(519 days)
Not Found
No
The document explicitly states the software "makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process," and there is no mention of AI, DNN, or ML.
No.
The device is intended for in vitro diagnostic use as an aid to the pathologist for analysis and viewing tissues and cells, and in the detection and semi-quantitative measurement of Ki-67 protein, which are diagnostic purposes, not therapeutic.
Yes
The device 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" and specifically "as an aid to the pathologist in the detection and semi-quantitative measurement of Ki-67 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue." These uses clearly define it as a diagnostic device.
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 IHC Ki-67 (30-9) Digital Read and Image Analysis applications are specifically intended for use as an aid in the assessment of Ki-67 status in breast cancer patients, which is a diagnostic application.
- Context: The device is used to analyze biological specimens (formalin-fixed, paraffin-embedded tissues) to provide information for diagnostic purposes (assessing proliferative activity and Ki-67 status).
The definition of an IVD generally includes devices used to examine specimens derived from the human body to provide information for diagnostic purposes. This device clearly fits that description.
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 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 semi-quantitative measurement of Ki-67 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. Ki-67 results are indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with Ventana Medical Systems, Inc. CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody Assay, it 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 Ki-67 (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 Ki-67 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- Ki-67 (30-9) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC Ki-67 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki-67 (30-9) Rabbit 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, 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.
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 CONFIRMIM Ki-67 (30-9) rabbit monoclonal primary antibody.
- Reagents for visualization, such as universal DAB chromogen o
- Associated materials for completing immunohistochemical staining according to the appropriate package insert
- Color printer if user wishes to print color copies
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 are reacted with the Ki-67 (30-9) 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
Digital images of microscope glass slides (scanned by iScan slide scanner)
Anatomical Site
Formalin-fixed, paraffin-embedded normal and neoplastic tissues (specifically breast tissue for Ki-67)
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
Description of the test set: 120 cases of formalin-fixed, paraffin-embedded normal and neoplastic tissue slides stained with Ki-67 (30-9) antibody.
Sample size: 120 cases for digital read performance, 120 cases for image analysis performance (evaluated by three pathologists at three sites).
Data source: Cases were stained using the Benchmark ULTRA stainer. Manual scores were used as the reference result.
Annotation protocol: Pathologists manually scored cases with a routine microscope, and then used the Virtuoso digital read or image analysis application. Data were evaluated as positive or negative for Ki-67 status using 0% to 10% as negative status, and >10% as positive status.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
DIGITAL READ PERFORMANCE
Study type: Concordance study
Sample size: 120 cases
Key results:
Agreement: Digital Read vs Manual (manual = true score) (ULTRA stainer) Negative= 0-10%; Positive=>10%
Positive Percent Agreement (PPA) n/N (%): 52/52 (100.0) (95% CI: 93.1-100)
Negative Percent Agreement (NPA) n/N (%): 56/68 (82.4) (95% CI: 71.6-89.6)
Overall Percent Agreement (OPA) n/N (%): 108/120 (90.0) (95% CI: 83.3-94.2)
IMAGE ANALYSIS PERFORMANCE
Study type: Concordance study
Sample size: 120 cases, evaluated by three pathologists at three sites.
Key results:
Agreement: Image Analysis vs Manual (manual = true score)
Positive Percent Agreement (PPA) n/N (%): 52/77 (67.5) (95% CI: 56.5-76.9)
Negative Percent Agreement (NPA) n/N (%): 40/41 (97.6) (95% CI: 87.4-99.6)
Overall Percent Agreement (OPA) n/N (%): 92/118 (78.0) (95% CI: 69.7-84.5)
Agreement: Site 1 Image Analysis vs Manual (manual = true score) Negative= 0-10%; Positive=>10%
Positive Percent Agreement (PPA) n/N (%): 54/67 (80.6) (95% CI: 69.6-88.3)
Negative Percent Agreement (NPA) n/N (%): 43/45 (95.6) (95% CI: 85.2-98.8)
Overall Percent Agreement (OPA) n/N (%): 97/112 (86.6) (95% CI: 79.1-91.7)
Agreement: Site 3 Image Analysis vs Manual (manual = true score) Negative= 0-10%; Positive=>10%
Positive Percent Agreement (PPA) n/N (%): 59/69 (85.5) (95% CI: 75.3-91.9)
Negative Percent Agreement (NPA) n/N (%): 49/50 (98.0) (95% CI: 89.5-99.6)
Overall Percent Agreement (OPA) n/N (%): 108/119 (90.8) (95% CI: 84.2-94.8)
Conclusions from Clinical Testing: The overall agreement between the digital read and the manual read at one site was 90.0%, and the overall agreements between image analysis and the manual read across three sites were 78.0%, 86.6%, and 90.8%, and the predetermined acceptance criterion for each measurement of 75% has been met.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Digital Read Performance:
Positive Percent Agreement (PPA)
Negative Percent Agreement (NPA)
Overall Percent Agreement (OPA)
Image Analysis Performance:
Positive Percent Agreement (PPA)
Negative Percent Agreement (NPA)
Overall Percent Agreement (OPA)
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/1 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. The words "A Member of the Roche Group" are written in a smaller font size below the main logo.
SECTION 6 510(k) SUMMARY
This 510(k) Summary is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K121033.
| 807.92 (a)(1): | Name: | Ventana Digital Pathology | |
|---|---|---|---|
| Address: | c/o Ammirati Regulatory Consulting | ||
| Los Altos, CA 94043 | |||
| Phone: | (650) 949-2768 | SEP 06 2012 | |
| FAX: | (650) 949-5347 | ||
| Contact: | Erika B. Ammirati | ||
| Consultant to Ventana Medical Systems, Inc. |
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
Product Codes: NOT, NON, OEO
807.92 (a)(3): Identification of the legally marketed predicate devices
This Virtuoso System for IHC Ki-67 (30-9) is substantially equivalent to its immediate predecessor with the same name, cleared under K111755 on February 22, 2012. The two Virtuoso systems are identical, with the sole difference being the automatic stainer that can be used with the reagents to stain the glass slides. The first Ki-67 submission qualified the Benchmark XT stainer, and this current submission qualified a second automatic stainer, the Benchmark ULTRA stainer.
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
Page 1 of 6
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View. CA 94043ff. 408 207 4200fF: 408 207 4299 ww.ventanadigitalpathology.com
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 circular design made up of eight arrow-like shapes pointing inward. A small circled "R" trademark symbol is located to the right of the word.
A Member of the Roche Group
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.
The Virtuoso software is designed to complement the routine Software: 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 CONFIRMIM Ki-67 (30-9) rabbit monoclonal primary antibody .
- Reagents for visualization, such as universal DAB chromogen o
- . Associated materials for completing immunohistochemical staining according to the appropriate package insert
- o 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 are reacted with the Ki-67 (30-9) 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
Page 2 of 6
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View, CA 9404317; 408 207 4299 www.ventanadigitalpathology.com
2
ENTANA A Member of the Roche Group
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 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 semi-quantitative measurement of Ki-67 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. Ki-67 results are indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with Ventana Medical Systems, Inc. CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody Assay, it 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 Ki-67 (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 Ki-67 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- Ki-67 (30-9) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC Ki-67 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View, CA 9404311: 408 207 4200F: 408 207 4299 ww.ventanadigitalpathology.com
3
Image /page/3/Picture/0 description: The image shows the Ventana logo. The logo consists of a circular design made up of arrow shapes pointing inward, followed by the word "VENTANA" in bold, sans-serif font. Below the word "VENTANA" is the text "A Member of the Roche Group".
807.92 (a)(6): Technological Similarities and Differences to the Predicate Devices
| Characteristic | Virtuoso™ IHC Ki-67 (30-9)
[Benchmark ULTRA Stainer] | Virtuoso™ IHC Ki-67 (30-9)
[Benchmark XT Stainer] K111755 |
|----------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| | This device is intended for in vitro diagnostic
(IVD) use. | SAME |
| Intended
Use/Indications
for 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. | SAME |
| | 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
semi-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 Ki-67 protein of breast cancer
patients (but is not the sole basis for
treatment). | SAME |
| 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 | Ventana iScan slide scanner, computer, color
monitor, proprietary software for Ki-67 (30-9) | Same |
| Platform Components | mouse, keyboard, windows web browser. | Same |
| Primary Antibody
(Assay) Reagent | Ventana CONFIRM™ Ki-67 (30-9)
(reagent is Class 1, 510(k) exempt) | Same |
| Ancillary
Reagents/Stainers | DAB universal chromogen kits,
Slides stained with Benchmark ULTRA
stainer | DAB universal chromogen kits
Slides stained with Benchmark XT
stainer |
| Localization of
IHC positive stain | Nucleus | Same |
| | Interpretation is performed by the pathologist. | |
The following chart describes similarities and differences between the two test systems.
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View. CA 94043fT: 408 207 4200fF: 408 207 4299 ww.ventanadigitalpathology.com
4
Image /page/4/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 located to the upper right of the last "A" in "VENTANA". Below the logo, in a smaller, italicized font, is the text "A Member of the Roche Group".
807.92 (b)(1/2): Brief Description of Clinical Data (Non-clinical data N/A)
DIGITAL READ PERFORMANCE
The Virtuoso System for IHC Ki-67 (30-9) with the Benchmark ULTRA stainer was clinically validated for digital reading (DR) via a concordance study where 120 cases were evaluated by the manual and DR methods by one pathologist at one site. Each case was scored manually with a routine microscope and as a digital image. The manual score (reference result) was compared to the digital read result.
The data were evaluated as positive or negative for Ki-67 status using 0% to 10% as negative status, and >10% as positive status.
Agreement: Digital Read vs Manual (manual = true score) (ULTRA stainer) Negative= 0-10%; Positive=>10%
| Manual Microscopic Read | |||
|---|---|---|---|
| Digital Read | Positive | Negative | Total |
| Positive | 52 | 12 | 64 |
| Negative | 0 | 56 | 56 |
| Total | 52 | 68 | 120 |
| Positive Percent Agreement (PPA) n/N (%) (95% CI) | 52/52 (100.0) (93.1-100) | ||
| Negative Percent Agreement (NPA) n/N (%) (95% CI) | 56/68 (82.4) (71.6-89.6) | ||
| Overall Percent Agreement (OPA) n/N (%) (95% CI) | 108/120 (90.0) (83.3-94.2) |
IMAGE ANALYSIS PERFORMANCE
The Virtuoso System for IHC Ki-67 (30-9) with the Benchmark ULTRA stainer was clinically validated for image analysis (IA) via a concordance study where 120 cases were evaluated by the manual and IA methods by three pathologists at three sites. Each case was scored manually with a routine microscope and by using the Virtuoso IA application. The manual score (reference result) was compared to the IA result.
The data were evaluated as positive or negative for Ki-67 status using 0% to 10% as negative status, and >10% as positive status.
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View. CA 9404377: 408 207 4299 www.ventanadigitalpathology.com
5
Image /page/5/Picture/0 description: The image shows the Ventana logo, which consists of a stylized sunburst symbol to the left of the word "VENTANA" in bold, sans-serif font. A registered trademark symbol appears to the upper right of the last "A" in "VENTANA". Below the logo is the text "A Member of the Roche Group" in a smaller, serif font, indicating Ventana's affiliation with the Roche Group.
| Manual Microscopic Read | |||
|---|---|---|---|
| Image Analysis | Positive | Negative | Total |
| Positive | 52 | 1 | 53 |
| Negative | 25 | 40 | 65 |
| Total | 77 | 41 | 118 |
| Positive Percent Agreement (PPA) n/N (%) (95% CI) | 52/77 (67.5) (56.5-76.9) | ||
| Negative Percent Agreement (NPA) n/N (%) (95% CI) | 40/41 (97.6) (87.4-99.6) | ||
| Overall Percent Agreement (OPA) n/N (%) (95% CI) | 92/118 (78.0) (69.7-84.5) |
Agreement: Site 1 Image Analysis vs Manual (manual = true score) Negative= 0-10%; Positive= >10%
Agreement: Site 2 Image Analysis vs Manual (manual = true score) Negative= 0-10%; Positive=>10%
| Manual Microscopic Read | ||||
|---|---|---|---|---|
| Image Analysis | Positive | Negative | Total | |
| Positive: >10% | 54 | 2 | 56 | |
| Negative: 0-10% | 13 | 43 | 56 | |
| Total | 67 | 45 | 112 | |
| Positive Percent Agreement (PPA) n/N (%) (95% CI) | 54/67 (80.6) (69.6-88.3) | |||
| Negative Percent Agreement (NPA) n/N (%) (95% CI) | 43/45 (95.6) (85.2-98.8) | |||
| Overall Percent Agreement (OPA) n/N (%) (95% CI) | 97/112 (86.6) (79.1-91.7) |
Agreement: Site 3 Image Analysis vs Manual (manual = true score) Negative= 0-10%; Positive=>10%
| Manual Microscopic Read | |||
|---|---|---|---|
| Image Analysis | Positive | Negative | Total |
| Positive: >10% | 59 | 1 | 60 |
| Negative: 0 - 10% | 10 | 49 | 59 |
| Total | 69 | 50 | 119 |
| Positive Percent Agreement (PPA) n/N (%) (95% CI) | 59/69 (85.5) (75.3-91.9) | ||
| Negative Percent Agreement (NPA) n/N (%) (95% CI) | 49/50 (98.0) (89.5-99.6) | ||
| Overall Percent Agreement (OPA) n/N (%) (95% CI) | 108/119 (90.8) (84.2-94.8) |
807.92 (b)(3): Conclusions from Clinical Testing
Concordance studies were performed for the Virtuoso System for IHC Ki-67 (30-9) with the Benchmark ULTRA stainer. The overall agreement between the digital read and the manual read at one site was 90.0%, and the overall agreements between image analysis and the manual read across three sites were 78.0%, 86.6%, and 90.8%, and the predetermined acceptance criterion for each measurement of 75% has been met.
Ventana Digital Pathology | 203 Ravendale Dr., Mountain View, CA 94043JT: 408 207 4299 ww.ventanadigitalpathology.com
6
Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its wing, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circle around the eagle. The text is in all caps and appears to be in a sans-serif font. The logo is black and white.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
September 6, 2013
VENTANA MEDICAL SYSTEMS INC. C/O MS. ERIKA AMMIRATI CONSULTANT 575 SHIRL YNN COURT LOS ALTOS CA 94022
Re: K121033
Trade/Device Name: Ventana Virtuoso System for IHC Ki67 (30-9) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: NQN, NOT, OEO Dated: August 21, 2013 Received: August 22, 2013
Dear Ms. Ammirati:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
7
Page 2-Ms. Erika Ammirati
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Maria M. Chan -S
Maria Chan, PhD Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
8
Indications for Use
510(k) Number (if known): K121033.
Device Name: Virtuoso™ System for JHC Ki-67 (30-9)
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 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 semi-quantitative measurement of Ki-67 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. K667 results are indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with Ventana Medical Systems, Inc. CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody Assay, it 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 Ki-67 (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 Ki-67 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- Ki-67 (30-9) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC Ki-67 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.
Prescription Use _ X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH; Office of in Vitro Diagnostics and Radiological Health (OIR)
Maria M. Chan -S
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
510(k): K121033