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.

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 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 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.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension® Creatine Kinase MB Flex® Reagent Cartridge (DF32) and CKI/MBI Calibrator (DC32):

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list "acceptance criteria" with numerical targets for performance metrics. Instead, it relies on demonstrating substantial equivalence to predicate devices. The performance is implied by the comparison tables, showing that the new devices perform comparably to the predicates in terms of intended use, technology, measuring range, and analytical sensitivity.

Without explicit acceptance criteria, we can infer the reported device performance from the comparison to the predicate devices.

Feature	Predicate Device (Roche CK-MB Reagent K003158) Acceptance Criteria (Implied by Predicate)	Dimension® (MBI) Flex® Reagent Cartridge (DF32) Reported Performance
Intended Use	Immunoinhibition assay for quantitative in vitro determination of CK-MB in human serum and plasma on Roche automated clinical chemistry analyzers.	Quantitative measurement of creatine kinase MB isoenzyme activity in human serum and plasma on the Dimension® clinical chemistry system.
Device Technology	Immunological UV Assay	Bichromatic rate
Measuring Range	3 - 2300 U/L	3 - 125 U/L
Analytical Sensitivity	3 U/L	3 U/L

For CKI (DF38):

Feature	Predicate Device (Roche CK-NAC Reagent K834502) Acceptance Criteria (Implied by Predicate)	Dimension® (CKI) Flex® Reagent Cartridge (DF38) Reported Performance
Intended Use	In vitro assay for quantitative determination of creatine kinase (CK) in human serum and plasma on Roche automated clinical chemistry analyzers.	Quantitative measurement of creatine kinase in human serum and plasma on the Dimension® Clinical Chemistry System.
Device Technology	UV Test	Bichromatic rate
Measuring Range	3-2300 U/L	7 - 1000 U/L
Analytical Sensitivity	3 U/L	7 U/L

For CKI/MBI Calibrator (DC32):

Feature	Predicate Devices (K990460, K003158) Acceptance Criteria (Implied by Predicate)	CKI/MBI Calibrator (DC32) Reported Performance
Intended Use	Calibration of quantitative Roche methods.	Calibration of CKI and MBI methods on the Dimension® clinical chemistry system.
Analyte	Creatine kinase (rabbit muscle) / Creatine kinase-MM (human) and CK-BB (porcine brain)	Creatine kinase (human source) and creatine kinase-MB (porcine source)
Matrix	Human serum	Human serum albumin
Form	Lyophilized	Liquid
Levels	Two levels	CKI - Three levelsMBI - Five levels

2. Sample Size Used for the Test Set and Data Provenance

The summary states: "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance."

Sample Size: The document does not specify the sample size used for the comparative testing (test set patients or samples).
Data Provenance: The document does not specify the data provenance (e.g., country of origin, retrospective or prospective nature of the samples). It only mentions "human serum and plasma" as sample types.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not applicable as the devices are in vitro diagnostic reagents and calibrators designed for quantitative laboratory measurement, not for interpretation by human experts. The "ground truth" in this context would be the measured values from the predicate devices or reference methods. The performance is assessed by analytical comparison, not expert consensus on diagnoses.

4. Adjudication Method for the Test Set

This is not applicable to this type of in vitro diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where human readers interpret medical images or conduct clinical assessments, and disagreements need resolution. For laboratory assays, performance is assessed through statistical methods comparing results to a reference.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This is not applicable. This submission concerns in vitro diagnostic reagents and calibrators, not an AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, an MRMC study and AI-assisted performance improvement are not relevant to this submission.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is not applicable. The device is an in vitro diagnostic reagent system that functions on a clinical chemistry analyzer. It is an algorithm-driven system in the sense that the analyzer's software processes the photometric measurements, but it's not a standalone "algorithm" in the context of AI or image interpretation. Its performance is its standalone performance on the Dimension® system, generating quantitative results. The comparison is made against existing predicate assays.

7. The Type of Ground Truth Used

The "ground truth" for proving substantial equivalence in this context is the results obtained from the legally marketed predicate devices (Roche CK-NAC Reagent, Roche CK-MB Reagent, and their respective calibrators). The comparative testing would involve analyzing samples with both the new device and the predicate to show similar results.

8. The Sample Size for the Training Set

This information is not applicable in the context of this submission. "Training set" typically refers to data used to train a machine learning model. These are chemical reagents and calibrators, whose performance is based on established biochemical reactions, not on data-driven machine learning models. Performance is validated through analytical studies, not an AI training process.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable for the same reasons as point 8.

Summary

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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
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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: (302) 631-0376 Fax: (302) 631-6299

E. Regulatory Information:

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

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

1. Classification: Class II
1. Product Code: CGS, Nad reduction/nadh oxidation, cpk or isoenzymes
1. 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
1. Classification: Class II
1. Product Code: JHS, Differential rate kinetic method, cpk or isoenzymes
1. Panel: Clinical Chemistry

CKI/MBI Calibrator (DC32)

1. Regulation section: 21 CFR & 862.1150 Calibrator
1. Classification: Class II
1. Product Code: JIX, Calibrator, Multi-Analyte Mixture
1. 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

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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)

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.

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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® ReagentCartridge (DF38)	CK-NAC Reagent (K834502)
IntendedUse	The CKI method is an in vitrodiagnostic test for the quantitativemeasurement of creatine kinase inhuman serum and plasma on theDimension® Clinical Chemistry System.	In vitro assay for the quantitativedetermination of creatine kinase (CK) inhuman serum and plasma on Rocheautomated clinical chemistry analyzers.
DeviceTechnology(detection)	Bichromatic rate	UV Test
MeasuringRange	7 - 1000 U/L	3-2300 U/L
AnalyticalSensitivity	7 U/L	3 U/L

Feature	Dimension® (MBI) Flex® ReagentCartridge (DF32)	CK-MB Reagent (K003158)
IntendedUse	The creatine kinase MB (MBI) methodis an in vitro diagnostic test for thequantitative measurement of creatinekinase MB isoenzyme activity inhuman serum and plasma on theDimension® clinical chemistry system.	Immunoinhibition assay for thequantitative in vitro determination of theMB isoenzyme of creatine kinase inhuman serum and plasma on Rocheautomated clinical chemistry analyzers.
DeviceTechnology(detection)	Bichromatic rate	Immunological UV Assay
MeasuringRange	3 - 125 U/L	3 - 2300 U/L
AnalyticalSensitivity	3 U/L	3 U/L

Feature	CKI/MBI Calibrator(DC32)	Calibrator forAutomated Systems(K990460)	Calibrator forAutomated Systems,CKMB (K003158)
IntendedUse	The CKI/MBI CAL is an invitro diagnostic productfor the calibration of theCreatine Kinase (CKI)and Creatine Kinase MB(MBI) methods on theDimension® clinicalchemistry system.	Calibrator for automatedsystems (C.f.a.s.) is foruse in the calibration ofquantitative Rochemethods on Roche clinicalchemistry analyzers asspecified in the valuesheet.	C.f.a.s. (Calibrator forautomated systems) CK-MB is for use in thecalibration of quantitativeRoche methods onRoche clinical chemistryanalyzers as specified inthe value sheet.
Analyte	Creatine kinase (human	Creatine kinase (rabbit	Creatine kinase-MM

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	source) and creatinekinase-MB (porcinesource)	muscle)	(human source) and CK-BB (porcine brain)
Matrix	Human serum albumin	Human serum	Human serum
Form	Liquid	Lyophilized	Lyophilized
Levels	CKI - Three levelsMBI - 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.

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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).

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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 (240) 276-0490. 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 (800) 638-2041 or (240) 276-3150 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

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Indications for Use

510(k) Number (if known): K081731

Device Name:

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

Indication For Use:

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

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Indications for Use

510(k) Number (if known): K081731

Device Name:

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

Indication For Use:

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

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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

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
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.(b)
Classification. Class II.