Albumin BCP

K193001 · SENTINEL CH. SpA · CJW · Dec 19, 2019 · Clinical Chemistry

Device Facts

• Record ID: K193001
• Device Name: Albumin BCP
• Applicant: SENTINEL CH. SpA
• Product Code: CJW · Clinical Chemistry
• Decision Date: Dec 19, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1035
• Device Class: Class 2

Indications for Use

The Albumin BCP assay is an in vitro diagnostic test used for the determination of albumin in human serum or plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases primarily involving the liver or kidneys. The assay is intended for professional use only. For In Vitro Diagnostic use only.

Device Story

Albumin BCP is an in vitro diagnostic reagent for quantitative albumin measurement in human serum or plasma. The device utilizes a colorimetric bromcresol purple (BCP) dye-binding method; albumin reacts with BCP at pH 5.0–5.5 to form a colored complex. The intensity of this complex, measured at 600/700 nm, is proportional to albumin concentration. The assay is intended for professional use in clinical laboratories using the AU680 Automatic Analyzer. Healthcare providers use the resulting albumin concentration to assist in diagnosing and monitoring liver and kidney diseases. The device is supplied as a ready-to-use liquid reagent.

Clinical Evidence

Bench testing only. Performance evaluated per CLSI guidelines (EP05-A3, EP06-A, EP17-A2, EP15-A3, EP07). Precision studies (N=60-240) showed total %CV between 1.6% and 2.2%. Linearity confirmed across 4.2–78.7 g/L. Method comparison (N=128) against predicate yielded a correlation coefficient (r) of 0.992. Matrix comparison (N=77) confirmed equivalency for lithium heparin and K2EDTA plasma. No clinical studies were performed.

Technological Characteristics

Colorimetric dye-binding assay using bromcresol purple. Reagents: acetate buffer (6.8%), stabilizer (4.38%), BCP (0.028%), detergent (0.045%), sodium azide (<0.1%). Liquid format. Standardized to ERM-DA 470k/IFCC. Operates on AU680 Automatic Analyzer. Measuring range 6.0–70 g/L. Reagent storage 15-30 °C.

Indications for Use

Indicated for the quantitative determination of albumin in human serum or plasma for the diagnosis and treatment of liver or kidney diseases. Intended for professional use only.

Regulatory Classification

Identification

An albumin test system is a device intended to measure the albumin concentration in serum and plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

Predicate Devices

• ADVIA Chemistry BCP assay (ALBP) (k132664)

Submission Summary (Full Text)

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FDA

U.S. FOOD &amp; DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K193001

B Applicant

Sentinel CH. SpA

C Proprietary and Established Names

Albumin BCP

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CJW | Class II | 21 CFR 862.1035 - Albumin Test System | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:

New Device

B Measurand:

Albumin

C Type of Test:

Colorimetric

## III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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## B Indication(s) for Use:

The Albumin BCP assay is an in vitro diagnostic test used for the determination of albumin in human serum or plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases primarily involving the liver or kidneys.

The assay is intended for professional use only.

For In Vitro Diagnostic use only.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

## D Special Instrument Requirements:

AU 680 Automatic Analyzer

## IV Device/System Characteristics:

### A Device Description:

Albumin BCP reagent is ready to use liquid reagent that is supplied in two configurations: fill volume of 20 mL in a 20 mL wedge or 50 mL in a 50 mL wedge, 6 wedges/kit. The ingredients in the reagent are acetate buffer (6.8%), stabilizer (4.38%), bromocresol purple (0.028%), detergent (0.045%), and sodium azide (&lt;0.1%).

### B Principle of Operation:

Albumin is measured using the colorimetric method where at pH 5.0 – 5.5, albumin reacts with bromocresol purple (BCP) forming a colored complex. The color intensity of this complex is proportional to the concentration of albumin present in the sample measurement as an endpoint reaction at 600/700nm.

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

ADVIA Chemistry Albumin BCP Reagent (ALBP)

### B Predicate 510(k) Number(s):

K132664

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C Comparison with Predicate(s):

| Device & Predicate Device(s): | K193001 | K132664 |
| --- | --- | --- |
| Device Trade Name | Albumin BCP | ADVIA Chemistry Albumin BCP assay (ALBP) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Determination of albumin in human serum and plasma. | Same |
| Measurement | Quantitative | Same |
| Specimen Types | Serum and Plasma | Same |
| Reagent | Single reagent | Same |
| Reagent | Liquid | Same |
| Principle | Colorimetric | Same |
| Standardization | ERM-DA 470k Reference Material | Same |
| General Device Characteristic Differences | | |
| Analytical Assay Range | 6.0 – 70.0 g/L | 6.0 – 80.0 g/L |
| Reference value | 35-52 g/L | 34 -50 g/L |

VI Standards/Guidance Documents Referenced:

- CLSI - EP05-A3: Evaluation of precision of Qualitative Measurement Procedures; Approved Guideline – Third Edition
- CLSI - EP06-A: Evaluation of linearity of Quantitative of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- CLSI – EP17-A2: Evaluation of detection Capability for Clinical Laboratory Measurement procedures; Approved Guidance -Second Edition
- CLSI – EP15-A3: User Verification of Precision and Estimation of Bias; Approved Guideline – Third Edition
- CLSI – EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guidance

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

The precision was determined based on recommendations in CLSI EP05-A3 guideline.

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Within run precision was established by testing two human serum-based control samples and one human serum sample pool. Each sample was tested in 20 replicates per run, for 3 runs for a total of 60 replicates per sample. Testing was performed on one AU680 Automatic analyzer using 3 reagent lots. The results for one representative lot are summarized in the table below.

| Sample | N | Mean (g/L) | SD | %CV |
| --- | --- | --- | --- | --- |
| Level 1 | 60 | 21.5 | 0.2 | 0.9 |
| Level 2 | 60 | 35.6 | 0.3 | 0.7 |
| Level 3 | 60 | 50.3 | 0.2 | 0.4 |

Within-laboratory precision was established by testing one human serum pool and two human serum-based control samples. Testing was performed for 20 days, 2 runs per day, 2 replicates per run for a total of 80 replicates per sample and a total of 240 total replicates. Testing was performed on one AU680 Automatic analyzer using four lots of reagents.

The results for one representative lot are summarized in the table below:

| Sample | N | Mean (g/L) | Total %CV |
| --- | --- | --- | --- |
| Level 1 | 80 | 26.6 | 2.2 |
| Level 2 | 80 | 40.7 | 2.1 |
| Level 3 | 80 | 50.5 | 1.6 |

## 2. Linearity:

The linearity studies were performed following the CLSI EP06-A guideline. The studies were performed on one AU680 analyzer using serum samples spiked with human albumin. Low and high concentration pools were mixed and serial dilution samples (N=12) were prepared and tested in triplicate. The results from each of three reagent lots were compared to expected values. All three lots yielded similar results. The results of the linear regression analysis from one representative lot run are summarized below:

| Sample range tested (g/L) | Slope | Intercept | Claimed measuring range (g/L) |
| --- | --- | --- | --- |
| 4.2 – 78.7 | 1.0 | 0.999 | 6.0 -70.0 |

The linear regression results support the claimed measuring range.

## 3. Analytical Specificity/Interference:

Interference studies were performed according to the CLSI EP07 guideline.

Two serum pools were created with albumin concentrations of 35 g/L and 50 g/L, which were spiked with potentially interfering substances. Results from the spiked samples were compared to results from the same serum sample pools without addition of the potential interferents (control samples). Significant interference was defined as more than ±10% bias from the test results of the spiked sample when compared to the control sample. The following substances did not cause interference at the concentrations listed below:

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| Interferent | Highest concentration tested that did not cause significant interference |
| --- | --- |
| Hemoglobin | 2000 mg/dL |
| Unconjugated bilirubin | 66 mg/dL |
| Conjugated bilirubin | 66 mg/dL |
| Lipids (triglycerides | 1200 mg/dL |

The sponsor includes the following limitations for potential interferences in their labeling:

- CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid) present in sera of patients with renal failure has been reported to give falsely low albumin values.
- Negative bias of approximately 10 % has been observed on samples from patients undergoing hemodialysis. Samples from patients with elevated serum creatinine levels, or undergoing treatment with peritoneal dialysis, were unaffected.

4. Assay Reportable Range:

6.0 – 70.0 g/L

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The assay is traceable to ERM-DA 470k Reference Material.

6. Detection Limit:

Detection limit studies for were evaluated based upon CLSI EP17-A2 guideline.

Limit of blank (LoB) studies were performed by testing 4 blank samples. Samples were tested in replicates of 5 over 3 days, using 3 lots of reagents for a total of 60 results per lot. LoB was defined as the highest result that can reasonably be expected from a blank sample for a given error probability with α=0.05. The highest LoB of the three lots is reported as the LoB in the labeling.

Limit of detection (LoD) studies were performed by testing 4 serum pool samples with low analyte concentrations approximately 4-fold higher than the LoB. Samples were tested in replicates of 5 over 3 days, using 3 lots of reagents, for a total of 60 results per lot. LoD was calculated using the following equation: LoD= LoB + (SD x 1.652). The highest LoD of the three lots is reported as the LoD in the labeling.

Limit of Quantitation studies were performed using 8 samples which were generated by diluting a sample with an album in concentration of 12 g/L. Each of the 8 samples were tested in 10 replicates over 3 days using 3 reagent lots for a total of 240 replicates per lot. The sponsor defines LoQ as the concentration corresponding to a coefficient of variation of 20%. The highest LoQ of the three lots is reported as the LoQ in the labeling.

The results are summarized in the table below:

| LoB | LoD | LoQ |
| --- | --- | --- |
| 0.3 g/L | 0.8 g/L | 1.5 g/L |

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7. Assay Cut-Off:
Not applicable.

8. Accuracy (Instrument):
Not applicable.

9. Carry-Over:
Not applicable.

## B Comparison Studies:

### 1. Method Comparison with Predicate Device:

A method comparison study was performed by testing 128 serum samples spanning the entire claimed assay range. Eight samples were contrived. Each sample was run in duplicate on the predicate device (ADVIA Chemistry Albumin BCP on the Siemens ADVIA 2400) and singlicate on the candidate device (Albumin BCP on the AU680 Automatic analyzer). The singlicate test result from candidate test system was compared to the average of the results from the comparator method using Passing-Bablok analysis. The results are summarized in the table below:

| Slope | Intercept | Correlation coefficient (r) | N | Sample concentration range tested (g/L) |
| --- | --- | --- | --- | --- |
| 0.94 | 1.01 | 0.992 | 128 | 7.8 – 67.1 |

### 2. Matrix Comparison:

A matrix comparison study was performed to demonstrate lithium heparin plasma and K2EDTA plasma equivalency to serum. A total of seventy-seven matched sample pairs were tested. Results obtained with serum samples using Albumin BCP on one AU680 were compared results obtained from either lithium heparin plasma or K2EDTA plasma samples. The table below summarizes the Passing-Bablok linear regression results:

| Specimen Type | N | Slope | Intercept | r | Sample range tested (g/L) |
| --- | --- | --- | --- | --- | --- |
| Lithium heparin plasma | 77 | 1.012 | -0.3395 | 0.995 | 13.4 – 65.7 |
| K2EDTA plasma | 77 | 1.00 | -0.200 | 0.996 | 13.4 – 65.7 |

The study results support the sponsor's claim that human serum and plasma (K2EDTA and lithium heparin) are acceptable sample types to be used with this assay.

## C Clinical Studies:

### 1. Clinical Sensitivity:

Not applicable.

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2. Clinical Specificity:

Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Not Applicable.

D Clinical Cut-Off:

Not applicable.

E Expected Values/Reference Range:

Expected values for the Albumin BCP assay are cited from literature*:

Adults (&lt; 60 years): 35 - 52 g/L

* Burtis CA, Ashwood ER, Bruns DE, editors. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th ed. St. Louis, MO: Elsevier Saunders; 2012:2148).

The sponsor recommends that each laboratory should establish its own reference ranges.

F Other Supportive Instrument Performance Characteristics Data:

Not applicable.

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

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

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