SIGMA DIAGNOSTICS INFINITY BUN REAGENT KIT by SIGMA DIAGNOSTICS, INC.

The Sigma Diagnostics INFINITY™ BUN Reagent is intended for the in vitro quantitative, diagnostic determination of Urea (or Urea Nitrogen) in human serum or urine on both automated and manual svstems.

The Sigma Diagnostics INFINITY™ BUN Reagent is a device intended to measure urea nitrogen (an end product of nitrogen metabolism) in serum. Measurements obtained by the device are used in the diagnosis and treatment of certain renal and metabolic diseases.

Device Description

The enzyme methodology employed in this reagent is based on the reaction first described by Talke and Schubert. To shorten and simplify the assay, the calculations are based on the discovery of Tiffany, et al.3 that urea concentration is proportional to absorbance change over a fixed time interval.

The series of reactions involved in the assay system is as follows:

Urea is hydrolyzed in the presence of water and urease to produce ammonia and carbon dioxide.
Urea + H2O Urease < 2NH3 + CO2
In the presence of glutamate dehydrogenase (GLDH) and reduced nicotinamide adenine dinucleotide (NADH), the ammonia combines with a-ketoglutarate (α-ΚG) to produce L-glutamate.
NH3 + α-KG + NADH ___ GLDH_____ GLDH____ L-Glutamate + NAD

INFINITY BUN reagent has the convenience of being a single vial reagent and also incorporates a patented dynamic stabilization process which regenerates NADH from NAD (oxidized NADH), thereby increasing the shelf life of the reagent.

AI/ML Overview

This 510(k) notification for the INFINITY™ BUN Reagent is a submission for an in vitro diagnostic device, not an AI/ML device, therefore, many of the requested categories related to AI/ML device studies are not applicable. The document states that the device is "substantially equivalent to, and is the same product as the TRACE Scientific BUN Reagent kit cleared by the FDA as K971477," indicating that performance is established through equivalence to a predicate device rather than a de novo study with acceptance criteria specific to this submission.

Here's a breakdown of the available information regarding acceptance criteria and device performance:

1. Table of Acceptance Criteria and Reported Device Performance:

Since this is an in vitro diagnostic (IVD) reagent intended to measure Urea Nitrogen, the typical acceptance criteria relate to analytical performance characteristics such as accuracy, precision, linearity, and interference. However, this 510(k) summary does not explicitly state specific acceptance criteria (e.g., a target accuracy percentage or precision coefficient of variation) or present a table of reported device performance data.

Instead, it relies on substantial equivalence to a previously cleared device. The implicit acceptance criterion is that the INFINITY™ BUN Reagent performs identically or equivalently to the TRACE Scientific BUN Reagent (K971477).

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

This information is not provided in the 510(k) summary. For IVD reagents, a "test set" typically refers to samples used in validation studies (e.g., patient samples, spiked samples, control materials). The document doesn't detail any specific studies conducted with this new reagent, as its equivalence is asserted.

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

This is not applicable/not provided. For an IVD reagent that measures a chemical analyte like Urea Nitrogen, "ground truth" is typically established through reference methods, certified reference materials, or highly accurate laboratory instruments, not through expert consensus in the way it would be for image analysis or clinical diagnosis by human experts.

4. Adjudication Method for the Test Set:

This is not applicable/not provided. Adjudication methods (e.g., 2+1, 3+1) are common in studies where multiple human readers interpret results, often in AI/ML performance studies to resolve discrepancies. This concept doesn't apply to the analytical performance of an IVD reagent.

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 is for an in vitro diagnostic reagent, not an AI-assisted diagnostic device. Therefore, no MRMC study or assessment of human reader improvement with AI assistance would have been performed or would be relevant.

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

This is not applicable. The INFINITY™ BUN Reagent is a chemical reagent, not an algorithm. Therefore, "standalone algorithm performance" is not a relevant concept for this device.

7. The Type of Ground Truth Used:

For the type of device described, the "ground truth" for evaluating its analytical performance would typically be:

Reference Methods: Comparison against established, highly accurate laboratory methods for Urea Nitrogen measurement.
Certified Reference Materials: Using materials with known, certified concentrations of Urea Nitrogen.
Split Sample Comparisons: Testing patient samples with the new reagent and a predicate/reference method.

However, the 510(k) summary does not explicitly state the type of ground truth used for any specific validation studies, as it's primarily a substantial equivalence claim. The references provided (Tietz Textbook, Talke and Schubert, Tiffany et al.) relate to the scientific principles and historical context of BUN measurement methodology, not specific ground truth establishment for a validation study of this particular reagent.

8. The Sample Size for the Training Set:

This is not applicable. The INFINITY™ BUN Reagent is a chemical reagent, not an AI/ML model that requires a "training set."

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

This is not applicable, as there is no "training set" for a chemical reagent.

Summary of Substantial Equivalence Claim:

The core of this 510(k) is the statement: "The Sigma Diagnostics INFINITY™ BUN Reagent (Procedure No. 63) is substantially equivalent to, and is the same product as the TRACE Scientific BUN Reagent kit cleared by the FDA as K971477." This means that the FDA's acceptance of this device's safety and effectiveness relies on its demonstrated equivalence (likely through comparative analytical performance studies, though not detailed here) to the predicate device, which has already been deemed safe and effective. The original predicate device (K971477) would have undergone its own validation studies to establish its performance characteristics against acceptance criteria relevant to its intended use.

Summary

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K982236

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

INFINITY™ BUN Reagent, Procedure 63

Sigma Diagnostics INFINITY™ BUN Reagent is intended for the in vitro quantitative, diagnostic determination of Urea (or Urea Nitrogen) in human serum or urine on both automated and manual svstems.

Urea is the major end product of protein nitrogen metabolism in humans. It constitutes the largest fraction of the non-protein nitrogen component of the blood. Urea is produced in the liver and excreted through the kidneys in the urine. Consequently, the circulating levels of urea depend upon protein intake, protein catabolism and kidney function. Elevated urea levels can occur with dietary changes, diseases which impair kidney function, liver diseases, congestive heart failure, diabetes, and infections.

The series of reactions involved in the assay system is as follows:

1. Urea is hydrolyzed in the presence of water and urease to produce ammonia and carbon dioxide.
  Urea + H2O Urease < 2NH3 + CO2
1. In the presence of glutamate dehydrogenase (GLDH) and reduced nicotinamide adenine dinucleotide (NADH), the ammonia combines with a-ketoglutarate (α-ΚG) to produce L-glutamate.
  NH3 + α-KG + NADH ___ GLDH_____ GLDH____ L-Glutamate + NAD

The Sigma Diagnostics INFINITY™ BUN Reagent (Procedure No. 63) is substantially equivalent to. and is the same product as the TRACE Scientific BUN Reagent kit cleared by the FDA as K971477.

References

1. Tietz Textbook of Clinical Chemistry, Burtis CA and Ashwood ER (Eds). Second Edition. WB Saunders Company, 1994
1. Talke H. Schubert GE. Klin Wochschr 19: 43:174
Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD. Clin Chem 18:829-40. 1972 3.

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Image /page/1/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized depiction of a human figure with outstretched arms, enclosed within a circular border. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper portion of the circle.

AUG - 5 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

William Gilbert, Ph.D. · Manager, Scientific Affairs Sigma Diagnostics Inc. 545 South Ewinq Avenue St. Louis, , Missouri 63103

Re : K982236 INFINITY™ BUN Reagent Regulatory Class: I Product Code: CDQ Dated: June 23, 1998 Received: June 25, 1998

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, Drug, and Cosmetic Act (Act). You may, 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 Regulations, Title 21, Parts 800 to 895. A 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 Register. 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 regulation (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 Sitman

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 | _of _l

510(k) Number (if known): _

Device Name: INFINITY™ BUN Reagent

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use__
(Per 21 CFR 801.109)

(Division Sign-Off
Division of Clinical Laboratory Devices
510(k) Number K982236
OR
Over-The-Counter Use__

Regulation Number and Section

§ 862.1770 Urea nitrogen test system.

(a)
Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.(b)
Classification. Class II.