(245 days)
Not Found
No
The document describes "image analysis algorithms" but does not mention AI, ML, or deep learning. The software is described as providing quantitative data to assist the pathologist and requiring "competent human intervention for all steps in the analysis process," which is not typical language for an AI/ML-driven system making independent interpretations.
No.
The device is an in vitro diagnostic aid for pathologists in analyzing tissue and cells, not providing direct therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states, "It is intended for in vitro diagnostic use as an aid to the pathologist...".
No
The device description explicitly states that the Virtuoso System is an "instrument-plus-software system" and lists hardware components including a slide scanner (iScan), computer, monitor, keyboard, and mouse.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "It is intended for in vitro diagnostic use as an aid to the pathologist..."
- Purpose: The device is used to analyze biological specimens (tissues and cells) outside of the body ("in vitro") to provide information that aids in diagnosis and assessment of clinical conditions (detection and semi-quantitative measurement of Ki67 protein in normal and neoplastic tissue, aid in the assessment of Ki-67 status in breast cancer patients).
- Accessory to an IVD: It is described as an "accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay," which is itself an assay used for diagnostic purposes.
- Clinical Validation: The document describes clinical validation studies, which are typical for IVD devices to demonstrate their performance in a clinical setting.
- Predicate Device: A predicate device (K092333; BioImagene's PATHIAMTM System with iScan for p53 and Ki-67) is listed, which is also an IVD device with a similar intended use.
All of these points strongly indicate that the Virtuoso system, as described, is an In Vitro Diagnostic device.
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 Ki67 (30-9) 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 Ki67 (30-9) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) assay is indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with this assay, the Virtuoso™ System for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC Ki67 (30-9) 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 Ki67 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 CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the Virtuoso™ System for Ki67 (30-9) Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.
Product codes (comma separated list FDA assigned to the subject device)
NON, NOT, OEO
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, paraffin-embedded 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 CONFIRM™ Ki-67 (30-9) rabbit monoclonal primary antibody .
- Reagents for visualization, such as universal DAB universal 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.
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 p53 (DO7) primary antibody, and are then visualized using 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 quantitative score for the FOV and an aggregate score over all the FOVs for the whole slide. The pathologist has the choice of accepting the result or overriding with his/her own score for some or all FOVs.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
normal and neoplastic breast tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
qualified pathologist
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 KI-67 (30-9) was clinically validated via two studies. The first (primary) study evaluated overall system performance across four sites in terms of 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. In the second study, scanner precision was evaluated in an isolated fashion among three pathologists for inter-pathologist reproducibility of the two Virtuoso applications, and intra-pathologist/inter-day reproducibility of the two Virtuoso applications was also evaluated.
Agreement/Concordance
-
Virtuoso Digital Read vs Manual Method: Each pathologist's Virtuoso digital read results were compared to their manual results. The data were categorized as "neg" and "pos" using Ki-67 classifications of less than or equal to 10% staining to describe negative, and greater than 10% to describe positive. The overall agreements across the four sites were: 92%, 81%, 86%, and 87%, respectively.
-
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: 88%, 86% and 81%, respectively.
Reproducibility
-
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 total agreements ranged from 98% to 100%.
- Image Analysis: The agreements ranged from 89% to 97%.
-
Inter-Pathologist (pair-wise comparisons, Pathologist 1 vs Pathologist 2, Pathologist 1 vs Pathologist 3, Pathologist 2 vs Pathologist 3)
- Digital Read: The percent total agreements ranged from 71% to 85%.
- Image Analysis: The percent agreements ranged from 84% to 93%.
Scanner Precision: When the iScan scanner was evaluated for inter-site and intra-site/inter-day precision, the percent agreements for three image analysis fields of views were in approximately 90% for every comparison.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Agreement/Concordance, Reproducibility
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
VENTANA®
A Member of the Roche Group
FEB 2 2 2012
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 K111755.
| 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 Ki-67 (30-9)
Common Name: Digital pathology and image analysis system for immunochemistry-stained slides
Classifications: 21 CFR § 864.1860- Immunohistochemistry reagents and kits
807.92 (a)(3): Identification of the legally marketed predicate devices
The Virtuoso System for IHC Ki-67 (30-9) is substantially equivalent to BioImagene's PATHIAMTM System with iScan for p53 and Ki-67 (BioImagene, Inc. [now Ventana Digital Pathology], Sunnyvale, CA), cleared under pre-market notification K092333 on October 27, 2010. Both devices are digital pathology and image analysis systems for the consistent assessment of pathology interpretations using immunohistochemically stained slides (in this case, stained for Ki-67 expression), and both systems include slide scanner hardware, and software that both automates the procedural steps and performs the analyses.
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
1
Image /page/1/Picture/0 description: The image shows the word "VENTANA" in all capital letters. To the left of the word is a symbol that looks like a star made up of arrowheads. To the right of the word is a registered trademark symbol.
A Member of the Roche Group
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 CONFIRM™ Ki-67 (30-9) rabbit monoclonal primary antibody .
- Reagents for visualization, such as universal DAB universal 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.
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 p53 (DO7) primary antibody, and are then visualized using 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 quantitative score for the FOV and an aggregate score over all the FOVs for the whole slide. The pathologist has the choice of accepting the result or overriding with his/her own score for some or all FOVs.
2
Image /page/2/Picture/0 description: The image shows the Ventana logo. The logo consists of a stylized sunburst symbol to the left of the word "VENTANA", with a registered trademark symbol next to the last "A". Below the word "VENTANA" is the text "A Member of the Roche Group".
807.92 (a)(5): Intended Use/ Indication(s) 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 Ki67 (30-9) 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 Ki67 (30-9) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) assay is indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with this assay, the Virtuoso™ System for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC Ki67 (30-9) 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 Ki67 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 CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the Virtuoso™ System for Ki67 (30-9) Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.
3
Image /page/3/Picture/0 description: The image shows the logo for Ventana, a member of the Roche Group. The logo consists of a stylized sunburst symbol to the left, followed by the word "VENTANA" in bold, uppercase letters. Below the word "VENTANA" is the text "A Member of the Roche Group" in a smaller, italicized font.
807.92 (a)(6): Technological Similarities and Differences to the Predicate Devices
The similarities and differences among the two test systems are described below.
| Characteristic | Virtuoso™ IHC Ki-67 (30-9) | PATHIAM™ with iScan for
p53 and Ki-67 K092333 |
|----------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended
Use/Indications
for 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 IHC Ki-67 (30-9) Digital Read and
Image Analysis applications are intended
for use as an aid to the pathologist in the
detection and quantitative measurement of
Ki-67 protein in formalin-fixed, paraffin-
embedded normal and neoplastic tissue.
When used with Ventana Medical
Systems, Inc. CONFIRM™ anti-Ki-67
(30-9) Rabbit Monoclonal Primary
Antibody, it is indicated for use as an aid
in the assessment p53 protein of breast
cancer patients (but is not the sole basis for
treatment). | This device is intended for in vitro
diagnostic (IVD) use.
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.
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 |
| Specimen Type | Formalin-fixed, paraffin-embedded tissue
stained by immunohistochemical technique | Same |
| System Operation
(Digital Read and
Image Analysis) | Histologic observation by a pathologist
through the viewer and image analysis
systems | Same |
| Hardware and
Software | BioImagene (now Ventana) iScan slide
scanner, computer, color monitor,
proprietary software for Ki-67 (30-9) | BioImagene (now Ventana) iScan slide
scanner, computer, color monitor,
proprietary software for p53 and Ki-67 |
| Platform Components | mouse, keyboard, windows web browser. | Same |
| Primary Antibody
(Assay) Reagent | Ventana CONFIRM™ Ki-67 (30-9)
(reagent is Class I, 510(k) exempt) | Dako p53 and Dako Ki-67
(reagents are Class I, 510(k) exempt) |
| Ancillary Reagents | DAB chromogen kits | Same |
| Localization of
IHC positive stain | Nucleus | Nucleus |
| Interpretation | Interpretation is performed by the
pathologist. | Same |
Page 4 of 8
4
Image /page/4/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. Below the word "VENTANA" is the text "A Member of the Roche Group" in a smaller font size.
807.92 (b)(1/2): Brief Description of Clinical Data (Non-clinical data N/A)
The Virtuoso System for IHC KI-67 (30-9) was clinically validated via two studies. The first (primary) study evaluated overall system performance across four sites in terms of 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. In the second study, scanner precision was evaluated in an isolated fashion among three pathologists for inter-pathologist reproducibility of the two Virtuoso applications, and intra-pathologist/inter-day reproducibility of the two Virtuoso applications was also evaluated. 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 Ki-67 classifications of less than or equal to 10% staining to describe negative, and greater than 10% to describe positive. The overall agreements across the four sites were: 92%, 81%, 86%, and 87%, respectively. The data, with the 95% confidence intervals (CI) around the agreements are shown below.
| Confusion Matrix | Site 1
(n = 120) | | Site 2
(n = 118) | | Site 3
(n = 114) | | Site 4
(n = 118) | | |
|----------------------|---------------------|----------------------|---------------------|----------------------|---------------------|--------------------|---------------------|--------------------|----|
| | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |
| Manual | Neg (≤10%) | 37 | 10 | 43 | 0 | 46 | 3 | 59 | 5 |
| | Pos (>10%) | 0 | 73 | 23 | 52 | 13 | 52 | 10 | 44 |
| Manual | % Agreement | 92%
(85% - 95%) | | 81%
(72% - 87%) | | 86%
(78% - 91%) | | 87%
(80% - 92%) | |
| | (95% CI) | | | | | | | | |
| Negative % Agreement | | 79%
(65% - 88%) | | 100%
(92% - 100%) | | 94%
(83% - 98%) | | 92%
(83% - 97%) | |
| Positive % Agreement | | 100%
(95% - 100%) | | 69%
(58% - 79%) | | 80%
(69% - 88%) | | 81%
(69% - 90%) | |
Ki-67 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: 88%, 86% and 81%, respectively. That data table, along with the 95% Cls, is presented below.
5
Image /page/5/Picture/0 description: The image shows the logo for Ventana. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in all caps. A registered trademark symbol is located to the right of the word. The text "A Member of the Roche Group" is located below the logo.
A Member of the Roche Group
| Confusion Matrix | Image Analysis | Site 1 | Site 2 | Site 3 | Site 4 | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| (n = 120) | (n = 117) | (n = 114) | (n = 117) | |||||||
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |||
| Manual | Neg (≤10%) | 37 | 10 | 40 | 2 | 42 | 7 | 41 | 22 | |
| Pos (>10%) | 5 | 68 | 14 | 61 | 9 | 56 | 0 | 54 | ||
| % Agreement | 88% | |||||||||
| (80% - 92%) | 86% | |||||||||
| (79% - 91%) | 86% | |||||||||
| (78% - 91%) | 81% | |||||||||
| (73% - 87%) | ||||||||||
| Negative % Agreement | 79% | |||||||||
| (65% - 88%) | 95% | |||||||||
| (84% - 99%) | 86% | |||||||||
| (73% - 93%) | 65% | |||||||||
| (53% - 76%) | ||||||||||
| Positive % Agreement | 93% | |||||||||
| (85% - 97%) | 81% | |||||||||
| (71% - 89%) | 86% | |||||||||
| (76% - 93%) | 100% | |||||||||
| (93% - 100%) |
Ki-67 Agreement: Image Analysis vs Manual (manual = true score)
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 98% to 100%, 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 | 3 | 2 | 1 | 1 | 1 | 1 |
| Pos | 37 | 0 | 37 | 0 | 36 | ||
| Session 2 | Neg | 2 | 1 | 0 | |||
| Pos | 38 | 0 | 37 | ||||
| % Agreement | 98% | 97% | 100% | ||||
| (95% CI) | (87% - 100%) | (87% - 100%) | (91% - 100%) |
6
Image /page/6/Picture/0 description: The image shows the word "VENTANA" in all caps, with a registered trademark symbol next to the last letter. To the left of the word is a circular design made up of arrow shapes pointing inward. Below the word "VENTANA" is the text "A Member of the Roche Group".
Image Analysis
The agreements between each of the three comparisons across three sessions with the same pathologist are shown below. The agreements ranged from 89% to 97%, and the data (with 95% CIs) are shown below.
| Intra-Pathologist Image Analysis | |||||||
|---|---|---|---|---|---|---|---|
| Confusion Matrix | Session 2 | Session 3 | Session 3 | ||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Session 1 | Neg | 8 | 5 | 7 | 3 | 7 | 1 |
| Pos | 30 | 1 | 0 | 29 | 0 | 30 | |
| Session 2 | Neg | 6 | 32 | 5 | 1 | ||
| Pos | 32 | 2 | 30 | ||||
| % Agreement | 89% | 97% | 92% | ||||
| (95% CI) | (76% - 96%) | (87% - 100%) | (79% - 97%) |
- b. Inter-Pathologist (pair-wise comparisons, Pathologist 1 vs Pathologist 2, Pathologist 1 vs Pathologist 3, Pathologist 2 vs Pathologist 3)
Digital Read
The reproducibility in the Virtuoso digital readings among three pathologists is shown below, along with the 95% CIs. The percent total agreements ranged from 71% to 85%.
| Inter-Pathologist Digital | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| 66 | 52 | 61 | 55 | 61 | 55 | |||
| Site 1 | Neg | 37 | 35 | 0 | 30 | 3 | ||
| Pos | 83 | 31 | 52 | 31 | 52 | |||
| Site 2 | Neg | 66 | 54 | 10 | ||||
| Pos | 52 | 7 | 45 | |||||
| % Agreement | 74% | 71% | 85% | |||||
| (95% CI) | (65%- | 81%) | (62%- | 78%) | (78%- | 91%) |
Image Analysis
The reproducibility in the Virtuoso image analysis interpretations among three pathologists is shown below, along with the 95% CIs. The percent agreements ranged from 84% to 93%.
7
Image /page/7/Picture/0 description: The image shows the word "VENTANA" in all capital letters. To the left of the word is a symbol that looks like a star made of arrows. A registered trademark symbol is to the right of the last letter.
A Member of the Roche Group
| Inter-Pathologist Image Analysis | ||||||
|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||
| Neg | Pos | Neg | Pos | Neg | Pos | |
| 54 | 63 | 52 | 63 | 52 | 63 | |
| Site 1 | 37 | 2 | 36 | 1 | ||
| 17 | 61 | 16 | 62 | |||
| Site 2 | 48 | 4 | ||||
| 4 | 59 | |||||
| % Agreement | 84% | 85% | 93% | |||
| (95% CI) | (76% - 89%) | (78% - 91%) | (87% - 96%) |
Scanner Precision
When the iScan scanner was evaluated for inter-site and intra-site/inter-day precision, the percent agreements for three image analysis fields of views were in approximately 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 Ki-67 (30-9). The test system was shown to be safe and effective for its intended use.
8
Image /page/8/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 text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines suggesting movement or connection.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Mr. Troy Quander Vice President, Regulatory Affairs Ventana Medical Systems, Inc. 1910 E. Innovation Park Drive Tuscon, Arizona 85755
FEB 2 2 2012
Re: K111755 Virtuoso™ System for IHC Ki-67 (30-9) Trade/Device Name: 21 CFR §864.1860 Regulation Number: Immunohistrochemistry reagents and kits Regulation Name: Class II Regulatory Class: NON, NOT, OEO Product Code: January 18, 2012 Dated: January 19, 2012 Received:
Dear Mr. Quander:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becomen on the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use starcu in the onerobate) to region of the Medical Device Amendments, or to commerce provision in May 20, 1978, the eccordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). and Cosmetic Herefore, market the device, subject to the general controls provisions of the Act. The T ou may, merelore, manel the act include requirements for annual registration, listing of general controls provisions of the rice, 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 If your device is elassified (boo abor regulations affecting your device can be found in Title 21, additional controllo. Entitions (CFR), Parts 800 to 895. 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 Please be advised that I DA 3 issuates Cra business with other requirements of the Act that I Drivias made a and regulations administered by other Federal agencies.
You must comply with all the Act's requirements, including, but not limited to: registration and r ou must comply with an the Fiel CFR Parts 801 and 809); medical device reporting Ilsung (21 CFR Part 007); laooinig (21 verse events) (21 CFR 803); and good manufacturing of 1920); (reporting of inculcal device relation as releases (QS) regulation (21 CFR Part 200). This practice requirements as bet relax teting your device as described in your Section 510(k)
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premarket notification. The FDA finding of substantial equivalence of your device to a legally premarked notification - 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 Parts 801 and 11 you desire openite and In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR 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 Tou thay of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
for 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
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INDICATIONS FOR USE
510(k) Number (if Known):
Virtuoso™ System for IHC Ki-67 (30-9) Device Name:
Indications for Use
Indication(s) 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 Ki67 (30-9) 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 Ki67 (30-9); protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) assay is indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with this assay, the Virtuoso™ System for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC Ki67 (30-9) 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 Ki67 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 CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the Virtuoso™ System for Ki67 (30-9) Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay 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)
Section 2- Indications for Use
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Office of In Vitro Dia Device Evaluation and
510(k) K111755.