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

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.

Sigma Diagnostics INFINITY™ Cholesterol Reagent is intended for the in vitro quantitative, diagnostic determination of cholesterol in human serum or plasma. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.

Device Description

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

Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase (CE) to cholesterol and free fatty acids. Cholesterol Esters CE Cholesterol + Fatty Acids
Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase (CO) to cholest-4-en-3-one and hydrogen peroxide. Cholesterol + O2 CO Cholest-4-3-one + H2O2
The hydrogen peroxide combines with hydroxybenzoic acid (HBA) and 4-aminoantipyrine (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 am.

2H2O2 + HBA + 4AAP POD Quinoneimine Dye + 4H2O

AI/ML Overview

Here's an analysis of the provided information regarding the Sigma Diagnostics INFINITY™ Cholesterol Reagent, structured according to your request:

Acceptance Criteria and Study Details

The provided documentation describes the Sigma Diagnostics INFINITY™ Cholesterol Reagent, which is an in vitro diagnostic device for the quantitative determination of cholesterol. The substantial equivalence claim is made against the TRACE Scientific Cholesterol Reagent Kit (K962890) and the Sigma Diagnostics Cholesterol Reagent, Procedure No. 352 (K872295).

1. Table of Acceptance Criteria and Reported Device Performance

For this specific device, the primary "acceptance criterion" demonstrated in the 510(k) summary is substantial equivalence to existing legally marketed devices, rather than a set of predefined performance thresholds for accuracy, precision, or other analytical metrics typical of new device validations.

Acceptance Criterion (Implicitly for Substantial Equivalence)	Reported Device Performance	Comments
Correlation with Predicate Device (K872295)	Regression Equation: INFINITY Cholesterol = 1.00 (Cholesterol 352) - 0.3	This regression equation indicates a very strong linear correlation with the predicate device, suggesting near-identical results across the tested range. A slope of 1.00 and an intercept of -0.3 indicate highly similar performance. The "acceptance" is implicitly that these correlation results demonstrate that the new device performs acceptably similarly to the predicate.
Same Product as K962890	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.	This statement establishes that the device is, in fact, the same product as a previously cleared device (K962890), which inherently means it meets the acceptance criteria of that prior clearance.

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

Sample Size for Test Set: 126 plasma samples
Data Provenance: The document does not explicitly state the country of origin. It can be inferred that the samples were likely obtained within the region where Sigma Diagnostics operates (St. Louis, Missouri is listed as their address). The study is retrospective as it involves correlation with an existing, already marketed device.

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

This information is not applicable in the context of this 510(k) submission.

The "ground truth" here is the measurement obtained from the predicate device (Sigma Diagnostics Cholesterol Reagent, Procedure No. 352). This is a comparative study against another diagnostic assay, not against a gold standard established by human experts interpreting images or complex clinical data.
Therefore, no human experts were used to establish the ground truth for these 126 samples. The "ground truth" is the quantitative result generated by the predicate assay.

4. Adjudication Method for the Test Set

This information is not applicable. As explained above, the "ground truth" is the quantitative result from a predicate device, not subjective interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done.
This type of study is relevant for imaging devices or AI-assisted diagnostic tools where human readers are involved. This submission concerns an in vitro diagnostic reagent, which provides a quantitative biochemical measurement, not a subjective interpretation.

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

Yes, in a sense, a standalone study was done. The device itself (the reagent and its associated chemistry) produces a quantitative result independently. The correlation study directly measures the performance of this "standalone" system against another "standalone" system (the predicate device). There is no "human-in-the-loop" component in the direct measurement process of cholesterol levels by these reagents.

7. The Type of Ground Truth Used

Comparative Reference: The ground truth for the 126 plasma samples was the cholesterol measurement obtained using the Sigma Diagnostics Cholesterol Reagent, Procedure No. 352 (K872295). This serves as a comparative reference method rather than a biological "gold standard" or pathology.

8. The Sample Size for the Training Set

Not applicable. This device is a chemical reagent, not a machine learning or AI algorithm in the contemporary sense. Therefore, there is no "training set" in the context of AI models. The "training" for such a system involves chemical formulation and optimization, not data-driven model training.

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

Not applicable. As there is no training set for an AI/ML model, the concept of establishing ground truth for it does not apply here. The development of the reagent involves chemical engineering and analytical validation against established scientific principles and methods.

Summary

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

K992803

SEP 1 3 1999 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 and plasma.

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

Cholesterol esters are enzymatically hydrolyzed by cholesterol esterase (CE) to cholesterol and free 1. farry acids. Cholesterol Esters CE Cholesterol + Fatty Acids
Free cholesterol, including that originally present, is then oxidized by cholesterol oxidase (CO) to 2. cholest-4-en-3-one and hydrogen peroxide .. Cholesterol + O2 _CO _CO _ Cholest-4-en-3-one + H2O2
The hydrogen peroxide combines with hydroxybenzoic acid (HBA) and 4-aminoantipyrine (AAP) 3. 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 am.

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.

Correlation studies to Sigma Diagnostics Cholesterol Reagent, Procedure No. 352 (K872295) using plasma samples yielded a regression equation of:

INFINITY Cholestero] = 1.00 (Cholesterol 352) - 0.3 (N=126)

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. Tictz N.W. 1976; p 2. રેણવાડી રહ્યારે તે અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને અને પાસની દર્ભાગના પાસની દર્ભાગના દિવસ દિવસ દિવસ દિવસ
Allain C.C., Poon L.S., Chan C.S.G., Richmond W. and Fu P.C. Clin. Chem., 1974; 20:470-475. 3. .
Roeschlau P., Bernt E. and Gruber W.A. Clin. Chem. Clin. Biochem. 1974; 12:226. 4.

Contact Person:

William R. Gilbert II, Ph.D. Manager, Scientific Affairs Sigma Diagnostics 545 South Ewing St. Louis, MO 63103 314-286-6693

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, with three curved lines above them, resembling a bird in flight.

SEP 1 3 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

William R. Gilbert, Ph.D. Manager, Scientific Affairs SIGMA DIAGNOSTICS® 545 South Ewing Avenue St. Louis, Missouri 63103

K992803 Re:

Trade Name: INFINITY™ CHOLESTEROL Reagent (Procedure No. 401) Regulatory Class: I reserved Product Code: CHH 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/cdrl/dsma/dsmamain.html".

Sincerely yours.

Steven Putman

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}------------------------------------------------

510(k) Number (if known):

Device Name: Sigma Diagnostics INFINITY™ Cholesterol Reagent

Indications For Use:

Seán Cogger
(Division Sign-Off)

Division of Clinical Laboratory Devices
Division of Clinical Laboratory Devices 510(k) Number .

(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

§ 862.1175 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.