VENTANA IMAGE ANALYSIS SYSTEM - PATHWAY HER2 (4B5)

K061613 · Tripath Imaging · NQN · Jan 10, 2007 · Hematology

Device Facts

• Record ID: K061613
• Device Name: VENTANA IMAGE ANALYSIS SYSTEM - PATHWAY HER2 (4B5)
• Applicant: Tripath Imaging
• Product Code: NQN · Hematology
• Decision Date: Jan 10, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

This antibody is intended for in vitro diagnostic (IVD) use. Ventana® Medical Systems' (VIAS) PATHWAY® anti-HER-2/neu (4B5) primary antibody (PATHWAY HER2 (4B5)) is a rabbit monoclonal antibody intended for laboratory use for semi-quantitative detection of HER2 antigen in sections of formalin fixed, paraffin embedded normal and neoplastic tissue on a Ventana automated slide immunohistochemistry slide staining device. It is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® treatment is considered.

Device Story

VIAS is an interactive histology imaging workstation; includes microscope, motorized stage, digital color camera, computer, monitor, and barcode reader. Pathologist manually screens slides; selects tumor regions of interest; acquires color images. Software separates DAB (brown) and hematoxylin (blue) dye components; calculates total membrane area and cytoplasmic area within marked regions. System computes normalized ratio of membrane area to cytoplasmic area; converts to continuous score (0-3.5) and discrete bins (0, 1+, 2+, 3+). System provides quantitative data to assist pathologist reproducibility; makes no independent diagnosis. Used in pathology labs; requires human intervention for all analytical steps. Benefits include standardized, reproducible quantification of HER2 protein expression to support clinical decision-making regarding Herceptin therapy.

Clinical Evidence

No clinical outcome data established. The PATHWAY anti-HER-2/neu (4B5) antibody was compared to the Ventana PATHWAY HER2 (clone CB11) Primary Antibody on an independent sample and demonstrated acceptably concordant results.

Technological Characteristics

Interactive histology imaging workstation. Components: microscope, motorized stage, digital color video camera, computer, monitor, keyboard, mouse, barcode reader. Software: proprietary interface on Windows XP, SQL Server database. Analysis: colorimetric pattern recognition, dye separation (DAB/hematoxylin), local contrast thresholding for membrane detection. Connectivity: standalone, no LIS interface. Sterilization: N/A (lab equipment).

Indications for Use

Indicated for use as an aid to qualified pathologists in the semi-quantitative detection of HER2 antigen in formalin-fixed, paraffin-embedded breast cancer tissue specimens to assess patients for Herceptin® treatment eligibility.

Regulatory Classification

Identification

Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.

Special Controls

(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.

Submission Summary (Full Text)

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Image /page/0/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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure with three wavy lines extending from its head.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

TriPath Imaging, Inc. c/o Bryan J. Tucker, Ph.D. Vice President, Clinical and Regulatory Affairs 4025 Stirrup creek Drive, Suite 400 Durham, NC 27703

JAN 1 0 2007

Re: k061613

Trade/Device Name: Ventana Image Analysis System - PATHWAY® HER (4B5) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NQN Dated: June 8, 2006 Received: June 9, 2006

Dear Dr. Tucker:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations. Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Robert Beckerf

Robert L. Becker, Jr., M.D., Ph.D. 4 Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known): K061613

Device Name: Ventana Image Analysis System - PATHWAY® HER2 (4B5)

Indications For Use:

The Ventana Image Analysis System (VIAS™) is an adjunctive computer-assisted image analysis system functionally connected to an interactive microscope. It is intended for use as an aid to the pathologist in the detection, classification and counting of cells of interest based on marker intensity, size and shape using appropriate controls to assure the validity of the VIAS scores.

In this application, the VIAS is intended to aid a qualified pathologist for the semi-quantitative detection of c-erbB-2 (HER2) antigen in formalin-fixed, paraffin-embedded normal and neoplastic tissue specimens immunohistochemically stained for the presence of HER2 proteins using Ventana® Medical Systems, Inc.'s (Ventana) PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody as well as Ventana's DAB copper chromogen and nuclear hematoxylin.

Ventana's PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® treatment is considered.

The VIAS is an adjunctive computer-assisted methodology to assist the reproducibility of a qualified pathologist in the acquisition and measurement of images from microscope slides of breast cancer specimens stained for the presence of HER2 receptor protein. The accuracy of the test result depends upon the quality of the immunohistochemical staining, It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the Ventana PATHWAY HER2 (4B5) to assure the validity of the VIAS-assisted HER2.

Note: All of the patients in the Herceptin® clinical trials were selected using a clinical trial assay. None of the patients in those trials were selected using PATHWAY anti-HER-2/neu (4B5). PATHWAY anti-HER-2/neu (4B5) was compared to Ventana's PATHWAY HER2 (clone CB11) Primary Antibody on an independent sample and found to provide acceptably concordant results. The actual correlation of PATHWAY anti-HER-2/neu (4B5) to clinical outcome has not been established.

| Prescription Use | X |
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| (Part 21 CFR 801 Subpart D) | |

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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Concurrence of CDRH, Qffice of In Vitro Diagnostic Devices (OIVD)

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**510(K)** K06/6/3