DIAZYME LDL-CHOLESTEROL REAGENT, CALIBRATOR AND CONTROLS

K072523 · General Atomics · LBR · Jan 22, 2008 · Clinical Chemistry

Device Facts

• Record ID: K072523
• Device Name: DIAZYME LDL-CHOLESTEROL REAGENT, CALIBRATOR AND CONTROLS
• Applicant: General Atomics
• Product Code: LBR · Clinical Chemistry
• Decision Date: Jan 22, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

The Diazyme LDL-Cholesterol reagent is intended for the in vitro quantitative determination of Low Density Lipoprotein Cholesterol in human serum or plasma. The reagents can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease. Elevated LDL Cholesterol is the primary target of cholesterol-lowering therapy Calibrator – For calibration of the Diazyme LDL-Cholesterol Reagent Assay in serum or plasma. For In Vitro Diagnostic Use Controls – To monitor the performance of the Diazyme LDL-Cholesterol Reagent. For In Vitro Diagnostic Use

Device Story

Diazyme LDL-Cholesterol reagent is an in vitro diagnostic assay for quantitative LDL-C measurement in human serum or plasma. The assay uses a modified polyvinyl sulfonic acid and polyethylene-glycol-methyl ether precipitation method to mask VLDL, chylomicrons, and HDL, rendering them inaccessible to cholesterol oxidase and cholesterol esterase. Addition of R2 reagent detergents releases LDL, which reacts with cholesterol oxidase and cholesterol esterase; the resulting H2O2 is quantified via the Trinder reaction. The device is intended for use in clinical laboratories by trained personnel using automated chemistry analyzers (e.g., Hitachi 917). Results are provided to physicians to assess cardiovascular risk and guide cholesterol-lowering therapy.

Clinical Evidence

Bench testing only. Performance studies included linearity (1.64-830 mg/dL), precision (within-run CV 0.7-1.0%, total CV 1.4-1.6%), and interference studies (no significant interference from triglycerides, ascorbic acid, bilirubin, or hemoglobin). Method comparison against the predicate (K971573) demonstrated a correlation coefficient of 0.996.

Technological Characteristics

Quantitative colorimetric Trinder reaction assay. Reagents: modified polyvinyl sulfonic acid and polyethylene-glycol-methyl ether. Analyzed on automated chemistry analyzers (Hitachi 917). Calibrators and controls are lyophilized human serum-based. Reportable range: 2-250 mg/dL. Stability: 12 months at 2-8°C.

Indications for Use

Indicated for in vitro quantitative determination of LDL-C in human serum or plasma to assist in diagnosis and treatment of patients at risk of coronary heart disease.

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

• Ultra N-Geneous LDL Cholesterol Reagent and Calibrator (k021316)
• Bio-Lipid Lipid Controls (k951749)

Submission Summary (Full Text)

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# K072523

### 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

| Submitter's name: | Diazyme Laboratories |
|--------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitter's address: | 12889 Gregg Court<br>Poway, CA 92064<br>USA |
| Name of Contact Person: | Charles Yu<br>Diazyme Laboratories<br>12889 Gregg Court<br>Poway, CA 92064<br>Phone: [phone]<br>Fax: [phone] |
| Date the Summary was Prepared: | August 22, 2007 |
| Name of the Device | Diazyme LDL-Cholesterol Reagent |
| Trade Name: | Diazyme LDL-Cholesterol Reagent |
| Common/Usual Name | Lipoprotein Test System |
| Device Classification Name | Low Density Lipoprotein Cholesterol Reagent |
| Product code: | LBR, JIS, JIX |
| Submission Type | 510k |
| Regulation Number | 862.1475 |
| Device Class | II |
| Predicate Device: | For the Lipoprotein test system, we are claiming equiva<br>lence [807.92(a) (3) to N-GENEOUS LDL CHOLES<br>TEROL REAGENT (k971573) manufactured by Genzyme<br>Diagnostics |

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## Substantial Equivalence Information

#### 1. Predicate device name(s):

Genzyme N-Geneous LDL Cholesterol Reagent

#### 2. Predicate 510(k) number(s):

K971573

#### 3. Comparison with predicate:

#### Indications for Use

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| The Diazyme LDL-Cholesterol Assay is<br>intended for the in vitro quantitative<br>determination of Low Density Lipoprotein<br>Cholesterol in human serum or plasma. The<br>reagents can assist in the diagnosis and<br>treatment of patients at risk of developing<br>coronary heart disease. Elevated LDL<br>cholesterol is the primary target of<br>cholesterol-lowering therapy. | For the direct, quantitative measurement of<br>low density lipoprotein cholesterol (LDL-<br>C) concentration in human serum or<br>plasma. | Same |

#### Principle

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| The assay is based on a modified polyvinyl<br>sulfonic acid (PVS) and polyethylene-glycol-<br>methyl ether (PEGME) coupled classic pre-<br>cipitation method with the improvements in<br>using optimized quantities of PVS/PEGME<br>and selected detergents. LDL, VLDL, and<br>chylomicron (CM) react with PVS and<br>PEGME and the reaction results in inaccessi-<br>bility of LDL, VLDL and CM by cholesterol<br>oxidase (CHOD) and cholesterol esterase<br>(CHER). The enzymes selectively react with<br>HDL to produce H2O2 which is detected<br>through a Trinder reaction. | This method is in a two reagent format and<br>depends on the properties of a unique de-<br>tergent. This detergent ( Reagent 1) solubi-<br>lizes only the non LDL lipoprotein parti-<br>cles. The cholesterol released is consumed<br>by cholesterol esterase and cholesterol oxi-<br>dase in a non color forming reaction. A<br>second detergent (Reagent 2) solubilizes<br>the remaining LDL particles and a chro-<br>mogenic coupler allows for color forma-<br>tion. The enzyme reaction with LDL-C in<br>the presence of the coupler produces color<br>that is proportional to the amount of LDL<br>cholesterol present in the sample. | Similar |

#### Test Objective

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|--------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| For the in vitro quantitative determination<br>of low density lipoprotein cholesterol in<br>human serum or plasma. | For the direct, quantitative measurement of<br>low density lipoprotein cholesterol (LDL-<br>C) concentration in human serum or<br>plasma. | Same |

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## Type of Test

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|---------------------------------|----------------------------------------------|-------------|
| Quantitative | Quantitative | Same |

#### Specimen Type

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|---------------------------------|----------------------------------------------|-------------|
| Human serum or plasma | Human serum or plasma | Same |

#### Product Type

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol<br>Reagent | Equivalency |
|---------------------------------|----------------------------------------------|-------------|
| Calibrator, Reagent, Instrument | Calibrator, Reagent, Instrument | Same |

#### Performance

| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol Reagent |
|------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|
| Reportable Range:<br>Serum: 2.04 - 250 mg/dL | Reportable Range:<br>Serum: 6.6-992mg/dL |
| Precision/Serum:<br>Within Run: 0.7% -1.0%<br>Total: 1.4%-1.6% | Precision/Serum:<br>Within Run: 0.62% -0.73%<br>Total: 1.73%-2.27% |
| Accuracy/Serum:<br>Correlation Coefficient: 0.9804<br>Slope/Intercept:<br>y = 1.0883x + 0.6078 mg/dL | Accuracy/Serum:<br>Correlation Coefficient: 0.96<br>Slope/Intercept:<br>y = 0.95x + 3.02mg/dL |

### Calibrator Comparison

| Diazyme LDL Cholesterol Calibrator | Genzyme N-Geneous LDL Cholesterol<br>Calibrator | Equivalency |
|---------------------------------------------------------------|-----------------------------------------------------------------------------|-------------|
| Lyophilized form | Lyophilized form | Same |
| LDL Cholesterol calibrator is traceable to NIST<br>SRM 1915b. | LDL N-Geneous calibrator is traceable to<br>the CDC HDL reference method**. | Same |

** National Reference System for Cholesterol. CRMLN LDL Cholesterol Protocol, May 2004.

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#### Rationale for Considering the Device Substantially Equivalent to Devices Approved for Interstate Commerce

Genzyme N-geneous LDL Cholesterol Reagent (k971573) was selected for comparing serum samples with to the results generated by Diazyme LDL-Cholesterol Reagent. Detailed performance characteristics and comparison analysis are given in this filing and demonstrate substantial equivalence to predicate device that is currently being legally marketed.

The Diazyme LDL-Cholesterol Reagent is similar to the approved predicate test. The minor differences in the performances of the tests should not affect the safety and effectiveness of the Diazyme LDL - Cholesterol Reagent and offers users an in-vitro diagnostic device to measure LDL Cholesterol in human serum or plasma.

In summary, the dissimilar features between the Diazyme LDL-Cholesterol Reagent and devices currently legally marketed do not affect the safety or effectiveness of the device. This is supported by the accuracy data comparing serum sample values obtained using the Diazyme LDL-Cholesterol Reagent with those obtained using the predicate device, Genzyme N-geneous LDL Cholesterol Reagent (k971573).

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#### Description of the Device

The assay is based on a modified polyvinyl sulfonic acid (PVS) and polyethylene-glycol methyl ether (PEGME) coupled classic precipitation method with the improvements in using optimized quantities of PVS/PEGME and selected detergents. LDL, VLDL. and chylomicron (CM) react with PVS and PEGME and the reaction results in inaccessibility of LDL, VLDL and CM by cholesterol oxidase (CHOD) and cholesterol esterase (CHER), whereas HDL reacts with the enzymes. Addition of R2 containing a specific detergent releases LDL from the PVS/PEGME complex. The released LDL reacts with the enzymes to produce H2O2 which is quantified by the Trinder reaction.

PVS HDL + LDL + VLDL + CM = + PEGME HDL + (LDL + VLDL + CM ) · PVS/PEGME HDL + CHER - -- Fatty Acid + H3O2 Detergent (LDL + VLDL + CM)· PVS/PEGME LDL + (VLDL + CM) · PVS/PEGME LDL + CHOD + CHER ------------------------------------------------------------------------------------------------------------------------------------------------------------Peroxidase 2H2O2 +4-AA+TODB -------------------------------------------------------------------------------------------------------------------------------------------------------------(2-max=560nm)

#### Intended Use of the Device:

The Diazyme LDL-Cholesterol Reagent is intended for the in vitro quantitative determination of Low Density Lipoprotein Cholesterol in human serum or plasma. The reagents can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease. Elevated LDL cholesterol is the primary target of cholesterol-lowering therapy.

#### Performance Characteristics

Diazyme LDL-Cholesterol Reagent is a homogeneous two-reagent enzymatic assay. The results are obtained in 10 minutes by measuring absorbance at 600 nm. The linearity of the assay is from 1.64 -830 mg/dL for serum samples. The assay offers excellent precision as shown in the tables below:

| Serum Testing | Level 1<br>95mg/dL LDL | Level 2<br>146mg/dL LDL | Level 3<br>210mg/dL LDL |
|----------------------|------------------------|-------------------------|-------------------------|
| Within-Run Precision | $C_v$ % = 1.0% | $C_v$ % = 0.8% | $C_v$ % = 0.7% |
| Total Precision | $C_v$ % = 1.6% | $C_v$ % = 1.5% | $C_v$ % = 1.4% |

In method comparison studies, samples tested with Diazyme LDL-Cholesterol Reagent showed good correlation with Genzyme N-geneous LDL Cholesterol Reagent (k971573) with correlation coefficients of 0.996 for serum samples.

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We have conducted interference studies by spiking normal pooled human serum samples with substances normally present in serum or plasma and found less than 10% interference at the indicated concentrations.

| Interference Study | |
|----------------------|---------------|
| Substance | Concentration |
| Triglycerides | 1000 mg/dL |
| Ascorbic acid | 10 mmol/L |
| Bilirubin | 40 mg/dL |
| Bilirubin Conjugated | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |

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Conclusion: Comparison analysis presented in this 510k submission filing in the comparison section, together with linearity, precision and interference and other detailed studies, demonstrates that the Diazyme LDL-Cholesterol Reagent has excellent accuracy and is safe and effective. There is no significant deviation between the results obtained by Diazyme LDL-Cholesterol Reagent and the legally marketed predicate device (k971573) when testing clinical patient samples and is therefore substantially similar.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its head turned to the left and its wings outstretched. The eagle is composed of three thick, black lines. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Public Health Service

JAN 22 2008

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

General Atomics Diazyme Laboratories Division c/o Mr. Charles Yu 12889 Gregg Court Poway, CA 92064

Re: k072523

Trade/Device Name: Diazyme LDL-Cholesterol Reagent Regulation Number: 21 CFR§862.1475 Regulation Name: Lipoprotein Test System Regulatory Class: Class I Product Code: LBR, JJX Dated: November 12, 2007 Received: November 15, 2007

Dear Mr. Yu:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

| 510(k) Number: | K 072523 |
|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | Diazyme LDL-Cholesterol Reagent |
| Indications for Use: | The Diazyme LDL-Cholesterol Assay is intended for the in vitro quantitative<br>determination of Low Density Lipoprotein Cholesterol in human serum or<br>plasma. The reagents can assist in the diagnosis and treatment of patients at<br>risk of developing coronary heart disease. Elevated LDL cholesterol is the<br>primary target of cholesterol-lowering therapy. |
| Calibrator: | For calibration of the Diazyme LDL-Cholesterol Reagent Assay in<br>serum or plasma.<br>For In Vitro Diagnostic Use |
| Controls: | To monitor the performance of Diazyme LDL-Cholesterol Reagent.<br>For In Vitro Diagnostic Use |

Prescription Use X (Part 21 CFR 801 Subpart D)

.

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

| Signature | Carol Benson Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) |
|-------------------|--------------------------------------------------------------------------------|
| Division Sign-Off | |

510(k) Summary

| Office of In Vitro Diagnostic Device | |
|--------------------------------------|----|
| Evaluation and Safety | 15 |

K072523: