COBAS INTEGRA REAGENT CASSETTES

K982382 · Roche Diagnostic Systems, Inc. · CFN · Sep 28, 1998 · Immunology

Device Facts

• Record ID: K982382
• Device Name: COBAS INTEGRA REAGENT CASSETTES
• Applicant: Roche Diagnostic Systems, Inc.
• Product Code: CFN · Immunology
• Decision Date: Sep 28, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5510
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The cassette COBAS INTEGRA x-1-Antitrypsin (AAT) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human x-1-antitrypsin in serum and plasma. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, a-1-antitrypsin deficiency has been associated with pulmonary emphysema. The cassette COBAS INTEGRA Immunoglobulin A (IGA/IGAP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin A in serum and plasma. addition to the standard application (IGA), the sensitive application (IGAP) is designed for the quantitative determination of low IgA concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The cassette COBAS INTEGRA Immunoglobulin M (IGM/IGMP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin M in serum and plasma. In addition to the standard application (IGM), the sensitive application (IGMP) is designed for the quantitative determination of low IgM concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The cassette COBAS INTEGRA Immunoglobulin G (Turbidimetric) (IGGT/IGGTC) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin G in serum, plasma (IGGT) and cerebrospinal fluid (IGGTC). Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Device Story

COBAS INTEGRA reagent cassettes are used with the COBAS INTEGRA 700 analyzer for automated in vitro diagnostic testing. The system accepts serum, plasma, or CSF samples. The analyzer uses absorbance, fluorescence polarization, and ion-selective electrodes to perform quantitative immunological assays. The system features robotic sample handling, random access, and barcode-based identification of reagents and samples. Reagents are stored on-board at 2-8°C. The analyzer processes up to 600 tests per hour. Healthcare providers use the quantitative results to aid in the diagnosis of liver disease, pulmonary emphysema, and immune system disorders. The system streamlines laboratory workflow through automation and integrated reagent management.

Clinical Evidence

Bench testing only. Performance evaluated via method comparison studies against predicate devices. Sample sizes ranged from 288 to 584. Results showed high correlation coefficients (r = 0.994 to 0.995) and linear regression slopes near 1.0. Precision studies reported total CVs between 1.2% and 3.2%.

Technological Characteristics

In vitro diagnostic reagent system for use on COBAS INTEGRA 700 analyzer. Methodology: Immunological/turbidimetric. Reagents provided in compact, preparation-free cassettes with barcode labels. Connectivity: Integrated system with automated sample/reagent handling. Storage: On-board refrigeration (2-8°C).

Indications for Use

Indicated for quantitative immunological determination of alpha-1-antitrypsin, IgA, IgM, and IgG in serum, plasma, and cerebrospinal fluid (IgG only). Aids in diagnosis of liver cirrhosis, pulmonary emphysema, and abnormal protein metabolism/immune deficiency. Includes sensitive applications for low-concentration samples (e.g., pediatric).

Regulatory Classification

Identification

An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Predicate Devices

• Boehringer Mannheim α-1-Antitrypsin Reagent (K972640)
• Boehringer Mannheim Immunoglobulin A Reagent (K955907)
• Boehringer Mannheim Immunoglobulin M Reagent (K955908)
• Boehringer Mannheim Immunoglobulin G Reagent (K800119)
• Behring Diagnostics Immunoglobulin G Reagent (K800119)

Submission Summary (Full Text)

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

Image /page/0/Picture/0 description: The image shows the word "Roche" written in black font inside of a hexagon. The hexagon is also black. The word "Roche" is centered inside of the hexagon.

SEP 2 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: 4982387-

#### 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 7, 1998

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

Branchburg Township 1080 U.S. Highway 202 t

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

Roche Diagnostic Systems, Inc. Somerville, New Jersey 08876 July 1998

#### 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>α-1-Antitrypsin Reagent Cassette<br>(AAT) | α-1-antitrypsin, antigen,<br>antiserum, control | DEM | 866.5130<br>Class II |
| Roche COBAS INTEGRA<br>Immunoglobulin A Reagent Cassette nephelometric methods<br>(IGA/IGAP) | Immunoglobulins. (G,A,M) | CFN | 866.5510<br>Class II |
| Roche COBAS INTEGRA<br>Immunoglobulin M Reagent Cassette nephelometric methods<br>(IGM/IGMP) | Immunoglobulins. (G,A,M) | CFN | 866.5510<br>Class II |
| Roche COBAS INTEGRA<br>Immunoglobulin G Reagent Cassette nephelometric methods<br>(IGGT/IGGTC) | Immunoglobulins, (G,A,M) | CFN | 866.5510<br>Class II |

## Table I

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

#### Identification of the legally marketed device to which the 510(k) sponsor claims III. 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>α-1-Antitrypsin Reagent Cassette<br>(AAT) | Boehringer Mannheim α-1-<br>Antitrypsin Reagent | 1/9/98 | K972640 |
| Roche COBAS INTEGRA<br>Immunoglobulin A Reagent Cassette<br>(IGA/IGAP) | Boehringer Mannheim<br>Immunoglobulin A Reagent | 2/9/96 | K955907 |
| Roche COBAS INTEGRA<br>Immunoglobulin M Reagent Cassette<br>(IGM/IGMP) | Boehringer Mannheim<br>Immunoglobulin M Reagent | 2/9/96 | K955908 |
| Roche COBAS INTEGRA<br>Immunoglobulin G Reagent Cassette<br>(IGGT/IGGTC) | Boehringer Mannheim<br>Immunoglobulin G Reagent and<br>Behring Diagnostics<br>Immunoglobulin G Reagent | 2/5/80 | K800119 |

## Table 2

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

Roche Diagnostic Systems, Inc. Somerville, New Jersey 08876 July 1998

#### 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, 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 modifications to four currently marketed reagent cassettes: Roche COBAS INTEGRA x-1-Antitrypsin Reagent Cassette (AAT); Roche COBAS INTEGRA Immunoglobulin A Reagent Cassette (IGA/IGAP); Roche COBAS INTEGRA Immunoglobulin M Reagent Cassette (IGM/IGMP); and Roche COBAS INTEGRA Immunoglobulin G Reagent Cassette (IGGT/IGGTC).

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

Tables 3-7 outline the technological characteristics (methodologies) of the COBAS INTEGRA Reagents in comparison to those of legally marketed predicate products.

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

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

Tables 3-7 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.

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

## COBAS INTEGRA α-1-Antitrypsin (AAT)

The cassette COBAS INTEGRA cx-1-Antitrypsin (AAT) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human a-1-antitrypsin in serum and plasma. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, a-1-antitrypsin deficiency has been associated with pulmonary emphysema.

| | COBAS INTEGRA<br>α-1-Antitrypsin<br>(AAT)<br>(modified) | COBAS INTEGRA<br>α-1-Antitrypsin<br>(AAT)<br>(cleared) K954992 | BM<br>Tina-Quant<br>α-1-antitrypsin<br>(K972640) |
|------------------------------|---------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|---------------------------------------------------------------------------------------|
| Intended Use | quantitative immunological<br>determination of α-1-antitrypsin in<br>serum and plasma | quantitative immunological<br>determination of α-1-<br>antitrypsin in serum | quantitative immunological<br>determination of α-1-antitrypsin<br>in serum and plasma |
| Performance Characteristics: | | | |
| Accuracy: | serum/plasma vs. BM | serum | vs. Behring Nepholometric |
| Sample size (n) | 288 | 284 | 123 |
| Corr. Coefficient (r) | 0.995 | 0.930 | 0.967 |
| Linear regression | $1.30x - 0.31$ g/L | $0.90x + 0.06$ g/L | $0.993x + 9.9$ mg/dL |

## Table 3 - COBAS INTEGRA a-1-Antitrypsin (AAT)

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

## COBAS INTEGRA Immunoglobulin A (IGA/IGAP)

The cassette COBAS INTEGRA Immunoglobulin A (IGA/IGAP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin A in serum and plasma. In addition to the standard application (IGA), the sensitive application (IGAP) is designed for the quantitative determination of low IgA concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

| | COBAS INTEGRA<br>Immunoglobulin A<br>(IGA/IGAP)<br>(modified) | | COBAS INTEGRA<br>Immunoglobulin A<br>(IGA/IGAP)<br>(cleared) K954457 | | BM<br>Tina-Quant<br>Immunoglobulin A Assay<br>(K955907) | | |
|----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|--------------------------------------------------------------------------------------------------------|---------------|---------------|
| Intended Use | quantitative immunological<br>determination of human<br>immunoglobulin A in serum<br>and plasma, and sensitive<br>application for the quantitative<br>determination of low IgA<br>concentration in e.g. pediatric<br>samples | | quantitative immunological<br>determination of human<br>immunoglobulin A in<br>serum, and sensitive<br>application for the<br>quantitative determination<br>of low IgA concentration in<br>e.g. pediatric samples | | quantitative determination of IgA in<br>serum and plasma on automated<br>clinical chemistry analyzers. | | |
| Affected Parameters: | | | | | | | |
| Predilution Factor | 21 | | 41 | | | | |
| Postdilution Factor | 13.5 | | 2.4 | | | | |
| Sample Volume | 5 uL | | 9 uL | | | | |
| R1 + water volume | 90 uL + 10 uL | | 90 uL | | | | |
| R2 + water volume | 5 uL + 5 uL | | 9 uL | | | | |
| First Calc. Cycle | T0 | | 19 | | | | |
| IGA Performance Characteristics: | | | | | | | |
| Precision: | Level 1 | Level 2 | Level 1 | Level 2 | Level 1 | Level 2 | Level 3 |
| Mean | 2.0 (g/L) | 6.2 (g/L) | 2.3 (g/L) | 3.5 (g/L) | 118.8 (mg/dL) | 227.7 (mg/dL) | 268.5 (mg/dL) |
| CV (%) within-run | 2.0 | 0.97 | 1.4 | 0.81 | 0.9 | 0.8 | 1.0 |
| CV (%) total | 2.3 | 1.2 | 2.8 | 1.8 | 2.2 | 1.8 | 2.1 |
| Accuracy: | vs. BM/Hitachi | | | | vs. Behring Nepholometric | | |
| Sample size (n) | 584 | | 400 | | 36 | | |
| Corr. Coefficient (r) | 0.994 | | 0.989 | | 0.99 | | |
| Linear regression | 1.023 x - 0.214 g/L | | 0.97 x - 0.05 g/L | | 0.83x + 20.6 mg/dL | | |
| Assay Range | 0.45 - 7.3 g/L<br>0.15 - 98.6 g/L (with rerun) | | 0.79 - 12.6 g/L<br>0.27 - 30.2 g/L (with rerun) | | 50 mg/dL- highest calibrator<br>20 - 6000 mg/dL (with rerun) | | |
| Sensitivity | 0.45 g/L | | 0.79 g/L | | 20 mg/dL | | |

Table 4 - COBAS INTEGRA Immunoglobulin A (IGA/IGAP)

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

## COBAS INTEGRA Immunoglobulin M (IGM/IGMP)

The cassette COBAS INTEGRA Immunoglobulin M (IGM/IGMP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin M in serum and plasma. In addition to the standard application (IGM), the sensitive application (IGMP) is designed for the quantitative determination of low IgM concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

| | | COBAS INTEGRA<br>Immunoglobulin M<br>(IGM/IGMP)<br>(modified) | | COBAS INTEGRA<br>Immunoglobulin M<br>(IGM/IGMP)<br>(cleared) K954457 | | BM Tina-Quant<br>Immunoglobulin M<br>Assay<br>(K955908) | | |
|----------------------------------|--|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|------------------------------------------------------------------------------------------------------------------|--------------|---------------|
| Intended Use | | quantitative immunological<br>determination of human<br>immunoglobulin M in serum<br>and plasma, and sensitive<br>application for the<br>quantitative determination of<br>low IgM concentration in e.g.<br>pediatric samples | | quantitative immunological<br>determination of human<br>immunoglobulin M in<br>serum, and sensitive<br>application for the<br>quantitative determination of<br>low IgM concentration in<br>e.g. pediatric samples | | For the quantitative determination<br>of IgM in serum and plasma on<br>automated clinical chemistry<br>analyzers | | |
| Affected Parameters: | | | | | | | | |
| Calibrator dilution ratio | | 1:3, 1:6, 1:12, 1:24, 1:48, 1:96 | | 1:6, 1:12, 1:24, 1:48, 1:96 | | | | |
| Predilution Factor | | 1:96 | | 41 | | | | |
| Postdilution Factor | | 21 | | 2.4 | | | | |
| Sample Volume | | 4.7 | | 26 uL | | | | |
| R1 + water volume | | 13 uL | | 65 uL + 10 uL | | | | |
| R2 | | 65 uL + 20 uL | | 16 uL | | | | |
| First Calc. Cycle | | 13 uL | | 19 | | | | |
| | | T0 | | | | | | |
| IGM Performance Characteristics: | | | | | | | | |
| Precision: | | Level 1 | Level 2 | Level 1 | Level 2 | Level 1 | Level 2 | Level 3 |
| Mean | | 0.55 (g/L) | 2.0 (g/L) | 0.6 (g/L) | 1.9 (g/L) | 55.4 (mg/dL) | 93.9 (mg/dL) | 134.8 (mg/dL) |
| CV (%) within-run | | 2.4 | 1.6 | 2.6 | 2.0 | 0.79 | 0.8 | 0.7 |
| CV (%) total | | 3.2 | 1.9 | 3.1 | 2.2 | 3.7 | 2.4 | 2.0 |
| Accuracy: | | vs. BM/Hitachi | | | | vs. Behring Nepholometric | | |
| Sample size (n) | | 556 | | 400 | | 39 | | |
| Corr. Coefficient (r) | | 0.994 | | 0.994 | | 0.979 | | |
| Linear regression | | $1.293 x + 0.341$ g/L | | $1.12 x - 0.06$ g/L | | $0.81x + 5.9$ mg/dL | | |
| Assay Range | | 0.16 - 5.18 g/L<br>0.05 - 24.35 g/L (with rerun) | | 0.31 - 5.0 g/L<br>0.11 - 12.1 g/L (with rerun) | | 25 mg/dL - highest calibrator<br>10 - 4000 mg/dL (with rerun) | | |
| Sensitivity | | 0.16 g/L | | 0.31 g/L | | 10 mg/dL | | |

### Table 5 - COBAS INTEGRA Immunoglobulin M (IGM/IGMP)

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

Image /page/8/Picture/2 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular fashion around a central emblem. The emblem consists of a stylized caduceus-like symbol, with three figures representing health and human services.

## SEP 28 1998

Ms. Rita Smith Senior Regulatory Affairs Associate Roche Diagnostic System, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 U.S. Hiqhway 202 Somerville, New Jersey 08876-3771

Re: K982382 Roche COBAS® INTEGRA Reagent Cassettes Trade Name: Regulatory Class: II Product Code: DEM, CFN, DAH, CZP, DEW Dated: July 7, 1998 Received: July 8, 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 legally marketed predicate 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 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 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 requlations.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

#### Page 2

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 leqally 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/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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

{10}------------------------------------------------

Page 1 of 2

510(k) Number (if known) K982382

Roche COBAS INTEGRA &-1-Antitrypsin Reagent Cassette (AAT) Device Name: Art. No. 07 5092 1

> Roche COBAS INTEGRA Immunoglobulin A Reagent Cassette (IGA/IGAP) Art. No. 07 3775 5

Roche COBAS INTEGRA Immunoglobulin M Reagent Cassette (IGM/IGMP) Art. No. 07 3777 1

Roche COBAS INTEGRA Immunoglobulin G Reagent Cassette (IGGT/IGGTC) Art. No. 07 6663 1

Indications for Use:

The cassette COBAS INTEGRA x-1-Antitrypsin (AAT) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human x-1-antitrypsin in serum and plasma. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, a-1-antitrypsin deficiency has been associated with pulmonary emphysema.

The cassette COBAS INTEGRA Immunoglobulin A (IGA/IGAP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin A in serum and plasma. addition to the standard application (IGA), the sensitive application (IGAP) is designed for the quantitative determination of low IgA concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

The cassette COBAS INTEGRA Immunoglobulin M (IGM/IGMP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin M in serum and plasma. In addition to the standard application (IGM), the sensitive application (IGMP) is designed for the quantitative determination of low IgM concentrations in e.g. pediatric samples. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

{11}------------------------------------------------

Page 2 of 2

The cassette COBAS INTEGRA Immunoglobulin G (Turbidimetric) (IGGT/IGGTC) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative immunological determination of human immunoglobulin G in serum, plasma (IGGT) and cerebrospinal fluid (IGGTC). Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

(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 | |

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