Creatinine2
Device Facts
| Record ID | K210452 |
|---|---|
| Device Name | Creatinine2 |
| Applicant | Abbott Ireland Diagnostics Division |
| Product Code | CGX · Clinical Chemistry |
| Decision Date | Mar 22, 2022 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1225 |
| Device Class | Class 2 |
Indications for Use
The Creatinine2 assay is used for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System. The Creatinine2 assay is to be used as an aid in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Device Story
Creatinine2 is an automated clinical chemistry assay for the ARCHITECT c System. It measures creatinine in human serum, plasma, or urine samples. The principle of operation is the Kinetic Alkaline Picrate method: at alkaline pH, creatinine reacts with picric acid to form a creatinine-picrate complex that absorbs light at 500 nm. The rate of absorbance increase is directly proportional to creatinine concentration. The assay is performed in a clinical laboratory setting by trained technicians. Results are provided to clinicians to assist in diagnosing and treating renal disease and monitoring dialysis patients. The device benefits patients by providing quantitative data for renal function assessment.
Clinical Evidence
Bench testing only. Precision studies (within-run, between-run, between-day) performed on three ARCHITECT c8000 instruments. Linearity established across 0.09–37.34 mg/dL (serum) and 2.54–740 mg/dL (urine). Interference testing conducted per CLSI EP07-A3. Method comparison against predicate (N=128 serum, N=129 urine) showed high correlation (r=1.00). No clinical studies performed.
Technological Characteristics
Colorimetric assay; kinetic alkaline picrate methodology. Reagents: R1 (sodium hydroxide), R2 (picric acid). Form factor: reagent kit for ARCHITECT c8000 System. Traceability: NIST SRM 967a (serum/plasma), NIST SRM 914a (urine).
Indications for Use
Indicated for the quantitation of creatinine in human serum, plasma, or urine to aid in the diagnosis and treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes.
Regulatory Classification
Identification
A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Predicate Devices
- Creatinine (k083809)
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K210452
B Applicant
Abbott Ireland Diagnostics Division
C Proprietary and Established Names
Creatinine2
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CGX | Class II | 21 CFR 862.1225 - Creatinine Test System | CH - Clinical Chemistry |
## II Submission/Device Overview:
A Purpose for Submission:
New device
B Measurand:
Creatinine
C Type of Test:
Quantitative, photometric/colorimetric
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
The Creatinine2 assay is used for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System.
The Creatinine2 assay is to be used as an aid in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
### D Special Instrument Requirements:
ARCHITECT c8000 System
## IV Device/System Characteristics:
### A Device Description:
The Creatinine2 assay is comprised of a reagent kit that is run on the ARCHITECT c8000 System. Each kit has two reagents; R1 and R2. R1 contains sodium hydroxide (0.8 mol/L) and R2 contains picric acid (5.500 g/L). The Creatinine2 assay is calibrated using the Consolidated Chemistry Calibrator, which is required but not provided with the kit. The product labeling recommends running controls containing creatinine, but these are not provided with the kit.
### B Principle of Operation:
The methodology of the Creatinine2 assay is that of a colorimetric assay. At alkaline pH, by addition of sodium hydroxide, creatinine in the sample chemically reacts with a picric acid reagent to form a creatinine-picrate complex. This reaction product has an absorbance at 500 nm. The rate of increase in absorbance is directly proportional to the concentration of creatinine in the sample.
## V Substantial Equivalence Information:
### A Predicate Device Name(s):
Creatinine
### B Predicate 510(k) Number(s):
k083809
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# C Comparison with Predicate(s):
| Device & Predicate Device(s): | k210452 | k083809 |
| --- | --- | --- |
| Device Trade Name | Creatinine2 | Creatinine |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | The assay is used for the quantitation of creatinine. | Same |
| Method | Kinetic alkaline picrate | Same |
| Traceability | NIST SRM 967 for serum/plasma and NIST SRM 914 for urine. | Same |
| General Device Characteristic Differences | | |
| Specimen types | Serum, K2EDTA plasma, lithium heparin plasma, sodium heparin plasma, and urine | Serum, lithium heparin plasma, sodium heparin plasma, and urine |
# VI Standards/Guidance Documents Referenced:
CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Third Edition.
CLSI EP07-A3 Interference Testing in Clinical Chemistry; Approved Guideline —Third Edition.
CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline—Second Edition.
# VII Performance Characteristics (if/when applicable):
## A Analytical Performance:
1. Precision/Reproducibility:
The sponsor provided separate precision studies supporting use of: (1) serum and (2) urine.
**Serum**
In the study, five serum based controls were internally prepared and also obtained from a commercial source. Each of the five samples was tested on three ARCHITECT c8000 instruments using three lots of creatinine reagent kits in duplicates per run, two runs per day, over 20 day for a total of 80 measurements per instrument/lot. The results for each sample per instrument/lot, presented in the table below were analyzed for variance by an ANOVA method for the factors of within-run, between-run, and between-day. The within-laboratory
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SD and %CV were estimated using the summation of the within-run, between-run, and between-day variance components.
Instrument 1/reagent lot 1
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 1.37 | 0.015 | 1.1 | 0.008 | 0.6 | 0.011 | 0.8 | 0.020 | 1.5 |
| Control 2 | 5.78 | 0.054 | 0.9 | 0.000 | 0.0 | 0.034 | 0.6 | 0.064 | 1.1 |
| Control 3 | 0.26 | 0.008 | 3.2 | 0.007 | 2.6 | 0.000 | 0.0 | 0.011 | 4.1 |
| Control 4 | 25.47 | 0.137 | 0.5 | 0.076 | 0.3 | 0.143 | 0.6 | 0.212 | 0.8 |
| Control 5 | 35.64 | 0.203 | 0.6 | 0.050 | 0.1 | 0.155 | 0.4 | 0.260 | 0.7 |
Instrument 2/reagent lot 2
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 1.42 | 0.015 | 1.0 | 0.013 | 0.9 | 0.046 | 3.3 | 0.050 | 3.5 |
| Control 2 | 5.91 | 0.035 | 0.6 | 0.037 | 0.6 | 0.138 | 2.3 | 0.147 | 2.5 |
| Control 3 | 0.25 | 0.008 | 3.1 | 0.007 | 2.6 | 0.005 | 1.9 | 0.011 | 4.5 |
| Control 4 | 26.00 | 0.121 | 0.5 | 0.203 | 0.8 | 0.538 | 2.1 | 0.588 | 2.3 |
| Control 5 | 36.36 | 0.130 | 0.4 | 0.182 | 0.5 | 0.744 | 2.0 | 0.777 | 2.1 |
Instrument 3/reagent lot 3
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 1.41 | 0.013 | 0.9 | 0.005 | 0.4 | 0.007 | 0.5 | 0.016 | 1.1 |
| Control 2 | 5.75 | 0.031 | 0.5 | 0.010 | 0.2 | 0.034 | 0.6 | 0.047 | 0.8 |
| Control 3 | 0.25 | 0.009 | 3.5 | 0.002 | 0.6 | 0.004 | 1.5 | 0.010 | 3.9 |
| Control 4 | 25.24 | 0.087 | 0.3 | 0.032 | 0.1 | 0.160 | 0.6 | 0.185 | 0.7 |
| Control 5 | 35.27 | 0.146 | 0.4 | 0.000 | 0.0 | 0.243 | 0.7 | 0.283 | 0.8 |
Urine
In the study, five human urine based controls were internally prepared and also obtained from a commercial source prepared. Each of the five samples was tested on three ARCHITECT c8000 instruments using three lots of creatinine reagent kits in duplicates per run, two runs per day, over 20 day for a total of 80 measurements per instrument/lot. The results for each sample per instrument/lot, presented in the table below were analyzed for variance by an ANOVA method for the factors of within-run, between-run, and between-day. The within-laboratory SD and %CV were estimated using the summation of the within-run, between-run, and between-day variance components.
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Instrument 1/reagent lot 1
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 56.93 | 0.516 | 0.9 | 0.000 | 0.0 | 0.887 | 1.6 | 1.027 | 1.8 |
| Control 2 | 129.69 | 1.309 | 1.0 | 0.000 | 0.0 | 1.885 | 1.5 | 2.295 | 1.8 |
| Control 3 | 5.29 | 0.185 | 3.5 | 0.028 | 0.5 | 0.118 | 2.2 | 0.221 | 4.2 |
| Control 4 | 273.71 | 1.700 | 0.6 | 0.593 | 0.2 | 1.974 | 0.7 | 2.671 | 1.0 |
| Control 5 | 690.32 | 5.197 | 0.8 | 0.000 | 0.0 | 5.588 | 0.8 | 7.631 | 1.1 |
Instrument 2/reagent lot 2
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 57.77 | 0.491 | 0.9 | 0.224 | 0.4 | 1.065 | 1.8 | 1.194 | 2.1 |
| Control 2 | 132.61 | 1.165 | 0.9 | 0.000 | 0.0 | 2.935 | 2.2 | 3.158 | 2.4 |
| Control 3 | 5.37 | 0.233 | 4.3 | 0.081 | 1.5 | 0.160 | 3.0 | 0.294 | 5.5 |
| Control 4 | 278.12 | 1.958 | 0.7 | 1.276 | 0.5 | 4.424 | 1.6 | 5.003 | 1.8 |
| Control 5 | 701.12 | 3.303 | 0.5 | 2.664 | 0.4 | 12.123 | 1.7 | 12.844 | 1.8 |
Instrument 3/reagent lot 3
| | | Within-Run | | Between-Run | | Between-Day | | Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (mg/dL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 56.29 | 0.526 | 0.9 | 0.000 | 0.0 | 0.577 | 1.0 | 0.781 | 1.4 |
| Control 2 | 128.92 | 0.772 | 0.6 | 0.572 | 0.4 | 1.593 | 1.2 | 1.860 | 1.4 |
| Control 3 | 5.25 | 0.246 | 4.7 | 0.077 | 1.5 | 0.000 | 0.0 | 0.258 | 4.9 |
| Control 4 | 269.85 | 1.539 | 0.6 | 0.000 | 0.0 | 3.396 | 1.3 | 3.728 | 1.4 |
| Control 5 | 678.57 | 3.928 | 0.6 | 1.835 | 0.3 | 8.666 | 1.3 | 9.690 | 1.4 |
2. Linearity:
Linearity of the Creatinine2 assay on the ARCHITECT c8000 across the analytical measurement range was established in two studies measuring samples at concentrations spanning the measurement range using one instrument and one reagent kit lot. In each study, a high level creatinine samples was inter-mixed with a low level creatinine samples with known dilutions to prepare samples which were uniformly distributed across the measurement range. At least one concentration was included which exceeded the claimed measurement range.
Serum:
Each of the 13 samples were measured in replicates of four on the ARCHITECT c8000 system. The observed creatinine concentrations versus the expected concentrations were assessed for a linear response. Based on the results, the sponsor concluded that the creatinine
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test system demonstrated a linearity over the claimed range of 0.09 to 37.34 mg/dL. The linear regression summary is given below.
| Range tested | Slope | Intercept | R² |
| --- | --- | --- | --- |
| 0.08 to 40.0 mg/dL | 0.999 | -0.01 | 0.9999 |
**Urine:**
Each of the 12 samples were measured in replicates of four. The observed creatinine concentrations versus the expected concentrations were assessed for a linear response. Based on the results, the sponsor concluded that the creatinine test system demonstrate linearity over the claimed range of 2.54 to 740 mg/dL. The linear regression summary is given below.
| Range tested | Slope | Intercept | R² |
| --- | --- | --- | --- |
| 1.24 to 871 mg/dL | 1.0049 | -0.11 | 1.0000 |
**3. Analytical Specificity/Interference:**
The analytical specificity of the creatinine assay on the ARCHITECT c8000 was established by conducting interference testing following the recommendations in CLSI EP07 ED3.
**Serum**
Interference from exogenous and endogenous substances was assessed using serum spiked with creatinine at two concentrations of 0.6 mg/dL and 2.0 mg/dL. Each spiked sample was further divided into two aliquots: test (with added interferent) and control (with no added interferent, except total protein with normal level of 7 g/dL). Each sample was tested in 10 replicates using one lot and one instrument. A substance was identified as an interferent if the difference in the mean between the control and test sample was outside of ±10% at the target levels.
The following table lists the highest concentration of each substance at which no significant interference was found. For any substances identified as an interferent, dose response testing and analysis was conducted to assess the highest concentration limit below which no significant interference is expected.
| Substance | Highest concentration tested at which no interference was observed |
| --- | --- |
| Endogenous | |
| Acetoacetate | 20 mg/dL |
| Conjugated Bilirubin | 20 mg/dL |
| Unconjugated Bilirubin | 8 mg/dL |
| Glucose | 250 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Triglycerides | 750 mg/dL |
| Exogenous | |
| Acetaminophen | 160 mg/dL |
| Acetohexamide | 0.5 mg/dL |
| Acetylcysteine | 150 mg/dL |
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| Substance | Highest concentration tested at which no interference was observed |
| --- | --- |
| Acetylsalicylic acid | 30 mg/dL |
| Ampicillin-Na | 80 mg/dL |
| Ascorbic acid | 60 mg/dL |
| Azlocillin | 0.7 g/dL |
| Biotin | 3510 ng/mL |
| Ca-dobesilate | 60 mg/dL |
| Cefotaxime | 53 mg/dL |
| Cefoxitin | 4.7 mg/dL |
| Cephalothin | 2 mg/dL |
| Cyclosporine | 2 mg/dL |
| Doxycycline | 20 mg/dL |
| Eltrombopag | 1 mg/dL |
| Hydroxocobalamin (Cyanokit) | 18.7 mg/dL |
| Ibuprofen | 220 mg/dL |
| Levodopa | 8 mg/dL |
| Methyldopa | 10 mg/dL |
| Metronidazole | 130 mg/dL |
| Nitrofurantoin | 0.3 mg/dL |
| Nitroglycerin | 0.015 mg/dL |
| Norfenefrine | 4 mg/dL |
| Phenylbutazone | 330 mg/dL |
| Rifampicin | 50 mg/dL |
| Sodium Heparin | 4 U/mL |
| Sulbactam | 240 mg/dL |
| Sulfamethoxazole | 40 mg/dL |
| Sulfapyridine | 30 mg/dL |
| Sulfasalazine | 500 mg/dL |
| Theophylline | 60 mg/dL |
| Trimethoprim | 5 mg/dL |
| Substance | Effect on test results when interferent is above the concentration limit in the table above |
| --- | --- |
| Conjugated Bilirubin | Decreased creatinine results |
| Unconjugated Bilirubin | Decreased creatinine results |
| Glucose | Increased creatinine results |
| Triglycerides | Increased creatinine results |
| Acetohexamide | Increased creatinine results |
| Azlocillin | Increased creatinine results |
| Cefoxitin | Increased creatinine results |
| Cephalothin | Increased creatinine results |
| Eltrombopag | Decreased creatinine results |
| Hydroxocobalamin (Cyanokit) | Increased creatinine results |
| Methyldopa | Decreased creatinine results |
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# Total Protein
Interference from total protein was assessed using serum spiked with creatinine at concentrations of 0.6, 1.5, and $2.0\mathrm{mg / dL}$ . The sponsor defined interference as $> \pm 10\%$ difference between the mean of the control and test sample.
| Creatinine conc. | Concentration lower limit with no significant interference | Concentration upper limit with no significant interference | Effect on test results when concentration below the lower limit | Effect on test results when concentration above the upper limit |
| --- | --- | --- | --- | --- |
| 0.6 mg/dL1 | 5.4 g/dL | 8.4 g/dL | Decreased creatinine results | Increased creatinine results |
| 1.5 mg/dL1 | 5.1 g/dL | 10 g/dL | Decreased creatinine results | Increased creatinine results |
| 2.0 mg/dL2 | - | 11 g/dL | Decreased creatinine results | Increased creatinine results |
Test results compared to a control sample with total protein concentration of $7.0\mathrm{g / dL}$ .
2Test results compared to a control sample with total protein concentration of $5.7\mathrm{g / dL}$
The sponsor includes the following limitations in the product labeling:
The Creatinine2 assay is susceptible to interference from cephalosporin class antibiotics and eltrombopag at therapeutically relevant interferent concentrations. The assay is also susceptible to interference from acetohexamide, bilirubin (conjugated and unconjugated), glucose, hydroxocobalamin, and total protein.
# Urine
Interference from exogenous and endogenous substances was assessed using a normal urine pool that was supplemented with a creatinine stock solution to yield a high creatinine sample with a target concentration of $400\mathrm{mg / dL}$ . A low creatinine sample was prepared by diluting a normal urine pool with artificial urine to yield a sample with a target concentration of 15 $\mathrm{mg / dL}$ . Each low and high sample was further divided into two aliquots: control (with no added interferent) and test (with added interferent). Each sample was tested in 10 replicates using one lot and one instrument. A substance was identified as an interferent if the difference in the mean between the control and test sample was outside of $\pm 10\%$ at target levels of $15\mathrm{mg / dL}$ and $400\mathrm{mg / dL}$ .
The following table lists the concentrations of each substance at which no significant interference was found. For any substances identified as an interferent, dose response testing and analysis was conducted to assess the highest concentration limit below which no significant interference is expected.
| Substance | Highest concentration tested at which no significant interference was observed |
| --- | --- |
| Endogenous and urine additives | |
| Acetic Acid | 6.25 mL/dL |
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| Substance | Highest concentration tested at which no significant interference was observed |
| --- | --- |
| Acetoacetate | 480 mg/dL |
| Ascorbate | 220 mg/dL |
| Boric Acid | 250 mg/dL |
| Glucose | 1000 mg/dL |
| Hydrochloric Acid (6N) | 2.5 mL/dL |
| Nitric Acid | 5.0 mL/dL |
| Protein | 50 mg/dL |
| Sodium Carbonate | 1.25 g/dL |
| Sodium Fluoride | 400 mg/dL |
| Sodium Oxalate | 60 mg/dL |
| Urobilinogen | 40 mg/dL |
| Exogenous | |
| Acetaminophen | 16 mg/dL |
| Acetylcysteine | 15 mg/dL |
| Biotin | 4250 ng/mL |
| Cefoxitin | 100 mg/dL |
| Cephalothin | 180 mg/dL |
| Homogentisic acid | 350 mg/dL |
| Hydroxocobalamin (Cyanokit) | 18 mg/dL |
| Ibuprofen | 22 mg/dL |
| Levodopa | 70 mg/dL |
| Methyldopa | 2 mg/dL |
| Nitrofurantoin | 15 mg/dL |
| Nitrofurazone | 0.3 mg/dL |
| Substance | Effect on test results when interferent is above the concentration limit in the table above |
| --- | --- |
| Cefoxitin | Increased creatinine results |
| Levodopa | Increased creatinine results |
4. Assay Reportable Range:
See section A.2 Linearity
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability
The Creatinine2 assay is traceable to the NIST SRM 967a (serum/plasma) or NIST SRM 914a (urine).
6. Detection Limit:
Detection capability studies of the creatinine assay on the ARCHITECT c8000 with serum and urine for limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) was conducted following the recommendations in CLSI EP17-A2.
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Serum
LoB
The LoB for the creatinine assay was evaluated using a zero-analyte sample. The sample was measured in 60 replicates using each of three lots of the Creatinine2 reagent kits and two instruments (total of six instrument and reagent lot combinations). The LoB was analyzed as the 95th percentile from n = 60 replicates.
LoD
The LoD was evaluated using eight low-level samples. The samples were tested in replicates of 10 using each of three lots of the Creatinine2 reagent kits and two instruments.
The LoD was analyzed using a parametric data analysis where the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
LoQ
To determine the LoQ, samples near the lower limit of the assay were run in replicates of 10 using each of three lots of the Creatinine2 reagent kits and two instruments. The LoQ was defined as the lowest concentration of analyte which has imprecision less than or equal to 20% CV.
Urine
LoB
The LoB for the creatinine assay was evaluated using a zero-analyte sample. The sample was measured in 60 replicates using each of three lots of the Creatinine2 reagent kits and two instruments (total of six instrument and reagent lot combinations). The LoB was analyzed as the 95th percentile from n = 60 replicates.
LoD
The LoD was evaluated using eight low-level samples. The samples were tested in replicates of 10 using each of three lots of the Creatinine2 reagent kits and two instruments. The LoD was analyzed using a parametric data analysis where the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
LoQ
To determine the LOQ, samples near the lower limit of the assay were run in replicates of 10 using each of three lots of the Creatinine2 reagent kits and two instruments. The LoQ was defined as the lowest concentration of analyte which has imprecision less than or equal to 20% CV.
The results from all studies, using the maximum value found across all lots and instruments are summarized in the table below.
| | LoB | LoD | LoQ |
| --- | --- | --- | --- |
| serum | 0.02 | 0.04 | 0.09 mg/dL |
| urine | 0.70 | 1.05 | 2.30 mg/dL |
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7. Assay Cut-Off:
Not applicable.
B Comparison Studies:
1. Method Comparison with Predicate Device:
The accuracy of the creatinine assay on the ARCHITECT c8000 for serum and urine was evaluated for agreement with the predicate device by an internal method comparison study.
Serum
In the study, a total of 128 serum samples were tested using three lots of the creatinine reagent kit, and one lot each of calibrator and controls across two instruments. 3.9% (5/128) of samples were prepared by spiking or diluting specimens. The data were analyzed by Passing-Bablok regression analysis comparing the first replicate of the candidate device result to the average of duplicates result of the comparator device:
| N | Concentration range, comparator device (mg/dL) | Regression Equation | r |
| --- | --- | --- | --- |
| 128 | 0.47 – 35.7 | y = 0.96x - 0.01 | 1.00 |
Urine
A total of 129 urine samples were tested using three lots of the creatinine reagent kit, and one lot each of calibrator and controls across two instruments. Less than 10% (7.0% [9/129]) of samples were prepared by spiking or diluting specimens. The data were analyzed by Passing-Bablok regression analysis comparing the first replicate of the candidate device result to the average of duplicates result of the comparator device:
| N | Concentration range, comparator device (mg/dL) | Regression Equation | r |
| --- | --- | --- | --- |
| 129 | 6.6 – 727.6 | y = 1.01x – 1.23 | 1.00 |
2. Matrix Comparison:
A matrix equivalency study was conducted to support use of the Creatinine2 assay with additional specimen matrix types claimed in the product labeling: K2EDTA plasma, lithium heparin plasma, lithium heparin (separator tube) plasma, serum (separator tube), and sodium heparin plasma. In the study, donor matched venous specimens were collected into tubes of each aforementioned anticoagulant. Each specimen was tested in singlicate using one lot of kit and one ARCHITECT c8000 instrument, and the result compared to the mean of triplicate serum measurements. A total of 11.3% (9/80) of the blood samples in the collection tubes were supplemented with creatinine stock solution to create samples that spanned the analytical measuring interval of the assay. A Passing-Bablok evaluation was performed, regressing the concentration from the first replicate of each donor's evaluation tube (y-axis) versus the mean concentration of the control tube (x-axis). The slope and intercept of the regression line, and the two-sided 95% CI around the slope and intercept were calculated. The results are summarized as follows, and support the claimed use of K2EDTA plasma,
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lithium heparin plasma, lithium heparin (separator tube) plasma, serum (separator tube), and sodium heparin plasma with the Creatinine2 assay:
| Collection Tube | N | Min | Max | r | Intercept (95% CI) | Slope (95% CI) |
| --- | --- | --- | --- | --- | --- | --- |
| Dipotassium EDTA | 80 | 0.38 | 21.46 | 1.00 | 0.02 (0.00, 0.03) | 0.98 (0.97, 1.00) |
| Lithium heparin | 80 | 0.39 | 23.24 | 1.00 | 0.01 (0.00, 0.03) | 0.98 (0.97, 1.00) |
| Sodium heparin | 80 | 0.40 | 20.75 | 1.00 | 0.02 (-0.01, 0.04) | 0.97 (0.95, 1.00) |
| Lithium heparin (separator tube) | 80 | 0.39 | 26.46 | 1.00 | 0.01 (0.00, 0.03) | 0.99 (0.97, 1.00) |
| Serum (separator tube) | 80 | 0.39 | 22.02 | 1.00 | 0.01 (0.00, 0.02) | 0.99 (0.98, 1.00) |
## C Clinical Studies:
1. Clinical Sensitivity: Not applicable.
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:
The expected values for creatinine in adults with serum and urine are from literature references.
Serum, adults
| Age | Range, mg/dL |
| --- | --- |
| 18 years - < 41 years Female | 0.5 - 1.0 |
| 18 years - < 41 years Male | 0.6 - 1.2 |
| 41 years - < 61 years Female | 0.5 - 1.1 |
| 41 years - < 61 years Male | 0.6 - 1.3 |
| 61 years and above Female | 0.5 - 1.2 |
| 61 years and above Male | 0.7 - 1.3 |
Source: Pagana K, Pagana T. Mosby's Manual of Diagnostic and Laboratory Tests. 5th ed. Mosby; 2014.
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Urine, random, adults
| Age | Range, mg/dL |
| --- | --- |
| Male < 40 years | 24 - 392 |
| Male ≥ 40 years | 22 - 328 |
| Female < 40 years | 16 - 327 |
| Female ≥ 40 years | 15 - 278 |
Source: Wu AHB, editor. Tietz Clinical Guide to Laboratory Tests. 4th ed. St. Louis, MO: Elsevier Saunders; 2006.
## 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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