DIMENSION CKI FLEX REAGENT CARTRIDGE, DIMENSION MBI FLEX REAGENT CARTRIDGE, AND CKI/MBI CALIBRATOR, MODELS DF38, DF32

K081731 · Siemens Healthcare Diagnostics · CGS · Aug 29, 2008 · Clinical Chemistry

Device Facts

• Record ID: K081731
• Device Name: DIMENSION CKI FLEX REAGENT CARTRIDGE, DIMENSION MBI FLEX REAGENT CARTRIDGE, AND CKI/MBI CALIBRATOR, MODELS DF38, DF32
• Applicant: Siemens Healthcare Diagnostics
• Product Code: CGS · Clinical Chemistry
• Decision Date: Aug 29, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Intended Use

The CKI method is an in vifro diagnostic test for the quantitative measurement of creatine kinase in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. The creatine kinase MB (MBI) method is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. The CKI/MBI CAL is an in vitro diagnostic product for the calibration of the Creatine Kinase (CKI) and Creatine Kinase MB (MBI) methods on the Dimension® clinical chemistry system.

Device Story

Prepackaged reagent cartridges for Dimension clinical chemistry systems; measure CK and CK-MB activity in human serum/plasma. CKI assay uses coupled enzyme reaction: CK catalyzes transphosphorylation of creatine phosphate to ADP, producing ATP; ATP used by hexokinase to phosphorylate glucose; G-6-PDH oxidizes resulting glucose-6-phosphate, reducing NADP to NADPH. MBI assay uses immunoinhibition: antibody inhibits CK-M subunit; B subunit activity measured via same coupled enzyme reaction. NADPH formation rate measured bichromatically at 340/540 nm; proportional to enzyme activity. Used in clinical laboratories; operated by trained personnel. Output provides quantitative enzyme activity levels; assists clinicians in diagnosing myocardial infarction and muscle disorders.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (n=80 per sample). Linearity per CLSI EP6-A (r=0.99997 for CKI; r=0.99992 for MBI). Detection limits (LoD) determined per CLSI EP17-A (CKI: 7 U/L; MBI: 3 U/L). Method comparison against IFCC reference method and Roche predicates showed high correlation (r=0.986-1.000). Interference testing per CLSI EP7-A2 showed <10% bias for common substances. Reference intervals confirmed via bridging study.

Technological Characteristics

Reagent cartridges utilize coupled enzyme reaction (Hexokinase/G-6-PDH) with bichromatic rate detection at 340/540 nm. Calibrator is liquid, human serum albumin-based, containing human CK and porcine CK-MB. System is an automated clinical chemistry analyzer. No specific software algorithm class or connectivity standards detailed beyond system-level integration.

Indications for Use

Indicated for quantitative measurement of creatine kinase (CK) and CK-MB isoenzyme in human serum/plasma to aid diagnosis/treatment of myocardial infarction and muscle diseases (e.g., Duchenne-type muscular dystrophy). For prescription use only.

Regulatory Classification

Identification

A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Predicate Devices

• Roche Diagnostic Systems Inc. CK-NAC Reagent (k834502)
• Roche Diagnostic Systems Inc. CK-MB Reagent (k003158)
• Roche Diagnostic Systems Inc. Calibrator for Automated Systems (k990460)

Submission Summary (Full Text)

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

### 510(k) Summary of Safety and Effectiveness for the Dimension® Creatine Kinase MB Flex® Reagent Cartridge (DF32) CKI/MBI Calibrator (DC32)

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

| A. 510(k) Number: | K081731 |
|-------------------|---------|
|-------------------|---------|

B. Date of Preparation: August 21, 2008

## C. Proprietary and Established Names:

Dimension® Creatine Kinase (CKI) Flex® Reagent Cartridge (DF38) Dimension® Creatine Kinase MB (MBI) Flex® Reagent Cartridge (DF32) CKI/MBI Calibrator (DC32)

## D. Applicant:

Siemens Healthcare Diagnostics Inc., P.O. Box 6101, Newark, DE 19714-6101 Victor M. Carrio, Senior Manager, Regulatory Affairs Office: [phone] Fax: [phone]

## E. Regulatory Information:

Dimension® Creatine Kinase (CKI) Flex® Reagent Cartridge (DF38)

1. Regulation section: 21 CFR § 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system

- 2. Classification: Class II
- 3. Product Code: CGS, Nad reduction/nadh oxidation, cpk or isoenzymes
- 4. Panel: Clinical Chemistry

Dimension® Creatine Kinase MB (MBI) Flex® Reagent Cartridge (DF32)

- 1. Regulation section: 21 CFR § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system
- 2. Classification: Class II
- 3. Product Code: JHS, Differential rate kinetic method, cpk or isoenzymes
- 4. Panel: Clinical Chemistry

CKI/MBI Calibrator (DC32)

- 1. Regulation section: 21 CFR & 862.1150 Calibrator
- 2. Classification: Class II
- 3. Product Code: JIX, Calibrator, Multi-Analyte Mixture
- 4. Panel: Clinical Chemistry

## F. Predicate Devices:

Roche Diagnostic Systems Inc. CK-NAC Reagent (K834502) Roche Diagnostic Systems Inc. CK-MB Reagent (K003158) Roche Diagnostic Systems Inc. Calibrator for Automated Systems (K990460) Roche Diagnostic Systems Inc. Calibrator for Automated Systems, CKMB (K003158)

### G. Device Description:

Dimension® (CKI) Flex® Reagent Cartridge (DF38)

In a coupled enzyme reaction, the creatine kinase in patient samples catalyzes the transphosphorylation of phosphate from creatine phosphate to adenosine

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

diphosphate (ADP) producing adenosine-triphosphate (ATP). Hexokinase (HK) phosphorylates glucose from the ATP to phosphorylate glucose. The resulting qlucose-6-phosphate is oxidized by qlucose-6-phosphate dehydrogenase (G-6-PDH) with the simultaneous reduction of nicotinamide adenine dinucleotide phosphate (NADP). The rate of formation of NADPH is directly proportional to the CK activity in the sample and is measured bichromatically at 340 and 540 nm.

#### Dimension® (MBI) Flex® Reagent Cartridge (DF32)

The activity of the CK-MM isoenzyme is inhibited by an antibody specific for the CK-M subunit. The activity of the B subunit of creatine kinase MB isoenzyme is not inhibited, and it is on this basis that CK-MB can be measured. In an enzyme coupled reaction, creatine kinase in patient samples catalyzes the transphosphorylation of creatine phosphate to adenosine-diphosphate (ADP), producing adenosine-triphosphate (ATP). Hexokinase (HK) uses the ATP to phosphorylate glucose_The resulting glucose-6-phosphate is oxidized by glucose-6phosphate dehydrogenase (G-6-PDH) with the simultaneous reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. The rate of formation of NADPH is measured bichromatically at 340, 540 nm and is directly proportional to CK-B activity in the sample.

#### CKI/MBI Calibrator (DC32)

CKI/MBI CAL is a liquid, multi-analyte, human serum albumin based product containing creatine kinase (human source) and creatine kinase MB (porcine source). The kit consists of four vials per level (2 and3) with 2.0 mL per vial. Level 1 calibrator for CKI/MBI is not included in the CKI/MBI CAL carton. Purified Water Diluent or reagent grade water is required for use as Calibrator Level 1. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.

#### H. Intended Use:

#### Dimension® (CKI) Flex® Reagent Cartridge (DF38)

The CKI method is an in vifro diagnostic test for the quantitative measurement of creatine kinase in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

#### Dimension® (MBI) Flex® Reagent Cartridge (DF32)

The creatine kinase MB (MBI) method is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

#### CKI/MBI Calibrator (DC32)

The CKI/MBI CAL is an in vitro diagnostic product for the calibration of the Creatine Kinase (CKI) and Creatine Kinase MB (MBI) methods on the Dimension® clinical chemistry system.

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

## l. Substantial Equivalence Information:

The Dimension® (CKI) Flex® Reagent Cartridge (DF38), (MBI) Flex® Reagent Cartridge (DF32), and the CKI/MBI Calibrator (DC32) were compared to the Roche Diagnostic Systems Inc. predicate devices CK-NAC Reagent (K834502), CK-MB Reagent (K003158), Calibrator for Automated Systems (K990460), and Calibrator for Automated Systems, CKMB (K003158). A comparison of the important similarities and differences between the devices and the predicates is provided in the following tables:

| Feature | Dimension® (CKI) Flex® Reagent<br>Cartridge (DF38) | CK-NAC Reagent (K834502) |
|-------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended<br>Use | The CKI method is an in vitro<br>diagnostic test for the quantitative<br>measurement of creatine kinase in<br>human serum and plasma on the<br>Dimension® Clinical Chemistry System. | In vitro assay for the quantitative<br>determination of creatine kinase (CK) in<br>human serum and plasma on Roche<br>automated clinical chemistry analyzers. |
| Device<br>Technology<br>(detection) | Bichromatic rate | UV Test |
| Measuring<br>Range | 7 - 1000 U/L | 3-2300 U/L |
| Analytical<br>Sensitivity | 7 U/L | 3 U/L |

| Feature | Dimension® (MBI) Flex® Reagent<br>Cartridge (DF32) | CK-MB Reagent (K003158) |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended<br>Use | The creatine kinase MB (MBI) method<br>is an <i>in vitro</i> diagnostic test for the<br>quantitative measurement of creatine<br>kinase MB isoenzyme activity in<br>human serum and plasma on the<br>Dimension® clinical chemistry system. | Immunoinhibition assay for the<br>quantitative <i>in vitro</i> determination of the<br>MB isoenzyme of creatine kinase in<br>human serum and plasma on Roche<br>automated clinical chemistry analyzers. |
| Device<br>Technology<br>(detection) | Bichromatic rate | Immunological UV Assay |
| Measuring<br>Range | 3 - 125 U/L | 3 - 2300 U/L |
| Analytical<br>Sensitivity | 3 U/L | 3 U/L |

| Feature | CKI/MBI Calibrator<br>(DC32) | Calibrator for<br>Automated Systems<br>(K990460) | Calibrator for<br>Automated Systems,<br>CKMB (K003158) |
|-----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended<br>Use | The CKI/MBI CAL is an in<br>vitro diagnostic product<br>for the calibration of the<br>Creatine Kinase (CKI)<br>and Creatine Kinase MB<br>(MBI) methods on the<br>Dimension® clinical<br>chemistry system. | Calibrator for automated<br>systems (C.f.a.s.) is for<br>use in the calibration of<br>quantitative Roche<br>methods on Roche clinical<br>chemistry analyzers as<br>specified in the value<br>sheet. | C.f.a.s. (Calibrator for<br>automated systems) CK-<br>MB is for use in the<br>calibration of quantitative<br>Roche methods on<br>Roche clinical chemistry<br>analyzers as specified in<br>the value sheet. |
| Analyte | Creatine kinase (human | Creatine kinase (rabbit | Creatine kinase-MM |

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

| | source) and creatine<br>kinase-MB (porcine<br>source) | muscle) | (human source) and CK-<br>BB (porcine brain) |
|--------|-------------------------------------------------------|-------------|----------------------------------------------|
| Matrix | Human serum albumin | Human serum | Human serum |
| Form | Liquid | Lyophilized | Lyophilized |
| Levels | CKI - Three levels<br>MBI - Five levels | Two levels | Two levels |

#### J. Conclusion:

The Dimension® (CKI) Flex® Reagent Cartridge (DF38), (MBI) Flex® Reagent Cartridge (DF32), and the CKI/MBI Calibrator (DC32) are substantially equivalent to the Roche Diagnostic Systems Inc. predicate devices CK-NAC Reagent (K834502), CK-MB Reagent (K003158), Calibrator for Automated Systems (K990460), and Calibrator for Automated Systems, CKMB (K003158). Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance.

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics Inc. c/o Mr. Victor M. Carrio P.O. Box 6101, Mailbox 514 Newark, DE 19714-6101

AUG 2 9 2008

Re: k081731

> Trade/Device Name: Dimension® Creatine Kinase (CKI) Flex® Reagent Cartridge (DF38), Dimension® Creatine Kinase MB (MBI) Flex® Reagent Cartridge (DF32) CK/MBI Calibrator (DC32)

Regulation Number: 21 CFR§ 862.1215

Regulation Name: Creatine Phosphokinase/Creatine Kinase or Isoenzymes Test System Regulatory Class: Class II Product Code: CGS, JHS, JIX Dated: June 17, 2008 Received: June 19, 2008

Dear Mr. Carrio:

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).

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

Page 2 -

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 this, permitte 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 nother 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 tollit the 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.

Yéan 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

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

## Indications for Use

510(k) Number (if known): K081731

Device Name:

Dimension® (MBI) Flex® Reagent Cartridge (DF32)

Indication For Use:

The creatine kinase MB (MBI) method is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)(081731

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

## Indications for Use

510(k) Number (if known): K081731

Device Name:

Dimension® (CKI) Flex® Reagent Cartridge (DF38)

Indication For Use:

The CKI method is an in vitro diagnostic test for the quantitative measurement of creatine kinase in human serum and plasma on the Dimension® clinical chemistry system. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)to81731

{8}------------------------------------------------

# Indications for Use

510(k) Number (if known): K081731

Device Name:

Dimension® CKI/MBI Calibrator (DC32)

Indication For Use:

The CKI/MBI CAL is an in vitro diagnostic product for the calibration of the Creatine Kinase (CKI) and Creatine Kinase MB (MBI) methods on the Dimension® clinical chemistry system.

Prescription Use _ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

______________________________________________________________________________________________________________________________________________________________________________

Distion Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K081731