VENTANA IMAGE ANALYSIS SYSTEM - HER2/NEU

K051282 · Tripath Imaging, Inc. · NOT · Aug 16, 2005 · Hematology

Device Facts

• Record ID: K051282
• Device Name: VENTANA IMAGE ANALYSIS SYSTEM - HER2/NEU
• Applicant: Tripath Imaging, Inc.
• Product Code: NOT · Hematology
• Decision Date: Aug 16, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2
• Attributes: AI/ML

AI Performance

Output	Acceptance	Observed	Dev DS	Test DS
HER-2/neu protein expression score	Not specified	Concordance between VIAS and Pathologist: 0.746 - 0.791; Kappa: 0.647 - 0.715	Training set of about 200 HER-2/neu slides used to derive conversion factor between system and manual scale	Comparison study: 201 formalin-fixed, paraffin-embedded breast tissue specimens evaluated by three board-certified pathologists and three different Ventana Image Analysis Systems

Intended 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 (HER-2/neu) in formalin-fixed, paraffin embedded normal and neoplastic tissue specimens immunohistochemically stained for the presence of HER-2/neu proteins using Ventana’s HER-2/neu reagents as well as Ventana’s DAB copper chromogen and nuclear hematoxylin. This particular application is an accessory to the Ventana PATHWAY™ Her2 (clone CB11) (Ventana Medical Systems, Inc., Tucson, Arizona) and the Ventana PATHWAY™ Her2 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 to assure the validity of the VIAS-assisted HER2 score.

Device Story

VIAS is an interactive histology imaging workstation for pathologists; comprises microscope, motorized stage, digital color camera, computer, monitor, and barcode reader. Pathologist manually selects tumor regions on stained breast cancer slides; system captures color images. Software performs colorimetric pattern recognition to separate DAB (brown) and hematoxylin (blue) dye components. System calculates total membrane area (DAB) and total cytoplasmic area (hematoxylin) within pathologist-selected regions; computes normalized ratio (membrane/cytoplasmic area) to account for cell size variation. Output is a continuous score (0 to 3.5) mapped to discrete bins (0, 1+, 2+, 3+). System provides quantitative data to supplement qualitative manual assessment; does not make independent interpretations. Used in pathology labs to improve reproducibility of HER2 scoring; assists clinical decision-making regarding Herceptin® eligibility.

Clinical Evidence

No clinical data provided. The document notes that the PATHWAY™ Her2 assay was compared to the DAKO HercepTest™ on an independent sample to demonstrate concordant results. The actual correlation of the PATHWAY™ Her2 assay to clinical outcome has not been established.

Technological Characteristics

Workstation-based interactive histology imaging system. Components: microscope, motorized stage, digital color video camera, computer, monitor. Software: Windows XP-based with proprietary UI. Sensing: Colorimetric pattern recognition via digital camera. Calibration: Black/white reference images required for dynamic range, white balancing, and shading correction. Connectivity: Standalone workstation. Sterilization: Not applicable (non-patient contacting).

Indications for Use

Indicated for use by qualified pathologists as an aid in the semi-quantitative detection of HER-2/neu protein in formalin-fixed, paraffin-embedded breast cancer tissue specimens to assist in the assessment of patients for whom Herceptin treatment is considered.

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.

Reference Devices

• Ventana PATHWAY™ Her2 (clone CB11)
• DAKO HercepTest™

Submission Summary (Full Text)

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

TriPath Imaging, Inc. c/o Mr. Bryan J. Tucker Vice President, Clinical and Regulatory Affairs 4025 Stirrup Creek Drive Ste. 400 Durham, NC 27703

AUG 1 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

## Re: k051282

Trade/Device Name: Ventana Image Analysis System – Her2/neu Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NOT Dated: May 16, 2005 Received: May 17, 2005

Dear Mr. 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.

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 legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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

Page 2 --

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety 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 Beckerh

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

Enclosure

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

## Indications for Use

510(k) Number (if known): K051282

Device Name: Ventana Image Analysis System - Her2/neu

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 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 (HER-2/neu) in formalin-fixed, paraffin embedded normal and neoplastic tissue specimens immunohistochemically stained for the presence of HER-2/neu proteins using Ventana's HER-2/neu reagents as well as Ventana's DAB copper chromogen and nuclear hematoxylin.

This particular application is an accessory to the Ventana PATHWAY™ Her2 (clone CB11) (Ventana Medical Systems, Inc., Tucson, Arizona) and the Ventana PATHWAY™ Her2 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 to assure the validity of the VIAS-assisted HER2 score.

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™ Her2. The PATHWAY™ Her2 was compared to the DAKO HercepTest™ on an independent sample and found to provide acceptably concordant results. The actual correlation of PATHWAY™ Her2 to clinical outcome has not been established.

Prescription Use (Part 21 CFR 801 Subpart D)

-

AND/OR

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Marie Chan
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K051282

Page 1 of __1__