COBRAS INTEGRA ACID PROSTATIC PHOSPHATASE (ACPP) COBAD INTEGRA BENZODIAZEPINES WITH B-GLUCURONIDASE (BNZGL)

K974695 · Roche Diagnostic Systems, Inc. · CKB · May 21, 1998 · Clinical Chemistry

Device Facts

• Record ID: K974695
• Device Name: COBRAS INTEGRA ACID PROSTATIC PHOSPHATASE (ACPP) COBAD INTEGRA BENZODIAZEPINES WITH B-GLUCURONIDASE (BNZGL)
• Applicant: Roche Diagnostic Systems, Inc.
• Product Code: CKB · Clinical Chemistry
• Decision Date: May 21, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1020
• Device Class: Class 2

Intended Use

The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of total and prostatic acid phosphatase in serum. The cassette Roche COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase.

Device Story

COBAS INTEGRA Reagent Cassettes are used with the COBAS INTEGRA Analyzer for in vitro diagnostic testing. The analyzer processes serum or urine samples using absorbance, fluorescence polarization, and ion-selective electrodes. For ACPP, the system measures catalytic activity of acid phosphatase. For Benzodiazepines, the system uses an automated ß-glucuronidase pre-treatment step to enhance metabolite detection via kinetic interaction of microparticles in solution. The analyzer features robotic sample handling, barcode identification, and refrigerated reagent storage. Results are provided to clinicians to assist in diagnostic decision-making. The system is designed for high-throughput clinical laboratory environments, operated by trained laboratory personnel.

Clinical Evidence

Bench testing only. Performance evaluated via precision (within-run and total CVs), assay range, and accuracy (correlation with GC/MS for benzodiazepines or predicate methods for ACPP). ACPP accuracy (n=260-264) showed correlation coefficients of 0.978-0.996. Benzodiazepine accuracy (n=50 positive samples) showed 100% agreement with GC/MS.

Technological Characteristics

Reagent cassettes for use on COBAS INTEGRA analyzer. ACPP: Hillmann method using naphthylphosphate and tartrate inhibition. Benzodiazepines: Kinetic interaction of microparticles (KIMS) with automated ß-glucuronidase sample pre-treatment. System utilizes absorbance, fluorescence polarization, and ion-selective electrodes. Barcode-enabled reagent identification and calibration.

Indications for Use

Indicated for quantitative determination of total and prostatic acid phosphatase in serum and semi-quantitative detection of benzodiazepines in human urine. Intended for clinical laboratory use.

Regulatory Classification

Identification

An acid phosphatase (total or prostatic) test system is a device intended to measure the activity of the acid phosphatase enzyme in plasma and serum.

Special Controls

*Classification.* Class II (special controls). 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.

Predicate Devices

• Roche Reagent for Acid Phosphatase (K831834)
• COBAS INTEGRA Benzodiazepines (K951595)

Submission Summary (Full Text)

{0}------------------------------------------------

K974695

MAY 2 | 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:________________________________________________________________________________________________________________________________________________

#### 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 December 12, 1997

James W. Haynes Contact: Regulatory Affairs Associate Phone: [phone] [phone] Fax:

{1}------------------------------------------------

#### Device Name: II.

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

| <i>Table</i> | <i>1</i> |
|--------------|----------|
|--------------|----------|

| Proprietary Name | Classification Name | Product Code | Regulation Number |
|-------------------------------------------------------------------|------------------------------------------------------|--------------|-------------------|
| COBAS INTEGRA Acid/ Prostatic<br>Phosphatase (ACPP) | Acid phosphatase (total or<br>prostatic) test system | CKB | 862.1020 |
| COBAS INTEGRA<br>Benzodiazepines with β-<br>glucuronidase (BNZGL) | Benzodiazepine test system | JXM | 862.3170 |

{2}------------------------------------------------

### 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.

| able<br>C<br>C | 1 |
|----------------|---|
|----------------|---|

| Product Name | Predicate Product Name | K number | Date of substantial<br>equivalence |
|---------------------------------------------------------------|------------------------------------------------------------------------------|----------|------------------------------------|
| COBAS INTEGRA Acid/ Prostatic<br>Phosphatase (ACPP) | Roche Reagent for Acid Phosphatase<br>(OEM from Reagents Applications, Inc.) | K831834 | 8/26/83 |
| COBAS INTEGRA Benzodiazepines<br>with β-glucuronidase (BNZGL) | COBAS INTEGRA Benzodiazepines<br>(BENZ) | K951595 | 9/8/95 |

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

The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. 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 107 other 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), and August 12, 1997 (K972250). COBAS INTEGRA Benzodiazepines was previously cleared on September 8, 1995.

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).

{3}------------------------------------------------

Through this submission, it is the intention of Roche to gain clearance for one additional COBAS Reagent Cassette and one optional application for a previously approved COBAS Reagent These are the COBAS INTEGRA Acid / Prostatic Phosphatase and the COBAS Cassette. INTEGRA Benzodiazepines with ß-glucuronidase, respectively.

### COBAS INTEGRA Acid / Prostatic Phosphatase:

The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of the total and prostatic acid phosphatase in serum.

### COBAS INTEGRA Benzodiazepines with ß-glucuronidase:

The cassette COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase. B-glucuronidase is added automatically as a diluent for sample pre-treatment enabling enhanced detection of metabolites of certain low-dose, short-acting benzodiazepines.

The intended use, clinical utility and methodology of each reagent cassette are further described in the test specific COBAS INTEGRA Method Manual sheets, contained in the test specific sections of this submission.

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

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

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

{4}------------------------------------------------

| | COBAS INTEGRA Acid/<br>Prostatic Phosphatase | Roche Reagent for Acid<br>Phosphatase |
|---------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|
| Intended Use | quantitative determination of both<br>total and prostatic acid phosphatase | quantitative determination of both<br>total and prostatic acid phosphatase |
| Methodology | Hillmann method with<br>naphthylphosphate.<br>Inhibition of prostatic acid<br>phosphatase by tartrate | Hillmann method with<br>naphthylphosphate.<br>Inhibition of prostatic acid<br>phosphatase by tartrate |
| Sample type | Serum | Serum |
| Calibrator | Fixed calibration factor<br>-no calibrator required | Fixed calibration factor<br>-no calibrator required |
| Controls | Roche Control Serum N and P<br>(human) | Not specified in labeling |
| Reagent<br>(active ingredients) | R1: Citrate (liquid)<br>1,5 Pentanediol<br>R2: Tartrate (liquid)<br>R3: 1-napthylphosphate<br>(granulate) | 1. α-naphthylphosphate (granulate)<br>2. L-Tartrate / Sodium citrate<br>(granulate)<br>3. Acetate Buffer |
| Performance Characteristics: Total Acid Phosphatase | | |
| Assay range | 0 - 100 U/L | Linear to 40 U/L |
| Sensitivity | $8.5 x 10^4$ △A/min per U/L of total<br>acid phosphatase | Not specified in labeling |
| Precision: | Level 1              Level 2 | Level 1              Level 2 |
| Mean | 4 U/L              11 U/L | 3.1 U/L              22.6 U/L |
| CV (within-run) | 4.5 %              2.5 % | 2.7 %              0.51 % |
| CV (total) | 5.7 %              4.6 % | NA              NA |
| Accuracy: | | |
| Sample size (n) | 260 | 118 |
| Corr. Coefficient | 0.978 | 0.990 |
| Linear regression | $1.54x$ - 0.1 U/L | 1.02 + 0.43 U/L |
| Performance Characteristics: Prostatic Acid Phosphatase | | |
| Precision: | Level 1              Level 2 | Not specified in labeling |
| Mean (U/L) | 1 U/L              3 U/L | |
| CV (within-run) | 23 %              9.4 % | |
| CV (total) | 25 %              15 % | |
| Accuracy: | | |
| Sample size (n) | 264 | 118 |
| Corr. Coefficient | 0.996 | 0.997 |
| Linear regression | $1.83x$ + 0.5 U/L | 1.00 - 0.07 U/L |

### Table 3 - COBAS INTEGRA Acid/ Prostatic Phosphatase

{5}------------------------------------------------

| | COBAS INTEGRA<br>Benzodiazepines with β-<br>glucuronidase | | | | COBAS INTEGRA<br>Benzodiazepines | | | | |
|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----|-------|-----|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|---------|---------|---------|
| Methodology | Kinetic interaction of microparticles<br>in a solution | | | | Kinetic interaction of microparticles<br>in a solution | | | | |
| Sample type | Urine | | | | Urine | | | | |
| Calibrator | Abuscreen OnLine Calibration Pack | | | | Abuscreen OnLine Calibration Pack | | | | |
| Controls | Abuscreen OnLine 1.5x Calibrator /<br>Positive Control<br>Abuscreen OnLine Negative<br>Control | | | | Abuscreen OnLine 1.5x Calibrator /<br>Positive Control<br>Abuscreen OnLine Negative Control | | | | |
| Cutoff | 100 ng/mL | | | | 100, 200 and 300 ng/mL | | | | |
| Reagent<br>(active ingredients) | R1: Sample Diluent<br>R2: Antibody reagent:<br>Benzodiazepines polyclonal<br>antibody (sheep) in buffer<br>R3: Microparticle reagent:<br>conjugated benzodiazepine<br>derivative microparticles in<br>buffer<br>β-glucuronidase (not provided) | | | | R1: Sample Diluent<br>R2: Antibody reagent:<br>Benzodiazepines polyclonal<br>antibody (sheep) in buffer<br>R3: Microparticle reagent:<br>conjugated benzodiazepine<br>derivative microparticles in<br>buffer | | | | |
| <b>Performance Characteristics:</b> | | | | | | | | | |
| Assay range | 0 - 200 ng/mL | | | | 0 - 300 ng/mL | | | | |
| Precision: | L1 | L2 | L3 | L4 | L5 | Level 1 | Level 2 | Level 3 | Level 4 |
| Mean (ng/mL) | 52 | 86 | 108 | 139 | 171 | 49 | 80 | 101 | 126 |
| % CV (within-run) | 5.1 | 3.0 | 5.2 | 4.4 | 3.4 | 7.1 | 4.3 | 4.4 | 4.4 |
| Sensitivity | 5.0 ng/mL of nordiazepam at > 95% confidence | | | | | 5.0 ng/mL of nordiazepam at > 95% confidence | | | |
| Accuracy<br>Positive Samples | INTEGRA<br>with β-gluc. | | GC/MS | | INTEGRA<br>(100 ng/mL cutoff) | | GC/MS | | |
| | + | - | + | - | + | - | + | - | |
| | 50 | 0 | 50 | 0 | 50 | 0 | 50 | 0 | |

## Table 4 - COBAS INTEGRA Benzodiazepines with ß-glucuronidase

: 、

{6}------------------------------------------------

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 three stripes forming its body and wings. The eagle is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 21 1996

Mr. James W. Haynes · Requlatory Affairs Associate Roche Diagnostic Systems, Inc. 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

Re: K974695/S001 COBAS INTEGRA Acid/Prostatic Phosphatase (ACPP)/COBAS INTEGRA Benzodiazepines with ß-Glucuronidase (BNZGL) Regulatory Class: II Product Code: CKB, JXM March 18, 1998 Dated: Received: March 19, 1998

Dear Mr. Haynes:

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 requlations 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 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 Read Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory 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.

{7}------------------------------------------------

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 Gutman

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

{8}------------------------------------------------

Page 1 _of _1

9741,95 510(k) Number (if known)

Device Name:

Roche COBAS INTEGRA Acid / Prostatic Phosphatase Reagent Cassette

Roche COBAS INTEGRA Benzodiazepines with β-glucuronidase

Indications for Use:

ﺐ ﺍﻟ

The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of total and prostatic acid phosphatase in serum.

The cassette Roche COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division: Medical Laboratory Devices
510(k) Number. K97495

Prescription Use (Per 21 CFR 801.109)

OR

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