VENTANA IMAGE ANALYSIS SYSTEM, MODEL KI-67

K053520 · Tripath Imaging, Inc. · NQN · Apr 11, 2006 · Hematology

Device Facts

• Record ID: K053520
• Device Name: VENTANA IMAGE ANALYSIS SYSTEM, MODEL KI-67
• Applicant: Tripath Imaging, Inc.
• Product Code: NQN · Hematology
• Decision Date: Apr 11, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2
• Attributes: Software as a Medical Device

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 in the acquisition and measurement of images to quantify the percentage of positively stained nuclei in paraffin embedded breast cancer tissue specimens immunohistochemically stained for the presence of Ki-67 proteins using Ventana’s reagents and nuclear hematoxylin. It is indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue when used with in vitro diagnostic reagents marketed for these indications. 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 Ki-67 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 Ki-67 kit to assure the validity of the VIAS-assisted Ki-67 assessment.

Device Story

Ventana Image Analysis System (VIAS) is an interactive, computer-supported bright-field microscopy system; assists pathologists in quantitative assessment of Ki-67 marker expression in IHC-stained breast cancer tissue. System components: microscope, motorized stage, digital color camera, computer, monitor, barcode reader. Pathologist manually screens slides; selects fields of interest; uses interactive drawing tools to refine regions of interest (ROI) by excluding stroma/normal cells. Device processes color images to separate DAB (brown) and hematoxylin (blue) components; calculates percentage of Ki-67 positive nuclei (0-100%). Algorithm corrects for cytoplasmic foreground staining noise. Output provides quantitative data to complement pathologist's qualitative interpretation; aids reproducibility of slide assessment. Used in pathology labs; requires human intervention for all analysis steps. System makes no independent interpretations; pathologist makes final clinical decision.

Clinical Evidence

No clinical studies performed. Analytical performance established via precision/reproducibility studies across three systems using nine slides (0-90% positivity). Concordance study compared system-assisted reads against manual reads by three board-certified pathologists on 207 breast tissue specimens. Results showed system-pathologist concordance (88.4-97.0%) comparable to inter-pathologist concordance (87.1-98.0%) at 1%, 5%, and 10% cutoffs. System-to-system reproducibility was 98.0-100%.

Technological Characteristics

Interactive bright-field microscopy system. Components: microscope, motorized stage, digital color camera, PC. Software performs image processing/quantification. Connectivity: standalone, no LIS interface. Staining: IHC (DAB/Hematoxylin). Algorithm: threshold-based calculation with cytoplasmic noise correction. Calibration: internal control based on mean DAB intensity in cytoplasm (min threshold 0.02).

Indications for Use

Indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue when used with in vitro diagnostic reagents marketed for these indications.

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 features a stylized depiction of an eagle or bird with three curved lines forming its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 1 1 2006

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

Re: k053520

Trade/Device Name: Ventana Image Analysis System-Ki-67 Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NQN Dated: December 16, 2005 Received: December 20, 2005

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 A. Roetker

Robert L. Becker, Jr., M.D., PH.D. 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): K053520

Device Name: Ventana Image Analysis System - Ki-67

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 in the acquisition and measurement of images to quantify the percentage of positively stained nuclei in paraffin embedded breast cancer tissue specimens immunohistochemically stained for the presence of Ki-67 proteins using Ventana's reagents and nuclear hematoxylin. It is indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue when used with in vitro diagnostic reagents marketed for these indications.

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 Ki-67 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 Ki-67 kit to assure the validity of the VIAS-assisted Ki-67 assessment.

Prescription Use - x (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 In Vitro Diagnostic Devices (OIVD)

chan

Division Slan-Off

Office of in Vitro Diagnosite Device Evaluation and Safety

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510(k) K05320