CHOLESTEROL; HDL-cholesterol ; LDL-cholesterol; TRIGLYCERIDES
Device Facts
| Record ID | K232404 |
|---|---|
| Device Name | CHOLESTEROL; HDL-cholesterol ; LDL-cholesterol; TRIGLYCERIDES |
| Applicant | Medicon Hellas S.A |
| Product Code | CHH · Clinical Chemistry |
| Decision Date | Aug 9, 2024 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1175 |
| Device Class | Class 1 |
Indications for Use
CHOLESTEROL: Reagent kit intended for the quantitative determination of cholesterol in human serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, of lipid and lipoprotein metabolism disorders. HDL-Cholesterol: Reagent kit intended for the quantitative determination of high-density lipoprotein in human serum. Measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. LDL-Cholesterol: Reagent kit intended for quantitative determination of low-density lipoprotein in human serum. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. TRIGLYCERIDES: Reagent kit intended for the quantitative determination of triglycerides (neutral fat) in human serum. Measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
Device Story
Reagent kits for quantitative determination of cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides in human serum; used on Diatron Pictus 500 analyzers in clinical laboratory settings. Principle of operation: enzymatic photometric assays (CHOD-PAP for cholesterol; selective detergent methods for HDL/LDL; GPO-POD for triglycerides). Reagents react with serum samples to produce colored complexes; light absorbance at 550 nm or 590 nm is measured; absorbance is directly proportional to analyte concentration. Healthcare providers use results to diagnose and monitor lipid disorders, atherosclerosis, diabetes, and metabolic diseases. Benefits include standardized, automated lipid profiling to guide clinical decision-making and patient treatment.
Clinical Evidence
Bench testing only. Performance evaluated per CLSI guidelines (EP05-A3, EP06, EP07, EP09c, EP17-A2). Precision (repeatability/within-lab) showed CVs generally <4%. Linearity confirmed (R² > 0.99). Interference testing showed no significant impact (≤±10%) from common endogenous/exogenous substances. Method comparison against predicate devices (N=93-163) showed high correlation (R² ≥ 0.997) and acceptable bias at medical decision points.
Technological Characteristics
Enzymatic photometric test systems. Reagents utilize cholesterol esterase, cholesterol oxidase, peroxidase, glycerokinase, and lipase. Detection via chromogenic oxidative coupling (550 nm or 590 nm). Form factor: liquid reagent kits for automated clinical chemistry analyzers (Diatron Pictus 500). Connectivity: standalone analyzer integration. Standards: CLSI EP05-A3, EP06-Ed02, EP07, EP09c, EP15-A3, EP17-A2, EP37.
Indications for Use
Indicated for quantitative determination of cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides in human serum to aid in the diagnosis and treatment of lipid and lipoprotein metabolism disorders, atherosclerosis, diabetes mellitus, and related liver, renal, or endocrine conditions.
Regulatory Classification
Identification
A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.
Predicate Devices
- Olympus Cholesterol Reagent (K925603)
- Direct HDL (K981224)
- Direct LDL (K981303)
- Olympus Triglyceride Reagent (K063804)
Related Devices
- K060854 — ABX PENTRA 400: LIPOPROTEINS · Horiba Abx · Aug 24, 2006
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
K232404
B Applicant
Medicon Hellas, S.A
C Proprietary and Established Names
CHOLESTEROL; HDL-Cholesterol; LDL-Cholesterol; TRIGLYCERIDES
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CHH | Class I, meets the limitations of exemptions 21 CFR 862.9(c)(4) | 21 CFR 862.1175 - Cholesterol (Total) Test System | CH - Clinical Chemistry |
| LBS | Class I, meets the limitations of exemptions 21 CFR 862.9(c)(4) | 21 CFR 862.1475 - Lipoprotein test system | CH - Clinical Chemistry |
| MRR | Class I, meets the limitations of exemptions 21 CFR 862.9(c)(4) | 21 CFR 862.1475 - Lipoprotein test system | CH - Clinical Chemistry |
| CDT | Class I, meets the limitations of exemptions 21 CFR 862.9(c)(4) | 21 CFR 862.1705 - Triglyceride 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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K232404 - Page 2 of 15
## II Submission/Device Overview:
### A Purpose for Submission:
New devices
### B Measurand:
- Cholesterol
- HDL-Cholesterol
- LDL-Cholesterol
- Triglycerides
### C Type of Test:
Quantitative, colorimetric assay
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
**CHOLESTEROL**: Reagent kit intended for the quantitative determination of cholesterol in human serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, of lipid and lipoprotein metabolism disorders.
**HDL-Cholesterol**: Reagent kit intended for the quantitative determination of high-density lipoprotein in human serum. Measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
**LDL-Cholesterol**: Reagent kit intended for quantitative determination of low-density lipoprotein in human serum. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
**TRIGLYCERIDES**: Reagent kit intended for the quantitative determination of triglycerides (neutral fat) in human serum. Measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism, or various endocrine disorders.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
For in vitro diagnostic use only.
### D Special Instrument Requirements:
For use on the Diatron Pictus 500 Clinical Chemistry Analyzer
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K232404 - Page 3 of 15
# IV Device/System Characteristics:
## A Device Description:
The CHOLESTEROL test system is a one reagent system supplied in liquid ready-to-use form containing 4-Chlorophenol (4.7 mmol/L), 4-Aminoantipyrine (1 mmol/L), Cholesterol esterase (≥ 500 U/L), Cholesterol oxidase (CHOD, ≥ 500 U/L) and Peroxidase (POD, ≥ 500 U/L). Materials required but not provided within the assay kit: MEDICON Clinical Chemistry Control Level 1 and 2, and MEDI-CAL calibrator.
The HDL-Cholesterol test system is a one reagent system supplied in liquid ready-to-use form containing Cholesterol esterase (< 1500 U/L), Cholesterol oxidase (< 1000 U/L), Peroxidase (POD, < 1300 U/L), Ascorbate oxidase (< 3000 U/L), Accelerator (< 1 mM), N,N-bis(4-sulfobytul)-m-toluidine disodium (DSBmT, < 1 mM), and 4-aminoantipyrine (< 1 mM). Materials required but not provided within the assay kit: MEDICON Clinical Chemistry Control Level 1 and 2, and MEDICON HDL calibrator.
The LDL-Cholesterol test system is a two-reagent system supplied in liquid ready-to-use form. Reagent 1 (R1) contains Detergent 1 (< 1%), 4-Aminoantipyrine (< 0.1%), Cholesterol oxidase (<1500 U/L), Cholesterol esterase (< 2500 U/L), Peroxidase (POD, < 1300 U/L). Reagent 2 (R2) contains Ascorbic oxidase (< 3000 U/L), Detergent 2 (< 1%), and N,N-bis(4-sulfobytul)-m-toluidine disodium (DSBmT, <1 mM). Materials required but not provided within the assay kit: MEDICON Clinical Chemistry Control Level 1 and 2, and MEDICON LDL calibrator.
The TRIGLYCERIDES test system is a two-reagent system supplied in liquid ready-to-use form. Reagent 1 (R1) contains Pipes buffer (240 mM), Peroxidase (POD, > 5000 U/L), Glycerokinase (> 1000 U/L), Lipoprotein lipase (> 15000 U/L), Adenosine triphosphate (ATP, 4.5 mM) and N-Ethyl-N-(2-hydroxy-3-sulfopropyl)-3-methylaniline sodium salt (TOOS, 4.8 mM). Reagent 2 (R2) contains 4-Aminoantipyrine (< 15 mmol/L) and glycerol-3-phosphate-oxidase (GPO, > 55000 U/L). Materials required but not provided within the assay kit: MEDICON Clinical Chemistry Control Level 1 and 2, and MEDI-CAL calibrator.
## B Principle of Operation:
The CHOLESTEROL test system uses the cholesterol oxidase peroxidase (CHOD-PAP) enzymatic colorimetric method. The cholesteryl esterase catalyzes the hydrolysis of cholesterol esters to cholesterol and free fatty acids. Free cholesterol, including that originally present in the sample, is then oxidized by the enzyme cholesterol oxidase to cholest-4-en-3-one, by using molecular oxygen as the electron acceptor and concurrently producing hydrogen peroxide (H₂O₂). The H₂O₂ produced is then used in a subsequent chromogenic oxidative coupling reaction, catalyzed by the enzyme peroxidase, in the presence of a redox indicator system, which leads to the formation of a colored compound, absorbing light at 550 nm. The increase in absorbance is directly proportional to the cholesterol concentration in the sample.
The HDL-Cholesterol test system uses the Accelerator Selective Detergent method. The determination of HDL-Cholesterol is based on the following reactions: LDL, VLDL, and chylomicrons are neutralized by the combined action of the enzymes Cholesterol Oxidase, Peroxidase, accelerators and DSBmT. HDL remaining in the sample is disrupted by the action of
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a selective detergent and cholesterol is converted to Δ4 Cholestenone by the enzymatic action of Cholesterol Esterase and Cholesterol Oxidase, with the subsequent production of H₂O₂, which reacts with DSBmT and 4-aminoantipyrine in the presence of Peroxidase to a colored complex that absorbs light at 590 nm. The absorbance measured is proportional to the concentration of HDL-Cholesterol in the sample.
The LDL-Cholesterol test system uses the Selective Detergent method. The method is in a two-reagent format and depends on the properties of a unique detergent. The first detergent solubilizes only the non-LDL lipoprotein particles. The cholesterol released is consumed by cholesterol esterase and cholesterol oxidase in a non-color forming reaction. The second detergent solubilizes the remaining LDL particles, and a chromogenic coupler allows for color formation. The enzyme reaction with LDL-C in the presence of the coupler at 590 nm produces color that is proportional to the amount of LDL cholesterol present in the sample.
The TRIGLYCERIDES test system uses the enzymatic glycerol-3-phosphate-peroxidase (GPO-POD) method. The method enzymatically hydrolyzes by lipase to free fatty acids and glycerol. Glycerol is phosphorylated by adenosine triphosphate (ATP) with glycerol kinase (GK) to produce glycerol-3-phosphate and adenosine diphosphate (ADP). Glycerol-3-phosphate-oxidase (GPO) oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate and H₂O₂. The catalytic action of peroxidase (POD) forms quinoneimine from H₂O₂, aminoantipyrine and TOOS. The absorption change at 550 nm is proportional to the concentration of triglycerides in the sample.
V Substantial Equivalence Information:
A Predicate Device Name(s):
Cholesterol: Olympus Cholesterol Reagent - K925603
HDL-Cholesterol: Direct HDL - K981224
LDL-Cholesterol: Direct LDL - K981303
Tryglycerides: Olympus Triglyceride Reagent - K063804
B Predicate 510(k) Number(s):
See section V(A) above.
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K232404 | K925603 |
| --- | --- | --- |
| Device Trade Name | CHOLESTEROL | Olympus Cholesterol Reagent |
| General Device Characteristic Similarities | | |
| Intended Use | Reagent intended for the quantitative determination of Cholesterol | Same |
| Sample Type | Serum | Same |
| General Device Characteristic Differences | | |
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K232404 - Page 5 of 15
| Device & Predicate Device(s): | K232404 | K925603 |
| --- | --- | --- |
| Measuring Range | 20 to 700 mg/dL | 50 to 700 mg/dL |
| Device & Predicate Device(s): | K232404 | K981224 |
| --- | --- | --- |
| Device Trade Name | HDL-Cholesterol | Direct HDL |
| General Device Characteristic Similarities | | |
| Intended Use | Reagent intended for the quantitative determination of high-density lipoprotein. | Same |
| General Device Characteristic Differences | | |
| Measuring Range | 6 to 200 mg/dL | 8 to 180 mg/dL |
| Sample Type | Serum | Serum or Plasma |
| Device & Predicate Device(s): | K232404 | K981303 |
| --- | --- | --- |
| Device Trade Name | LDL-Cholesterol | Direct LDL |
| General Device Characteristic Similarities | | |
| Intended Use | Reagent intended for the quantitative determination of low-density lipoprotein. | Same |
| General Device Characteristic Differences | | |
| Measuring Range | 3 to 800 mg/dL | 1 to 600 mg/dL |
| Sample Type | Serum | Serum or Plasma |
| Device & Predicate Device(s): | K232404 | K063804 |
| --- | --- | --- |
| Device Trade Name | TRIGLYCERIDES | Olympus Triglyceride Reagent |
| General Device Characteristic Similarities | | |
| Intended Use | Reagent intended for the quantitative | Same |
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K232404 - Page 6 of 15
| Device & Predicate Device(s): | K232404 | K063804 |
| --- | --- | --- |
| | determination of triglycerides | |
| Measuring Range | 10 to 1,000 mg/dL | Same |
| General Device Characteristic Differences | | |
| Sample Type | Serum | Serum or Plasma |
## VI Standards/Guidance Documents Referenced:
Clinical and Laboratory Standards Institute (CLSI) Guideline EP05-A3: User Protocol for Evaluation of Qualitative Test Performance.
CLSI Guideline EP06 2nd Edition: Evaluation of the Linearity of Quantitative Measurement Procedures.
CLSI Guideline EP07 3rd Edition: Interference Testing in Clinical Chemistry.
CLSI Guideline EP09c 3rd Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples.
CLSI Guideline EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.
## VII Performance Characteristics (if/when applicable):
### A Analytical Performance:
1. Precision/Reproducibility:
A precision study for each candidate assay was conducted following the recommendations in the CLSI EP05-A3 guideline. Precision was assessed using multiple levels of pooled serum samples, and tested in 2 replicates per run, 2 runs per day for 20 days for a total of 80 measurements per level. One operator conducted the study using one lot of reagents using one instrument. The results are summarized below for a single lot:
a. Repeatability (Within-run precision)
| Analyte | Pool | Mean (mg/dL) | SD (mg/dL) | %CV |
| --- | --- | --- | --- | --- |
| Cholesterol | Level 1 | 92 | 1.5 | 1.6 |
| | Level 2 | 241 | 3.3 | 1.4 |
| | Level 3 | 345 | 4.9 | 1.4 |
| HDL-Cholesterol | Level 1 | 31 | 0.7 | 2.3 |
| | Level 2 | 57 | 0.7 | 1.2 |
| LDL-Cholesterol | Level 1 | 98 | 1.0 | 1.0 |
| | Level 2 | 126 | 2.2 | 1.8 |
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| Analyte | Pool | Mean (mg/dL) | SD (mg/dL) | %CV |
| --- | --- | --- | --- | --- |
| Cholesterol | Level 1 | 92 | 0 | 0 |
| | Level 2 | 241 | 4.9 | 2.0 |
| HDL-Cholesterol | Level 1 | 31 | 0.6 | 2.0 |
| | Level 2 | 57 | 0.4 | 0.8 |
| | Level 1 | 98 | 1.2 | 1.2 |
| LDL-Cholesterol | Level 2 | 126 | 2.9 | 2.3 |
| | Level 3 | 156 | 2.3 | 1.5 |
| | Level 4 | 193 | 3.1 | 1.6 |
| | Level 1 | 41 | 0.6 | 1.6 |
| Triglycerides | Level 2 | 148 | 3.1 | 2.1 |
| | Level 3 | 399 | 5.2 | 1.3 |
c. Within-laboratory precision
| Analyte | Pool | Mean (mg/dL) | SD (mg/dL) | %CV |
| --- | --- | --- | --- | --- |
| Cholesterol | Level 1 | 92 | 2.1 | 2.3 |
| | Level 2 | 241 | 6.9 | 2.9 |
| | Level 3 | 345 | 10.3 | 3.0 |
| HDL-Cholesterol | Level 1 | 31 | 1.2 | 3.8 |
| | Level 2 | 57 | 1.5 | 2.6 |
| LDL-Cholesterol | Level 1 | 98 | 3.8 | 3.9 |
| | Level 2 | 126 | 4.4 | 3.5 |
| | Level 3 | 156 | 5.6 | 3.6 |
| | Level 4 | 193 | 6.1 | 3.2 |
| Triglycerides | Level 1 | 41 | 0.9 | 2.1 |
| | Level 2 | 148 | 4.5 | 3.0 |
| | Level 3 | 399 | 7.2 | 1.8 |
2. Linearity:
A linearity study for each candidate assay was conducted following the recommendations in the CLSI EP06 2nd Edition guideline. The linearity was assessed using pooled serum samples spanning the target analyte concentration range which were prepared by serial dilution of a known high-level sample. A total of 11 to 13 samples were prepared for the linearity assessment. For each sample, four replicates were tested by one operator using one
K232404 - Page 7 of 15
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instrument. The mean values of four replicates of each pool were compared to the expected target values to determine the deviation from linearity. For all samples, the deviation from linearity was less than $7\%$ . The linear regression results are given in the table below for a single new lot:
| Analyte | Slope | Intercept | R2 |
| --- | --- | --- | --- |
| Cholesterol | 1.001 | 0.409 | 0.9997 |
| HDL-Cholesterol | 1.033 | -0.668 | 0.9984 |
| LDL-Cholesterol | 1.009 | -0.400 | 0.9996 |
| Triglycerides | 0.978 | -0.236 | 0.9994 |
# 3. Analytical Specificity/Interference:
An interference study for each candidate assay was evaluated following the recommendations in the CLSI EP07 $3^{\mathrm{rd}}$ Ed. guideline. Serum samples at two analyte concentrations near the medical decision concentrations were evaluated for each substance. The samples were divided into two aliquots: control with no added interferent and test with added interferent. Each sample was measured in two replicates. The study tested for possible interference from common endogenous substances, and exogenous substances such as medications or supplements likely to be used by the target patient population. The following tables list the concentration of each substance at which no significant interference was detected; defined as a difference of less than or equal $\pm 10\%$ between the test sample and control.
| Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Acetaminophen | 15.6 mg/dL |
| N-Acetylcysteine | 15 mg/dL |
| Acetylsalicylic Acid | 3.0 mg/dL |
| Ampicillin | 7.5 mg/dL |
| L-Ascorbic acid | 5.25 mg/dL |
| Atorvastatin | 0.075 mg/dL |
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Calcium Dobesilate | 6 mg/dL |
| Cefotaxime | 52.8 mg/dL |
| Cefoxitin | 660 mg/dL |
| Cyclosporine | 0.18 mg/dL |
| Dipyrone | 3.3 mg/dL |
| Dobutamine | 0.121 mg/dL |
| Doxycycline | 1.8 mg/dL |
| Fenofibrate | 4.5 mg/dL |
| Hemoglobin | 500 mg/dL |
| Heparin | 330 U/dL |
| Ibuprofen | 21.9 mg/dL |
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| Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Intralipid | 2000 mg/dL |
| Levodopa | 0.75 mg/dL |
| Methotrexate | 136 mg/dL |
| Methyldopa | 2.25 mg/dL |
| Metronidazole | 12.3 mg/dL |
| Phenylbutazone | 32.1 mg/dL |
| Pravastatin | 0.0207 mg/dL |
| Rifampicin | 4.8 mg/dL |
| Rosuvastatin | 0.111 mg/dL |
| Simvastatin | 0.168 mg/dL |
| Theophylline | 6 mg/dL |
| Triglycerides | 1500 mg/dL |
| HDL-Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Acetaminophen | 15.6 mg/dL |
| N-Acetylcysteine | 15 mg/dL |
| Acetylsalicylic Acid | 3 mg/dL |
| Ampicillin | 7.5 mg/dL |
| L-Ascorbic acid | 5.25 mg/dL |
| Atorvastatin | 0.075 mg/dL |
| Bilirubin (conjugated) | 40.0 mg/dL |
| Bilirubin (unconjugated) | 40.0 mg/dL |
| Calcium Dobesilate | 6 mg/dL |
| Cefotaxime | 52.8 mg/dL |
| Cefoxitin | 660 mg/dL |
| Cyclosporine | 0.18 mg/dL |
| Dipyrone | 3.3 mg/dL |
| Dobutamine | 0.121 mg/dL |
| Doxycycline | 1.8 mg/dL |
| Fenofibrate | 4.5 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Heparin | 330 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Intralipid | 2000 mg/dL |
| Levodopa | 0.75 mg/dL |
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| HDL-Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Methotrexate | 136 mg/dL |
| Methyldopa | 1.35 mg/dL |
| Metronidazole | 12.3 mg/dL |
| Phenylbutazone | 32.1 mg/dL |
| Pravastatin | 0.0207 mg/dL |
| Rifampicin | 4.8 mg/dL |
| Rosuvastatin | 0.111 mg/dL |
| Simvastatin | 0.168 mg/dL |
| Theophylline | 6.0 mg/dL |
| Triglycerides | 1500 mg/dL |
| LDL-Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Acetaminophen | 15.6 mg/dL |
| N-Acetylcysteine | 15 mg/dL |
| Acetylsalicylic Acid | 3 mg/dL |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Ampicillin | 7.5 mg/dL |
| L-Ascorbic acid | 5.25 mg/dL |
| Atorvastatin | 0.075 mg/dL |
| Bilirubin (conjugated) | 40.0 mg/dL |
| Bilirubin (unconjugated) | 40.0 mg/dL |
| Calcium Dobesilate | 6 mg/dL |
| Cefotaxime | 52.8 mg/dL |
| Cefoxitin | 660 mg/dL |
| Dipyrone | 3.3 mg/dL |
| Dobutamine | 0.121 mg/dL |
| Doxycycline | 1.8 mg/dL |
| Fenofibrate | 4.5 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Intralipid | 1500 mg/dL |
| Levodopa | 0.75 mg/dL |
| Methotrexate | 136 mg/dL |
| Methyldopa | 2.25 mg/dL |
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| LDL-Cholesterol | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Metronidazole | 12.3 mg/dL |
| Phenylbutazone | 32.1 mg/dL |
| Pravastatin | 0.0207 mg/dL |
| Rifampicin | 4.8 mg/dL |
| Rosuvastatin | 0.0111 mg/dL |
| Simvastatin | 0.168 mg/dL |
| Theophylline | 6.0 mg/dL |
| Triglycerides | 3000 mg/dL |
| Triglycerides | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Acetaminophen | 15.6 mg/dL |
| N-Acetylcysteine | 15 mg/dL |
| Acetylsalicylic Acid | 3 mg/dL |
| Ampicillin | 7.5 mg/dL |
| L-Ascorbic acid | 5.25 mg/dL |
| Atorvastatin | 0.075 mg/dL |
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Calcium Dobesilate | 6 mg/dL |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Cefotaxime | 52.8 mg/dL |
| Cefoxitin | 660 mg/dL |
| Dipyrone | 3.3 mg/dL |
| Dobutamine | 15.6 mg/dL |
| Doxycycline | 1.8 mg/dL |
| Fenofibrate | 4.5 mg/dL |
| Hemoglobin | 400 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Levodopa | 0.75 mg/dL |
| Methotrexate | 136 mg/dL |
| Methyldopa | 1.575 mg/dL |
| Metronidazole | 12.3 mg/dL |
| Phenylbutazone | 32.1 mg/dL |
| Pravastatin | 0.0207 mg/dL |
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| Triglycerides | |
| --- | --- |
| Substance tested | Highest concentration tested at which no significant interference was observed |
| Rifampicin | 4.8 mg/dL |
| Rosuvastatin | 0.0111 mg/dL |
| Simvastatin | 0.168 mg/dL |
| Theophylline | 6.0 mg/dL |
# 4. Assay Reportable Range:
The reportable ranges for each analyte are given in the table below:
| Analyte | Reportable Range (mg/dL) |
| --- | --- |
| Cholesterol | 25 to 700 |
| HDL-Cholesterol | 6 to 180 |
| LDL-Cholesterol | 3 to 800 |
| Triglycerides | 10 to 1000 |
# 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability
The candidate assays and their respective calibrators are traceable to NIST standard reference materials (SRM 1952a, SRM 1951c and SRM 909c).
On-Board Stability
The stability protocols and acceptance criteria were reviewed and determined to be adequate. All reagents demonstrated on-board stability of 28 days.
# 6. Detection Limit:
Protocols for the determination of the limit of blank (LoB), the limit of detection (LoD) and the limit of quantification (LoQ) were performed in accordance with the recommendations in the CLSI Guideline EP17-A2. The LoB and LoD studies were carried out using blanks and low-level samples (60 each) over 3 days. The LoQ study used 10 serum samples that spanned the low end of linearity that were measured 5 times per day over 3 days for a total of 150 measurements per sample. The studies were performed on one Diatron Pictus 500 Clinical Chemistry Analyzer.
The resulting LoB, LoD and LoQ for the four measurands are summarized below:
| Analyte | LoB (mg/dL) | LoD (mg/dL) | LoQ (mg/dL) |
| --- | --- | --- | --- |
| Cholesterol | 2.5 | 4.4 | 4.6 |
| HDL-Cholesterol | 1.0 | 3.0 | 5.8 |
| LDL-Cholesterol | 1.0 | 2.0 | 3.0 |
| Triglycerides | 4.0 | 5.5 | 9.7 |
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7. Assay Cut-Off:
Not applicable.
B Comparison Studies:
1. Method Comparison with Predicate Device:
To establish the accuracy of the Medicon Hellas assays, a method comparison study was conducted to evaluate the analytical agreement to a comparator method for each of the 4 analytes. Serum samples were tested in singlicate on the Diatron PICTUS 500 Analyzer and the comparators. The results of the method comparison studies are summarized as follows:
Regression Analysis
| Analyte | N | Slope | Intercept | R² | Range (mg/dL) |
| --- | --- | --- | --- | --- | --- |
| Cholesterol | 93 | 0.9769 | 5.098 | 0.999 | 44 to 666 |
| HDL-Cholesterol | 141 | 1.018 | -0.028 | 0.997 | 6 to 177 |
| LDL-Cholesterol | 107 | 0.9821 | 1.750 | 0.999 | 5 to 721 |
| Triglycerides | 163 | 0.999 | 2.041 | 0.999 | 26 to 975 |
Predicted Bias at Medical Decision Points
An estimate of the predicated bias at the medical decision points was calculated as the percent difference between the regression line and the unity line at each medical decision point.
| Analyte | Medical Decision Point | %Bias (95% CI) |
| --- | --- | --- |
| Cholesterol | 90 mg/dL | 3.4 % (1.4 to 5.1 %) |
| | 240 mg/dL | -0.2 % (-0.7 to 0.4 %) |
| | 260 mg/dL | -0.3 % (-0.9 to 0.3 %) |
| | 350 mg/dL | -0.9 % (-1.4 to -0.1 %) |
| HDL-Cholesterol | 35 mg/dL | 1.8 % (0.6 to 2.9 %) |
| | 60 mg/dL | 1.8 % (1.2 to 2.4 %) |
| LDL-Cholesterol | 100 mg/dL | -0.0 % (-0.7 to 0.8 %) |
| | 130 mg/dL | -0.4 % (-1.2 to 0.8 %) |
| | 160 mg/dL | -0.7 % (-1.5 to 0.1 %) |
| | 190 mg/dL | -0.9 % (-1.8 to 0.0 %) |
| Triglycerides | 40 mg/dL | -2.8 % (1.0 to 4.9 %) |
| | 150 mg/dL | -0.9 % (-1.3 to -0.4 %) |
| | 400 mg/dL | -1.8 % (-2.2 to -1.1 %) |
2. Matrix Comparison:
Not applicable
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{13}
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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
E Expected Values/Reference Range:
The expected values for total cholesterol, HDL cholesterol, and triglycerides were identified in the labeling as:
| Analyte | Concentration (mg/dL) | Adult Classification |
| --- | --- | --- |
| Cholesterol | < 200 | Desirable Levels |
| | 200 - 239 | Marginally High Levels |
| | > 239 | Undesirable Levels |
Source: National Cholesterol Education Program. Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 01-3670, May 2001.
| Analyte | Concentration (mg/dL) | Adult Classification |
| --- | --- | --- |
| HDL Cholesterol | ≤ 40 | High Risk |
| | ≥ 60 | Low Risk |
Source: National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106:3143-3421.
| Analyte | Concentration (mg/dL) | Adult Classification |
| --- | --- | --- |
| LDL Cholesterol | < 100 | Optimal |
| | 100 - 129 | Near or above optimal |
| | 130 - 159 | Borderline high |
{14}
| Analyte | Concentration (mg/dL) | Adult Classification |
| --- | --- | --- |
| | 160 - 189 | High |
| | ≥ 190 | Very High |
Source: National Cholesterol Education Program. Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 01-3670, May 2001.
| Analyte | Concentration (mg/dL) | Adult Classification |
| --- | --- | --- |
| Triglycerides | < 150 | Normal |
| | 150 - 199 | Borderline high |
| | 200 - 499 | High |
| | ≥ 500 | Very high |
Source: National Cholesterol Education Program. Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 01-3670, May 2001.
## 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.
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