SYNCHRON SYSTEMS HDL CHOLESTEROL (HDL), SYNCHRON SYSTEMS LIPID PLUS CALIBRATORS 1 & 2, MODELS A15625/A16747

K042195 · Beckman Coulter, Inc. · LBS · Sep 16, 2004 · Clinical Chemistry

Device Facts

• Record ID: K042195
• Device Name: SYNCHRON SYSTEMS HDL CHOLESTEROL (HDL), SYNCHRON SYSTEMS LIPID PLUS CALIBRATORS 1 & 2, MODELS A15625/A16747
• Applicant: Beckman Coulter, Inc.
• Product Code: LBS · Clinical Chemistry
• Decision Date: Sep 16, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

HDL reagent, when used in conjunction with SYNCHRON LX® System(s) and SYNCHRON® Systems Lipid Plus Calibrator, is intended for the quantitative determination of HDL Cholesterol (HDL) in the high density lipoprotein (HDL) fraction of human serum or plasma. HDL reagent, when used in conjunction with SYNCHRON CX® CE/DELTA/PRO System(s) and SYNCHRON® Systems Lipid Plus Calibrator, is intended for the quantitative determination of HDL Cholesterol (HDL) in the high density lipoprotein (HDL) fraction of human serum or plasma. The SYNCHRON Systems Lipid Plus Calibrators 1& 2, in conjunction with specified assays on the SYNCHRON® Systems, are intended to provide points of reference in the measurement of selected human lipids and proteins.

Device Story

SYNCHRON Systems HDL Reagent is a liquid, ready-to-use diagnostic reagent for use on SYNCHRON CX and LX clinical chemistry systems. The device performs a homogeneous assay to measure HDL cholesterol concentration in human serum or plasma samples. Principle of operation involves a specific detergent to selectively dissolve HDL, followed by cholesterol esterase and cholesterol oxidase reactions to produce hydrogen peroxide; this reacts with a chromogen to form a colored product measured via timed-endpoint photometry. The system requires Lipid Plus Calibrators for reference. The assay is intended for clinical laboratory use by trained personnel. Results assist clinicians in evaluating lipid profiles and cardiovascular risk. The device provides a quantitative measurement of HDL cholesterol levels, aiding in the diagnosis and management of lipid metabolism disorders.

Clinical Evidence

Bench testing only. Precision studies (NCCLS EP5-A) showed within-run CVs of 1.2-2.8% and total imprecision CVs of 2.4-6.1%. Linearity established from 5-135 mg/dL (r=0.999). Method comparison against predicate (k040767) using Deming regression showed high correlation (r=0.993-0.994). Interference studies confirmed no significant interference from hemoglobin, bilirubin, lipemia, ascorbic acid, or IgG. Matrix comparison studies validated use with heparin and EDTA anticoagulants.

Technological Characteristics

Liquid, ready-to-use reagent in bar-coded cartridges. Homogeneous enzymatic assay (cholesterol oxidase/esterase). Photometric timed-endpoint detection. Calibrators are stabilized human serum. Standards referenced: NCCLS EP5-A, EP6-P, EP7, EP9-A, and prEN ISO 17511. Traceable to NIST SRM 19516.

Indications for Use

Indicated for quantitative determination of HDL cholesterol in human serum or plasma for clinical diagnostic use. No specific patient population, age, or gender restrictions are stated.

Regulatory Classification

Identification

A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.

Predicate Devices

• SYNCHRON Systems HDLD Reagent (K040767)
• SYNCHRON Systems Lipid Calibrator (K983640)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k042195

B. Purpose for Submission:
New device

C. Analyte:
HDL Cholesterol

D. Type of Test:
Quantitative

E. Applicant:
Beckman Coulter, Inc.

F. Proprietary and Established Names:
SYNCHRON® Systems HDL Cholesterol (HDL) Reagent
SYNCHRON® Systems Lipid Plus Calibrators 1 & 2

G. Regulatory Information:
1. Regulation section:
862.1475, Lipoprotein Test System
862.1150, Calibrator, Secondary
2. Classification:
Class I that meets the limitations of exemptions 862.9 (c) (9), Class II
3. Product Code:
LBS, JIT
4. Panel:
75

H. Intended Use:
1. Intended use(s):
See Indications for Use
2. Indication(s) for use:
HDL reagent, when used in conjunction with SYNCHRON LX® System(s)
and SYNCHRON Systems Lipid Plus Calibrator, is intended for the

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quantitative determination of HDL Cholesterol (HDL) in the high density lipoprotein (HDL) fraction of human serum or plasma.

HDL reagent, when used in conjunction with SYNCHRON CX® CE/DELTA/PRO System(s) and SYNCHRON Systems Lipid Plus Calibrator, is intended for the quantitative determination of HDL Cholesterol (HDL) in the high density lipoprotein (HDL) fraction of human serum or plasma.

The SYNCHRON® Systems Lipid Plus Calibrator 1 & 2, in conjunction with specified assays on the SYNCHRON® Systems, are intended to provide points of reference in the measurement of selected human lipids and proteins.

3. Special condition for use statement(s):
Prescription Use only

4. Special instrument Requirements:
SYNCHRON® CX CE/DELTA/PRO and LX Systems

I. Device Description:
The SYNCHRON® Systems HDL Reagent is supplied in a ready-to-use liquid format and filled into bar-coded cartridges, which are placed directly onto the appropriate SYNCHRON System. SYNCHRON Systems Lipid Plus Calibrators 1 & 2 are supplied as stabilized liquid calibrators prepared from human serum.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Beckman Coulter SYNCHRON® Systems HDLD Reagent
2. Predicate K number(s):
k040767
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Same | Same |
| Analytical range | 5 – 135 mg/dL | Same |
| Reagents | Liquid, ready to use | Same |
| Sample type | Serum or plasma | Same |
| Differences | | |
| Item | Device | Predicate |
| Sample size | 4 μl | 3 μl |
| Methodology | uses cholesterol oxidase acceleration and dissolving of HDL by use of a specific detergent | uses solubilization polyanion |

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## K. Standard/Guidance Document Referenced (if applicable):

NCCLS EP5-A, NCCLS EP6-P, NCCLS EP7, NCCLS EP9-A, National Cholesterol Education Program Adult Treatment Panel III (ATP III)

## L. Test Principle:

The SYNCHRON® Systems HDL method is a homogenous assay without the need for any off-line pretreatment or centrifugation steps. The method is based on accelerating the reaction of cholesterol oxidase to form non-reactive lipid complexes, and selectively dissolving HDL using a specific detergent. The HDL cholesterol is converted with cholesterol esterase and cholesterol oxidase to form hydrogen peroxide, which is then coupled with a chromogen to form a colored product. HDL reagent is used to measure the cholesterol concentration by a timed-endpoint method.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

**a. Precision/Reproducibility:**

Within-run and total precision studies were designed from NCCLS EP5-A using multi-level control materials (number of data points = 80 for each level) based on the data from one system each for SYNCHRON CX and LX, run for 20 days, 2 runs per day, 2 observations per run. On the SYNCHRON CX Systems within-run % CV ranged from 1.5 % to 2.8 %; total imprecision, % CV ranged from 2.4 % to 5.1 %. On the SYNCHRON LX systems within run % CV ranged from 1.2 % to 2.3 %; total imprecision % CV ranged from 2.6 % to 6.1 %.

**b. Linearity/assay reportable range:**

The linear range of the assay was established as 5 – 135 mg/dL. Linearity studies were designed using NCCLS EP6-P. Serial dilutions of high serum samples were used. SYNCHRON systems values were plotted versus the sample dilution and an appropriate line fitted by standard linear regression. For the SYNCRON CX Systems, y = 1.0013x – 0.5601, r = 0.999. For the SYNCHRON LX systems, y = 1.0004x – 0.6862, r = 0.999.

**c. Traceability (controls, calibrators, or method):**

The SYNCHRON® Systems Lipid Plus Calibrators 1 & 2 is traceable to NIST SRM 19516. The traceability process is based on prEN ISO 17511. Labeling for the SYNCHRON® Systems HDL Cholesterol (HDL) Reagent contains the statement that the assay has not been certified per NCEP guidelines.

**d. Detection limit:**

Analytical sensitivity is defined as the concentration that can be distinguished from zero with 95 % confidence. The sensitivity for the method was established as 5 mg/dL.

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e. Analytical specificity:
Studies were performed to assess common or known substances that could interfere with the method. The following substances were tested for interference:

| Substance | Source | Maximum Level Tested | Observed Effect on Analyte |
| --- | --- | --- | --- |
| Hemoglobin | RBC hemolysate | 500 mg/dL | NSI |
| Bilirubin | Porcine | 30 mg/dL | NSI |
| Lipemia | Intralipid | 4+ (1800 mg/dL) | NSI |
| Ascorbic Acid | n/a | 100 mg/dL | NSI |
| Immunoglobulin IgG | Human | 5000 mg/dL | NSI |

NSI = No significant interference (within ± 6 mg/dL or 6 %)

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:
Method comparison experiments were designed using NCCLS EP9-A and employed Deming regression to assess the data. The correlation test results were obtained using the predicate SYNCHRON Systems HDLD Reagents (k040767) and the candidate SYNCHRON systems HDL reagents. Additional comparison studies were conducted versus the SYNCHRON Systems HDLC method.

| Instrument | Slope | Intercept | r | n | Range of Values | Comparison Method |
| --- | --- | --- | --- | --- | --- | --- |
| SYNCHRON CX | 0.992 | -2.8 | 0.994 | 79 | 11-134 mg/dL | SYNCHRON HDLD |
| SYNCHRON LX | 1.000 | -2.8 | 0.993 | 79 | 9-135 mg/dL | SYNCHRON HDLD |
| SYNCHRON CX | 1.037 | -5.1 | 0.979 | 79 | 11-130 mg/dL | SYNCHRON HDLC |
| SYNCHRON LX | 1.047 | -4.0 | 0.980 | 79 | 10-131 mg/dL | SYNCHRON HDLC |

b. Matrix comparison:
Serum versus plasma studies were performed to substantiate the use of heparin and EDTA anticoagulants. For each anticoagulant, a minimum of 50 healthy volunteers were drawn with values ranging from 14 mg/dL to 120 mg/dL.

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Summary Data for SYNCHRON CX Systems

| Anticoagulant | Level of Anticoagulant Tested | Deming Regression Analysis |
| --- | --- | --- |
| Sodium Heparin | 14 units/mL | Y = 0.985x + 0.5; r = 0.995 |
| Lithium Heparin | 14 units/mL | Y = 0.959x + 0.6; r = 0.993 |
| EDTA | 1.5 units/mL | Y = 0.946x – 1.1; r = 0.996 |

Summary Data for SYNCHRON LX Systems

| Anticoagulant | Level of Anticoagulant Tested | Deming Regression Analysis |
| --- | --- | --- |
| Sodium Heparin | 14 units/mL | Y = 1.030x -3.2; r = 0.992 |
| Lithium Heparin | 14 units/mL | Y = 0.958x + 0.5; r = 0.991 |
| EDTA | 1.5 units/mL | Y = 0.952x – 1.4; r = 0.993 |

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)

4. Clinical cut-off: Not applicable

5. Expected values/Reference range:
The reference Interval for HDL is based on the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III); Executive Summary. NIH Publication No. 01-3670, National Institutes of Health. Bethesda. Maryland: May 2001.

Cardiovascular Risk Units
High < 40 mg/dL
Low ≥ 60 mg/dL

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