(132 days)
Not Found
No
The document explicitly states that the software "makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process," which is contrary to the typical function of AI/ML algorithms in image analysis. While it uses "image analysis algorithms," these are not described as being based on AI/ML, and the lack of mention of training/test sets for model development further suggests the absence of AI/ML.
No.
The device is intended for in vitro diagnostic use as an aid to the pathologist for analysis and review, not for direct therapeutic intervention. It explicitly states it is an "aid to the pathologist" and is used to assess HER2 protein levels, which "is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered." This identifies the device as a diagnostic tool, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" section explicitly states, "It is intended for in vitro diagnostic use as an aid to the pathologist...". It further specifies its use in the "detection and semi-quantitative measurement of HER2 protein," which is a diagnostic function.
No
The device description explicitly states that the Virtuoso System is an "instrument-plus-software system" and includes a slide scanner (iScan) as a hardware component.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement in Intended Use: The "Intended Use / Indications for Use" section clearly states: "It is intended for in vitro diagnostic use as an aid to the pathologist..."
- Purpose of the Device: The device is designed to analyze biological specimens (formalin-fixed, paraffin-embedded tissues) to provide information about a patient's health status (detection and semi-quantitative measurement of HER2 protein in the context of breast cancer). This aligns directly with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, treatment, or prevention of disease.
- Accessory to an IVD: The device is described as an "accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody," which is itself indicated for use as an aid in the assessment of breast cancer patients. This further reinforces its role within the IVD workflow.
- Clinical Validation: The document describes clinical studies performed to validate the performance of the system in a clinical setting, which is typical for IVD devices.
N/A
Intended Use / Indications for Use
The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.
The Virtuoso™ System for IHC HER2 (4B5) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
NOTE: The IHC HER2 4B5 Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on 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 PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the iScan System for IHC HER2 4B5 Digital Read and Image Analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
Product codes (comma separated list FDA assigned to the subject device)
OEO, NOT
Device Description
The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffinembedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports. The iScan slide scanning device captures digital images of Hardware: formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor. Software: The Virtuoso software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
breast cancer specimens, formalin-fixed, paraffin-embedded normal and neoplastic tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
qualified pathologist / pathology laboratories
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The Virtuoso System for IHC HER2 (4B5) was clinically validated via two studies.
The first (primary) study evaluated overall system performance in terms of: (1) agreement between the reference manual method (with a traditional microscope) and both the digital read (DR) and image analysis (IA) applications of the Virtuoso system, (2) intra-pathologist/inter-day reproducibility of the two Virtuoso applications, and (3) inter-pathologist reproducibility of the two Virtuoso applications.
In the second study, scanner precision was evaluated in an isolated fashion via a cross-over design from the primary study. In this second study, a subset of the clinical cases (n = 40) was scanned two more times with two different scanners at two separate locations. This study evaluated scanner precision of the image analysis application only for both inter-scanner precision and intra-scanner/inter-day precision, as the image analysis application is the more sensitive of the two applications, and it generates an instrument-generated HER2 score that is not affected by memory bias as would be the case with human interpretations.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Agreement/Concordance:
- Virtuoso Digital Read vs Manual Method: Overall agreements across three sites were 93%, 83%, and 91%.
- Virtuoso Image Analysis vs Manual Method: Overall agreements across three sites were 92%, 82%, and 88%.
Reproducibility:
- Intra-Pathologist/Inter-Day Digital Read: Agreements between three comparisons across three sessions ranged from 90% to 95%.
- Intra-Pathologist/Inter-Day Image Analysis: Agreements were 100% for each comparison.
- Inter-Pathologist Manual Read: Agreements ranged from 85% to 90%.
- Inter-Pathologist Digital Read: Percent total agreements ranged from 90% to 92%, satisfying the minimum requirement of 75%.
- Inter-Pathologist Image Analysis: Percent agreements ranged from 93% to 95%, satisfying the minimum requirement of 75%.
Scanner Precision:
- Inter-site and intra-site/inter-day precision of the iScan scanner: Percent agreements for three image analysis fields of views were in excess of 90% for every comparison.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 864.1860 Immunohistochemistry reagents and kits.
(a)
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.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(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.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.
0
Image /page/0/Picture/0 description: The image shows the date OCT 12 2011 at the top. Below the date is the Ventana logo, which includes a stylized sunburst design to the left of the word "VENTANA" in all caps. Underneath the logo is the text "A Member of the Roche Group".
SECTION 7 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K111543.
| 807.92 (a)(1): Name: | Ventana Digital Pathology |
|---|---|
| Address: | 919 Hermosa Court |
| Sunnyvale, CA 94085 | |
| Phone: | (408) 207-4200 |
| FAX: | (408) 207-4299 |
| Contact: | Mr. Indu Lakshman |
807.92 (a)(2): Device name- trade name and common name, and classification
Trade name: Virtuoso™ System for IHC HER2 (4B5)
Common Name: Digital pathology and image analysis system for immunochemistry-stained slides
Classifications: 21 CFR § 864.1860- Immunohistochemistry reagents and kits
Product Codes: OEO, NOT
807.92 (a)(3): Identification of the legally marketed predicate devices
The Virtuoso System for IHC HER2 (4B5) is substantially equivalent to the Aperio ScanScope® XT System (Aperio Technologies, Inc., Vista, CA) cleared under pre-market notification number K080654 on August 14, 2009. Both devices are digital pathology and image analysis systems for the consistent assessment of pathology interpretations using immunohistochemically stained slides; both systems include slide scanner hardware, and software that both automates the procedural steps and performs the analyses.
In terms of technology, the Virtuoso System for IHC HER2 (4B5) is also substantially equivalent to the BioImagene PATHIAM™ System with iScan for p53 and Ki-67 (Biolmagene, Inc., Sunnyvale, CA), cleared under pre-market notification K092333 on October 27, 2010. Both of these systems include the same slide scanner (iScan) and other hardware components. The software algorithms for the two systems is different, as this Virtuoso submission is for the breast tumor marker HER2, while the PATHIAM System is for the breast turnor markers p53 and Ki-67.
Page 1 of 10
1
Image /page/1/Picture/0 description: The image shows the logo for Ventana, a member of the Roche Group. The logo consists of a stylized sun-like symbol with eight arrow-shaped rays pointing inward, followed by the word "VENTANA" in bold, sans-serif font. Below the logo, the text "A Member of the Roche Group" is written in a smaller, serif font.
807.92 (a)(4): Device Description
General Description
The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffinembedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports.
The iScan slide scanning device captures digital images of Hardware: formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor.
Software: The Virtuoso software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
Additional Materials Required:
- Ventana PATHWAY® anti-HER2/neu (4B5) rabbit monoclonal primary . antibody
- . Reagents for visualization, such as universal DAB chromogen
- Associated materials for completing immunohistochemical staining according . to the appropriate package insert
- Color printer if user wishes to print color copies .
Device Quality Control
The quality of results depends on the laboratory following the quality control instructions recommended in the labeling of the immunohistochemistry (IHC) reagents. The software also performs a quality check on the digital images to determine if they are suitable for further analysis using "Image Quality Assessment" algorithms:
2
Image /page/2/Picture/0 description: The image shows the Ventana logo. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in bold, sans-serif font. To the right of the word is a registered trademark symbol. Below the logo is the text "A Member of the Roche Group" in a smaller font.
Summary of Procedure
Samples are obtained as formalin-fixed, paraffin-embedded tissue blocks. Histologic sections are prepared and mounted onto glass slides. Slides are reacted with the HER2 (4B5) primary antibody, and are then visualized using universal DAB. Prepared slides are loaded into the Virtuoso system scanner and scanned. The resulting digital images are reviewed by the pathologist on a computer monitor, and appropriate fields of view (FOVs) are then selected for analysis by the Virtuoso software. The Virtuoso software produces a semi-quantitative result of 0, 1+, 2+, or 3+, and the pathologist has the choice of accepting the result or overriding with his/her own score.
807.92 (a)(5): Intended Use
The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.
The Virtuoso™ System for IHC HER2 (4B5) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
NOTE: The IHC HER2 4B5 Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on 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 PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the iScan System for IHC HER2 4B5 Digital Read and Image Analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
3
Image /page/3/Picture/0 description: The image shows the Ventana logo, which consists of a stylized sun-like symbol on the left and the word "VENTANA" in bold, sans-serif font on the right. A registered trademark symbol is present next to the last letter. Below the logo, there is a line of text that reads "A Member of the Roche Group" in a smaller, serif font.
807.92 (a)(6): Technological Similarities and Differences to the Predicate Devices
The similarities and differences among the analogous test systems are described below.
| Characteristic | Virtuoso™ IHC HER2
(4B5) | Aperio ScanScope® XT
System
K080564 | PATHIAM™ with iScan
for p53 and Ki-67
K092333 |
|----------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | This device is intended for
in vitro diagnostic (IVD)
use. | This device is intended for
in vitro diagnostic (IVD)
use. | This device is intended for
in vitro diagnostic (IVD)
use. |
| | The Virtuoso System
provides automated digital
slide creation, management,
analysis, and viewing. It is
intended for IVD use as an
aid to the pathologist in the
display, detection, counting,
review and classification of
tissues and cells of clinical
interest based on particular
morphology, color, size,
intensity, pattern and shape. | The ScanScope® System is
an automated digital slide
creation, management,
viewing and analysis
system. It is intended for
IVD use as an aid to the
pathologist in the display,
detection, counting and
classification of tissues and
cells of clinical interest
based on particular color,
intensity, size, pattern and
shape. | The PATHIAM System is
intended as an aid to the
pathologist to detect, count,
and classify cells of clinical
interest based on
recognition of cellular
objects of particular color,
size, and shape, using
appropriate controls to
assure the validity of the
scores. |
| Intended
Use/Indications
for Use | The IHC HER2 (4B5)
Digital Read and Image
Analysis applications are
intended for use as an aid to
the pathologist in the
detection and semi-
quantitative measurement of
HER2 protein in formalin-
fixed, paraffin-embedded
normal and neoplastic
tissue. HER2 results are
indicated for use as an aid
in the management,
prognosis and prediction of
therapy outcomes in breast
cancer. When used with
Ventana Medical Systems,
Inc. PATHWAY® anti-
HER2/neu (4B5) Rabbit
Monoclonal Primary
Antibody, it is indicated for
use as an aid in the
assessment of breast cancer | The IHC HER2 Tunable
Image Analysis application
is intended for use as an
accessory to the Dako
HercepTest™ to aid in the
detection and semi-
quantitative measurement of
HER2/neu (c-erbB-2) in
formalin-fixed, paraffin-
embedded normal and
neoplastic tissue. When
used with the Dako
HercepTest™, it is
indicated for use as an aid
in the assessment of breast
cancer patients for whom
HERCEPTIN®
(Trastuzumab) treatment is
being considered. | The p53/Ki-67 applications
are intended for use as an
aid to the pathologist to
quantify the percentage of
positively stained nuclei in
formalin-fixed, paraffin-
embedded breast tissue
specimens stained with
specific monoclonal
antibodies and visualized
with DAB chromogen to
detect both wild-type and
mutant nuclear proteins, as
specified in the instructions
for these reagents |
| | patients for whom
HERCEPTIN®
(Trastuzumab) treatment is
being considered. | | |
| Characteristic | Virtuoso™ IHC
HER2 (4B5) | Aperio ScanScope® XT
System
K080564 | PATHIAMTM with iScan
for p53 and Ki-67-
K092333 |
| Specimen Type | Formalin-fixed, paraffin-
embedded tissue stained by
immunohistochemical
technique | Same | Same |
| System Operation
(Digital Read and
Image Analysis) | Histologic observation by a
pathologist through the
viewer and image analysis
systems | N/A- also, the Aperio
system utilizes a tunable
model vs a pre-calibrated,
locked model | Same as Virtuoso HER2
(4B5) |
| Hardware and
Software | BioImagene (now Ventana)
iScan slide scanner,
computer, color monitor,
proprietary software for
HER2 (4B5) | Automated digital slide
scanner, computer, color
monitor, and image analysis
software and digital
pathology information
management software | BioImagene (now Ventana)
iScan slide scanner,
computer, color monitor,
proprietary software for p53
and Ki-67 |
| Platform Components | mouse, keyboard, windows
web browser. | mouse and keyboard | Same as Virtuoso HER2
(4B5) |
| Primary Antibody
(Assay) Reagent | Ventana PATHWAY HER2
(4B5) (P990081 S003) | Dako Reagents for HER2 | Dako p53) and Dako Ki-67
(reagents are Class I. 510(k)
exempt) |
| Ancillary Reagents | DAB chromogen kits | Same | Same |
| Localization of
IHC positive stain | Cytoplasmic membrane | Cytoplasmic membrane | Nucleus |
| Interpretation | Interpretation is performed
by the pathologist. | Same | Same |
4
Image /page/4/Picture/0 description: The image shows the Ventana Medical Systems logo. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in bold, uppercase letters. A registered trademark symbol is located to the upper right of the last letter.
807.92 (b)(1/2): Brief Description of Clinical Data (Non-clinical data N/A)
The Virtuoso System for IHC HER2 (4B5) was clinically validated via two studies. The first (primary) study evaluated overall system performance in terms of: (1) agreement between the reference manual method (with a traditional microscope) and both the digital read (DR) and image analysis (IA) applications of the Virtuoso system, (2) intra-pathologist/inter-day reproducibility of the two Virtuoso applications, and (3) inter-pathologist reproducibility of the two Virtuoso applications.
In the second study, scanner precision was evaluated in an isolated fashion via a cross-over design from the primary study. In this second study, a subset of the clinical cases (n = 40) was scanned two more times with two different scanners at two separate locations. This study evaluated scanner precision of the image analysis application only for both inter-scanner precision and intra-
5
Image /page/5/Picture/0 description: The image shows the word "VENTANA" in bold, black letters. To the left of the word is a symbol that looks like a sun made of arrows. A registered trademark symbol is to the right of the word.
scanner/inter-day precision, as the image analysis application is the more sensitive of the two applications, and it generates an instrument-generated HER2 score that is not affected by memory bias as would be the case with human interpretations. The data from both studies are summarized below.
Agreement/Concordance
- Virtuoso Digital Read vs Manual Method a.
Each pathologist's Virtuoso digital read results were compared to their manual results. The data were categorized as "neg" and "pos" using HER2 classifications of 0 and 1+ to describe negative, and 2+ and 3+ to describe positive. The overall agreements across the three sites were: 93%, 83%, and 91%, respectively. The data, with the 95% confidence intervals (CI) around the agreements are shown below.
| 2 x 2 Table | |||||||
|---|---|---|---|---|---|---|---|
| Confusion Matrix | Digital | ||||||
| Site 1 | |||||||
| (n = 119) | Site 2 | ||||||
| (n = 120) | Site 3 | ||||||
| (n = 118) | |||||||
| Neg Pos | Neg Pos | Neg Pos | |||||
| Manual | Neg (0, 1+) | 64 | 4 | 51 | 1 | 54 | 4 |
| Pos (2+, 3+) | 4 | 47 | 20 | 48 | 7 | 53 | |
| % Agreement | 93% | 83% | 91% | ||||
| (95% CI) | (87% - 97%) | (75% - 88%) | (84% - 95%) |
Agreement: Digital Read vs Manual (manual = true score)
b. Virtuoso Image Analysis vs Manual Method
The same analysis as performed for digital read was performed for image analysis. The overall agreements across the three sites were: 92%, 82%, and 88%, respectively. That data table, along with the 95% Cls, is presented below.
Agreement: Image Analysis vs Manual (manual = true score)
2 x 2 Table
6
Image /page/6/Picture/0 description: The image shows the Ventana logo. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in capital letters. A registered trademark symbol is present to the right of the word "VENTANA".
| Confusion Matrix | Image Analysis | ||||||
|---|---|---|---|---|---|---|---|
| Site 1 | Site 2 | Site 3 | |||||
| (n = 117) | (n = 120) | (n = 120) | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Manual | Neg (0, 1+) | 67 | 0 | 52 | 0 | 59 | 1 |
| Pos (2+, 3+) | 9 | 41 | 22 | 46 | 14 | 46 | |
| % Agreement | 92% | 82% | 88% | ||||
| (95% CI) | (86% - | 96%) | (74% - | 88%) | (80% - | 92%) |
Reproducibility
- a. Intra-Pathologist/Inter-Day (pair-wise comparisons, Session 1 vs Session 2, Session 1 vs Session 3, Session 2 vs Session 3)
Digital Read
The agreements between each of the three comparisons across three sessions with the same pathologist are shown below. The total agreements ranged from 90% to 95%, and the data (with 95% CIs) are shown below.
| Intra-Pathologist Digital | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Session 2 | Session 3 | Session 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| Session 1 | Neg | 17 | 17 | 0 | 17 | 0 | ||
| Pos | 22 | 2 | 20 | 4 | 18 | |||
| Session 2 | Neg | 19 | 19 | 0 | ||||
| Pos | 21 | 3 | 18 | |||||
| % Agreement | 95% | 90% | 93% | |||||
| (95% CI) | (83% - 99%) | (76% - 96%) | (80% - 97%) |
Image Analysis
The agreements between each of the three comparisons across three sessions with the same pathologist are shown below. The agreements were 100% for each comparison.
7
Image /page/7/Picture/0 description: The image shows the word "VENTANA" in all caps with a registered trademark symbol. To the left of the word is a symbol that looks like a sun or asterisk. The font is sans-serif and the text is black on a white background.
| Intra-Pathologist Image Analysis | |||||||
|---|---|---|---|---|---|---|---|
| Confusion Matrix | Session 2 | Session 3 | Session 3 | ||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Session 1 | Neg | 24 | 24 | 23 | 23 | 23 | 23 |
| Pos | 16 | 0 | 0 | 0 | 0 | 16 | |
| Session 2 | Neg | 24 | 23 | 0 | |||
| Pos | 16 | 0 | 16 | ||||
| % Agreement | 100% | 100% | 100% | ||||
| (95% CI) | (91% - 100%) | (91% - 100%) | (91% - 100%) |
- b. Inter-Pathologist (pair-wise comparisons, Pathologist 1 vs Pathologist 2, Pathologist 1 vs Pathologist 3, Pathologist 2 vs Pathologist 3)
Manual Read
The three manual readings across the three pathologists were compared to each other. There was no acceptance criterion for this evaluation, as this aspect of the study assesses the differences in the human component of IHC interpretations. The agreements ranged from 85% to 90%, indicating commonality among the three pathologists.
| Inter-Pathologist Manual | |||||||
|---|---|---|---|---|---|---|---|
| Site 2 | Site 3 | Site 3 | |||||
| Confusion Matrix | Neg | Pos | Neg | Pos | Neg | Pos | |
| Site 1 | Neg | 51 | 17 | 58 | 10 | 60 | 60 |
| Pos | 1 | 50 | 2 | 49 | 60 | 60 | |
| Site 2 | Neg | 52 | 68 | 60 | 60 | 48 | 4 |
| Pos | 68 | 51 | 2 | 49 | 12 | 56 | |
| % Agreement | 85% | 90% | 87% | ||||
| (95% CI) | (77% - 90%) | (83% - 94%) | (79% - 92%) |
Digital Read
The reproducibility in the Virtuoso digital readings among the three pathologists is shown below, along with the 95% CIs. The percent total agreements ranged from 90% to 92%, satisfying the minimum requirement of 75%.
8
Image /page/8/Picture/0 description: The image shows the Ventana Medical Systems logo. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in bold, sans-serif font, with a registered trademark symbol. Below the word "VENTANA" is the text "A Member of the Roche Group" in a smaller font size.
| Inter-Pathologist Digital | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| Site 1 | Neg | 68 | 71 | 49 | 61 | 57 | 61 | 57 |
| Pos | 51 | 65 | 3 | 58 | 8 | |||
| Site 2 | Neg | 71 | 59 | 10 | ||||
| Pos | 49 | 2 | 47 | |||||
| % Agreement | 92% | 91% | 90% | |||||
| (95% CI) | (86% - 96%) | (84% - 95%) | (83% - 94%) |
Page 9 of 10
9
Image /page/9/Picture/0 description: The image shows the Ventana logo, which includes a stylized sun-like symbol on the left and the word "VENTANA" in bold, sans-serif font to the right. A registered trademark symbol is present next to the last "A" in "VENTANA". Below the logo, the text "A Member of the Roche Group" is displayed in a smaller, serif font, indicating Ventana's affiliation with the Roche Group.
Image Analysis
The reproducibility in the Virtuoso image analysis interpretations among the three pathologists is shown below, along with the 95% Cls. The percent agreements ranged from 93% to 95%, satisfying the minimum requirement of 75%.
| Inter-Pathologist Image Analysis | |||||||
|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | ||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Site 1 | Neg | 71 | 5 | 71 | 5 | ||
| Pos | 2 | 40 | 1 | 41 | |||
| Site 2 | Neg | 69 | 5 | ||||
| Pos | 4 | 42 | |||||
| % Agreement | 94% | 95% | 93% | ||||
| (95% CI) | (88% - 97%) | (89% - 98%) | (86% - 96%) | ||||
| 76 | 74 | 46 | 73 | 47 | 73 | 47 | |
| 42 | 74 | 46 |
Scanner Precision
When the iScan scanner was evaluated for inter-site and intra-site/inter-day precision, the percent agreements for three image analysis filed of views were in excess of 90% for every comparison.
807.92 (b)(3): Conclusions from Clinical Testing
Concordance, reproducibility, and precision studies were performed for the Virtuoso System for IHC HER2 (4B5). The test system was shown to be safe and effective for its intended use.
10
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/10/Picture/1 description: The image shows the logo for the United States Department of Health and Human Services. The logo features a stylized depiction of a human figure with outstretched arms, symbolizing care and protection. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the figure.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Ventana Digital Pathology c/o Mr. Indu Lakshman Senior Director QA/ RA 919 Hermosa Court Sunnyvale, CA 94085
OCT 1 2 2011
Re: K111543
Trade/Device Name: Ventana Virtuoso™ System for HER2 (4B5) Regulation Number: 21 CFR §864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Codes: NOT, OEO Dated: September 27, 2011 Received: September 28, 2011
Dear Mr. Lakshman:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determind the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predically quivalent (for the industions for prior to May 28, 1976, the enactment date of the Medical Devices marketed in interstate commerce
have been reclassified in accordance with the maintents, 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 class II (Special Controls), it may be subject to such i additional controls. Existing major regulations affecting your device to such
additional controls. Existing major regulations affecting your device can be found in Title 21 of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish firsther 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 administed by other Fequirements of the Act or
all the Act's requirements including, but not limited to all the Act's requirements, including by oner Federal agencies. You must comply with labeling (21 CFR Parts 801 and 809); medical device reporting (21 CFR Part 807);
adverse events) (21 CFR 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing of medical device-relation quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin maketing and of the ( ( ( ) a gamest (11 OF IT all 820). This letter will allow you to begin makes
your device as described in your Section 510(k) premarket notification. The FDA f
11
Page 2 – Mr. Indu Lakshman
substantial equivalence of your device to a legally marketed predicate device results in a classification for your device to a legally marketed proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), and 809), and 809), and please contact the Office of your device on our labeling regulation (21 CFR Parts 801 and 800
Also, please note the requiried. "Mich and in all result and Safety at (301) 796 Also, please note the regulation and Sate Device Evaluation and Satety at (301) 796-5450.
CFR Part 807 97) For questions roceding the only of reference to premarket notific CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR
regulation (21 CFR Part 803), please go to regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International on your responsibilities under the Act from the Division the Division 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
for Reena Philip
Maria M. Chan, Ph.D.
Maria M. Chan, 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
12
INDICATIONS FOR USE
510(k) Number (if Known):
111543
Device Name: Virtuoso™ System for IHC HER2 (4B5)
Indications for Use
The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.
The Virtuoso™ System for IHC HER2 (4B5) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detections. and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-mbedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHMS, Inc.
PATHWA Y® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being
The IHC HER2 4B5 Digital Read and Image Analysis applications are adjunctive NOTE: computer-assisted methodologies for the qualified pathologist in the acquisitions are adjunctive measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on 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 PATHWAY® anti-HER-2/neu (4B5) Rabbit Monocloal Primary Antibody assay used to the the validity of the iScan System for IHC HERZ 4BS Digital Read and Image Analysis soces The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
| 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 Diagnostics (OIVD) Division Sign-Off | |
|---|---|
| Office of In Vitro Diagnostic Device Evaluation and Safety | |
| 510K | K111543 |