TINA-QUANT ALBUMIN GEN.2
Device Facts
| Record ID | K113072 |
|---|---|
| Device Name | TINA-QUANT ALBUMIN GEN.2 |
| Applicant | Roche Diagnostics Operations |
| Product Code | DCF · Immunology |
| Decision Date | May 14, 2012 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5040 |
| Device Class | Class 2 |
Indications for Use
The Tina-quant Albumin Gen.2 assay is an immunoturbidimetric assay intended for the quantitative determination of albumin in human urine on Roche/Hitachi cobas c systems. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases.
Device Story
In vitro diagnostic assay; utilizes immunoturbidimetric principle; anti-albumin antibodies react with albumin in human urine samples to form antigen/antibody complexes; agglutination measured turbidimetrically; performed on Roche/Hitachi cobas c 311 analyzers; operated by laboratory personnel; output provides quantitative albumin concentration; aids clinicians in diagnosing kidney and intestinal diseases.
Clinical Evidence
Bench testing only. Precision evaluated over 21 days (n=84/sample) with CVs < 3%. Linearity validated per CLSI EP6-A (slope 0.97, r=0.998). Analytical specificity tested against endogenous interferents (bilirubin, hemoglobin) and common drugs; no interference observed. Method comparison with predicate (n=69) showed good correlation (r=0.972, y=1.04x-0.42).
Technological Characteristics
Immunoturbidimetric assay; utilizes anti-albumin antibodies; reagent stability 12 weeks at 2-8°C; measuring range 12-200 mg/L; automated analysis on Roche/Hitachi cobas c 311 platform; includes prozone check for high-dose hook effect up to 40,000 mg/L.
Indications for Use
Indicated for quantitative determination of albumin in urine to aid in diagnosis of kidney and intestinal diseases. For prescription use only.
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
- Tina-quant Albumin Gen.2 - cobas c 501 urine assay (K101203)
Related Devices
- K983774 — UALB · Abbott Laboratories · Jan 28, 1999
- K101203 — TINA-QUANT ALBUMIN GEN 2 · Roche Diagnostics · Sep 10, 2010
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k113072
B. Purpose for Submission:
New device
C. Measurand:
Albumin (microalbumin) in urine
D. Type of Test:
Quantitative, immunoturbidimetric
E. Applicant:
Roche Diagnostics
F. Proprietary and Established Names:
Tina-quant Albumin Gen.2
G. Regulatory Information:
1. Regulation section:
21 CFR 866.5040, Albumin immunological test system
2. Classification:
Class II
3. Product code:
DCF
4. Panel:
Immunology (82)
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H. Intended Use:
1. Intended use(s):
Refer to indications for use below.
2. Indication(s) for use:
The Tina-quant Albumin Gen. 2 assay is an immunoturbidimetric assay intended for the quantitative determination of albumin in urine on Roche/Hitachi cobas c systems. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases
3. Special conditions for use statement(s):
For prescription use only
4. Special instrument requirements:
Roche/Hitachi Cobas c311 analyzer
I. Device Description:
The Tina-quant Albumin Gen. 2 assay consists of three reagents:
R1 TRIS buffer: 50 mmol/L, pH 8.0; PEG: 4.2 %; EDTA: 2.0 mmol/L; preservative
R2 Polyclonal anti-human albumin antibodies (sheep); TRIS buffer: 100 mmol/L, pH7.2; preservative
R3 Reagent for antigen excess check. Albumin in diluted serum (human); NaCl: 150 mmol/L; phosphate buffer: 50 mmol/L, pH 7.0; preservative
The calibrator is C.f.a.s. PUC (cleared under k050026) and the recommended control materials are Precinorm / Precipath PUC (cleared under k050026) and Precinorm / Precipath Protein (cleared under k981401). The calibrator and controls are sold separately.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Roche Tina-quant albumin gen 2 (Roche/Hitachi Cobas c501 analyzer only)
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2. Predicate 510(k) number(s):
k101203
3. Comparison with predicate:
| Similarities (to urine) | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Indications for Use | Same | Quantitative measurement of albumin in urine. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases. |
| Assay Type | Same | Immunoturbidimetric |
| Detection Limit | Same | Limit of Blank (LoB) 2 mg/L Limit of Detection (LoD) 3 mg/L Limit of Quantitation (LoQ) 12 mg/L |
| Calibrator | Same | C.f.a.s. (Calibrator for Automated Systems) PUC (Proteins in Urine/CSF) |
| Calibration Frequency | Same | Calibrate after reagent lot change and as required following quality control procedures |
| Reagent Stability | Same | On-board in use: 12 weeks at 2-8°C |
| Analytical Specificity | Icterus: No conjugated bilirubin interference was observed up to 50 mg/dL bilirubin. Hemolysis: No hemolysis interference was observed to 400 mg/dL hemoglobin | Icterus: No conjugated bilirubin interference was observed up to an I index of 52. The I Index Value corresponds to approximately 1 mg/dL bilirubin. Hemolysis: No hemolysis interference was observed up to an H index of 487. The H Index Value corresponds approximately to 1 mg/dL hemoglobin |
| Precision performance | Same | Repeatability: CVs < 2% Between Day: CVs < 3% Total: CVs < 3% |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Sample Types | Urine Only | Serum, plasma, urine, and CSF |
| Analyzer | Roche Hitachi Cobas c311 | Roche Hitachi Cobas c501 |
| Measuring Range | 12 – 200 mg/L | 12 – 400 mg/L |
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# K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP5-A2, Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline - 2nd edition
- CLSI EP6, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach
- CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
# L. Test Principle:
The Roche Tina-quant Albumin Gen 2 assay is an immunoturbidimetric assay for the quantitative in vitro determination of albumin in human urine on the Roche/Hitachi cobas c 311 analyzer. The test principle is a particle enhanced immunoturbidimetric assay. Human albumin (the antigen) agglutinates with latex particles coated with anti-albumin antibodies. The precipitate is determined turbidimetrically following agglutination.
# M. Performance Characteristics (if/when applicable):
# 1. Analytical performance:
# a. Precision/Reproducibility:
This data was collected as follows:
Specimen description: urine controls and human urine
Number of analyzers: one
Number of days/reps: two reps/run, two runs/day over 21 days
Lots of reagent used: one
Number of calibrations: one
Operators: one
Repeatability
| Sample type | Urine Control | Urine Control | Human Urine | Human Urine | Human Urine |
| --- | --- | --- | --- | --- | --- |
| n | 84 | 84 | 84 | 84 | 84 |
| Mean (mg/L) | 36.9 | 124.8 | 15.6 | 47.4 | 172.8 |
| SD | 0.260 | 1.592 | 0.241 | 0.500 | 3.056 |
| CV% | 0.70 | 1.28 | 1.54 | 1.05 | 1.77 |
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Intermediate Precision (Between Day)
| Sample type | Urine Control | Urine Control | Human Urine | Human Urine | Human Urine |
| --- | --- | --- | --- | --- | --- |
| n | 84 | 84 | 84 | 84 | 84 |
| Mean (mg/L) | 36.9 | 124.8 | 15.6 | 47.4 | 172.8 |
| SD | 0.567 | 2.183 | 0.227 | 0.624 | 3.170 |
| CV% | 1.54 | 1.75 | 1.46 | 1.32 | 1.83 |
Intermediate Precision (Total)
| Sample type | Urine Control | Urine Control | Human Urine | Human Urine | Human Urine |
| --- | --- | --- | --- | --- | --- |
| n | 84 | 84 | 84 | 84 | 84 |
| Mean (mg/L) | 36.9 | 124.8 | 15.6 | 47.4 | 172.8 |
| SD | 0.731 | 2.779 | 0.362 | 0.897 | 4.580 |
| CV% | 1.98 | 2.23 | 2.32 | 1.89 | 2.65 |
# b. Linearity/assay reportable range:
To determine the linearity of the Tina-quant Albumin Gen.2 cobas c 311 urine assay, two dilution series were prepared using high analyte level native human urine samples. The diluent used was NaCl. Albumin levels were measured and the recovered value was compared to the theoretical value. Pure samples (0% and $100\%$ ) were run n=6, with mean measured value reported. Diluted samples were run n=3 with mean measured values reported.
Data were calculated per EP6-A guidelines. The linearity data were analyzed with regards to linear, quadratic, and cubic polynomials. A linearity check was performed with a first order (linear) regression and then with higher order models (quadratic and cubic).
Linear regression produces the following:
Slope: 0.97 (95% CI 0.96 to 0.98)
Intercept: 0.90 (95% CI -0.31 to 2.10)
Correlation Coefficient: 0.998
The claimed measuring range for the assay is $12 - 200\mathrm{mg / L}$
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The extended measuring range using automated rerun with dilution was validated by performing an experiment comparing the instrument auto-rerun result with a simple manual dilution. Two cobas c 311 analyzers were used. Three samples were manually diluted in triplicate per analyzer and the recoveries were compared to the instrument auto-rerun results. All auto-rerun results were within $\pm 4\%$ of the manual dilution results.
A known high-dose hook effect occurs with this assay. Due to the antigen excess check reagent R3, no unflagged high-dose hook effect should occur up to an albumin concentration of $40,000\mathrm{mg/L}$ in urine samples. The sponsor verified the correct flagging with 2 serially spiked samples up to $41,000\mathrm{mg/L}$ analyzed on the cobas c311 analyzer.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The C.f.a.s. PUC calibrator, Precinorm PUC/Precipath PUC and Precinorm Protein/Precipath Protein controls are traceable to the reference preparation IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in Human Serum).
d. Detection limit:
The analytical limits at low levels are as follows:
Limit of Blank $2\mathrm{mg/L}$
Limit of Detection $3\mathrm{mg/L}$
Limit of Quantitation $12\mathrm{mg/L}$
e. Analytical specificity:
The effects of endogenous interference on the quantitation of albumin by the Tina-quant Albumin Gen.2 cobas c 311 urine assay were determined on the cobas c 311 analyzer. Pooled human urine samples were spiked with varying levels of interferents. The resulting sample series (ten dilution steps per sample) were tested in triplicate and the median values used to calculate recovery, by comparing the measured albumin concentration to the expected albumin concentration (which is the albumin concentration when no interferent was added). All recoveries were within $\pm 10\%$.
The following compounds were tested at the concentrations listed:
Conjugated bilirubin 69 mg/dL
Hemoglobin 788 mg/dL
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| Acetone | 60 mmol/L |
| --- | --- |
| Ammonium chloride | 6.4 g/L |
| Calcium | 40 mmol/L |
| Creatinine | 20 g/L |
| γ-globulin | 500 mg/L |
| Glucose | 35.0 g/L |
| Urea | 800 mmol/L |
| Uric acid | 1.2 g/L |
| Urobilinogen | 200 mg/L |
No interference was found at therapeutic concentrations of the following drugs in urine.
- Acetaminophen
- N-Acetyl cysteine
- Salicyluric Acid
- Ascorbic Acid
- Calcium dobesilate
- Na2-Cefoxitin
- Gentamycin Sulfate
- Ibuprofen
- Levodopa
- Methyldopa
- Ofloxacin
- Phenzopyridine
- Doxycycline
f. Assay cut-off:
Not applicable
2. Comparison studies:
a. Method comparison with predicate device:
The Tina-quant Albumin Gen.2 was compared to the predicate device. All samples were tested in singlicate by the new device and the predicate device. There were no retests or discards. Linear regression using Passing-Bablock produced the following:
$$
n = 69
$$
$$
y = 1.04x - 0.42
$$
$$
\text{Pearson's } r = 0.972
$$
Sample concentration range: $13.0 - 189.6\ \mathrm{mg/L}$
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b. Matrix comparison:
Not applicable. This device is only being cleared for urine on the c311 at this time.
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:
2nd morning urine:¹
Adults:
< 20 mg albumin/g creatinine or
< 2.26 g (34.35 μmol) albumin/mol creatinine
Children (3-5 years):²
< 20 mg/L (0.304 μmol/L, 2 mg/dL) albumin
< 37 mg albumin/g creatinine
24-hour urine:³
< 20 mg/L (0.304 μmol/L, 2 mg/dL)
< 30 mg/24 h (0.456 μmol/24 h)
1. Hofmann W, Guder WG. A diagnostic program for quantitative analysis of proteinuria. J Clin Chem Clin Biochem 1989;27:589-600.
2. Hubbuch A. Results of a multicenter study of provisional reference ranges for albumin in urine of children and adults. Roche publication.
3. Hasslacher CH. Aid Endokrin Stoffw 1989;10:60-63.
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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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