ADVIA IMS DIRECT HDL CHOLESTEROL ASSAY

K050632 · Bayer Healthcare, LLC · LBS · May 26, 2005 · Clinical Chemistry

Device Facts

• Record ID: K050632
• Device Name: ADVIA IMS DIRECT HDL CHOLESTEROL ASSAY
• Applicant: Bayer Healthcare, LLC
• Product Code: LBS · Clinical Chemistry
• Decision Date: May 26, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

This in vitro method is intended to quantitatively measure HDL Cholesterol in human serum and plasma on the Bayer ADVIA® IMS systems. Measurements of HDL Cholesterol are used in assessing cardiovascular risk.

Device Story

The Bayer ADVIA IMS Direct HDL Cholesterol Assay is an immunoturbidometric in vitro diagnostic test used on the Bayer ADVIA IMS Analyzer. It processes human serum or plasma samples to quantify HDL cholesterol levels. The assay utilizes two premixed liquid reagents (R1 and R2) loaded directly onto the analyzer. The system performs an automated reaction sequence involving sample incubation and measurement of turbidity changes. The resulting HDL cholesterol concentration is used by clinicians to assess cardiovascular disease risk. The device is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Precision studies (N=40 per level) showed within-run CVs of 1.3-3.0% and total CVs of 1.8-3.3%. Linearity was established from 7-90 mg/dL (r=0.9987). Method comparison against the predicate (ADVIA 1650) yielded r=0.988. Interference testing confirmed no significant deviation (≤10%) with bilirubin (up to 30 mg/dL conjugated/20 mg/dL unconjugated), hemoglobin (500 mg/dL), and lipids (1000 mg/dL). Matrix comparison confirmed equivalency between serum, lithium heparin plasma, and potassium-EDTA plasma.

Technological Characteristics

In vitro diagnostic reagent system for automated chemistry analyzers. Quantitative colorimetric/enzymatic assay principle. Analytical range: 7-90 mg/dL. Designed for use on Bayer ADVIA IMS platform. No specific materials or software algorithms described beyond standard automated clinical chemistry instrumentation.

Indications for Use

Indicated for in vitro diagnostic measurement of HDL cholesterol in human serum and plasma for cardiovascular disease risk assessment. For professional use only.

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

• Bayer ADVIA Chemistry Direct HDL Cholesterol Assay (k982341)

Submission Summary (Full Text)

{0}

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

A. 510(k) Number:
k050632

B. Purpose for Submission: Notification of intent to manufacture and market the device: Bayer ADVIA® IMS Direct HDL Cholesterol Assay.

C. Measurand:
Direct HDL (High Density Lipoprotein) Cholesterol

D. Type of Test:
Immunoassay

E. Applicant:
Bayer HealthCare Diagnostics Division

F. Proprietary and Established Names:
Proprietary - Direct HDL Cholesterol for the ADVIA IMS
Established – Lipoprotein test system

G. Regulatory Information:
1. Regulation section:
21 CFR 862.1475 Lipoprotein Test System
2. Classification:
Class I, meets the limitations of exemptions 21 CFR 862.9 (c) (4). The device is an in vitro device that is intended for assessing the risk of cardiovascular disease.
3. Product code:
LBS

{1}

4. Panel:
75, Clinical Chemistry

H. Intended Use:

1. Intended use(s):
Please see indications for use below.

2. Indication(s) for use:
The Bayer ADVIA IMS Direct HDL Cholesterol (D-HDL) method is for in vitro diagnostic use to measure HDL Cholesterol in human serum and plasma. Such measurements are used in the risk assessment of cardiovascular diseases.

3. Special conditions for use statement(s):
For professional use only

4. Special instrument requirements:
For use on the Bayer ADVIA IMS Analyzer

I. Device Description:
The Bayer ADVIA IMS D-HDL reagent pack consists of two bottles R1 and R2. Each bottle is premixed ready to use reagent loaded directly upon the Bayer ADVIA IMS.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Bayer ADVIA Chemistry Direct HDL Cholesterol Assay

2. Predicate 510(k) number(s):
k982341

{2}

3. Comparison with predicate:

| | ADVIA IMS Direct HDL Cholesterol | ADVIA Chemistry Direct HDL Cholesterol (Predicate device) |
| --- | --- | --- |
| Intended use | Similar | Similar |
| Summary | Similar | Similar |
| Principle | Similar | Similar |
| Reagents | Two liquid reagents contained in system specific packaging | Two liquid reagents contained in system specific packaging |
| Storage | 2-8°C | 2-8°C |
| Stability | 45 days on-system without recalibration | 1 month on-system without recalibration |
| Precautions | Similar | Similar |
| Indications of Deterioration | Similar | Similar |
| Performance Characteristics | Similar | Similar |
| Limitations | Similar | Similar |
| Parameters | R1,14.2 uL; R2, 14.3 uL; Sample 1.5uL; 2-minute incubation of R1+S; 45 seconds final reaction | R1, 80uL; R2, 25uL; Sample pre-dilution 1+4 then 5uL. 5 minute incubation R1+S;2.7 minutes final reaction |

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

Bayer uses protocols similar to those recommended in the following Clinical Laboratory and Standards Institute (CLSI) documents EP5-A Precision performance of clinical chemistry devices, EP9-A Method comparison and bias estimation using patient samples, EP-7 Interference testing in clinical chemistry, H18-A2 Procedures for the handling and processing of blood specimens

This method is not currently certified by the Cholesterol Reference Method Laboratory Network

L. Test Principle:

Immunoturbidometric

{3}

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within run precision was performed on two systems B23 and B44 for ten days with two runs and two cups per run.

Table 1 System B23
| | Days | Runs | N | Mean mg/dL | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV |
| Control Level 1 | 10 | 20 | 40 | 37.04 | 1.05 | 2.8 | 1.21 | 3.3 |
| Human Serum Pool | 10 | 20 | 40 | 54.84 | 0.80 | 1.5 | 1.03 | 1.9 |
| Calibrator | 10 | 20 | 40 | 82.55 | 1.04 | 1.3 | 1.47 | 1.8 |

Table 2 System B44
| | Days | Runs | N | Mean mg/dL | Within Run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV |
| Control Level 1 | 10 | 20 | 40 | 34.52 | 1.04 | 3.0 | 1.08 | 3.1 |
| Human Serum Pool | 10 | 20 | 40 | 54.37 | 1.18 | 2.2 | 1.47 | 2.7 |
| Calibrator | 10 | 20 | 40 | 81.29 | 1.67 | 2.1 | 2.13 | 2.6 |

b. Linearity/assay reportable range:

A total of ten samples were prepared by mixing 0.9% saline and a high serum linearity pool that was prepared in-house. From the derived theoretical values (x) versus obtained values (y) with levels ranging from 7 mg/dL to 85 mg/dL, the following regression equation was obtained: y = 1.01207x - 0.22402, r = 0.9987.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The single level ADVIA Chemistry HDL/LDL Cholesterol calibrator is used to calibrate the ADVIA IMS DHDL method. This calibrator was previously approved for use on the ADVIA 1650 and 2400 systems. The calibrator is traceable via patient sample correlation to the Designated Comparison Method established by the National Cholesterol Education Program.

{4}

d. Detection limit:

Based upon the linearity data, the analytical range was established as $7 - 90\mathrm{mg / dL}$

e. Analytical specificity:

Interference was evaluated by spiking human serum pools with hemoglobin, unconjugated bilirubin, conjugated bilirubin, and triglycerides. Intermediate dilutions were determined by diluting the spiked sample with undiluted sample. The observed recovery was considered to be of no clinical significance if the deviation for these potential interferences was $\leq 10\%$ . Bilirubin (unconjugated) up to a level of $30\mathrm{mg / dL}$ , bilirubin (conjugated) up to a level of $20\mathrm{mg / dL}$ , hemoglobin up to a level of $500\mathrm{mg / dL}$ , and lipids up to a level of $1000\mathrm{mg / dL}$ did not interfere with the assay.

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Correlation was evaluated with human serum or plasma as appropriate in a protocol similar to CLSI document EP9-A. Regression data for each method indicate the linear least-squares fit between the ADVIA IMS system (y) and the predicate system/method (x).

Serum

| Comparison Method | N | Regression Equation (y=) | R | Sy,x | Range of Analyte Concentration |
| --- | --- | --- | --- | --- | --- |
| ADVIA 1650 | 100 | 0.986 + 0.03 0.986 + 1.16 | 0.988 | 0.06 | 0.36 – 2.23mmol/L |
| | | | | 2.29 | 13.80 – 86.20 mg/dL |

Plasma

| Comparison Method | N | Regression Equation (y=) | R | Sy,x | Range of Analyte Concentration |
| --- | --- | --- | --- | --- | --- |
| Plasma, lithium heparin | 35 | 0.973-0.00 | 0.988 | 0.05 | 0.88 – 2.26 mmol/L |
| | | 0.973-0.02 | | 2.11 | 33.80 – 87.10 mg/dL |
| Plasma, di-potassium EDTA | 35 | 0.978-0.01 | 0.988 | 0.06 | 0.88 – 2.26 mmol/L |
| | | 0.978-0.22 | | 2.13 | 33.80 – 87.10 mg/dL |

{5}

b. Matrix comparison:

The serum/plasma equivalency study was run on the ADVIA IMS with matched human serum, lithium heparin plasma and potassium-EDTA plasma samples. The results are summarized below.

| y | x | Slope | Intercept | Sy.x | r | n | Serum Range (mg/dL) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Lithium heparin plasma | serum | 0.973 | -0.02 | 2.11 | 0.988 | 35 | 33.8-87.1 |
| Potassium-EDTA plasma | serum | 0.978 | -0.22 | 2.13 | 0.988 | 35 | 33.8-87.1 |

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable

4. Clinical cut-off:

Not applicable

5. Expected values/Reference range:

Guidelines for reference ranges have been suggested by the Panel of the National Institutes of Health's Cholesterol Consensus Development Conference and adopted by the National Cholesterol Education Program.

The suggested guidelines of the Panel are as follows:

HDL Cholesterol

<1.0 mmol/L (40.00 mg/dL)

≥1.6 mmol/L (60.00 mg/dl)

Classification

Low (undesirable, High risk)

High (desirable, Low risk)

{6}

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

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