The MULTIGENT Creatinine (Enzymatic) assay is a device intended to measure creatinine levels in human serum, plasma, and urine using the ARCHITECT c8000 System and the AEROSET System. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a component of various calculations for determination or estimation of creatinine clearance, glomerular filtration rate (GFR) or estimated GFR (eGFR).

Device Description

MULTIGENT Creatinine (Enzymatic) Assay is an in vitro diagnostic device for the quantitative determination of creatinine in human serum, plasma, or urine. Creatinine in the sample is hydrolyzed by creatininase to creatine. Creatine is in turn hydrolyzed by creatinase to sarcosine and urea. Sarcosine from this reaction is oxidized by sarcosine oxidase to glycine and formaldehyde, with the concomitant production of hydrogen peroxide. The H2O2 reacts with 4-aminoantipyrine and ESPMT (N-Ethyl-N-sulfopropyl-m-toluidine) in the presence of peroxidase to yield a quinoneimine dye. The resulting change in absorbance at 548 nm is proportional to the creatinine concentration in the sample.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the MULTIGENT Creatinine (Enzymatic) assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by demonstrating "acceptable correlation" and "acceptable cross-platform correlation" with the predicate device (Roche Creatinine Plus assay on the Hitachi 911 Analyzer) and between the two systems for the MULTIGENT Creatinine (Enzymatic) assay (AEROSET and ARCHITECT c8000). Specific correlation coefficients (r), slopes, and Y-intercepts are provided as evidence of this acceptable performance. Similarly, precision is evaluated by acceptable total %CV values, and the analytical measurement range (AMR) is established.

Acceptance Criteria Category	Specific Acceptance Criteria (Implicit)	Reported Device Performance (MULTIGENT Creatinine Enzymatic)
Method Comparison (vs. Predicate)	High correlation (r close to 1), slope close to 1, small Y-intercept.	AEROSET vs. Roche Creatinine Plus (Hitachi 911):
		Serum: r = 0.999, slope = 1.000, Y-intercept = -0.015 mg/dL
		Urine: r = 0.999, slope = 0.964, Y-intercept = -1.03 mg/dL
		ARCHITECT c8000 vs. Roche Creatinine Plus (Hitachi 911):
		Serum: r = 0.999, slope = 1.011, Y-intercept = -0.100 mg/dL
		Urine: r = 1.000, slope = 0.986, Y-intercept = 0.49 mg/dL
Cross-Platform Correlation (MULTIGENT)	High correlation (r close to 1), slope close to 1, small Y-intercept.	ARCHITECT c8000 vs. AEROSET:
		Serum: r = 0.999, slope = 1.011, Y-intercept = -0.079 mg/dL
		Urine: r = 1.000, slope = 1.022, Y-intercept = -0.49 mg/dL
Precision (20-day inter-assay total %CV)	Acceptable low %CV values.	AEROSET:
		Serum Level 1 (0.647 mg/dL): 1.95%
		Serum Level 2 (1.826 mg/dL): 1.30%
		Serum Level 3 (6.606 mg/dL): 0.72%
		Urine Level 1 (68.769 mg/dL): 1.31%
		Urine Level 2 (121.937 mg/dL): 1.23%
		ARCHITECT c8000:
		Serum Level 1 (0.654 mg/dL): 3.17%
		Serum Level 2 (1.827 mg/dL): 1.72%
		Serum Level 3 (6.604 mg/dL): 0.95%
		Urine Level 1 (69.940 mg/dL): 1.46%
		Urine Level 2 (124.724 mg/dL): 1.16%
Analytical Measurement Range (AMR) Claim	Established lower and upper linearity limits.	Serum AMR Claim: 0.10 to 40.00 mg/dL
		Urine AMR Claim: 2.50 to 400.00 mg/dL

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

The document does not explicitly state the number of samples (test set size) used for the method comparison or precision studies. It only mentions that "Comparative performance studies were conducted" and "Precision studies were conducted." The provenance of the data (country of origin, retrospective/prospective) is also not specified.

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

This information is not applicable. For an in vitro diagnostic (IVD) assay like this, the "ground truth" is typically established by comparative analysis against a legally marketed predicate device (Roche Creatinine Plus) and by analytical methods like IDMS traceability for calibrators, not by human experts adjudicating diagnoses.

4. Adjudication Method for the Test Set

This is not applicable for this type of IVD device. The performance is assessed through quantitative measurements and statistical comparisons, not expert adjudication.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is more common for imaging devices where human interpretation is involved. This device is an automated in vitro diagnostic assay.

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

The device is an in vitro diagnostic assay, meaning it operates standalone without human-in-the-loop performance in terms of interpretation or decision-making beyond the initial sample loading and result review. The reported performance is the standalone performance of the assay on the specified systems.

7. The Type of Ground Truth Used

The ground truth for comparison was established by:

Comparison to a Legally Marketed Predicate Device: The Roche Creatinine Plus assay on the Hitachi 911 Analyzer served as the primary comparative standard.
Traceability to IDMS: Both the predicate and the new assay's calibrators are traceable to IDMS (Isotope Dilution Mass Spectrometry) analysis, which is considered a gold standard for creatinine measurement.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning. This is an IVD device, and its development likely involved traditional analytical chemistry R&D and validation, not machine learning model training.

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

As there is no mention of a "training set" in the machine learning sense, this question is not applicable. The assay's analytical performance (linearity, precision, correlation) is evaluated against established analytical methods and reference standards.

Summary

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K073634

JUN 1 9 2008

510(k) Summary

Submitter's Name/Address SENTINEL CH. Via Robert Koch, 2 20152 Milan - Italy

Contact Person Fabio Rota Technical Director +39 02 3455148 Fax: +39 02 34551464

Date of Preparation of this Summary: March 28th, 2008 Device Trade or Proprietary Name: MULTIGENT Creatinine (Enzymatic) Device Common/Usual Name or Creatinine Test System Classification Name: Classification Number/Class: Class II / 862, 1225 Product Code: JFY

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.

The assigned 510(k) number is: K073634.

Test Description:

Creatinine - (Enzymatic). 510(k) March 29, 2008

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Substantial Equivalence:

The MULTIGENT Creatinine (Enzymatic) assay is substantially equivalent to the Roche Creatinine assay (K003261) on the Hitachi 911 Analyzer. Both assays yield similar Performance Characteristics.

Similarities :

Both assays can be used for the quantitative determination of creatinine by . means of a calibrated rate assay.
. Both assays utilize calibrators that are traceable to IDMS analysis through values of standard reference materials assigned by this method.
. Both assays are based on the same three-step enzymatic conversion of creatinine to glycine with the concomitant production of hydrogen peroxide.
. Both assays utilize reagents in an R1 and R2 format.
Both assays yield similar results. #
. Both assays use human serum, plasma, and urine

Differences:

None

Intended Use:

The MULTIGENT Creatinine (Enzymatic) assay is used for the quantitative determination of creatinine in human serum, plasma, or urine.

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Performance Characteristics:

Comparative performance studies were conducted using the AEROSET System and the ARCHITECT c8000 System. The MULTIGENT Creatinine (Enzymatic) assay method comparison yielded acceptable correlation with the Roche Creatinine Plus assay on the Hitachi 911 Analyzer.

MULTIGENT Creatinine (Enzymatic) AEROSET System vs. Roche Creatinine Plus - Hitachi 911 Analyzer: This comparison showed a correlation coefficient (r) of 0.999, slope of 1.000, and Y-intercept of -0.015 mg/dL for the serum application, and a correlation coefficient (r) of 0.999, slope of 0.964, and Y-intercept of -1.03 mg/dL for the urine application.
MULTIGENT Creatinine (Enzymatic) - ARCHITECT c8000 System vs. Roche Creatinine Plus - Hitachi 911 Analyzer: This comparison showed a correlation coefficient (r) of 0.999, slope of 1.011, and Y-intercept of -0.100 mg/dL for the serum application and a correlation coefficient (r) of 1.000, slope of 0.986, and Y-intercept of 0.49 mg/dL for the urine application.

MULTIGENT Creatinine (Enzymatic) - ARCHITECT c8000 vs. MULTIGENT Creatinine (Enzymatic) - AEROSET System: This comparison showed a correlation coefficient (r) of 0,999 slope of 1.011, and Y-intercept of -0.079 mg/dL for the serum application and a correlation coefficient of 1.000, slope of 1.022, and Y-intercept of -0.49 mg/dL for the urine application.

Conclusion - Method Comparison: When used on either the AEROSET System or the ARCHITECT c8000 system, the MULTIGENT Creatinine (Enzymatic) assay method yielded acceptable correlation when compared with the Roche Creatinine Plus assay on the Hitachi 911. The MULTIGENT Creatinine (Enzymatic) assay also yielded acceptable cross-platform correlation between the ARCHITECT c8000 System and the AEROSET System.

Creatinine - (Enzymatic). 510(k) March 29, 2008

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Precision studies were conducted using the MULTIGENT Creatinine (Enzymatic) assay.

On the AEROSET System, the total %CV values for 20-day inter-assay precision are:

Serum Level 1 (0.647 mg/dL) is 1.95% Serum Level 2 (1.826 mg/dL) is 1.30% Serum Level 3 (6.606 mg/dL) is 0.72% Urine Level 1 (68.769 mg/dL) is 1.31% Urine Level 2 (121.937 mg/dL) is 1.23%

On the ARCHITECT c8000 System, the total %CV values for 20-day inter-assay precision are:

Serum Level 1 (0.654 mg/dL) is 3.17% Serum Level 2 (1.827 mg/dL) is 1.72% Serum Level 3 (6.604 mg/dL) is 0.95% Urine Level 1 (69.940 mg/dL) is 1.46% Urine Level 2 (124.724 mg/dL) is 1.16%

Analytical Measurement Range (AMR):

The lower linearity limit of the MULTIGENT Creatinine (Enzymatic) assay is 0.08 mg/dL for the serum application, and 2.39 mg/dL for the urine application. The MULTIGENT Creatinine (Enzymatic) assay is linear to 40.73 mg/dL for the serum application and 424.53 mg/dL for the urine application.

Serum AMR Claim: 0.10 to 40.00 mg/dL Urine AMR Claim: 2.50 mg/dL to 400.00 mg/dL

Conclusion for 510(k) Summary:

These method comparison, precision and AMR data demonstrate that the analytical performance of the MULTIGENT Creatinine (Enzymatic) assay on the ARCHITECT c8000 System and the AEROSET System is substantially equivalent to the performance of the Roche Creatinine Plus assay on the Hitachi 911 Analyzer. Comparability of results between these two methods is established through both the similarity of the procedure and the traceability of calibration through standard reference materials value assigned by IDMS.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 1 9 2008

Sentinel CH Spa. c/o Mr. Fabio Rota Technical Director Via Robert Koch, 2 20152 Milano, Italy

Re: K073634 Trade/Device Name: MULTIGENT Creatinine (Enzymatic) Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: JFY Dated: June 4, 2008 Received: June 11, 2008

Dear Mr. Rota:

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 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 (240) 276-0490. 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 (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.

Yean 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): K07363

Device Name:

Indications For Use:

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 Diagnostics Devices (OIVD)

Page 1 of _

Carol Benson

Jivision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

K073634

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.