Atellica CH Creatinine_2 (Crea_2), Atellica CH Chemistry Calibrator (CHEM CAL)
Device Facts
| Record ID | K161494 |
|---|---|
| Device Name | Atellica CH Creatinine_2 (Crea_2), Atellica CH Chemistry Calibrator (CHEM CAL) |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | CGX · Clinical Chemistry |
| Decision Date | Nov 15, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1225 |
| Device Class | Class 2 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K161494 · Nov 15, 2016 | Atellica CH Creatinine_2 (Crea_2), Atellica CH Chemistry Calibrator (CHEM CAL) | Siemens Healthcare Diagnostics, Inc. | Remnant de-identified patient clinical samples (serum and urine) | Remnant de-identified patient samples were used to perform a method comparison between the new device and the predicate device to demonstrate substantial equivalence. | Method comparison; Remnant clinical samples; Performance validation |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Method comparison study using remnant de-identified patient samples | Patients providing serum and urine samples in a clinical setting; Sample Size: 140 (Serum), 109 (Urine) | ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (k070727) | Method agreement (correlation and regression analysis) |
Indications for Use
The Atellica™ CH Creatinine_2 (Crea_2) assay is an in vitro diagnostic test used for the quantitative measurement of creatinine in human serum, plasma (lithium heparin), and urine, using the Atellica™ CH Analyzer. Creatinine measurements are used in the diagnosis and treatment of certain renal diseases, and in monitoring renal dialysis patients. The Atellica™ CH Chemistry Calibrator (CHEM CAL) is used for calibrating the Crea_2 assay using the Atellica™ CH Analyzer.
Device Story
The Atellica CH Creatinine 2 (Crea 2) is an in vitro diagnostic assay for the Atellica CH Analyzer. It utilizes a modified Jaffe method where creatinine reacts with picric acid in an alkaline medium to form a red-colored creatinine-picrate complex. The system measures the rate of complex formation at 505/571 nm, which is proportional to creatinine concentration. The device incorporates rate blanking to minimize bilirubin interference and applies an automatic 0.3 mg/dL subtraction to correct for positive bias caused by nonspecific serum/plasma protein interactions. The assay is used by laboratory technicians in clinical settings to provide quantitative results that assist healthcare providers in diagnosing renal disease and managing dialysis patients. The Atellica CH Chemistry Calibrator (CHEM CAL) is a bovine serum-based, lyophilized product used to calibrate the assay.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP05-A3 (n=80 replicates per sample). Linearity evaluated per CLSI EP06-A (r=1.000 serum, r=0.999 urine). Method comparison (n=143 serum, n=109 urine) vs predicate showed high correlation (r=0.999). Interference testing per CLSI EP07-A2 showed no significant bias for common endogenous/exogenous substances. Reference intervals validated via transference per CLSI EP28-A3c.
Technological Characteristics
Photometric/colorimetric assay; modified kinetic Jaffe method (alkaline picrate). Reagents: sodium hydroxide, picric acid. Calibrator: lyophilized bovine serum base. Analyzed on Atellica CH Analyzer. Measuring range: 0.15-30.00 mg/dL (serum/plasma), 3.00-245.00 mg/dL (urine). Traceable to NIST SRM 914 and IDMS reference method. Calibration interval: 60 days.
Indications for Use
Indicated for quantitative measurement of creatinine in human serum, lithium heparin plasma, and urine to aid in diagnosis and treatment of renal diseases and monitoring of renal dialysis patients.
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
- ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (k070727)
- ADVIA Chemistry Calibrator (k050374)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k161494
B. Purpose for Submission:
New Device
C. Measurand:
Creatinine
D. Type of Test:
Quantitative, photometric/colorimetric method
E. Applicant:
Siemens Healthcare Diagnostics, Inc.
F. Proprietary and Established Names:
Atellica CH Creatinine_2 (Crea-2)
Atellica CH Chemistry Calibrator (CHEM CAL)
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CGX | II | 21 CFR 862.1225, Creatinine test system | Chemistry (75) |
| JIT | II | 21 CFR 862.1150, Calibrator | Chemistry (75) |
H. Intended Use:
1. Intended use(s):
See Indications for use below.
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2. Indication(s) for use:
The Atellica™ CH Creatinine_2 (Crea_2) assay is an in vitro diagnostic test used for the quantitative measurement of creatinine in human serum, plasma (lithium heparin), and urine, using the Atellica™ CH Analyzer. Creatinine measurements are used in the diagnosis and treatment of certain renal diseases, and in monitoring renal dialysis patients.
The Atellica™ CH Chemistry Calibrator (CHEM CAL) is used for calibrating the Crea_2 assay using the Atellica™ CH Analyzer.
3. Special conditions for use statement(s):
For Prescription use only.
4. Special instrument requirements:
Atellica™ CH Analyzer
I. Device Description:
Atellica CH Crea_2 reagents has 2 major reagent packs. Reagent pack 1 (P1) contains 34.0 mL of sodium hydroxide (0.8) mol/L, and reagent pack 2 (P) contains 44.6 ml of picric acid (25 mmol/L).
The Atellica CH Chemistry Calibrator (CHEM CAL) is a one level lyophilized calibrator formulated from a bovine serum base product. The calibrator is supplied as a pack of 12 vials; each will hold 3ml after reconstitution.
All human sources materials were tests by FDA approved methods and found to be negative for HIV-1, HIV-2, and HBsAg.
The Atellica CH Analyzer has been previously cleared as the Trinidad CH System under k151767; the new name of the system is the Atellica CH Analyzer.
J. Substantial Equivalence Information:
1. Predicate device name(s):
ADVIA Chemistry Enzymatic Creatinine_2 (ECRE-2)
ADVIA Chemistry Calibrator
3. Predicate 510(k) number(s):
k070727
k050374
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# 4. Comparison with predicate:
Assay:
| Similarities/Differences | | |
| --- | --- | --- |
| Item | k161494 Atellica CH Creatinine_(Crea_2)2 Candidate Device | k070727 ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) Predicate Device |
| Intended Use : | Is intended for the quantitative measurement of creatinine in human serum, plasma (lithium heparin), and urine. | Same |
| Device Technology: | Modified Jaffe methodology (creatinine alkaline picrate) with photometric detection. | Enzymatic reaction of Fossati, Prencipe, and Berti |
| Sample Type: | Serum, Lithium Heparin Plasma and urine | Serum, Lithium Heparin plasma, K2EDTA plasma and urine |
| Reference Interval: | Serum/plasma Males 0.70-1.30 mg/dL Females 0.55 -1.02 mg/dL Urine: Males 950 - 2490 mg/day Females 600 - 1800 mg/day | Serum/Plasma: Males 0.6 - 1.1 mg/dL Females 0.5 - 0.8 mg/dL Urine Males 800 - 2000 mg/day Females 600 - 1800 mg/day |
| Standardization: | IDMS Reference Method | SRM967 |
| Calibration Frequency: | 60 days | Same |
| Analytical Measuring Range | Serum and plasma: 0.15-30.00 mg/dL Urine: 3.00-245.00 mg/dL | Serum/Plasma: 0.10 - 30.00 mg/dL Urine: 1.0 - 245.00 mg/dL |
| Interferences | Bilirubin (Unconjugated) - 10 mg/dL Bilirubin (Conjugated) - 20 mg/dL (Intralipid®) - 500 mg/dL Hemoglobin - 500 mg/dL | Bilirubin (Unconjugated) - 30 mg/dL Bilirubin (Conjugated) - 30 mg/dL Lipemia (Intralipid®) - 100 mg/dL Hemoglobin - 500 mg/dL |
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Calibrator:
| Similarities/Differences | | |
| --- | --- | --- |
| Item | k161494 Atellica CH Chemistry Calibrator (CHEM CAL) candidate Device | k050374 ADVIA Chemistry Calibrator Predicate Device |
| Intended Use : | Is intended for in vitro diagnostic use in calibrating the Creatinine assay. | Same |
| Calibrator Matrix: | Bovine Serum Base | Same |
| Calibrator Form: | Lyophilized | Same |
| Number of Calibrator Levels: | One | Same |
| Value assignment | Traceable to IDMS Reference Method and NIST SRM 914 | Traceable to NIST SRM914 |
## K. Standard/Guidance Document Referenced (if applicable):
The following guidelines from the Clinical and Laboratory Standards Institute (CLSI) were referenced:
- EP07-A2: Interference Testing of Clinical Chemistry; Approved Guideline
- EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Guideline - Third Edition
- EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline
- EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
- EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline
- EP28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition
## L. Test Principle:
The Atellica™ CH Creatinine_2 (Crea_2) assay is used to measure the creatinine concentration in human serum, plasma (lithium heparin), and urine using the Atellica™ CH Analyzer. The technique used is based on modified kinetic Jaffe technique with rate blanking and intercept correction. In the presence of a strong base such as sodium hydroxide, picrate reacts with creatinine to form a red chromophore. The rate of complex formation is measured at 505/571 nm and is proportional to the creatinine concentration in the sample. Rate blanking is used to reduce interference.
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M. Performance Characteristics (if/when applicable):
1. Analytical performance:
All performance studies were performed on the Atellica™ CH Analyzer.
a. Precision/Reproducibility:
Precision testing was performed in accordance with CLSI EP05-A3. Testing was performed two times a day in 2 replicates for 20 non-consecutive days for a total of 80 replicates. This study was performed using 3 serum pools with mean concentration values of 1.16 mg/dL, 19.31 mg/dL, and 26.00 mg/dL, 2 serum QC samples with mean concentration values of 1.97 mg/dL and 6.35 mg/dL, 1 serum sample with a mean concentration value 0.38 mg/dL and 1 plasma pool with a mean concentration value of 0.66 mg/dL. The urine precision study was performed using 2 levels of urine QC samples with mean concentration values of 59.62 mg/dL and 133.31 mg/dL, and 1 urine pool sample with a mean concentration value of 188.61 mg/dL. The results are summarized as below:
| Sample Type | n | Mean mg/dL (μmol/L) | Repeatability | | Within-Lab Precision | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD mg/dL (μmol/L) | CV (%) | SD mg/dL (μmol/L) | CV (%) |
| Serum | 80 | 0.38 (34) | 0.01 (0.5) | 1.7 | 0.010 (0.9) | 2.8 |
| Plasma pool | 80 | 0.66(58) | 0.01 (0.7) | 1.2 | 0.018 (1.6) | 2.8 |
| Serum Pool | 80 | 1.16 (103) | 0.01 (0.9) | 0.8 | 0.017(1.5) | 1.5 |
| Serum QC | 80 | 1.97 (174) | 0.02 (1.6) | 0.9 | 0.024 (2.1) | 1.2 |
| Serum QC | 80 | 6.35 (561) | 0.04 (3.7) | 0.7 | 0.062 (5.5) | 1.0 |
| Serum Pool | 80 | 19.31 (1707) | 0.04 (3.4) | 0.2 | 0.117 (10.3) | 0.6 |
| Serum Pool | 80 | 26.00 (2298) | 0.05 (4.7) | 0.2 | 0.145 (12.8) | 0.6 |
| Urine QC | 80 | 59.62 (5270) | 0.15 (13.5) | 0.3 | 0.376 (33.2) | 0.6 |
| Urine QC | 80 | 133.31 (11785) | 0.33 (29.4) | 0.2 | 0.961 (85.0) | 0.7 |
| Urine | 80 | 188.61 (16673) | 0.52 (46.1) | 0.3 | 1.779 (157.3) | 0.9 |
b. Linearity/assay reportable range:
A linearity study was performed in accordance with CLSI EP06-A. Samples were prepared by mixing high and low concentration samples to span the measurement interval; 12 samples were used to evaluate the entire measuring interval for serum and 10 samples were used to evaluate the entire measuring interval for urine. Five replicates were tested for each sample and the mean of these replicates was used for the calculation. The concentrations for serum samples ranged from 0.09 - 32.58 ng/dL and the concentrations for urine samples ranged from 0.20 - 278.43 mg/dL.
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The regression statistics of the serum linearity study:
$$
Y = 1.004x + 0.085, r = 1.000
$$
The regression statistics of the urine linearity study:
$$
Y = 0.986x + 0.049, r = 0.999
$$
The results of the linearity studies support the claimed measuring intervals for 0.15-30.00 mg/dL for serum and plasma specimens and 3.00-245.00 mg/dL for urine samples for the Atellica CH Creatinine_2 (Crea_2) assay on the Atellica™ CH Analyzer.
Validation of the automatic dilution function has been performed and the extended reportable range for serum is determined to be 60 mg/dl for serum and 735 mg/dL in urine. Both sample types have been shown to be accurately diluted (manually or by auto-dilution) in this range.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:
The Atellica CH Chemistry Calibrator (CHEM CAL) is traceable to NIST SRM 914 via value assignment (see below).
Additionally 49 serum samples were tested across the assay range were tested on Isotope Dilution Mass Spectrometry (IDMS) to demonstrate standardization of the assay.
| Specimen type | Comparison Assay (x) | N | R | Regression Equation | Sample Range |
| --- | --- | --- | --- | --- | --- |
| Serum | IDMS | 49 | 0.999 | y=0.96x + 0.05 | 0.41 – 32.09 mg/dL |
Manufacturing and value assignment for the calibrator:
The calibrator is manufactured with a bovine serum albumin base. Assigned lot-specific calibrator values used for the ADVIA Chemistry Calibrator will be utilized for the calibration of Atellica CH Creatinine_2 assay on the Atellica CH Analyzer. The target assigned value range is 7.6 to 9.6 mg/dL. A master lot is created and values are assigned on an ADVIA Chemistry system calibrated with NIST SRM 914; the master lot is used to assign the values of the commercial lots. The % recovery of the commercial lot is compared to the % recovery of the Master Lot and the previously released lot. The % recovery error limit is ±5%. The imprecision limit is 2.0% CV.
Stability: All studies were completed in accordance with CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents.
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Reagent Stability:
The 12 month shelf claim was established by an accelerated stability study. A real time stability study to support a claim of 12 months shelf life is ongoing. Unopened product is stable until the expiration date on the product stored at 15-25°C. All protocols and acceptance criteria were reviewed and found acceptable.
An open bottle stability study was conducted to ensure the reagent performed consistently throughout the claimed in use/onboard stability. The study results support the claim of on-board stability of 17 days at 15-25°C. All protocols and acceptance criteria were reviewed and found to be acceptable.
Calibrator Stability:
The shelf life of the unopened vial of calibrator is 24 months when stored at 2-8°C. Open vial/onboard calibrator is stable for 48 hours at 2-8°C. All protocols and acceptance criteria were reviewed and found acceptable.
Calibration Interval:
The calibration interval was evaluated in studies completed in accordance with CLSI EP25-A. The study completed confirmed the calibration interval of 60 days. The protocol and acceptance criteria were reviewed and found to be acceptable.
d. Detection limit:
The Limit of Blank (LoB) and Limit of Detection (LoD) and the Limit of Quantitation(LoQ) of the Atellica CH Creatinine_2 (Crea_2) on the Atellica CH Analyzer were evaluated in accordance with CLSI EP17-A2. A brief protocol summary and the results are presented in the table below:
| Atellica CH Creatinine_2 (Crea_2) - Limit of Detection Results (Serum/Plasma) | | |
| --- | --- | --- |
| Limit | Protocol | Value obtained |
| LoB | 4 samples with no analyte were tested 5 times for 3 days, one run per day, 3 reagent lots | 0.03 mg/dL |
| LoD | 4 low analyte samples were tested 5 times for 3 days, one run per day, 3 reagent lots | 0.08 mg/dL |
| LoQ | 5 replicates of ten low samples on three reagent lots for three days. | 0.13mg/dL |
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| Atellica CH Creatinine_2 (Crea_2) - Limit of Detection Results (Urine) | | |
| --- | --- | --- |
| Limit | Protocol | Value obtained |
| LoB | 4 samples with no analyte were tested 5 times for 3 days, one run per day, 3 reagent lots | 0.35 mg/dL |
| LoD | 4 low analyte samples were tested 5 times for 3 days, one run per day, 3 reagent lots | 0.51 mg/dL |
| LoQ | 5 replicates of ten low samples on three reagent lots for three days. | 2.57mg/dL |
The values obtained from this study support the claimed LoQ for serum creatinine of 0.13mg/dL and LoD of 0.08 mg/dL. The LoQ for urine creatinine is 2.57 mg/dL and the LoD is 0.51 mg/dL.
e. Analytical specificity:
The evaluation of potential interferents followed the recommendations in CLSI EP7-A2. Interference studies were performed for the creatinine measurement function by evaluating potential interfering substances using a "paired difference worst case scenario" approach, where interfering compounds were spiked at low or high levels into fresh serum or urine sample pools. Bias was defined as the difference in results between the control samples (without the interferent) and the test sample (containing the interferent) expressed in percent; results with a bias exceeding 10% was considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference.
No significant interference was detected for these endogenous substances at the following Concentrations in serum :
| Substance in Serum | Minimum concentration tested without interference |
| --- | --- |
| Hemoglobin | 500 mg/dL |
| Bilirubin, conjugated | 20 mg/dL |
| Bilirubin, unconjugated | 10 mg/dL |
| Lipemia ( Intralipid ) | 500 mg/dL |
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The following exogenous substances showed less than $10\%$ bias in the Crea_2 assay in serum.
| Substance in Serum | Minimum concentration Interference |
| --- | --- |
| Glucose | 182 mg/dL |
| Ascorbate | 3.0 mg/dL |
| Total Protein | 11.7 g/dL |
| Total Protein | 12.0 g/dL |
| Cefoxitin | 3.75 mg/dL |
| Cefoxitin | 5 mg/dL |
| Cephalexin | 25 mg/dL |
| Pyruvate | 7.5 mg/dL |
| Acetoacetate | 20 mg/dL |
| Potassium Oxalate | 500 mg/dL |
| Dopamine (LevaDopa) | 75 mg/dL |
| Albumin Serum | 6000 mg/dL |
| Amikacin | 8 mg/dL |
| Caffeine | 6 mg/dL |
| Carbamazepine | 3 mg/dL |
| Cephradine | 25 mg/dL |
| Chloramphenicol | 5 mg/dL |
| Chlordiazepoxide | 1mg/dL |
| Cimetidine | 2 mg/dL |
| Dextran | 6000 mg/dL |
| Diazepam | 0.51 mg/dL |
| Digoxin | 6.1 ng/mL |
| EDTA | 200 mg/dL |
| Erythromycin | 6 mg/dL |
| Ethanol - Serum | 400 mg/dL |
| Ethosuximide | 25 mg/dL |
| Furosemide | 6 mg/dL |
| Gentamicin | 1 mg/dL |
| IgG | 5000 mg/dL |
| Isopropanol | 1 g/dL |
| Lidocaine | 1.2 mg/dL |
| Nicotine | 0.10 mg/dL |
| Nortriptyline | 1000 ng/mL |
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| Substance in Serum | Minimum concentration Interference |
| --- | --- |
| Penicillin G(1654) | 25 U/mL |
| Pentobarbital | 8 mg/dL |
| Phenobarbital | 10 mg/dL |
| Phenytoin | 5 mg/dL |
| Primidone | 4 mg/dL |
| Propoxyphene | 0.16 mg/dL |
| Sodium Fluoride | 400 mg/dL |
| Theophylline | 4 mg/dL |
| Triglyceride | 1500 mg/dL |
| Triglyceride | 2500 mg/dL |
| Urea | 500 mg/dL |
| Uric acid | 20 mg/dL |
| Valproic Acid | 50 mg/dL |
| Vancomycin | 10 mg/dL |
| In Urine: Substances | Minimum concentration without interference |
| --- | --- |
| 6N HCL @ 0.01%HCl | 0.01% HCl |
| 1% w/v Boric Acid | 1% w/v |
| pH 4 | pH 4 |
| pH 9 | pH 9 |
| Ascorbate | 3.0 mg/dL |
| Glucose | 2000 mg/dL |
| Conjugated Bilirubin | 50 mg/dL |
| Hemoglobin | 100 mg/dL |
| Acetaminophen | 200 mg/dL |
| N-Acetyl cysteine | 2 mg/dL |
| Ibuprofen | 500 mg/dL |
| Acetic Acid | 25 mL/24 hr collection |
| Albumin - Urine | 0.5 g/dL |
| Ethanol - Urine | 1 g/dL |
| Gamma Globulin | 0.5 g/dL |
| Nitric Acid | 0.6 % |
| Oxalic Acid | 0.1g/dL |
| Sodium carbonate | 5 g/24 hr collection. |
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f. Assay cut-off:
Not applicable.
## 2. Comparison studies:
a. Method comparison with predicate device:
A method comparison study was performed following the recommendations in CLSI EP09-A3. A total of 143 serum samples and 109 urine samples were tested on the predicate device and on the candidate device, Atellica CH Creatinine_2 (Crea_2) assay on the Atellica CH Analyzer. Samples tested in the study included 10 spiked serum samples and 10 diluted urine samples to cover the lower end of the claimed assay ranges of 0.15-30 mg/dL (serum) and 3.00-245.00 mg/dL (urine). One replicate of each sample was tested on both test systems, and used in the analysis. Three of the serum samples were excluded from the analysis because they were below the predicate's measuring interval. Weighted Deming statistics were used to calculate the regression equation below:
Serum: y = 0.98x + 0.0 r = 0.999
Urine: y = 0.95x + 0.07 r = 0.999
b. Matrix comparison:
A total of fifty eight serum and lithium heparin plasma samples were tested on the Atellica CH Creatinine_2 (Crea_2) assay on the Atellica CH Analyzer. Seven samples were spiked with creatinine to cover the upper end of the claimed measuring range. One replicate of each sample was tested and used in the analysis.
The table below summarizes the weighted Deming linear regression statistics of the matrix comparison study
| Specimen Type | Comparison Assay (x) | N | r | Regression Equation | Sample Range (mg/dL) |
| --- | --- | --- | --- | --- | --- |
| Plasma (Lithium heparin) | Atellica CH Crea_2 – Serum | 58 | 1.000 | y = 1.00x – 0.01 | 0.68 – 24.87 |
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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:
Transference as defined in CLSI EP28-A3c was used to validate established reference ranges for serum and plasma creatinine. The sponsor performed a study to verify that the reference ranges, provided in literature and cited in the labeling, could be transferred to the candidate device. The study demonstrated that the published reference ranges could be transferred.
| Group | Specimen type | Reference Interval common unit (SI unit) |
| --- | --- | --- |
| Adult males | Serum/plasma^{1} | 0.70 - 1.30 mg/dL (62 - 115 μmol/L) |
| Adult females | Serum/plasma^{2} | 0.55 - 1.02 mg/dL (49 - 90 μmol/L) |
| Adult males | Urine^{3} | 950 - 2490 mg/day (8.4 - 22.0 mmol/day) |
| Adult females | Urine^{4} | 600- 1800 mg/day (5.3 - 15.9 mmol/day) |
The expected ranges presented in the proposed package insert were established from scientific literature with references listed below.
1. Burtis CA, Ashwood ER, eds. Tietz Fundamentals of Clinical Chemistry. 5<sup>th</sup>ed. Philadelphia, PA:WB Saunders Co; 2001:23-25, 422.
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2. Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem. 2008;54(3):559-566.
3. Junge W, Wilke B, Halabi A, Klein G. Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffé method. Clin Chim Acta. 2004;344(1-2):137-48.
4. Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd Philadelphia, PA: WB Saunders Co; 1999:1809.
Published 24 hour urine reference intervals are recommended because of difficulty in obtaining 24 hr. urine samples. Siemens recommends that each laboratory should come up with their own reference intervals for the diagnostic evaluation of the patients results.
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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