TOTAL BILIRUBIN REAGENT SET

K040391 · Pointe Scientific, Inc., · CIG · Jun 2, 2004 · Clinical Chemistry

Device Facts

• Record ID: K040391
• Device Name: TOTAL BILIRUBIN REAGENT SET
• Applicant: Pointe Scientific, Inc.,
• Product Code: CIG · Clinical Chemistry
• Decision Date: Jun 2, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

This product is to be used in a diagnostic laboratory setting, by qualified laboratory personnel, for the quantitative determination of direct and total bilirubin in human serum. It is intended for in vitro diagnostic use only. Studies suggest that direct and total bilirubin measurements provide information to assist in the assessment of liver function and conditions such as hemolytic and obstructive jaundice.

Device Story

Pointe Scientific Direct and Total Bilirubin assays are quantitative colorimetric reagents for use on Hitachi clinical chemistry analyzers. Input: human serum samples. Principle: bilirubin couples with diazonium salt (DPD) in acidic medium to form azobilirubin; measured spectrophotometrically. Output: bilirubin concentration (mg/dL). Used in diagnostic laboratories by qualified technologists. Results assist clinicians in assessing liver function and conditions like hemolytic or obstructive jaundice.

Clinical Evidence

No clinical data provided; device relies on analytical performance characteristics typical of in vitro diagnostic test systems.

Technological Characteristics

Quantitative colorimetric assay. Reagents: liquid, ready-to-use, containing acid buffers and DPD stabilizers. Sensing: spectrophotometric measurement of azobilirubin. Form factor: reagent kits for automated clinical chemistry analyzers (Hitachi 704, 717, 747, 911, 912).

Indications for Use

Indicated for the quantitative determination of direct and total bilirubin in human serum to assist in the assessment of liver function and conditions such as hemolytic and obstructive jaundice in a clinical laboratory setting.

Regulatory Classification

Identification

A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Predicate Devices

• Roche Total Bilirubin Reagent (K910591)
• Roche Direct Bilirubin Reagent (K910593)

Submission Summary (Full Text)

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

A. 510(k) Number:
K040391

B. Purpose for Submission:
Clearance of two sets of secondary reagents

C. Analyte:
Total and Direct Bilirubin

D. Type of Test:
Quantitative Colorimetric Assay

E. Applicant:
Pointe Scientific, Inc.

F. Proprietary and Established Names:
Hitachi Direct Bilirubin Reagent
Hitachi Total Bilirubin Reagent

G. Regulatory Information:
1. Regulation section:
21 CFR § 862.1110, Bilirubin (total or direct) test system
2. Classification:
Class II
3. Product Code:
CIG, Diazo Colorimetry, Bilirubin
4. Panel:
Clinical Chemistry (75)

H. Intended Use:
1. Intended use(s):
The Pointe Scientific Direct and Total Bilirubin assays are to be used in a diagnostic laboratory setting, by qualified laboratory technologists, for the quantitative determination of Direct or Total Bilirubin in human serum. They are intended for in vitro diagnostic use only.

Direct and Total bilirubin measurements provide information to assist in assessment of liver function and conditions such as hemolytic and obstructive jaundice.

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2. Indication(s) for use:
See intended use

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

4. Special instrument Requirements:
Hitachi clinical chemistry analyzers (validated on Hitachi 704, 717, 747, 911, 912 analyzers)

I. Device Description:

Both the Total and Direct bilirubin reagents consist of two ready-to-use liquid reagents (see device comparison below for information on their make-up).

J. Substantial Equivalence Information:

1. Predicate device name(s):
Roche Total Bilirubin Reagent and Roche Direct Bilirubin Reagent

2. Predicate K number(s):
K910591 and K910593, respectively

3. Comparison with predicate:

The devices share the same intended use with their predicates.

Total Bilirubin:

| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay Range | 0 – 30 mg/dL | 0 – 20 mg/dL |
| Reagents | Reagent 1: Acid buffer 50 mmol/L
Reagent 2: Acid Buffer >30 mmol/L, >2.0 mmol/L DPD Stabilizers | Reagent 1: Sulfanilic Acid 32.2 mmol/L, DMSO, Ethylene glycol, buffers, stabilizers
Reagent 2: Sodium Nitrite 109 mmol/L, buffers, fillers, stabilizers |

Direct Bilirubin:

| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay range | 0 – 10 mg/dL | 0 – 20 mg/dL |
| Reagents | Reagent 1: Acid buffer 50 mmol/L
Reagent 2: Acid Buffer >30 mmol/L, >2.0 mmol/L DPD Stabilizers | Reagent 1: Hydrochloric acid 0.05 mol/L
Reagent 2: Sulfanilic acid 25.7 mmol/L, Hydrochloric acid 0.7 mol/L, Sodium Nitrite 2.7 mmol/L, Sodium Bicarbonate 13.9 mmol/L |

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

NCCLS Guideline EP5-A - Evaluation of Precision Performance of Clinical Chemistry Devices

# L. Test Principle:

Azobilirubin is produced when bilirubin in the sample is coupled with a diazonium salt (DPD) in a strongly acidic medium. The amount of azobilirubin produced can be measured spectrophotometrically and is proportional to the bilirubin concentration in the sample.

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

1. Analytical performance:

a. Precision/Reproducibility:

Assay imprecision was tested according to NCCLS Guideline EP5-A. Samples were assayed in duplicate twice per day for 20 days. Results are summarized below (units = mg/dL):

Total Bilirubin:

| | Within Day | | | Total | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | % CV | Mean | SD | % CV |
| Sample 1 | 1.0 | 0.037 | 3.61 | 1.0 | 0.043 | 4.24 |
| Sample 2 | 5.8 | 0.060 | 1.04 | 5.8 | 0.085 | 1.46 |

Direct Bilirubin:

| | Within Day | | | Total | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | % CV | Mean | SD | % CV |
| Sample 1 | 1.0 | 0.0042 | 2.01 | 1.9 | 0.088 | 4.57 |
| Sample 2 | 5.5 | 0.074 | 1.35 | 5.8 | 0.082 | 1.51 |

b. Linearity/assay reportable range:

To evaluate assay linearity, samples from a commercially available linearity set were assayed in duplicate and the mean recovered value was plotted against the expected value. Results are summarized as follows:

Total Bilirubin: Observed = (0.99703)Expected + 0.23428

Range Tested = 0.5 to 20.5 mg/dL

Direct Bilirubin: Observed = (1.0241)Expected - 0.38489

Range Tested = 0.5 to 20.5 mg/dL

The reportable range of the Total Bilirubin assay is 0.1 to 30 mg/dL. The reportable range of the Direct Bilirubin assay is 0.1 to 10 mg/dL. Assay results for both assays that are below 0.1 should be reported as <0.1 mg/dL.

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

The package insert recommends that quality control be performed using control sera with known bilirubin values.

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d. Detection limit:

The sensitivity of the assay is defined as the $\Delta A / \mathrm{mg} / \mathrm{dL}$ and is $0.086 / \mathrm{mg} / \mathrm{dL}$ for the Total Bilirubin assay and $0.016 / \mathrm{mg} / \mathrm{dL}$ for the Direct Bilirubin assay.

e. Analytical specificity:

Non-interference is defined as recovery within +/- 10%:

Triglycerides up to $1000\mathrm{mg / dL}$ and Hemoglobin up to $500\mathrm{mg / dL}$ do not significantly interfere with the Total Bilirubin assay.

Triglycerides up to $500\mathrm{mg / dL}$ and Hemoglobin up to $100\mathrm{mg / dL}$ do not significantly interfere with the Direct Bilirubin assay.

f. Assay cut-off: Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Total Bilirubin:

Seventy-six (76) serum samples (2 controls, 5 linearity standards, 11 spiked serum samples, 48 normal samples, and 10 elevated samples) were evaluated on the device and the predicate. Samples with concentrations above the useable range of the predicate device were diluted 1:1 with saline for measurement on the predicate assay. The resulting regression statistics were Device = 1.01(Predicate) + 0.09, r = 0.999.

Direct Bilirubin:

Sixty-two (62) serum samples (2 controls, 3 linearity standards, 5 spiked serum samples, 48 normal samples, and 4 elevated samples) were evaluated on the device and the predicate. The resulting regression statistics were Device = 1.02(Predicate) - 0.07, r = 0.996.

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

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5. Expected values/Reference range:

Total Bilirubin:
Adults and Infants older than 1 month: 0.2 – 1.0 mg/dL
Infants: Full Term Newborn
Up to 24hrs: 2.0 to 6.0 mg/dL
Up to 48 hrs: 6.0 to 10.0 mg/dL
Days 3-5: 4.8 to 8.0 mg/dL
Direct Bilirubin:
Adults and Infants older than 1 month: 0 – 0.5 mg/dL

The sponsor recommends that laboratories establish their own normal reference ranges for their demographics.

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