HITACHI CLINICAL ANALYZER S TEST REAGENT CATRIDGE FOR: CHOLESTROL, HDL, LDL, AND TRIGLYCERIDE
Device Facts
| Record ID | K111753 |
|---|---|
| Device Name | HITACHI CLINICAL ANALYZER S TEST REAGENT CATRIDGE FOR: CHOLESTROL, HDL, LDL, AND TRIGLYCERIDE |
| Applicant | Hitachi Chemical Diagnostics, Inc. |
| Product Code | CHH · Clinical Chemistry |
| Decision Date | Dec 14, 2011 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1175 |
| Device Class | Class 1 |
Indications for Use
The Hitachi Clinical Analyzer with S TEST reagent cartridges for total cholesterol (CHO), HDL cholesterol (HDL), LDL cholesterol (LDL), and triglycerides (TG) is intended for the quantitative measurements of CHO, HDL, LDL, and TG in serum or heparinized plasma. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, and lipid and lipoprotein metabolism disorders. HDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. LDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. Triglyceride 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
Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system for clinical/physician office labs. It uses single-use plastic reagent cartridges containing two reservoirs (R1, R2) and a reaction cell. User places cartridges on a carousel; system uses a single probe to mix samples and reagents. Principle of operation is quantitative photometric analysis; multi-wavelength photometer measures absorbance of reddish-purple pigment produced by enzymatic reactions (COD-POD for cholesterol; direct enzymatic for HDL/LDL; lipase/glycerol kinase for triglycerides). Cartridges include dot code labels with chemistry parameters and calibration factors. Output is quantitative concentration of analytes displayed on an operations screen. Healthcare providers use these results to diagnose and manage lipid disorders, atherosclerosis, and metabolic diseases. System includes printer and data storage for quality control.
Clinical Evidence
No clinical trials were performed. Evidence consists of analytical bench testing, including precision/reproducibility studies (n=30 replicates per sample per site across three POL sites), linearity/reportable range validation, analytical specificity (interference testing per CLSI EP7-A2), and method comparison studies against reference methods (n=50-113 samples per analyte). Results showed high correlation (r=0.97-0.99) and precision (CVs 0.4%-4.5%).
Technological Characteristics
Bench-top wet chemistry analyzer. Reagent cartridges: plastic, 13.5mm x 28mm x 20.2mm, with dot code labels. Sensing: multi-wavelength photometer (bichromatic monitoring). Energy: electrical. Connectivity: includes operations screen and printer. Software: embedded, utilizes chemistry parameters and calibration factors from cartridge dot codes.
Indications for Use
Indicated for quantitative measurement of total cholesterol, HDL, LDL, and triglycerides in serum or heparinized plasma for patients requiring diagnosis and treatment of lipid/lipoprotein metabolism disorders, atherosclerosis, diabetes mellitus, nephrosis, liver obstruction, or endocrine disorders. For use in clinical or physician office laboratories.
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
- Roche/Hitachi cobas 6000 (k060373)
- Roche/Hitachi total cholesterol test reagent (k031824)
- Roche/Hitachi HDL test reagent (k033610)
- Roche/Hitachi LDL test reagent (k012287)
- Roche/Hitachi TG test reagent (k972250)
Related Devices
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- K042443 — SPOTCHEM HDL, TOTAL CHOLESTEROL AND TRIGLYCERIDE REAGENT TESTS AND PANEL · Arkray, Inc. · Nov 24, 2004
- K080125 — APOLOWAKO T-CHO, HDL-C, TG AND ANALYZER, MODELS 993-23501, 999-23601, 995-23701 AND 993-25201 · Wako Chemicals USA, Inc. · Jul 18, 2008
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number:
k111753
B. Purpose for Submission:
New submission for clearance of Hitachi Cholesterol, HDL, LDL and triglycerides for use on the Hitachi Clinical Analyzer
C. Measurand:
Cholesterol (CHO)
HDL cholesterol (HDL)
LDL cholesterol (LDL)
Triglycerides (TG)
D. Type of Test:
Quantitative Photometric
E. Applicant:
Hitachi Chemical Diagnostics, Inc.
F. Proprietary and Established Names:
Hitachi Clinical Analyzer S TEST Reagent Cartridges- Cholesterol (CHO), HDL cholesterol (HDL), LDL cholesterol (LDL), and triglycerides (TG)
G. Regulatory Information:
1. Regulation section:
21CFR 862.1705: Triglyceride test system.
21CFR 862.1175: Cholesterol (total) test system.
21CFR 862.1475: Lipoprotein test system.
21CFR 862.2160: Discrete photometric chemistry analyzer for clinical use.
2. Classification:
Class I, meets limitations per 21 CFR 862.9(c)(4); Class I
3. Product code:
CDT - Lipase Hydrolysis/Glycerol Kinase Enzyme, Triglycerides
CHH - Enzymatic Esterase--Oxidase, Cholesterol
LBS - LDL & VLDL Precipitation, Cholesterol Via Esterase-Oxidase, HDL
MRR - System, Test, Low Density, Lipoprotein
JJE - Analyzer, Chemistry (Photometric, Discrete), For Clinical Use
4. Panel:
Chemistry (75)
H. Intended Use:
1. Intended use(s):
See Indications (s) for use below
2. Indication(s) for use:
The Hitachi Clinical Analyzer with S TEST reagent cartridges for total cholesterol (CHO), HDL cholesterol (HDL), LDL cholesterol (LDL), and triglycerides (TG) is intended for the quantitative measurements of CHO, HDL, LDL, and TG in serum or heparinized plasma. The test system is intended for use
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in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
- Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, and lipid and lipoprotein metabolism disorders.
- HDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
- LDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.
- Triglyceride 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.
3. Special conditions for use statement(s):
Prescription use only
4. Special instrument requirements:
Hitachi Clinical Analyzer
I. Device Description:
The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.
The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters, calibration factors, and other production-related information e.g., expiration dating. The dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H)
CHO Reagent #1:
- 4-aminoantipyrine 1.6 mmol/L
- cholesterol esterase (Microbial) >0.2 U/mL
- Peroxidase (Horseradish) >1.6 U/mL
CHO Reagent #2:
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- Cholesterol oxidase (Microbial) 2 U/mL
N-ethyl-N-sulfobutyl-m-toluidine, disodium salt 1.5 mmol/L
**HDL Reagent #1:**
- N, N-Bis (4-sulfobutyl)-m-toluidine disodium salt (DSBmT) 0.5 mmol/L
- Cholesterol oxidase (isolated from microorganism) 1.0 U/mL
- Bis (2-hydroxyethyl) iminotris (hydroxymethyl) methane (Bis-Tris) (pH 6.0) 50 mmol/L
- Peroxidase (isolated from horseradish) <1.3 ppm U/mL
**HDL Reagent #2:**
- 4-aminoantipyrine 1.0 mmol/L
- Surfactant
- Bis (2-hydroxyethyl) iminotris (hydroxymethyl) methane (Bis-Tris) (pH 6.0) 50 mmol/L
- Cholesterol esterase (isolated from microorganism) ≥1.0 U/mL
**LDL Reagent #1:**
- 4-Aminoantipyrine 0.01%
- Cholesterol esterase (Microbial) <2.5 U/mL
- Cholesterol oxidase (Microbial) 1.2 U/mL
- Peroxidase (Horseradish) <1.3 ppm U/mL
- Surfactant 1
- Good’s Buffer (pH 6.3)
**LDL Reagent #2:**
- Surfactant 2
- N,N-bis (4-sulfobutyl)-m-toluidine, disodium salt (DSBmT) 0.04%
- Good’s Buffer (pH 6.3)
**TG Reagent #1:**
- 2’-Deoxyadenosine-5’-triphosphate sodium salt 3.0 mmol/L
- Glycerokinase (Flavobacterium meningosepticum) 1.0 IU/mL
- L-α-Glycerophosphate oxidase (Streptococcus sp.) 6.0 IU/mL
- N,N-Bis(4-sulfobutyl)-3-methylaniline disodium salt 1.0 mmol/L
- Catalase (Micrococcus lysodeikticus) 800 U/mL
- Good’s Buffer (pH 6.5) 50 mmol/L
**TG Reagent #2:**
- Lipoprotein lipase (Chromobacterium viscosum) 100 IU/mL
- 4-aminoantipyrine 1.6 mmol/L
- Peroxidase (Horseradish) 30 U/mL
- Good’s Buffer (pH 6.2) 50 mmol/L
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# J. Substantial Equivalence Information:
1. Predicate device name(s):
Instrument portion: Roche/Hitachi cobas 6000- k060373
Total cholesterol: Roche/Hitachi test reagent- k031824
HDL: Roche/Hitachi test reagent- k033610
LDL: Roche/Hitachi test reagent- k012287
TG: Roche/Hitachi test reagent- k972250
2. Predicate 510(k) number(s):
See predicate device names(s) above
3. Comparison with predicate:
| Characteristic | Hitachi S TEST Systems | PREDICATE(S) |
| --- | --- | --- |
| Instrument Platform | Hitachi Clinical Analyzer | Roche cobas 6000 - k060373 |
| | | |
| Cholesterol | K number- k111753 | Roche K number- k031824 |
| Indications for Use | Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood, and lipid and lipoprotein metabolism disorders. | Same |
| Device Class, Regulation Code | Class I (meets limitations per 21 CFR 862.9(c)(4)), 21 CFR 862.1175 | Same |
| Classification Product Code | CHH | Same |
| Intended Use | Quantitative determination of total cholesterol | Same |
| Test Principle | Enzymatic method (COD-POD method) | Enzymatic (cholesterol esterase and cholesterol oxidase) |
| Specimen Type | Serum and heparinized plasma | Same |
| Reportable Range | 4 to 400 mg/dL | 3.86 to 800 mg/dL |
| Detection Wavelength | 600/800 nm | 700/505 nm |
| Precision | %CVs range from 0.5% to 1.4% (POL testing) | %CVs range from 1.4% to 1.6% (from product labeling) |
| | | |
| HDL | K number- k111753 | Roche K number- k033610 |
| Indications for Use | HDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. | Same |
| Device Class, Regulation Code | Class I (meets limitations per 21 CFR 862.9(c)(4)), 21 CFR 862.1475 | Same |
| Classification Product Code | LBS | Same |
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| Characteristic | Hitachi S TEST Systems | PREDICATE(S) |
| --- | --- | --- |
| Intended Use | Quantitative determination of HDL cholesterol | Same |
| Test Principle | Enzymatic direct method | Enzymatic (cholesterol esterase and cholesterol oxidase) after removal of LDL and VLDL |
| Specimen Type | Serum and heparinized plasma | Same |
| Reportable Range | 8 mg/dL to 150 mg/dL | 3 to 121 mg/dL |
| Detection Wavelength | 600/700 nm | 700/600 nm |
| Precision | %CVs range from 1.0% to 4.5% (from POL testing) | %CVs range from 0.9% to 1.5% (from product labeling) |
| LDL | K number- k111753 | Roche K number- k033610 |
| Indications for Use | LDL measurements (lipoproteins) are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. | Same |
| Device Class, Regulation Code | Class I (meets limitations per 21 CFR 862.9(c)(4)), 21 CFR 862.1475 | Same |
| Classification Product Code | MRR | Same |
| Intended Use | Quantitative determination of LDL cholesterol | Same |
| Test Principle | Enzymatic direct method | Homogeneous enzymatic colorimetric |
| Specimen Type | Serum and heparinized plasma | Same |
| Reportable Range | 8 to 400 mg/dL | 3.86 to 548 mg/dL |
| Detection Wavelength | 546/660 nm | 700/600 nm |
| Precision | %CVs range from 1.3% to 2.0% (from POL testing) | %CVs range from 1.9% to 2.7% (from product labeling) |
| | | |
| Triglycerides | K number- k111753 | Roche K number- k972250 |
| Indications for Use | Triglyceride 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. | Same |
| Device Class, Regulation Code | Class I (meets limitations per 21 CFR 862.9(c)(4)), 21 CFR 862.1705 | Same |
| Classification Product Code | CDT | Same |
| Intended Use | Quantitative determination of triglycerides | Same |
| Test Principle | Enzymatic method | Enzymatic and colorimetric |
| Specimen Type | Serum and heparinized plasma | Same (plus EDTA plasma) |
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| Characteristic | Hitachi S TEST Systems | PREDICATE(S) |
| --- | --- | --- |
| Reportable Range | 7 mg/dL to 800 mg/dL | 8.85 to 885 mg/dL |
| Detection Wavelength | 570/700 nm | 700/505 nm |
| Precision | %CVs range from 1.1% to 4.1%
(from POL testing) | %CVs range from 1.6% to 2.0%
(from product labeling) |
K. Standard/Guidance Document Referenced (if applicable):
CLSI - Protocols for Determination of Limits of Detection and Limits of Quantitation - EP17-A
CLSI - Evaluation of Precision Performance of Clinical Chemistry Devices - EP05-A2
CLSI - Interference Testing in Clinical Chemistry - EP07-A2
L. Test Principle:
Cholesterol
The cholesterol in the sample is cleaved into cholesterol esters and free cholesterol. The cholesterol esters become free cholesterol through the action of cholesterol esterase (CE). The free cholesterol is then oxidized by cholesterol oxidase (COD) to produce hydrogen peroxide, esters and free cholesterol. The cholesterol esters become free cholesterol through the action of cholesterol esterase (CE). The hydrogen peroxide oxidizes and condenses 4-aminoaminoantipyrine and N-ethyl-N-sulfobutyl-m-toluidine (ESBmT) under the influence of peroxidase (POD) to produce a reddish-purple pigment. Total cholesterol concentration is determined by measuring the absorbance of this reddish-purple pigment. The difference in absorbance, monitored bichromatically at 600 nm/800 nm, is directly proportional to the cholesterol concentration in the sample.
HDL
By using a special surface-active agent that preferentially solubilizes HDL and not other lipoproteins (LDL, VLDL, and chylomicrons), the HDL cholesterol is measured via a quickly initiated enzymatic reaction. Therefore, only HDL cholesterol is specifically measured. The released hydrogen peroxide oxidizes and condenses 4-aminoaminoantipyrine and N,N'-bis(4-sulfobutyl)-m-toluidine disodium salt (DSBmT) in the presence of peroxidase (POD) to produce a reddish-purple pigment. HDL cholesterol concentration is determined by measuring the absorbance of this reddish-purple pigment. The difference in absorbance, monitored bichromatically at 600 nm/700 nm is directly proportional to the HDL concentration in the sample.
LDL
The method, using a combination of two surfactants, is based on the principle that each lipoprotein reacts with different surfactants, depending on their intrinsic physicochemical property. In the first reaction, Surfactant 1 changes the structure of only those lipoproteins other than LDL (i.e., chylomicron [CM], VLDL, and HDL), and the resulting micellar cholesterol is consumed by the cholesterol oxidase and the cholesterol esterase in a colorless reaction. In the second reaction, the remaining LDL is modified by Surfactant 2, and that form of cholesterol is measured in a color reaction.
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# Triglyceride
Free glycerol in the sample is converted to glycerol-3-phosphoric acid through the action of glycerol kinase (GK) and the adenosine triphosphate (ATP) substrate. Glycerol-3-phosphoric acid is converted to hydrogen peroxide via the action of glycerol-3-phosphate oxidase (GPO); peroxide is then decomposed into water and oxygen via the action of catalase. The neutral fat in the sample is quickly hydrolyzed into glycerol and fatty acid by the lipoprotein lipase (LPL) contained in the second reagent. The glycerol product is converted to glycerol-3-phosphoric acid via the action of GK and the ATP substrate, which in turn produces hydrogen peroxide via the action of GPO. The hydrogen peroxide oxidizes/condenses 4-aminoantipyrine and N-ethyl-N-sulfobutyl-m-toluidine (ESBmT), via the action of peroxidase (POD) to produce a reddish purple pigment. The original neutral fat concentration (triglyceride) is determined by measuring the absorbance of the reddish purple pigment produced. The difference in absorbance between the final reading and the blank, monitored bichromatically at $600\mathrm{nm} / 800\mathrm{nm}$, is directly proportional to the triglyceride concentration.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
Three levels of serum samples (A, B, and C) were tested by three POL sites, six times a day for five days. The precision estimates are described below.
Total Cholesterol (mg/dL) n = 30 replicates per sample per site
| Site | Sample | Mean | Within-run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| Site 1 | A | 121.3 | 0.8 | 0.6% | 0.8 | 0.7% |
| Site 2 | A | 123.5 | 0.9 | 0.7% | 1.2 | 1.0% |
| Site 3 | A | 123.5 | 1.2 | 1.0% | 1.5 | 1.2% |
| | | | | | | |
| Site 1 | B | 182.6 | 1.1 | 0.6% | 1.3 | 0.7% |
| Site 2 | B | 185.0 | 1.1 | 0.6% | 1.3 | 0.7% |
| Site 3 | B | 185.4 | 1.2 | 0.6% | 1.3 | 0.7% |
| | | | | | | |
| Site 1 | C | 242.3 | 0.9 | 0.4% | 1.1 | 0.5% |
| Site 2 | C | 245.8 | 1.2 | 0.5% | 1.4 | 0.6% |
| Site 3 | C | 247.1 | 1.8 | 0.7% | 3.4 | 1.4% |
HDL Cholesterol (mg/dL) n = 30 replicates per sample per site
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| Site | Sample | Mean | Within-run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| Site 1 | A | 37.3 | 1.3 | 3.4% | 1.7 | 4.5% |
| Site 2 | A | 36.3 | 0.6 | 1.6% | 0.7 | 2.0% |
| Site 3 | A | 35.8 | 0.7 | 2.0% | 1.3 | 3.7% |
| | | | | | | |
| Site 1 | B | 67.1 | 0.5 | 0.8% | 0.6 | 1.0% |
| Site 2 | B | 68.0 | 0.5 | 0.8% | 1.1 | 1.6% |
| Site 3 | B | 64.6 | 0.7 | 1.0% | 0.8 | 1.3% |
| | | | | | | |
| Site 1 | C | 105.9 | 1.5 | 1.4% | 2.0 | 1.9% |
| Site 2 | C | 106.3 | 1.1 | 1.0% | 1.4 | 1.3% |
| Site 3 | C | 102.7 | 1.3 | 1.3% | 1.6 | 1.6% |
**LDL Cholesterol (mg/dL) n = 30 replicates per sample per site**
| Site | Sample | Mean | Within-run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| Site 1 | A | 41.0 | 0.6 | 1.5% | 0.7 | 1.7% |
| Site 2 | A | 42.5 | 0.8 | 1.9% | 0.8 | 1.8% |
| Site 3 | A | 41.3 | 0.8 | 2.0% | 0.8 | 2.0% |
| | | | | | | |
| Site 1 | B | 108.9 | 1.3 | 1.2% | 1.4 | 1.3% |
| Site 2 | B | 112.3 | 1.5 | 1.4% | 1.7 | 1.5% |
| Site 3 | B | 109.1 | 2.3 | 2.1% | 2.2 | 2.0% |
| | | | | | | |
| Site 1 | C | 183.5 | 2.6 | 1.4% | 3.1 | 1.7% |
| Site 2 | C | 191.3 | 2.4 | 1.2% | 3.5 | 1.8% |
| Site 3 | C | 181.2 | 2.6 | 1.4% | 3.1 | 1.7% |
**Triglycerides (mg/dL) n = 30 replicates per sample per site**
| Site | Sample | Mean | Within-run Precision | | Total Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD (mg/dL) | %CV | SD (mg/dL) | %CV |
| Site 1 | A | 32.1 | 0.8 | 2.6% | 1.1 | 3.4% |
| Site 2 | A | 33.6 | 1.1 | 3.3% | 1.1 | 3.3% |
| Site 3 | A | 31.4 | 1.2 | 4.0% | 1.3 | 4.1% |
| | | | | | | |
| Site 1 | B | 115.0 | 3.0 | 2.6% | 3.5 | 3.0% |
| Site 2 | B | 120.2 | 1.4 | 1.2% | 1.5 | 1.3% |
| Site 3 | B | 115.4 | 2.2 | 1.9% | 2.8 | 2.4% |
| | | | | | | |
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| Site 1 | C | 291.0 | 1.9 | 0.7% | 3.4 | 1.2% |
| --- | --- | --- | --- | --- | --- | --- |
| Site 2 | C | 301.5 | 3.7 | 1.2% | 3.5 | 1.2% |
| Site 3 | C | 289.1 | 2.5 | 0.9% | 3.3 | 1.1% |
# b. Linearity/assay reportable range:
Linearity/calibration sets were prepared for testing using 8 to 15 serial dilutions per assay system. The samples were assigned their reference values arithmetically and were tested in duplicate by the Hitachi Clinical Analyzer, and the mean Hitachi results (y-axis) were plotted against the assigned values (x-axis).
| | Linearity (range tested) | Regression analysis | reportable range claimed |
| --- | --- | --- | --- |
| CHO: | 1 to 435 mg/dL | y = 1.007x + 0.8519 R² = 0.9997 | 4 to 400 mg/dL |
| HDL: | 4 mg/dL to 485 mg/dL | y = 1.0133x + 1.9909 R² = 0.9977 | 8 mg/dL to 150 mg/dL |
| LDL: | 3 to 430 mg/dL | y = 0.9924x - 0.5934 R² = 0.9991 | 8 to 400 mg/dL |
| TG: | 2 to 848 mg/dL | y = 1.0301x + 2.0439 R² = 0.9994 | 7 mg/dL to 800 mg/dL |
# c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Each S Test cartridge lot is calibrated using standard material traceable to:
CHO: NIST SRM 911
- TG: HECTEF (Healthcare Technology Foundation) standard serum JCCRM 224.
- HDL: HECTEF (Healthcare technology foundation) standard serum for measuring lipids
- LDL: Beta-Quantification Reference Method (CDC)
Methods have not been CRMLN certified
# d. Detection limit:
Per CLSI EP17-A blank samples for each reagent system were assayed 20 times per day for three days for a total of 60 replicate results to determine LOB and LOD. Low samples were assayed 20 times with the specific reagent cartridges to determine the detection limits below:
CHO: $0.7\mathrm{mg / dL}$
HDL: $0.6\mathrm{mg / dL}$
LDL: $0.8\mathrm{mg / dL}$
TG: $2.5\mathrm{mg / dL}$
The minimum measuring ranges of the assays were established based on linearity studies (see M1b above).
# e. Analytical specificity:
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The studies followed CLSI EP7-A2. The data demonstrated that none of the four analytes were affected by high levels of the following substances at the levels noted below. The interference claim for each is defined by the sponsor as the highest level of interferent that is within 10% of the neat sample.
- Hemoglobin: no interference up to 1000 mg/dL for CHO and LDL; 500 mg/dL for HDL and TG
- Unconjugated bilirubin: no interference up to 50 mg/dL for CHO, HDL, and TG; 25 mg/dL for LDL
- Lipemia: no interference up to 2000 mg/dL for CHO; up to 614 mg/dL for HDL and LDL (TG: N/A)
- Ascorbic acid: no interference up to 50 mg/dL with any of the four test systems
f. Assay cut-off:
Not Applicable
2. Comparison studies:
a. Method comparison with predicate device:
**Cholesterol**
**Patient Correlation (POL sites)**
A series of serum specimens were assayed on the HITACHI Clinical Analyzer at three sites using S TEST CHO (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
POL ACCURACY DATA SUMMARY- Total Cholesterol mg/dL
| Site # | n | Range | Regression Equation | “r” | CI* Slope | CI Intercept |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 52 | 60 to 329 | y = 0.97x +2.5 | 0.99 | 0.95 to 0.98 | -1.1 to 6.1 |
| 2 | 50 | 60 to 334 | y = 0.98x +4.1 | 0.99 | 0.95 to 1.00 | -1.0 to 9.3 |
| 3 | 51 | 60 to 333 | y = 1.00x +0.7 | 0.97 | 0.94 to 1.08 | -13.7 to 15.2 |
*95% Confidence Interval
**Patient Correlation (in-house laboratory site)**
A series of serum specimens with were assayed on the HITACHI Clinical Analyzer using S TEST CHO (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
IN-HOUSE LAB ACCURACY DATA SUMMARY- Total Cholesterol
n = 113, range = 5 mg/dL to 374 mg/dL
y = 0.98x + 2.2 r = 0.99
95% CI of slope = 0.96 to 1.00 95% CI of y-intercept = -1.7 to 6.1
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# HDL
## Patient Correlation (POL sites)
A series of serum specimens were assayed on the HITACHI Clinical Analyzer at three sites using S TEST HDL (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
POL ACCURACY DATA SUMMARY- HDL mg/dL
| Site # | n | Range | Regression Equation | “r” | CI Slope | CI Intercept |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 52 | 15 to 111 | y = 0.96x +7.6 | 0.98 | 0.91 to 1.00 | 4.9 to 10.3 |
| 2 | 50 | 16 to 114 | y = 0.97x +7.9 | 0.98 | 0.91 to 1.03 | 4.8 to 11.0 |
| 3 | 51 | 14 to 115 | y = 0.93x +7.8 | 0.99 | 0.89 to 0.98 | 5.3 to 10.3 |
CI = 95% confidence interval
## Patient Correlation (in-house laboratory site)
A series of serum specimens were assayed on the HITACHI Clinical Analyzer using S TEST HDL (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
IN-HOUSE LAB ACCURACY DATA SUMMARY- HDL
n = 109, range = 9 mg/dL to 140 mg/dL
y = 0.99x +5.4
r = 0.99
95% CI of slope = 0.96 to 1.03
95% CI of y-intercept = 3.6 to 7.3
# LDL
## Patient Correlation (POL sites)
A series of serum specimens were assayed on the HITACHI Clinical Analyzer at three sites using S TEST LDL (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results.
POL ACCURACY DATA SUMMARY- LDL mg/dL
| Site # | n | Range | Regression Equation | “r” | CI Slope | CI Intercept |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 52 | 26 to 274 | y = 0.94x +3.8 | 0.99 | 0.90 to 0.99 | -1.7 to 9.4 |
| 2 | 50 | 26 to 283 | y = 0.95x +3.6 | 0.98 | 0.89 to 1.01 | -3.5 to 10.8 |
| 3 | 51 | 25 to 276 | y = 0.93x +6.4 | 0.98 | 0.89 to 0.98 | 0.6 to 12.3 |
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CI = 95% confidence interval
## Patient Correlation (in-house laboratory site)
A series of serum specimens were assayed on the HITACHI Clinical Analyzer using S TEST LDL (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results.
### IN-HOUSE LAB ACCURACY DATA SUMMARY- LDL
n = 113, range = 8 mg/dL to 370 mg/dL
y = 0.94x + 7.6 r = 0.98
95% CI of slope = 0.90 to 0.97 95% CI of y-intercept = 3.0 to 12.1
## Triglyceride
### Patient Correlation (POL sites)
A series of serum samples with TG values ranging from 33 mg/dL to 643 mg/dL were assayed on the HITACHI Clinical Analyzer at three sites using S TEST TG (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
### POL ACCURACY DATA SUMMARY- TG mg/dL
| Site # | n | Range | Regression Equation | “r” | CI Slope | CI Intercept |
| --- | --- | --- | --- | --- | --- | --- |
| 1 | 52 | 36 to 619 | y = 1.05x+4.9 | 0.99 | 1.04 to 1.07 | 1.4 to 8.4 |
| 2 | 52 | 21 to 712 | y = 0.94x + 3.3 | 0.99 | 1.10 to 1.14 | -5.7 to 2.4 |
| 3 | 51 | 35 to 605 | y = 1.07x -6.5 | 0.99 | 1.05 to 1.10 | -10.1 to -2.9 |
CI = 95% confidence interval
### Patient Correlation (in-house laboratory site)
A series of serum specimens were assayed on the HITACHI Clinical Analyzer using S TEST TG (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:
### IN-HOUSE LAB ACCURACY DATA SUMMARY- TG
n = 111, range = 19 mg/dL to 761 mg/dL
y = 1.04x + 6.7 r = 0.99
95% CI of slope = 1.03 to 1.05 95% CI of y-intercept = 4.4 to 9.0
## b. Matrix comparison:
Serum/Plasma Comparison Study
A study was performed to validate the use of heparinized plasma as well as serum for the Hitachi Clinical Analyzer with S TEST reagent cartridges. Forty
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(40) matched serum/plasma samples that spanned the dynamic range were assayed in singleton and the results were compared using least squares linear regression (plasma = y-axis). The performance characteristics were as follows.
Cholesterol (mg/dL)
y = 1.00x -3.0
correlation coefficient (r) = 0.999
95% confidence interval of the slope = 0.99 to 1.01
95% confidence interval of the y-intercept = -5.5 to -0.6
Range = 12 to 393 mg/dL
HDL (mg/dL)
y = 1.00x -2.8
correlation coefficient (r) = 0.999
95% confidence interval of the slope = 0.98 to 1.02
95% confidence interval of the y-intercept = -4.6 to zero
Range = 17 to 135 mg/dL
LDL (mg/dL)
y = 1.00x -3.9
correlation coefficient (r) = 0.999
95% confidence interval of the slope = 0.99 to 1.01
95% confidence interval of the y-intercept -5.8 to -2.0
Range = 16 to 380 mg/dL
TG (mg/dL)
y = 1.00x -1.3
correlation coefficient (r) = 0.999
95% confidence interval of the slope = 0.98 to 1.00
95% confidence interval of the y-intercept = -4.5 to 2.0
Range = 7 to 781 mg/dL
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):
None
4. Clinical cut-off:
Not applicable. Clinical studies are not typically submitted for this device type.
5. Expected values/Reference range*:
Cholesterol: Desirable: <200 mg/dL, Borderline: 200-239 mg/dL, High: >239 mg/dL)
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HDL: HDL: <40 = Low, ≥60 = High
LDL: Optimal: <100 mg/dL, Near optimal: 100 – 129 mg/dL, Borderline high: 130 – 159 mg/dL, High: 160 – 189, Very high: >189 mg/dL
Triglycerides: TG: <150 = normal, 150 – 199 = borderline high, 200-499 = high, ≥500 = very high
* Third Report of National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults (Adult Treatment Panel III); Executive Summary, 2002
## N. Instrument Name:
Hitachi Clinical Analyzer
## 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:
Automatic, allocation or Key input for sample ID before starting analysis.
4. Specimen Sampling and Handling:
Sample cup, serum or plasma
5. Calibration:
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Factory Calibrated
6. Quality Control:
Range settings for Quality Control and storage up to 160 samples in “control run list”
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above:
None
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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