Medicon Hellas Albumin, Medicon Hellas Calcium, Medicon Hellas Creatinine, Medicon Hellas Urea Nitrogen, Medicon Hellas Glucose, Medicon Hellas Total Bilirubin, Medicon Hellas Direct Bilirubin
Device Facts
| Record ID | K200898 |
|---|---|
| Device Name | Medicon Hellas Albumin, Medicon Hellas Calcium, Medicon Hellas Creatinine, Medicon Hellas Urea Nitrogen, Medicon Hellas Glucose, Medicon Hellas Total Bilirubin, Medicon Hellas Direct Bilirubin |
| Applicant | Medicon Hellas S.A |
| Product Code | CIX · Clinical Chemistry |
| Decision Date | Sep 21, 2021 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1035 |
| Device Class | Class 2 |
Indications for Use
Medicon Hellas Albumin: Reagent for the quantitative measurement of albumin in serum. Albumin measurements are used in the diagnosis and treatments of numerous diseases involving primarily the liver or kidneys. Medicon Hellas Calcium: Reagent for the quantitative measurement of calcium in serum or urine. 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). Medicon Hellas Creatinine: Reagent for the quantitative measurement of creatinine in serum and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis. Medicon Hellas Glucose: Reagent for the quantitative measurement of glucose in serum and urine. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. Medicon Hellas Direct Bilirubin: Reagent for the quantitative measurement of direct bilirubin (conjugated) in serum. Measurements of the level of direct bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block. Medicon Hellas Total Bilirubin: Reagent for the quantitative measurements of total bilirubin in serum. Measurements of the levels of total bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block. Medicon Hellas Urea Nitrogen: Reagent for the quantitative measurement of urea nitrogen in serum and urine. Measurements are used in the diagnosis and treatment of certain renal and metabolic diseases.
Device Story
Reagents for quantitative in vitro diagnostic measurement of analytes (albumin, calcium, creatinine, glucose, direct/total bilirubin, urea nitrogen) in human serum/urine; used with Diatron Pictus 500 clinical chemistry analyzer. Principle of operation: photometric determination (monochromatic/bi-chromatic/turbidimetric) using endpoint or kinetic methods; photodiode detector measures absorbance changes at specific wavelengths. Analyzer automatically calculates concentration based on stored method parameters. Used in clinical laboratories by trained personnel. Output provides quantitative analyte levels to assist physicians in diagnosing/treating liver, kidney, metabolic, and bone diseases. Benefits include standardized diagnostic testing for patient management.
Clinical Evidence
Bench testing only. Studies included method comparison (CLSI EP09c, N>=70 specimens), linearity (CLSI EP06-A), sensitivity (LoB/LoD/LoQ per CLSI EP17-A2), precision (CLSI EP05-A3, 20 days), and interference testing (CLSI EP07-A/EP37). Results confirmed performance equivalent to predicate devices with high correlation (R2 > 0.98) and acceptable CVs.
Technological Characteristics
Photometric detection using photodiode; monochromatic/bi-chromatic/turbidimetric optical modes; endpoint and kinetic measurement; 12 wavelengths (340-750nm); linear absorbance range -0.1 to 3.6. Reagents are liquid-stable for use on Diatron Pictus 500 analyzer. Standardized clinical chemistry assays.
Indications for Use
Indicated for quantitative measurement of albumin, calcium, creatinine, glucose, direct/total bilirubin, and urea nitrogen in human serum or urine to aid in diagnosis/treatment of liver, kidney, metabolic, and carbohydrate disorders. Prescription use only.
Regulatory Classification
Identification
An albumin test system is a device intended to measure the albumin concentration in serum and plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.
Predicate Devices
- Beckman Coulter Albumin (k924368)
- Beckman Coulter Calcium (k061575)
- Beckman Coulter Creatinine (k934361)
- Beckman Coulter Glucose (k944406)
- Abbott Architect Direct Bilirubin (K022180)
- Beckman Coulter Total Bilirubin (k924964)
- Beckman Coulter Urea Nitrogen (BUN) (k944250)
Related Devices
- K131488 — ACE ALBUMIN REAGENT, ACE TOTAL PROTEIN REAGENT, ACE CALCIUM-ARSENAZO REAGENT AND ACE PHOSPHORUS REAGENT · Alfa Wassermann Diagnostics Technologies, LLC · Aug 19, 2013
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
k200898
B Applicant
Medicon Hellas, S.A
C Proprietary and Established Names
Medicon Hellas Albumin, Medicon Hellas Calcium, Medicon Hellas Creatinine, Medicon Hellas Urea, Medicon Hellas Glucose, Medicon Hellas Total Bilirubin, Medicon Hellas Direct Bilirubin
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CIX | Class II | 21 CFR 862.1035 - Albumin Test System | CH - Clinical Chemistry |
| CDQ | Class II | 21 CFR 862.1770 - Urea nitrogen test system | CH - Clinical Chemistry |
| 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 |
| CIG | Class II | 21 CFR 862.1110 - Bilirubin (total or direct) test system | CH - Clinical Chemistry |
| CFR | Class II | 21 CFR 862.1345 - Glucose test system | CH - Clinical Chemistry |
| CIG | Class II | 21 CFR 862.1110 - Bilirubin (total or direct) test system | CH - Clinical Chemistry |
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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## II Submission/Device Overview:
### A Purpose for Submission:
New device.
### B Measurand:
Albumin, calcium, creatinine, glucose, direct and total bilirubin, and urea nitrogen.
### C Type of Test:
Quantitative, colorimetric methods
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
**Medicon Hellas Albumin:** Reagent for the quantitative measurement of albumin in serum. Albumin measurements are used in the diagnosis and treatments of numerous diseases involving primarily the liver or kidneys.
**Medicon Hellas Calcium:** Reagent for the quantitative measurement of calcium in serum or urine. 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).
**Medicon Hellas Creatinine:** Reagent for the quantitative measurement of creatinine in serum and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.
**Medicon Hellas Glucose:** Reagent for the quantitative measurement of glucose in serum and urine. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
**Medicon Hellas Direct Bilirubin:** Reagent for the quantitative measurement of direct bilirubin (conjugated) in serum. Measurements of the level of direct bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block.
**Medicon Hellas Total Bilirubin:** Reagent for the quantitative measurements of total bilirubin in serum. Measurements of the levels of total bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
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Medicon Hellas Urea Nitrogen: Reagent for the quantitative measurement of urea nitrogen in serum and urine. Measurements are used in the diagnosis and treatment of certain renal and metabolic diseases.
## C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
## D Special Instrument Requirements:
Diatron Pictus 500 clinical chemistry analyzer
## IV Device/System Characteristics:
### Device Description:
#### Medicon Hellas Albumin - Reagent Composition:
Succinic acid buffer (pH 4.2±0.1): 500 mM
Bromocresol green: 0.75 mM
Brij 35: 0.9%
Non reactive ingredients, preservative
#### Medicon Hellas Calcium - Reagent Composition:
MES buffer (pH 6.5): 100 mmol/L
Arsenazo III: 1.5 mmol/L
Non reactive ingredients, preservative
#### Medicon Hellas Creatinine - Reagent Composition:
**Reagent 1:**
NaOH: 1.0 M
Detergent: 0.4 %
Non-reactive components and preservatives
**Reagent 2:**
Picric acid: 22 mM
Non-reactive components and preservatives
#### Medicon Hellas Glucose - Reagent Composition:
**Reagent 1:**
Tris Buffer (pH 7.8): 150 mM
NAD+: 3 mM
ATP: 3 mM
Non reactive components and preservatives
**Reagent 2:**
Tris Buffer (pH 7.8): 0.5 M
Hexokinase: < 22 kU/L
G-6-PDH: < 26 kU/L
Non reactive components and preservatives
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# Medicon Hellas Direct Bilirubin - Reagent Composition:
Reagent 1:
Sulfanilic acid: 32 mM
Hydrochloric acid: 165 mM
Reagent 2 (R2):
Sodium nitrite: 60 mM
# Medicon Hellas Total Bilirubin - Reagent Composition:
Reagent 1:
DPD: 2.2 mM
HCl: 120 mM
Surfactants
Reagent 2:
HCl: 120 mM
# Medicon Hellas Urea Nitrogen - Reagent Composition:
Reagent 1:
Tris buffer (pH 7.4): 150 mM
Urease: ≤ 30 kU/L
GLDH: ≤ 1 kU/L
ADP: 10 mM
α-Ketoglutarate: 10 mM
Non-reactive ingredients and preservatives.
Reagent 2:
Tris buffer (pH 7.7): 20 mM
NADH: 0.32 mM
Non-reactive ingredients and preservatives.
# A Principle of Operation:
# Medicon Hellas Albumin:
The bromocresol green (BCG) method is applied, without serum blank. The bi-chromatic photometric determination of albumin is based on albumin binding the anionic dye bromocresol green in mildly acidic pH. The increase raise in absorbance at 620/750 nm is proportional to the concentration of albumin in the sample. The sample volume used for the assay is 2 μL.
# Medicon Hellas Calcium:
Calcium ions react with Arsenazo III dye in acidic pH, to form a violet complex. The absorbance at 650/750 nm is proportional to the concentration of calcium in serum or urine samples. The analyzer photometer reads the absorbance at time intervals dictated by the method application stored in the analyzer memory, and the change in absorbance is calculated automatically. The sample volume used for the assay is 2 μL for serum or urine samples.
# Medicon Hellas Creatinine:
Creatinine forms a yellow-orange complex with picrate anions in alkaline medium. The rate of change of absorbance of the complex at 505/700 nm is proportional to creatinine concentration in
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serum or urine samples. The sample volume used for the assay is 22 μL for serum or urine samples.
## Medicon Hellas Glucose (Hexokinase):
The determination of glucose, according to the hexokinase method, is based on the following reactions, using 2 μL of sample for serum or urine samples.
$$
\begin{array}{l}
\text{Glucose} + \text{ATP} \xrightarrow{\text{Hexokinase}} 6\text{-phosphate glucose} + \text{ADP} \\
6\text{-phosphate glucose} + \text{NAD} \xrightarrow{\text{G-6PDH}} 6\text{-phosphate gluconic acid} + \text{NADH} \\
\end{array}
$$
The concentration of glucose is determined bi-chromatically by the absorbance change at 340/380 nm.
## Medicon Hellas Direct Bilirubin:
The modified Malloy-Evelyn method is applied on serum samples. Direct (conjugated) bilirubin reacts with diazotised sulfanilic acid in acidic pH to form azobilirubin, a colored chromophore. The absorbance of chromophore at 550/650 nm is proportional to the concentration of direct bilirubin in the sample. The free (unbound) bilirubin fraction does not react. The reaction is an end-point type. The sample volume used for the assay is 8 μL
## Medicon Hellas Total Bilirubin:
The DPD method is applied, whereby 3,5-dichlorophenyldiazonium tetrafluoroborate (DPD) binds directly to total bilirubin in acidic medium, forming azobilirubin, whose rate of absorbance at 550/700 nm is proportional to the concentration of total bilirubin in the sample. The analyzer photometer reads the absorbance at time intervals dictated by the method application stored in the analyzer memory, and the change in absorbance is calculated automatically. The sample volume used by the assay is 20 μL.
## Medicon Hellas Urea Nitrogen:
Urea Nitrogen is determined according to the following reactions, using 7 μL of sample for serum and urine samples:
$$
\begin{array}{l}
\text{Urea} + \mathrm{H_2O} \xrightarrow{\text{Urease}} 2 \mathrm{NH_3} + \mathrm{CO_2} \\
2 \mathrm{NH_4^+} + 2\text{-}\alpha\text{-Ketoglutarate} + 2 \mathrm{NADH} \xrightarrow{\text{GLDH}} 2\text{-L-Glutamate} + 2 \mathrm{NAD^+} + 2 \mathrm{H_2O} \\
\end{array}
$$
The rate of absorbance change at 340/380 nm is proportional to the urea nitrogen concentration in the sample.
For all assays the analyzer photometer reads the absorbances at time intervals dictated by the method application stored in the analyzer memory, and the change in absorbance is calculated automatically.
## V Substantial Equivalence Information:
### A Predicate Device Name(s):
Beckman Coulter (BC) AU Albumin, Calcium, Creatinine, Direct Bilirubin, Glucose, Total Bilirubin and Urea Nitrogen Reagents
Abbott Diagnostics (AD) Direct Bilirubin Reagent
K200898 - Page 5 of 20
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B Predicate 510(k) Number(s):
k924368, k061575, k934361, k022180, k944406, k924964 and k944250
C Comparison with Predicate(s):
Device Comparison Table: Albumin
| Device & Predicate Device(s): | k200898 | k924368 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Albumin | BC AU Albumin Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of albumin in serum samples | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 1.5-6.0 g/dL | 1.5-6.0 mg/dL |
Device Comparison Table: Calcium
| Device & Predicate Device(s): | k200898 | k061575 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Calcium | BC AU Calcium Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of calcium in serum or urine samples | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
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K200898 - Page 7 of 20
| General Device Characteristic Differences | | |
| --- | --- | --- |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 4.0-18.0 mg/dL (serum)
1.5-40.0 mg/dL (urine) | 4.0-18.0 mg/dL
0.1-40.0 mg/dL |
## Device Comparison Table: Creatinine
| Device & Predicate Device(s): | k200898 | k934361 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Creatinine | BC AU Creatinine Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of creatinine in serum or urine samples | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 0.2-25.0 mg/dL (serum)
1.1-300.0 mg/dL (urine) | 0.2-25.0 mg/dL (serum)
1.0-300.0 mg/dL (urine) |
## Device Comparison Table: Direct Bilirubin
| Device & Predicate Device(s): | k200898 | k022180 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Direct Bilirubin | AD Direct Bilirubin Assay |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determination of direct | Same |
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Device Comparison Table: Glucose
| Device & Predicate Device(s): | k200898 | k022180 |
| --- | --- | --- |
| | bilirubin in human serum samples. | |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Architect c8000 System |
| Wavelengths | 12 (340-750 nm) | 16 (340-804 nm) |
| Measuring Range | 0.2-15.0 mg/dL | 0.05-16.9 mg/dL |
| Device & Predicate Device(s): | k200898 | k944406 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Glucose | BC AU Glucose Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of glucose in serum or urine samples | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 10-700 mg/dL (serum)
10-700 mg/dL (urine) | 10-800 mg/dL (serum)
10-700 mg/dL (urine) |
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Device Comparison Table: Total Bilirubin
| Device & Predicate Device(s): | k200898 | k924964 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Total Bilirubin | BC AU Total Bilirubin Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of total bilirubin in serum | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 0.1-30.0 mg/dL | 0.0-30.0 mg/dL |
Device Comparison Table: Urea Nitrogen
| Device & Predicate Device(s): | k200898 | k944250 |
| --- | --- | --- |
| Device Trade Name | Medicon Hellas Urea Nitrogen | BC AU Urea Nitrogen Reagent |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Quantitative determinations of urea nitrogen in serum or urine samples | Same |
| Mode of Detection | Photometric | Same |
| Analytical Measure | Endpoint and kinetic with sample blanking | Same |
| General Device Characteristic Differences | | |
| Instrument Platform | Diatron Pictus 500 | Beckman Coulter AU2700 Analyzer (k002982) |
| Wavelengths | 12 (340-750 nm) | 13 (340-800 nm) |
| Measuring Range | 3-100 mg/dL (serum) | 2-130 mg/dL (serum) |
K200898 - Page 9 of 20
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24-1300 mg/dL (urine) 20-1300 mg/dL (urine)
VI Standards/Guidance Documents Referenced:
CLSI EP05-A3 - Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition.
CLSI EP06-A – Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
CLSI EP07-A3 – Interference Testing in Clinical Chemistry; Approved Guideline – Third Edition
CLSI EP09c – Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Third Edition.
CLSI EP17-A2 – Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition
CLSI EP37 - Supplemental Tables for Interference Testing in Clinical Chemistry - First Edition.
VII Performance Characteristics (if/when applicable):
1. Analytical Performance:
a) Precision/Reproducibility:
Precision studies were conducted according to the CLSI EP05-A3 guideline.
Within-run precision:
Control samples (low, medium and high levels) were tested using 20 replicates per level. Testing was performed on one Pictus 500 analyzer using three lots of reagents except for Calcium and Urea Nitrogen, for which two lots of reagents were used.
Total precision:
Control samples (low, medium and high levels) were tested in duplicate, twice a day, for 20 days, for a total of 80 results per level. Testing was performed on one Pictus 500 analyzer using three lots of reagents except for Calcium and Urea Nitrogen, for which two lots of reagents were used.
The within-run and total precision results for a representative reagent lot for each analyte are presented in the tables below.
K200898 - Page 10 of 20
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| Albumin | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | g/dL | 3.1 | 0.07 | 2.21 | 3.1 | 0.16 | 5.25 | 3.1 | 0.18 | 5.70 |
| | 2 | g/dL | 4.0 | 0.06 | 1.45 | 4.0 | 0.15 | 3.80 | 4.0 | 0.19 | 4.80 |
| | 3 | g/dL | 5.2 | 0.07 | 1.37 | 5.2 | 0.12 | 2.36 | 5.3 | 0.24 | 4.61 |
| Calcium | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 5.9 | 0.07 | 1.16 | 5.9 | 0.20 | 3.37 | 5.9 | 0.32 | 5.44 |
| | 2 | mg/dL | 8.6 | 0.09 | 1.06 | 8.6 | 0.13 | 1.51 | 8.6 | 0.35 | 4.07 |
| | 3 | mg/dL | 12.7 | 0.10 | 0.82 | 12.7 | 0.25 | 1.95 | 12.7 | 0.44 | 3.49 |
| Urine control | 1 | mg/dL | 6.2 | 0.16 | 2.59 | 6.2 | 0.09 | 1.48 | 6.2 | 0.23 | 3.73 |
| | 2 | mg/dL | 12.9 | 0.25 | 1.90 | 12.9 | 0.49 | 3.82 | 12.9 | 0.67 | 5.21 |
| | 3 | mg/dL | 30.6 | 0.40 | 1.31 | 30.6 | 0.90 | 2.95 | 30.6 | 1.07 | 3.51 |
| Creatinine | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 1.3 | 0.03 | 2.41 | 1.3 | 0.05 | 3.63 | 1.3 | 0.08 | 6.40 |
| | 2 | mg/dL | 4.9 | 0.05 | 1.08 | 4.9 | 0.22 | 4.58 | 4.9 | 0.23 | 4.71 |
| | 3 | mg/dL | 9.6 | 0.10 | 1.04 | 9.6 | 0.22 | 2.30 | 9.6 | 0.28 | 2.92 |
| Urine control | 1 | mg/dL | 63.4 | 1.31 | 2.07 | 63.4 | 1.68 | 2.66 | 63.4 | 2.15 | 3.39 |
| | 2 | Mg/dL | 100.6 | 1.39 | 1.38 | 100.6 | 1.84 | 1.83 | 100.6 | 2.31 | 2.29 |
| | 3 | mg/dL | 308.6 | 3.81 | 1.23 | 308.6 | 6.16 | 2.00 | 308.6 | 7.25 | 2.35 |
| Direct Bilirubin | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 0.7 | 0.02 | 3.11 | 0.7 | 0.02 | 2.31 | 0.7 | 0.03 | 4.98 |
| | 2 | mg/dL | 1.8 | 0.04 | 2.46 | 1.8 | 0.06 | 3.14 | 1.8 | 0.08 | 4.70 |
| | 3 | mg/dL | 7.5 | 0.19 | 2.48 | 7.5 | 0.17 | 2.29 | 7.5 | 0.34 | 4.52 |
| Glucose | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 66 | 1.1 | 1.72 | 66 | 0.9 | 1.35 | 66 | 1.9 | 2.88 |
| | 2 | mg/dL | 101 | 1.0 | 0.99 | 101 | 1.5 | 1.48 | 101 | 1.8 | 1.78 |
| | 3 | mg/dL | 303 | 2.9 | 0.96 | 303 | 6.3 | 2.08 | 303 | 9.5 | 3.13 |
| Urine control | 1 | mg/dL | 14 | 0.5 | 3.63 | 14 | 0.2 | 1.12 | 14 | 1.0 | 6.86 |
| | 2 | mg/dL | 134 | 2.2 | 1.67 | 134 | 1.2 | 0.93 | 134 | 3.2 | 2.43 |
| | 3 | mg/dL | 532 | 7.9 | 1.49 | 532 | 7.6 | 1.43 | 532 | 17.9 | 3.36 |
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| Total Bilirubin | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 1.4 | 0.01 | 0.92 | 1.4 | 0.02 | 1.69 | 1.4 | 0.04 | 2.97 |
| | 2 | mg/dL | 5.5 | 0.02 | 0.38 | 5.5 | 0.08 | 1.38 | 5.5 | 0.20 | 3.56 |
| | 3 | mg/dL | 9.6 | 0.05 | 0.57 | 9.6 | 0.17 | 1.79 | 9.6 | 0.27 | 2.86 |
| Urea Nitrogen | | | Repeatability (N=20) | | | Between Run (N=2x2, 20 days) | | | Within Lab/Total (N=2x2, 20 days) | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Level | U/M | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Serum control | 1 | mg/dL | 10 | 0.2 | 1.94 | 10 | 0.2 | 2.24 | 10 | 0.3 | 2.97 |
| | 2 | mg/dL | 19 | 0.4 | 2.14 | 19 | 0.5 | 2.56 | 19 | 0.6 | 3.34 |
| | 3 | mg/dL | 51 | 0.5 | 1.07 | 51 | 1.6 | 3.16 | 51 | 1.7 | 3.34 |
| Urine control | 1 | mg/dL | 371 | 6.7 | 1.81 | 371 | 8.7 | 2.35 | 371 | 11.5 | 3.10 |
| | 2 | mg/dL | 700 | 11.8 | 1.69 | 700 | 20.4 | 2.92 | 700 | 23.6 | 3.37 |
b) Linearity:
Linearity studies were conducted according to the CLSI EP06-A guideline.
For each analyte and sample type series of nine levels were prepared by serial dilution of a known high level sample to produce samples with concentrations spanning the corresponding claimed measuring intervals. Three reagent lots were evaluated. For each reagent lot, each level was tested in quadruplicate on the Pictus P500 Analyzer. Results from each level were averaged and compared against the expected values using linear regression analysis. The results of the linearity studies support the claimed measuring ranges. The regression analysis results for a representative reagent lot for each analyte are summarized below.
| Analyte | Sample Matrix | Claimed Measurement Range | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- |
| Albumin | Serum | 1.5 – 6.0 g/dL | 0.9641 | 0.16 | 0.9992 |
| Calcium | Serum | 4.0 – 18.0 mg/dL | 0.9903 | 0.14 | 0.9999 |
| | Urine | 2.0 – 40.0 mg/dL | 1.0232 | -0.42 | 0.9993 |
| Creatinine | Serum | 0.3 – 25.0 mg/dL | 0.9856 | 0.09 | 0.9997 |
| | Urine | 1.2 – 300.0 mg/dL | 0.9822 | 2.97 | 0.9996 |
| Direct Bilirubin | Serum | 0.2 - 15.0 mg/dL | 1.0048 | 0.07 | 0.9992 |
| Glucose Hexokinase | Serum | 10 - 700 mg/dL | 1.0039 | 3.3 | 0.9999 |
| | Urine | 10 - 660 mg/dL | 0.9808 | 4.3 | 0.9996 |
| Total Bilirubin | Serum | 0.1 – 30.0 mg/dL | 0.9867 | 0.20 | 0.9999 |
| Urea Nitrogen | Serum | 3 - 100 mg/dL | 0.9942 | 1.27 | 0.9996 |
| | Urine | 24 - 1300 mg/dL | 0.9970 | 6.55 | 0.9992 |
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c) Analytical Specificity/Interference:
Interference studies were conducted according to the CLSI EP07-A guideline and measured the effect of endogenous and exogenous substances on neat samples assayed using each of the Medicon reagents on the Pictus 500 Clinical Analyzer.
Serum and urine sample pools at low and high levels of each analyte were prepared, then spiked with increasing concentrations of the interference compounds. The spiked and control samples were tested in duplicate, and the results were averaged. In each case, the spiked sample result mean was compared to the control (zero interferent) mean result, and bias values were calculated. Non-interference levels were defined as the concentration at which the spiked sample value was ≤ ±10% of the control sample value for both serum and urine samples. The results of the interference studies for each candidate reagent are summarized below:
Albumin:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Unconjugated Bilirubin | 20 mg/dL |
| | Conjugated Bilirubin | 20 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | Triglycerides | 3000 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Aminosalicylic Acid | 45.5 mg/dL |
| | Ibuprofen | 21.9 mg/dL |
Calcium:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Unconjugated Bilirubin | 20 mg/dL |
| | Conjugated Bilirubin | 20 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | Triglycerides | 3000 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Ibuprofen | 21.9 mg/dL |
| Urine | Conjugated Bilirubin | 50 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | L-ascorbic acid | 500 mg/dL |
| | Glucose | 10 g/dL |
| | Magnesium | 4 mmol/L |
| | Albumin | 500 mg/dL |
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| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| | Boric Acid | 500 mg/dL |
| | Ibuprofen | 21.9 mg/dL |
| | IgG | 500 mg/dL |
| | pH | 6.0 |
| | Specific Gravity | 1.01-1.03 |
## Creatinine:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Bilirubin | 10 mg/dL |
| | Hemoglobin | 220 mg/dL |
| | Triglycerides | 1200 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Cefazolin | 40 mg/dL |
| | Cefoxitin | 6.0 mg/dL |
| | Cephalothin | 12 mg/dL |
| | Chloramphenicol | 7.8 mg/dL |
| | Dopamine | 0.062 mg/dL |
| | Etamsylate | 6.0 mg/dL |
| | Flucytosine | 20.4 mg/dL |
| | Furosemide | 1.59 mg/dL |
| | Ibuprofen | 23.9 mg/dL |
| | Streptomycin | 25.8 mg/dL |
| Urine | Bilirubin | 40 mg/dL |
| | Hemoglobin | 5.0 g/L |
| | Glucose | 3000 mg/dL |
| | L-ascorbic acid | 50 mg/dL |
| | Boric Acid | 500 mg/dL |
| | pH | 2-12 |
| | Specific Gravity | 1.01-1.03 |
## Direct Bilirubin:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Hemoglobin | 40 mg/dL |
| | Triglycerides | 3000 mg/dL |
| | L-ascorbic acid | 2.7 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic | 3.0 mg/dL |
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Glucose:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Acetaminophen | 15.6 mg/L |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Albumin | 7.5 g/L |
| | Bilirubin | 20 mg/dL |
| | Conjugated Bilirubin | 20 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | Ibuprofen | 21.9 mg/dL |
| | IgG | 7500 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Triglycerides | 3000 mg/dL |
| | Uric Acid | 20 mg/dL |
| Urine | Albumin | 500 mg/dL |
| | Calcium | 50 mg/dL |
| | Conjugated Bilirubin | 50 mg/dL |
| | Creatinine | 300 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | IgG | 500 mg/dL |
| | L-ascorbic acid | 500 mg/dL |
| | Urea | 6000 mg/dL |
| | Uric Acid | 250 mg/dL |
| | pH | 2-12 |
| | Specific Gravity | 1.01-1.03 |
Total Bilirubin:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Bilirubin | N/A |
| | Hemoglobin | 75 mg/dL |
| | Triglycerides | 1800 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Ibuprofen | 21.9 mg/dL |
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Urea Nitrogen:
| Sample Matrix | Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- | --- |
| Serum | Bilirubin | 20 mg/dL |
| | Conjugated Bilirubin | 20 mg/dL |
| | Hemoglobin | 250 mg/dL |
| | Triglycerides | 3000 mg/dL |
| | L-ascorbic acid | 3.0 mg/dL |
| | Acetaminophen | 15.6 mg/dL |
| | Acetylsalicylic Acid | 3.0 mg/dL |
| | Aminosalicylic Acid | 45.5 mg/dL |
| | Cefoxitin | 220 mg/dL |
| | Chloramphenicol | 7.8 mg/dL |
| | Ibuprofen | 23.9 mg/dL |
| | Methyldopa | 2.25 mg/dL |
| | Streptomycin | 25.8 mg/dL |
| Urine | Conjugated Bilirubin | 40 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | L-Ascorbic Acid | 50 mg/dL |
| | Albumin | 500 mg/dL |
| | Furosemide | 1.59 mg/dL |
| | Glucose | 5000 mg/dL |
| | pH | 2-12 |
| | Specific Gravity | 1.01-1.03 |
For creatinine, glucose, direct bilirubin, total bilirubin and urea nitrogen, the sponsor included the following limitations in their labeling:
“Do not use hemolyzed, contaminated or turbid sample specimens.”
d) Assay Reportable Range:
See Section VII.1.b – Linearity above.
e) Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The Medicon reagents are traceable to the following reference materials:
| Parameter | Reference Material |
| --- | --- |
| Albumin | IRMM reference material ERM-DA470 |
| Calcium | NIST reference material SRM 956b and SRM909b and by the Atomic Absorption Reference Method |
| Creatinine | NIST reference material 909b level 2/SRM967 level 2 and by the reference method ID-GC/MS |
| Direct Bilirubin | NIST reference material SRM 916a |
| Glucose (Hexokinase) | NIST reference material SRM917b and SRM965a |
| Total Bilirubin | NIST reference material SRM 916a |
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| Parameter | Reference Material |
| --- | --- |
| Urea | NIST reference material SRM 909b |
f) 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.
Limit of blank (LoB) and limit of detection (LoD) studies were performed by testing 5 blank samples and 5 low level samples 4 times a day for a total of 60 measurements in 3 days, using 2 or 3 reagent lots. Data was analyzed using non-parametrical statistical analysis. The LoD was calculated from LoB using the following equation: $\mathrm{LoB} + 1.654\mathrm{SD}$ .
To determine limit of quantitation (LoQ), 10 low level samples were measured 5 times each day for a total of 150 measurements in 3 days. LoQ was defined using an imprecision acceptance criterion of $\leq 20\%$ CV.
The results are summarized in the table below:
| Analyte | Sample Matrix | LoB | LoD | LoQ |
| --- | --- | --- | --- | --- |
| Albumin | Serum | 0.3 g/dL | 0.4 g/dL | 0.5 g/dL |
| Calcium | Serum | 0.2 mg/dL | 0.5 mg/dL | 0.5 mg/dL |
| | Urine | 0.8 mg/dL | 1.3 mg/dL | 1.5 mg/dL |
| Creatinine | Serum | 0.10 mg/dL | 0.2 mg/dL | 0.2 mg/dL |
| | Urine | 0.6 mg/dL | 1.0 mg/dL | 1.1 mg/dL |
| Glucose | Serum | 1.0 mg/dL | 1.7 mg/dL | 4.0 mg/dL |
| | Urine | 1.0 mg/dL | 2.4 mg/dL | 6.0 mg/dL |
| Direct Bilirubin | Serum | 0.07 mg/dL | 0.11 mg/dL | 0.17 mg/dL |
| Total Bilirubin | Serum | 0.00 mg/dL | 0.01 mg/dL | 0.09 mg/dL |
| Urea Nitrogen | Serum | 1.0 mg/dL | 1.9 mg/dL | 3.1 mg/dL |
| | Urine | 16.0 mg/dL | 20.9 mg/dL | 23.7 mg/dL |
g) Assay Cut-Off:
Not applicable.
2. Comparison Studies:
a) Method Comparison with Predicate Device:
Performance of the Medicon Albumin, Calcium, Creatinine, Glucose, Total Bilirubin and Urea Nitrogen reagents for serum and (where applicable) urine assayed on the Pictus 500 analyzer was compared with the predicate devices, Beckman Coulter reagents assayed on the AU2700 analyzer. Performance of the Medicon Direct Bilirubin reagent assayed on the Pictus 500 analyzer was compared to predicate device, Abbott Diagnostics (AD) Direct Bilirubin reagent assayed on the AD Architect c8000 analyzer.
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Between 77-126 human serum and urine samples were tested in singlicate on the candidate and predicate systems using at least three lots of Medicon reagents. Less than 10% of samples were spiked or diluted to cover the analytical measurement ranges. Results were analyzed using Deming regression statistics for Albumin, Calcium, Creatinine, Glucose, Total Bilirubin and Urea Nitrogen, and the weighted Deming approach was used for Direct Bilirubin.
The summary of the results for a representative lot are provided in the table below:
| Analyte | Sample Matrix | N | Sample concentration range tested | Slope | Intercept | R² |
| --- | --- | --- | --- | --- | --- | --- |
| Albumin | Serum | 112 | 1.6-5.9 g/dL | 1.0180 | 0.05 | 0.9862 |
| Calcium | Serum | 94 | 4.0-18.0 mg/dL | 1.0099 | -0.3 | 0.9949 |
| | Urine | 81 | 2.3-39.9 mg/dL | 0.9888 | -0.8 | 0.9965 |
| Creatinine | Serum | 126 | 0.3-25.0 mg/dL | 1.0207 | -0.10 | 0.9989 |
| | Urine | 98 | 1.9-286.9 mg/dL | 0.9904 | -0.81 | 0.9992 |
| Direct Bilirubin | Serum | 77 | 0.2-14.7 mg/dL | 0.9656 | -0.01 | 0.9978 |
| Glucose | Serum | 99 | 13-696 mg/dL | 0.9715 | 2.7 | 0.9992 |
| | Urine | 100 | 10-656 mg/dL | 1.0222 | -0.9 | 0.9989 |
| Total Bilirubin | Serum | 95 | 0.3-29.1 mg/dL | 1.0125 | -0.06 | 0.9996 |
| Urea Nitrogen | Serum | 116 | 3-93 mg/dL | 1.0001 | -0.2 | 0.9983 |
| | Urine | 81 | 31-1244 mg/dL | 0.9844 | 21.9 | 0.9972 |
b) Matrix Comparison:
Not applicable.
3. Clinical Studies:
a) Clinical Sensitivity:
Not applicable.
b) Clinical Specificity:
Not applicable.
c) Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.
4. Clinical Cut-Off:
Not applicable.
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# 5. Expected Values/Reference Range:
The following reference ranges, cited from the scientific literature, were included in the labeling. The labeling also states “Reference intervals may vary with age, sex, sample type, diet and geographical location. Each laboratory should determine its own reference intervals as dictated by good laboratory practices.”
| Analyte | Sample Matrix | Reference Range |
| --- | --- | --- |
| Albumin^{1} | Serum | 3.5 – 5.0 g/dL |
| Calcium^{1,2} | Serum | 8.4-10.2 mg/dL |
| | Urine | 12.39 ± 8.19 mg/dL |
| Creatinine^{1,3} | Serum | Female: 0.6-1.2 mg/dL
Male: 0.7-1.3 mg/dL |
| | Urine | 22.6-300 mg/dL |
| Glucose^{1,4,5} | Serum | 70 – 105 mg/dL |
| | Urine | 1 – 15 mg/dL |
| Direct Bilirubin^{6} | Serum | <0.3 mg/dL |
| Total Bilirubin^{1} | Serum | 0.2 – 1.0 mg/dL |
| Urea Nitrogen^{1} | Serum | 7-21 mg/dL |
| | Urine | 800-1333 mg/dL |
1) Tietz, NW, ed. Clinical Guide to Laboratory Tests. 3rd. ed. Philadelphia: W.B. Saunders Company Ltd., 1995.
2) Topal, C., Algun, E, Sayarlioglu, H, Erkoc, R, Soyoral, Y, Dogan, E, Sekeroglu, R and Cekici, S. Diurnal Rhythm of Urinary Calcium Excretion in Adults. Ren. Fail 2008, 30(5): 499-501.
3) Aydogu, M, Oral, S and Akgur, SA. The impact of creatinine reference value. Normalization of urinary drug concentrations. J. Forensic Sci. 2021; 00, 1-7.
4) Thomas L. Blood glucose. In Thomas L, ed. Clinical laboratory diagnostics. Use and assessment of clinical laboratory results. Frankfurt/Main: TH-Books Verlagsgesellschaft 1998:131-137.
5) Sacks DB, Bruns DE, Goldstein DE, MacLaren NK et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002; 48:436-72.
6) Limbach, HJ, Schmidt-Gayk, H, Watch, S, Kiral, H, Lorenz, S, Fahr, A, Turnwald-Maschler, A, Holfelder, M and Porch, G in Laboratory Test Index, 16th edition 2001.
# VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
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IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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