EZ HDL CHOLESTEROL REAGENT(PROCEDURE 354)/EZ HDL CALIBRATOR (354-5)

K972041 · Sigma Diagnostics, Inc. · LBS · Jul 22, 1997 · Clinical Chemistry

Device Facts

• Record ID: K972041
• Device Name: EZ HDL CHOLESTEROL REAGENT(PROCEDURE 354)/EZ HDL CALIBRATOR (354-5)
• Applicant: Sigma Diagnostics, Inc.
• Product Code: LBS · Clinical Chemistry
• Decision Date: Jul 22, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

Sigma Diagnostics EZ HDL™ Reagent (Procedure 354) is a device intended to measure HDL cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving 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 measurements.

Device Story

EZ HDL™ Cholesterol Reagent is an in vitro diagnostic assay for measuring HDL-C in serum and plasma. The assay uses a two-reagent system: Reagent 1 contains anti-human B-lipoprotein antibody to bind non-HDL lipoproteins (LDL, VLDL, chylomicrons), forming complexes that block enzyme reactions; Reagent 2 contains cholesterol esterase and cholesterol oxidase, which react specifically with HDL-C. The resulting hydrogen peroxide reacts with FDAOS, 4-aminoantipyrine, and peroxidase to produce a blue color complex. The device is used in clinical laboratories; technicians measure the absorbance of the blue complex at approximately 600nm. The concentration is calculated using the EZ HDL™ Calibrator. Results assist clinicians in assessing coronary heart disease (CHD) risk and managing lipid metabolism disorders.

Clinical Evidence

Bench testing only. Comparison studies against the Dextran Sulphate precipitation method (n=97 serum samples) yielded a correlation coefficient of 0.980 and regression equation y = 0.82x + 7.48. Comparison against the Phosphotungstic Acid procedure yielded a correlation coefficient of 0.990 and regression equation y = 0.97x + 5.07. The device is linear to 180 mg/dL and compatible with triglyceride concentrations up to 2100 mg/dL. Precision data indicates acceptable day-to-day reproducibility.

Technological Characteristics

In vitro diagnostic reagent system using enzymatic colorimetric assay. Components: anti-human B-lipoprotein antibody, cholesterol esterase, cholesterol oxidase, FDAOS, 4-aminoantipyrine, and peroxidase. Measures absorbance at ~600nm. Compatible with serum and plasma. Linearity up to 180 mg/dL; triglyceride interference threshold 2100 mg/dL.

Indications for Use

Indicated for the measurement of HDL cholesterol in human plasma and serum to assist in the diagnosis and treatment of lipid and lipoprotein metabolism disorders. For prescription use.

Regulatory Classification

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.

Predicate Devices

• Cholesterol Reference Method Laboratory Network standardized 50K molecular weight Dextran Sulphate precipitation method

Reference Devices

• Sigma Diagnostics 352-7 Phosphotungstic Acid procedure

Submission Summary (Full Text)

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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.

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.

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

1. 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 [phone]

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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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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# NOT WRITE BE...
Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use __________