ROCHE C0BAS INTEGRA SERUM BARBITURATES REAGENT CASSETTE, ABUSCREEB ONLINE SERUM BARBITURATES CALIBRATORS, ROCHE COBAS IN

K982551 · Roche Diagnostic Systems, Inc. · DIS · Aug 18, 1998 · Clinical Toxicology

Device Facts

• Record ID: K982551
• Device Name: ROCHE C0BAS INTEGRA SERUM BARBITURATES REAGENT CASSETTE, ABUSCREEB ONLINE SERUM BARBITURATES CALIBRATORS, ROCHE COBAS IN
• Applicant: Roche Diagnostic Systems, Inc.
• Product Code: DIS · Clinical Toxicology
• Decision Date: Aug 18, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3150
• Device Class: Class 2

Intended Use

The cassette COBAS INTEGRA Serum Barbiturates contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose. The Abuscreen ONLINE Serum Barbiturates Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Barbiturates on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of barbiturates in human specimens. The cassette COBAS INTEGRA Serum Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of benzodiazepines and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of benzodiazepine use or overdose. The Abuscreen ONLINE Serum Benzodiazepines Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Benzodiazepines on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of benzodiazepines in human specimens.

Device Story

System consists of COBAS INTEGRA Analyzer and specific reagent cassettes (SBARB, SBENZ) with associated calibrators. Analyzer uses fluorescence polarization to measure drug concentrations in human serum or plasma samples. System features automated random sample access, robotics, and barcode identification for reagents and samples. Used in clinical laboratory settings for toxicological screening; results assist physicians in managing drug use or overdose cases. Benefits include rapid, preparation-free testing and integrated workflow management.

Clinical Evidence

Bench testing only. Performance evaluated via precision studies (within-run and total CVs reported) and accuracy studies comparing results against GC/MS and predicate FPIA/EIA methods. Sensitivity and assay ranges were established for both barbiturate and benzodiazepine assays.

Technological Characteristics

Methodology: Fluorescence polarization. Reagents: Polyclonal antibody (sheep), fluorescein-labeled drug derivative, buffer, and stabilizers. System: COBAS INTEGRA Analyzer (automated, random access, barcode-enabled). Connectivity: Integrated system. Form factor: Compact, preparation-free reagent cassettes. Storage: 2-8°C on-board stability.

Indications for Use

Indicated for the detection of barbiturates or benzodiazepines and their metabolites in human serum or heparinized plasma for toxicological screening in the management of drug use or overdose.

Regulatory Classification

Identification

A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). A barbiturate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Predicate Devices

• Abbott ADX Barbiturates (K890690)
• Abbott TDX Benzodiazepines Serum (K883730)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the text "K982551" written in a handwritten style. Below the text is the Roche logo, which consists of the word "Roche" inside of a hexagon. The text and logo are both black and are set against a white background.

AUG 1 8 1998

# 510(k) Summary

# Roche COBAS® INTEGRA Reagent Cassettes

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: K982551

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

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 July 20, 1998

Rita Smith Contact: Senior Regulatory Affairs Associate Phone: [phone] [phone] Fax:

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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.

| Product Name | Classification<br>Name | Product<br>Code | CFR<br>Number and<br>Regulatory Class |
|-------------------------------------------------------|----------------------------------------|-----------------|---------------------------------------|
| COBAS INTEGRA<br>Serum Barbiturates (SBARB) | Enzyme Immunoassay,<br>Barbiturates | DIS | 862.3150<br>Class II |
| Abuscreen ONLINE Serum<br>Barbiturates Calibrators | Calibrators. Drug Specific | DLJ | 862.3200<br>Class II |
| COBAS INTEGRA Serum<br>Benzodiazepines (SBENZ) | Enzyme Immunoassay,<br>Benzodiazepines | JXM | 862.3170<br>Class II |
| Abuscreen ONLINE Serum<br>Benzodiazepines Calibrators | Calibrators. Drug Specific | DLJ | 862.3200<br>Class II |

### Table 1

### 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.

! 【

| Product Name | Predicate Product<br>Name | Date<br>Predicate<br>Cleared | Predicate<br>510(k)<br>Number |
|-------------------------------------------------------|-------------------------------------|------------------------------|-------------------------------|
| COBAS INTEGRA<br>Serum Barbiturates (SBARB) | Abbott ADX Barbiturates | 8/25/89 | K890690 |
| Abuscreen ONLINE Serum<br>Barbiturates Calibrators | Abbott ADX Barbiturates | 8/25/89 | K890690 |
| COBAS INTEGRA Serum<br>Benzodiazepines (SBENZ) | Abbott TDX Benzodiazepines<br>Serum | 11/29/88 | K883730 |
| Abuscreen ONLINE Serum<br>Benzodiazepines Calibrators | Abbott TDX Benzodiazepines<br>Serum | 11/29/88 | K883730 |

| able | 1 |
|------|---|
| ું જ | 2 |

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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 109 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); May 21, 1998 (K974695) and June 5, 1998 (K980996).

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 two additional COBAS Reagent Cassettes and their associated calibrator sets. These are: the COBAS INTEGRA Serum Barbiturates (SBARB) Reagent Cassette, the Abuscreen ONLINE Serum Barbiturates Calibrators, the COBAS INTEGRA Serum Benzodiazepines (SBENZ) Reagent Cassette, and the Abuscreen ONLINE Serum Benzodiazepines Calibrators,

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

Tables 3-4 outline the technological characteristics (methodologies) of the COBAS INTEGRA Reagents and their corresponding calibrators in comparison to those of legally marketed predicate products.

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

Tables 3-4 demonstrate the results of clinical and nonclinical studies performed using the COBAS INTEGRA Reagent Cassettes. 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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### COBAS INTEGRA Serum Barbiturates (SBARB)

The cassette COBAS INTEGRA Serum Barbiturates contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose.

### Abuscreen ONLINE Serum Barbiturates Calibrators

The Abuscreen ONLINE Serum Barbiturates Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Barbiturates on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of barbiturates in human specimens.

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# Table 3 - COBAS INTEGRA Serum Barbiturates (SBARB) and Abuscreen ONLINE Serum Barbiturates Calibrators

| COBAS INTEGRA Serum<br>Barbiturates and Abuscreen ONLINE<br>Serum Barbiturates Calibrators | | Abbott ADX Barbiturates<br>(cleared) K890690 | | | | |
|--------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------|------------------------|------------------|
| Intended Use | for the detection of barbiturates and their<br>metabolites in human serum or heparinized<br>plasma, intended for used in toxicological<br>screenings where the analytical result is used<br>in the management of barbiturate use or<br>overdose | | for the detection of various barbiturates<br>and metabolites in human serum or<br>plasma, measurements obtained are used<br>in the diagnosis and treatment of<br>barbiturates use or overdose, intended to<br>be used solely in toxicological screening<br>situations | | | |
| Methodology | fluorescence polarization | | fluorescence polarization | | | |
| Sample type | Serum and Plasma | | Serum and Plasma | | | |
| Reagents | R1: Antibody Reagent:<br>Anti-secobarbital polyclonal (sheep)<br>R2: Diluent: buffer with stabilizer<br>R3: Tracer: fluorecein-labeled secobarbital<br>derivative in buffer with stabilizer | | S: barbiturates serum antiserum (sheep)<br>P: pretreatment solution buffer with<br>surfactant and protein stabilizers<br>T: barbiturates serum fluorescein tracer in<br>buffer with surfactant and protein<br>stabilizers | | | |
| Controls | COBAS-FP TDM Multianalyte Controls<br>(K951595) [Level I and II] | | Trilevel serum barbiturates controls<br>contained in ADX kit | | | |
| Calibrators | Abuscreen ONLINE Serum Barbiturates<br>Calibrators | | Barbiturates Calibrators contained in ADX<br>kit | | | |
| Matrix: | human serum | | human serum | | | |
| Levels (µg/mL): | Cal 1: 0<br>Cal 2: 0.5<br>Cal 3: 1<br>Cal 4: 2<br>Cal 5: 4 | | A: 0.0<br>B: 2<br>C: 5<br>D: 10<br>E: 20<br>F: 40 | | | |
| Performance Characteristics: | | | | | | |
| Assay range | 0.03 - 4 µg/mL<br>0.03 - 80 µg/mL (with postdilution) | | 0.70 - 40 µg/mL | | | |
| Cutoff Conc. | 0.5 µg/mL | | 2.0 µg/mL | | | |
| Sensitivity | 0.03 µg/mL | | 0.07 µg/mL | | | |
| Precision:<br>Mean (µg/mL) | Level 1 | Level 2 | Level 3 | | | |
| | 0.5 | 1.1 | 1.9 | Level 1<br>2.70 | Level 2<br>7.07 | Level 3<br>26.27 |
| % CV (within-run) | 4.1 | 4.1 | 2.3 | 3.18 | 3.47 | 4.38 |
| % CV (total) | 5.0 | 4.2 | 2.9 | 4.00 | 3.92 | 4.73 |
| Accuracy:<br>(see package inserts<br>for more detail) | GC/MS | INTEGRA | FPIA | EIA | | |
| | +<br>37<br>10 | 35<br>12 | 24<br>23 | 13<br>34 | GC/MS<br>+<br>79<br>14 | ADX<br>69<br>123 |

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## COBAS INTEGRA Serum Benzodiazepines (SBENZ)

The cassette COBAS INTEGRA Serum Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of benzodiazepines and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of benzodiazepine use or overdose.

### Abuscreen ONLINE Serum Benzodiazepines Calibrators

The Abuscreen ONLINE Serum Benzodiazepines Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Benzodiazepines on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of benzodiazepines in human specimens.

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# Table 4 - COBAS INTEGRA Serum Benzodiazepines (SBENZ) and Abuscreen ONLINE Serum Benzodiazepines Calibrators

| | COBAS INTEGRA Serum | | | Abbott TDX Benzodiazepines | | | |
|-------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------|---------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------|---------|-------------------|
| | Benzodiazepines and Abuscreen | | | | | | |
| | | ONLINE Serum Benzodiazepines | | | | | (cleared) K890690 |
| | | Calibrators | | | | | |
| Intended Use | for the detection of benzodiazepines and<br>their metabolites in human serum or<br>heparinized plasma, intended for used in<br>toxicological screenings where the analytical<br>result is used in the management of<br>benzodiazepine use or overdose | | | for the detection of various<br>benzodiazepines and metabolites in human<br>serum or plasma, measurements obtained<br>are used in the diagnosis and treatment of<br>benzodiazepine use or overdose, intended<br>to be used solely in toxicological screening<br>situations | | | |
| Methodology | fluorescence polarization | | | fluorescence polarization | | | |
| Sample type | Serum and Plasma | | | Serum and Plasma | | | |
| Reagents | R1: Antibody Reagent:<br>Anti-benzodiazepine polyclonal (sheep)<br>R2: Diluent: buffer with stabilizer<br>R3: Tracer: fluorecein-labeled<br>benzodiazepine derivative in buffer with<br>stabilizer | | | W: wash solution<br>S: barbiturates serum antiserum (sheep)<br>P: pretreatment solution buffer with<br>surfactant and protein stabilizers<br>T: barbiturates serum fluorescein tracer in<br>buffer with surfactant and protein<br>stabilizers | | | |
| Calibrators | Abuscreen ONLINE Serum Benzodiazepines<br>Calibrators | | | Benzodiazepines Calibrators contained in<br>TDX kit | | | |
| Matrix: | human serum | | | human serum | | | |
| Levels (ng/mL): | Cal 1: 0<br>Cal 2: 25<br>Cal 3: 50<br>Cal 4: 100<br>Cal 5: 200 | | | A: 0.0<br>B: 50<br>C: 100<br>D: 200<br>E: 400<br>F: 1000 | | | |
| Performance Characteristics: | | | | | | | |
| Assay range | 3 - 200 ng/mL<br>3 - 2000 ng/mL (with postdilution) | | | 12 - 1000 ng/mL | | | |
| Cutoff Conc. | 3 ng/mL | | | 12.0 ng/mL | | | |
| Sensitivity | 3 ng/mL | | | 12.0 ng/mL | | | |
| Precision: | Level 1 | Level 2 | Level 3 | Level 1 | Level 2 | Level 3 | |
| Mean (µg/mL) | 25.1 | 34.5 | 128.9 | 74.88 | 302.82 | 687.40 | |
| % CV (within-run) | 5.5 | 1.9 | 1.1 | 3.19 | 1.86 | 3.41 | |
| % CV (total) | 5.4 | 2.7 | 2.0 | 4.98 | 3.73 | 5.98 | |
| Accuracy:<br>(see package inserts<br>for more detail) | GC/MS<br>+<br>- | INTEGRA | FPIA<br>EIA | GC/ES<br>+<br>- | TDX | | |
| | 46<br>28 | 46<br>20 | 41<br>16<br>22<br>8 | 76<br>38 | 76<br>83 | | |

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Image /page/8/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle. In the center of the circle is an abstract symbol that resembles a stylized human figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 1 8 1998

Rita Smith Senior Regulatory Affairs Associate Roche Diagnostics Systems, Inc. 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

Re : K982551 Roche COBAS® INTEGRA Serum and Abuscreen ONLINE Serum Barbiturates & Benzodiazepines Cassettes and Calibrators Regulatory Class: II Product Code: DIS, JXM, DLJ Dated: July 20, 1998 Received: July 22, 1998

Dear Ms. Smith: ... ...

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, Druq, 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, labelinq, and prohibitions aqainst 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. ਬੈ substantially equivalent determination assumes compliance with 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 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 requlations.

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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 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 _ 2 _

510(k) Number (if known) K 982551

Roche COBAS INTEGRA Serum Barbiturates Cassette (SBARB) Device Name: Art. No. 07 6670 4

> Abusceen ONLINE Serum Barbiturates Calibrators Art. No. 07 6672 0

Roche COBAS INTEGRA Serum Benzodiazepines Cassette (SBENZ) Art. No. 07 6669 0

Abuscreen ONLINE Serum Benzodiazepines Calibrators Art. No. 07 6671 2

Indications for Use:

ા :

The cassette COBAS INTEGRA Serum Barbiturates contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose.

The Abuscreen ONLINE Serum Barbiturates Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Barbiturates on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of barbiturates in human specimens.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use (Per 21 CFR 801.109) |
|---------------------------------------|
|---------------------------------------|

OR

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

(Division Sign-Off)

Division of Clinical Laboratory Devices

| 510(k) Number | K982551 |
|---------------|---------|
|---------------|---------|

າ ໄປ ເ

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Page 2 of of 2 _ _

Indications for Use (continued):

The cassette COBAS INTEGRA Serum Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of benzodiazepines and their metabolites in human serum or heparinized plasma. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of benzodiazepine use or overdose.

The Abuscreen ONLINE Serum Benzodiazepines Calibrators are designed for calibration of the cassette COBAS INTEGRA Serum Benzodiazepines on the COBAS INTEGRA chemistry systems. The calibrators are used in the determination of values in the measurement of benzodiazepines in human specimens.