COBAS INTEGRA LDL DIRECT REAGENT CASSETTE ROCHE CALIBRATOR LDL DIRECT

K982848 · Roche Diagnostic Systems, Inc. · MRR · Oct 1, 1998 · Clinical Chemistry

Device Facts

• Record ID: K982848
• Device Name: COBAS INTEGRA LDL DIRECT REAGENT CASSETTE ROCHE CALIBRATOR LDL DIRECT
• Applicant: Roche Diagnostic Systems, Inc.
• Product Code: MRR · Clinical Chemistry
• Decision Date: Oct 1, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

The cassette COBAS INTEGRA LDL Direct (LDL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative determination of LDL-cholesterol direct concentration in serum and plasma. Low density lipoprotein cholesterol measurement, in conjunction with other lipid determinations, has been shown to be useful in assessing the risk of coronary heart disease. The Roche Calibrator LDL Direct is intended for use as calibrator in quantitative Low Density Lipoprotein cholesterol assays. It is recommended for use with LDL Direct reagents on COBAS® chemistry systems. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens.

Device Story

COBAS INTEGRA LDL Direct is an in vitro diagnostic reagent system for quantitative LDL-cholesterol measurement in serum/plasma. Used on COBAS INTEGRA 700 analyzer; system utilizes absorbance, fluorescence polarization, and ion-selective electrodes. Principle of operation: two-step enzymatic reaction; first step uses detergent to hydrolyze HDL, VLDL, and chylomicrons into colorless products while LDL remains intact; second step uses a second detergent and coupler to release and react with LDL-cholesterol to produce color. Analyzer automates sample handling, reagent management, and barcode identification. Healthcare providers use results to assess coronary heart disease risk. System provides high-throughput, random-access testing in clinical laboratory settings.

Clinical Evidence

Bench testing only. Performance evaluated via precision (within-run CV 1.4-1.8%, total CV 1.9-2.1%) and accuracy studies. Accuracy compared against beta-quantification and Friedewald formula (n=276, r=0.964; n=150, r=0.954).

Technological Characteristics

Reagent system consists of liquid enzymes, detergents, and couplers. Analyzers utilize absorbance, fluorescence polarization, and ion-selective electrodes. System features automated barcode reading, random sample access, and refrigerated on-board storage (2-8°C).

Indications for Use

Indicated for quantitative determination of LDL-cholesterol in human serum and plasma to assess coronary heart disease risk. For use by clinical laboratory professionals on COBAS INTEGRA 700 systems.

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

• Roche Reagent for LDL Direct (K924674)
• Roche Calibrator Serum (K922043)

Submission Summary (Full Text)

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OCT 1 1998

Image /page/0/Picture/1 description: The image contains the number 982848 at the top. Below the number is a hexagon with the word "Roche" inside. The text and hexagon are black and the background is white.

# 510(k) Summary

# Roche COBAS® INTEGRA LDL Direct and Roche Calibrator LDL Direct

In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary is provided as outlined in 21 CFR 807.92.

The assigned 510(k) number is: k982848

#### I. Identification of 510(k) Sponsor:

Roche Diagnostic Systems, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

510(k) Submission dated August 6, 1998

Rita Smith Contact: Senior Regulatory Affairs Associate

Phone: [phone] [phone] Fax:

Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

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#### II. Device Name:

The device name, including both the trade/proprietary name and the classification name are provided in the table below.

## Table 1

| Product Name | Classification<br>Name | Product<br>Code | CFR<br>Number and<br>Regulatory Class |
|-------------------------------------|----------------------------------------|-----------------|---------------------------------------|
| COBAS INTEGRA<br>LDL Direct (LDL-D) | Low Density Lipoprotein test<br>system | MRR | 862.1475<br>Class I |
| Roche Calibrator LDL Direct | Calibrator, Secondary | JIT | 862.1150<br>Class II |

## III. Identification of the legally marketed device to which the 510(k) sponsor claims equivalence:

The following table identifies the legally marketed devices to which Roche Diagnostic Systems, Inc. claims equivalence.

## Table 2

| Product Name | Predicate Product<br>Name | Date<br>Predicate<br>Cleared | Predicate<br>510(k)<br>Number |
|-------------------------------------|------------------------------|------------------------------|-------------------------------|
| COBAS INTEGRA<br>LDL Direct (LDL-D) | Roche Reagent for LDL Direct | 1/6/93 | K924674 |
| Roche Calibrator LDL Direct | Roche Calibrator Serum | 6/16/92 | K922043 |

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## VI. Brief discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence:

Tables 3 demonstrates the results of clinical and nonclinical studies performed using the COBAS INTEGRA LDL Direct Reagent Cassette. The significant performance characteristics relied upon for a determination of substantial equivalence are summarized in this chart. This information concludes that the performance of this device is essentially equivalent to other legally marketed devices of a similar kind.

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#### Description of the Device/Statement of Intended Use: IV.

The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer, which is also known as the COBAS INTEGRA 700. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer along with 108 Roche COBAS INTEGRA Reagent Cassettes were previously cleared on September 8. 1995 (K951595); January 25, 1996 (K954992); July 23, 1996 (K961824); October 31, 1996 (K963292); January 21, 1997 (K964457); August 12. 1997 (K972250): and May 21. 1998 (K974695).

The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents. For additional information on the COBAS INTEGRA Analyzer and its constituent modules, please refer to the Operator's Manual in Volumes 1 through 2, pages 92-703, of the original 510(k) submission (K951595).

Through this submission, it is the intention of Roche to gain clearance for the new reagent cassette, COBAS INTEGRA LDL Direct and its associated calibrator, Roche Calibrator LDL Direct.

### V. Summary of the technological characteristics of the new device in comparison to those of the predicate.

Tables 3 outlines the technological characteristics (methodologies) of the COBAS INTEGRA LDL Direct in comparison to those of legally marketed predicate products.

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## COBAS INTEGRA LDL DIRECT

The cassette COBAS INTEGRA LDL Direct (LDL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative determination of LDLcholesterol direct concentration in serum and plasma. Low density lipoprotein cholesterol measurement, in conjunction with other lipid determinations, has been shown to be useful in assessing the risk of coronary heart disease.

## ROCHE CALIBRATOR LDL DIRECT

The Roche Calibrator LDL Direct is intended for use as calibrator in quantitative Low Density Lipoprotein cholesterol assays. It is recommended for use with LDL Direct reagents on COBAS® chemistry systems. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens.

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# Table 3

| COBAS INTEGRA LDL Direct<br>and<br>Roche Calibrator LDL Direct | | Roche Reagents for LDL Direct<br>(K924674)<br>and<br>Roche Calibrator Serum (K922043) | | |
|----------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|-----------------------|
| Intended Use: | | | | |
| Reagent | for the quantitative determination of LDL-<br>cholesterol direct concentration in serum and<br>plasma | intended for use in direct, quantitative<br>determination of low-density lipoprotein<br>(LDL) cholesterol in serum or plasma | | |
| Calibrator | intended for use as calibrator in quantitative<br>Low Density Lipoprotein cholesterol assays on<br>COBAS chemistry systems | calibrator intended for use on COBAS<br>chemistry instruments with Roche clinical<br>chemistry reagents | | |
| Reagents | Enzymes and detergent (liquid)Coupler and detergent (liquid) | a suspension of polystyrene beads<br>coated with goat polyclonal antibodies<br>to human apolipoproteins in buffer with<br>0.1% sodium azide.controls, 2 levelscholesterol separation tubes | | |
| Principle | HDL, VLDL and chylomicrons are specifically<br>hydrolyzed by a detergent. Through a series of<br>chemical reactions only a colorless product is<br>produced from these particles. During this first<br>step, LDL particles remain intact and a second<br>detergent with a coupler is added to release<br>cholesterol in the LDL particles. This<br>cholesterol then undergoes an enzymatic<br>reaction in the presence of coupler to produce<br>color. | Affinity purified goat polyclonal antisera to<br>specific human apolipoproteins facilitates<br>the removal of HDL and VLDL in the<br>specimen. After centrifugation, LDL<br>remains in the filtrate solution. | | |
| Calibrator | | | | |
| Matrix: | human serum | human serum | | |
| Approx. Value: | 2.85 mmol/L (110 mg/dL) | 51.4 mg/dL | | |
| Performance Characteristics: | | | | |
| Precision: | Level 1 | Level 2 | | |
| Mean | 2.72 mmol/L<br>(105 mg/dL) | 5.12 mmol/L<br>(198 mg/dL) | | |
| Within Run CV | 1.4 | 1.8 | | |
| Total CV | 1.9 | 2.1 | | |
| Linearity | 14.0 mmol/L (540 mg/dL) | 500 mg/dL | | |
| Accuracy: | COBAS<br>MIRA | Beta-quant-<br>ification | Friedewald<br>formula | Beta-quantification |
| Sample size (n) | 276 | 150 | 276 | 74 |
| Corr. Coefficient (r) | 0.964 | 0.954 | 0.963 | 0.96 |
| Linear regression | y = 0.85x +<br>0.7 mmol/L | y= 0.95x +<br>0.1 mmol/L | y = 0.97x +<br>0.5 mmol/L | y = 1.05x + 4.8 mg/dL |

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Image /page/6/Picture/2 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 symbol of three human profiles facing right, stacked on top of each other.

OCT 1 1998 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Maria Feijoo . Manager, Regulatory Affairs Roche Diagnostic Systems, Inc. 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

Re : K982848 COBAS® INTEGRA LDL Direct Reagent Cassette Roche® Calibrator LDL Direct Regulatory Class: I & II Product Code: MRR, JIT August 11, 1998 Dated: Received: August 12, 1998

Dear Ms. Feijoo:

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 Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with and e 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 requlatory . .... In addition, FDA may publish further announcements action. 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 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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Page 1 of 1

1982848 510(k) Number (if known)

Device Name:

COBAS INTEGRA LDL Direct Reagent Cassette (LDL-D), Art. No. 07 6674 7

Roche Calibrator LDL Direct , Art. No. 07 6675 5

Indications for Use:

The cassette COBAS INTEGRA LDL Direct (LDL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative determination of LDL-cholesterol direct concentration in serum and plasma. Low density lipoprotein cholesterol measurement, in conjunction with other lipid determinations, has been shown to be useful in assessing the risk of coronary heart disease.

The Roche Calibrator LDL Direct is intended for use as calibrator in quantitative Low Density Lipoprotein cholesterol assays. It is recommended for use with LDL Direct reagents on COBAS® chemistry systems. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens.

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

OR

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number 982848

Over-The-Counter Use (Optional Format 1-2-96)