Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a chemical assay based on enzymatic reactions and spectrophotometric measurement. There is no mention of AI, ML, or any computational analysis beyond standard data processing for calculating concentrations from absorbance measurements. The performance studies focus on traditional analytical validation metrics.

Therapeutic

No.
Explanation: This device is for in vitro diagnostic use to measure creatinine levels in biological samples, which are then used in the diagnosis and treatment of renal diseases. It does not directly provide therapy.

Diagnostic

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."

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic assay that measures creatinine concentration through enzymatic reactions, which is a chemical process, not a software-only function. It is used with the Atellica CH Analyzer, which is a hardware instrument.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The very first sentence explicitly states "The Atellica® CH Enzymatic Creatinine 3 (ECre3) assay is for in vitro diagnostic use...". This is the most direct confirmation.
Device Description: The description details how the assay measures creatinine in human biological samples (serum, plasma, urine) using chemical reactions. This is characteristic of an in vitro diagnostic test.
Performance Studies: The document describes performance studies conducted to validate the assay's accuracy and reliability for diagnostic purposes, including comparisons to a predicate device and a reference method (IDMS).
Predicate Device: The mention of a predicate device (ADVIA® Chemistry Enzymatic Creatinine_2) is common for IVDs seeking regulatory clearance, as it demonstrates substantial equivalence to a previously approved device.
Intended User/Care Setting: "Prescription Use" is a common classification for IVDs used in clinical settings.

All of these elements strongly indicate that the Atellica CH ECre3 assay is an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Atellica® CH Enzymatic Creatinine 3 (ECre3) assay is for in the quantitative determination of creatinine in human serum, plasma (lithium heparin and dipotassium EDTA), 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

JFY

Device Description

The Atellica CH ECre3 assay measures the concentration of creatinine through a series of coupled enzymatic reactions and is based upon the method developed by Masaru and Mitsutaka. The Atellica CH ECre3 assay uses a series of coupled enzymatic reactions. In a "pretreatment" reaction, endogenous creatine and sarcosine are removed from a test sample by creatinase and sarcosine oxidase. The level of creatinine in a test sample is then determined through coupled enzymatic reactions. First, creatinine is enzymatically converted by creatininase into creatine. Creatine is then enzymatically converted to sarcosine by creatinase. This is followed by the oxidation of sarcosine by sarcosine oxidase to produce hydrogen peroxide. In the presence of peroxidase, the hydrogen peroxide allows for the oxidative condensation of 4-aminoantipyrine and N-ethyl-N-(3-methylphenyl)-N'-succinyl-ethylenediamine to produce a reddish purple quinone pigment. The absorbance of this quinone pigment is measured as an endpoint reaction at 545/694 nm.

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

Prescription Use Only.

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)

Substantial equivalence was demonstrated by testing several performance characteristics including measuring interval, expected values reference interval, precision, method comparison, interference, and specimen equivalence by method comparison. The performance studies gave acceptable results compared to the Predicate Device.

Detection Capability:
Serum/plasma: LoB 0.05 (4) mg/dL (µmol/L), LoD 0.10 (9) mg/dL (µmol/L), LoQ 0.15 (13) mg/dL (µmol/L)
Urine: LoB 0.15 (13) mg/dL (µmol/L), LoD 0.50 (44) mg/dL (µmol/L), LoQ 2.00 (177) mg/dL (µmol/L)

Precision (Within-Lab):
Serum samples (N=80 for each):
Serum 1 (0.41 mg/dL): SD 0.013 mg/dL, CV 3.2%
Serum 2 (0.75 mg/dL): SD 0.015 mg/dL, CV 2.0%
Serum 3 (1.29 mg/dL): SD 0.030 mg/dL, CV 2.3%
Serum QC 1 (1.91 mg/dL): SD 0.024 mg/dL, CV 1.3%
Serum QC 2 (3.11 mg/dL): SD 0.026 mg/dL, CV 0.8%
Serum 4 (8.89 mg/dL): SD 0.055 mg/dL, CV 0.6%
Serum 5 (18.52 mg/dL): SD 0.093 mg/dL, CV 0.5%
Serum 6 (26.49 mg/dL): SD 0.121 mg/dL, CV 0.5%
Urine samples (N=80 for each):
Urine 1 (42.82 mg/dL): SD 0.322 mg/dL, CV 0.8%
Urine QC 1 (86.41 mg/dL): SD 0.497 mg/dL, CV 0.6%
Urine 2 (185.06 mg/dL): SD 0.831 mg/dL, CV 0.4%

Reproducibility (Total Reproducibility, N=225 for each):
Serum samples:
Serum 1 (0.44 mg/dL): SD 0.013 mg/dL, CV 2.9%
Serum QC 1 (0.79 mg/dL): SD 0.014 mg/dL, CV 1.7%
Serum 2 (0.95 mg/dL): SD 0.037 mg/dL, CV 3.9%
Serum QC 2 (1.88 mg/dL): SD 0.016 mg/dL, CV 0.8%
Serum QC 3 (6.82 mg/dL): SD 0.032 mg/dL, CV 0.5%
Serum 3 (7.96 mg/dL): SD 0.045 mg/dL, CV 0.6%
Serum 4 (26.86 mg/dL): SD 0.148 mg/dL, CV 0.6%
Urine samples:
Urine 1 (42.30 mg/dL): SD 0.225 mg/dL, CV 0.5%
Urine 2 (189.56 mg/dL): SD 1.267 mg/dL, CV 0.7%

Assay Comparison to ADVIA Chemistry ECRE_2:
Serum (N=105): y = 0.99x + 0.02 mg/dL, r = 1.000 (Range: 0.18–28.41 mg/dL)
Urine (N=102): y = 0.98x + 0.05 mg/dL, r = 0.999 (Range: 4.71–240.47 mg/dL)
Assay Comparison to Isotope Dilution Mass Spectrometry (IDMS):
Serum/Plasma (N=47): y = 1.01x + 0.01 mg/dL, r = 0.991 (Range: 0.35–26.70 mg/dL)

Specimen Equivalency (compared to Serum):
Lithium heparin plasma (N=55): y = 0.99x + 0.00 mg/dL, r = 1.000 (Range: 0.50–26.91 mg/dL)
Dipotassium EDTA plasma (N=55): y = 0.97x + 0.02 mg/dL, r = 0.998 (Range: 0.50–26.91 mg/dL)

Interfering Substances (Bias > 10% considered interference):
Hemoglobin (serum): 6.0% at 1.00 mg/dL analyte, -3.2% at 8.25 mg/dL analyte
Bilirubin, conjugated (serum): -6.2% at 0.97 mg/dL analyte, -3.1% at 8.76 mg/dL analyte
Bilirubin, unconjugated (serum): -4.1% at 0.97 mg/dL analyte, -1.6% at 8.66 mg/dL analyte
Lipemia (Intralipid®) (serum): -3.8% at 1.06 mg/dL analyte, -2.6% at 8.06 mg/dL analyte

Non-Interfering Substances (Bias

Regulation Number and Section

§ 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.

Summary

0

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left side of the image is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

November 24, 2021

Siemens Healthcare Diagnostics Inc. Ian Thompson Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, New York 10591

Re: K212223

Trade/Device Name: Atellica® CH Enzymatic Creatinine 3 (ECre3) Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Code: JFY Dated: July 15, 2021 Received: July 16, 2021

Dear Ian Thompson:

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. 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 located at https://www.accessdata.fda.gov/scripts/cdrl/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.

1

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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531 -542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation -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.

Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K212223

Device Name Atellica® CH Enzymatic Creatinine 3 (ECre3)

Indications for Use (Describe)

The Atellica® CH Enzymatic Creatinine 3 (ECre3) assay is for in the quantitative determination of creatinine in human serum, plasma (lithium heparin and dipotassium EDTA), 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)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

X Prescription Use (Part 21 CFR 801 Subpart D)

_ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

This 510(k) Summary 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: K212223

1. Date Prepared
  July 15, 2021

2. Applicant Information

| Contact: | Ian Thompson
Regulatory Clinical Affairs Specialist |
|----------|--------------------------------------------------------|
| Address: | 511 Benedict Avenue
Tarrytown, NY 10591-5097 |
| Email: | ian_thompson@siemens-healthineers.com |

Regulatory Information 3.

Atellica® CH Enzymatic Creatinine_3 (ECre3) assay

Trade Name:	Atellica® CH Enzymatic Creatinine_3 (ECre3)
Common Name:	Enzymatic Method, Creatinine
Classification Name:	Creatinine test system
FDA Classification:	Class II
Review Panel:	Clinical Chemistry
Product Code:	JFY
Regulation Number:	21 CFR 862.1225

4. Predicate Device Information

Predicate Device Name: ADVIA® Chemistry Enzymatic Creatinine_2 (ECRE_2)

510(k) Number: K070727

5. Intended Use / Indications For Use

The Atellica® CH Enzymatic Creatinine_3 (ECre3) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin and dipotassium EDTA), and urine using the Atellica® CH Analyzer. Such measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.

Special Conditions for Use Statement(s): For Prescription Use Only.

6. Device Description

The Atellica CH ECre3 assay measures the concentration of creatinine through a series of coupled enzymatic reactions and is based upon the method developed by Masaru and Mitsutaka.

4

The Atellica CH ECre3 assay uses a series of coupled enzymatic reactions. In a "pretreatment" reaction, endogenous creatine and sarcosine are removed from a test sample by creatinase and sarcosine oxidase. The level of creatinine in a test sample is then determined through coupled enzymatic reactions. First, creatinine is enzymatically converted by creatininase into creatine. Creatine is then enzymatically converted to sarcosine by creatinase. This is followed by the oxidation of sarcosine by sarcosine oxidase to produce hydrogen peroxide. In the presence of peroxidase, the hydrogen peroxide allows for the oxidative condensation of 4-aminoantipyrine and N-ethyl-N-(3-methylphenyl)-N'-succinyl-ethylenediamine to produce a reddish purple quinone pigment. The absorbance of this quinone pigment is measured as an endpoint reaction at 545/694 nm.545 / 694 nm.

Purpose of Submission 7.

The purpose of this submission is a premarket notification for a new device: Atellica CH Enzymatic Creatinine_3 (ECre3) assay.

8. Comparison of Candidate Device and Predicate Device

The table below describes the similarities and differences between the Atellica CH Enzymatic Creatinine_3 (ECre3) assay (Candidate Device), and the ADVIA® Chemistry Enzymatic Creatinine_2 (ECRE_2) (Predicate Device).

Substantial equivalence was demonstrated by testing several performance characteristics including measuring interval, expected values reference interval, precision, method comparison, interference, and specimen equivalence by method comparison. The performance studies gave acceptable results compared to the Predicate Device.

Feature	Candidate Device	Predicate Device
	Atellica® CH Enzymatic Creatinine_3
(ECre3)	ADVIA Chemistry Enzymatic
Creatinine_2 (ECRE_2)
Intended Use	The Atellica CH Enzymatic
Creatinine_3 (ECre3) assay is for in
vitro diagnostic use in the quantitative
determination of creatinine in human
serum, plasma (lithium heparin and
dipotassium EDTA), and urine using
the Atellica CH Analyzer.	For in vitro diagnostic use in the
quantitative determination of
creatinine in human serum, plasma
(lithium heparin and potassium
EDTA), and urine on ADVIA
Chemistry systems.
Indications for Use	Such measurements are used in the
diagnosis and treatment of renal
diseases and in monitoring renal
dialysis.	Same
Sample Type	Serum, plasma (lithium heparin and
dipotassium EDTA), urine	serum, plasma (lithium heparin,
potassium EDTA), urine
Units of Measure	mg/dL	Same

5

Feature	Candidate Device	Predicate Device
	Atellica® CH Enzymatic Creatinine_3
(ECre3)	ADVIA Chemistry Enzymatic
Creatinine_2 (ECRE_2)
Assay Range /
Measuring Interval	Serum/Plasma: 0.15–30.00 mg/dL
Urine: 2.00–245.00 mg/dL	Serum/Plasma: 0.10–30.00 mg/dL
Urine: 1.00-245.00 mg/dL
Expected Values
Serum/Plasma	Males: 0.73-1.18 mg/dL
Females: 0.55-1.02 mg/dL	Males: 0.6-1.1 mg/dL
Females: 0.5-0.8 mg/dL
Expected Values
Urine	Males: 800–2000 mg/day
Females: 600-1800 mg/day	Same
Assay Principle	Enzymatic (Creatininase)	Same
Standardization	NIST SRM 967	Same
Calibration	Single point	Same
Calibrators	Atellica CH Chemistry Calibrator
(CHEM CAL)	ADVIA Chemistry Calibrator
(K050374)

Standard/Guidance Document References 9.

The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:

Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition. (CLSI EP05-A3).
. Interference Testing in Clinical Chemistry (CLSI EP07-ED3).
Measurement Procedure Comparison and Bias Estimation Using Patient Samples (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 Reagents: Approved Guideline (CLSI EP25-A).
. Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition (CLSI EP28-A3c).
Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking (CLSI EP34-ED1).

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Performance Characteristics for Atellica® CH Enzymatic Creatinine_3 10. (ECre3) Assay

Detection Capability 10.1

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).

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 ≤ Limit of Quantitation (LoQ).

The Limit of Quantitation (LoQ) corresponds to the lowest concentration of creatinine in a sample at which the total analytical error is ≤ 0.10 mg/dL for serum and plasma and ≤ 1.50 mg/dL for urine. The assay is designed to have an LoQ ≤ 0.15 mg/dL (13 µmol/L) for serum and plasma and ≤ 2.00 mg/dL (177 umol/L) for urine.

Detection capability was determined in accordance with CLSI Document EP17-A2.

Specimen Type	Detection Capability	mg/dL (µmol/L)
Serum/plasma	LoB	0.05 (4)
	LoD	0.10 (9)
	LoQ	0.15 (13)
Urine	LoB	0.15 (13)
	LoD	0.50 (44)
	LoQ	2.00 (177)

The study supports the following detection capability claims:

10.2 Precision

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 days. The following results were obtained:

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| Specimen Type | Na | Mean
mg/dL (µmol/L) | Repeatability | | Within-Lab | |
|---------------|----|------------------------|-----------------------|------------|----------------------|-----------|
| | | | SDb
mg/dL (µmol/L) | CVc
(%) | SD
mg/dL (µmol/L) | CV
(%) |
| Serum 1 | 80 | 0.41 (36) | 0.009 (0.8) | 2.2 | 0.013 (1.1) | 3.2 |
| Serum 2 | 80 | 0.75 (66) | 0.008 (0.7) | 1.1 | 0.015 (1.3) | 2.0 |
| Serum 3 | 80 | 1.29 (114) | 0.010 (0.9) | 0.8 | 0.030 (2.7) | 2.3 |
| Serum QC 1 | 80 | 1.91 (169) | 0.012 (1.1) | 0.6 | 0.024 (2.1) | 1.3 |
| Serum QC 2 | 80 | 3.11 (275) | 0.009 (0.8) | 0.3 | 0.026 (2.3) | 0.8 |
| Serum 4 | 80 | 8.89 (786) | 0.021 (1.9) | 0.2 | 0.055 (4.9) | 0.6 |
| Serum 5 | 80 | 18.52 (1637) | 0.039 (3.4) | 0.2 | 0.093 (8.2) | 0.5 |
| Serum 6 | 80 | 26.49 (2342) | 0.054 (4.8) | 0.2 | 0.121 (10.7) | 0.5 |
| Urine 1 | 80 | 42.82 (3785) | 0.064 (5.7) | 0.1 | 0.322 (28.5) | 0.8 |
| Urine QC 1 | 80 | 86.41 (7639) | 0.156 (13.8) | 0.2 | 0.497 (43.9) | 0.6 |
| Urine 2 | 80 | 185.06 (16,359) | 0.320 (28.3) | 0.2 | 0.831 (73.5) | 0.4 |

a Number of results.

b Standard deviation. °Coefficient of variation.

10.3 Reproducibility

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, between-day, between-lot, between-instrument, and reproducibility (total). The following results were obtained:

| | | | Repeatability | | Between-Day | | Between-Lot | | Between-
Instrument | | Total
Reproducibility | |
|------------------|-----|---------------------------|--------------------------|------------|-------------------------|-----------|-------------------------|-----------|-------------------------|-----------|--------------------------|-----------|
| Specimen
Type | Na | Mean
mg/dL
(µmol/L) | SDb
mg/dL
(µmol/L) | CVc
(%) | SD
mg/dL
(µmol/L) | CV
(%) | SD
mg/dL
(µmol/L) | CV
(%) | SD
mg/dL
(µmol/L) | CV
(%) | SD
mg/dL
(µmol/L) | CV
(%) |
| Serum 1 | 225 | 0.44
(39) | 0.008
(0.8) | 1.9 | 0.005
(0.4) | 1.1 | 0.008
(0.7) | 1.9 | 0.000
(0.0) | 0.0 | 0.013(1.1) | 2.9 |
| Serum QC 1 | 225 | 0.79
(70) | 0.011
(0.9) | 1.3 | 0.004
(0.3) | 0.5 | 0.008
(0.7) | 1.0 | 0.000
(0.0) | 0.0 | 0.014(1.2) | 1.7 |
| Serum 2 | 225 | 0.95
(84) | 0.014
(1.2) | 1.4 | 0.034
(3.0) | 3.5 | 0.000
(0.0) | 0.0 | 0.007
(0.6) | 0.7 | 0.037
(3.3) | 3.9 |
| Serum QC 2 | 225 | 1.88
(166) | 0.011
(1.0) | 0.6 | 0.008
(0.7) | 0.4 | 0.009
(0.8) | 0.5 | 0.000
(0.0) | 0.0 | 0.016
(1.4) | 0.8 |
| Serum
QC 3 | 225 | 6.82
(603) | 0.016
(1.4) | 0.2 | 0.022
(1.9) | 0.3 | 0.000
(0.0) | 0.0 | 0.017
(1.5) | 0.2 | 0.032
(2.8) | 0.5 |
| Serum 3 | 225 | 7.96
(703) | 0.021
(1.8) | 0.3 | 0.034
(3.0) | 0.4 | 0.000
(0.0) | 0.0 | 0.019
(1.7) | 0.2 | 0.045
(3.9) | 0.6 |
| Serum 4 | 225 | 26.86
(2374) | 0.051
(4.5) | 0.2 | 0.105
(9.3) | 0.4 | 0.039
(3.5) | 0.1 | 0.082
(7.2) | 0.3 | 0.148
(13.1) | 0.6 |
| Urine 1 | 225 | 42.30
(3739) | 0.106
(9.3) | 0.2 | 0.102
(9.0) | 0.2 | 0.000
(0.0) | 0.0 | 0.171
(15.1) | 0.4 | 0.225
(19.9) | 0.5 |
| Urine 2 | 225 | 189.56
(16,757) | 0.379
(33.5) | 0.2 | 0.401
(35.4) | 0.2 | 0.503
(44.5) | 0.3 | 1.024
(90.5) | 0.5 | 1.267
(112.0) | 0.7 |

ª Number of results.

b Standard deviation.

°Coefficient of variation.

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Assay Comparison 10.4

The Atellica CH ECre3 assay (y) was designed to have a correlation coefficient of ≥ 0.950 and a slope of 1.00 ± 0.05 compared to the ADVIA Chemistry ECRE 2 assay. Assay comparison for serum was determined using the Deming regression model and for urine using the Weighted Deming regression model in accordance with CLSI Document EP09c. The following results were obtained:

Specimen	Comparative Assay (x)	Regression Equation
Serum	ADVIA Chemistry ECRE_2	y = 0.99x + 0.02 mg/dL
(y = 0.99x + 2 µmol/L)	0.18–28.41 mg/dL
(16–2511 µmol/L)	105	1.000
Urine	ADVIA Chemistry ECRE_2	y = 0.98x + 0.05 mg/dL
(y = 0.98x + 4 µmol/L)	4.71–240.47 mg/dL
(416–21,258 µmol/L)	102	0.999
Serum/Plasma	Isotope Dilution Mass
Spectrometry (IDMS)	y = 1.01x + 0.01 mg/dL
(y = 1.01x + 1 µmol/L)	0.35–26.70 mg/dL
(31–2360 µmol/L)	47	0.991

a Number of samples tested.

b Correlation coefficient.

10.5 Specimen Equivalency

The specimen equivalency was determined using the Deming regression model in accordance with CLSI Document EP09c. The following results were obtained:

| Specimen (y) | Reference
Specimen (x) | Regression Equation | Sample Interval | Na | rb |
|----------------------------|---------------------------|--------------------------------------------------|--------------------------------------|----|-------|
| Lithium heparin
plasma | Serum | y = 0.99x + 0.00 mg/dL
(y = 0.99x + 0 μmol/L) | 0.50–26.91 mg/dL
(44–2379 μmol/L) | 55 | 1.000 |
| Dipotassium
EDTA plasma | Serum | y = 0.97x + 0.02 mg/dL
(y = 0.97x + 2 μmol/L) | 0.50–26.91 mg/dL
(44–2379 μmol/L) | 55 | 0.998 |

ª Number of samples tested.

b Correlation Coefficient.

10.6 Interferences

10.6.1 Hemolysis, Icterus, and Lipemia (HIL)

The Atellica CH ECre3 assay is designed to have ≤ 10% interference from hemoglobin, bilirubin, and lipemia. 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. Bias > 10% is considered interference. Analyte results should not be corrected based on this bias.

Interference testing was performed in accordance with CLSI Document EP07. The following results were obtained for serum:

| Substance | Substance Concentration
Conventional Units (SI Units) | Analyte Concentration
Conventional Units (SI Units) | Bias
% |
|------------|----------------------------------------------------------|--------------------------------------------------------|-----------|
| Hemoglobin | 200 mg/dL (2.0 g/L) | 1.00 mg/dL (88 µmol/L) | 6.0 |
| | 1000 mg/dL (10.0 g/L) | 8.25 mg/dL (729 µmol/L) | -3.2 |

9

510(k) Summary

	25 mg/dL (427.5 µmol/L)	0.97 mg/dL (86 µmol/L)	-6.2
Bilirubin, conjugated	25 mg/dL (427.5 µmol/L)	8.76 mg/dL (774 µmol/L)	-3.1
Bilirubin, unconjugated	25 mg/dL (427.5 µmol/L)	0.97 mg/dL (86 µmol/L)	-4.1
	25 mg/dL (427.5 µmol/L)	8.66 mg/dL (766 µmol/L)	-1.6
Lipemia (Intralipid®)	2000 mg/dL (20.0 g/L)	1.06 mg/dL (94 µmol/L)	-3.8
	2000 mg/dL (20.0 g/L)	8.06 mg/dL (713 µmol/L)	-2.6

Non-Interfering Substances 10.6.2

The following substances do not interfere with the Atellica CH ECre3 assay when present in serum, lithium heparin plasma, dipotassium EDTA plasma, and urine at the concentrations indicated in the tables below. Bias due to these substances is ≤ 10% at an analyte concentration of 1.00 mg/dL and 8.00 mg/dL for serum and 40.00 mg/dL and 180.00 mg/dL for urine.

Serum

| Substance | Highest Concentration with No Interference
Conventional Units (SI Units) | Analyte Concentration
Conventional Units (SI Units) | % |
|-----------------------------------|------------------------- | Acetaminophen | 200 µg/mL (1.3 mmol/L) | | 200 µg/mL (1.3 mmol/L) | Calcium dobesilate
(Dexium) | 0.38 mg/dL (9.1 µmol/L) | | 0.38 mg/dL (9.1 µmol/L) | Cefoxitin | 6600 µg/mL (15.4 mmol/L) | | 6600 µg/mL (15.4 mmol/L) | Cephalexin | 200 µg/mL (575.7 µmol/L) | | 200 µg/mL (575.7 µmol/L) | Dicynone (Etamsylate) | 0.59 mg/dL (22.4 µmol/L) | | 0.59 mg/dL (22.4 µmol/L) | DL-proline | 11.5 mg/dL (998.9 µmol/L) | | 11.5 mg/dL (998.9 µmol/L) | Dobutamine | 5 µg/mL (16.6 µmol/L) | | 5 µg/mL (16.6 µmol/L) | Dopamine | 10 µg/mL (65.3 µmol/L) | | 10 µg/mL (65.3 µmol/L) | Ethylglycine (N-
ethylglycine) | 6 µg/mL (58.2 µmol/L) | | 6 µg/mL (58.2 µmol/L) | Fluorocytosine | 200 µg/mL (1549 µmol/L) | | 200 µg/mL (1549 µmol/L) | Levodopa (L-dopa) | 15 µg/mL (76.1 µmol/L) | | 15 µg/mL (76.1 µmol/L) | Metamizole (Sulpyrine) | 25 mg/L (750 µmol/L) | | 25 mg/L (750 µmol/L) Tested
--------------------------------------------------------------|--------------------------------------------------------|------|
| 0.94 mg/dL (83 µmol/L) | 1.1 |
| 8.32 mg/dL (735 µmol/L) | -0.2 |
| 1.02 mg/dL (90 µmol/L) | -6.9 |
| 8.74 mg/dL (773 µmol/L) | -2.1 |
| 1.04 mg/dL (92 µmol/L) | -8.7 |
| 7.44 mg/dL (658 µmol/L) | -1.1 |
| 0.92 mg/dL (81 µmol/L) | 1.1 |
| 7.90 mg/dL (698 µmol/L) | -0.4 |
| 1.01 mg/dL (89 µmol/L) | -8.9 |
| 8.64 mg/dL (764 µmol/L) | -2.1 |
| 0.98 mg/dL (87 µmol/L) | 3.1 |
| 8.49 mg/dL (751 µmol/L) | 0.2 |
| 0.98 mg/dL (87 µmol/L) | -5.1 |
| 8.62 mg/dL (762 µmol/L) | -2.3 |
| 1.02 mg/dL (90 µmol/L) | -6.9 |
| 8.74 mg/dL (773 µmol/L) | -2.1 |
| 1.01 mg/dL (89 µmol/L) | 0.0 |
| 8.66 mg/dL (766 µmol/L) | -0.2 |
| 1.07 mg/dL (95 µmol/L) | -0.9 |
| 7.94 mg/dL (702 µmol/L) | -0.1 |
| 1.03 mg/dL (91 µmol/L) | -4.9 |
| 8.63 mg/dL (763 µmol/L) | -2.3 |
| 0.97 mg/dL (86 µmol/L) | -5.2 |
| 8.37 mg/dL (740 µmol/L) | -4.2 |

10

Serum
Substance	Highest Concentration Tested
with No Interference
Conventional Units (SI Units)	Analyte Concentration
Conventional Units (SI Units)	%
Methyl dopa	11.3 µg/mL (53.5 µmol/L)	1.02 mg/dL (90 µmol/L)	-8.8
	11.3 µg/mL (53.5 µmol/L)	7.47 mg/dL (660 µmol/L)	-4.3
N-acetyl-p-benzoquinine
imine (NAPQI)	0.4 mg/L (26.8 µmol/L)	1.02 mg/dL (90 µmol/L)	-2.9
	0.4 mg/L (26.8 µmol/L)	8.72 mg/dL (771 µmol/L)	-0.3
N-Acetyl Cysteine (NAC)	37.5 mg/dL (2.3 mmol/L)	0.98 mg/dL (87 µmol/L)	-7.1
	37.5 mg/dL (2.3 mmol/L)	8.36 mg/dL (739 µmol/L)	-0.7
Phenindionea	5 mg/dL (225 µmol/L)	0.97 mg/dL (86 µmol/L)	-5.2
	5 mg/dL (225 µmol/L)	7.76 mg/dL (686 µmol/L)	-4.3
Phenylbutazone	321 µg/mL (1040.9 µmol/L)	0.99 mg/dL (88 µmol/L)	-3.0
	321 µg/mL (1040.9 µmol/L)	8.43 mg/dL (745 µmol/L)	-1.5
Rifampicin	2.4 mg/dL (29.2 µmol/L)	1.02 mg/dL (90 µmol/L)	-2.0
	2.4 mg/dL (29.2 µmol/L)	8.57 mg/dL (758 µmol/L)	-0.6
Salicylate	200 µg/mL (1448 µmol/L)	0.99 mg/dL (88 µmol/L)	1.0
	200 µg/mL (1448 µmol/L)	8.41 mg/dL (743 µmol/L)	-0.2

ª Use of this assay is not recommended for patients being treated with phenindione due to the reported falsely depressed results from phenindione metabolites. Sankaralingam A, Karim Y, Swaminathan R. Phenindione interferes with measurement of creatinine. Clin Biochem. 2013;46(18):1912–1913.

Urine

| Substance | Highest Concentration Tested
with No Interference
Conventional Units (SI Units) | Analyte Concentration
Conventional Units (SI Units) | % |
|----------------------|---------------------------------------------------------------------------------------|--------------------------------------------------------|------|
| 6N HCl | 0.01% | 41.72 mg/dL (3688 µmol/L) | 0.3 |
| | 0.01% | 188.42 mg/dL (16,656 µmol/L) | -0.6 |
| pH 4 | 4.0 pH | 42.73 mg/dL (3777 µmol/L) | -3.9 |
| | 4.0 pH | 191.39 mg/dL (16,919 µmol/L) | -2.3 |
| pH 9 | 9.0 pH | 42.73 mg/dL (3777 µmol/L) | -5.4 |
| | 9.0 pH | 190.45 mg/dL (16,836 µmol/L) | -3.8 |
| Acetaminophen | 200 mg/dL (13.2 mmol/L) | 40.36 mg/dL (3568 µmol/L) | 1.2 |
| | 200 mg/dL (13.2 mmol/L) | 183.14 mg/dL (16,190 µmol/L) | 2.5 |
| Acetic Acid | 25 mL/24 hr collection | 41.92 mg/dL (3706 µmol/L) | -0.6 |
| | 25 mL/24 hr collection | 187.47 mg/dL (16,572 µmol/L) | -0.6 |
| Albumin | 0.5 g/dL (5 g/L) | 42.50 mg/dL (3757 µmol/L) | -0.5 |
| | 0.5 g/dL (5 g/L) | 192.04 mg/dL (16,976 µmol/L) | 0.4 |
| Ascorbate | 3 mg/dL (199.9 µmol/L) | 41.94 mg/dL (3707 µmol/L) | 0.0 |
| | 3 mg/dL (199.9 µmol/L) | 190.30 mg/dL (16,823 µmol/L) | -0.4 |
| Boric acid | 1% w/v | 42.69 mg/dL (3774 µmol/L) | -0.4 |
| | 1% w/v | 190.59 mg/dL (16,848 µmol/L) | -0.6 |
| Conjugated bilirubin | 50 mg/dL (855 µmol/L) | 37.01 mg/dL (3272 µmol/L) | -0.9 |
| | 50 mg/dL (855 µmol/L) | 168.09 mg/dL (14,859 µmol/L) | -0.5 |
| Ethanol | 1 g/dL (216.9 mmol/L) | 41.43 mg/dL (3662 µmol/L) | 0.2 |
| | 1 g/dL (216.9 mmol/L) | 187.49 mg/dL (16,574 µmol/L) | -0.3 |
| Gamma Globulin | 0.5 g/dL (5 g/L) | 42.71 mg/dL (3776 µmol/L) | -0.5 |
| | 0.5 g/dL (5 g/L) | 192.42 mg/dL (17,010 µmol/L) | -0.5 |
| Glucose | 2000 mg/L (111.1 mmol/L) | 40.31 mg/dL (3563 µmol/L) | 0.6 |

11

	2000 mg/L (111.1 mmol/L)	181.95 mg/dL (16,084 µmol/L)	0.7
Hemoglobin	100 mg/L (0.1 g/L)	40.34 mg/dL (3566 µmol/L)	-0.3
	100 mg/L (0.1 g/L)	178.21 mg/dL (15,754 µmol/L)	0.6
Ibuprofen	500 mg/dL (24.3 mmol/L)	40.34 mg/dL (3566 µmol/L)	0.7
	500 mg/dL (24.3 mmol/L)	183.38 mg/dL (16,211 µmol/L)	0.4
N-Acetylcysteine	2 mg/dL (122.6 µmol/L)	40.06 mg/dL (3541 µmol/L)	-0.1
	2 mg/dL (122.6 µmol/L)	180.00 mg/dL (15,912 µmol/L)	0.1
Nitric Acid	0.6%	42.49 mg/dL (3756 µmol/L)	-0.2
	0.6%	187.60 mg/dL (16,584 µmol/L)	0.3
Oxalic acid	0.1 g/dL (11.1 mmol/L)	40.31 mg/dL (3563 µmol/L)	-0.3
	0.1 g/dL (11.1 mmol/L)	182.59 mg/dL (16,141 µmol/L)	-0.3
Sodium carbonate	5 g/24 hr collection	40.15 mg/dL (3549 µmol/L)	-0.6
	5 g/24 hr collection	180.93 mg/dL (15,994 µmol/L)	-0.2

Clinical Study 11.

Not applicable.

11.1 Expected Values

Siemens Healthineers has verified the reference interval for serum, plasma and urine for the Atellica CH ECre3 assay, in accordance with CLSI Document EP28-A3c.

Group Specimen Type	Reference Interval	Conventional Units (SI Units)
Malesa	Serum/plasma	0.73–1.18 mg/dL
(65–104 µmol/L)
Femalesa	Serum/plasma	0.55–1.02 mg/dL
(49–90 µmol/L)
Males	Urineb	800–2000 mg/day
Females	Urineb	600–1800 mg/day

a These data were verified on the Atellica CH Analyzer.

6 Wu, AHB. Tietz Clinical Guide to Laboratory Tests. 4th ed. Philadelphia, PA: WB Saunders Company; 2006:316.

12. Linearity

Linearity testing was performed in accordance with CLSI Document EP06-A.

The assay is linear for the measuring interval from 0.15-30.00 mg/dL (13-2652 µmol/L) for Serum/plasma and from 2.00–245.00 mg/dL (177–21,658 µmol/L) for Urine.

13. Standardization

The assay is traceable to the National Institute of Standards and Technology (NIST) Standard Reference Material SRM967.

Assigned values for calibrators are traceable to this standardization.

Clinical Cut-off 14.

Not applicable.

12

Conclusion 15.

The results from the performance studies support that the Candidate Device, Atellica CH Enzymatic Creatinine_3 (ECre3) assay, is substantially equivalent to the Predicate Device, ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) assay (K070727).