Sigma Diagnostics EZ HDL™ Reagent (Procedure 354) is a device intended to measure HDL cholesterol in plasma and serum. Cholesterol measurements and HDL cholesterol measurements are used in the diagnosis and treatment of disorders of lipid and lipoprotein metabolism. Sigma Diagnostics EZ HDL™ Calibrator (354-5) is a device intended for medical purposes for use in a HDL cholesterol test system to establish points of reference that are used in the determination of values in the measurement of HDL cholesterol in plasma and serum.

Device Description

Anti human B-lipoprotein antibody in Reagent 1 binds to lipoproteins (LDL, VLDL, and chylomicrons) other than HDL. The antigen-antibody complexes formed block enzyme reactions when Reagent 2 is added. Cholesterol esterase (CHE) and cholesterol oxidase (CO) in Reagent 2 react only with HDL-C. Hydrogen peroxide produced by the enzyme reactions with HDL-C yields a blue color complex upon oxidase condensation with FDAOS and 4-aminoantipyrine (4AA) in the presence of peroxidase (POD), By measuring the absorbance of the blue color complex produced, at approximately 600nm, the HDL-C concentration in the sample can be calculated with the absorbance of the EZ HDL™ Calibrator.

AI/ML Overview

This document describes the Summary of Safety and Effectiveness for the EZ HDL™ Cholesterol, Procedure No. 354 device.

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria Category	Specific Criteria/Metric	Acceptance Value	Reported Device Performance (EZ HDL™ Cholesterol)
Equivalence to Reference Method	Correlation Coefficient (vs. Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method)	Not explicitly stated as a numerical 'acceptance value', but implied to be high for "substantial equivalency".	0.980
Equivalence to Reference Method	Regression Equation (vs. Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method)	Not explicitly stated as a numerical 'acceptance value', but implied to be close to y=x (i.e., slope near 1, intercept near 0) for "substantial equivalency".	y = 0.82x + 7.48
Equivalence to Predicate Device	Correlation Coefficient (vs. Sigma Diagnostics 352-7 Phosphotungstic Acid procedure)	Not explicitly stated as a numerical 'acceptance value', but implied to be high for "substantial equivalency".	0.990
Equivalence to Predicate Device	Regression Equation (vs. Sigma Diagnostics 352-7 Phosphotungstic Acid procedure)	Not explicitly stated as a numerical 'acceptance value', but implied to be close to y=x (i.e., slope near 1, intercept near 0) for "substantial equivalency".	y = 0.97x + 5.07
Precision	Within-run precision	Acceptable values for replication	"indicate acceptable values can be replicated"
Precision	Total precision	Acceptable values for replication	"indicate acceptable values can be replicated on a day to day basis"
Linearity	Upper limit of linear range	Not explicitly stated as a numerical 'acceptance value', but needs to be sufficient for clinical use.	180 mg/dL
Interference	Triglyceride concentration interference	Not explicitly stated as a numerical 'acceptance value', but needs to be sufficient for clinical use.	Up to 2100 mg/dL

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

Sample Size: 97 serum samples were used for the comparison study against the Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is implied to be clinical samples used in a laboratory setting.

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

Number of Experts: Not applicable. The "ground truth" was established by recognized reference methods or predicate devices, not by expert interpretation of data.
Qualifications of Experts: Not applicable.

4. Adjudication Method for the Test Set:

Adjudication Method: Not applicable. The comparison was quantitative against established methods, not subjective interpretation requiring adjudication among experts.

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

MRMC Study: No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic reagent, not an imaging or diagnostic device that relies on human reader interpretation. The study was a comparison of quantitative measurements.
Effect Size: Not applicable.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Standalone Performance: Yes, the entire study focuses on the standalone performance of the EZ HDL™ Cholesterol Reagent. The effectiveness is demonstrated by its performance in measuring HDL-C concentrations compared to reference and predicate methods, without human interpretation as part of the measurement process itself beyond standard laboratory procedures.

7. The Type of Ground Truth Used:

Ground Truth Type: The ground truth was established by recognized reference methods and predicate devices.
- Reference Method: Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method.
- Predicate Device: Sigma Diagnostics 352-7 Phosphotungstic Acid procedure.

8. The Sample Size for the Training Set:

Training Set Sample Size: The document does not describe a separate "training set" as would be used for a machine learning algorithm. This device is a chemical reagent-based assay. Its development would involve internal validation and optimization, but the provided summary focuses on the final performance validation using test samples.

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

Training Set Ground Truth Establishment: Not applicable, as a distinct training set in the context of machine learning is not described. The performance of the reagent is based on its chemical reactions and analytical characteristics, which would have been optimized during its development using established analytical chemistry principles and potentially internal comparisons to reference methods.

Summary

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JUL 22 1997

SUMMARY OF SAFETY AND EFFECTIVENESS

EZ HDLTM CHOLESTEROL, PROCEDURE NO. 354

Blood total cholesterol levels have long been known to be related to coronary heart disease (CHD). In recent years, in addition to total cholesterol, high dcnsity lipoprotein cholesterol (HDL-C) has become an important tool used to assess an individual risk of developing CHD since a strong negative relationship between HDL-C concentration and the incidence of CHD was reported. Thus, there has been substantial interest in HDL-C measurements, and most clinical laboratories routinely perform HDL-C analysis. Selective chemical precipitation techniques are widely used for the determination of HDL-C such as heparinmanese, dextran sulfate-magnesium, and phosphotungstate-magnesium2 However, these techniques require physical separation via centrifugation, which is not suited to large scale lab use.

The safety and effectiveness of the Sigma Diagnostics EZ HDL™ Cholesterol Reagent, Procedure 354 is demonstrated by its substantial equivalency to a Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method. Both HDL test systems are used to measure HDL-C concentrations in serum and plasma. In comparison studies against this Dextran Sulphate mcthod, a correlation coefficient of 0.980 and regression equation y = 0.82x + 7.48 were obtained with 97 serum samples. In additional comparison studies against the Sigma Diagnostics 352-7 Phosphotungstic Acid procedure, a correlation cocflicient of 0.990 and regression equation y = 0.97x +5.07 were obtained. Within run precision and total precision on serum samples indicate acceptable values can be replicated on a day to day basis. Sigma Diagnostics EZ HDL™ Cholesterol Reagent has been determined to be linear to 180 mg/dL and can be used with samples with triglyceride concentrations up to 2100 mg/dL.

REFERENCES

Rifai N. Warnick GR, Ed. Laboratory Measurement of Lipids, Lipoproteins and Apolipoproteins. AACC Press, Washington, DC, USA, 1994

Burtis CA, Ashwood ER, Ed. Tietz Textbook of Clinical Chemistry, 2nd ed., Saunders, 2. Philadelphia, 1994

Date of Preparation: July 1997 Contact: William R. Gilbert (314) 771-3122

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Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three stripes representing the three branches of government. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 2 2 1997

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

K972041 Re : EZ HDL™ Cholesterol Reagent/Calibrator Requlatory Class: I & II Product Code: LBS, JIS May 30, 1997 Dated: Received: June 2, 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, 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. ਸ substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, 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.

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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 ene regaracion enorification" (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 Litman

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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(Division Sign-Off)
Division of Clinical Laboratory Device
510(k) Number. K92041

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use __________

Regulation Number and Section

§ 862.1475 Lipoprotein test system.

(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(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.