(167 days)
No
The device description and performance studies focus on a chemical reaction-based assay with standard analytical corrections (rate blanking, intercept correction). There is no mention of AI or ML in the device description, intended use, or performance evaluation.
No
This device is an in vitro diagnostic assay used for the quantitative determination of creatinine, which aids in the diagnosis and monitoring of renal diseases. It does not provide any treatment or therapeutic action.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is "for in vitro diagnostic use" and that "Such measurements are used in the diagnosis and treatment of renal diseases".
No
The device is an in vitro diagnostic assay and calibrator, which are chemical reagents and materials, not software. It is used with a hardware analyzer (Atellica CH Analyzer).
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "The Atellica™ CH Creatinine 2 (Crea 2) assay is for in vitro diagnostic use..." and "The Atellica™ CH Chemistry Calibrator (CHEM CAL) is for in vitro diagnostic use...". This is the most direct confirmation.
- Purpose: The intended use describes the quantitative determination of creatinine in human samples (serum, plasma, urine) for use in the "diagnosis and treatment of renal diseases, and in monitoring renal dialysis." This aligns perfectly with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes.
- Device Description: The description details a chemical reaction (Jaffe method) used to measure a substance (creatinine) in biological samples. This is a typical characteristic of an in vitro diagnostic assay.
- Performance Studies: The performance studies described (Detection Limit, LOQ, Linearity, Precision, Interferences, Method Comparison, Matrix Equivalency, Reference Interval) are all standard types of studies conducted to validate the performance of an IVD device.
- Predicate Device: The mention of a predicate device (ADVIA Chemistry Enzymatic Creatinine_2) with a K number (K070727) indicates that this device is being compared to a previously cleared IVD device, which is a common pathway for regulatory clearance of new IVDs.
All of these factors strongly indicate that this device is intended for and functions as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The Atellica™ CH Creatinine 2 (Crea 2) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin), and urine using the Atellica™ CH Analyzer. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.
The Atellica™ CH Chemistry Calibrator (CHEM CAL) is for in vitro diagnostic use in calibrating the Crea_2 assay using the Atellica™ CH Analyzer.
Product codes (comma separated list FDA assigned to the subject device)
CGX, JIT
Device Description
ATELLICA CH CREATININE 2 (CREA 2)
The Atellica CH Creatinine_2 (Crea_2) assay is based on the reaction of picric acid with creatinine in an alkaline medium as described in the original procedure of Jaffe. Creatinine reacts with picric acid in an alkaline medium to produce a red-colored creatinine-picrate complex. The rate of complex formation is measured at 505/571 nm and is proportional to the creatinine concentration. The Atellica CH Creatinine 2 (Crea_2) assay is a modification of the Jaffe method using rate blanking and intercept correction. Rate blanking is used to minimize bilirubin interference. Also, because nonspecific serum/plasma protein interactions with this reagent have been found to produce a positive bias of approximately 0.3 mg/dL (26.5 umol/L), serum/plasma measurements are automatically corrected by subtracting 0.3 mg/dL (26.5 umol/L) from each result.
Reaction Equation
OH. Creatinine + Picric acid Creatinine-Picrate
Serum, lithium heparin plasma and urine specimens may be used. The reagent is stored unopened at 2 - 8 °C and is stable for use on system for 17 days. Calibration is performed every 60 days for a reagent lot or every 6 days for an individual pack.
ATELLICA CH CHEMISTRY CALIBRATOR (CHEM CAL)
The Atellica CH Chemistry Calibrator (CHEM CAL) is a 1 level lyophilized calibrator product prepared from bovine serum base product. The product is stored at 2 - 8 °C. The Atellica CH Chemistry Calibrator is stable for 48 hours at 2 - 8 °C after being opened, rehydrated and securely recapped.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
Not Found
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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
DETECTION LIMIT
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.
Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach.
LoB Rank Position = 0.5 +0.95*B, where B=total reps=60; Rank = 57.5
Results: LoB = 0.03 mg/dL serum, 0.35 mg/dL urine. LoD = 0.08 mg/dL serum, 0.51 mg/dL urine.
LOQ
The Limit of Quantitation (LoQ) for serum was determined as described in CLSI Document EP17-A2. Total Error is calculated using: TE = bias + 2 * SD.
Five replicates of ten low samples were processed on three reagent lots for three days on five calibrations per day, on one instrument for a total of 75 measurements per reagent lot per sample. For serum, the measured LoQ was 0.13 mg/dL in support of the LoQ claim of 0.15 mg/dL for serum and plasma samples. For urine, the measured LoQ was 2.57 mg/dL in support of the LoQ claim of 3.00 mg/dL for urine samples. The LoQ claims for serum and urine are each based a total of 2250 determinations with a total error goal of ≤ ±0.1 mg/dL for serum specimens and ≤ ±1.5 mg/dL for urine specimens.
LINEARITY STUDY
Linearity was evaluated with 12 samples which spanned the assay measuring interval for serum and plasma specimens and 10 samples which spanned the assay measuring interval for urine specimens. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A). The high sample was prepared by spiking native serum or urine pools with purified creatinine. Low pools were created by diluting serum and urine samples with a 6% BSA or 0.9% saline solution respectively. Five replicates were measured for each sample. The mean of these replicates was used for the calculations.
The assay was considered linear across the measuring interval if the p values of nonlinear terms in the quadratic and cubic fit equations are nonsignificant (p ≤ 0.05). If the p-value is > 0.05, then the allowable bias is ≤ 5% or 0.15 mg/dL, whichever is greater.
PRECISION STUDIES
Precision testing was performed in accordance with CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline - Third Edition. Precision was tested n = 2 replicates, two times a day for at least 20 days for a total of 80 replicates with controls, serum and plasma pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3.
Summary provided in a table with Repeatability and Within-Lab Precision for various sample types (Serum, Plasma Pool, Serum Pool, Serum QC, Urine QC, Urine).
INTERFERENCES
CLSI EP7-A2 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 measurand in serum and urine pools.
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. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference. This study was conducted as needed for both serum pools.
No interference was detected at a wide range of analyte concentrations for various substances in Serum and Urine.
METHOD COMPARISON
The predicate device selected for the method comparison study was the ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (K070727). Remnant de-identified samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. The study included native and spiked samples to properly span the assay intervals.
These studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization 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-A3, demonstrated good agreement between the Atellica CH Creatinine_2 (Crea_2) and the predicate ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) assay with patient samples.
The results across the full assay intervals were analyzed using weighted Deming regression. One replicate of each sample was tested and used in the analysis.
Comparison Assay (x): ADVIA Ecre_2. N=140 for Serum, r=0.999, Regression Equation y = 0.98x + 0.00 mg/dL, Sample Range 0.12-28.89 mg/dL. N=109 for Urine, r=0.999, Regression Equation y = 0.95x +0.07 mg/dL, Sample Range 3.57 - 238.85 mg/dL.
Comparison Assay (x): Isotope Dilution Mass Spectrometry (IDMS). N=49 for Serum, r=0.999, Regression Equation y = 0.96x + 0.05 mg/dL, Sample Range 0.41 - 32.09 mg/dL.
These data demonstrate good agreement with IDMS.
MATRIX EQUIVALENCY
Serum and lithium heparin plasma equivalency was demonstrated by testing fifty eight matched samples. Some samples were spiked with creatinine to obtain samples spanning the assay measuring intervals. The weighted Deming linear regression statistics for Plasma (Lithium heparin) vs. Atellica CH Crea_2 – Serum: N=58, r=1.000, Regression Equation y = 1.00x – 0.01 mg/dL, Sample Range 0.68 – 24.87 mg/dL.
REFERENCE INTERVAL
Reference intervals for healthy adults were verified on the Atellica CH Analyzer in accordance with CLSI Document EP28-A3c. Values are provided as guidance.
Adult males Serum/plasma: 0.70 - 1.30 mg/dL (62 - 115 µmol/L)
Adult females Serum/plasma: 0.55 - 1.02 mg/dL (49 - 90 µmol/L)
Adult males Urine: 950 - 2490 mg/day (8.4 - 22.0 mmol/day)
Adult females Urine: 600 - 1800 mg/day (5.3 - 15.9 mmol/day)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Key metrics reported are LoB, LoD, LoQ, Regression (R), bias, SD, CV.
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.
ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (K070727), ADVIA Chemistry Calibrator (K050374)
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.
Not Found
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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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
November 15, 2016
SIEMENS HEALTHCARE DIAGNOSTICS, INC. LAURA DUGGAN, PH.D. REGULATORY TECHNICAL SPECIALIST 500 GBC DRIVE, PO BOX 6101 MS 514 NEWARK DE 19711
Re: K161494
Trade/Device Name: Atellica CH Creatinine 2 (Crea 2); Atellica™ CH Chemistry Calibrator (CHEM CAL) Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: II Product Code: CGX, JIT Dated: September 26, 2016 Received: September 27, 2016
Dear Dr. Laura 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 (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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" (21 CFR 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/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education 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.
Sincerely yours,
Katherine Serrano -S
For: 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
2
Indications for Use
510(k) Number (if known)
Device Name
Atellica CH Creatinine 2 (Crea 2);Atellica™ CH Chemistry Calibrator (CHEM CAL)
Indications for Use (Describe)
The Atellica™ CH Creatinine 2 (Crea 2) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin), and urine using the Atellica™ CH Analyzer, Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.
The Atellica™ CH Chemistry Calibrator (CHEM CAL) is for in vitro diagnostic use in calibrating the Crea 2 assay using the Atellica™ CH Analyzer.
| 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) |
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10. 510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
ASSIGNED 510(K) NUMBER
The assigned 510(k) number is
APPLICANT AND DATE
Laura J. Duggan, Ph. D., RAC Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: laura.j.duggan@siemens.com Phone: 302-631-7654 Fax: 302-631-6299
November 11, 2016
MANUFACTURER
Siemens Healthcare Diagnostics Inc. 511 Benedict Ave Tarrytown, NY 10591 Registration Number: 2432235
REGULATORY INFORMATION
Regulatory Submission for the Atellica™ CH Creatinine_2 (Crea_2) and Atellica™ CH Chemistry Calibrator (CHEM CAL)
| Common Name: | Alkaline Picrate, Colorimetry,
Creatinine | Calibrator, Secondary |
|-------------------------|----------------------------------------------|------------------------------------------------|
| Proprietary Name: | Atellica CH Creatinine_2
(Crea_2) | Atellica CH Chemistry Calibrator
(CHEM CAL) |
| Classification
Name: | Creatinine Test System | Calibrator |
| Regulation
Number: | 21CFR862.1225 | 21CFR862.1150 |
| Classification: | Class II | Class II |
| Product Code: | CGX | JIT |
| Panel: | Clinical Chemistry | Clinical Chemistry |
| Predicate Device: | ADVIA Chemistry Enzymatic | ADVIA Chemistry Calibrator |
4
| Creatinine_2 (ECRE_2) | (K050374) | |
|---|---|---|
| (K070727) |
DEVICE DESCRIPTION
ATELLICA CH CREATININE 2 (CREA 2)
The Atellica CH Creatinine_2 (Crea_2) assay is based on the reaction of picric acid with creatinine in an alkaline medium as described in the original procedure of Jaffe. Creatinine reacts with picric acid in an alkaline medium to produce a red-colored creatinine-picrate complex. The rate of complex formation is measured at 505/571 nm and is proportional to the creatinine concentration. The Atellica CH Creatinine 2 (Crea_2) assay is a modification of the Jaffe method using rate blanking and intercept correction. Rate blanking is used to minimize bilirubin interference. Also, because nonspecific serum/plasma protein interactions with this reagent have been found to produce a positive bias of approximately 0.3 mg/dL (26.5 umol/L), serum/plasma measurements are automatically corrected by subtracting 0.3 mg/dL (26.5 umol/L) from each result.
Reaction Equation
OH. Creatinine + Picric acid Creatinine-Picrate
Serum, lithium heparin plasma and urine specimens may be used. The reagent is stored unopened at 2 - 8 °C and is stable for use on system for 17 days. Calibration is performed every 60 days for a reagent lot or every 6 days for an individual pack.
ATELLICA CH CHEMISTRY CALIBRATOR (CHEM CAL)
The Atellica CH Chemistry Calibrator (CHEM CAL) is a 1 level lyophilized calibrator product prepared from bovine serum base product. The product is stored at 2 - 8 °C. The Atellica CH Chemistry Calibrator is stable for 48 hours at 2 - 8 °C after being opened, rehydrated and securely recapped.
INTENDED USE/INDICATIONS FOR USE
ATELLICA CH CREATININE_2 (CREA_2)
The Atellica™ CH Creatinine 2 (Crea 2) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin), and urine using the Atellica™ CH Analyzer. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.
5
The Atellica™ CH Chemistry Calibrator (CHEM CAL) is for in vitro diagnostic use in calibrating the Crea_2 assay using the Atellica™ CH Analyzer.
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
Below is a features comparison for the Atellica CH Creatinine_2 (Crea_2) assay and the Chemistry calibrator (CHEM CAL) vs. their predicates:
| Feature | Predicate Device:
ADVIA Chemistry Enzymatic
Creatinine_2 (ECRE_2)
(K070727) | New Device:
Atellica CH Creatinine_2
(Crea_2) |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use : | For in vitro diagnostic use in
the quantitative
determination of creatinine
in human
serum, plasma (lithium
heparin and K2EDTA), and
urine on ADVIA Chemistry
systems. | The Atellica™ CH
Creatinine_2 (Crea_2) assay
is for in vitro diagnostic use in
the quantitative determination
of creatinine in human serum,
plasma (lithium heparin), and
urine using the Atellica™ CH
Analyzer. |
| Indications for Use: | Such measurements are
used in the diagnosis and
treatment of renal diseases,
and in monitoring renal
dialysis | Same |
| Device Technology: | Enzymatic reaction of
Fossati, Prencipe, and Berti | Reaction of picric acid with
creatinine in an alkaline
medium as described in the
original
procedure of Jaffe. |
| Sample Type: | Serum, Lithium Heparin | Serum, Lithium Heparin |
| | plasma, K2-EDTA plasma
and urine | plasma, and urine |
| Reference Interval: | 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 | 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 |
| Standardization: | SRM967 | IDMS Reference Method |
| Calibration
Frequency: | 60 days | Same |
| Analytical Measuring
Interval: | Serum/Plasma:
0.10 – 30.00 mg/dL
Urine:
1.0 – 245.00 mg/dL | Serum and plasma:
0.15–30.00 mg/dL
Urine: 3.00–245.00 mg/dL |
| Interferences: | Bilirubin (Unconjugated) –
30 mg/dL
Bilirubin (Conjugated) – 30
mg/dL
Lipemia (Intralipid®) – 1000
mg/dL
Hemoglobin - 500 mg/dL | Bilirubin (Unconjugated) – 10
mg/dL
Bilirubin (Conjugated) – 20
mg/dL
Lipemia (Intralipid®) – 500
mg/dL
Hemoglobin - 500 mg/dL |
| Calibrators: | ADVIA Chemistry Calibrator
(K050374) | Atellica CH Chemistry
Calibrator |
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| Feature | Predicate Device: | New Device: |
|---|---|---|
| ADVIA Chemistry Calibrator | ||
| (K050374) | Atellica CH Chemistry | |
| Calibrator (CHEM CAL) | ||
| Intended Use : | For in vitro diagnostic use in | |
| the calibration of chemistry | The AtellicaTM CH Chemistry | |
| Calibrator (CHEM CAL) is for |
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| | assays on ADVIA®
Chemistry systems. | in vitro diagnostic use in
calibrating the Crea_2 assay
using the Atellica™ CH
Analyzer. |
|---------------------------------|----------------------------------------|---------------------------------------------------------------------------------------------------|
| Calibrator Matrix: | Bovine Serum Base | Same |
| Calibrator Form: | Lyophilized | Same |
| Number of Calibrator
Levels: | One | Same |
SUMMARY OF PERFORMANCE TESTING
Assay performance comparison results for the Atellica CH Creatinine_2 (Crea_2) with the Atellica CH Chemistry Calibrator (CHEM CAL) were obtained by processing the appropriate body fluids. Summary statistics for each are provided. These data demonstrate substantial equivalency of the Atellica CH Creatinine 2 (Crea 2) and the Atellica CH Chemistry Calibrator (CHEM CAL) versus the predicate devices. The following data represent typical assay performance.
DETECTION LIMIT
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.
Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach.
LoB Rank Position = 0.5 +0.95*B, where B=total reps=60; Rank = 57.5
| Atellica CH Creatinine_2 (Crea_2) - Limit of Detection Results | ||
|---|---|---|
| Limit | Protocol | Result |
| LoB | 4 samples with no analyte | |
| were tested (N=5) for 3 | ||
| days, one run per day, 3 | ||
| reagent lots | 0.03 mg/dL serum | |
| 0.35 mg/dL urine |
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| LoD | 4 low analyte samples
were tested (N=5) for 3
days, one run per day, 3
reagent lots | 0.08 mg/dL serum
0.51 mg/dL urine |
| ----- | ---------------------------------------------------------------------------------------------- | -------------------------------------- |
|---|
The nonparametric approach described in EP17-A2 was followed to determine the Limit of Detection.
LOQ
The Limit of Quantitation (LoQ) for serum was determined as described in CLSI Document EP17-A2. Total Error is calculated using: TE = bias + 2 * SD.
Five replicates of ten low samples were processed on three reagent lots for three days on five calibrations per day, on one instrument for a total of 75 measurements per reagent lot per sample. For serum, the measured LoQ was 0.13 mg/dL in support of the LoQ claim of 0.15 mg/dL for serum and plasma samples. For urine, the measured LoQ was 2.57 mg/dL in support of the LoQ claim of 3.00 mg/dL for urine samples. The LoQ claims for serum and urine are each based a total of 2250 determinations with a total error goal of ≤ ±0.1 mg/dL for serum specimens and ≤ ±1.5 mg/dL for urine specimens.
LINEARITY STUDY
Linearity was evaluated with 12 samples which spanned the assay measuring interval for serum and plasma specimens and 10 samples which spanned the assay measuring interval for urine specimens. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A). The high sample was prepared by spiking native serum or urine pools with purified creatinine. Low pools were created by diluting serum and urine samples with a 6% BSA or 0.9% saline solution respectively. Five replicates were measured for each sample. The mean of these replicates was used for the calculations.
The assay was considered linear across the measuring interval if the p values of nonlinear terms in the quadratic and cubic fit equations are nonsignificant (p ≤ 0.05). If the p-value is > 0.05, then the allowable bias is ≤ 5% or 0.15 mg/dL, whichever is greater.
PRECISION STUDIES
Precision testing was performed in accordance with CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline -
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Third Edition. Precision was tested n = 2 replicates, two times a day for at least 20 days for a total of 80 replicates with controls, serum and plasma pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3. The data are summarized in the following table.
| Repeatability | Within-Lab Precision | |||||||
|---|---|---|---|---|---|---|---|---|
| Sample Type | n | Mean | ||||||
| mg/dL (µmol/L) | SDa | |||||||
| mg/dL (µmol/L) | CVb | |||||||
| (%) | SDa | |||||||
| mg/dL (µmol/L) | CVb | |||||||
| (%) | ||||||||
| 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 |
) = standard deviation
CV = coefficient of variation
INTERFERENCES
CLSI EP7-A2 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 measurand in serum and urine pools.
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. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference. This study was conducted as needed for both serum pools.
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| Approximate Concentration (within 15%) of Analytes in Test Pools | |||
|---|---|---|---|
| Analyte | Matrix | Low | High |
| Creatinine | Serum | 1.50 mg/dL | 5.00 mg/dL |
| Creatinine | Urine | 40.00 mg/dL | 180.00 mg/dL |
No interference was detected at the following analyte concentrations.
Compounds tested for interference in Serum
| Substance | Substance Test Concentration
Common Unit (SI Unit) |
|----------------------|-------------------------------------------------------|
| Glucose | 182 mg/dL (10.1 mmol/L) |
| Ascorbate | 3.0 mg/dL (171 mmol/L) |
| Total Protein | 11.7 g/dL (117 g/L) |
| Cefoxitin | 3.75 mg/dL (88 mmol/L) |
| Cephalexin | 25 mg/dL (720 mmol/L) |
| Pyruvate | 7.5 mg/dL (852 µmol/L) |
| Acetoacetate | 20 mg/dL (1959 µmol/L) |
| Potassium Oxalate | 500 mg/dL (30 mol/L) |
| Dopamine (LevaDopa) | 75 mg/dL (3.8 mol/L) |
| Albumin | 6000 mg/dL (60 g/L) |
| Amikacin | 8 mg/dL (137 µmol/L) |
| Caffiene | 6 mg/dL (308 µmol/L)) |
| Carbamezepine | 3 mg/dL (127 µmol/L) |
| Cephradine | 25 mg/dL (769 µmol/L) |
| Chloramphenicol | 5 mg/dL (155 µmol/L) |
| Chlordiazepoxide | 1 mg/dL (33.3 µmol/L) |
| Cimetidine | 2 mg/dL (2652 µmol/L) |
| Dextran | 6000 mg/dL (1500 µmol/L) |
| Diazepam | 0.51 mg/dL (18 µmol/L) |
| Digoxin | 6.1 ng/mL (7.8 nmol/L) |
| EDTA | 200 mg/dL (2 g/L) |
| Erythromycin | 6 mg/dL (81.6 µmol/L) |
| Ethanol | 400 mg/dL (86.8 mmol/L) |
| Ethosuximide | 25 mg/dL (1770 µmol/L) |
| Furosemide | 6 mg/dL (181 µmol/L) |
| Gentamicin | 1 mg/dL (21 µmol/L) |
| IgG | 5000 mg/dL (5000 g/L) |
| Isopropanol | 1 g/dL (166 mmol/L) |
| Lidocaine | 1.2 mg/dL (51.2 µmol/L) |
| Nicotine | 0.1 mg/dL (6.2 µmol/L) |
| Nortriptyline | 1000 ng/mL (3797 µmol/L) |
| Penicillin G(1654) | 25 U/mL (25000 U/L) |
| Pentobarbital | 8 mg/dL (354 µmol/L) |
| Phenobarbitol | 10 mg/dL (431 µmol/L) |
| Phenytoin | 5 mg/dL (198 µmol/L) |
| Primidone | 4 mg/dL (183 µmol/L) |
| Propoxyphene | 0.16 mg/dL (4.91 µmol/L) |
| Sodium Fluoride | 400 mg/dL (4 g/L) |
| Theophylline | 4 mg/dL (222 µmol/L) |
| Triglyceride | 2500 mg/dL (17 mmol/L |
| Urea | 500 mg/dL (28.3 mmol/L) |
| Uric acid | 20 mg/dL (1190 µmol/L) |
| Valproic Acid | 50 mg/dL (3467 µmol/L) |
| Vancomycin | 10 mg/dL (69 µmol/L) |
| Substance | Substance Test Concentration
Common Unit (SI Unit) |
| 6N HCL | 0.01% HCI |
| Boric Acid | 1% w/v |
| pH 4 | |
| pH 9 | |
| Ascorbate | 3.0 mg/dL (171 mmol/L) |
| Glucose | 2000 mg/dL (111 mmol/L) |
| Conjugated Bilirubin | 50 mg/dL (855 umol/L) |
| Hemoglobin | 100 mg/dL (62.2 umol/L) |
| Acetaminophen | 200 mg/dL (1324 umol/L) |
| N-Acetyl cysteine | 2 mg/dL (123 mmol/L) |
| Ibuprofen | 500 mg/dL (24 mol/L) |
| Acetic Acid | 25 mL/24 hr collection |
| 6N Nitric Acid | 0.60% |
| Ethanol | 1 g/dL (217 mmol/L) |
| Gamma Globulin | 0.5 g/dL (5 g/L) |
| Human Serum Albumin | 0.5 g/dL (5 g/L) |
| Oxalic Acid | 0.1 g/dL (110 mmol/L) |
| Sodium carbonate | 5 g/24 hr collection |
Compounds tested for interference in Urine
METHOD COMPARISON
The predicate device selected for the method comparison study was the ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (K070727). Remnant de-identified
..............................................................................................................................................................................
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samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. The study included native and spiked samples to properly span the assay intervals.
These studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization 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-A3, demonstrated good agreement between the Atellica CH Creatinine_2 (Crea_2) and the predicate ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) assay with patient samples.
The table below also summarizes the data for comparison between Isotope Dilution Mass Spectrometry (IDMS) and the Atellica Creatinine 2 (Crea 2) assay. These data demonstrate good agreement with IDMS.
The results across the full assay intervals were analyzed using weighted Deming regression. One replicate of each sample was tested and used in the analysis.
| Specimen
Type | Comparison Assay
(x) | N | r | Regression
Equation | Sample Range |
|------------------|----------------------------------------------|-----|-------|---------------------------|------------------------|
| Serum | ADVIA Ecre_2 | 140 | 0.999 | y = 0.98x + 0.00
mg/dL | 0.12-28.89
mg/dL |
| Urine | ADVIA Ecre_2 | 109 | 0.999 | y = 0.95x +0.07
mg/dL | 3.57 - 238.85
mg/dL |
| Serum | Isotope Dilution Mass
Spectrometry (IDMS) | 49 | 0.999 | y = 0.96x + 0.05
mg/dL | 0.41 - 32.09
mg/dL |
MATRIX EQUIVALENCY
Serum and lithium heparin plasma equivalency was demonstrated by testing fifty eight matched samples. Some samples were spiked with creatinine to obtain samples spanning the assay measuring intervals. The table below summarizes the weighted Deming linear regression statistics. One replicate of each sample was tested and used in the analysis.
| Specimen Type | Comparison Assay (x) | N | r | Regression Equation | Sample Range |
|---|---|---|---|---|---|
| Plasma | |||||
| (Lithium heparin) | Atellica CH Crea_2 – Serum | 58 | 1.000 | $y = 1.00x – 0.01$ mg/dL | 0.68 – 24.87 mg/dL |
REFERENCE INTERVAL
Reference intervals for healthy adults were verified on the Atellica CH Analyzer in accordance with CLSI Document EP28-A3c. As with all in vitro diagnostic assays, each laboratory should determine its own reference interval for the diagnostic evaluation of patient results. Consider these values as guidance only.
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| Group | Specimen type | Reference Interval
common unit (SI unit) |
|---------------|---------------|---------------------------------------------|
| Adult males | Serum/plasma1 | 0.70 - 1.30 mg/dL (62 - 115 µmol/L) |
| Adult females | Serum/plasma² | 0.55 - 1.02 mg/dL (49 - 90 µmol/L) |
| Adult males | Urine3 | 950 - 2490 mg/day (8.4 - 22.0 mmol/day) |
| Adult females | Urine" | 600 - 1800 mg/day (5.3 - 15.9 mmol/day) |
-
- Burtis CA, Ashwood ER, eds. Tietz Fundamentals of Clinical Chemistry. 5th ed. Philadelphia, PA: WB Saunders Co: 2001:23-25, 422.
-
- 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.
-
- 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.
-
- Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, PA: WB Saunders Co; 1999:1809.
CONCLUSION
The Atellica CH Creatinine 2 (Crea 2) and the Atellica CH Chemistry Calibrator (CHEM CAL) are substantially equivalent to the ADVIA Chemistry Enzymatic Creatinine_2 (ECRE 2) (K070727) and the ADVIA Chemistry Calibrator (K050374) in principle and performance based on the similarity of device designs and function demonstrated through method comparison and other performance attributes.