Atellica CH Creatinine_2 (Crea_2), Atellica CH Chemistry Calibrator (CHEM CAL)

K161494 · Siemens Healthcare Diagnostics, Inc. · CGX · Nov 15, 2016 · Clinical Chemistry

Device Facts

• Record ID: K161494
• Device Name: Atellica CH Creatinine_2 (Crea_2), Atellica CH Chemistry Calibrator (CHEM CAL)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CGX · Clinical Chemistry
• Decision Date: Nov 15, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Intended Use

The Atellica™ CH Creatinine_2 (Crea_2) assay is an in vitro diagnostic test used for the quantitative measurement of creatinine in human serum, plasma (lithium heparin), and urine, using the Atellica™ CH Analyzer. Creatinine measurements are used in the diagnosis and treatment of certain renal diseases, and in monitoring renal dialysis patients. The Atellica™ CH Chemistry Calibrator (CHEM CAL) is used for calibrating the Crea_2 assay using the Atellica™ CH Analyzer.

Device Story

The Atellica CH Creatinine 2 (Crea 2) is an in vitro diagnostic assay for the Atellica CH Analyzer. It utilizes a modified Jaffe method where creatinine reacts with picric acid in an alkaline medium to form a red-colored creatinine-picrate complex. The system measures the rate of complex formation at 505/571 nm, which is proportional to creatinine concentration. The device incorporates rate blanking to minimize bilirubin interference and applies an automatic 0.3 mg/dL subtraction to correct for positive bias caused by nonspecific serum/plasma protein interactions. The assay is used by laboratory technicians in clinical settings to provide quantitative results that assist healthcare providers in diagnosing renal disease and managing dialysis patients. The Atellica CH Chemistry Calibrator (CHEM CAL) is a bovine serum-based, lyophilized product used to calibrate the assay.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A3 (n=80 replicates per sample). Linearity evaluated per CLSI EP06-A (r=1.000 serum, r=0.999 urine). Method comparison (n=143 serum, n=109 urine) vs predicate showed high correlation (r=0.999). Interference testing per CLSI EP07-A2 showed no significant bias for common endogenous/exogenous substances. Reference intervals validated via transference per CLSI EP28-A3c.

Technological Characteristics

Photometric/colorimetric assay; modified kinetic Jaffe method (alkaline picrate). Reagents: sodium hydroxide, picric acid. Calibrator: lyophilized bovine serum base. Analyzed on Atellica CH Analyzer. Measuring range: 0.15-30.00 mg/dL (serum/plasma), 3.00-245.00 mg/dL (urine). Traceable to NIST SRM 914 and IDMS reference method. Calibration interval: 60 days.

Indications for Use

Indicated for quantitative measurement of creatinine in human serum, lithium heparin plasma, and urine to aid in diagnosis and treatment of renal diseases and monitoring of renal dialysis patients.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• ADVIA Chemistry Enzymatic Creatinine_2 (ECRE_2) (k070727)
• ADVIA Chemistry Calibrator (k050374)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a stylized eagle with three heads facing to the right. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

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.

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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 [phone] or [phone] 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 [phone] or [phone] 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

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## Indications for Use

510(k) Number (if known)

k161494

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) | |
|----------------------------------------------------------------------------|---------------------------------------------------------------------------|
| <div> <span>☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> <span>☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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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: [e-mail] Phone: [phone] Fax: [phone]

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,<br>Creatinine | Calibrator, Secondary |
|-------------------------|----------------------------------------------|------------------------------------------------|
| Proprietary Name: | Atellica CH Creatinine_2<br>(Crea_2) | Atellica CH Chemistry Calibrator<br>(CHEM CAL) |
| Classification<br>Name: | Creatinine Test System | Calibrator |
| Regulation<br>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 |

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| | 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.

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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:<br>ADVIA Chemistry Enzymatic<br>Creatinine_2 (ECRE_2)<br>(k070727) | New Device:<br>Atellica CH Creatinine_2<br>(Crea_2) |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use : | For in vitro diagnostic use in<br>the quantitative<br>determination of creatinine<br>in human<br>serum, plasma (lithium<br>heparin and K2EDTA), and<br>urine on ADVIA Chemistry<br>systems. | The Atellica™ CH<br>Creatinine_2 (Crea_2) assay<br>is for in vitro diagnostic use in<br>the quantitative determination<br>of creatinine in human serum,<br>plasma (lithium heparin), and<br>urine using the Atellica™ CH<br>Analyzer. |
| Indications for Use: | Such measurements are<br>used in the diagnosis and<br>treatment of renal diseases,<br>and in monitoring renal<br>dialysis | Same |
| Device Technology: | Enzymatic reaction of<br>Fossati, Prencipe, and Berti | Reaction of picric acid with<br>creatinine in an alkaline<br>medium as described in the<br>original<br>procedure of Jaffe. |
| Sample Type: | Serum, Lithium Heparin | Serum, Lithium Heparin |
| | plasma, K2-EDTA plasma<br>and urine | plasma, and urine |
| Reference Interval: | Serum/Plasma<br>Males 0.6 – 1.1 mg/dL<br>Females 0.5 – 0.8 mg/dL<br>Urine<br>Males 800 – 2000 mg/day<br>Females 600 – 1800 mg/day | Serum/plasma<br>Males 0.70-1.30 mg/dL<br>Females 0.55 -1.02 mg/dL<br>Urine :<br>Males 950 – 2490 mg/day<br>Females 600 – 1800 mg/day |
| Standardization: | SRM967 | IDMS Reference Method |
| Calibration<br>Frequency: | 60 days | Same |
| Analytical Measuring<br>Interval: | Serum/Plasma:<br>0.10 – 30.00 mg/dL<br>Urine:<br>1.0 – 245.00 mg/dL | Serum and plasma:<br>0.15–30.00 mg/dL<br>Urine: 3.00–245.00 mg/dL |
| Interferences: | Bilirubin (Unconjugated) –<br>30 mg/dL<br>Bilirubin (Conjugated) – 30<br>mg/dL<br>Lipemia (Intralipid®) – 1000<br>mg/dL<br>Hemoglobin - 500 mg/dL | Bilirubin (Unconjugated) – 10<br>mg/dL<br>Bilirubin (Conjugated) – 20<br>mg/dL<br>Lipemia (Intralipid®) – 500<br>mg/dL<br>Hemoglobin - 500 mg/dL |
| Calibrators: | ADVIA Chemistry Calibrator<br>(k050374) | Atellica CH Chemistry<br>Calibrator |

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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| Feature | Predicate Device: | New Device: |
|----------------|----------------------------------------------------------------|-------------------------------------------------------------|
| | ADVIA Chemistry Calibrator<br>(k050374) | Atellica CH Chemistry<br>Calibrator (CHEM CAL) |
| Intended Use : | For in vitro diagnostic use in<br>the calibration of chemistry | The AtellicaTM CH Chemistry<br>Calibrator (CHEM CAL) is for |

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| | assays on ADVIA®<br>Chemistry systems. | in vitro diagnostic use in<br>calibrating the Crea_2 assay<br>using the Atellica™ CH<br>Analyzer. |
|---------------------------------|----------------------------------------|---------------------------------------------------------------------------------------------------|
| Calibrator Matrix: | Bovine Serum Base | Same |
| Calibrator Form: | Lyophilized | Same |
| Number of Calibrator<br>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<br>were tested (N=5) for 3<br>days, one run per day, 3<br>reagent lots | 0.03 mg/dL serum<br>0.35 mg/dL urine |

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| LoD | 4 low analyte samples<br>were tested (N=5) for 3<br>days, one run per day, 3<br>reagent lots | 0.08 mg/dL serum<br>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<br>mg/dL (µmol/L) | SDa<br>mg/dL (µmol/L) | CVb<br>(%) | SDa<br>mg/dL (µmol/L) | CVb<br>(%) | | |
| 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<br>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<br>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<br>Type | Comparison Assay<br>(x) | N | r | Regression<br>Equation | Sample Range |
|------------------|----------------------------------------------|-----|-------|---------------------------|------------------------|
| Serum | ADVIA Ecre_2 | 140 | 0.999 | y = 0.98x + 0.00<br>mg/dL | 0.12-28.89<br>mg/dL |
| Urine | ADVIA Ecre_2 | 109 | 0.999 | y = 0.95x +0.07<br>mg/dL | 3.57 - 238.85<br>mg/dL |
| Serum | Isotope Dilution Mass<br>Spectrometry (IDMS) | 49 | 0.999 | y = 0.96x + 0.05<br>mg/dL | 0.41 - 32.09<br>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<br>(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.

{12}------------------------------------------------

| Group | Specimen type | Reference Interval<br>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) |

- 1. Burtis CA, Ashwood ER, eds. Tietz Fundamentals of Clinical Chemistry. 5th ed. Philadelphia, PA: WB Saunders Co: 2001:23-25, 422.
- 2. Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem. 2008;54(3):559-566.
- 3. Junge W, Wilke B, Halabi A, Klein G. Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffé method. Clin Chim Acta. 2004;344(1-2):137-48.
- 4. Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd 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.