ADVIA CHEMISTRY ENZYMATIC CREATININE_2

K070727 · Siemens Medical Solutions Diagnostics · JFY · Aug 3, 2007 · Clinical Chemistry

Device Facts

• Record ID: K070727
• Device Name: ADVIA CHEMISTRY ENZYMATIC CREATININE_2
• Applicant: Siemens Medical Solutions Diagnostics
• Product Code: JFY · Clinical Chemistry
• Decision Date: Aug 3, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Intended Use

The ADVIA Chemistry Enzymatic Creatinine_2 is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma, and urine on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

Device Story

ADVIA Chemistry Enzymatic Creatinine_2 is an in vitro diagnostic reagent system for quantitative creatinine measurement in human serum, plasma, or urine. Used on ADVIA Chemistry 1200/1650/1800/2400 systems; operated by laboratory personnel. Principle: enzymatic assay using creatininase, creatinase, sarcosine oxidase, and horseradish peroxidase. Sample mixed with two liquid reagents; creatinine converted to creatine, then hydrolyzed to sarcosine, then decomposed to form hydrogen peroxide. Peroxidase-catalyzed oxidative condensation with HMMPS and 4-aminoantipyrine produces blue pigment. Concentration determined via endpoint absorbance measurement. Output provides creatinine levels to clinicians for renal disease diagnosis, treatment, and dialysis monitoring.

Clinical Evidence

No clinical trials performed. Analytical performance established via bench testing. Precision evaluated per CLSI EP-5A2 (10-day study, 3 instruments). Linearity/reportable range (0.1–30 mg/dL serum; 1–245 mg/dL urine) validated using CAP linearity panels and NIST-traceable materials. Method comparison against predicate (n=44-60 per group) showed high correlation (r=0.99-1.00). Interference testing conducted for common endogenous substances and medications. IDMS reference method correlation (y = 0.981x - 0.01; r = 0.999) confirmed accuracy.

Technological Characteristics

Enzymatic colorimetric endpoint assay. Reagents: two liquid, ready-to-use. Standardization: ID-MS (SRM 967). Analyzers: ADVIA Chemistry 1200/1650/1800/2400. Sensing principle: spectrophotometric absorbance of blue pigment. Analytical range: 0.1-30.0 mg/dL (serum/plasma), 1.0-245 mg/dL (urine).

Indications for Use

Indicated for quantitative determination of creatinine in human serum, plasma, and urine to aid in diagnosis and treatment of renal diseases and monitoring of renal dialysis. Prescription use only.

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 Systems Creatinine_2 (k973993)
• ADVIA® Chemistry Systems Enzymatic Creatinine (k991576)

Submission Summary (Full Text)

{0}------------------------------------------------

K070727

# 510(k) Summary

AUG - 3 2007

| Submitter information | |
|--------------------------------------------------|--------------------------------------------------|
| Contact person: | Philip Liu |
| | Manager, Regulatory Affairs & Compliance |
| Address: | Siemens Medical Solutions Diagnostics |
| | 511 Benedict Avenue |
| | Tarrytown, NY 10591 |
| Phone: | 914-524-2443 |
| | 914-524-2500 (fax) |
| Date summary prepared: | July 27, 2007 |
| Device Trade or Proprietary Name: | ADVIA® Chemistry Enzymatic Creatinine_2 (ECRE_2) |
| Device Common/Usual Name or Classification Name: | Enzymatic Method, Creatinine Test System |
| Classification Number/Class: | JFY / Class II |

This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92.

The assigned 510(k) number is:

#### Predicate Devices:

| | Predicate Device #1 | Predicate Device #2 |
|---------------|-----------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| Device Name | ADVIA® Chemistry Systems<br>Creatinine_2 | ADVIA® Chemistry Systems<br>Enzymatic Creatinine |
| Common name | Creatinine Test System | Creatinine Test System |
| 510(k) Number | k973993 | k991576 |
| Manufacturer | Siemens Medical Solutions<br>Diagnostics (formerly Bayer<br>HealthCare LLC) | Siemens Medical Solutions<br>Diagnostics (formerly Bayer<br>HealthCare LLC) |

### Device Description:

The ADVIA Chemistry Enzymatic Creatinine_2 is used for the in vitro quantitative determination of creatinine in human serum, plasma and urine on the ADVIA®

{1}------------------------------------------------

Chemistry Systems. The proposed labeling indicates the ADVIA Chemistry Enzymatic Creatinine 2 reagents can be used on the ADVIA Chemistry 1200 / 1650 / 1800 / 2400 Systems.

The principle of the method is based on the enzymatic method employing creatininase, creatinase, sarcosine oxidase, horseradish peroxidase and N-(3-sulfopropy))-3methoxy-5-methylaniline (HMMPS) as the color agent. When a sample is mixed with Reagent 1 and Reagent 2, creatinine in the sample is converted to creatine by the action of creatininase. The creatine formed is hydrolyzed by creatinase to produce sarcosine and urea. The sarcosine is then decomposed by sarcosine oxidase to form glycine, formaldehyde and hydrogen peroxide. In the presence of peroxidase (POD), the hydrogen peroxide formed yields a blue pigment by quantitative oxidative condensation with N-(3-sulfopropy)-3-methoxy-5-methylaniline (HMMPS) and 4aminoantipyrine. The creatinine concentration is obtained by measuring the absorbance of blue color. The increase in optical absorbance is determined as an endpoint assay, which is proportional to the concentration of creatinine in the sample.

#### Statement of Intended Use:

The ADVIA Chemistry Enzymatic Creatinine 2 assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma or urine on the ADVIA® Chemistry Systems. Such measurements are used in the diagnosis and treatment of renal disease, and in monitoring renal dialysis.

#### Comparison to the Predicate Device:

#### Similarities

| | ADVIA Chemistry<br>Enzymatic Creatinine_2<br>(ECRE_2)<br>( <i>new device</i> ) | ADVIA Chemistry Creatinine_2<br>(CREA_2)<br>( <i>predicate device</i> ) | ADVIA Chemistry Enzymatic<br>Creatinine<br>(CREA_E)<br>( <i>predicate device</i> ) |
|---------------------------------|--------------------------------------------------------------------------------|-------------------------------------------------------------------------|------------------------------------------------------------------------------------|
| Intended Use | Quantitative determination of<br>creatinine | Quantitative determination of<br>creatinine | Quantitative determination of<br>creatinine |
| Specimen Type | Human serum or plasma<br>(lithium heparin / K₂EDTA) or<br>urine | Human serum or plasma<br>(lithium heparin) or urine | Human serum or plasma<br>(lithium heparin) |
| Calibration | Single point | Single point | Single point |
| Expected Values<br>Serum/plasma | *Males: 0.6 - 1.1 mg/dL<br>*Females: 0.5 - 0.8 mg/dL | Males: 0.7 - 1.3 mg/dL<br>Females: 0.5 - 1.1 mg/dL | **Males: 0.9 - 1.3 mg/dL<br>**Females: 0.6 - 1.1 mg/dL |
| Expected Values<br>Urine | *Males: 800 - 2000 mg/day<br>*Females: 600 - 1800 mg/day | *Males: 800 – 2000 mg/day<br>*Females: 600 - 1800 mg/day | Not Applicable |

*Tietz NW. Clinical Guide to Laboratory Tests, 400 Edition

** Tietz NW. Clinical Guide to Laboratory Tests, 3d Edition

{2}------------------------------------------------

## Differences

| | ADVIA Chemistry Enzymatic<br>Creatinine_2 (ECRE_2)<br>( <i>new device</i> ) | ADVIA Chemistry<br>Creatinine_2<br>(CREA_2)<br>( <i>predicate device</i> ) | ADVIA Chemistry Enzymatic<br>Creatinine<br>(CREA_E)<br>( <i>predicate device</i> ) |
|-----------------|-----------------------------------------------------------------------------|----------------------------------------------------------------------------|------------------------------------------------------------------------------------|
| Principle | Enzymatic (Creatininase) | Jaffe, alkaline picrate, kinetic<br>with blank rate correction | Enzymatic (Creatinine<br>Deiminase / GLDH) |
| Reaction Type | Colorimetric Endpoint | Colorimetric Rate | Colorimetric Rate |
| Reagents | Two liquid reagents, ready to<br>use | Two liquid reagents, ready to<br>use | Two lyophilized reagents,<br>requiring reconstitution |
| Standardization | ID-MS (SRM 967) | HPLC candidate reference<br>method | HPLC candidate reference<br>method |

### Performance:

Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, method comparison, interfering substances, serum/plasma equivalency, and analytical range. The following tables summarize the precision (total), interfering substances, analytical range, and method comparison results.

All of the evaluation studies gave acceptable results compared to the predicate devices. These studies support that the ADVIA Chemistry Enzymatic Creatinine_2 assay is substantially equivalent to the ADVIA Chemistry Creatinine_2 assay and the ADVIA Chemistry Enzymatic Creatinine assay that are currently marketed.

#### Imprecision (Serum)

| ADVIA Chemistry Enzymatic Creatinine_2 | | | ADVIA Chemistry Creatinine_2 | | ADVIA Chemistry Enzymatic Creatinine | | | | |
|----------------------------------------|--------------|---------------|------------------------------|---------------|--------------------------------------|---------------|--------------|---------------|--------------|
| ADVIA 1650 | ADVIA 2400 | ADVIA 1200 | ADVIA 1650 | | ADVIA 1650 | | | | |
| Level (mg/dL) | Total CV (%) | Level (mg/dL) | Total CV (%) | Level (mg/dL) | Total CV (%) | Level (mg/dL) | Total CV (%) | Level (mg/dL) | Total CV (%) |
| 1.29 | 1.1 | 1.28 | | 1.29 | 1.1 | -- | -- | -- | -- |
| 1.76 | 0.9 | 1.75 | 0.8 | 1.73 | 1.1 | 1.5 | 5.7 | 0.9 | 6.4 |
| 3.07 | 1.1 | 3.06 | 0.9 | 3.04 | 0.9 | -- | -- | 6.1 | 2.3 |
| 8.80 | 0.6 | 8.81 | 1.4 | 8.79 | 0.9 | 8.4 | 3.4 | 9.5 | 2.0 |

#### Imprecision (Urine)

| ADVIA Chemistry Enzymatic Creatinine_2 | | | | | | ADVIA Chemistry Creatinine_2 | | | | | | |
|----------------------------------------|------------------|-----------------|------------------|-----------------|------------------|------------------------------|------------------|-----------------|------------------|-----------------|------------------|-----------------|
| | ADVIA 1650 | | ADVIA 2400 | | ADVIA 1200 | | ADVIA 1650 | | ADVIA 1200 | | ADVIA 2400 | |
| | Level<br>(mg/dL) | Total CV<br>(%) | Level<br>(mg/dL) | Total CV<br>(%) | Level<br>(mg/dL) | Total CV<br>(%) | Level<br>(mg/dL) | Total CV<br>(%) | Level<br>(mg/dL) | Total CV<br>(%) | Level<br>(mg/dL) | Total CV<br>(%) |
| | 41.56 | 1.3 | 41.13 | 1.0 | 42.34 | 1.0 | -- | -- | -- | -- | -- | -- |
| | 77.27 | 1.0 | 77.54 | 0.9 | 79.78 | 1.1 | 81.5 | 4.3 | 79.7 | 2.1 | 80.7 | 2.1 |
| | 130.59 | 0.9 | 131.33 | 0.9 | 133.09 | 1.0 | 202.7 | 1.8 | 182.5 | 1.9 | 199.7 | 1.4 |

Siemens Medical Solutions Diagnostics ADVIA Chemistry Enzymatic Creatinine 2 Premarket Notification 510(k) Section 5 - 510(k) Summary

{3}------------------------------------------------

| Specimen type,<br>System (y) | Comparison System (x) | N | Regression<br>Equation | Sy.x<br>(mg/dL) | r | Sample<br>Range<br>(mg/dL) |
|------------------------------|------------------------------------|----|------------------------|-----------------|-------|----------------------------|
| Serum, ADVIA<br>1200 | ADVIA 1200<br>Creatinine 2 | 60 | $Y = 1.017x + 0.03$ | 0.07 | 1.000 | 0.3 – 12.3 |
| Serum, ADVIA<br>1200 | ADVIA 1200<br>Enzymatic Creatinine | 28 | $Y = 0.933x + 0.11$ | 0.14 | 1.000 | 0.5 - 25.6 |
| Serum, ADVIA<br>1650 | ADVIA 1650<br>Creatinine 2 | 60 | $Y = 1.018x - 0.04$ | 0.13 | 1.000 | 0.3 - 11.9 |
| Serum, ADVIA<br>1650 | ADVIA 1650<br>Enzymatic Creatinine | 42 | $Y = 0.957x + 0.04$ | 0.12 | 1.000 | 0.6 - 25.7 |
| Serum, ADVIA<br>2400 | ADVIA 2400<br>Creatinine 2 | 60 | $Y = 1.026x - 0.03$ | 0.13 | 1.000 | 0.3 - 12.1 |
| Serum, ADVIA<br>2400 | ADVIA 2400<br>Enzymatic Creatinine | 42 | $Y = 0.954x + 0.01$ | 0.07 | 1.000 | 0.6 - 25.4 |
| Urine, ADVIA<br>1200 | ADVIA 1200<br>Creatinine 2 | 46 | $Y = 1.042x + 0.41$ | 1.80 | 1.000 | 20.0 - 238.1 |
| Urine, ADVIA<br>1650 | ADVIA 1650<br>Creatinine 2 | 49 | $Y = 1.019x - 0.99$ | 1.88 | 1.000 | 17.8 - 239.4 |
| Urine, ADVIA<br>2400 | ADVIA 2400<br>Creatinine 2 | 44 | $Y = 1.025x + 2.47$ | 2.99 | 0.999 | 18.9 - 218.1 |

## Correlation (y = ADVIA Chemistry Enzymatic Creatinine_2, x = comparison system)

#### Interfering Substances (Enzymatic Creatinine 2)

| Interfering<br>Substance | Conc.<br>(mg/dL) | Creatinine conc. (mg/dL) | | | Effect<br>(% change) | | |
|--------------------------|------------------|--------------------------|---------------|---------------|----------------------|---------------|---------------|
| | (mg/dL) | ADVIA<br>1200 | ADVIA<br>1650 | ADVIA<br>2400 | ADVIA<br>1200 | ADVIA<br>1650 | ADVIA<br>2400 |
| Hemoglobin | 500 | 0.94 | 0.92 | 0.91 | 7.5 | 6.6 | 6.6 |
| | 1000 | 3.08 | 3.06 | 3.00 | -2.8 | -3.8 | -2.2 |
| Lipids (Intralipid) | 1000 | 0.91 | 0.88 | 0.87 | 6.6 | -5.7 | -1.2 |
| | 1000 | 3.09 | 3.03 | 2.97 | -2.4 | -5.3 | -4.2 |
| Bilirubin, free | 30.0 | 0.96 | 1.01 | 0.94 | -8.9 | -7.4 | -9.6 |
| | 22.5 | 3.05 | 3.05 | 3.22 | -6.6 | -6.1 | -9.8 |
| Bilirubin, conjugated | 30.0 | 0.92 | 0.90 | 0.91 | -2.7 | -5.6 | -5.5 |
| | 30.0 | 2.96 | 2.97 | 2.94 | -4.6 | -5.4 | -6.0 |

#### Analytical Range – Serum/Plasma

| Platform | ADVIA Chemistry Enzymatic<br>Creatinine 2 |
|------------|-------------------------------------------|
| ADVIA 1650 | 0.1 - 30.0 mg/dL |
| ADVIA 2400 | 0.1 - 30.0 mg/dL |
| ADVIA 1200 | 0.1 - 30.0 mg/dL |

{4}------------------------------------------------

#### Analytical Range - Urine

| Platform | ADVIA Chemistry Enzymatic<br>Creatinine 2 |
|------------|-------------------------------------------|
| ADVIA 1650 | 1.0 - 245 mg/dL |
| ADVIA 2400 | 1.0 - 245 mg/dL |
| ADVIA 1200 | 1.0 - 245 mg/dL |

## Conclusions:

The ADVIA Chemistry Enzymatic Creatinine 2 assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Diagnostics (formerly Bayer HealthCare LLC) ADVIA Chemistry Creatinine_2 (k973993) and Enzymatic Creatinine methods (k991576).

{5}------------------------------------------------

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which features three figures in profile facing to the right. The figures are arranged in a way that they appear to be interconnected. Encircling the caduceus is the text "DEPARTMENT OF HUMAN SERVICES - USA" in a circular arrangement.

Public Health Service

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

AUG - 3 2007

Siemens Medical Solutions Diagnostics c/o Mr. Philip Liu, Manager, Regulatory Affairs & Compliance 511 Benedict Avenue Tarrytown, NY 10591

Re: k070727 Trade Name: Advia Chemistry Enzymatic Creatinine-2 Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: JFY Dated: July 20, 2007 Received: July 23, 2007

Dear Mr. Liu:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{6}------------------------------------------------

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{7}------------------------------------------------

# Indications for Use

510(k) Number (if known): KD10727

Device Name: ADVIA CHEMISTRY ENZYMATIC CREATININE_2

Indications For Use:

For in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma, and urine on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson

**Division Sign-Off**

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1_

070727