ROCHE COBAS INTEGRA ALKALINE PHOSPHATASE IFCC LIQUID REAGENT CASSETTE, ROCHE COBAS INTEGRA PANCREATIC A-AMYLASE EPS REAE

K981897 · Roche Diagnostic Systems, Inc. · CJE · Aug 26, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981897
• Device Name: ROCHE COBAS INTEGRA ALKALINE PHOSPHATASE IFCC LIQUID REAGENT CASSETTE, ROCHE COBAS INTEGRA PANCREATIC A-AMYLASE EPS REAE
• Applicant: Roche Diagnostic Systems, Inc.
• Product Code: CJE · Clinical Chemistry
• Decision Date: Aug 26, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1050
• Device Class: Class 2

Intended Use

The cassette COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6) contain an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of alkaline phosphatase in serum and plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. The cassette COBAS INTEGRA a-Amylase EPS Pancreatic (AMY-P / AMYUP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of pancreatic or-amylase in serum, plasma, and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas). The cassette COBAS INTEGRA C-reactive Protein (Latex), (CRPLX) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human C-reactive protein in serum and plasma..... Measurements of C-reactive protein aids in evaluation of the amount of injury to

Device Story

COBAS INTEGRA Reagent Cassettes are in vitro diagnostic consumables used with the COBAS INTEGRA Analyzer. The system accepts serum, plasma, or urine samples. The analyzer employs absorbance, fluorescence polarization, and ion-selective electrode measuring principles to perform clinical chemistry, immunology, and therapeutic drug monitoring. Barcode readers identify samples and reagent cassettes. The system automates sample processing, reagent handling, and measurement. Results are provided to clinicians to assist in the diagnosis and treatment of liver, bone, parathyroid, intestinal diseases, and pancreatitis, or to evaluate tissue injury. The device is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Performance evaluated via precision (within-run and total CVs), assay range, sensitivity, and accuracy (correlation coefficients and linear regression) compared to predicate devices. Sample sizes ranged from 106 to 252. Correlation coefficients (r) were 0.993–0.999, indicating high equivalence to predicate methods.

Technological Characteristics

Reagent cassettes for automated clinical chemistry analyzer. Methodologies: enzymatic colorimetric (ALP, Amylase) and particle-enhanced immunoturbidimetric (CRP). Reagents include enzymes, monoclonal antibodies (mouse), and latex particles. System uses absorbance, fluorescence polarization, and ion-selective electrodes. On-board storage at 2-8°C. Barcode-identified.

Indications for Use

Indicated for quantitative determination of alkaline phosphatase (serum/plasma) for liver, bone, parathyroid, and intestinal disease diagnosis; pancreatic alpha-amylase (serum, plasma, urine) for pancreatitis diagnosis; and C-reactive protein (serum/plasma) for evaluation of tissue injury.

Regulatory Classification

Identification

An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Predicate Devices

• COBAS INTEGRA Alkaline Phosphatase IFCC (ALP) (K951595)
• Boehringer Mannheim/ Hitachi Pancreatic α-Amylase liquid (K895880)
• COBAS INTEGRA C-Reactive Protein (CRP) (K951595)

Submission Summary (Full Text)

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

Image /page/0/Picture/1 description: The image shows the Roche logo. The logo consists of the word "Roche" in bold, sans-serif font, enclosed within a hexagon. The hexagon is outlined in black, and the word "Roche" is also in black.

# 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: k981897

#### 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 May 29, 1998

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

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

#### 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 Name | Product Code | CFR Number and Regulatory Class |
|----------------------------------------------------------------------|---------------------------------------------------------|--------------|---------------------------------|
| COBAS INTEGRA<br>Alkaline Phosphatase IFCC liquid<br>(ALPL2) (ALPL6) | Nitrophenylphosphate, alkaline phosphatase or isoenzyme | CJE | 862.1050<br>Class II |
| COBAS INTEGRA αAmylase EPS<br>Pancreatic<br>(AMY-P / AMYUP) | Catalytic methods, Amylase | JFJ | 862.1070<br>Class II |
| COBAS INTEGRA C-Reactive<br>Protein (Latex) (CRPLX) | C-reactive protein Immunological test system | DCN | 862.5270<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>Alkaline Phosphatase IFCC liquid<br>(ALPL2) (ALPL6) | COBAS INTEGRA Alkaline<br>Phosphatase IFCC (ALP) | 9/8/95 | K951595 |
| COBAS INTEGRA αAmylase EPS<br>Pancreatic<br>(AMY-P / AMYUP) | Boehringer Mannheim/ Hitachi<br>Pancreatic<br>α-Amylase liquid | 12/19/89 | K895880 |
| COBAS INTEGRA C-Reactive<br>Protein (Latex) (CRPLX) | COBAS INTEGRA C-Reactive<br>Protein (CRP) | 9/8/95 | K951595 |

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

#### 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 three additional COBAS Reagent Cassettes. These are the COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6), the COBAS INTEGRA a-Amylase EPS Pancreatic (AMY-P / AMYUP), and the COBAS INTEGRA C-Reactive Protein (Latex), (CRPLX).

Note: The Alkaline Phosphatase reagent cassette in two sizes: the 200 test cassette (ALPL2) and the 600 test cassette (ALPL6).

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

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

Tables 3-5 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 3-5 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 Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6)

The cassettes COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6) contain an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of alkaline phosphatase in serum and plasma.

| | COBAS INTEGRA Alkaline<br>Phosphatase IFCC liquid (ALPL2<br>and ALPL6)<br>(proposed) | | COBAS INTEGRA Alkaline<br>Phosphatase IFCC (ALP)<br>(cleared) K951595 | |
|------------------------------|--------------------------------------------------------------------------------------------------------|---------|--------------------------------------------------------------------------------------------------------|---------|
| Intended Use | quantitative determination of the catalytic<br>activity of alkaline phosphatase in serum<br>and plasma | | quantitative determination of the<br>catalytic activity of alkaline phosphatase<br>in serum and plasma | |
| Methodology | enzymatic colorimetric using<br>4-Nitrophenylphosphate (IFCC) | | enzymatic colorimetric using<br>4-Nitrophenylphosphate (IFCC) | |
| Sample type | Serum and Plasma | | Serum and Plasma | |
| Calibrator | Roche Calibrator (human)<br>(K942706) | | Roche Calibrator (human)<br>(K942706) | |
| Controls | Roche Control Serum N and P (human)<br>(K972214) | | Roche Control Serum N and P (human)<br>(K972214) | |
| Reagents | AMP in vial B (liquid)<br>4-Nitrophenylphosphate in vial C (liquid) | | AMP in vial A and B (liquid)<br>4-Nitrophenylphosphate in vial C<br>(granulate) | |
| Performance Characteristics: | | | | |
| Assay range | 0-1500 U/L | | 0 - 2300 U/L | |
| Sensitivity | 3.7 x 10-4 ΔA/min per U/L of ALP | | 4.0 x 10-4 ΔA/min per U/L of ALP | |
| Precision: | Level 1 | Level 2 | Level 1 | Level 2 |
| Mean (U/L) | 45 | 236 | 85 | 451 |
| % CV (within-run) | 2.3 | 0.55 | 1.2 | 1.3 |
| % CV (total) | 2.7 | 1.3 | 1.6 | 2.0 |
| Accuracy: | | | | |
| Sample size (n) | 252 | | 234 | |
| Corr. Coefficient (r) | 0.999 | | 0.999 | |
| Linear regression | 1.00x + 0.15 U/L | | 1.06x - 6 U/L | |

## Table 3 - COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6)

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

## COBAS INTEGRA α-Amylase EPS Pancreatic (AMY-P / AMYUP):

The cassette Roche COBAS INTEGRA α-Amylase EPS Pancreatic (AMY-P / AMYUP) contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the quantitative determination of the catalytic activity of pancreatic cu-amylase in serum, plasma, and urine.

| | | COBAS INTEGRA α-Amylase<br>EPS Pancreatic<br>(AMY-P / AMYUP)<br>(proposed) | Boehringer Mannheim/Hitachi<br>Pancreatic A-Amylase<br>liquid reagent<br>(cleared) K895880 | |
|------------------------------|------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------|---------|
| Methodology | Enzymatic colorimetric using substrate<br>4,6-ethylidene-p-nitrophenyl-α-D-<br>malto-heptaoside | | Enzymatic colorimetric using substrate<br>4,6-ethylidene-p-nitrophenyl-α-D-malto-<br>heptaoside | |
| Sample type | Serum, plasma and urine | | Serum, plasma, and urine | |
| Calibrator | Roche Calibrator (human)<br>(K942706) | | Calibrator for automated systems | |
| Controls | Roche Control Serum N and P (human)<br>(K972214) | | Precinorm® U, Precinorm® E,<br>Precipath® U, Precipath® E | |
| Reagents | -enzyme, two monoclonal antibodies<br>(mouse)<br>in vial A (liquid)<br>-substrate in vial C (liquid) | | R1 enzyme, two monoclonal antibodies<br>(mouse)<br>R2 substrate | |
| Performance Characteristics: | | | | |
| Assay range | Serum/Plasma and Urine:<br>0 - 1500 U/L | | Serum/Plasma and Urine:<br>0 - 1500 U/L | |
| Sensitivity | Serum/Plasma and Urine:<br>$2.8 x 10^{-4}$ ΔA/min per U/L of pancreatic<br>α-amylase | | Serum/Plasma and Urine:<br>3 U/L | |
| Precision (Serum): | Level 1 | Level 2 | Level 1 | Level 2 |
| Mean (U/L) | 32 | 184 | 35.7 | 53.9 |
| % CV (within-run) | 1.2 | 0.91 | 0.9 | 0.5 |
| % CV (total) | 1.7 | 1.6 | 1.5 | 1.9 |
| Precision (Urine): | Level 1 | Level 2 | Level 1 | Level 2 |
| Mean (U/L) | 59 | 180 | 31.7 | 98.4 |
| % CV (within-run) | 1.094 | 0.8796 | 0.8 | 0.4 |
| % CV (total) | 1.2 | 1.1 | 1.7 | 0.8 |
| Accuracy (Serum): | | | | |
| Sample size (n) | 246 | | 51 | |
| Corr. Coefficient (r) | 0.999 | | 1.000 | |
| Linear regression | 1.03x + 0.3 U/L | | 1.11x + 0.2 | |
| Accuracy (Urine): | | | | |
| Sample size (n) | 106 | | 51 | |
| Corr. Coefficient (r) | 0.999 | | 1.000 | |
| Linear regression | 1.00x + 1.4 U/L | | 1.18x + 0.4 | |

### Table 4 - COBAS INTEGRA α-Amylase EPS Pancreatic (AMY-P/AMYUP)

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

### COBAS INTEGRA C-Reactive Protein (Latex) (CRPLX)

The cassette C-reactive Protein (Latex), (CRPLX) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human C-reactive protein in serum and plasma.

| | COBAS INTEGRA C-Reactive<br>Protein (Latex) (CRPLX)<br>(proposed) | COBAS INTEGRA C-Reactive<br>Protein (CRP)<br>(cleared) K951595 |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|
| Intended Use | quantitative immunological determination<br>of human C-reactive protein in serum and plasma | quantitative immunological<br>determination of human C-reactive<br>protein in serum and plasma |
| Methodology | Particle enhanced immunoturbidimetric | Immunoturbidimetric |
| Sample type | Serum and Plasma | Serum and Plasma |
| Calibrator | CRP T Standard (K951595) | CRP T Standard (K951595) |
| Controls | CRP T Control (K954992)<br>CRP T N Control (Exempt) | CRP T Control (K954992) |
| Reagents | R1 BSA and immunoglobulins (mouse),<br>vials A & B<br>R2 Latex particles coated with anti-CRP<br>(mouse), vial C (liquid) | R1 Accelerator, vials A & B<br>R2 Anti-CRP T antiserum (sheep). vial<br>C |
| Performance Characteristics: | | |
| Assay range | 0 - 160 mg/L | 5 - 160 mg/L |
| Sensitivity | 0.25 mg/L | 5 mg/L |
| Precision: | Level 1 | Level 2 |
| Mean (mg/L) | 6.2 | 142 |
| | Level 1 | Level 2 |
| | 53 | 114 |
| % CV (within-run) | 1.8 | 1.5 |
| | 2.0 | 2.4 |
| % CV (total) | 2.9 | 2.7 |
| | 2.5 | 2.4 |
| Accuracy: | | |
| Sample size (n) | 244 | 234 |
| Corr. Coefficient (r) | 0.993 | 0.999 |
| Linear regression | $1.07x - 6.2 mg/L$ | $1.10x + 5.5 mg/L$ |

## Table 5 - COBAS INTEGRA C-Reactive Protein (Latex) (CRPLX)

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

Image /page/7/Picture/1 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 an abstract symbol that resembles a stylized caduceus or a representation of the human form.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 26 1998

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

Re : K981897 Roche COBAS® INTEGRA Reagent Cassettes Regulatory Class: II Product Code: CJE, JFJ, DCK Dated: August 13, 1998 Received: August 17, 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, 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. ਸੇ 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 requlation 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 requlations.

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

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-----------

{9}------------------------------------------------

Page 1 of 1 .

510(k) Number (if known): K981897

Roche COBAS INTEGRA Alkaline Phosphatase liguid Reagent Cassette Device Name: (ALPL2) (ALPL6) Art. No. 07 6673 9, 07 5996 1

> Roche COBAS INTEGRA Pancreatic a-Amylase EPS Reagent Cassette (AMY-P / AMYUP) Art. No. 07 6662 3

> Roche COBAS INTEGRA C-Reactive Protein (Latex) Reagent Cassette (CRPLX) Art. No. 07 6493 0

Indications for Use:

The cassette COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6) contain an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of alkaline phosphatase in serum and plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The cassette COBAS INTEGRA a-Amylase EPS Pancreatic (AMY-P / AMYUP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of pancreatic or-amylase in serum, plasma, and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas).

The cassette COBAS INTEGRA C-reactive Protein (Latex), (CRPLX) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human C-reactive protein in serum and plasma..... Measurements of C-reactive protein aids in evaluation of the amount of injury to குக்குடி (ff)

Division of Clinical Laboratory Devices

510(k) Number __

(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 of Clinical Laboratory Devices | |
| 510(k) Number | K981897 |

| Prescription Use<br>(Per 21 CFR 801.109) | OR | Over-The-Counter Use<br>(Optional Format 1-2-96) |
|------------------------------------------|----|--------------------------------------------------|
|------------------------------------------|----|--------------------------------------------------|