(89 days)
No
The device description details a chemical reaction-based assay with standard analytical corrections (rate blanking, intercept correction) and performance studies typical of in vitro diagnostics. There is no mention of AI or ML in the description, intended use, or performance studies.
No.
This device is for in vitro diagnostic use to measure creatinine levels, which aids in the diagnosis and monitoring of renal diseases, but it does not directly treat or provide therapy to a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay's measurements are "used in the diagnosis and treatment of renal diseases."
No
The device is an in vitro diagnostic assay, which involves chemical reactions and analysis of biological samples, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states "The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic use". It also describes its use in the quantitative determination of creatinine in human samples (serum, plasma, urine) for the diagnosis and treatment of renal diseases and monitoring renal dialysis. This clearly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens from the human body to provide information for diagnosis, monitoring, or treatment.
- Device Description: The description details a chemical assay performed on biological samples, which is characteristic of an in vitro diagnostic test.
- Performance Studies: The document describes performance studies (Detection Capability, Precision, Reproducibility, Assay Comparison, Specimen Equivalence, Interferences) that are standard for evaluating the performance of an IVD.
- Predicate Device: The mention of a predicate device (Atellica® CH Creatinine_2 (Crea_2)) with a K number (K161494) indicates that this device is being compared to a previously cleared IVD, which is a common regulatory pathway for new IVDs.
N/A
Intended Use / Indications for Use
The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin, dipotassium EDTA, and sodium 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.
Product codes
CGX
Device Description
The Atellica CH Crea3 assay is based on the reaction of picrate with creatinine in an alkaline medium to produce a red chromophore creatinine picrate complex. The rate of complex formation is measured at 505/571 nm and is proportional to the creatinine concentration. The Atellica CH Crea3 assay is a modification of the Jaffe method, using rate blanking and intercept correction. Rate blanking is used to minimize bilirubin interference. Also, because non-specific serum/plasma protein interactions with this reagent have been found to produce a positive bias of approximately 0.3 mg/dL (26.5 µmol/L), serum/plasma measurements are automatically corrected by subtracting 0.3 mg/dL (26.5 µmol/L) from each result.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Detection Capability
The Limit of Blank (LoB) corresponds to the highest measurement result that is likely to be observed for a blank sample. The assay is designed to have an LoB = 0.950 and a slope of 1.00 +- 0.05 for serum samples and correlation coefficient of >= 0.950 and a slope of 0.000 +- 3.00 for urine samples, compared to the Atellica CH Creatinine 2 (Crea_2) assay on the Atellica CH analyzer. Assay comparison was determined using the Weighted Deming regression model in accordance with CLSI Document EP09C-ED3.
Serum: y = 1.00x - 0.04 mg/dL, sample range 0.44 to 28.64, n=151, r=1.000.
Urine: y = 1.00x + 0.14 mg/dL, sample range 12.60 to 237.06, n=113, r=1.000.
Specimen Equivalence (Atellica® CH Creatinine_3 (Crea3))
The specimen equivalency was determined using the Weighted Deming regression model in accordance with CLSI Document EP09-A3.
Sodium Heparin vs Serum: y = 1.00x + 0.00 mg/dL, sample range 0.60 to 27.26, n=50, r=0.999.
Lithium Heparin vs Serum: y = 0.99x + 0.06 mg/dL, sample range 0.60 to 27.26, n=50, r=0.999.
Dipotassium EDTA vs Serum: y = 0.98x + 0.04 mg/dL, sample range 0.60 to 27.26, n=50, r=0.998.
Interferences (Atellica® CH Creatinine_3 (Crea3)) - Hemolysis, Icterus, and Lipemia (HIL)
Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in percent. The Atellica® CH Crea3 assay is designed to have 10% or 0.15 mg/dL whichever is greater for serum/plasma is considered interference. Analyte results should not be corrected based on this bias. Interference testing was performed in accordance with CLSI Document EP07-ED3.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Detection Capability Results:
Serum/plasma: LoB = 0.05 mg/dL, LoD = 0.10 mg/dL, LoQ = 0.15 mg/dL.
Urine: LoB = 0.50 mg/dL, LoD = 1.00 mg/dL, LoQ = 3.00 mg/dL.
Precision Results (Repeatability and Within-Lab total coefficient of variation):
Serum 1 (Mean 0.38 mg/dL): Repeatability SD=0.006 mg/dL, CV=1.6%; Within-Lab SD=0.012 mg/dL, CV=3.2%.
Serum 2 (Mean 0.73 mg/dL): Repeatability SD=0.023 mg/dL, CV=3.2%; Within-Lab SD=0.029 mg/dL, CV=4.0%.
Serum 3 (Mean 0.73 mg/dL): Repeatability SD=0.006 mg/dL, CV=0.8%; Within-Lab SD=0.019 mg/dL, CV=2.6%.
Serum 4 (Mean 1.18 mg/dL): Repeatability SD=0.007 mg/dL, CV=0.6%; Within-Lab SD=0.019 mg/dL, CV=1.6%.
Serum QC 1 (Mean 1.85 mg/dL): Repeatability SD=0.007 mg/dL, CV=0.4%; Within-Lab SD=0.024 mg/dL, CV=1.3%.
Serum QC 2 (Mean 6.21 mg/dL): Repeatability SD=0.011 mg/dL, CV=0.2%; Within-Lab SD=0.067 mg/dL, CV=1.1%.
Serum 5 (Mean 17.39 mg/dL): Repeatability SD=0.035 mg/dL, CV=0.2%; Within-Lab SD=0.189 mg/dL, CV=1.1%.
Serum 6 (Mean 28.54 mg/dL): Repeatability SD=0.056 mg/dL, CV=0.2%; Within-Lab SD=0.317 mg/dL, CV=1.1%.
Urine 1 (Mean 56.74 mg/dL): Repeatability SD=0.102 mg/dL, CV=0.2%; Within-Lab SD=0.746 mg/dL, CV=1.3%.
Urine 2 (Mean 135.80 mg/dL): Repeatability SD=0.206 mg/dL, CV=0.2%; Within-Lab SD=1.601 mg/dL, CV=1.2%.
Urine QC 1 (Mean 195.79 mg/dL): Repeatability SD=0.253 mg/dL, CV=0.1%; Within-Lab SD=2.376 mg/dL, CV=1.2%.
Reproducibility Results (Coefficient of Variation):
Serum 1 (Mean 0.40 mg/dL): Repeatability %CV=3.5, Between-DAY %CV=1.8, Between-LOT %CV=2.8, Between-SYSTEM %CV=1.5, Reproducibility %CV=5.0.
Serum 2 (Mean 0.72 mg/dL): Repeatability %CV=2.1, Between-DAY %CV=2.9, Between-LOT %CV=1.0, Between-SYSTEM %CV=1.9, Reproducibility %CV=4.2.
Serum 3 (Mean 1.21 mg/dL): Repeatability %CV=0.7, Between-DAY %CV=1.2, Between-LOT %CV=1.1, Between-SYSTEM %CV=1.1, Reproducibility %CV=2.1.
Serum QC 1 (Mean 1.90 mg/dL): Repeatability %CV=0.6, Between-DAY %CV=1.1, Between-LOT %CV=0.3, Between-SYSTEM %CV=0.7, Reproducibility %CV=1.5.
Serum QC 2 (Mean 6.31 mg/dL): Repeatability %CV=0.5, Between-DAY %CV=0.8, Between-LOT %CV=0.4, Between-SYSTEM %CV=0.6, Reproducibility %CV=1.2.
Serum 4 (Mean 17.62 mg/dL): Repeatability %CV=0.3, Between-DAY %CV=0.6, Between-LOT %CV=0.0, Between-SYSTEM %CV=0.5, Reproducibility %CV=0.9.
Serum 5 (Mean 28.76 mg/dL): Repeatability %CV=0.4, Between-DAY %CV=0.7, Between-LOT %CV=0.3, Between-SYSTEM %CV=0.5, Reproducibility %CV=1.0.
Urine 1 (Mean 57.23 mg/dL): Repeatability %CV=0.4, Between-DAY %CV=0.8, Between-LOT %CV=0.3, Between-SYSTEM %CV=1.2, Reproducibility %CV=1.5.
Urine 2 (Mean 137.89 mg/dL): Repeatability %CV=0.4, Between-DAY %CV=0.6, Between-LOT %CV=0.3, Between-SYSTEM %CV=1.1, Reproducibility %CV=1.4.
Urine QC 1 (Mean 199.45 mg/dL): Repeatability %CV=0.5, Between-DAY %CV=0.8, Between-LOT %CV=0.3, Between-SYSTEM %CV=1.2, Reproducibility %CV=1.6.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
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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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
December 4, 2024
Siemens Healthcare Diagnostics Inc. Elisha Caban Regulatory Affairs Professional 511 Benedict Ave Tarrytown, New York 10591
Re: K242685
Trade/Device Name: Atellica® CH Creatinine 3 (Crea3) Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Code: CGX Dated: September 6, 2024 Received: September 6, 2024
Dear Elisha Caban:
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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
1
(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
2
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D. Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Submission Number (if known)
Device Name
Atellica® CH Creatinine_3 (Crea3)
| Indications for Use (Describe) |
|---|
| -------------------------------- |
The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin, dipotassium EDTA, and sodium 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.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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4
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is:K242685
1. Date Prepared
November 7, 2024
2. Applicant Information
| Manufacturer Name: | Siemens Healthcare Diagnostics, Inc. |
|---|---|
| Contact: | Elisha Caban |
| Address: | Regulatory Affairs Professional |
| 511 Benedict Ave | |
| Tarrytown, NY 10591 USA | |
| Email: | elisha.caban@Siemens-Healthineers.com |
3. Regulatory Information
| Information | Atellica® CH Creatinine_3
(Crea3) |
|---------------------------|----------------------------------------------|
| Trade Name | Atellica® CH Creatinine_3
(Crea3) |
| Device | Alkaline Picrate, Colorimetry,
Creatinine |
| Regulation Description | Creatinine test system |
| FDA Device Classification | Class II |
| Review Panel | Clinical Chemistry |
| Product Code | CGX |
| Regulation Number | 21 CFR 862.1225 |
Predicate Device Information 4.
| Candidate Device | Predicate Device | Predicate 510(k) Clearance# |
|---|---|---|
| Atellica® CH Creatinine_3 | ||
| (Crea3) | Atellica® CH Creatinine_2 | |
| (Crea_2) | K161494 |
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| Product | Intended Use |
|---|---|
| Atellica® CH | |
| Creatinine_3 | |
| (Crea3) | The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic |
| use in the quantitative determination of creatinine in human serum, | |
| plasma (lithium heparin, dipotassium EDTA, and sodium 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. Intended Use / Indications For Use
Special Conditions for Use Statement(s): For Prescription Use Only.
| 6. | Device Description |
|---|---|
| ---- | -------------------- |
| Product | Device Description |
|---|---|
| Atellica® CH | |
| Creatinine_3 | |
| (Crea3) | The Atellica CH Crea3 assay is based on the reaction of picrate with |
| creatinine in an alkaline |
The Atellica CH Crea3 assay reacts with picrate in an alkaline medium
to produce a red chromophore creatinine picrate complex. The rate of
complex formation is measured at 505/571 nm and is proportional to
the creatinine concentration. The Atellica CH Crea3 assay is a
modification of the Jaffe method, using rate blanking and intercept
correction. Rate blanking is used to minimize bilirubin interference.
Also, because non-specific serum/plasma protein interactions with this
reagent have been found to produce a positive bias of
approximately0.3 mg/dL (26.5 $\mu$ mol/L), serum/plasma measurements
are automatically corrected by subtracting 0.3 mg/dL (26.5 $\mu$ mol/L)
from each result. |
Purpose of Submission 7.
The purpose of this submission is a premarket notification for the new devices:
- Atellica® CH Creatinine_3 (Crea3) assay .
8. Comparison of Candidate Device and Predicate Device
Atellica® CH Creatinine 3 (Crea3) assay 8.1
The table below describes the similarities and differences between the Atellica® CH Creatinine_3 (Crea3) assay (Candidate Device), and the Atellica® CH Creatinine_2 (Crea_2) assay (Predicate Device).
The performance and accuracy of the Candidate Device are substantially equivalent to those of the Predicate Device. The method comparison of the Candidate Device and the Predicate Device demonstrates acceptable correlation between the two methods.
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| Feature | Candidate Device | Predicate Device |
|---|---|---|
| Atellica® CH Creatinine_3 (Crea3) | Atellica® CH Creatinine_2 (Crea_2) | |
| Intended Use | The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin, dipotassium EDTA, and sodium heparin), and urine using the Atellica® CH Analyzer. | 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. | Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis. |
| Sample Type | Serum, lithium heparin plasma, dipotassium EDTA plasma, sodium heparin plasma, urine | Serum, Plasma (Lithium Heparin), urine. |
| Units of Measure | mg/dL | Same |
| Assay Range / Measuring Interval | Serum 0.15 mg/dL to 30.00 mg/dL | |
| Urine 3.00 mg/dL to 245.00 mg/dL | Same | |
| Expected Values | Serum/plasma | |
| Adult Males: 0.70 – 1.30 mg/dL | ||
| Adult Females: 0.55 – 1.02 mg/dL | ||
| Urine | ||
| Adult Males 950 - 2490 mg/day | ||
| Adult Female 600 - 1800 mg/day | Same | |
| Assay Principle | Enzymatic | Same |
| Standardization | NIST SRM 967 | Same |
| Calibration | Single point | Same |
| Calibrators | Atellica® CH CHEM CAL (CHEM CAL) | Same |
Table 1: Comparison Table of Candidate Device and Predicate Device
9. Standard/Guidance Document References
The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission for both the Atellica® CH Creatinine 3 (Crea3) assay.
7
- Evaluation of Precision of Quantitative Measurement Procedures-Third Edition. (CLSI . EP05-A3).
- . Interference Testing in Clinical Chemistry, 3rd Edition (CLSI EP07-ED3).
- Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3rd Edition (CLSI EP09C-ED3).
- Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; ● Approved Guideline-Second Edition (EP17-A2).
- Evaluation of Stability of In Vitro Diagnostic Medical Laboratory Test Reagents,200 Edition ● (CLSI EP25-ED2).
- Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Third ● Edition. (CLSI EP28-A3C).
- Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and ● Spiking, 1st Edition (CLSI EP34-ED1).
- Evaluation of the Linearity of Quantitative Measurement Procedures, 200 st Edition (CLSI EP06-ED2).
- . EP32-R Metrological Traceability and its Implementation
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Performance Characteristics for Atellica® CH Creatinine 3 (Crea3) 10. Assav
Detection Capability 10.1
Atellica® CH Creatinine_3 (Crea3) 10.1.1
The Limit of Blank (LoB) corresponds to the highest measurement result that is likely to be observed for a blank sample. The assay is designed to have an LoB ≤ Limit of Detection (LoD) for serum and urine samples.
The Limit of Detection (LoD) corresponds to the lowest concentration of Creatinine that can be detected with a probability of 95%. The assay is designed to have an LoD ≤ 0.15 mg/dL for serum/plasma and ≤ 3.00 mg/dL for urine.
The Limit of Quantitation (LoQ) corresponds to the lowest concentration of Creatinine in a sample at which the within lab imprecision is ≤ 20%CV for serum and plasma. The assay is designed to have an LoQ ) ≤ 0.15 mg/dL for serum/plasma with ≤ 0.10 mg/dL total analytical error and ≤ 3.00 mg/dL for urine with ≤ 1.50 mg/dL total analytical error.
Detection capability was determined in accordance with CLSI Document EP17-A2.
The following results were obtained:
Table 2: Crea3 Instructions for Use Detection Capability Claims
| Specimen Type | Detection Capability | Result
mg/dL |
|---------------|----------------------|-----------------|
| Serum/plasma | LoB | 0.05 |
| | LoD | 0.10 |
| | LoQ | 0.15 |
| Urine | LoB | 0.50 |
| | LoD | 1.00 |
| | LoQ | 3.00 |
10.2 Precision
Atellica® CH Creatinine 3 (Crea3) 10.2.1
Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed on the Atellica® CH Analyzer in duplicate in 2 runs per day for 20 davs. The following results were obtained:
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| Specimen
| Type | Na | Repeatability | Within-Lab | |||
|---|---|---|---|---|---|---|
| Mean | ||||||
| mg/dL | SDb | |||||
| mg/dL | CVc | |||||
| (%) | SD | |||||
| mg/dL) | CV | |||||
| (%) | ||||||
| Serum 1 | 80 | 0.38 | 0.006 | 1.6 | 0.012 | 3.2 |
| Serum 2 | 80 | 0.73 | 0.023 | 3.2 | 0.029 | 4.0 |
| Serum 3 | 80 | 0.73 | 0.006 | 0.8 | 0.019 | 2.6 |
| Serum 4 | 80 | 1.18 | 0.007 | 0.6 | 0.019 | 1.6 |
| Serum QC 1 | 80 | 1.85 | 0.007 | 0.4 | 0.024 | 1.3 |
| Serum QC 2 | 80 | 6.21 | 0.011 | 0.2 | 0.067 | 1.1 |
| Serum 5 | 80 | 17.39 | 0.035 | 0.2 | 0.189 | 1.1 |
| Serum 6 | 80 | 28.54 | 0.056 | 0.2 | 0.317 | 1.1 |
| Urine 1 | 80 | 56.74 | 0.102 | 0.2 | 0.746 | 1.3 |
| Urine 2 | 80 | 135.80 | 0.206 | 0.2 | 1.601 | 1.2 |
| Urine QC 1 | 80 | 195.79 | 0.253 | 0.1 | 2.376 | 1.2 |
Table 3: Crea3 Instructions for Use Precision Claims
ª Number of results.
b Standard deviation.
°Coefficient of variation.
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10.3 Reproducibility
Atellica® CH Creatinine_3 (Crea3) 10.3.1
Reproducibility was determined in accordance with CLSI Document EP05-A3. Samples were assayed n=5 in 1 run for 5 days using 3 instruments and 3 reagent lots. The data were analyzed to calculate the following components of precision: repeatability, betweenday, between-lot, between-instrument, and reproducibility (total). The following results were obtained:
Table 4: Atellica® CH Creatinine 3 (Crea3) Instructions for Use Reproducibility Claims
| Mean | Repeatability | Between-DAY | Between-LOT | Between-SYSTEM | Reproducibility | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Na | mg/dL | µmol/L | mg/dL | µmol/L | %CVc | mg/dL | µmol/L | %CV | mg/dL | µmol/L | %CV | mg/dL | µmol/L | %CV | mg/dL | µmol/L | %CV | |
| Sample | ||||||||||||||||||
| Serum 1 | 225 | 0.40 | 35 | 0.014 | 1.2 | 3.5 | 0.007 | 0.6 | 1.8 | 0.011 | 1.0 | 2.8 | 0.006 | 0.5 | 1.5 | 0.020 | 1.8 | 5.0 |
| Serum 2 | 225 | 0.72 | 64 | 0.015 | 1.3 | 2.1 | 0.021 | 1.9 | 2.9 | 0.007 | 0.6 | 1.0 | 0.014 | 1.2 | 1.9 | 0.030 | 2.7 | 4.2 |
| Serum 3 | 225 | 1.21 | 107 | 0.009 | 0.8 | 0.7 | 0.015 | 1.3 | 1.2 | 0.013 | 1.1 | 1.1 | 0.013 | 1.1 | 1.1 | 0.025 | 2.2 | 2.1 |
| Serum QC 1 | 225 | 1.90 | 168 | 0.011 | 1.0 | 0.6 | 0.021 | 1.9 | 1.1 | 0.006 | 0.5 | 0.3 | 0.014 | 1.2 | 0.7 | 0.028 | 2.5 | 1.5 |
| Serum QC 2 | 225 | 6.31 | 558 | 0.030 | 2.7 | 0.5 | 0.052 | 4.6 | 0.8 | 0.023 | 2.0 | 0.4 | 0.040 | 3.5 | 0.6 | 0.076 | 6.7 | 1.2 |
| Serum 4 | 225 | 17.62 | 1558 | 0.048 | 4.2 | 0.3 | 0.113 | 10.0 | 0.6 | 0.000 | 0.0 | 0.0 | 0.090 | 8.0 | 0.5 | 0.152 | 13.4 | 0.9 |
| Serum 5 | 225 | 28.76 | 2542 | 0.105 | 9.3 | 0.4 | 0.192 | 17.0 | 0.7 | 0.079 | 7.0 | 0.3 | 0.153 | 13.5 | 0.5 | 0.278 | 24.6 | 1.0 |
| Urine 1 | 225 | 57.23 | 5059 | 0.213 | 18.8 | 0.4 | 0.475 | 42.0 | 0.8 | 0.177 | 15.6 | 0.3 | 0.681 | 60.2 | 1.2 | 0.875 | 77.4 | 1.5 |
| Urine 2 | 225 | 137.89 | 12189 | 0.511 | 45.2 | 0.4 | 0.842 | 74.4 | 0.6 | 0.385 | 34.0 | 0.3 | 1.577 | 139.4 | 1.1 | 1.898 | 167.8 | 1.4 |
| Urine QC 1 | 225 | 199.45 | 17631 | 0.913 | 80.7 | 0.5 | 1.659 | 146.7 | 0.8 | 0.655 | 57.9 | 0.3 | 2.398 | 212.0 | 1.2 | 3.125 | 276.3 | 1.6 |
a Number of results.
b Standard deviation.
° Coefficient of variation.
11
10.4 Assay Comparison
Atellica® CH Creatinine_3 (Crea3)
The Atellica® CH Creatinine 3 (Crea3) assay (y) was designed to have a correlation coefficient of ≥ 0.950 and a slope of 1.00 ± 0.05 for serum samples and correlation coefficient of ≥ 0.950 and a slope of 0.000 ± 3.00 for urine samples, compared to the Atellica CH Creatinine 2 (Crea_2) assay on the Atellica CH analyzer. Assay comparison was determined using the Weighted Deming regression model in accordance with CLSI Document EP09C-ED3. The following results were obtained:
| Specimen
Type | Comparison
Assay (x) | Regression Equation | Sample Range mg/dL | Na | rb |
|------------------|-----------------------------------------|------------------------|--------------------|-----|-------|
| Serum | Atellica CH
Creatinine_2
(Crea_2) | y = 1.00x - 0.04 mg/dL | 0.44 to
28.64 | 151 | 1.000 |
| Urine | Atellica CH
Creatinine_2
(Crea_2) | y = 1.00x + 0.14 mg/dL | 12.60 to 237.06 | 113 | 1.000 |
Table 5: Atellica® CH Creatinine_3 (Crea3) Instructions for Use Method Comparison Claims
a Number of samples tested.
b Correlation coefficient.
Specimen Equivalence 10.5
Atellica® CH Creatinine_3 (Crea3) 10.5.1
The specimen equivalency was determined using the Weighted Deming regression model in accordance with CLSI Document EP09-A3. The following results were obtained:
| Table 6: Atellica® CH Creatinine 3 (Crea3) Instructions for Use Specimen Equivalence Claims | ||||
|---|---|---|---|---|
| Specimen (y) | Reference Specimen (x) | Regression Equation | Sample Range mg/dL (µmol/L) | Na | rb | ||
|---|---|---|---|---|---|---|---|
| Sodium Heparin | Serum | $y = 1.00x + 0.00 mg/dL$ $y = 1.00x + 0 µmol/L$ | 0.60 | ||||
| (53) | to | ||||||
| to | 27.26 | ||||||
| (2410) | 50 | 0.999 | |||||
| Lithium Heparin | Serum | $y = 0.99x + 0.06 mg/dL$ $y = 0.99x + 5 µmol/L$ | 0.60 | ||||
| (53) | to | ||||||
| to | 27.26 | ||||||
| (2410) | 50 | 0.999 | |||||
| Dipotassium EDTA | Serum | $y = 0.98x + 0.04 mg/dL$ $y = 0.98x + 4 µmol/L$ | 0.60 | ||||
| (53) | to | ||||||
| to | 27.26 | ||||||
| (2410) | 50 | 0.998 |
ª Number of samples tested.
b Correlation Coefficient.
12
10.6 Interferences
10.6.1.1 Atellica® CH Creatinine_3 (Crea3)
10.6.1.2 Hemolysis, Icterus, and Lipemia (HIL)
Bias is the difference in the results between the control sample (does not contain the interferent) and the test sample (contains the interferent) expressed in percent. The Atellica® CH Crea3 assay is designed to have ≤ 10% interference from hemoglobin, billirubin, and lipemia. Bias > 10% or 0.15 mg/dL whichever is greater for serum/plasma is considered interference. Analyte results should not be corrected based on this bias.
Interference testing was performed in accordance with CLSI Document EP07-ED3. The following results were obtained:
| Substance | Substance
Concentration
(mg/dL) | Analyte
Concentration
(mg/dL) | Bias |
|-----------------------------------------|---------------------------------------|-------------------------------------|-------------|
| Hemoglobin | 1000 | 0.65 | 0.14 mg/dL |
| Hemoglobin | 1000 | 2.05 | 6.3% |
| Conjugated Bilirubin | 45 | 0.59 | -0.14 mg/dL |
| Conjugated Bilirubin | 40 | 2.03 | -8.5% |
| Unconjugated Bilirubin | 45 | 0.59 | -0.07 mg/dL |
| Unconjugated Bilirubin | 60 | 2.07 | -6.8% |
| Lipemia (from
Intralipid®) | 2250 | 0.62 | -0.06 mg/dL |
| Lipemia (from
Intralipid®) | 3000 | 1.92 | 8.3% |
| Lipemia (from
Triglyceride Fraction) | 3000 | 0.54 | 0.00 mg/dL |
| Lipemia (from
Triglyceride Fraction) | 3000 | 1.79 | 0.0% |
| Substance | Substance
Concentration | Analyte Concentration (mg/dL) | Bias (%) |
| Acetaminophen | 160 mg/L | 0.60 | 0.00 mg/dL |
| Acetaminophen | 160 mg/L | 2.08 | -0.5% |
| Acetoacetate | 20 mg/dL | 0.63 | 0.01 mg/dL |
| Acetoacetate | 20 mg/dL | 2.13 | -0.5% |
| Acetylcysteine (N-Acetylcysteine) | 150 mg/L | 0.60 | 0.00 mg/dL |
| Acetylcysteine (N-Acetylcysteine) | 150 mg/L | 2.05 | 0.5% |
| Acetylsalicylic Acid | 30 mg/L | 0.60 | 0.01 mg/dL |
| Acetylsalicylic Acid | 30 mg/L | 2.08 | 0.5% |
| Ampicillin-Na | 80 mg/L | 0.60 | 0.01 mg/dL |
| Ampicillin-Na | 80 mg/L | 2.03 | -0.5% |
| Ascorbic Acid | 60 mg/L | 0.60 | 0.01 mg/dL |
| Ascorbic Acid | 60 mg/L | 2.08 | 0.0% |
| Azlocillin | 7 g/L | 0.55 | 0.00 mg/dL |
| Azlocillin | 7 g/L | 1.98 | -1.0% |
| Biotin | 4250 ng/mL | 0.63 | -0.01 mg/dL |
| Biotin | 4250 ng/mL | 2.12 | -0.5% |
| Ca-Dobesilate | 60 mg/L | 0.60 | 0.01 mg/dL |
| Ca-Dobesilate | 60 mg/L | 2.03 | -0.5% |
| Cefotaxime | 53 mg/dL | 0.63 | 0.01 mg/dL |
| Cefotaxime | 53 mg/dL | 2.13 | 0.0% |
| Cyclosporine | 2 mg/L | 0.64 | 0.02 mg/dL |
| Cyclosporine | 2 mg/L | 2.04 | 1.5% |
| Doxycycline | 20 mg/L | 0.62 | -0.01 mg/dL |
| Doxycycline | 20 mg/L | 2.13 | 0.5% |
| Eltrombopag | 300 mg/L | 0.59 | 0.15 mg/dL |
| Eltrombopag | 300 mg/L | 2.08 | 1.4% |
| Ibuprofen | 220 mg/L | 0.64 | 0.00 mg/dL |
| Ibuprofen | 220 mg/L | 2.14 | 0.0% |
| Levodopa | 700 mg/L | 42.01 | -1.4% |
| Levodopa | 700 mg/L | 186.99 | -1.6% |
| Methyldopa | 100 mg/L | 0.63 | 0.03 mg/dL |
| Methyldopa | 100 mg/L | 2.09 | -2.9% |
| Metronidazole | 130 mg/L | 0.60 | 0.02 mg/dL |
| Metronidazole | 130 mg/L | 2.03 | 1.0% |
| Nitrofurantoin | 0.3 mg/dL | 0.64 | 0.01 mg/dL |
| Nitrofurantoin | 0.3 mg/dL | 2.04 | 1.0% |
| Nitroglycerin | 0.015 mg/L | 0.65 | 0.01 mg/dL |
| Substance | Substance
Concentration | Analyte Concentration (mg/dL) | Bias (%) |
| Nitroglycerin | 0.015 mg/L | 2.13 | 0.0% |
| Norfenefrine | 4 mg/L | 0.63 | -0.02% |
| Norfenefrine | 4 mg/L | 2.13 | 0.5% |
| Phenylbutazone | 330 mg/L | 0.64 | 0.03% |
| Phenylbutazone | 330 mg/L | 2.14 | 0.0% |
| Rifampicin | 50 mg/L | 0.60 | 0.01% |
| Rifampicin | 50 mg/L | 2.05 | 1.5% |
| Sodium Heparin | 4 U/mL | 0.65 | -0.04% |
| Sodium Heparin | 4 U/mL | 2.13 | 0.0% |
| Sulbactam | 240 mg/L | 0.60 | 0.05% |
| Sulbactam | 240 mg/L | 2.03 | 1.5% |
| Sulfamethoxazole | 40 mg/dL | 0.64 | 0.00% |
| Sulfamethoxazole | 40 mg/dL | 2.14 | -0.5% |
| Sulfapyridine | 30 mg/dL | 0.63 | -0.04% |
| Sulfapyridine | 30 mg/dL | 2.12 | 0.0% |
| Sulfasalazine | 500 mg/L | 0.64 | -0.07% |
| Sulfasalazine | 500 mg/L | 2.14 | -7.9% |
| Theophylline (1.3-dimethylxanthine) | 60 mg/L | 0.60 | 0.02% |
| Theophylline (1.3-dimethylxanthine) | 60 mg/L | 2.03 | -0.5% |
| Trimethoprim | 5 mg/dL | 0.64 | 0.00% |
| Trimethoprim | 5 mg/dL | 2.14 | 0.0% |
Table 7: Atellica® CH Creatinine_3 (Crea3) Instructions for Use Interference HIL Claims
10.6.1.3 Non-Interfering Substances
The following substances do not interfere with the Atellica® CH Creatinine 3 (Crea3) assay when present in serum, plasma and urine at the concentrations indicated in the tables below. Bias due to these substances is ≤ 10% or ±0.15 mg/dL for Serum and plasma and ≤ 10% for Urine.
13
Table 8: Atellica® CH Creatinine_3 (Crea3) Non-Interfering Substance for Serum
14
510(k) Summary of Safety and Effectiveness
15
| Interference beyond ±10% for Serum | ||||
|---|---|---|---|---|
| Substance | Substance
Concentration | Analyte
Concentration
(mg/dL) | Bias |
|--------------------------------|----------------------------|-------------------------------------|-------------|
| Cefoxitin | 23.5 mg/L | 0.62 | 0.07 mg/dL |
| | 47 mg/L | 2.13 | 7.5% |
| | 1650 mg/L | 0.58 | 5.37 mg/dL |
| | 1650 mg/L | 2.11 | 243.6% |
| | 6600 mg/L | 0.58 | 20.85 mg/dL |
| | 6600 mg/L | 2.11 | 947.9% |
| Cephalothin | 135 mg/dL | 0.60 | 0.64 mg/dL |
| | 11 mg/dL | 2.13 | 2.3% |
| | 45 mg/dL | 0.60 | 0.20 mg/dL |
| | 45 mg/dL | 2.07 | 11.1% |
| | 180 mg/dL | 0.60 | 0.87 mg/dL |
| | 180 mg/dL | 2.07 | 44.0% |
| Glucose | 250 mg/dL | 0.59 | 0.14 mg/dL |
| | 250 mg/dL | 2.09 | 5.7% |
| | 500 mg/dL | 0.59 | 0.27 mg/dL |
| | 500 mg/dL | 2.09 | 11.5% |
| | 1000 mg/dL | 0.59 | 0.51 mg/dL |
| | 1000 mg/dL | 2.09 | 22.5% |
| Total Protein | 10 g/dL | 0.68 | 0.13 mg/dL |
| | 10 g/dL | 2.23 | 2.2% |
| | 15 g/dL | 2.30 | 5.7% |
| | 15 g/dL | 0.65 | 0.45 mg/dL |
| Acetohexamide | 1.0 mg/dL | 0.59 | 0.11 mg/dL |
| | 1.5 mg/dL | 2.11 | 7.6% |
| | 2.0 mg/dL | 0.59 | 0.22 mg/dL |
| | 2.0 mg/dL | 2.11 | 10.4% |
| Hydroxocobalamin
(Cyanokit) | 250 mg/L | 0.62 | 0.11 mg/dL |
| | 250 mg/L | 2.14 | 7.9% |
| | 500 mg/L | 0.62 | 0.22 mg/dL |
| | 2259 mg/L | 0.59 | 1.13 mg/dL |
| | 500 mg/L | 2.14 | 14.5% |
| | 2259 mg/L | 2.07 | 49.3% |
Table 9: Atellica® CH Creatinine_3 (Crea3) Non-Interfering Substance for Urine
| Substance | Substance Concentration | Analyte Concentration (mg/dL) | Bias (%) |
|---|---|---|---|
| 6N HCL | 0.01% | 42.42 | -0.4 |
| 6N HCL | 0.01% | 169.55 | -0.1 |
| 6N Nitric Acid | 0.60% | 42.42 | -0.5 |
| 6N Nitric Acid | 0.60% | 169.55 | -0.1 |
| Acetaminophen | 200 mg/dL | 42.48 | 0.0 |
| Acetaminophen | 200 mg/dL | 170.03 | -0.8 |
| Acetic Acid | 25 mL/24-hr collection | 45.85 | -0.8 |
| Substance | Substance Concentration | Analyte Concentration (mg/dL) | Bias (%) |
| Acetic Acid | 25 mL/24-hr collection | 182.56 | -0.2 |
| Ascorbate | 3.0 mg/dL | 42.52 | -0.4 |
| Ascorbate | 3.0 mg/dL | 170.02 | -1.0 |
| Boric Acid | 1% w/v | 44.86 | -1.5 |
| Boric Acid | 1% w/v | 177.59 | -1.0 |
| Conjugated Bilirubin | 50 mg/dL | 42.52 | -0.5 |
| Conjugated Bilirubin | 50 mg/dL | 170.02 | -1.1 |
| Ethanol | 1 g/dL | 39.18 | 2.7 |
| Ethanol | 1 g/dL | 160.56 | -1.2 |
| Gamma Globulin | 0.5 g/dL | 41.29 | -0.1 |
| Gamma Globulin | 0.5 g/dL | 163.63 | 0.2 |
| Glucose | 2000 mg/dL | 42.52 | 0.8 |
| Glucose | 2000 mg/dL | 170.02 | -1.3 |
| Hemoglobin | 100 mg/dL | 42.39 | 0.1 |
| Hemoglobin | 100 mg/dL | 169.04 | 0.2 |
| Human Serum Albumin | 0.5 g/dL | 41.29 | -0.5 |
| Human Serum Albumin | 0.5 g/dL | 163.63 | 0.2 |
| Ibuprofen | 500 mg/dL | 42.44 | -0.3 |
| Ibuprofen | 500 mg/dL | 164.10 | -0.1 |
| Levodopa | 700 mg/L | 42.81 | -1.4 |
| Levodopa | 700 mg/L | 186.99 | -1.6 |
| N-Acetyl-Cysteine | 2 mg/dL | 42.42 | -0.5 |
| N-Acetyl Cysteine | 2 mg/dL | 169.55 | 0.0 |
| Oxalic Acid | 0.1 g/dL | 42.52 | -0.4 |
| Oxalic Acid | 0.1 g/dL | 170.02 | -1.3 |
| pH 4 | pH 4 | 43.89 | -3.3 |
| pH 4 | pH 4 | 176.86 | -0.2 |
| pH 9 | pH 9 | 43.89 | 0.0 |
| pH 9 | pH 9 | 176.86 | -0.6 |
| Sodium Carbonate | 5 g/24-hr collection | 44.44 | -0.4 |
| Sodium Carbonate | 5 g/24-hr collection | 177.50 | 0.1 |
| Substance | Substance | ||
| Concentration | Analyte | ||
| Concentration | |||
| (mg/dL) | Bias % | ||
| Cefoxitin | 3300 mg/L | 42.55 | 7.3% |
| 6600 mg/L | 188.03 | 7.7% | |
| 4950 mg/L | 42.55 | 11.3% | |
| 6600 mg/L | 42.55 | 15.4% |
16
510(k) Summary of Safety and Effectiveness
17
Interference beyond ±10% for Urine
Clinical Study 11.
Atellica® CH Creatinine_3 (Crea3) 11.1.1
Not applicable.
11.2 Expected Values
11.2.1 Atellica® CH Creatinine 3 (Crea3)
Table 10: Atellica® CH Creatinine_3 (Crea3) Instructions for Use for Expected Values
| Group | Sample Type | Reference Interval |
|---|---|---|
| Males | Serum/Plasma | 0.70 - 1.30 mg/dL (62 - 115 µmol/L) |
| Females | Serum/Plasma | 0.55 - 1.02 mg/dL (49 - 90 umol/L) |
| Males | Urine | 950 - 2490 mg/day (8.4 - 22.0 mmol/day) |
| Females | Urine | 600-1800 mg/day (5.3 - 15.9 mmol/day) |
12. Standardization
Atellica® CH Creatinine_3 (Crea3) Atellica® CH Crea3 12.1.1
The assay shall be traceable to the reference material SRM967, from the National Institute of Standards and Technology (NIST).
Clinical Cut-off 13.
Atellica® CH Creatinine_3 (Crea3) 13.1.1
Not applicable.
18
Conclusion 14.
Atellica® CH Creatinine_3 (Crea3) 14.1
The results from the performance studies support that the Candidate Device, Atellica® CH Creatinine_3 (Crea3) assay, is substantially equivalent to the Predicate Device, Atellica CH Creatinine_2 (Crea_2) assay (K161494).