(293 days)
Not Found
No
The document describes "image analysis algorithms" but explicitly states the software "makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process." There is no mention of AI, ML, or training/test sets for such models.
No
The device is an in vitro diagnostic (IVD) device intended as an aid to the pathologist for diagnosis, not for direct therapeutic intervention. It assists in the assessment of p53 status in breast cancer patients, which aids in diagnosis and treatment planning, but does not itself treat the condition.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "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..." and further specifies its use in "detection and semi-quantitative measurement of p53 (DO-7) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue," all of which fall under the scope of diagnostic activities.
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:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Virtuoso system is "intended for in vitro diagnostic use as an aid to the pathologist".
- Specific Application: The description of the Virtuoso™ System for p53 (DO-7) further clarifies its use "for in vitro diagnostic use as an aid to the pathologist in the detection and semi-quantitative measurement of p53 (DO-7) protein".
- Accessory to an IVD: It is described as an "accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody assay," which is itself an assay used for diagnostic purposes.
- Clinical Context: The device is used to analyze tissue samples (formalin-fixed, paraffin-embedded normal and neoplastic tissue) and provides information to aid in the assessment of p53 status in breast cancer patients, which is a clinical diagnostic application.
The device processes biological samples (tissue sections) and provides information used in the diagnosis and assessment of a disease (breast cancer) in a clinical setting, which aligns with the definition of 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 p53 (DO-7) 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 p53 (DO-7) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-p53 assay is indicated for the assessment of p53 protein where mutations have been linked to tumor proliferation. When used with this assay, the Virtuoso™ System for p53 (DO-7) is indicated for use as an aid in the assessment of p53 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC p53 (DO-7) 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 p53 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-p53 (DO-7) Mouse Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC p53 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody to clinical outcome has not been established.
Product codes (comma separated list FDA assigned to the subject device)
NOT, NON, 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.
Hardware: The iScan slide scanning device captures digital images of 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.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Digital images of formalin-fixed, paraffin-embedded tissues on glass slides.
Anatomical Site
Breast cancer patients, normal and neoplastic tissue in formalin-fixed, paraffin-embedded histologic sections.
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
The Virtuoso System for IHC p53 (DO-7) was clinically validated via two studies. The first (primary) study evaluated overall system performance. The data from both studies are summarized below.
Study 1:
Sample size: Site 1 (n = 119), Site 2 (n = 119), Site 3 (n = 117), Site 4 (n = 114 for Agreement/Concordance DR vs Manual), Site 4 (n = 105 for Agreement/Concordance IA vs Manual). The sample size for reproducibility studies varied for pair-wise comparisons and across sessions/pathologists.
Data source: Formalin-fixed, paraffin-embedded normal and neoplastic tissue stained with p53 (DO-7) primary antibody.
Annotation protocol: The primary study evaluated 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. It also evaluated intra-pathologist/inter-day reproducibility of the two Virtuoso applications (3 sessions), and inter-pathologist reproducibility (3 sites) of the two Virtuoso applications. P53 classifications were categorized as "neg" (less than or equal to 10%) and "pos" (greater than 10%).
Study 2:
Sample size: A subset of the clinical cases (n = 40) from the primary study.
Data source: Subset of clinical cases from the primary study.
Annotation protocol: Scanner precision was evaluated in an isolated fashion via a cross-over design. This study evaluated inter-scanner precision and intra-scanner/inter-day precision for the image analysis application only.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study type: Clinical validation studies (agreement/concordance, reproducibility, scanner precision).
Sample size: Variable, as mentioned in the test set description.
AUC: Not Found
MRMC: Not Found
Standalone performance: Not Found
Key results:
Agreement/Concordance:
- Virtuoso Digital Read vs Manual Method: Overall agreements across four sites were 93%, 95%, 94%, and 82%.
- Virtuoso Image Analysis vs Manual Method: Overall agreements across four sites were 92%, 97%, 91%, and 90%.
Reproducibility:
- Intra-Pathologist/Inter-Day Digital Read: Total agreements ranged from 90% to 95%.
- Intra-Pathologist/Inter-Day Image Analysis: Agreements ranged from 80% to 93%.
- Inter-Pathologist Manual Read: Agreements ranged from 87% to 92%.
- Inter-Pathologist Digital Read: Percent total agreements ranged from 94% to 99%.
- Inter-Pathologist Image Analysis: Percent agreements ranged from 94% to 97%.
Scanner Precision:
- Inter-site and intra-site/inter-day precision: Percent agreements for three image analysis field of views were approximately 90% for every comparison.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Agreement:
-
Digital Read vs Manual (manual = true score):
- Site 1: Negative % Agreement 100% (95% CI: 95% - 100%), Positive % Agreement 83% (95% CI: 69% - 91%)
- Site 2: Negative % Agreement 93% (95% CI: 86% - 97%), Positive % Agreement 100% (95% CI: 89% - 100%)
- Site 3: Negative % Agreement 95% (95% CI: 87% - 98%), Positive % Agreement 93% (95% CI: 81% - 98%)
- Site 4: Negative % Agreement 74% (95% CI: 63% - 82%), Positive % Agreement 97% (95% CI: 87% - 100%)
-
Image Analysis vs Manual (manual = true score):
- Site 1: Negative % Agreement 99% (95% CI: 93% - 100%), Positive % Agreement 80% (95% CI: 67% - 89%)
- Site 2: Negative % Agreement 95% (95% CI: 89% - 98%), Positive % Agreement 100% (95% CI: 89% - 100%)
- Site 3: Negative % Agreement 95% (95% CI: 87% - 98%), Positive % Agreement 83% (95% CI: 69% - 92%)
- Site 4: Negative % Agreement 91% (95% CI: 82% - 96%), Positive % Agreement 89% (95% CI: 76% - 96%)
Reproducibility (percent agreement shown for pair-wise comparisons):
-
Intra-Pathologist Digital Read (Session 1 vs Session 2): 98% (87% - 100%)
-
Intra-Pathologist Digital Read (Session 1 vs Session 3): 95% (83% - 99%)
-
Intra-Pathologist Digital Read (Session 2 vs Session 3): 93% (80% - 97%)
-
Intra-Pathologist Image Analysis (Session 1 vs Session 2, 93% (80% - 97%)
-
Intra-Pathologist Image Analysis (Session 1 vs Session 3, 98% (83% - 99%)
-
Intra-Pathologist Image Analysis (Session 2 vs Session 3, 100% (87% - 100%)
-
Inter-Pathologist Manual (Site 1 vs Site 2): 87% (80% - 92%)
-
Inter-Pathologist Manual (Site 1 vs Site 3): 92% (86% - 96%)
-
Inter-Pathologist Manual (Site 2 vs Site 3): 91% (84% - 95%)
-
Inter-Pathologist Digital (Site 1 vs Site 2): 99% (95% - 100%)
-
Inter-Pathologist Digital (Site 1 vs Site 3): 94% (88% - 97%)
-
Inter-Pathologist Digital (Site 2 vs Site 3): 95% (89% - 98%)
-
Inter-Pathologist Image Analysis (Site 1 vs Site 2): 97% (93% - 99%)
-
Inter-Pathologist Image Analysis (Site 1 vs Site 3): 94% (88% - 97%)
-
Inter-Pathologist Image Analysis (Site 2 vs Site 3): 97% (92% - 99%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
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.
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Image /page/0/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 on 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, serif font.
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 K111872.
| 807.92 (a)(1): Name: | Ventana Digital Pathology |
|---|---|
| Address: | 919 Hermosa Court |
| Sunnyvale, CA 94085 |
| Phone: | (520) 229-4184 |
|---|---|
| FAX: | (520) 229-5960 |
| Contact: | Mr. Troy Quander |
807.92 (a)(2): Device name- trade name and common name, and classification
| Trade name: | Virtuoso™ System for IHC p53 (DO-7) |
|---|---|
| Common Name: | Digital pathology and image analysis system for |
| immunochemistry-stained slides | |
| Classifications: | 21 CFR § 864.1860- Immunohistochemistry reagents and kit |
Product Codes: NOT, NON, OEO
807.92 (a)(3): Identification of the legally marketed predicate devices
The Virtuoso System for IHC p53 (DO-7) is substantially equivalent to BioImagene's PATHIAM™ 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 p53 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
Page 1 of 8
APR 1 9 2012
1
VENTANA
A Member of the Roche Group
(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.
Hardware: The iScan slide scanning device captures digital images of 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™ P53 (DO-7) mouse 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 (DO-7) 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
2
A Member of the Roche Group
VENTANA
pathologist has the choice of accepting the result or overriding with his/her own score for some or all FOVs.
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 p53 (DO-7) 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 p53 (DO-7) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ antip53 (DO-7) Mouse Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-p53 assay is indicated for the assessment of p53 protein where mutations have been linked to tumor proliferation. When used with this assay, the Virtuoso™ System for p53 (DO-7) is indicated for use as an aid in the assessment of p53 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC p53 (D0-7) 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 p53 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-p53 (DO-7) Mouse Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC p53 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody to clinical outcome has not been established.
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Image /page/3/Picture/0 description: The image shows the logo for Ventana Medical Systems, Inc. The logo consists of a stylized sun-like symbol on the left, followed by the word "VENTANA" in bold, uppercase letters. To the right of the word "VENTANA" is a superscripted registered trademark symbol. Below the logo is the text "A Member of the Roche Group" in a smaller font size.
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 p53 (DO-7) | 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 p53 (DO-7) Digital Read and
Image Analysis applications are intended
for use as an aid to the pathologist in the
detection and semi-quantitative
measurement of p53 protein in formalin-
fixed, paraffin-embedded normal and
neoplastic tissue. When used with Ventana
Medical Systems, Inc. CONFIRM™ anti-
p53 (DO-7) Mouse 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 | Biolmagene (now Ventana) iScan slide
scanner, computer, color monitor,
proprietary software for p53 (DO-7) | 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™ p53 (DO-7)
(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 |
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.
.
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807.92 (b)(1/2): Brief Description of Clinical Data (Non-clinical data N/A)
The Virtuoso System for IHC p53 (DO-7) was clinically validated via two studies. The first (primary) study evaluated overall system performance across four sites 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 of the Virtuoso system, (2) intra-pathologist/inter-day reproducibility of the two Virtuoso applications (3 sessions), and (3) interpathologist reproducibility (3 sites) 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 intrascanner/inter-day precision, as the image analysis application is the more objective of the two applications and 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 p53 classifications of less than or equal to 10% to describe negative, and greater than 10% to describe positive. The overall agreements across the four sites were: 93%, 95%, 94% and 82%, respectively. The data, with the 95% confidence intervals (CI) around the agreements are shown below.
| Confusion Matrix | | Site 1
(n = 119) | | Site 2
(n = 119) | | Site 3
(n = 117) | | Site 4
(n = 114) | |
|----------------------|-------------|---------------------|-------|---------------------|-------|---------------------|------|---------------------|-------|
| | | Digital | | | | | | | |
| | | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos |
| Manual | Neg (≤10%) | 73 | 0 | 82 | 6 | 71 | 4 | 56 | 20 |
| | Pos (>10%) | 8 | 38 | 0 | 31 | 3 | 39 | 1 | 37 |
| | % Agreement | 93% | | 95% | | 94% | | 82% | |
| | (95% CI) | (87% - | 97%) | (89% - | 98%) | (88% - | 97%) | (73% - | 88%) |
| Negative % Agreement | | 100% | | 93% | | 95% | | 74% | |
| (95% CI) | | (95% - | 100%) | (86% - | 97%) | (87% - | 98%) | (63% - | 82%) |
| Positive % Agreement | | 83% | | 100% | | 93% | | 97% | |
| (95% CI) | | (69% - | 91%) | (89% - | 100%) | (81% - | 98%) | (87% - | 100%) |
Agreement: Digital Read vs Manual (manual = true score) n53 (DO-7)
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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 four sites were: 92%, 97%, 91%, and 90%, respectively. That data table, along with the 95% CIs, is presented below.
| Image Analysis | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 1 | ||||||||
| (n = 119) | Site 2 | ||||||||
| (n = 119) | Site 3 | ||||||||
| (n = 117) | Site 4 | ||||||||
| (n = 105) | |||||||||
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | ||
| Manual | Neg (≤10%) | 72 | 1 | 84 | 4 | 71 | 4 | 61 | 6 |
| Pos (>10%) | 9 | 37 | 0 | 31 | 7 | 35 | 4 | 34 | |
| % Agreement | 92% | 97% | 91% | 90% | |||||
| (95% CI) | (85% - 95%) | (92% - 99%) | (84% - 95%) | (83% - 95%) | |||||
| Negative % Agreement | 99% | 95% | 95% | 91% | |||||
| (95% CI) | (93% - 100%) | (89% - 98%) | (87% - 98%) | (82% - 96%) | |||||
| Positive % Agreement | 80% | 100% | 83% | 89% | |||||
| (95% CI) | (67% - 89%) | (89% - 100%) | (69% - 92%) | (76% - 96%) |
Agreement: Image Analysis vs Manual (manual = true score) p53 (DO-7)
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.
| p53 Intra-Pathologist Digital- 10% | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Session 2 | Session 3 | Session 3 | ||||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||||
| Session | |||||||||
| 1 | Neg | 27 | 26 | 1 | 25 | 2 | 25 | 15 | |
| Pos | 13 | 0 | 13 | 0 | 13 | ||||
| Session | |||||||||
| 2 | Neg | 26 | 24 | 2 | |||||
| Pos | 14 | 1 | 13 | ||||||
| % Agreement | 98% | 95% | 93% | ||||||
| (95% CI) | (87% - | 100%) | (83% - | 99%) | (80% - | 97%) |
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Image Analysis
The agreements between each of the three comparisons across three sessions with the same pathologist are shown below. The agreements ranged from 80% to 93%, and the data (with 95% CIs) are shown below.
| p53 Intra-Pathologist Image Analysis- 10% | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Session 2 | Session 3 | Session 3 | ||||||
| Neg | Pos | Neg | Pos | Neg | Pos | ||||
| 26 | 14 | 25 | ો રે | ટર | ો રે | ||||
| Session | Neg | 25 | 24 | 24 | |||||
| 1 . | Posl | । રે | 2 | 13 | 14 | ||||
| Session | Negl | 26 | 25 | ||||||
| 2 | Pos | 14 | 0 | 14 | |||||
| % Agreement | 93% | વે રેજી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્ | 98% | ||||||
| (95% CI) | (80% - | 97%) | (83% - | 99%) (187% - | 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 three pathologists were compared to each other. The agreements ranged from 87% to 92%, indicating some human variation among the three pathologists.
| Inter-Pathologist Manual | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| Site 1 | Neg | 74 | 88 | 31 | 76 | 42 | 76 | 42 |
| Pos | 46 | 73 | 0 | 70 | 3 | |||
| Site 2 | Neg | 15 | 31 | 6 | 39 | |||
| Pos | 88 | 76 | 11 | |||||
| 31 | 0 | 31 | ||||||
| % Agreement | 87% | 92% | 91% | |||||
| (95% CI) | (80% - 92%) | (86% - 96%) | (84% - 95%) |
Ventana Digital Pathology | 919 Hermosa Court, Sunnyvale, CA 94085 |T: 408 207 4299 www.ventanadigitalpathology.com | powered by BioImagene
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Image /page/7/Picture/0 description: The image shows the Ventana logo, which includes a stylized sun-like symbol on the left and the word "VENTANA" in capital letters. To the right of the word "VENTANA" is a registered trademark symbol. Below the logo is the text "A Member of the Roche Group" in a smaller font size.
Digital Read
The reproducibility in the Virtuoso digital readings among three pathologists is shown below, along with the 95% Cls. The percent total agreements ranged from 94% to 99%.
| Inter-Pathologist Digital | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| Site 1 | Neg | 81 | 81 | 0 | 74 | 6 | ||
| Pos | 38 | 1 | 37 | 1 | 37 | |||
| Site 2 | Neg | 82 | 75 | 6 | ||||
| Pos | 37 | 0 | 37 | |||||
| % Agreement | 99% | 94% | 95% | |||||
| (95% CI) | (95% - | 100%) | (88% - | 97%) | (89% - | 98%) |
Image Analysis
The reproducibility in the Virtuoso image analysis interpretations among three pathologists is shown below, along with the 95% Cls. The percent agreements ranged from 94% to 97%.
| Inter-Pathologist Image Analysis | ||||||||
|---|---|---|---|---|---|---|---|---|
| Confusion Matrix | Site 2 | Site 3 | Site 3 | |||||
| Neg | Pos | Neg | Pos | Neg | Pos | |||
| Site 1 | Neg | 81 | 81 | 0 | 76 | 4 | ||
| Pos | 38 | 3 | 35 | 3 | 35 | |||
| Site 2 | Neg | 84 | 79 | 4 | ||||
| Pos | 35 | 0 | 35 | |||||
| % Agreement | 97% | 94% | 97% | |||||
| (95% CI) | (93% - | 99%) | (88% - | 97%) | (92% - | 99%) |
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 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 p53 (DO-7). The test system was shown to be safe and 'effective for its intended use.
Ventana Digital Pathology | 919 Hermosa Court, Sunnyvale, CA 94085 |T: 408 207 4299 www.ventanadigitalpathology.com | powered by Biolmagene
8
DEPARTMENT OF HEALTH & HUMAN SERVICES
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 border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle or bird with outstretched wings, symbolizing the department's mission to protect and promote the health and well-being of Americans.
Public Health Service
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
APR 1 9 2012
Re: K111872
Trade/Device Name: Virtuoso" System for IHC p53 (DO-7) Regulation Number: 21 CFR §864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NON, NOT, OEO Dated: April 3, 2012 Received: April 4, 2012
Dear Mr. Quander:
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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (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 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 or any I vith all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter requirements as over marketing your device as described in your Section 510(k) premarket
9
Page 2 - Mr. Troy Quander
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 Parts 801 and 809), please contact the Office of 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 Division 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.
Maria M Chan
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 p53 (DO-7) Device Name:
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 p53 (DO-7) 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 p53 (DO-7) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-p53 assay is indicated for the assessment of p53 protein where mutations have been linked to tumor proliferation. When used with this assay, the Virtuoso™ System for p53 (DO-7) is indicated for use as an aid in the assessment of p53 status in breast cancer patients (but is not the sole basis for treatment).
Note: The IHC p53 (D0-7) 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 p53 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-p53 (DO-7) Mouse Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC p53 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody to clinical outcome has not been established.
Over-The-Counter Use AND/OR Prescription Use X (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D) Olvision Sign-Office of In Vitro Diagnostic Device Evaluation and Safety K111872
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics (OIVD)