(157 days)
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No
The device description and performance studies focus on a standard chemical reaction (modified kinetic Jaffe technique) and its measurement using a bichromatic rate technique. There is no mention of AI, ML, or any computational methods beyond standard data analysis for performance evaluation.
No.
This device is an in vitro diagnostic test used for the quantitative measurement of creatinine, which aids in the diagnosis and monitoring of renal diseases but does not directly treat or prevent them.
Yes
The "Intended Use / Indications for Use" section explicitly states "The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine... Creatinine measurements are used in the diagnosis and treatment of certain renal disease, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes." This directly indicates its role in diagnosis.
No
The device is an in vitro diagnostic test that uses a chemical reaction and a clinical chemistry system (hardware) to measure creatinine. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states: "The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine..." This directly identifies the device as an IVD.
- Nature of the Test: The device performs a chemical analysis of biological samples (serum, plasma, and urine) outside of the body ("in vitro") to provide diagnostic information (creatinine levels for diagnosis and treatment of renal disease, monitoring dialysis, etc.). This is the core function of an IVD.
- Device Description: The description details a chemical reaction and measurement process applied to the sample, which is characteristic of an in vitro test.
- Performance Studies: The document describes various performance studies (Method Comparison, Precision, Limit of Detection, Linearity, Analytical Specificity, etc.) that are standard for evaluating the performance of an IVD.
- Predicate Device: The mention of a "Predicate Device" with a K number (K925668) indicates that this device is being compared to a previously cleared medical device, which is a common process for IVDs seeking regulatory clearance.
All of these points strongly support the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. Creatinine measurements are used in the diagnosis and treatment of certain renal disease, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Product codes (comma separated list FDA assigned to the subject device)
CGX
Device Description
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. The CRE2 method uses a modified kinetic Jaffe technique. In the presence of a strong base such as sodium hydroxide, picrate reacts with creatinine to form a red chromophore. The rate of increasing absorbance at 510 nm due to the formation of this chromophore is directly proportional to the creatinine concentration in the sample and is measured using a bichromatic (510, 600nm) rate technique. Bilirubin is oxidized by potassium ferricyanide to prevent interference.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Method Comparison (Predicate Device):
- Sample Size: 191 serum patient samples and 113 urine samples.
- Data Source: Remnant de-identified serum samples. No patient history information was obtained. All samples were native.
- Annotation Protocol: Not explicitly stated, but samples were tested in duplicate and only the first result was used for analysis. Linear regression was used for analysis.
Method Comparison (IDMS Reference Method):
- Sample Size: 48 patient samples.
- Data Source: Remnant de-identified serum samples. No patient history information was obtained. All samples were native.
- Annotation Protocol: Samples were tested in duplicate and only the first result was used for analysis. Linear regression was used for analysis.
Serum Plasma Equivalency:
- Sample Size: 56 matched serum and lithium heparin plasma samples.
- Data Source: Fresh, never frozen samples. Eight spiked sample sets were prepared by spiking equal amounts of purified creatinine into matched serum and lithium heparin plasma samples.
- Annotation Protocol: One replicate of each sample was processed. Linear regression statistics were summarized.
Precision:
- Sample Size: Two serum pools, three levels of BioRad Multiqual material, two levels of BioRad Liguicheck material, and two urine pools.
- Annotation Protocol: Testing performed over 20 days, two separate runs with two test samples for each test material. Analysis of variance (ANOVA) was used to evaluate the data consistent with CLSI EP05-A2 recommendations.
Limit of Blank and Limit of Detection:
- Sample Size:
- Serum LoB: 4 samples with no analyte tested (N=5) for 3 days, one run per day, 2 reagent lots.
- Serum LoD: 4 low patient serum samples tested (N=5) for 3 days, one run per day, 2 reagent lots.
- Urine LoB: 4 samples with no analyte tested (N=5) for 3 days, one run per day, 2 reagent lots.
- Urine LoD: 4 low patient urine samples tested (N=5) for 3 days, one run per day, 2 reagent lots.
- Annotation Protocol: Evaluated in accordance with CLSI EP17-A2. The nonparametric approach described in EP-17A2 was followed to determine the Limit of Detection.
Linearity (Measurement Range):
- Sample Size: 12 equally spaced serum samples and 12 equally spaced urine samples.
- Annotation Protocol: Samples spanned the assay range, prepared by mixing high and low creatinine concentration samples across the measurement range as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A).
Analytical Specificity (Non-interfering Substances):
- Data Source: Fresh sample pools containing either low or high levels of creatinine analyte in both serum pools and urine pools, spiked with various substances.
- Annotation Protocol: CLSI EP7A2 was followed for interference testing using a "paired difference worst case scenario" approach.
Analytical Specificity (Interfering Substances):
- Annotation Protocol: Evaluated according to CLSI EP7-A2. Bias exceeding 10% was considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference, conducted at two Creatinine analyte concentrations if both sample pools showed significant interference.
Hemolysis, Icterus, Lipemia (HIL) Interference:
- Annotation Protocol: Evaluated according to CLSI EP7-A2. Bias exceeding 10% was considered interference.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison (Predicate Device):
- Study Type: Method comparison, split sample method comparison following EP09-A2.
- Sample Size: 191 serum patient samples, 113 urine samples.
- Key Results:
- Serum: Slope = 1.00, Intercept = -0.08 mg/dL, Correlation Coefficient = 0.999 (Range 0.4 - 19.8 mg/dL).
- Urine: Slope = 1.04, Intercept = -3.58 mg/dL, Correlation Coefficient = 0.996 (Range 13.5 - 372.7 mg/dL).
- Demonstrated good agreement between the new device and the predicate device.
Method Comparison (IDMS Reference Method):
- Study Type: Method comparison.
- Sample Size: 48 patient samples.
- Key Results:
- Serum: Slope = 1.04, Intercept = 0.02 mg/dL, Correlation Coefficient = 0.997 (Range 0.18-6.32 mg/dL).
Serum Plasma Equivalency:
- Study Type: Equivalency study.
- Sample Size: 56 matched samples.
- Key Results: Slope = 1.05, Intercept = -0.02, Correlation Coefficient (r) = 0.998 (Range 0.50 - 17.35).
Precision:
- Study Type: Precision testing in accordance with CLSI EP05-A2.
- Key Results:
- Serum Pool 1: Mean 1.32 mg/dL, Repeatability SD 0.04, %CV 3.0; Within-Lab SD 0.04, %CV 3.2.
- Serum Pool 2: Mean 15.79 mg/dL, Repeatability SD 0.19, %CV 1.2; Within-Lab SD 0.19, %CV 1.2.
- BioRad Multiqual Level 1: Mean 0.71 mg/dL, Repeatability SD 0.03, %CV 4.7; Within-Lab SD 0.04, %CV 5.1.
- BioRad Multiqual Level 2: Mean 1.79 mg/dL, Repeatability SD 0.04, %CV 2.1; Within-Lab SD 0.05, %CV 2.8.
- BioRad Multiqual Level 3: Mean 7.04 mg/dL, Repeatability SD 0.07, %CV 1.0; Within-Lab SD 0.09, %CV 1.3.
- Urine Pool 1: Mean 39.31 mg/dL, Repeatability SD 1.52, %CV 3.9; Within-Lab SD 1.53, %CV 3.9.
- Urine Pool 2: Mean 339.56 mg/dL, Repeatability SD 4.28, %CV 1.3; Within-Lab SD 4.59, %CV 1.4.
- BioRad Liquicheck Level 1: Mean 62.28 mg/dL, Repeatability SD 0.61, %CV 1.0; Within-Lab SD 1.41, %CV 2.3.
- BioRad Liquicheck Level 2: Mean 142.80 mg/dL, Repeatability SD 1.56, %CV 1.1; Within-Lab SD 3.39, %CV 2.4.
Limit of Blank and Limit of Detection:
- Study Type: Evaluation in accordance with CLSI EP17-A2.
- Key Results:
- Serum LoB: 0.05 mg/dL.
- Serum LoD: 0.1 mg/dL.
- Urine LoB: 1.0 mg/dL (determined as 0.87 mg/dL).
- Urine LoD: 2.0 mg/dL (determined as 1.51 mg/dL).
Limit of Quantitation:
- Study Type: Evaluation consistent with CLSI Guideline EP17-A2.
- Key Results:
- Serum and plasma LoQ: 0.15 mg/dL.
- Urine LoQ: 5.00 mg/dL.
Linearity (Measurement Range):
- Study Type: Linearity evaluation as described in CLSI EP06-A.
- Key Results:
- Serum (0.15 - 22.00 mg/dL): Slope = 1.01, Intercept = -0.01, Correlation Coefficient = 1.0.
- Urine (3.00 - 425.34 mg/dL): Slope = 0.998, Intercept = -0.41, Correlation Coefficient = 1.0.
Analytical Specificity (Interfering Substances):
- Study Type: Interference study according to CLSI EP7-A2.
- Key Results (Substances showing >10% bias):
- Serum/Plasma: Acetone, Bilirubin (unconjugated), Cefoxitin, Cephalothin, Glucose, Intralipid 20%, Pyruvate, Triglycerides.
- Urine: Ascorbic Acid.
Hemolysis, Icterus, Lipemia (HIL) Interference:
- Study Type: Interference study according to CLSI EP7-A2.
- Key Results (Substances showing >10% bias):
- Hemoglobin (at 1000 mg/dL, -11.1% difference at ~1.4 mg/dL CRE2 result).
- Bilirubin (conjugated) (at 40 mg/dL, -17.2% difference at ~1.4 mg/dL CRE2 result).
- Bilirubin (unconjugated) (at 20 mg/dL, -20.2% difference at ~1.5 mg/dL CRE2 result).
- Intralipid 20% (at 1500 mg/dL, 11.3% difference at ~1.35 mg/dL CRE2 result).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Correlation Coefficient ranges from 0.996 to 1.0 for method comparison and linearity studies.
Precision (%CV) ranges from 1.0% to 5.1% for different analytes and levels.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1225 Creatinine test system.
(a)
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.(b)
Classification. Class II.
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5. 510(k) Summary
5.1 Description
Dimension® Creatinine (CRE2) Flex® reagent cartridge
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
5.2. Assigned 510(k) number
The assigned 510(k) number is: K132638
5.3 Applicant and Date
Laura J. Duggan Applicant: Siemens Healthcare Diagnostics Inc. P.O. Box 6101 Newark, DE 19714-6101
Auqust 22, 2013 Date:
5.4 Proprietary and Established Names
Dimension® Creatinine (CRE2) Flex® reagent cartridge
Common Name
Creatinine
5.5 Regulatory Information
Dimension® Creatinine (CRE2) Flex® reagent cartridge
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. Creatinine measurements are used in the diagnosis and treatment of certain renal disease, in monitoring renal dialysis, and as a calculation basis for measuring other urine analvtes.
1
Classification Name: Requlation Section: Classification: Product Code: Panel:
Creatinine test system 21CFR862.1225 - Creatinine test system Class II CGX Clinical Chemistry
5.6 Predicate Device
The predicate device used to demonstrate substantial equivalence to the Dimension® Creatinine (CRE2) Flex® reagent cartridge is the Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA) previously cleared under K925668.
5.7 Device Description / Test Principle
The CRE2 method uses a modified kinetic Jaffe technique. In the presence of a strong base such as sodium hydroxide, picrate reacts with creatinine to form a red chromophore. The rate of increasing absorbance at 510 nm due to the formation of this chromophore is directly proportional to the creatinine concentration in the sample and is measured using a bichromatic (510, 600nm) rate technique. Bilirubin is oxidized by potassium ferricyanide to prevent interference.
5.8 Intended Use
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. Creatinine measurements are used in the diagnosis and treatment of certain renal disease. in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
5.9 Indication(s) for Use
The CRE2 method is an in vitro diaqnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. Creatinine measurements are used in the diagnosis and treatment of certain renal disease, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
5.10 Substantial Equivalence Information
Both the Dimension® Creatinine (CRE2) Flex® reagent cartridge and the predicate Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA) employ prepackaged reagents for use on automated clinical chemistry test systems. A comparison of the similarities and differences between the devices is provided in the following tables:
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| New Device | Predicate Device | |||
|---|---|---|---|---|
| Feature | Dimension® Creatinine (CRE2) | |||
| Flex® reagent cartridge (K132638) | Creatinine Method for Use on the | |||
| Dimension® Clinical Chemistry | ||||
| System (CREA) (K925668) | ||||
| Intended Use | The CRE2 method is an in vitro | |||
| diagnostic test for the quantitative | ||||
| measurement of creatinine in | ||||
| human serum, plasma, and urine | ||||
| on the Dimension® clinical | ||||
| chemistry system. Creatinine | ||||
| measurements are used in the | ||||
| diagnosis and treatment of certain | ||||
| renal disease, in monitoring renal | ||||
| dialysis, and as a calculation basis | ||||
| for measuring other urine | ||||
| analytes. | The CREA method used on the | |||
| Dimension® clinical chemistry | ||||
| system is an in vitro diagnostic test | ||||
| intended for the quantitative | ||||
| determination of creatinine in | ||||
| human serum, plasma and urine. | ||||
| Device | ||||
| Technology | ||||
| (detection) | Modified Jaffe Methodology | |||
| (creatinine alkaline picrate) with | ||||
| photometric detection | Same | |||
| Detection | ||||
| Conditions | Wavelength = 510 and 600 nm | |||
| Type of Measurement = | ||||
| Bichromatic rate | Same | |||
| Sample Volume | 20 pl | Same | ||
| Reagents | Reagent 1 = Lithium Picrate (125 | |||
| mM) | ||||
| Reagent 2 = Sodium Hydroxide | ||||
| (2000 mM) with potassium | ||||
| ferricyanide (2.7 mM) | Same | |||
| Reagent Volumes | Volume of Reagent 1 used = 74 µL | |||
| Volume of Reagent 2 used = 18 µL | ||||
| Volume of Diluent used = 258 µL | Same | |||
| Calibration | ||||
| Interval | 90 days - same reagent lot | Same |
Similarities for the Dimension® Creatinine (CRE2) Flex® reagent cartridge:
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.
:
3
| Limit of
Blank/Analytical
| Sensitivity | Limit of Blank: 0.05 mg/dL | Analytical Sensitivity : 0.05 mg/dL |
|---|---|---|
| Calibration | Chem 1 Calibrator (K860021) | |
| 3 levels (n=3) | Same (K860021) |
Differences for the Dimension® Creatinine CRE2 Flex® reagent cartridge:
| Feature | New Device
Dimension® Creatinine (CRE2)
Flex® reagent cartridge (K132638) | Predicate Device
Creatinine Method for Use on the
Dimension® Clinical Chemistry
System (CREA) (K925668) |
|----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Measuring Range
(serum) | 0.15 - 20.00 mg/dL | 0 - 20.0 mg/dL |
| Measuring Range
(urine) | 5.00 - 400.00 mg/dL | 0 - 200.0 mg/dL |
| Expected Values | Serum and Plasma
Males: 0.70 -- 1.30 mg/dL
Females: 0.55 - 1.02 mg/dL
Urine
Males: 0.95 - 2.49 g/24 hr
Females: 0.60 - 1.80 g/24 hr | Serum
Males: 0.8 – 1.3 mg/dL
Females: 0.6 - 1.0 mg/
Urine
Males: 0.6 – 2.5 g/24 hr
Females: 0.6 – 1.5 g/24 hr |
| Interferences | No significant interference at a
Creatinine concentration of 1.5
mg/dL from:
Hemoglobin at 500 mg/dL
Bilirubin (conjugated) at 20 mg/dL,
Bilirubin (unconjugated) at 10
mg/dL
Lipemia (Intralipid) at 1000 mg/dL. | No significant interference at a
Creatinine concentration of 1.7
mg/dL from:
Hemoglobin at 1000 mg/dL,
Bilirubin (unconjugated) at 5 mg/dL
Lipemia (Intralipid) at 200 mg/dL |
.
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5.11 Standard/Guidance Document Reference
- Stability Testing of In Vitro Diagnostic Reagents (CEN 13640) .
- CLSI EP07-A2; Interference Testing in Clinical Chemistry; Approved Guideline· .
- CLSI EP09-A2-IR; Method Comparison and Bias Estimation Using Patient Samples; . Approved Guideline
- CLSI EP05-A2; Evaluation of Precision Performance of Quantitative Measurement . Methods: Approved Guideline
- CLSI EP06-A; Evaluation of the Linearity of Quantitative Measurement .
- CLSI EP17-A2: Protocols for Determination of Limits of Detection and Limits of . Quantitation
- CLSI C28-A3c; Defining, Establishing, and Verifying Reference Intervals in the . Clinical Laboratory: Approved Guideline - Third Edition
- In Vitro Diagnostic Creatinine Test System Guidance for Industry July 2, 1998 .
- In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submissions . Jan. 1997
- . Format for Traditional and Abbreviated 510(k)'s - Guidance for Industry and Staff -Nov. 17, 2005
- Guidance for Industry and FDA Staff: Administrative Procedures for CLIA . Categorization - May 7, 2008
- eCopy Program for Medical Device Submissions Guidance for Industry and Food . and Drug Administration Staff - December 31, 2012,
- Refuse to Accept Policy for 510(k)s Guidance for Industry and Food and Drug o Administration Staff - December 31, 2012
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5.12 Performance Characteristics
The following data represent typical method performance. These data were collected on the Dimension EXL 200 integrated chemistry system.
5.12.1 Method Comparison
The predicate device selected for the method comparison was the Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA) cleared under K925668. Remnant de-identified serum samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. All of the samples were native.
These studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D orqanization personnel. The personnel conducting the study were laboratory technicians with training similar to personnel who would conduct the tests in a hospital laboratory setting. They were trained on the operation of both the device and the predicate device. A split sample method comparison, following EP09-A2, demonstrated good agreement between the Dimension® Creatinine (CRE2) Flex® reagent cartridge and the predicate Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA) with serum patient samples.
One hundred ninety one serum patient samples across the assay range were tested on the Dimension® Creatinine (CRE2) Flex® reagent cartridge and the Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA). In a second study, 113 urine samples were tested on the Dimension® Creatinine (CRE2) Flex® reagent cartridge and the Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA). The results across the full assay range were analyzed by linear regression. Although the samples were tested in duplicate, only the first result was used for the analvsis.
| Comparative
Method | Range
(mg/dL) | Slope | Intercept
(mg/dL) | Correlation
Coefficient | n | Sample
type |
|-------------------------|------------------|-------|----------------------|----------------------------|-----|----------------|
| Dimension
CREA Assay | 0.4 - 19.8 | 1.00 | -0.08 | 0.999 | 191 | serum |
| Dimension
CREA Assay | 13.5 - 372.7 | 1.04 | -3.58 | 0.996 | 113 | urine |
The model equation for the regression statistics is: [results for Dimension® CRE2 Flex® reagent cartridge] = slope x [comparative method results] + intercept.
An additional study was completed comparing the Dimension® Creatinine (CRE2) Flex® reagent cartridge for the IDMS reference method. Remnant de-identified serum samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. All of the samples were native.
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Forty eight patient samples were tested on the Dimension® Creatinine (CRE2) Flex® reagent cartridge and the IDMS reference method. The results were analyzed by linear regression. Although the samples were tested in duplicate, only the first result was used for the analysis.
| Comparative
Method | Range
(mg/dL) | Slope | Intercept
(mg/dL) | Correlation
Coefficient | n | Sample
type |
|-----------------------------|------------------|-------|----------------------|----------------------------|----|----------------|
| IDMS
Reference
Method | 0.18-6.32 | 1.04 | 0.02 | 0.997 | 48 | serum |
The model equation for the reqression statistics is: [results for Dimension® Creatinine (CRE2) Flex® reagent cartridge] = slope x [comparative method results] + intercept.
5.12.2 Serum Plasma Equivalency
Serum and lithium heparin plasma equivalency was demonstrated for the Dimension® Creatinine (CRE2) Flex® reagent cartridge. Fifty six matched serum and lithium heparin plasma samples were tested using the Dimension® Creatinine (CRE2) Flex® reagent cartridge. The table below summarizes the linear regression statistics.
| Serum vs. | Slope | Intercept | Correlation
Coefficient (r) | Range | n |
|---------------------------|-------|-----------|--------------------------------|--------------|----|
| Lithium Heparin
Plasma | 1.05 | -0.02 | 0.998 | 0.50 - 17.35 | 56 |
One replicate of each sample was processed. All samples in the study were fresh and never frozen. The eight spiked sample sets were prepared by spiking equal amounts of purified creatinine into the matched serum and lithium heparin plasma samples.
5.12.3 Precision
Precision testing was performed in accordance with CLSI EP05-A2 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline ~ Second Edition. Samples consisted of two (2) serum pools, three (3) levels of BioRad Multiqual material, two (levels) of BioRad Liguicheck material and two (2) urine pools. Testing was performed over twenty (20) days, two (2) separate runs with two test samples for each test material. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A2. The data are summarized in the following table:
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| Repeatability | Within-Lab | |||||
|---|---|---|---|---|---|---|
| Sample | Mean | |||||
| (mg/dL) | SD | %CV | SD | %CV | ||
| Serum | Serum Pool 1 | 1.32 | 0.04 | 3.0 | 0.04 | 3.2 |
| Serum Pool 2 | 15.79 | 0.19 | 1.2 | 0.19 | 1.2 | |
| BioRad Multiqual Level 1 | 0.71 | 0.03 | 4.7 | 0.04 | 5.1 | |
| BioRad Multiqual Level 2 | 1.79 | 0.04 | 2.1 | 0.05 | 2.8 | |
| BioRad Multiqual Level 3 | 7.04 | 0.07 | 1.0 | 0.09 | 1.3 | |
| Urine | Urine Pool 1 | 39.31 | 1.52 | 3.9 | 1.53 | 3.9 |
| Urine Pool 2 | 339.56 | 4.28 | 1.3 | 4.59 | 1.4 | |
| BioRad Liquicheck Level 1 | 62.28 | 0.61 | 1.0 | 1.41 | 2.3 | |
| BioRad Liquicheck Level 2 | 142.80 | 1.56 | 1.1 | 3.39 | 2.4 |
.
BioRad® is a registered trademark of Bio-Rad Laboratories, Irvine, CA 92618, USA. Multiqual® is a registered trademark of Bio-Rad Laboratories, Irvine, CA 92618, USA. Liquichek™ is a trademark of Bio-Rad Laboratories, Irvine, CA 92618, USA.
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5.12.4 Limit of Blank and Limit of Detection
The Limit of Blank (LoB) and Limit of Detection (LoD) were evaluated in accordance with CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation: Approved Guideline.
| Dimension® Creatinine (CRE2) Flex® reagent cartridge
| Limit of Detection Results with Serum | ||||||
|---|---|---|---|---|---|---|
| Limit | Protocol | Value | ||||
| LoB | 4 samples with no analyte | |||||
| were tested (N=5) for 3 days, | ||||||
| one run per day, 2 reagent | ||||||
| lots, | 0.05 mg/dL | |||||
| LoD | 4 low patient serum samples | |||||
| were tested (N=5) for 3 days, | ||||||
| one run per day, 2 reagent | ||||||
| lots | 0.1 mg/dL. |
| Limit | Protocol | Value |
|---|---|---|
| LoB | 4 samples with no analyte | |
| were tested (N=5) for 3 days, | ||
| one run per day, 2 reagent | ||
| lots, | 1.0 mg/dL | |
| LoD | 4 low patient urine samples | |
| were tested (N=5) for 3 days, | ||
| one run per day, 2 reagent | ||
| lots | 2.0 mg/dL |
The nonparametric approach described in EP-17A2 was followed to determine the Limit of Detection.
LoB = Mean of Blank Measurement + 1.645 x Standard Deviation of Blank Measurements LoD = Limit of Blank + CpSDs
• Co is a correction factor for the 95% CI normal variate to account for bias in · the SDs estimate.
· SDs is an estimate of method imprecision pooled from replicates of the low analyte samples
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The LoB was determined to be 0.05 mg/dL with serum samples and is consistent with the claim of 0.05 mq/dL. With urine samples, the LoB was determined to be 0.87 mg/dL and is consistent with the claim of 1.0 mg/dL.
The LoD was determined to be 0.08 mg/dL with serum samples and is consistent with the claim of 0.1 mg/dL. With urine samples, the LoD was determined to be 1.51 mg/dL. and is ' consistent with the claim of 2.0 mg/dL.
5.12.5 Limit of Quantitation
The Limit of Quantitation (LoQ) for the Dimension® Creatinine (CRE2) Flex® reagent cartridge for serum and plasma is 0.15 mg/dL and based on allowable total error of 0.15 mg/dL, determined consistent with CLSI Guideline EP17-A2.
The Limit of Quantitation (LoQ) for the Dimension® Creatinine (CRE2) Flex® reagent cartridge for urine is 5.00 mg/dL and based on allowable total error of 3.00 mg/dL, determined consistent with CLSI Guideline EP17-A2.
5.12.6 Linearity (Measurement Range)
Linearity was evaluated for serum and urine samples by using 12 equally spaced samples which spanned the assay range. Each was prepared by mixing high and low creatinine concentration samples across the measurement range as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A).
Regression Statistics
| Range of samples | Slope | Intercept | Correlation
Coefficient | N |
|-------------------------------|-------|-----------|----------------------------|----|
| serum
0.15* - 22.00 mg/dL | 1.01 | -0.01 | 1.0 | 12 |
| urine
3.00* - 425.34 mg/dL | 0.998 | -0.41 | 1.0 | 12 |
*represents the LoQ
5.13 Analytical Specificity
5.13.1 Non-interfering Substances
CLSI EP7A2 was followed for the interference testing. The interference study was conducted using a "paired difference worst case scenario" approach where these compounds were spiked into fresh sample pools containing either low or high levels of creatinine analyte in both serum pools and urine pools.
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| LOW pool (~ 1.5mg/dL) | HIGH pool (~ 5.0 mg/dL) | ||||||
|---|---|---|---|---|---|---|---|
| Substance | Concentration of | ||||||
| Substance | |||||||
| (mg/dL) | Mean | Control | % Diff | mean | control | % Diff | |
| Acetaminophen | 20 | 1.35 | 1.37 | -2% | 4.90 | 4.75 | 3% |
| Acetoacetate | 20 | 1.43 | 1.43 | 0% | 4.83 | 4.81 | 0% |
| Amikacin | 8 | 1.39 | 1.37 | 1% | 4.76 | 4.75 | 0% |
| Ampicillin | 5.3 | 1.39 | 1.37 | 1% | 4.72 | 4.75 | -1% |
| Ascorbic Acid | 6 | 1.41 | 1.39 | 2% | 4.90 | 4.74 | 3% |
| Caffeine | 6 | 1.38 | 1.37 | 1% | 4.76 | 4.75 | 0% |
| Carbamazepine | 3 | 1.39 | 1.39 | 0% | 4.77 | 4.84 | -1% |
| Cephalexin | 25 | 1.46 | 1.43 | 2% | 4.88 | 4.81 | 1% |
| Cephapirin | 25 | 1.46 | 1.43 | 2% | 4.86 | 4.87 | 0% |
| Cephradine | 25 | 1.43 | 1.43 | 0% | 4.88 | 4.87 | 0% |
| Chloramphenicol | 5 | 1.41 | 1.36 | 3% | 4.76 | 4.79 | -1% |
| Chlordiazepoxide | 1 | 1.37 | 1.38 | -1% | 4.79 | 4.72 | 1% |
| Chlorpromazine | 0.2 | 1.36 | 1.37 | -1% | 4.77 | 4.70 | 1% |
| Cholesterol Supertrate | 503 | 1.31 | 1.31 | 0% | 4.42 | 4.35 | 2% |
| Cimetidine | 2 | 1.37 | 1.37 | 0% | 4.74 | 4.75 | 0% |
| Dextran 40 | 6000 | 1.55 | 1.49 | 4% | 4.98 | 5.04 | -1% |
| Diazepam | 0.51 | 1.39 | 1.38 | 1% | 4.76 | 4.72 | 1% |
| Digoxin | 6.1ng/mL | 1.42 | 1.41 | 0% | 4.72 | 4.71 | 0% |
| EDTA | 200 | 1.37 | 1.36 | 0% | 4.86 | 4.80 | 1% |
| Erythromycin | 6 | 1.38 | 1.36 | 1% | 4.72 | 4.79 | -1% |
| Ethanol | 400 | 1.39 | 1.39 | 0% | 4.77 | 4.74 | 0% |
| Ethosuximide | 25 | 1.39 | 1.37 | 1% | 4.74 | 4.75 | 0% |
| Furosemide | 6 | 1.40 | 1.36 | 2% | 4.77 | 4.79 | 0% |
| Gentamicin | 1 | 1.38 | 1.39 | 0% | 4.72 | 4.74 | -1% |
| Heparin (196 Units/mg) | 3 U/mL | 1.38 | 1.37 | 1% | 4.74 | 4.74 | 0% |
| Ibuprofen | 50 | 1.41 | 1.39 | 2% | 4.80 | 4.84 | -1% |
| Immunoglobulin G (IgG) | 5000 | 1.56 | 1.49 | 5% | 5.07 | 5.04 | 1% |
| Isopropanol | 1.0 g/dL | 1.38 | 1.36 | 1% | 4.81 | 4.80 | 0% |
| Lidocaine | 1.2 | 1.39 | 1.36 | 2% | 4.79 | 4.79 | 0% |
| Lithium | 2.2 | 1.37 | 1.37 | 0% | 4.73 | 4.70 | 0% |
| Nicotine | 0.1 | 1.40 | 1.39 | 0% | 4.82 | 4.84 | 0% |
| Nortriptyline | 1000 ng/mL | 1.40 | 1.36 | 2% | 4.85 | 4.80 | 1% |
| Penicillin G (1654 Units/mg) | 25 U/mL | 1.37 | 1.37 | 0% | 4.71 | 4.70 | 0% |
| Pentobarbital | 8 | 1.41 | 1.37 | 3% | 4.74 | 4.79 | -1% |
| Phenobarbital | 10 | 1.39 | 1.37 | 1% | 4.79 | 4.79 | 0% |
| Phenytoin | 5 | 1.38 | 1.38 | 0% | 4.81 | 4.72 | 2% |
| Potassium oxalate | 500 mg/dL | 1.46 | 1.43 | 2% | 4.90 | 4.81 | 2% |
| Primidone | 4 | 1.40 | 1.39 | 1% | 4.75 | 4.84 | -2% |
| DM CRE2 | Serum/Plasma Substances | ||||||
| LOW pool (~1.5mg/dL) | HIGH pool (~ 5.0 mg/dL) | ||||||
| Substance | Concentration of | ||||||
| Substance | |||||||
| (mg/dL) | Mean | Control | % Diff | mean | control | % Diff | |
| Protein, Albumin | 6000 | 1.49 | 1.49 | 0% | 4.73 | 5.20 | -9% |
| Protein, Total | 12g/dL | 1.57 | 1.49 | 6% | 4.95 | 4.98 | -1% |
| Salicylic acid | 60 | 1.41 | 1.36 | 4% | 4.79 | 4.79 | 0% |
| Sodium fluoride | 400 | 1.35 | 1.34 | 1% | 4.59 | 4.59 | 0% |
| Theophylline | 4 | 1.39 | 1.37 | 1% | 4.83 | 4.75 | 2% |
| Urea | 500 | 1.42 | 1.37 | 3% | 4.80 | 4.70 | 2% |
| Uric acid | 20 | 1.40 | 1.39 | 0% | 4.98 | 4.77 | 4% |
| Valproic acid | 50 | 1.38 | 1.37 | 1% | 4.76 | 4.75 | 0% |
| Vancomycin | 10 | 1.42 | 1.39 | 2% | 4.81 | 4.74 | 1% |
| DM CRE2 | Urine Substances | ||||||
| Substance | Concentration of | ||||||
| Substance | |||||||
| (mg/dL) | LOW pool (~40 mg/dL) | HIGH pool (~175 mg/dL) | |||||
| Mean | Control | % Diff | mean | control | % Diff | ||
| 50% Acetic Acid | 25mL/24 hr collection | 41.23 | 40.82 | 1% | 180.56 | 178.44 | 1% |
| 6N Hydrochloric Acid | 0.6% | 41.76 | 41.41 | 1% | 180.84 | 181.20 | 0% |
| 6N Nitric Acid | 0.6% | 41.95 | 41.41 | 1% | 181.85 | 181.20 | 0% |
| Acetone | 100 mg/dL | 41.53 | 42.10 | -1% | 181.95 | 183.29 | -1% |
| Bilirubin (conjugated) | 2 mg/dL | 41.39 | 41.05 | 1% | 179.95 | 180.73 | 0% |
| Boric Acid | 1% w/v | 40.46 | 41.91 | -3% | 183.69 | 183.76 | 0% |
| Ethanol | 1 g/dL | 41.44 | 42.20 | -2% | 180.88 | 184.21 | -2% |
| Gamma Globulin | 0.5 g/dL | 41.24 | 41.69 | -1% | 182.54 | 180.88 | 1% |
| Glucose | 2 g/dL | 41.06 | 41.69 | -2% | 178.55 | 180.88 | -1% |
| Hemoglobin | 115 mg/dL | 42.09 | 41.93 | 0% | 183.40 | 179.88 | 2% |
| Human Serum Albumin | 0.5 g/dL | 40.55 | 41.49 | -2% | 180.8 | 179.8 | 1% |
| Oxalic Acid | 0.1 g/dL | 39.94 | 39.50 | 1% | 173.04 | 172.25 | 0% |
| Sodium Carbonate | 5g/24 hr collection | 41.26 | 40.74 | 1% | 179.24 | 180.10 | 0% |
| Sodium Fluoride | 1% w/v | 41.65 | 41.91 | -1% | 184.79 | 183.76 | 1% |
.
and the comments of the comments of
:
11
5.13.2 Interfering Substances
The CRE2 method was evaluated for interference according to CLSI EP7-A2. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference. These studies were conducted at
12
two Creatinine analyte concentrations, if both sample pools show significant interference. This study was conducted as needed for both serum pools and urine pools.
| Substance | Concentration
of Substance | Mean Test CRE2
Result (mg/dL) | Mean Control
CRE2 Result
(mg/dL) | %Diff |
|--------------------------|-------------------------------|----------------------------------|----------------------------------------|--------|
| Serum/Plasma Sample Type | | | | |
| Acetone | 18.75 mg/dL | 1.56 | 1.41 | 11% |
| Acetone | 75 mg/dL | 5.37 | 4.84 | 11% |
| Bilirubin (unconj) | 20 mg/dL | 1.20 | 1.50 | -20.2% |
| Cefoxitin | 5 mg/dL | 1.62 | 1.43 | 13% |
| Cephalothin | 12.5 mg/dL | 1.57 | 1.41 | 12% |
| Glucose | 500 mg/dL | 1.60 | 1.43 | 12% |
| Intralipid 20% | 1500 mg/dL | 1.50 | 1.35 | 11.3% |
| Pyruvate | 10.5 mg/dL | 5.71 | 4.81 | 19% |
| Triglycerides | 3000 mg/dL | 1.42 | 1.22 | 16% |
| Urine Sample Type | | | | |
| Ascorbic Acid | 0.15 g/dL | 44.29 | 39.97 | 11% |
| Ascorbic Acid | 0.3 g/dL | 199.52 | 178.25 | 12% |
5.13.3 Hemolysis, Icterus, Lipemia (HIL) Interference
The CRE2 method was evaluated for interference according to CLSI EP7-A2. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference.
| DM CRE2 | HIL Interference | |||
|---|---|---|---|---|
| Substance | Concentration of | |||
| Substance (mg/dL) | Mean Test CRE2 | |||
| Result (mg/dL) | Mean Control CRE2 | |||
| Result (mg/dL) | % Difference | |||
| Hemoglobin | 1000 | 4.54 | 4.69 | -3.2% |
| Hemoglobin | 1000 | 1.24 | 1.4 | -11.1% |
| Hemoglobin | 500 | 1.37 | 1.44 | -4.9% |
| Bilirubin (conj) | 40 | 4.79 | 4.86 | -1.3% |
| Bilirubin (conj) | 40 | 1.16 | 1.40 | -17.2% |
| Bilirubin (conj) | 20 | 1.38 | 1.46 | -5.5% |
| Bilirubin (unconj) | 40 | 4.79 | 4.89 | -2.0% |
| Bilirubin (unconj) | 20 | 1.20 | 1.50 | -20.2% |
| Bilirubin (unconj) | 10 | 1.32 | 1.46 | -9.6% |
| Intralipid 20% | 2000 | 4.66 | 4.56 | 2.2% |
| Intralipid 20% | 1500 | 1.50 | 1.35 | 11.3% |
| Intralipid 20% | 1000 | 1.49 | 1.39 | 7.2% |
13
5.14 Conclusion
The Dimension® Creatinine (CRE2) Flex® reagent cartridge (DF33B) is substantially equivalent in principle and performance to the Creatinine Method for Use on the Dimension® Clinical Chemistry System (CREA) cleared under K925668. Comparative testing described in the submission demonstrates substantially equivalent performance.
14
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/14/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.
Public Health Service
Food and Orug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 27, 2014
SIEMENS HEALTHCARE DIAGNOSTICS INC. LAURA DUGGAN, PH.D. REGULATORY TECHNICAL SPECIALIST P.O. BOX 6101 NEWARK DE 19714
Re: K132638
Trade/Device Name: Dimension® Creatinine (CRE2) Flex® reagent cartridge Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: II Product Code: CGX Dated: November 13, 2013 Received: November 14, 2013
Dear Dr. Duggan:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
15
Page 2-Dr. Duggan
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803). please go to
http://www.fda.gov/MedicalDevices/Safetw/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometries/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor.You/Industry/default.htm.
Sincerely vours.
CourtneyH.Lias-S
Courtney H. Lias. Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
16
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K132638
Device Name
Dimension® Creatinine (CRE2) Flex® reagent cartridge
Indications for Use (Describe)
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension® clinical chemistry system. Creatinine measurements are treatment of certain rend disease. in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
[] Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signalure)
uth A. Chesler
FORM FDA 3881 (1/14)
PSC Pobliching Services (101) 413-4740 EF
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.