Panel (ALP, ALT, AST, BUN and CREA). The sponsor defined significant interference as bias $>10\%$ between the test and control samples.
| Analyte | Highest concentrations tested that did not show significant interference | | | |
| --- | --- | --- | --- | --- |
| | Hemolysis (Hemoglobin) | Icterus Bilirubin (unconjugated) | Icterus Bilirubin (conjugated) | Lipemia (Intralipid) |
| ALP | 600 mg/dL | 66.4 mg/dL | 32.7 mg/dL | 1032 mg/dL |
| ALT | 243 mg/dL | 60.3 mg/dL | 18.2 mg/dL | 411 mg/dL |
| AST | 202 mg/dL | 15.9 mg/dL | 32.7 mg/dL | 189.9 mg/dL |
| BUN | 600 mg/dL | 66.4 mg/dL | 29.3 mg/dL | 1032 mg/dL |
| CREA | 224 mg/dL | 13.1 mg/dL | 2.6 mg/dL | 390.8 mg/dL |
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| Substances | Effect of exogenous substances | | |
| --- | --- | --- | --- |
| | Test Concentration | Affected Test Item | Effect |
| Acetaminophen | 20 mg/dL | No significant interference | |
| Acetylsalicylic acid | 65 mg/dL | No significant interference | |
| Ampicillin | 5 mg/dL | No significant interference | |
| Ascorbic acid | 6 mg/dL | No significant interference | |
| Caffeine | 6 mg/dL | No significant interference | |
| Cephalothin | 30 mg/dL | No significant interference | |
| Cimetidine | 2 mg/dL | No significant interference | |
| Ibuprofen | 50 mg/dL | CREA | 11.8% increase |
| Salicylic acid | 60 mg/dL | ALT | 16.3% decrease |
| Theophylline | 4 mg/dL | ALP | 14.4% decrease |
The interfering substance with significant interference (>10% bias) are as follows:
- ALP concentrations are decreased by 14.4% when 4 mg/dL Theophylline is present in the sample.
- Salicylic Acid at 60 mg/dL causes a 16.3% decrease in ALT levels.
- Creatinine levels are increased by 11.8% in the presence of 50 mg/dL Ibuprofen.
h. Assay cut-off:
Not applicable.
2. Comparison studies:
a. Method comparison with predicate device:
POC Method comparison, whole blood and serum
The method comparison study was performed at three POC sites using 8 analyzers and a total of 9 POC operators. A total of 120 lithium heparinized venous whole blood and serum samples were tested using the skyla Clinical Chemistry Analyzer and Comprehensive Metabolic Panel and compared to matched serum samples analyzed using ALP, ALT, AST, BUN and Creatinine assays on the Beckman Coulter AU2700. The results of the overall performance of the device at all the sites are summarized in the tables below.
Summary Result of Method Comparison, Lithium heparin whole blood
| Analyte | Correlation Coefficient | Slope | Intercept | N | Sample range tested |
| --- | --- | --- | --- | --- | --- |
| ALP | 0.9987 | 0.9963 | 1.5568 | 221 | 41 – 1421 U/L |
| ALT | 0.9978 | 1.0029 | -0.1760 | 185 | 20 – 491 U/L |
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Summary Result of Method Comparison, Serum
| Analyte | Correlation Coefficient | Slope | Intercept | N | Sample range tested |
| --- | --- | --- | --- | --- | --- |
| ALT | 0.9989 | 1.0013 | 1.0197 | 174 | 20 – 998 U/L |
| BUN | 0.9981 | 0.9935 | -0.0710 | 210 | 2.4 – 118 mg/dL |
| CREA | 0.9978 | 1.0121 | -0.0737 | 191 | 0.6 – 19.7 mg/dL |
b. Matrix comparison:
Studies were performed using matched serum, lithium heparin venous whole blood, and lithium heparinized plasma. A total of 40 human samples were analyzed using the skyla Clinical Chemistry Analyzer. The linear regression analyses are as follows:
| Test | Matrix | Slope | Intercept | Correlation Coefficient | Sample range |
| --- | --- | --- | --- | --- | --- |
| ALP (U/L) | Serum vs. Plasma | 0.994 | 1.5 | 0.9997 | 44-1407 |
| | WB vs. Serum | 0.996 | 1.4 | 0.9997 | 45-1392 |
| ALT (U/L) | Serum vs. Plasma | 1.002 | -1.3 | 0.9998 | 21-485 |
| | WB vs. Serum | 0.993 | 1.2 | 0.9997 | 21-592 |
| AST (U/L) | Serum vs. Plasma | 0.988 | 3.6 | 0.9987 | 20-953 |
| | WB vs. Serum | 0.988 | 3.8 | 0.9989 | 20-998 |
| BUN (mg/dL) | Serum vs. Plasma | 1.011 | -0.45 | 0.9989 | 7.7-90.2 |
| | WB vs. Serum | 0.982 | 0.71 | 0.9990 | 7.8-91.7 |
| CREA (mg/dL) | Serum vs. Plasma | 0.960 | 0.13 | 0.9965 | 0.7-19.3 |
| | WB vs. Serum | 1.004 | -0.02 | 0.9971 | 0.6-19.8 |
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The results of the matrix comparison study support the sponsor claim that serum, lithium heparin plasma and venous lithium heparin whole blood samples can be tested with these assays.
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:
The following expected values are provided in the product insert based on the literature¹:
| Analyte | | Reference range | Reference range (SI units) |
| --- | --- | --- | --- |
| ALP | | 37 – 108 U/L | 37 – 108 U/L |
| ALT | | 10 - 40 U/L | 10 - 40 U/L |
| AST | | 10 – 42 U/L | 10 – 42 U/L |
| BUN | | 9 – 23 mg/dL | 3.2 – 8.2 mmol urea/L |
| Creatinine | Male | 0.7 – 1.3 mg/dL | 62 – 115 μmol/L |
| | Female | 0.6 – 1.1 mg/dL | 53 – 97 μmol/L |
¹C. A. Burtis, E. R. Ashwood, and D. E. Bruns. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed., Elsevier Saunders, St. Louis, 2006
N. Instrument Name:
skyla Clinical Chemistry Analyzer
Minicare C300 Clinical Chemistry Analyzer
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O. System Descriptions:
1. Modes of Operation:
Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?
Yes ☐ X or No ☐
Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?
Yes ☐ or No ☐ X
2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ X or No ☐
3. Specimen Identification:
The user can utilize an external barcode scanner or touch screen display to manually enter patient information.
4. Specimen Sampling and Handling:
The following type of sampling devices are acceptable on the Skyla Chemistry Clinical Chemistry Analyzer and Minicare C300 Clinical Chemistry Analyzer:
- lithium-heparinized venous whole blood
- heparinized plasma
- serum
5. Calibration:
The Analyzer performs automatic system calibrations every time the instrument is powered on. The barcode on every manufactured reagent disc contains all information required for calibration of the test items. The analyzer will automatically read the barcode information during testing.
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6. Quality Control:
The sponsor recommends using BIO-RAD Lyphochek Assayed Chemistry Control / two levels (Level 1 and Level 2). The following recommendations are included in package insert:
- Quality control should be performed on each day the instrument is used.
- Users should follow local, state and federal regulations for quality control materials testing.
- Quality control should be analyzed when a new lot of discs are used on the analyzer.
- Quality control should be performed after analyzer has been turned off for any reason or reinitializing the analyzer.
- Quality control should be performed after routine maintenance procedures.
- Before a new batch of reagents is used for testing.
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
Not applicable.
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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