Sigma Diagnostics Creatinine Reagent is intended to measure creatinine levels in serum, plasma, Sigma Diagos monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Device Description

The Sigma Diagnostics procedure is a modification of the Jaffe reaction and is highly adaptable to automation. The rate of color change following the addition of a serum, plasma or urine sample to an alkaline picrate solution is measured between 480 and 520 nm and is proportional to the creatinine concentration in the test specimen.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Sigma Diagnostics Creatinine Reagent, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Criteria/Metric	Reported Device Performance	Comments
Method Comparison	Correlation Coefficient (Serum)	0.999	Against Boehringer Mannheim Diagnostics (BMD) using manual procedure.
	Regression Equation (Serum)	y = 1.11x + 0.05	Against BMD using manual procedure.
	Correlation Coefficient (Urine)	0.998	Against BMD using manual procedure.
	Regression Equation (Urine)	y = 1.13x - 0.17	Against BMD using manual procedure.
Precision	Within-run precision (Serum)	Acceptable values can be replicated	Details on specific CV% or standard deviation not provided, but stated as acceptable.
	Total precision (Serum)	Acceptable values can be replicated	Details on specific CV% or standard deviation not provided, but stated as acceptable.
Linearity	Linear Range	Up to 25 mg/dL	Confirmed as linear.

Study Information

2. Sample sizes used for the test set and the data provenance:

Test Set Sample Size:
- Serum samples: 128
- Urine samples: The exact number is not explicitly stated, but derived from "comparison studies against BMD using the manual procedure a correlation coefficient of 0.998 and a regression equation y = 1.13x -0.17 was obtained with urine samples." It implies a similar comparative study was performed.
Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be retrospective method comparison studies, using existing samples to compare the Sigma Diagnostics Creatinine Reagent against a predicate device.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable (N/A): This study is a method comparison for an in vitro diagnostic (IVD) device measuring a biochemical analyte (creatinine). The "ground truth" for method comparison studies like this is typically the result obtained from the predicate device (Boehringer Mannheim Diagnostics Creatinine Reagent), not expert consensus. Therefore, expert involvement in establishing ground truth for the test set measurements is not relevant in the way it would be for image-based diagnostics.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

None: Adjudication methods are typically used in studies involving human interpretation or subjective assessment. For analytical performance studies of IVD devices comparing quantitative measurements, adjudication is not a standard practice. The "ground truth" is established by the reference method (predicate device measurements).

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:

N/A: This is an in vitro diagnostic device for measuring creatinine. MRMC studies and "human readers improve with AI" are concepts specific to AI-powered diagnostics that analyze images or complex data requiring human interpretation. This device performs a biochemical measurement.

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

Standalone (algorithm/reagent only) performance was done: The study focuses solely on the analytical performance of the Sigma Diagnostics Creatinine Reagent in measuring creatinine concentrations, comparing its results directly to those of the predicate device (Boehringer Mannheim Diagnostics Creatinine Reagent). There is no "human-in-the-loop" component in the described performance evaluation.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" or reference standard for this study was the results obtained from the legally marketed predicate device, Boehringer Mannheim Diagnostics Creatinine Reagent (No. 1050702). This is a common form of ground truth for demonstrating substantial equivalence of a new IVD device to an existing one.

8. The sample size for the training set:

N/A: This document describes analytical performance testing for a chemical reagent, not a machine learning model. Therefore, there is no "training set" in the context of AI/ML.

9. How the ground truth for the training set was established:

N/A: As there is no training set for an AI/ML model, the concept of establishing ground truth for a training set is not applicable here.

Summary

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972743

SUMMARY OF SAFETY AND EFFECTIVENESS

CREATININE, PROCEDURE NO. 558

Creatine is synthesized in the kidney, liver and pancreas. I It is transported in blood to other organs such as muscle and brain where it is phosphocreatine. Some free creatine in muscle is converted to creatinine daily and the amount of creatinine produced is proportional to muscle mass. In the absence of renal disease, excretion rate of creatinine in an individual is relatively constant. Therefore, measurement of creatinine clearance is useful in detecting renal disease and estimating the extent of impairment of renal function.2

The Sigma Diagnostics procedure is a modification of the Jaffe reaction3 and is highly adaptable to automation. The rate of color change following the addition of a serum, plasma or urine sample to an alkaline picrate solution is measured between 480 and 520 nm and is proportional to the creatinine concentration in the test specimen.

The safety and effectiveness of the Sigma Diagnostics Creatinine Reagent, Procedure 558 is demonstrated by its substantial equivalency to Boehringer Mannheim Diagnostics Creatinine Reagent. No. 1050702. Both Creatinine test systems are used to measure creatinine concentrations in serum, plasma, or urine and the reaction principles are similar. In comparison studies against BMD using the manual procedure a correlation coefficient of 0.999 and a regression equation y = 1.11x + 0.05 was obtained with 128 serum samples. In comparison studies against BMD using the manual procedure a correlation coefficient of 0.998 and a regression equation y = 1.13x -0.17 was obtained with urine samples. With-in run precision and total precision on serum samples indicate acceptable values can be replicated on a day to day basis. Sigma Diagnostics Creatinine reagent has been determined to be linear to 25 mg/dL.

REFERENCES

Tietz NW: Textbook of Clinical Chemistry. WB Saunders. Philadelphia, 1986, pp 1. 1271-1281.
1. Bowers LD, Wong ET: Kinetic serum creatinine assays. II. An initial evaluation and review. Clin Chem 26:255, 1980.
1. Jaffe M: Uber den Niederschlag, welchen Picrinsaure in normalen Harn erzeugt und uber eine neue Reaction des Kreatinins. Hoppe Seylers Z Physiol Chem 10:391, 1886.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

000 2 6 997

William R. Gilbert, Ph.D. . Manager, Scientific Affairs Sigma Diagnostics 545 South Ewinq Avenue St. Louis, MO 63103

Re: K972743 Sigma Diagnostics Creatinine Reaqent Requlatory Class: II Product Code: CGX Dated: July 18, 1997 Received: July 23, 1997

Dear Dr. Gilbert:

We have reviewed your Section 510 (k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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, Druq, and Cosmetic Act (Act). You mav, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਬੈ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

sincerely yours,
Steven Bitman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 __of__1 __

510(k) Number (if known):

Device Name: _Sigma Diagnostics Creatinine Reagent

Indications For Use:

Sigma Diagnostics Creatinine Reagent is intended to measure creatinine levels in serum, plasma, Sigma Diagos monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Carol Benson for Alfred Montgomery

(Division Sign-Off)

Division of Clinical Laboratory Devices
510(k) Number K972743

Prescription Usej (Per 21 CFR 801.109)

Over-The-Counter Use

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.