CR-E reagent, when used in conjunction with SYNCHRON® Systems, UniCel® DxC Systems and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX® Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) concentration in human serum, plasma or urine (urine is not available on the SYNCHRON CX PRO Systems).

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.

Device Description

CR-E reagent is used to measure the creatinine concentration by an enzymatic method. This enzymatic creatinine method utilizes a multi-step approach ending with a photometric end-point reaction.

The SYNCHRON Enzymatic Creatinine (CR-E) Reagent is designed for optimal performance on the SYNCHRON LX, UniCel® DxC 600/800, and SYNCHRON CX® PRO Clinical Systems. The reagent kit contains two 200-test cartridges that are packaged separately from the associated calibrator.

AI/ML Overview

Here's an analysis of the provided text regarding the SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent, structured according to your request:

Acceptance Criteria and Device Performance Study for SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Analyte: Creatinine	Analyte: Creatinine
Matrix (Serum): Limit of Detection (Analytical Sensitivity) = 0.1 mg/dL (Extended from 0.2 mg/dL)	Matrix (Serum): Limit of Detection (Analytical Sensitivity) = 0.1 mg/dL
Matrix (Urine): Limit of Detection (Analytical Sensitivity) = 10 mg/dL (Unchanged)	Matrix (Urine): Limit of Detection (Analytical Sensitivity) = 10 mg/dL
Intended Use: Quantitative determination of creatinine in human serum, plasma, or urine for diagnosis/treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes.	Intended Use: Device performs as intended for quantitative determination of creatinine in human serum, plasma, or urine for diagnosis/treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes. (Implied by substantial equivalence and performance data supporting equivalency).

Note: The primary acceptance criterion highlighted in the document is the successful extension of the Limit of Detection (Analytical Sensitivity) for serum samples to 0.1 mg/dL, replacing the previous 0.2 mg/dL. The urine sample LoD remained unchanged and met the existing criterion. The overall performance is implicitly tied to demonstrating "substantial equivalence" to the predicate device.

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

The document states: "Performance data from validation testing supports equivalency." However, it does not explicitly provide the sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective nature of the data). This information is typically found in the detailed validation reports submitted to the FDA, but is not included in this summary.

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

The document does not provide information on the number of experts used or their qualifications to establish ground truth. For in vitro diagnostic devices like this, ground truth is typically established by comparing the device's results to a recognized reference method or to results from a legally marketed predicate device, rather than expert consensus on individual cases.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for a test set. This type of method is usually applied in studies involving subjective interpretation (e.g., imaging studies) rather than quantitative chemical assays. For this device, the "ground truth" would be the result from a reference method or the predicate device, and the comparison would be statistical.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for devices where human readers interpret observations (e.g., radiology AI). The SYNCHRON® Systems Enzymatic Creatinine Reagent is an automated in vitro diagnostic device, where the measurement is quantitative and performed by the instrument.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone study was done. The SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent is an automated assay run on the SYNCHRON LX, UniCel® DxC 600/800, and SYNCHRON CX® PRO Clinical Systems. The "performance data from validation testing" that "supports equivalency" would inherently be a standalone evaluation of the reagent's analytical performance on these instruments. There is no human interpretation component where the results are subsequently re-evaluated by a human to influence the device's performance.

7. Type of Ground Truth Used

The type of ground truth used is comparison to a legally marketed predicate device (K091742) and, implicitly, to established analytical methods for creatinine measurement. The validation testing would involve comparing the CR-E reagent's results against a gold standard or a well-characterized reference method, likely by linearity, precision, and accuracy studies, or by demonstrating concordance with the predicate device. The primary change here is an extended Limit of Detection for serum, which would have been validated against samples with known low creatinine concentrations.

8. Sample Size for the Training Set

The document does not specify the sample size for the training set. For an in vitro diagnostic reagent, there isn't typically a "training set" in the machine learning sense. Instead, the reagent's formulation and assay parameters are developed and optimized through extensive R&D and early validation studies using various concentrations of known analytes and patient samples. The "training" is part of the product development and optimization process, not a distinct "training set" as understood in AI/ML validation studies.

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

As explained in point 8, the concept of a "training set ground truth" isn't directly applicable in the same way it would be for an AI/ML algorithm. However, throughout the development and optimization of the reagent, the "ground truth" for determining assay parameters and performance would have been established by:

Reference Methods: Using highly accurate and precise reference methods (e.g., isotope dilution mass spectrometry) to determine the true creatinine concentration in control materials and patient samples.
Known Concentrations: Preparing solutions with precisely known concentrations of creatinine.
Comparison to Predicate: Benchmarking performance against the legally marketed predicate device (Beckman Coulter SYNCHRON Systems Enzymatic Creatinine (CR-E) reagent, K091742) during development and optimization.

Summary

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Summary of Safety & Effectiveness SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent

093458

1.0 Submitted By:

Marine Boyajian Senior Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-110 Brea, California 92822-8000 Telephone: (714) 961-6536 FAX: (714) 961-4234

DEC - 4 2009

2.0 Date Submitted:

November 04, 2009

3.0 Device Name(s):

Proprietary Names 3.1

SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent
3.2 Classification Name Enzymatic Method Creatinine (21 CFR § 862.1225)

4.0 Predicate Device:

The SYNCHRON Systems Enzymatic Creatinine (CR-E) Reagent claims substantial equivalence to the Beckman Coulter SYNCHRON Systems Enzymatic Creatinine (CR-E) reagent currently in commercial distribution, FDA 510(k) Number K091742.

Candidate(s)	Predicate	Manufacturer	DocketNumber
SYNCHRON SystemsEnzymatic Creatinine (CR-E)Reagent	SYNCHRON SystemsEnzymatic Creatinine (CR-E)Reagent	BeckmanCoulter, Inc	K091742

5.0 Description:

CR-E reagent is used to measure the creatinine concentration by an enzymatic method. This enzymatic creatinine method utilizes a multi-step approach ending with a photometric end-point reaction.

6.0 Intended Use:

CR-E reagent, when used in conjunction with SYNCHRON® System(s), UniCel® DxC System(s) and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) concentration in human serum, plasma or urine (urine is not available on the
SYNCHRON CX® PRO Systems).

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.

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Comparison to Predicate(s): 7.0 (Description of the Modification to the Legally Marketed Device)

The modification to the SYNCHRON Systems CR-E assay involves extending the Limit of Detection (Beckman Coulter uses the term Analytical Sensitivity to characterize Limit of Detection in its product labeling) to 0.1 mg/dL for serum samples. The Limit of Detection for urine samples remains unchanged.

The current claimed Analytical Sensitivity for creatinine determination by the CR-E assay (cleared under FDA 510(k) Number K091742) is 0.2 mg/dL for serum and 10 mg/dL for urine (on SYNCHRON LX/UniCel DxC Clinical Systems only).

8.0 Summary of Performance Data:

Performance data from validation testing supports equivalency.

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Beckman Coulter, Inc. c/o Ms. Marine Boyajian Senior Regulatory Affairs Specialist 200 S. Kraemer Blvd., M/S W-110 Brea, CA 92822-8000

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

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Re: K093458

Trade Name: SYNCHRON Systems Enzymatic Creatinine (CR-E) Reagent Regulation Number: 21 CFR §862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Codes: JFY Dated: November 4, 2009 Received: November 6, 2009

Dear Ms. Boyajian:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney C. Harper, Ph.D. 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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Indication for Use

8093458 510(k) Number (if known):

Device Name: SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent

Indication For Use:

CR-E reagent, when used in conjunction with SYNCHRON® Systems, UniCel® DxC Systems and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX® Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) concentration in human serum,
plasma or urine (urine is not available on the SYNCHRON CX PRO Systems).

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.

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)

signature

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

510(k) K093458

Regulation Number and Section

§ 862.1225 Creatinine test system.

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