SYNCHRON SYSTEMS MICROALBUMIN (MA) REAGENT, MODEL 475100

K082251 · Beckman Coulter, Inc. · DCF · Apr 8, 2009 · Immunology

Device Facts

• Record ID: K082251
• Device Name: SYNCHRON SYSTEMS MICROALBUMIN (MA) REAGENT, MODEL 475100
• Applicant: Beckman Coulter, Inc.
• Product Code: DCF · Immunology
• Decision Date: Apr 8, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5040
• Device Class: Class 2

Indications for Use

MA reagent, when used in conjunction with SYNCHRON CX® System(s) and SYNCHRON CX® MA Calibrator, is intended for the quantitative determination of albumin (MA) concentration in human urine. Measurement of albumin in urine aids in the diagnosis of kidney dysfunction.

Device Story

The SYNCHRON Systems Microalbumin (MA) Reagent is an in vitro diagnostic reagent used on SYNCHRON CX systems to measure albumin concentration in human urine. The device utilizes a turbidimetric method where albumin in the urine sample reacts with a goat anti-human albumin polyclonal antibody to form insoluble antigen-antibody complexes. The system automatically proportions one part sample to 24 parts reagent into a cuvette and monitors the change in absorbance at 380 nm. This absorbance change is proportional to the albumin concentration, which the system calculates using a non-linear calibration curve. The device is intended for use in clinical laboratory settings by trained personnel. Results assist healthcare providers in diagnosing kidney dysfunction by identifying elevated albumin levels in urine.

Clinical Evidence

No clinical data. Analytical performance demonstrated via bench testing on the CX4 CE system. Precision studies (N=80) showed total CVs ranging from 1.5% to 16.3%. Linearity confirmed across 0.2-30 mg/dL (R²=0.9997). Method comparison against predicate (N=111) yielded Y = 0.990X - 0.11 (r=0.987). Interference testing confirmed no significant interference from common substances (ascorbic acid, creatinine, glucose, etc.). LoB < 0.1 mg/dL; LoD < 0.2 mg/dL.

Technological Characteristics

Turbidimetric immunoassay; goat anti-human albumin polyclonal antibody; phosphate buffer with PEG; 380 nm absorbance detection; non-linear calibration curve; automated sample/reagent proportioning (1:24 ratio).

Indications for Use

Indicated for the quantitative determination of albumin concentration in human urine to aid in the diagnosis of kidney dysfunction. No specific age or gender restrictions provided.

Regulatory Classification

Identification

An albumin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the albumin (a plasma protein) in serum and other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases.

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

Predicate Devices

• IMMAGE Immunochemistry Systems Microalbumin (MA) Reagent (K965035)

Submission Summary (Full Text)

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

A. 510(k) Number:
k082251

B. Purpose for Submission:
New device

C. Measurand:
Urine Albumin (microalbumin)

D. Type of Test:
Quantitative, turbidimetric method

E. Applicant:
Beckman Coulter, Inc.

F. Proprietary and Established Names:
SYNCHRON® Systems Microalbumin (MA) Reagent

G. Regulatory Information:
1. Regulation section:
21 CFR 866.5040
2. Classification:
Class II
3. Product code:
DCF
4. Panel:
Immunology (82)

H. Intended Use:
1. Intended use(s):
See Indication for use below.

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2. Indication(s) for use:
MA reagent, when used in conjunction with SYNCHRON CX® System(s) and SYNCHRON CX® MA Calibrator, is intended for the quantitative determination of albumin (MA) concentration in human urine. Measurement of albumin in urine aids in the diagnosis of kidney dysfunction

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

4. Special instrument requirements:
SYNCHRON CX4 system.

I. Device Description:
The SYNCHRON® System Microalbumin (MA) Reagent kit consists of the following:

Reagents:
1. Reagent A: Reaction Buffer, in a 33 mL cartridge.
2. Reagent B: MA antibody specific (goat) for human albumin, in a 7.2 mL cartridge.

Calibrators:
SYNCHRON CX Systems MA Calibrator set (previously cleared – k994325) consists of 6 levels of calibrators (Levels 1- 6, 1 x 3 mL bottles), for use on SYNCHRON CX Systems only. MA Calibrator is designed for the generation of a 6-point calibration curve which defines the analytical range for the SYNCHRON Systems MA assay. The calibrator is prepared with pH buffered human serum albumin.

Each serum or plasma donor unit used in the preparation of this material was tested by US FDA approved methods and found to be negative for antibodies to HIV and HCV and nonreactive for HbsAg.

J. Substantial Equivalence Information:
1. Predicate device name(s):
IMMAGE Immunochemistry Systems Microalbumin (MA) Reagent
2. Predicate 510(k) number(s):
K965035

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3. Comparison with predicate:
Similarities and Differences between the predicate device and the candidate device:

| Attribute | IMMAGE Immunochemistry Systems Microalbumin (MA) Reagent (Predicate device) | SYNCHRON® Systems Microalbumin (MA) Reagent (Candidate device) |
| --- | --- | --- |
| Intended Use | For the quantitative determination of micro quantities of albumin (MA) in human urine by nephelometry. Measurement of microalbumin in urine aids in the diagnosis of kidney diseases. | For the quantitative determination of albumin in human urine by turbidimetric method. Measurement of albumin in urine aids in the diagnosis of kidney dysfunction. |
| Antibodies | Goat anti-human albumin polyclonal Antibodies | Same |
| Buffer | Phosphate buffer with PEG | Same |
| Calibration | Use single point adjusted non-linear calibration | Same |
| Initial measuring range | 0.2-4.0 mg/dL | 0.2-30 mg/dL |
| Extended measuring range | 4-864 mg/dL | 24-97 mg/dL |

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

CLSI EP05-A - Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline.
CLSI EP06-A2 - An Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
CLSI EP17-A - Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
CLSI EP07-A2 – Interference testing in Clinical Chemistry; Approved Guideline
EN ISO 17511 - In vitro diagnostic medical devices -- Measurement of quantities in biological samples -- Metrological traceability of values assigned to calibrators and control materials

L. Test Principle:

MA reagent is used to measure the albumin concentration by a turbidimetric method. In the reaction, albumin combines with specific antibody to form insoluble antigen-antibody complexes. The Synchron System(s) automatically proportions the appropriate sample and reagent volumes into the cuvette. The ratio used is one part sample to 24 parts reagent. The system monitors the change in absorbance at 380

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nanometers. This change in absorbance is proportional to the concentration of albumin in the sample and is used by the system to calculate and express albumin concentration based upon a non-linear calibration curve.

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

Analytical performance was demonstrated on the CX4 CE system.

## 1. Analytical performance:

### a. Precision/Reproducibility:

Precision studies were designed according to the CLSI EP05-A guideline. Three levels of urine control materials were measured twice a day in duplicates for 20 days (N=80). The results are summarized below:

**Synchron CX4:**

| Sample ID | Mean (mg/dL) | Within-run S.D. (mg/dL) | Total S.D. (mg/dL) | Within-run (CV %) | Total (CV %) |
| --- | --- | --- | --- | --- | --- |
| Level 1 | 0.8 | 0.08 | 0.13 | 9.7 | 16.3 |
| Level 2 | 3.0 | 0.14 | 0.23 | 4.5 | 7.5 |
| Level 3 | 40.1 | 0.42 | 0.59 | 1.0 | 1.5 |

### b. Linearity/assay reportable range:

The claimed measuring range for the device is 0.2-30 mg/dL.

Linearity studies were designed according to the CLSI EP06-A guideline. A high patient urine sample was used to prepare 7 different levels of microalbumin concentration. All samples were measured 4 times on the CX4CE analyzer. Concentration of samples ranged from 0.2 mg/dL to 30 mg/dL (0.2, 0.3, 0.45, 0.6, 1, 3, 6, 12, 18, 24, and 30). An appropriate line was fitted by standard linear regression and the following slope and R² measurements were obtained.

| Analyzer | Regression equation for linearity | R² |
| --- | --- | --- |
| CX4CE | y = 1.031x- 0.1482 | 0.9997 |

Extended measuring range studies (ORDAC) were performed using 8 concentrations ranging from 20-100 mg/dL (20, 25, 30, 40, 60, 80 and 100).

The sponsor claimed that the reportable range is 0.2 to 30 mg/dL and the extended range is 24 to 90 mg/dL.

| Analyzer | Regression equation for ext. linearity | R² |
| --- | --- | --- |
| CX4CE | y = 0.9726x- 1.3438 | 0.9997 |

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

The SYNCHRON CX® Systems MA Calibrator (six levels) is designed for use on the SYNCHRON CX Systems. Calibrators are traceable to the IFCC

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reference preparation for plasma proteins, BCR-470. Traceability process is based on EN ISO 17511. Traceability statements for the calibrator are included in the instructions for use included with the calibrator kit.

Calibrators are stable between +2°C to +8°C until date of expiration. Exposure of Urine Protein Calibrator to temperatures greater than 32°C (90°F) may adversely affect performance. Once opened, the reagent is stable for 60 days unless the expiration date is exceeded. Users are instructed to not freeze the reagent.

d. Detection limit:

Studies on limit of detection were performed according to CLSI EP17 guideline. Limit of blank (LoB) and Limit of detection(LoD) were determined by using saline (0 mg/dL), protein free urine (0 mg/dL), diluted urine protein control (0.2 mg/dL) and diluted urine protein control (0.3 mg/dL). All samples were run in 10 replicates over a period of six days on the CX4CE analyzer. Limit of Blank (LoB) is less than 0.1 mg/dL. The Limit of Detection (LoD) was calculated using the mean and SD for the low sample measurements:

$$
\mathrm{LoD} = \mathrm{LoB} + 1.653 * \mathrm{SD}
$$

The Limit of Detection (LoD) is less than 0.2 mg/dL.

e. Analytical specificity:

Interference studies were designed according to the CLSI EP7-A2 guideline. Three levels of patient samples or pools were spiked with the known interference substances and analyzed on the Sychron CX 4 CE analyzer. No significant interference was defined as the observed value for Microalbumin values ≤ 2.3 mg/dL is ≤± 0.25 mg/dL and values &gt; 2.3 mg/dL is &lt; 10.8% difference of the expected value (neat sample). The sponsor claimed that there was no significant interference (&lt;10.8% or ≤± 0.25 mg/dL) by the following interferents:

- Ascorbic acid to 500 mg/dL
- Calcium up to 130 mg/dL
- Citrate up to 50 mg/dL
- Creatinine up to 160 mg/dL
- Glucose up to 200 mg/dL
- Magnesium up to 400 mg/dL
- Oxalate up to 30 mg/dL
- Urea up to 140 mg/dL

The sponsor has the following limitations in the labeling:

- Do not use turbid samples. Samples should be centrifuged before testing if they have debris in them.

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- Do not use samples contaminated with blood.
- If serum proteins carryover is suspected, a saline sample should be assayed prior to assaying the patient samples.

f. Assay cut-off:
Not applicable

2. Comparison studies:
a. Method comparison with predicate device:
A method comparison study was performed based on the CLSI EP9-A guideline. A total of 111 urine samples were evaluated using Synchron CX4 (candidate) and IMMAGE (predicate). Deming regression analyses were used to evaluate the correlations between results. Correlation regression is summarized below:

$$Y = 0.990X - 0.11, r = 0.987$$, range of sample tested = 0.2-27 mg/dL (X= IMMAGE and Y= Synchron CX4)

b. Matrix comparison:
Not applicable.

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:
Reference intervals were taken from the literature:

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*Reference: American Diabetes Association Position statement on Diabetic Neuropathy - Diabetes Care (20): S24 – S27.

**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.

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