INFINITY CHOLESTEROL REAGENT (PROCEDURE NO. 401) by SIGMA DIAGNOSTICS, INC.

This reagent is based on the formulation of Allain et al. and the modification of Roeschlaus with further improvements to render the reagent stable in solution.

Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase (CE) to cholesterol 1. and free fatty acids. Cholesterol Esters CE Cholesterol + Fatty Acids
Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase 2. (CO) to cholest-4-en-3-one and hydrogen peroxide .. Cholesterol + O2 CQCQ Cholest-4-en-3-one + H2O2
1. The hydrogen peroxide combines with hydroxybenzoic acid (HBA) and 4aminoantipyrine (AAP) in the presence of peroxidase (POD) to form a chromophore (quinoneimine dye) which may be quantitated at 500-550 nm. For bichromatic analyzers the blank wavelength should be set to 600 or 650 nm. 2H2O2 + HBA + 4AAP POD> Quinoneimine Dye + 4H2O

AI/ML Overview

This 510(k) notification for the INFINITY™ Cholesterol Reagent (K980667) does not contain information about acceptance criteria or a study proving that a device meets acceptance criteria in the context of a typical AI/ML medical device submission.

Instead, this document is a notification for a reagent (an in vitro diagnostic product) and focuses on demonstrating substantial equivalence to a previously cleared device. Therefore, many of the requested categories related to AI/ML device studies (sample sizes, expert ground truth, MRMC studies, standalone performance) are not applicable here.

Here's a breakdown based on the provided text, highlighting what is (and isn't) present:

1. Table of Acceptance Criteria and Reported Device Performance:

This document does not contain a table of acceptance criteria or a detailed report of device performance in the way an AI/ML device submission would, with metrics like sensitivity, specificity, or AUC.
The primary "performance" stated is that the new reagent is "substantially equivalent to, and is the same product as the TRACE Scientific Cholesterol Reagent Kit cleared by FDA as K962890." This implies that its performance (accuracy, precision, linearity, etc.) is expected to be comparable to the predicate device. However, specific values are not provided in this public summary.

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

Not applicable / Not provided. The document is for a reagent, not an AI/ML device that uses a "test set" of patient data for performance evaluation in the usual sense. Performance testing for reagents would typically involve laboratory validation studies using reference materials, spiked samples, and patient samples, but the details (sample sizes, provenance) are not included in this summary.

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

Not applicable. This concept of "expert ground truth" is relevant for AI/ML devices interpreting images or data where human experts provide labels. For a cholesterol reagent, the "ground truth" would be established by reference methods or certified reference materials in a lab setting.

4. Adjudication method for the test set:

Not applicable. As above, this is for AI/ML device evaluations.

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:

Not applicable. This is explicitly for AI/ML devices where human readers might interact with AI.

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

Not applicable. This is for AI/ML algorithms. The reagent performs a chemical reaction, not an algorithmic interpretation.

7. The type of ground truth used:

For an in vitro diagnostic reagent, the "ground truth" would generally be established by:
- Reference methods: Highly accurate and precise laboratory methods (e.g., isotope dilution mass spectrometry for cholesterol) for comparison.
- Certified Reference Materials (CRMs): Materials with assigned analyte values determined through rigorous testing.
- Method comparison studies: Comparing results from the new reagent with an established, FDA-cleared method (the predicate device in this case).
The specific methods for establishing ground truth for the reagent's performance claims (implied by substantial equivalence) are not detailed in this summary.

8. The sample size for the training set:

Not applicable / Not provided. Reagents generally don't have "training sets" in the AI/ML sense. Development involves formulation, optimization, and stability testing, not retrospective data training.

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

Not applicable.

Summary of what the document does provide regarding "acceptance criteria" and "study":

The core of this 510(k) is the claim of Substantial Equivalence. The "study" indicated here is implicitly a comparison between the INFINITY™ Cholesterol Reagent and its predicate, the TRACE Scientific Cholesterol Reagent Kit (K962890). The acceptance criteria for this type of submission are that the new device (reagent) performs as well as or in a manner comparable to the predicate device for its intended use. This would typically involve:

Analytical Performance Studies: Comparing accuracy, precision, linearity, limit of detection, interference, etc., of the new reagent against the predicate.
Clinical Performance Studies (less common for reagents unless there's a novel claim): Demonstrating the reagent provides clinically relevant results comparable to the predicate.

However, the specific data from these studies, including acceptance criteria and detailed results, are not present in this public 510(k) summary. The summary simply states the conclusion of substantial equivalence.

Summary

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

APR 2 1 1998

K980667

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS INFINITYTM Cholesterol Reagent, Procedure 401

Sigma Diagnostics INFINITY™ Cholesterol Reagent is intended for the in vitro quantitative, diagnostic determination of cholesterol in human serum.

Measurement of serum cholesterol levels can serve as an indicator of liver function, biliary function, intestinal absorption, propensity toward coronary artery disease, thyroid function and adrenal disease. Cholesterol levels are important in the diagnosis and classification of hyperlipoproteinaemias. Stress, age, gender, hormonal balance and pregnancy affect normal cholesterol levels. 1,2

This reagent is based on the formulation of Allain et al.3 and the modification of Roeschlaus with further improvements to render the reagent stable in solution.

Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase (CE) to cholesterol 1. and free fatty acids. Cholesterol Esters CE Cholesterol + Fatty Acids
Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase 2. (CO) to cholest-4-en-3-one and hydrogen peroxide .. Cholesterol + O2 CQ__CQ_ Cholest-4-en-3-one + H2O2
1. The hydrogen peroxide combines with hydroxybenzoic acid (HBA) and 4aminoantipyrine (AAP) in the presence of peroxidase (POD) to form a chromophore (quinoneimine dye) which may be quantitated at 500-550 nm. For bichromatic analyzers the blank wavelength should be set to 600 or 650 nm. 2H2O2 + HBA + 4AAP _ POD_> Quinoneimine Dye + 4H2O

The Sigma Diagnostics INFINITY™ Cholesterol Reagent Kit (Procedure No. 401) is substantially equivalent to, and is the same product as the TRACE Scientific Cholesterol Reagent Kit cleared by FDA as K962890.

References

Searcy R.L. "Diagnostic Biochemistry." McGraw-Hill, New York, NY. 1969. 1.
Ellefson R.D. and Caraway W.T. "Fundamentals of Clinical Chemistry." Ed. Tietz N.W. 2. 1976; p 506.
Allain C.C., Poon L.S., Chan C.S.G., Richmond W. and Fu P.C. Clin. Chem., 1974; 3. 20:470-475.
1. Roeschlau P., Bernt E. and Gruber W.A. Clin. Chem. Clin. Biochem. 1974; 12:226.

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

Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 21 1996

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

Re : K980667 INFINITY™ Cholesterol Reagent (Procedure No. 401) Regulatory Class: I Product Code: СНН Dated: February 19, 1998 Received: February 20, 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 Requlations, 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 Druq 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.

{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 qeneral 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 Gutman

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 ___________________________________________________________________________________________________________________________________________________________________

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: Sigma Diagnostics INFINITY™ Cholesterol Reagent_

Indications For Use:

Sigma Diagnostics INFINITY™ Cholesterol Reagent is intended for the in vitro quantitative, diagnostic determination of cholesterol in human serum.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K-980667

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 862.1175 Cholesterol (total) test system.

(a)
Identification. A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.