Mission Urinalysis Reagent Strips (Microalbumin/Creatinine)
Device Facts
| Record ID | K150330 |
|---|---|
| Device Name | Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) |
| Applicant | ACON Laboratories, Inc. |
| Product Code | JIR · Clinical Chemistry |
| Decision Date | Apr 30, 2015 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1645 |
| Device Class | Class 1 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K150330 · Apr 30, 2015 | Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) | ACON Laboratories, Inc. | Clinical site patient urine specimens | Clinical accuracy study comparing the Mission Urinalysis Reagent Strips to a predicate device using 390 patient urine specimens collected at three clinical sites. | Clinical accuracy; Point-of-care; Urine specimens |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Comparative clinical accuracy study | Patients at three clinical sites; Sample Size: 390 urine specimens; Number of Sites: 3 | CLINITEK Microalbumin Reagent Strips (K972706) | Agreement of Albumin-to-Creatinine (A:C) ratios |
Indications for Use
The Mission Urinalysis Reagent strips (Microalbumin/Creatinine) are intended for the semi quantitative measurement of albumin and creatinine in urine samples using the Mission U120 Urine Analyzer. These measurements are used to assist diagnosis for kidney function. It is intended for professional use only at point-of-care locations.
Device Story
Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) are firm plastic strips with two reagent pads for semi-quantitative detection of albumin and creatinine in urine. Used with Mission U120 Urine Analyzer; a reflectance photometer. Strips are dipped in urine; analyzer measures light intensity/color reflected from pads. Albumin detected via dye-binding (sulfonephthalein); creatinine detected via peroxidase-like activity of copper-creatinine complex. System calculates albumin-to-creatinine ratio. Used at point-of-care by professionals; results available within one minute. Assists clinicians in assessing kidney function and screening for microalbuminuria. Benefits include rapid, point-of-care diagnostic information for early detection of kidney damage.
Clinical Evidence
Clinical study of 390 urine specimens compared Mission Urinalysis Reagent Strips (read by Mission U120) against the predicate device. Overall exact agreement for positive albumin results was 89.2%, with 100% agreement within ±1 block. Agreement for A:C ratio cutoffs (<30 mg/g) was 94.3% (positive) and 91.6% (negative). Precision studies (within-run and between-run) showed >99% agreement with target concentrations. Interference studies evaluated common substances (e.g., Hemoglobin, Human IgG) per EP7-A2 guidelines.
Technological Characteristics
Plastic reagent strips with two pads. Microalbumin pad: bis(3',3''-diiodo-4',4''-dihydroxy-5',5''-dinitrophenyl)-3,4,5,6-tetrabromosulfonephthalein. Creatinine pad: copper acetate, diisopropylbenzene dihydroperoxide, 3,3',5,5'-tetramethylbenzidine. Colorimetric sensing principle. Requires Mission U120 Urine Analyzer for readout. Storage: 2-30°C. Shelf life: 24 months closed, 3 months opened.
Indications for Use
Indicated for professional use at point-of-care locations to assist in the diagnosis of kidney function by measuring albumin and creatinine in urine samples.
Regulatory Classification
Identification
A urinary protein or albumin (nonquantitative) test system is a device intended to identify proteins or albumin in urine. Identification of urinary protein or albumin (nonquantitative) is used in the diagnosis and treatment of disease conditions such as renal or heart diseases or thyroid disorders, which are characterized by proteinuria or albuminuria.
Predicate Devices
- CLINITEK Microalbumin Reagent Strips (k972706)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k150330
B. Purpose for Submission:
New device
C. Measurand:
Urine Creatinine and Albumin
D. Type of Test:
Semi-quantitative colorimetric reagent strip test
E. Applicant:
Acon Laboratories, Inc.
F. Proprietary and Established Names:
Mission Urinalysis Reagent Strips (Microalbumin/Creatinine)
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JIR | I | 21 CFR §862.1645
Urinary protein or albumin (nonquantitative) test system | Chemistry (75) |
| JFY | II | 21 CFR §862.1225
Creatinine test system | Chemistry (75) |
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H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:
The Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) are intended for the semi-quantitative measurement of albumin and creatinine in urine samples using the Mission U120 Urine Analyzer. These measurements are used to assist diagnosis for kidney function. It is intended for professional use only at point-of-care locations.
3. Special conditions for use statement(s):
For prescription use only.
For point-of-care use.
Not for visual read.
4. Special instrument requirements:
Mission U120 Urine Analyzer (k070929)
I. Device Description:
The Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) are plastic strips that contain two reagent pads to test for small amounts of albumin in urine (microalbuminuria), creatinine in urine, and also to determine the albumin-to-creatinine ratio in urine. The strip results are read on the Mission U120 Urine Analyzer (k070929). The product is packaged with a desiccant pack in a plastic bottle.
Composition of the Mission Urinalysis Reagent Strips (Microalbumin/Creatinine):
| Key Components | Material/Description |
| --- | --- |
| Microalbumin Pad | bis(3',3''-diiodo-4',4''-dihydroxy-5',5''-dinitrophenyl)-3,4,5,6-tetrabromosulfonephthalein; buffer; non-reactive ingredients |
| Creatinine Pad | copper acetate; diisopropylbenzene dihydroperoxide; 3,3',5,5'-tetramethylbenzidine; buffer; nonreactive ingredients |
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J. Substantial Equivalence Information:
1. Predicate device name(s):
CLINITEK Microalbumin Reagent Strips read on Clinitek Status Analyzer
2. Predicate 510(k) number(s):
k972706
3. Comparison with predicate:
| Similarities and Differences | | |
| --- | --- | --- |
| Item | Proposed Device Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) | Predicate Device CLINITEK Microalbumin Reagent Strips (k972706) |
| Intended Use | For the semi-quantitative measurement of albumin and creatinine in urine samples. | Same |
| Specimen | Urine | Same |
| Test time | 1 minute | Same |
| Printed/Displayed Results | Albumin: 10, 30, 80, 150 mg/L
Creatinine: 10, 50, 100, 200, 300 mg/dL | Same |
| Albumin:creatinine ratio
Printed/Displayed Results | <30 mg/g (normal)
30-300 mg/g (Abnormal)
> 300 mg/g (High Abnormal) | Same |
| Storage | 2 to 30°C | 15 to 30°C |
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP07-A2, Interference Testing in Clinical Chemistry, Approved Guideline- Second Edition.
L. Test Principle:
The albumin test is based on affinity binding of albumin to a sulfonephthalein dye at a constant pH. The development of pale green to aqua blue indicates the presence of albumin.
The creatinine test is based on the peroxidase-like activity of a copper creatinine complex that catalyzes the reaction of diisopropylbenzene dihydroperoxide and 3,3',5,5'-
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tetramethylbenzidine. The resulting color ranges from orange through green to blue.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
To evaluate within run and total precision, three lots of Mission Urinalysis Test Strips (Microalbumin/Creatinine) were used to test urine albumin concentrations of 10, 30, and 150 mg/L and urine creatinine concentrations of 10, 50, and 300 mg/dL. Within-run precision was evaluated at 3 point of care (POC) sites by 3 POC personnel testing each level of the control solution in 20 replicates in one day. Between run precision was evaluated by 3 POC personnel at each of 3 POC sites testing each of the three levels in singlet, 2 runs per day, for 20 days. The samples were blind labeled samples. The exact match block agreement precision study test results are summarized in the tables below:
POC Site 1
| Analyte | Concentration | Result (Exact Match/Total) | | |
| --- | --- | --- | --- | --- |
| | | Operator 1 | Operator 2 | Operator 3 |
| Albumin | 10mg/L | 14/14 | 14/14 | 12/12 |
| | 30 mg/L | 14/14 | 14/14 | 12/12 |
| | 150 mg/L | 14/14 | 14/14 | 12/12 |
| Creatinine | 10 mg/dL | 14/14 | 14/14 | 12/12 |
| | 50 mg/dL | 14/14 | 14/14 | 12/12 |
| | 300 mg/dL | 14/14 | 14/14 | 12/12 |
POC site 2
| Analyte | Concentration | Result (Exact Match/Total) | | |
| --- | --- | --- | --- | --- |
| | | Operator 1 | Operator 2 | Operator 3 |
| Albumin | 10mg/L | 14/14 | 14/14 | 12/12 |
| | 30 mg/L | 14/14 | 14/14 | 12/12 |
| | 150 mg/L | 14/14 | 14/14 | 12/12 |
| Creatinine | 10 mg/dL | 14/14 | 14/14 | 12/12 |
| | 50 mg/dL | 14/14 | 14/14 | 12/12 |
| | 300 mg/dL | 14/14 | 14/14 | 12/12 |
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POC site 3
| Analyte | Concentration | Result (Exact Match/Total) | | |
| --- | --- | --- | --- | --- |
| | | Operator 1 | Operator 2 | Operator 3 |
| Albumin | 10mg/L | 14/14 | 14/14 | 12/12 |
| | 30 mg/L | 14/14 | 14/14 | 12/12 |
| | 150 mg/L | 14/14 | 14/14 | 12/12 |
| Creatinine | 10 mg/dL | 13/14 | 14/14 | 12/12 |
| | 50 mg/dL | 14/14 | 14/14 | 12/12 |
| | 300 mg/dL | 14/14 | 14/14 | 12/12 |
The combined precision data for the POC sites is summarized below:
| Analyte | Conc. | | Total Agreement within same block | Total Agreement within ± 1 block |
| --- | --- | --- | --- | --- |
| Albumin | 10 mg/L | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 120/120 | 120/120 |
| 30 mg/L | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 120/120 | 120/120 |
| 150 mg/L | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 119/120 | 120/120 |
| Creatinine | 10 mg/dL | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 119/120 | 120/120 |
| 50 mg/dL | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 120/120 | 120/120 |
| 300 mg/dL | Within-run | 60/60 | 60/60 |
| 100% | 100% |
| Between run | 120/120 | 120/120 |
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b. Linearity/assay reportable range:
This assay reports color block outputs of 10 mg/L, 30 mg/L, 80 mg/L, 150 mg/L for albumin, and 10 mg/dL, 50 mg/dL, 100 mg/dL, 200 mg/dL, 300 mg/dL for creatinine.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability and Expected values: No calibrators or controls are being cleared with this submission.
Stability: Real time and accelerated stability studies were performed for closed vial stability and real time stability study was performed for open vial stability. The study protocol and acceptance criteria was reviewed and found acceptable. Stability data support the following manufacturer's claim: The strip can be stored in 2°C to 30°C (35.6 °F to 30 °F) in closed package to 24 months, opened package stable for at least 3 months from the manufacture date.
Temperature: Studies were performed to validate the optimal temperature range for testing Mission Urinalysis Reagent Strips (Microalbumin/Creatinine) on the Mission U120 analyzer. The study protocol and acceptance criteria was reviewed and found acceptable. The temperature study data showed that correct Microalbumin/Creatinine results can be obtained by the Mission U120 Urine Analyzer at temperatures between 2°C and 45°C.
Humidity: Studies were performed to validate the optimal humidity range for testing Mission Urinalysis Reagent Strips (Microalbumin/Creatinine). The study protocol and acceptance criteria was reviewed and found acceptable. The results demonstrated that the strips were stable up to 50% humidity for over 24 hrs, and at humidity conditions above 60%, the strip was stable for 1 hr.
d. Detection limit:
The cutoff of the assay at each color block was validated by spiking or diluting a pooled urine sample with albumin and creatinine to achieve 4 levels of albumin and 5 levels of creatinine. Each level was further adjusted to concentrations below and above the midpoint concentration of each of these levels. Each sample was tested by three operators with 3 lots of strips for 3 days generating 81 data points for each level. The cutoffs for each color block are defined as the lowest and highest concentrations of analyte tested at which over 50% of the results are positive for each color block.
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Results for each concentration tested at each color block are shown below:
| | | Same block Agreement | | | |
| --- | --- | --- | --- | --- | --- |
| | Conc. Tested | 10 mg/L | 30 mg/L | 80 mg/L | 150 mg/L |
| Albumin | 300 mg/L | 0% | 0% | 0% | 100% (81/81) |
| | 225 mg/L | 0% | 0% | 0% | 100% (81/81) |
| | 150 mg/L | 0% | 0% | 0% | 100% (81/81) |
| | 137.5 mg/L | 0% | 0% | 19.8% (16/81) | 80.2% (65/81) |
| | 125 mg/L | 0% | 0% | 38.3% (31/81) | 61.7% (50/81) |
| | 103.5 mg/L | 0% | 0% | 51.9% (42/81) | 48.4% (40/81) |
| | 80 mg/L | 0% | 0% | 100% (81/81) | 0% |
| | 60.5 mg/L | 0% | 12.3% (10/81) | 87.7% (71/81) | 0% |
| | 55 mg/L | 0% | 30.9% (25/81) | 69.1% (56/81) | 0% |
| | 49.5 mg/L | 0% | 60.5% (49/81) | 39.5% (32/81) | 0% |
| | 30 mg/L | 0% | 100% (81/81) | 0% | 0% |
| | 22 mg/L | 13.6% (11/81) | 86.4% (70/81) | 0% | 0% |
| | 20 mg/L | 18.5% (15/81) | 81.5% (66/81) | 0% | 0% |
| | 18 mg/L | 50.6% (41/81) | 49.4% (40/81) | 0% | 0% |
| | 10 mg/L | 100% (81/81) | 0% | 0% | 0% |
| | 7.5 mg/L | 100% (81/81) | 0% | 0% | 0% |
| | 5 mg/L | 100% (81/81) | 0% | 0% | 0% |
| | 2.5 mg/L | 100% (81/81) | 0% | 0% | 0% |
| | 0 mg/L (water) | 100% (81/81) | 0% | 0% | 0% |
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| | | Same block Agreement | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Conc. Tested | 10 mg/dL | 50 mg/dL | 100 mg/dL | 200 mg/dL | 300 mg/dL |
| Creatinine | 600 mg/dL | 0% | 0% | 0% | 0% | 100% (81/81) |
| | 450 mg/dL | 0% | 0% | 0% | 0% | 100% (81/81) |
| | 300 mg/dL | 0% | 0% | 0% | 0% | 100% (81/81) |
| | 275 mg/dL | 0% | 0% | 0% | 13.6% (11/81) | 86.4% (70/81) |
| | 250 mg/dL | 0% | 0% | 0% | 49.4% (40/81) | 50.6% (41/81) |
| | 225 mg/dL | 0% | 0% | 0% | 81.5% (66/81) | 18.5% (15/81) |
| | 200 mg/dL | 0% | 0% | 0% | 100% (81/81) | 0% |
| | 165 mg/dL | 0% | 0% | 23.5% (19/81) | 76.5% (62/81) | 0% |
| | 150 mg/dL | 0% | 0% | 44.7% (37/81) | 54.3% (44/81) | 0% |
| | 135 mg/dL | 0% | 0% | 51.9% (42/81) | 48.1% (39/81) | 0% |
| | 100 mg/dL | 0% | 0% | 100% (81/81) | 0% | 0% |
| | 82.5 mg/dL | 0% | 27.2% (22/81) | 72.8% (59/81) | 0% | 0% |
| | 75 mg/dL | 0% | 51.9% (42/81) | 48.1% (39/81) | 0% | 0% |
| | 67.5 mg/dL | 0% | 59.3% (48/81) | 40.7% (33/81) | 0% | 0% |
| | 50 mg/dL | 0% | 100% (81/81) | 0% | 0% | 0% |
| | 33 mg/dL | 18.5% (15/81) | 81.5% (66/81) | 0% | 0% | 0% |
| | 30 mg/dL | 28.4% (23/81) | 71.6% (58/81) | 0% | 0% | 0% |
| | 27.5 mg/dL | 55.6% (45/81) | 44.4% (36/81) | 0% | 0% | 0% |
| | 10 mg/dL | 100% (81/81) | 0% | 0% | 0% | 0% |
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| | | Same block Agreement | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Conc. Tested | 10 mg/dL | 50 mg/dL | 100 mg/dL | 200 mg/dL | 300 mg/dL |
| | 7.5 mg/dL | 100% (81/81) | 0% | 0% | 0% | 0% |
| | 5 mg/dL | 100% (81/81) | 0% | 0% | 0% | 0% |
| | 2.5 mg/dL | 100% (81/81) | 0% | 0% | 0% | 0% |
| | 0 mg/dL (water) | 0% | 0% | 0% | 0% | 0% |
Summary of the performance at each color block for the tested analyte concentrations:
| Analyte | Color block | Low Concentration cut-off (mg/L) | High Concentration cut-off (mg/L) |
| --- | --- | --- | --- |
| Albumin (mg/L) | 10 | 0 | 18 |
| | 30 | 20 | 49.5 |
| | 80 | 55 | 103.5 |
| | 150 | 125 | >150 |
| Creatinine (mg/dL) | 10 | 0 | 27 |
| | 50 | 30 | 75 |
| | 100 | 82.5 | 135 |
| | 200 | 150 | 225 |
| | 300 | 250 | >300 |
e. Analytical specificity:
Interference studies were performed to evaluate the effects of potential interferents commonly found in urine on the performance of Mission Urinalysis Reagent strips, using CLSI EP7-A2 as a guide. Testing was done with contrived urine samples at 3 levels of albumin (10, 30, 150 mg/L) and creatinine (10, 100, 300 mg/dL) and different concentrations of the listed compounds with 3 lots of strips. Interference is defined as a change in output of $\geq \pm 1$ color block between spiked and unspiked control sample. The results are summarized in the table below:
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| Interferent | Conc. Tested | Interference on the Testing Result | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Result of Albumin | | | Result of Creatinine | | |
| | | 10 mg/L | 30 mg/L | 150 mg/L | 10 mg/dL | 100 mg/dL | 300 mg/dL |
| Ammonium | 100 mg/dL | --* | -- | -- | -- | -- | -- |
| Ascorbic acid | 200 mg/dL | -- | -- | -- | -- | -- | -- |
| Bilirubin | 170 mg/dL | -- | -- | -- | -- | -- | -- |
| Calcium chloride | 275 mg/dL | -- | -- | -- | -- | -- | -- |
| Citric acid | 75 mg/dL | -- | -- | -- | -- | -- | -- |
| Creatine | 10 mg/dL | -- | -- | -- | -- | -- | -- |
| Creatinine | 600 mg/dL | -- | -- | -- | n/a** | n/a | n/a |
| Fructose | 100 mg/dL | -- | -- | -- | -- | -- | -- |
| Galactose | 80 mg/dL | -- | -- | -- | -- | -- | -- |
| Glucose | 5000 mg/dL | -- | -- | -- | -- | -- | -- |
| Glycine | 450 mg/dL | -- | -- | -- | -- | -- | -- |
| Hemoglobin | 10 mg/dL | +1 | +1 | -- | +1 | +1 | -- |
| Lactose | 10 mg/dL | -- | -- | -- | -- | -- | -- |
| Lithium | 250 mg/dL | -- | -- | -- | -- | -- | -- |
| Oxalic acid | 70 mg/dL | -- | -- | -- | -- | -- | -- |
| Potassium chloride | 1500 mg/dL | -- | -2 | -2 | -- | -- | -- |
| Riboflavin | 10 mg/dL | -- | -- | -- | -- | -- | -- |
| Sodium acetate | 2.25 mg/dL | -- | -- | -- | -- | -- | -- |
| Sodium bicarbonate | 1500 mg/dL | +2 | +1 | -- | -- | -- | -- |
| Sodium chloride | 5500 mg/dL | -- | -- | -- | -- | -- | -- |
| Sodium nitrate | 10 mg/dL | -- | -- | -- | -- | -- | -- |
| Sodium nitrite | 10 mg/dL | -- | -- | -- | -- | -- | -- |
| Sodium phosphate | 500 mg/dL | -- | -- | -- | -- | -- | -- |
| Theophylline | 100 mg/dL | -- | -- | -- | -- | -- | -- |
| Urea | 400 mg/dL | -- | -- | -- | -- | -- | -- |
| Uric acid | 150 mg/dL | -- | -- | -- | -- | -- | -- |
| Blood | 0.05% | +2 | +1 | -- | +1 | +1 | -- |
| Leucocyte | 2500 leu/μL | -- | -- | -- | -- | -- | -- |
| Human IgG | 25 mg/dL | +1 | +1 | -- | -- | -- | -- |
*-- indicates that the no interference was observed at these interferent and analyte levels.
**n/a: creatinine was not tested as an interfering substance for the creatinine test pad
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# Specific Gravity and pH:
To test the effects of specific gravity, 5 fresh urine samples were pooled and separated into 9 aliquots with approximate specific gravities of 1.000, 1.005, 1.010, 1.015, 1.020, 1.025, 1.030, 1.035 and 1.040. The samples were spiked or diluted to achieve the desired albumin (10, 80, and 150 mg/L) and creatinine (10, 100, 300 mg/dL) concentrations. Interference was defined by the sponsor as results being ≥ 1 block outside the expected color block. The results showed that urine specific gravity range of 1.005 to 1.040 does not affect the results of the albumin test, but specific gravity at 1.000 will generate a false low result on the albumin test. Specific gravity from 1.000 to 1.030 will not affect the results of creatinine test; however specific gravity higher than or equal to 1.035 will generate a false high result on the creatinine test.
To test the effects of pH, 5 fresh urine samples were pooled and separated into 7 aliquots. The pH of the aliquots was adjusted to a range of 4.00 to 10.00 in 1 pH unit increments and were spiked or diluted with albumin and creatinine, respectively. Interference was defined by the sponsor as results being ≥ 1 block outside the expected color block. Samples were tested in replicates of 5, using three lots of each format of the devices, and results showed that urine pH range of 4.00 to 9.00 does not affect the results of the albumin test but samples at pH 10.0 would generate false high results. Urine sample pH from 4 to 10 did not affect the creatinine test results.
The sponsor includes the following in the labeling regarding potentially interfering substances:
Results of the substances at the indicated concentration were found to interfere with the albumin and/or creatinine test are summarized in the table below:
| Substances | Conc. Tested | Interference on the Albumin Result | Interference on the Creatinine Result |
| --- | --- | --- | --- |
| Human IgG | 25 mg/dL | +1 Block | N/A |
| Sodium Bicarbonate | 1500 mg/dL | +1 to +2 Blocks | N/A |
| Potassium Chloride | 1500 mg/dL | -2 Blocks | N/A |
| Hemoglobin | 10 mg/dL | +1 to +2 Blocks | +1 Block |
| Blood | 0.05% | +1 Block | +1 Block |
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The Urinalysis Reagent Strips (Urine) may be affected by substances that cause abnormal urine color such as drugs containing azo dyes (e.g. Pyridium, Azo Gantrisin, Azo Gantanol), nitrofurantoin (Microdantin, Furadantin), and riboflavin. Urine specimen contaminated with soaps, detergents, antiseptics, or skin cleansers may also affect test results.
For albumin, a pH ≥10.0 or a specific gravity of 1.000 will affect albumin test results; whereas, a specific gravity ≥1.035 will generate falsely elevated results for creatinine.
## Sample Carryover study:
The sponsor performed a carryover study to evaluate the interference of the reagent pad to each other on the Microalbumin/Creatinine reagent strip when read by the Mission U120 analyzer. Three concentration of albumin (10, 30, and 150 mg/L) and creatinine (10, 50, and 300 mg/dL) were tested. The reagent strip was dipped into the urine sample and removed. The strip was held vertically to allow excess liquid from the microalbumin pad to run onto the creatinine pad before blotting and testing on the analyzer. The process was repeated to allow excess liquid from the creatinine pad to run onto the Microalbumin pad before blotting and testing on the analyzer. Interference was defined by the sponsor as results being outside the expected color block. Each urine concentration was tested in replicates of 5. The results of the study demonstrated no interference between the reagent pads was observed when liquid form one reagent pad is carried over to another reagent pad and tested on the Mission U120 analyzer.
## Dipping/wetting time study:
The sponsor performed a study to evaluate the effect of different dipping and wetting times of the Microalbumin/Creatinine reagent strip in urine on the Mission U120 Analyzer albumin and creatinine result reading. Three concentration of albumin (10, 30, and 150 mg/L) and creatinine (10, 50, and 300 mg/dL) were tested. The strips were dipped into the urine samples and allowed to remain in the urine for 2s, 5s and 10s. Then, the strips were removed from the urine sample but allowed to remain wet (not blotted) for 0 s, 15s, 30s, 60s, 90s, 2min, 3 min, 5 min, and 10 min before placing the strip on the analyzer for testing. Testing was performed for each time point in replicates of 5. Interference was defined by the sponsor as results being ≥ 1 block outside the expected color block. Data from the study showed that to generate the correct testing results, the optimum ranges of strip dipping time and strip wetting time for Microalbumin/Creatinine strips are listed below:
| Reagent | Range of strip dipping time | Range of strip wetting time |
| --- | --- | --- |
| Microalbumin | 0-10s | 0s-10 min |
| Creatinine | 0-10s | 0s-1 min |
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f. Assay cut-off:
See detection limits (M. 1. d.) above.
## 2. Comparison studies:
a. Method comparison with predicate device:
Method comparison studies were performed to evaluate the accuracy of the Mission Urinalysis Microalbumin/Creatinine Reagent Strips read by the Mission U120 Urine Analyzer compared to the predicate, the Clinitek Microalbumin Reagent Strips read by the Clinitek Status Analyzer. Testing was performed at 3 point-of-care (POC) sites by 9 operators (3 per site). One hundred and twenty total urine samples were randomly collected from patients at each of the 3 POC sites for a total of 360 native samples. An additional ten samples at each site (8% of the total number of samples tested) were contrived to cover the entire measuring range, for an overall total of 390 samples. Each intended user tested approximately the same number of samples at each site. Three lots of strips were used for the study.
The method comparison data for urine albumin and creatinine testing for each of the 3 sites are shown in the tables below:
| Albumin (Site 1, n= 130) | Predicate Device | | | | |
| --- | --- | --- | --- | --- | --- |
| | | 10 mg/L | 30 mg/L | 80 mg/L | 150 mg/L |
| Mission Urinalysis Reagent Strips | 10 mg/L | 61 | 3 | 0 | 0 |
| | 30 mg/L | 6 | 24 | 3 | 0 |
| | 80 mg/L | 0 | 2 | 11 | 2 |
| | 150 mg/L | 0 | 0 | 0 | 18 |
| Total | | 67 | 29 | 14 | 20 |
| Agreement at same block | | 91.0% | 82.8% | 78.6% | 90.0% |
| Agreement within ±1 block | | 100% | 100% | 100% | 100% |
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| Albumin (Site 2, n= 130) | Predicate Device | | | | |
| --- | --- | --- | --- | --- | --- |
| | | 10 mg/L | 30 mg/L | 80 mg/L | 150 mg/L |
| Mission Urinalysis Reagent Strips | 10 mg/L | 17 | 3 | 0 | 0 |
| | 30 mg/L | 4 | 17 | 5 | 0 |
| | 80 mg/L | 0 | 2 | 18 | 9 |
| | 150 mg/L | 0 | 0 | 1 | 54 |
| Total | | 21 | 22 | 24 | 63 |
| Agreement at same block | | 81.0% | 77.3% | 75.0% | 81.5% |
| Agreement within ± 1 block | | 100% | 100% | 100% | 100% |
| Albumin (Site 3, n= 130) | Predicate Device | | | | |
| --- | --- | --- | --- | --- | --- |
| | | 10 mg/L | 30 mg/L | 80 mg/L | 150 mg/L |
| Mission Urinalysis Reagent Strips | 10 mg/L | 42 | 3 | 0 | 0 |
| | 30 mg/L | 10 | 30 | 4 | 0 |
| | 80 mg/L | 0 | 4 | 21 | 2 |
| | 150 mg/L | 0 | 0 | 1 | 13 |
| Total | | 52 | 37 | 26 | 15 |
| Agreement at same block | | 80.8% | 81.1% | 80.8% | 86.7% |
| Agreement within ± 1 block | | 100% | 100% | 100% | 100% |
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| Creatinine (Site 1, n= 130) | Predicate Device | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | 10 | 50 | 100 | 200 | 300 |
| Mission Urinalysis Reagent Strips | 10 | 10 | 2 | 0 | 0 | 0 |
| | 50 | 0 | 29 | 4 | 0 | 0 |
| | 100 | 0 | 6 | 29 | 4 | 0 |
| | 200 | 0 | 0 | 6 | 26 | 1 |
| | 300 | 0 | 0 | 0 | 1 | 12 |
| Total | | 10 | 37 | 39 | 31 | 13 |
| Agreement at same block | | 100% | 82.7% | 74.4% | 83.9% | 92.3% |
| Agreement within ±1 block | | 100% | 100% | 100% | 100% | 100% |
| Creatinine (Site 2, n= 130) | Predicate Device | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | 10 | 50 | 100 | 200 | 300 |
| Mission Urinalysis Reagent Strips | 10 | 15 | 3 | 0 | 0 | 0 |
| | 50 | 1 | 39 | 3 | 0 | 0 |
| | 100 | 0 | 3 | 26 | 4 | 0 |
| | 200 | 0 | 0 | 4 | 22 | 1 |
| | 300 | 0 | 0 | 0 | 1 | 8 |
| Total | | 16 | 45 | 33 | 27 | 9 |
| Agreement at same block | | 93.8% | 86.7% | 78.8% | 81.5% | 88.9% |
| Agreement within ±1 block | | 100% | 100% | 100% | 100% | 100% |
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16
| Creatinine (Site 3, n= 130) | Predicate Device | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | 10 | 50 | 100 | 200 | 300 |
| Mission Urinalysis Reagent Strips | 10 | 10 | 4 | 0 | 0 | 0 |
| | 50 | 3 | 36 | 5 | 0 | 0 |
| | 100 | 0 | 4 | 32 | 4 | 0 |
| | 200 | 0 | 0 | 2 | 20 | 0 |
| | 300 | 0 | 0 | 0 | 0 | 10 |
| Total | | 13 | 44 | 39 | 24 | 10 |
| Agreement at same block | | 76.9% | 81.8% | 82.1% | 83.3% | 100% |
| Agreement within ±1 block | | 100% | 100% | 100% | 100% | 100% |
For all three sites combined:
| Albumin | Predicate Device | | | | |
| --- | --- | --- | --- | --- | --- |
| | | 10 mg/L | 30 mg/L | 80 mg/L | 150 mg/L |
| Mission Urinalysis Reagent Strips | 10 mg/L | 120 | 9 | 0 | 0 |
| | 30 mg/L | 20 | 71 | 12 | 0 |
| | 80 mg/L | 0 | 8 | 50 | 13 |
| | 150 mg/L | 0 | 0 | 2 | 85 |
| Total | | 140 | 88 | 64 | 98 |
| Agreement at same block | | 85.7% | 80.7% | 78.1% | 86.7% |
| Agreement within ± 1 block | | 100% | 100% | 100% | 100% |
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17
| Creatinine | Predicate Device | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | 10 mg/dL | 50 mg/dL | 100 mg/dL | 200 mg/dL | 300 mg/dL |
| Mission Urinalysis Reagent Strips | 10 mg/dL | 35 | 9 | 0 | 0 | 0 |
| | 50 mg/dL | 4 | 104 | 12 | 0 | 0 |
| | 100 mg/dL | 0 | 13 | 87 | 12 | 0 |
| | 200 mg/dL | 0 | 0 | 12 | 68 | 2 |
| | 300 mg/dL | 0 | 0 | 0 | 2 | 30 |
| Total | | 39 | 126 | 111 | 82 | 32 |
| Agreement at same block | | 89.7% | 82.5% | 78.4% | 82.9% | 98.3% |
| Agreement within ± 1 block | | 100% | 100% | 100% | 100% | 100% |
Albumin to creatinine ratio percent agreement for all three sites combined:
| Albumin:Creatinine Ratio (n=390) | Predicate Device | | |
| --- | --- | --- | --- |
| Mission Urinalysis (Microalbumin/Creatinine) Reagent Strips | <30 mg/g | 30-300 mg/g | >300 mg/g |
| <30 mg/g | 164 | 12 | 0 |
| 30-300 mg/g | 15 | 112 | 11 |
| >300 mg/g | 0 | 4 | 72 |
| Total | 179 | 128 | 83 |
| Agreement at same block | 91.6% | 87.5% | 86.7% |
| Agreement within ± 1 block | 100% | 100% | 100% |
The agreement of albumin to creatinine ratios of positive and negatives at cutoff of $<30 \, \mathrm{mg/g}$ were $94.3\%$ and $91.6\%$ respectively. Of the 211 positive results, $5.7\%$
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(12/211) were negative. Of the 179 assays, albumin to creatinine ratio negative results, 8.4% (15/179) were positive. In summary, the overall exact agreement between Mission Urinalysis Strips (Microalbumin/Creatinine) and the predicate for positive albumin results was 89.2%, and the overall agreement for ±1 block was 100%.
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:
The expected values are included in the labeling and are taken from literature references.
Normally, albumin is present in urine at concentrations < 20 mg/L¹. Results of 20-200 mg/L may indicate microalbuminuria. It is associated with early-stage kidney disease when a small amount of albumin, also called microalbumin, is consistently present in urine. Clinical albuminuria is indicated by results of > 200 mg/L. These levels can be predictive of albumin excretion rates of 30-300 mg/24 hours and >300 mg/24 hours, respectively²⁻³. Exercise, acute illness and fever, and urinary tract infections may temporarily elevate urinary albumin excretions. Creatinine concentrations of 10-300 mg/dL are normally present in urine.
Albumin is normally present in urine at concentrations of <30 mg albumin/g creatinine. Microalbuminuria is indicated at a ratio result of 30-300 mg/g (abnormal) and clinical albuminuria at a ratio of >300 mg/g (high abnormal)⁴.
1. Burtis, C.A. and Ashwood, E.R.: Tietz Textbook of Clinical Chemistry, 3rd ed. Philadelphia: Saunders; 1999; pp. 483-484.
2. Mangili, R. et al.: Prevalence of Hypertension and Microalbuminuria in Adult Type 1
18
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(Insulin-Dependent) Diabetic patients Without Renal Failure in Italy-Validation of Screening Techniques to Detect Microalbuminuria. Acta Diabetol. 29: 156-166; 1992.
3. American Diabetes Association, Clinical Practice Recommendations, Diabetes Care, Vol. 31, Suppl. 1, January 2008
4. Position Statement: Diabetic Nephropathy. Diabetes Care 20: S24-S27; 1997.
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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