LIQUID N-GENEOUS HDL CHOLESTEROL KIT/CALIBRATOR

K971162 · Genzyme Corp. · LBS · Jun 16, 1997 · Clinical Chemistry

Device Facts

• Record ID: K971162
• Device Name: LIQUID N-GENEOUS HDL CHOLESTEROL KIT/CALIBRATOR
• Applicant: Genzyme Corp.
• Product Code: LBS · Clinical Chemistry
• Decision Date: Jun 16, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

For the quantitative determination of high-density lipoprotein Cholesterol (HDL-C) in human serum and plasma. For in vitro diagnostic use. For the calibration of the Liquid N-geneous HDL Cholesterol assay. For in vitro diagnostic use.

Device Story

The Genzyme Liquid N-geneous™ HDL Cholesterol Kit is a two-reagent homogeneous assay used in clinical and physician office laboratories. It utilizes a unique detergent that selectively solubilizes HDL particles while inhibiting enzyme reactions with LDL, VLDL, and chylomicron cholesterol. This selective solubilization allows for the direct quantitative measurement of HDL-C in human serum and plasma samples. The device is operated by laboratory personnel. Results are provided to healthcare providers to assist in lipid profile assessment and clinical decision-making regarding cardiovascular health. The assay eliminates the need for manual pretreatment or precipitation steps required by older methods.

Clinical Evidence

Bench testing and comparative performance studies were conducted. 92 serum samples were tested against the PTA method and 54 against the CDC Designated Comparison Method. Correlation coefficients were 0.991 and 0.992 respectively. Precision studies (within-run and between-run) across three HDL levels (<35, 35-60, >60 mg/dL) showed CVs ranging from 0.28% to 1.49%. Physician office laboratory (POL) studies (n=40) confirmed performance met NCEP goals (CVs ≤6% at ≥42 mg/dL; SD ≤2.5 mg/dL at <42 mg/dL).

Technological Characteristics

Two-reagent homogeneous enzymatic assay. Principle: Selective detergent-based solubilization of HDL particles followed by enzymatic cholesterol reaction. Form factor: Liquid reagent kit (also available in lyophilized format). Connectivity: Standalone diagnostic assay. Software: None.

Indications for Use

Indicated for the quantitative determination of HDL-C in human serum and plasma for in vitro diagnostic use. No specific patient population, age, or gender restrictions are stated.

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

• Sodium Phosphotungstate MgCl₂ (PTA) method

Reference Devices

• Center for Disease Control (CDC) Designated Comparison Method (DCM)
• Abell-Kendall method

Submission Summary (Full Text)

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K911162

Genzyme Corporation
One Kendall Square
Cambridge, MA 02139

510(k) PREMARKET NOTIFICATION

June 16, 1997

Liquid N-geneous™ HDL Cholesterol Reagent Kit March 28, 1997

# ATTACHMENT 1

## 510(k) Summary Of Safety and Effectiveness Information Upon Which An Equivalence Determination Could be Made

| Trade or Proprietary Name: | Genzyme Liquid N-geneous™ HDL Cholesterol Kit |
| --- | --- |
| Common or Usual Name: | Homogeneous assay for high density lipoprotein cholesterol |
| Classification Name: | High density lipoprotein cholesterol test |
| Manufacturer: | Genzyme Diagnostics
One Kendall Square
Cambridge, MA 02139-1562 |

Contact Person: Nancy E. Isaac, Associate Director, Regulatory Affairs [phone] or Beth A. Crowley, Regulatory Associate [phone].

The use of the Liquid Genzyme N-geneous™ HDL Cholesterol Kit in clinical and physician's office laboratory settings is substantially equivalent to the Sodium Phosphotungstate MgCl₂ (PTA) method. The Genzyme Liquid N-geneous™ HDL Cholesterol Kit is a two-reagent homogeneous method for the direct quantitative determination of high density lipoprotein cholesterol (HDL-C) in human serum and plasma.

In both user settings, the principle of the test is based upon a unique detergent which selectively solubilizes only the HDL. This unique detergent also strongly inhibits the reaction of the enzymes with cholesterol contained in the low density lipoprotein (LDL), very low density lipoprotein (VLDL) and chylomicron particles. Consequently, only the cholesterol in the resultant micell complexes of the detergent and lipids is subject to the enzyme reactions, leading to the selective determination of HDL cholesterol.

Comparative performance studies were conducted using the Liquid N-geneous™ HDL Cholesterol Kit and two reference methods: Sodium Phosphotungstate MgCl₂ and the Center for Disease Control (CDC) designated comparison method (DCM). When samples contained triglyceride levels &gt;200 mg/dL, the HDL reference method (ultracentrifugation, chemical precipitation and Abell-Kendall) was performed. Based on the Lipid Research Clinics (LRC) population studies, patient serum samples with HDL values between 27-91 mg/dL (5th and 95th percentile, respectively) were used for these comparative studies.

Ref. dHDL/n.300 - Ver. 8
34

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K971162

510(k) PREMARKET NOTIFICATION

Genzyme Corporation

One Kendall Square

Cambridge, MA 02139

Liquid N-geneous™ HDL

Cholesterol Reagent Kit

March 28, 1997

Ninety two serum samples, with HDL values between 25 and 91 mg/dL, were tested at Genzyme Corporation using the Liquid N-geneous™ HDL and the PTA precipitation methods. Of these 92 samples, 54 were tested with the CDC Designated Comparison Method for samples with triglyceride levels &lt;200 mg/dL and the HDL reference method (ultracentrifugation, precipitation and Abell-Kendall) for samples with triglyceride levels &gt;200 mg/dL.

| Liquid N-geneous™ HDL | vs. Phosphotungstate (n = 92) | vs. CDC Method (n = 54) |
| --- | --- | --- |
| Slope | 0.960 | 1.056 |
| Intercept (mg/dL) | 3.97 | -0.736 |
| Correlation Coefficient (r) | 0.991 | 0.992 |
| Mean (mg/dL) | Ng: 51.3
PTA: 49.3 | Ng: 54.3
CDC: 52.0 |
| Standard Deviation (mg/dL) | Ng: 13.7
PTA: 14.1 | Ng: 12.2
CDC: 11.5 |
| Mean Difference (mg/dL) | 2.0 | 2.2 |
| Mean Percent Difference | 4.7% | 4.1% |

Precision studies were conducted using the Liquid N-geneous™ HDL Cholesterol Test Kit. Both within-run and between-run studies were performed using frozen serum pools at three target levels of HDL cholesterol as determined by the National Cholesterol Education Program (NCEP): &lt;35 mg/dL (low); 35-60 mg/dL (mid); and &gt;60 mg/dL (high).

| Within-Run | Low (<35 mg/dL) | Mid (35-60 mg/dL) | High (>60 mg/dL) |
| --- | --- | --- | --- |
| n | 20 | 20 | 20 |
| Sample Range (mg/dL) | 22.6 - 23.5 | 55.1 - 56.7 | 84.3 - 85.0 |
| Mean (mg/dL) | 22.9 | 55.8 | 84.7 |
| SD (mg/dL) | 0.23 | 0.44 | 0.24 |
| %CV | 0.99 | 0.79 | 0.28 |
| Between-Run | Low (<35 mg/dL) | Mid (35-60 mg/dL) | High (>60 mg/dL) |
| --- | --- | --- | --- |
| n | 40 | 40 | 40 |
| Sample Range (mg/dL) | 22.6 - 24.1 | 54.5 - 57.1 | 83.7 - 87.8 |
| Mean (mg/dL) | 23.4 | 55.7 | 85.6 |
| SD (mg/dL) | 0.35 | 0.73 | 1.00 |
| %CV | 1.49 | 1.31 | 1.17 |

In separate comparative performance studies, three physician office laboratories (POL) analyzed separate sets of 40 serum samples using the lyophilized format of Genzyme's N-geneous™ HDL Cholesterol Reagent Kit. Split samples from the same 40 specimens were also analyzed at

Ref. dHDL/n.300 - Ver. 8
35

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K971162

510(k) PREMARKET NOTIFICATION

Genzyme Corporation
One Kendall Square
Cambridge, MA 02139

Liquid N-geneous™ HDL Cholesterol Reagent Kit March 28, 1997

Genzyme, which acted as the reference laboratory. The correlation coefficient between the reference testing site and the POL testing sites for this study were:

| Parameter | Site #1 | Site #2 | Site #3 |
| --- | --- | --- | --- |
| Slope | 1.11 | 1.12 | 0.93 |
| Intercept (mg/dL) | -1.44 | -5.90 | 1.25 |
| Correlation Coefficient (r) | 0.97 | 0.99 | 0.99 |

In the same study, the three POL sites compared their Genzyme N-geneous™ HDL Cholesterol Reagent Kit results to their respective current HDL methods for each of these 40 patient samples. The correlation coefficient for these comparisons were:

| Parameter | Site #1 | Site #2 | Site #3 |
| --- | --- | --- | --- |
| Slope | 0.88 | 1.05 | 0.77 |
| Intercept (mg/dL) | 2.90 | -1.32 | 11.1 |
| Correlation Coefficient (r) | 0.97 | 0.99 | 0.98 |

Precision studies were conducted using the lyophilized N-geneous™ HDL Cholesterol Test Kit. Both within-run and between-run studies were performed using frozen serum pools at three target levels of HDL cholesterol as determined by the National Cholesterol Education Program (NCEP): &lt;35 mg/dL (low); 35-60 mg/dL (mid); and &gt;60 mg/dL (high). It was determined that each POL site achieved the NCEP goals of CVs ≤6% at ≥42 mg/dL, and ≤2.5 mg/dL SD at &lt;42 mg/dL, when using the Genzyme N-geneous™ HDL Cholesterol Kit.

These data demonstrate that the performance of the N-geneous™ HDL Cholesterol Kit in both the clinical and physician office laboratories is substantially equivalent to the performance of the Sodium Phosphotungstate MgCl₂ and CDC Designated Comparison Methods.

In lieu of a 510(k) statement under 513(i) of the Act, this information is provided as a 510(k) summary for disclosure to any other persons/companies without the specific written authorization from Genzyme Corporation.

Ref. dHDL/n.300 - Ver. 8

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DEPARTMENT OF HEALTH &amp; HUMAN SERVICES
Public Health Service
Food and Drug Administration
2098 Gaither Road
Rockville MD 20850

JUN 16 1997

Nancy E. Isaac
Associate Director, Regulatory Affairs
Genzyme Corporation
One Kendall Square
Cambridge, Massachusetts 02139

Re: K971162
Liquid N-geneous™ HDL Cholesterol Kit/Cholesterol Calibrator
Regulatory Class: I &amp; II
Product Code: LBS, JIS
Dated: March 28, 1997
Received: March 31, 1997

Dear Ms. Isaac:

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 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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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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 [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 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 [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,

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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Page 1 of 1

D(k) Number (if known): K971162

Vice Name: Liquid N-geneous HDL Cholesterol Kit and N-geneous HDL Cholesterol Calibrator

ifications For Use:

For the quantitative determination of high-density lipoprotein Cholesterol (HDL-C) in human serum and plasma.

For in vitro diagnostic use.

For the calibration of the Liquid N-geneous HDL Cholesterol assay.

For in vitro diagnostic use.


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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Description Use ☑
(Per 21 CFR 801.109)

OR

Over-The-Counter Use ☐

(Optional Format 1-2-96)

RECEIVED
4 Apr 97 09 35
FDA/CDRH/ODE/04
4400