SIGMA DIAGNOSTICS INFINITY BUN REAGENT, MODELS 63-25, 63-100P, 63-500P, 63-2000P, 64-20, 64-100P 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, plasma or urine on both automated and manual systems.

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

Device Description

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

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. 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 (a-KG) to produce L-glutamate.
NH3 + a-KG + NADH __ 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

The provided text describes a 510(k) summary for the INFINITY™ BUN Reagent, an in vitro diagnostic device. The primary goal of this submission is to demonstrate substantial equivalence to a predicate device, not to establish new acceptance criteria or perform a de novo study the way an AI/ML product might. Therefore, many of the requested categories (like MRMC study, sample sizes for training/test sets, expert qualifications for ground truth, and adjudication methods) are not applicable or not explicitly detailed in this type of submission for a chemical reagent.

Here's a breakdown of the information provided in relation to your request, with an emphasis on what is present and what is absent:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this type of device are primarily based on demonstrating substantial equivalence to a previously cleared predicate device. This is typically shown through correlation studies.

Acceptance Criteria Category	Acceptance Criteria	Reported Device Performance (from K992800 Summary)
Substantial Equivalence	Demonstrated through correlation with a legally marketed predicate device, typically involving a regression analysis showing close agreement.	Correlation studies to Sigma Diagnostics BUN Reagent, Procedure No. 67 (K863196) using plasma samples yielded a regression equation of: `INFINITY BUN = 0.95 (BUN 63) + 1.1`
Predicate Device Match	The device must be the same product as, or substantially equivalent to, a previously cleared device.	"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."

Study Information

Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Sample Size (Test Set): N=126 plasma samples were used for the correlation study.
- Data Provenance: Not specified (e.g., country of origin). The nature of the samples (plasma) suggests they are biological samples, likely collected for clinical testing, though whether they were retrospective or prospectively collected is not stated.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
- Not Applicable: For a chemical reagent, "ground truth" is typically established by the reference method or the predicate device's measurement. There are no "experts" in the sense of human interpretation like radiologists for this type of device. The ground truth for the correlation study would be the results obtained by the predicate device (Sigma Diagnostics BUN Reagent, Procedure No. 67).
Adjudication method (e.g., 2+1, 3+1, none) for the test set
- Not Applicable: Adjudication methods are relevant for subjective interpretations (e.g., image analysis by multiple readers). For a quantitative chemical assay, the comparison is directly between the numerical results of the new device and the predicate device, not an adjudicated interpretation.
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
- Not Applicable: This is an in vitro diagnostic (IVD) reagent, not an AI/ML device that assists human readers. Therefore, an MRMC study is not relevant.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
- This refers to an "algorithm only" performance. For this IVD reagent, the performance is standalone in the sense that the device itself performs the measurement. There isn't an "algorithm" in the modern AI sense, but rather a chemical reaction and spectrophotometric reading that yields a quantitative result. The correlation study directly assesses this standalone performance against a predicate.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- Ground Truth Type: The "ground truth" for the correlation study was the quantitative measurement obtained from the predicate device (Sigma Diagnostics BUN Reagent, Procedure No. 67). This is a direct comparative measurement rather than an expert consensus or pathology result.
The sample size for the training set
- Not Applicable / Not Provided: This is a chemical reagent, not an AI/ML model that requires "training data." The device's performance is inherent in its chemical formulation and reaction kinetics.
How the ground truth for the training set was established
- Not Applicable / Not Provided: As there is no "training set" for this type of device, this question is not relevant.

Summary

{0}------------------------------------------------

Kg92800

SEP 2 8 1999

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

INFINITY™ BUN Reagent, Procedure 63

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 enzyme methodology employed in this reagent is based on the reaction first described by Talke and Schubert.2 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:

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 (a-KG) to produce L-glutamate.
  NH3 + a-KG + NADH __ 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.

Correlation studies to Sigma Diagnostics BUN Reagent, Procedure No. 67 (K863196) using plasma samples yielded a regression equation of:

INFINITY BUN = 0.95 (BUN 63) + 1.1 (N=126)

References

l . 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
1. Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD. Clin Chem 18:829-40, 1972

{1}------------------------------------------------

Image /page/1/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 lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

SEP 2 8 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

William R. Gilbert, Ph.D. Manager, Scientific Affairs Sigma Diagnostics® Clinical Technical Services 545 South Ewing Avenue St. Louis, Missouri 63103

Re: K992800

Trade Name: Infinity™ BUN Reagent (Procedure No. 63) Regulatory Class: II Product Code: CDQ Dated: August 16, 1999 Received: August 19, 1999

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 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). 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 (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 action. In addition, FDA may publish further announcements 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.

{2}------------------------------------------------

Page 2

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/dsma/dsmamain.html".

Sincerely yours,

Steven Dutman

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

{3}------------------------------------------------

Page 1 of 1

510(k) Number (if known): 499280

Device Name: INFINITY™ BUN Reagent

Indications For Use:

De an Conger
(Division Off)
Division of Clinical Laboratory Devices

510(k) Num -- r

(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) √

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.