(344 days)
No
The device description and performance studies focus on image acquisition, storage, viewing, and manual interpretation by pathologists. There is no mention of automated analysis, algorithms, or learning processes that would indicate AI/ML.
Yes
This device aids pathologists in the semi-quantitative measurement of HER2/neu, which is used to assess breast cancer patients for whom HERCEPTIN (Trastuzumab) treatment is being considered. This directly relates to guiding therapy.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states "The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI)..." and further, "as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue". This clearly indicates its role in disease diagnosis.
No
The device description explicitly states that the system is composed of both hardware (VL4 Scanner) and software components. While the application itself is software, it is part of a larger system that includes a physical scanner.
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 device is "intended for in vitro diagnostic use as an aid to pathology professionals". It also specifies its use in the detection and semi-quantitative measurement of HER2/neu in digital images of tissue stained with the Dako HercepTest™, which is itself an IVD indicated for assessing breast cancer patients for HERCEPTIN® treatment.
- Device Description: The device is designed to process and analyze biological samples (FFPE tissue sections) for diagnostic purposes.
- Performance Studies: The document describes performance studies (Clinical Comparison, Precision & Reproducibility, Inter-Scanner/Intra-Reader) that are typical for validating an IVD device. These studies assess the device's accuracy, reproducibility, and agreement with established methods (manual microscopy).
- Predicate Devices: The mention of predicate devices (K071671 Aperio ScanScope XT System; K111543 Virtuoso™ IHC HER2) further indicates that this device is being compared to other devices intended for similar diagnostic purposes.
All these factors strongly support the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
Product codes
OEO
Device Description
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended to aid pathology professionals in creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The system is composed of the following components:
- · VL4 Scanner: A hardware device that captures and compresses bright field images of tissue samples.
- · Data and Workflow Infrastructure: A set of networked applications which enables case data entry, acquisition, indexing, storage and acceptance of digital images, workflow management, and retrieval of case and image data.
- · Histology Workstation: The application which permits the histologist to review or enter case data and check quality of scanned images.
- · Pathology Workstation: The application which allows the pathologist to retrieve case data and review and annotate slide images.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Bright field images of tissue samples.
Anatomical Site
Formalin-fixed, paraffin-embedded (FFPE) breast cancer tissue sections.
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Pathology professionals, histologists, pathologists, lab professionals.
Clinical laboratory setting.
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
Clinical Comparison to Manual Microscopy:
- Sample size: 200 breast cancer cases (controls and specimen slides).
- Data source: Slides stained with the Dako HercepTest™.
- Annotation protocol: Four pathologists read cases using a conventional manual microscope (MM) and the Omnyx IDP (M-WSI), with a minimum 2-week washout period between modalities. Each pathologist reviewed WSIs from different VL4 scanners. Scores were binned into 0/1+ (neg) and 1+/2+ (pos) and trichotomous (0/1+, 2+, 3+) score categories.
Inter-Scanner/Intra-Reader:
- Sample size: 80 regions of interest (ROIs) extracted from WSIs of forty (40) HercepTest™ slides, with even distribution of score categories.
- Data source: ROIs obtained from three (3) different scanners, located in three different laboratory locations within GE Healthcare and operated by three independent operators.
- Annotation protocol: A single pathologist manually scored all ROIs based on the Dako HercepTest™ scoring guidelines. Each read session (for each scanner) was separated by a minimum of 1 week washout period, with the inclusion of wildcard ROIs.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Comparison to Manual Microscopy:
- Study Type: Clinical comparison study.
- Sample Size: 200 breast cancer cases.
- Key Results:
- Pairwise percent agreement between all pathologists on both MM and M-WSI modalities (inter-reader/intra-modality) was determined for both binned (0/1+ = neg; 1+/2+ = pos) and trichotomous (0/1+, 2+, 3+) score categories.
- Percent agreement between MM vs. M-WSI (inter-modality/intra-reader) for each pathologist was determined.
- The pairwise inter-reader/intra-modality percent agreements did not differ significantly between MM and M-WSI.
- High percent agreements between MM and M-WSI for each pathologist when examined by binary or trichotomous score category.
Precision & Reproducibility - Intra-Reader/Inter-Day:
- Study Type: Precision & Reproducibility study.
- Sample Size: Set of 40 HercepTest™ stained slides.
- Key Results: Three pathologists performed three independent readings of the slides using the M-WSI modality, with each read separated by a minimum one-week washout, including wildcards. Results presented as trichotomous and binary analysis, with additional negative and positive percent agreements (NPA and PPA).
Inter-Scanner/Intra-Reader:
- Study Type: Inter-scanner variability study.
- Sample Size: 80 regions of interest (ROIs) extracted from WSIs of 40 HercepTest™ slides.
- Key Results:
- Percent agreement between each of the scanner pairs were determined based on the ROI scores.
- When analyzed trichotomously (0/1+, 2+ and 3+), the inter-scanner/intra-reader variability had high percent agreement across all pairwise scanner comparisons.
- Data suggests very high reproducibility among scanners and indicates that M-WSI inter-scanner variability is primarily due to the subjectivity of score interpretation of the readers and not by scanner to scanner variability.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Inter-Reader/Intra-Modality (MM) - Trichotomous score categories:
- Pathologist 1 vs Pathologist 2: 85.9% (80%-90%)
- Pathologist 1 vs Pathologist 3: 88.0% (83%-92%)
- Pathologist 1 vs Pathologist 4: 80.5% (74%-85%)
- Pathologist 2 vs Pathologist 3: 87.9% (83%-92%)
- Pathologist 2 vs Pathologist 4: 82.1% (76%-87%)
- Pathologist 3 vs Pathologist 4: 87.2% (82%-91%)
Inter-Reader/Intra-Modality (M-WSI) - Trichotomous score categories:
- Pathologist 1 vs Pathologist 2: 83.4% (78%-88%)
- Pathologist 1 vs Pathologist 3: 73.4% (67%-79%)
- Pathologist 1 vs Pathologist 4: 82.4% (76%-87%)
- Pathologist 2 vs Pathologist 3: 74.4% (68%-80%)
- Pathologist 2 vs Pathologist 4: 83.5% (78%-88%)
- Pathologist 3 vs Pathologist 4: 64.4% (57%-71%)
Inter-Reader/Intra-Modality (MM) - Binary score categories:
- Overall Percent Agreement (95% CI):
- P1-P2: 91.0% (86%-94%)
- P1-P3: 93.5% (89%-96%)
- P1-P4: 86.7% (81%-91%)
- P2-P3: 93.5% (89%-96%)
- P2-P4: 86.2% (81%-90%)
- P3-P4: 89.7% (85%-93%)
- Average Positive Agreement (95% CI):
- P1-P2: 89.9% (85%-94%)
- P1-P3: 92.9% (88%-96%)
- P1-P4: 86.9% (81%-91%)
- P2-P3: 92.7% (88%-96%)
- P2-P4: 86.3% (81%-90%)
- P3-P4: 90.0% (85%-93%)
- Average Negative Agreement (95% CI):
- P1-P2: 91.8% (87%-95%)
- P1-P3: 94.0% (90%-96%)
- P1-P4: 86.5% (81%-91%)
- P2-P3: 94.1% (90%-96%)
- P2-P4: 86.0% (80%-90%)
- P3-P4: 89.5% (84%-93%)
Inter-Reader/Intra-Modality (M-WSI) - Binary score categories:
- Overall Percent Agreement (95% CI):
- P1-P2: 89.9% (85%-93%)
- P1-P3: 83.9% (78%-88%)
- P1-P4: 86.7% (81%-91%)
- P2-P3: 86.9% (82%-91%)
- P2-P4: 86.7% (81%-91%)
- P3-P4: 73.9% (67%-80%)
- Average Positive Agreement (95% CI):
- P1-P2: 88.9% (83%-93%)
- P1-P3: 79.2% (72%-85%)
- P1-P4: 87.2% (82%-91%)
- P2-P3: 82.7% (76%-88%)
- P2-P4: 86.9% (81%-91%)
- P3-P4: 70.3% (63%-77%)
- Average Negative Agreement (95% CI):
- P1-P2: 90.8% (86%-94%)
- P1-P3: 86.9% (82%-91%)
- P1-P4: 86.2% (80%-90%)
- P2-P3: 89.5% (85%-93%)
- P2-P4: 86.5% (81%-91%)
- P3-P4: 76.8% (71%-82%)
Intra-Reader/Inter-Modality (MM vs. M-WSI) - Binary score categories:
- Overall Percent Agreement (95% CI):
- Pathologist 1: 92.5% (88%-96%)
- Pathologist 2: 91.5% (87%-95%)
- Pathologist 3: 89.4% (79%-89%)
- Pathologist 4: 93.0% (88%-96%)
- Negative Percent Agreement (95% CI):
- Pathologist 1: 94.5% (88%-98%)
- Pathologist 2: 89.9% (82%-95%)
- Pathologist 3: 67.4% (57%-76%)
- Pathologist 4: 94.3% (88%-97%)
- Positive Percent Agreement (95% CI):
- Pathologist 1: 90.4% (82%-95%)
- Pathologist 2: 92.8% (86%-96%)
- Pathologist 3: 100% (97%-100%)
- Pathologist 4: 91.5% (83%-96%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 1 - Trichotomous score categories:
- Read 1 vs Read 2: 62.5% (47%-76%)
- Read 1 vs Read 3: 77.5% (62%-88%)
- Read 2 vs Read 3: 85.0% (71%-93%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 1 - Binary score categories:
- Overall % Agreement (95% CI):
- R1-R2: 70.0% (55%-82%)
- R1-R3: 85.0% (71%-93%)
- R2-R3: 85.0% (71%-93%)
- Negative % Agreement (95% CI):
- R1-R2: 66.7% (50%-80%)
- R1-R3: 85.7% (72%-93%)
- R2-R3: 80.0% (63%-90%)
- Positive % Agreement (95% CI):
- R1-R2: 72.7% (58%-84%)
- R1-R3: 84.2% (70%-93%)
- R2-R3: 88.0% (76%-94%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 2 - Trichotomous score categories:
- Read 1 vs Read 2: 95.0% (83%-99%)
- Read 1 vs Read 3: 97.5% (87%-100%)
- Read 2 vs Read 3: 97.5% (87%-100%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 2 - Binary score categories:
- Overall % Agreement (95% CI):
- R1-R2: 95.0% (83%-99%)
- R1-R3: 97.5% (87%-100%)
- R2-R3: 97.5% (87%-100%)
- Negative % Agreement (95% CI):
- R1-R2: 94.1% (81%-98%)
- R1-R3: 97.1% (85%-99%)
- R2-R3: 97.1% (85%-99%)
- Positive % Agreement (95% CI):
- R1-R2: 95.7% (85%-99%)
- R1-R3: 97.8% (88%-100%)
- R2-R3: 97.8% (88%-100%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 3 - Trichotomous score categories:
- Read 1 vs Read 2: 90.0% (77%-96%)
- Read 1 vs Read 3: 90.0% (77%-96%)
- Read 2 vs Read 3: 95.0% (83%-99%)
Intra-Reader/Inter-Day (M-WSI) for Pathologist 3 - Binary score categories:
- Overall % Agreement (95% CI):
- R1-R2: 97.5% (87%-100%)
- R1-R3: 100.0% (91%-100%)
- R2-R3: 97.5% (87%-100%)
- Negative % Agreement (95% CI):
- R1-R2: 95.7% (79%-99%)
- R1-R3: 100.0% (85%-100%)
- R2-R3: 95.7% (79%-99%)
- Positive % Agreement (95% CI):
- R1-R2: 98.2% (91%-100%)
- R1-R3: 100.0% (94%-100%)
- R2-R3: 98.2% (91%-100%)
Inter-Scanner/Intra-Reader - Trichotomous score categories:
- Scanner 1 vs Scanner 2: 95.0% (88%-98%)
- Scanner 1 vs Scanner 3: 88.8% (80%-94%)
- Scanner 2 vs Scanner 3: 91.3% (83%-96%)
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.
0
K13/140
APR 0 1 2014
510(k) Summary for the Omnyx, LLC. Omnyx Manual Read of the Digital HER2 Application
SUBMITTER/510(K) HOLDER 1.
Omnyx, LLC 1251 Waterfront Place Pittsburgh, PA 15222
Contact Person: Michael C. Montalto, Ph.D. Telephone: 732-457-8135
CONSULTANT/CONTACT 2.
Aptiv Solutions 62 Forest Street Suite 300 Marlborough, MA 01752 Telephone: (main) 508-597-6000 (direct) 508-835-1688 508-597-5789 Facsimile:
Primary Contact: Gail E. Radcliffe, Ph.D. Date Prepared: April 19, 2012
DEVICE NAME 3.
| Proprietary Name: | Omnyx Manual Read of the Digital HER2 Application |
|---|---|
| Common/Usual Name: | Digital Pathology Device |
| Classification: | Class II |
| Product Code: | OEO (automated digital image manual interpretation microscope) |
PREDICATE DEVICES 4.
1
5. DEVICE DESCRIPTION
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended to aid pathology professionals in creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The system is composed of the following components:
- · VL4 Scanner: A hardware device that captures and compresses bright field images of tissue samples.
- · Data and Workflow Infrastructure: A set of networked applications which enables case data entry, acquisition, indexing, storage and acceptance of digital images, workflow management, and retrieval of case and image data.
- · Histology Workstation: The application which permits the histologist to review or enter case data and check quality of scanned images.
- · Pathology Workstation: The application which allows the pathologist to retrieve case data and review and annotate slide images.
Hardware:
The Omnyx™ VL4 scanner is an automated imaging system that can be loaded with up to 4 slides at a time. The VL4 Scanner outputs its images and metadata to the Omnyx Digital Archive, which receives and stores the images and data.
Software:
The Omnyx software is composed of 1) the VL4 scanner software which performs tissue identification, scan planning, focusing, image acquisition, stitching and compression of digital slide images and sends them to the Digital Archive and 2) the DPS software that manages the Histologist and Pathologist workstation functions, image viewer, workflow service, database, interface engine, APLIS service, digital archive, image store and the administrator client application.
2
Principles of Operation:
FFPE tissue sections are stained with the Dako HercepTest™ according to the package insert. Slides are then scanned and digitized using the Omnyx VL4 Scanner. Whole slide images are transferred automatically to the Omnyx Digital Archive (DA) where they are indexed and stored. The Workflow Server contains patient information. These files are then accessed using the Histology Workstation or the Pathologist Workstation. The Histology Workstation is used by histologists or other lab professionals to perform quality checks on scanned slides, confirm that IHC slides/case associations are correct and order re-cuts and re-stains. It also enables the histologist to enter case data manually. The Pathologist Workstation enables the pathologist to flag significant cases and regions of interest. It also allows the pathologist to review the digital HercepTest™ IHC whole slide image (WSI) via the Omnyx Image Viewer and is used by the pathologist for functions such as annotating images and making measurements.
6. INDICATIONS FOR USE/ INTENDED USE
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, managing, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalinfixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
3
7. SUMMARY OF TECHNOLOGICAL CHARACTERISTICS COMPARED TO THE PREDICATE DEVICES
The following table summarizes the similarities and differences between the Omnyx Manual Read of the Digital HER2 Application and the predicate devices Aperio ScanScope XT System and Virtuoso™ IHC HER2.
| Proposed Device | Predicate | Predicate | |
|---|---|---|---|
| Omnyx Manual Read of the | Aperio ScanScope XT System | Virtuoso™ IHC HER2 | |
| Comparators | Digital HER2 Application | (K071671) | (K111543) |
| Intended use | The Omnyx Manual Read of | ||
| the Digital HER2 | |||
| Application on the Omnyx | |||
| IDP System is intended for | |||
| in vitro diagnostic use as an | |||
| aid to pathology | |||
| professionals for creating, | |||
| receiving, managing, storing, | |||
| annotating, measuring, and | |||
| viewing digital Whole Slide | |||
| Images (WSI) from | |||
| formalin-fixed, paraffin- | |||
| embedded (FFPE) tissue | |||
| sections stained with the | |||
| Dako HercepTest™. | The ScanScope system is an | ||
| automated digital slide creation, | |||
| management, viewing and | |||
| analysis system. It is intended | |||
| for in vitro diagnostic use as an | |||
| aid to the pathologist in the | |||
| display, detection, counting and | |||
| classification of tissues and cells | |||
| of clinical interest based on | |||
| particular color, intensity, size, | |||
| pattern and shape. | This device is intended for in vitro | ||
| (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,
intensity, size, pattern and shape. |
| | The Omnyx Manual Read
of the Digital HER2
Application on the Omnyx
IDP System is intended for
use as an aid to the
pathologist in the detection
and semi-quantitative
measurement of HER2/neu
(c-erbB-2) in digital images
of FFPE breast cancer tissue
immunohistochemically
stained with the Dako
HercepTest™ and viewed on
a computer monitor. Dako
HercepTest™ is indicated
for use as an aid in the
assessment of breast cancer
patients for whom
HERCEPTIN®
(Trastuzumab) treatment is
being considered. | The IHC HER2 Manual Read of
a Digital Slide application is
intended for use as an aid to the
pathologist in the detection and
semi-quantitative measurement
of HER2/neu (c-erbB-2) in
formalin-fixed, paraffin-
embedded normal and neoplastic
tissue immunohistochemically
stained for HER-2 receptors on a
computer monitor. HER2 results
are indicated for use as an aid in
the management, prognosis and
prediction of therapy outcomes in
breast cancer. | The Virtuoso™ System for IHC HER2
(4B5) is for digital read and image
analysis applications. This particular
Virtuoso system is intended for use as an
aid to the pathologist in the detection
and semi-quantitative measurement of
HER2 protein in formalin-fixed,
paraffin-embedded normal and
neoplastic tissue. This device is an
accessory to the Ventana Medical
Systems, Inc. PATHWAY® anti-
HER2/neu (4B5) Rabbit Monoclonal
Primary Antibody. The PATHWAY®
anti-HER2/neu (4B5) Rabbit
Monoclonal Primary Antibody is
indicated for use as an aid in the
assessment of breast cancer patients for
whom HERCEPTIN® (Trastuzumab)
treatment is being considered.
Note: The IHC HER2 (4B5) Digital
Read and Image Analysis applications
are adjunctive computer-assisted
methodologies for the qualified
pathologist in the acquisition and
measurement of images from
microscope glass slides of breast cancer |
| | | The IHC HER2 Manual Read of
a Digital Slide application is
intended for use as an accessory
to the Dako HercepTest™ to aid
in the detection and semi-
quantitative measurement of
HER2/neu (c-ebB-2) in formalin-
fixed, paraffin-embedded normal
and neoplastic tissue
immunohistochemically stained
for HER-2 receptors on a
computer monitor. When used
with the Dako HercenTest, it is | specimens stained for the presence of |
| | Proposed Device | Predicate | Predicate |
| | Omnyx Manual Read of the | Aperio ScanScope XT System | Virtuoso™ IHC HER2 |
| Comparators | Digital HER2 Application | (K071671) | (K111543) |
| | | indicated for use as an aid in the
assessment of breast cancer
patients for whom HERCEPTIN®
(Trastuzumab) treatment is being
considered. Note: The actual
correlation of the Dako
HercepTest™ to Herceptin®
clinical outcome has not been
established. | HER-2/neu receptor protein. The
pathologist should verify agreement
with the Image Analysis software
application score. The accuracy of the
test results depends on the quality of the
immunohistochemical staining. It is the
responsibility of a qualified pathologist
to employ appropriate morphological
studies and controls as specified in the
instructions for the PATHWAY® anti-
HER-2.neu (4B5) Rabbit Monoclonal
Primary Antibody assay used to assure
the validity of the iScan System for IHC
HER2 Digital Read and Image Analysis
scores. The actual correlation of
PATHWAY® anti-HER-2/neu (4B5) to
clinical outcome has not been
established. |
| Specimen Type | Formalin-fixed, paraffin-
embedded normal and
neoplastic tissue
immunohistochemically stained | Same | Same |
| Device
Components | Automated digital slide scanner,
computer, color monitor,
keyboard, and digital pathology
information management
software | Automated digital microscope
slide scanner, computer, color
monitor, keyboard and digital
pathology information
management software | BioImagene (now Ventana) iScan slide
scanner, computer, color monitor,
proprietary software for HER2 (4B5) |
| Image
Acquisition | Tile sensor technology | Line scanning technology | Same |
| Light Source | LED | Tungsten light | Same |
| Primary
Antibody
(Assay)
Reagent | Dako Reagents for HER2
(HercepTest™) | Same | Ventana PATHWAY HER2 (4B5)
(P990081 S003) |
| Interpretation (
Modes of
Operation) | Interpretation is performed by
the pathologist ( Manual digital
read) | Same | Manual and Automated |
Similarities/Differences of Omnyx Manual Read of the Digital HER2 Application with Predicate Devices
Omnyx, LLC Traditional 510(k) K131140 Manual Read of the Digital HER2 Application on the Omnyx IDP System
4
.
,
i
5
- SUMMARY OF NON-CLINICAL AND CLINICAL PERFORMANCE TESTING AS BASIS FOR SUBSTANTIAL EQUIVALENCE
CLINICAL COMPARISON TO MANUAL MICROSCOPY
Each of the four (4) pathologists read 200 breast cancer cases, comprising of both the controls and specimen slides stained with the Dako HercepTest™, using a conventional manual microscope (MM) and the Omnyx™ IDP (M-WSI), separated by at least a 2 week washout period. Three (3) VL4 scanners were installed in separate laboratories, with each scanner associated with a different scanner technician. Each pathologist reviewed WSIs obtained from different VL4 scanners, although two (2) of the pathologists received WSIs from the same VL4 scanner. The pairwise percent agreement between all pathologist on both MM and M-WSI modalities (inter-reader/intra-modality) was determined for both binned (0/1+ = neg; 1+/2+ = pos) and trichotomous (0/1+, 2+, 3+) score categories. Furthermore, in order to determine how well each pathologist could recapitulate a slide score for each slide when read on each modality, an analysis of the percent agreement between MM vs. M-WSI (inter-modality/intra-reader) for each pathologist was determined.
| Inter-Reader/
Intra-Modality
| (MM) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | ||
| Pathologist 1 | 0+ | 46 | 9 | 1 | 0 | 50 | 6 | 0 | 0 | 46 | 9 | 0 | 0 | ||||||||||||
| 1+ | 7 | 18 | 8 | 1 | 7 | 22 | 6 | 0 | 1 | 30 | 3 | 0 | |||||||||||||
| 2+ | 0 | 7 | 28 | 4 | 1 | 6 | 32 | 0 | 0 | 23 | 15 | 0 | |||||||||||||
| 3+ | 1 | 0 | 6 | 63 | 0 | 0 | 11 | 59 | 0 | 0 | 12 | 56 | |||||||||||||
| Pathologist 2 | 0 | 50 | 3 | 1 | 0 | 43 | 9 | 1 | 0 | ||||||||||||||||
| 1+ | 7 | 23 | 4 | 0 | 3 | 30 | 2 | 0 | |||||||||||||||||
| 2+ | 1 | 7 | 34 | 1 | 1 | 22 | 19 | 0 | |||||||||||||||||
| 3+ | 0 | 0 | 10 | 58 | 0 | 1 | 8 | 56 | |||||||||||||||||
| Pathologist 3 | 0 | 46 | 11 | 0 | 0 | ||||||||||||||||||||
| 1+ | 1 | 32 | 1 | 0 | |||||||||||||||||||||
| 2+ | 0 | 19 | 26 | 2 | |||||||||||||||||||||
| 3+ | 0 | 0 | 3 | 54 | |||||||||||||||||||||
| % Agreement (95% CI) | |||||||||||||||||||||||||
| (Trichotomous) | 85.9% (80%-90%) | 88.0% (83%-92%) | 80.5% (74%-85%) | 87.9% (83%-92%) | 82.1% (76%-87%) | 87.2% (82%-91%) |
Inter-Reader/Intra-Modality on Glass (MM) between four (4) pathologists - Trichotomous score categories
6
| Inter-Reader/
| Intra-Modality | Pathologist 2 | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (M-WSI) | 04 | 1+ | 2+ | 34 | 04 | 14 | 2+ | 34 | 0+ | 14 | 24 | 3+ | 0+ | 1+ | 24 | ਤੇ + | 04 | 1+ | 24 | 34 | 04 | 1+ | 2+ | 34 | |
| 0 | 48 | હ | O | 0 | 28 | 21 | ટ | 0 | 29 | 22 | 0 | 0 | |||||||||||||
| 1+ | শ | 22 | 11 | 1 | 1 | 11 | 23 | 3 | 0 | તે વ | ਤੇ | 0 | |||||||||||||
| Pathologist 1 | 24 | 0 | 7 | 26 | ર | ਹੈ | 0 | Pathologist 4 | |||||||||||||||||
| Pathologist 3 | |||||||||||||||||||||||||
| Pathologist 4 | |||||||||||||||||||||||||
| Pathologist 4 | |||||||||||||||||||||||||
| Pathologist 3 | |||||||||||||||||||||||||
| 20 | |||||||||||||||||||||||||
| 16 | |||||||||||||||||||||||||
| । | |||||||||||||||||||||||||
| 19 | |||||||||||||||||||||||||
| 19 | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| 2 | |||||||||||||||||||||||||
| રવ | |||||||||||||||||||||||||
| ୧୧ | |||||||||||||||||||||||||
| ﻠ | |||||||||||||||||||||||||
| 7 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 21 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 28 | |||||||||||||||||||||||||
| 20 | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| 28 | |||||||||||||||||||||||||
| ﻠﺴﺎ | |||||||||||||||||||||||||
| র্ব | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| 2 | |||||||||||||||||||||||||
| 12 | |||||||||||||||||||||||||
| 20 | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| ਤੇ ਤੋ | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 22 | |||||||||||||||||||||||||
| । ਰੇ | |||||||||||||||||||||||||
| 20 | |||||||||||||||||||||||||
| 22 | |||||||||||||||||||||||||
| 2 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 3 | |||||||||||||||||||||||||
| 64 | |||||||||||||||||||||||||
| ತಿ | |||||||||||||||||||||||||
| ട | |||||||||||||||||||||||||
| ટે પે | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 25 | |||||||||||||||||||||||||
| ന | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 26 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 4 | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| 40 | |||||||||||||||||||||||||
| 8 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 7 | |||||||||||||||||||||||||
| 18 | |||||||||||||||||||||||||
| 1 | |||||||||||||||||||||||||
| 64.4% (57%-71%) | |||||||||||||||||||||||||
| 73.4% (67%-79%) | |||||||||||||||||||||||||
| 82.4% (76%-87%) | |||||||||||||||||||||||||
| 74.4% (68%-80%) | |||||||||||||||||||||||||
| 83.5% (78%-88%) | |||||||||||||||||||||||||
| 34 | 1 | 0 | 7 | દર્ભ | 0 | 0 | |||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| Pathologist 2 | 1+ | ||||||||||||||||||||||||
| 2+ | |||||||||||||||||||||||||
| 34 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 1+ | |||||||||||||||||||||||||
| Pathologist 3 | 2+ | ||||||||||||||||||||||||
| 3+ | ટર્ટ | ||||||||||||||||||||||||
| % Agreement (95% Cl) | |||||||||||||||||||||||||
| (Trichotomous) | 83.4% (78%-88%) |
Inter-Reader/Intra-Modality on Digital (M-WSI) between four (4) pathologists – Trichotomous score categories
To calculate the negative & positive percent agreements, the 4x4 binary agreements are binned into a 2x2 table with 0/1+ (Negative) combined and 2+/3+ (Positive) combined. Since neither pathologist can be considered a reference in each pairwise reader comparison, analysis for negative and positive score categories is provided as Average Negative Agreement (ANA) and Average Positive Agreement (APA).
| Inter-Reader/
Intra-Modality
| (MM) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |||
| Pathologist 1 | Neg | 80 | 10 | 85 | 6 | 86 | 3 | |||||||
| Pos | 8 | 101 | 7 | 102 | 23 | 83 | ||||||||
| Pathologist 2 | Neg | 83 | 5 | 85 | 3 | |||||||||
| Pos | 8 | 103 | 24 | 83 | ||||||||||
| Pathologist 3 | Neg | 90 | 1 | |||||||||||
| Pos | 19 | 85 | ||||||||||||
| Overall Percent | ||||||||||||||
| Agreement | ||||||||||||||
| (95% CI) | 91.0% | |||||||||||||
| (86%-94%) | 93.5% | |||||||||||||
| (89%-96%) | 86.7% | |||||||||||||
| (81%-91%) | 93.5% | |||||||||||||
| (89%-96%) | 86.2% | |||||||||||||
| (81%-90%) | 89.7% | |||||||||||||
| (85%-93%) | ||||||||||||||
| Average Positive | ||||||||||||||
| Agreement | ||||||||||||||
| (95% CI) | 89.9% | |||||||||||||
| (85%-94%) | 92.9% | |||||||||||||
| (88%-96%) | 86.9% | |||||||||||||
| (81%-91%) | 92.7% | |||||||||||||
| (88%-96%) | 86.3% | |||||||||||||
| (81%-90%) | 90.0% | |||||||||||||
| (85%-93%) | ||||||||||||||
| Average Negative | ||||||||||||||
| Agreement | ||||||||||||||
| (95% CI) | 91.8% | |||||||||||||
| (87%-95%) | 94.0% | |||||||||||||
| (90%-96%) | 86.5% | |||||||||||||
| (81%-91%) | 94.1% | |||||||||||||
| (90%-96%) | 86.0% | |||||||||||||
| (80%-90%) | 89.5% | |||||||||||||
| (84%-93%) |
Inter-Reader/Intra-Modality on Glass (MM) between four (4) pathologists - Binary score categories
7
| Inter-Reader/
Intra-Modality
| (M-WSI) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |
| Pathologist 1 | 80 | 12 | 61 | 31 | 85 | 3 | ||||||
| Pathologist 1 | 8 | 99 | 1 | 106 | 22 | 78 | ||||||
| Pathologist 2 | 62 | 26 | 83 | 1 | ||||||||
| Pathologist 2 | 0 | 111 | 24 | 80 | ||||||||
| Pathologist 3 | 58 | 0 | ||||||||||
| Pathologist 3 | 49 | 81 | ||||||||||
| Overall Percent | ||||||||||||
| Agreement | ||||||||||||
| (95% CI) | 89.9% | |||||||||||
| (85%-93%) | 83.9% | |||||||||||
| (78%-88%) | 86.7% | |||||||||||
| (81%-91%) | 86.9% | |||||||||||
| (82%-91%) | 86.7% | |||||||||||
| (81%-91%) | 73.9% | |||||||||||
| (67%-80%) | ||||||||||||
| Average Positive | ||||||||||||
| Agreement | ||||||||||||
| (95% CI) | 88.9% | |||||||||||
| (83%-93%) | 79.2% | |||||||||||
| (72%-85%) | 87.2% | |||||||||||
| (82%-91%) | 82.7% | |||||||||||
| (76%-88%) | 86.9% | |||||||||||
| (81%-91%) | 70.3% | |||||||||||
| (63%-77%) | ||||||||||||
| Average Negative | ||||||||||||
| Agreement | ||||||||||||
| (95% Cl) | 90.8% | |||||||||||
| (86%-94%) | 86.9% | |||||||||||
| (82%-91%) | 86.2% | |||||||||||
| (80%-90%) | 89.5% | |||||||||||
| (85%-93%) | 86.5% | |||||||||||
| (81%-91%) | 76.8% | |||||||||||
| (71%-82%) |
Inter-Reader/Intra-Modality on Digital (M-WSI) between four (4) pathologists - Binary score categories
The inter-modality/intra-reader agreement results evaluating glass vs. digital (MM vs. M-WSI) for all four (4) pathologists are shown below. The washout period between the glass and digital reads was a minimum of 2 weeks.
| Inter-Modality/Intra-Reader
| (MM vs. M-WSI) | Glass (MM) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Digital (M-WSI) | Pathologist 1 | Pathologist 2 | Pathologist 3 | Pathologist 4 | ||||||||||||
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | |
| 0 | 50 | 4 | 0 | 0 | 47 | 3 | 2 | 1 | 29 | 1 | 0 | 0 | 29 | 0 | 2 | 0 |
| 1+ | 6 | 26 | 6 | 0 | 5 | 25 | 5 | 0 | 25 | 7 | 0 | 0 | 16 | 54 | 5 | 0 |
| 2+ | 0 | 5 | 32 | 2 | 0 | 7 | 30 | 7 | 4 | 24 | 21 | 0 | 0 | 6 | 20 | 0 |
| 3+ | 0 | 0 | 1 | 67 | 2 | 0 | 6 | 60 | 0 | 2 | 28 | 58 | 0 | 0 | 3 | 5 |
Intra-Reader/Inter-Modality comparing agreement between glass and digital (MM vs. M- WSI) for each of the four (4) pathologists . Trichotomous score categories
To calculate the negative & positive percent agreements, the 4x4 binary agreement tables are binned into a 2x2 table with 0/1+ (Negative) combined and 2+/3+ (Positive) combined. Since the glass scores for each pathologist is used as their respective reference, the analysis is provided as Negative Percent Agreement (NPA) and Positive Percent Agreement (PPA), with the glass reads as the imperfect reference.
8
| Glass (MM) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Inter-Modality/Intra-Reader | ||||||||
| (MM vs. M-WSI) | Pathologist 1 | Pathologist 2 | Pathologist 3 | Pathologist 4 | ||||
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |
| Digital (M-WSI) | ||||||||
| Neg | 86 | 8 | 80 | 8 | 62 | 0 | 99 | 7 |
| Digital (M-WSI) | ||||||||
| Pos | 5 | 75 | 9 | 103 | 30 | 107 | 6 | 75 |
| Overall Percent Agreement | ||||||||
| (95% CI) | 92.5% | |||||||
| (88%-96%) | 91.5% | |||||||
| (87%-95%) | 89.4% | |||||||
| (79%-89%) | 93.0% | |||||||
| (88%-96%) | ||||||||
| Negative Percent Agreement | ||||||||
| (95% CI) | 94.5% | |||||||
| (88%-98%) | 89.9% | |||||||
| (82%-95%) | 67.4% | |||||||
| (57%-76%) | 94.3% | |||||||
| (88%-97%) | ||||||||
| Positive Percent Agreement | ||||||||
| (95% CI) | 90.4% | |||||||
| (82%-95%) | 92.8% | |||||||
| (86%-96%) | 100% | |||||||
| (97%-100%) | 91.5% | |||||||
| (83%-96%) |
Intra-Reader/Inter-Modality comparing agreement between glass and digital (MM vs. M- WSI) for each of the four (4) pathologists - Binary score categories
The pairwise inter-reader/intra-modality percent agreements do not differ significantly between MM and M-WSI. Additionally, there are high percent agreements between MM and M-WSI for each pathologist when examined by binary or trichotomous score category.
PRECISION & REPRODUCIBILITY
INTRA-READER/INTER-DAY
In order to compare the intra-reader variability on digital M-WSI, three (3) pathologist performed three (3) independent readings of a set of the HercepTest™ stained slides (n=40) using the M-WSI modality. Each of the three reads was separated by a minimum one week wash out, with the inclusion of wildcards. The results are presented as both trichotomous and binary analysis, with additional negative and positive percent agreements (NPA and PPA).
| Intra-Reader/Inter-Day
| (M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Read 1 | 0 | 6 | 3 | 1 | 0 | 8 | 2 | 0 | 0 | ||||
| 1+ | 0 | 3 | 11 | 0 | 0 | 8 | 6 | 0 | |||||
| 2+ | 0 | 0 | 4 | 3 | 0 | 0 | 4 | 3 | |||||
| 3+ | 0 | 0 | 0 | 9 | 0 | 0 | 0 | 9 | |||||
| Read 2 | 0 | 6 | 0 | 0 | 0 | ||||||||
| 1+ | 2 | 4 | 0 | 0 | |||||||||
| 2+ | 0 | 6 | 10 | 0 | |||||||||
| 3+ | 0 | 0 | 0 | 12 | |||||||||
| % Agreement (95% CI) | |||||||||||||
| (Trichotomous) | 62.5% (47%-76%) | 77.5% (62%-88%) | 85.0% (71%-93%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 1 – Trichotomous score categories
9
| Intra-Reader/Inter-Day
(M-WSI)
| Pathologist 1 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 12 | 12 | 18 | 6 | ||
| Pos | 0 | 16 | 0 | 16 | |||
| Read 2 | Neg | 12 | 0 | ||||
| Pos | 6 | 22 | |||||
| Overall % Agreement | |||||||
| (95% CI) | 70.0% (55%-82%) | 85.0% (71%-93%) | 85.0% (71%-93%) | ||||
| Negative % Agreement | |||||||
| (95% CI) | 66.7% (50%-80%) | 85.7% (72%-93%) | 80.0% (63%-90%) | ||||
| Positive % Agreement | |||||||
| (95% CI) | 72.7% (58%-84%) | 84.2% (70%-93%) | 88.0% (76%-94%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 1 - Binary score categories
| Intra-Reader/Inter-Day
| (M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||||
| Read 1 | 0 | 8 | 0 | 0 | 0 | 8 | 0 | 0 | 0 | ||||||
| 1+ | 0 | 8 | 1 | 0 | 1 | 8 | 0 | 0 | |||||||
| 2+ | 0 | 1 | 10 | 0 | 0 | 1 | 10 | 0 | |||||||
| 3+ | 0 | 0 | 0 | 12 | 0 | 0 | 0 | 12 | |||||||
| Read 2 | 1 | 8 | 0 | 0 | 0 | ||||||||||
| 1+ | 1 | 8 | 0 | 0 | |||||||||||
| 2+ | 0 | 1 | 10 | 0 | |||||||||||
| 3+ | 0 | 0 | 0 | 12 | |||||||||||
| % Agreement (95% CI) | |||||||||||||||
| (Trichotomous) | 95.0% (83%-99%) | 97.5% (87%-100%) | 97.5% (87%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 2 - Trichotomous score categories
| Intra-Reader/Inter-Day
(M-WSI)
| Pathologist 2 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 16 | 1 | 17 | 0 | ||
| Read 1 | Pos | 1 | 22 | 1 | 22 | ||
| Read 2 | Neg | 17 | 0 | ||||
| Pos | 1 | 22 | |||||
| Overall % Agreement | |||||||
| (95% CI) | 95.0% (83%-99%) | 97.5% (87%-100%) | 97.5% (87%-100%) | ||||
| Negative % Agreement | |||||||
| (95% CI) | 94.1% (81%-98%) | 97.1% (85%-99%) | 97.1% (85%-99%) | ||||
| Positive % Agreement | |||||||
| (95% CI) | 95.7% (85%-99%) | 97.8% (88%-100%) | 97.8% (88%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 2 - Binary score categories
10
| Intra-Reader/Inter-Day
| (M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Read 1 | 0 | 5 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | ||||
| 1+ | 3 | 3 | 0 | 0 | 1 | 5 | 0 | 0 | |||||
| 2+ | 0 | 1 | 15 | 3 | 0 | 0 | 15 | 4 | |||||
| 3+ | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 10 | |||||
| Read 2 | 1 | 5 | 3 | 0 | 0 | ||||||||
| 1+ | 1 | 2 | 1 | 0 | |||||||||
| 2+ | 0 | 0 | 14 | 1 | |||||||||
| 3+ | 0 | 0 | 0 | 13 | |||||||||
| % Agreement (95% CI) | |||||||||||||
| (Trichotomous) | 90.0% (77%-96%) | 90.0% (77%-96%) | 95.0% (83%-99%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 3 - Trichotomous score categories
| Intra-Reader/Inter-Day
(M-WSI)
| Pathologist 3 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 11 | 0 | 11 | 0 | ||
| Pos | 1 | 28 | 0 | 29 | |||
| Read 2 | Neg | 11 | 1 | ||||
| Pos | 0 | 28 | |||||
| Overall % Agreement | |||||||
| (95% CI) | 97.5% (87%-100%) | 100.0% (91%-100%) | 97.5% (87%-100%) | ||||
| Negative % Agreement | |||||||
| (95% CI) | 95.7% (79%-99%) | 100.0% (85%-100%) | 95.7% (79%-99%) | ||||
| Positive % Agreement | |||||||
| (95% CI) | 98.2% (91%-100%) | 100.0% (94%-100%) | 98.2% (91%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 3 - Binary score categories
.
11
INTER-SCANNER/INTRA-READER
To determine the scanner variability, we performed a subjective inter-scanner study. A set of 80 regions of interest (ROIs) extracted from WSIs of forty (40) HercepTest™ slides, with even distribution of the score categories, were obtained from three (3) different scanners. The three scanners were located in three different laboratory locations within GE Healthcare and operated by three independent operators. Each read session (for each scanner) was separated by a minimum of 1 week washout period, with the inclusion of wildcard ROIs during each scanner's ROI reads. All ROIs were manually scored by a single pathologist based on the Dako HercepTest™ scoring guidelines. Percent agreement between each of the scanner pairs were determined based on the ROI scores.
| Inter-Scanner/Intra-Reader | Scanner 2 | Scanner 3 | Scanner 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Scanner 1 | 0 | 25 | 2 | 0 | 0 | 26 | 1 | 0 | 0 | ||||
| 1+ | 3 | 11 | 1 | 0 | 3 | 10 | 2 | 0 | |||||
| 2+ | 0 | 0 | 19 | 3 | 0 | 1 | 15 | 6 | |||||
| 3+ | 0 | 0 | 0 | 16 | 0 | 0 | 0 | 16 | |||||
| Scanner 2 | 0 | 26 | 2 | 0 | 0 | ||||||||
| 1+ | 3 | 9 | 1 | 0 | |||||||||
| 2+ | 0 | 1 | 15 | 4 | |||||||||
| 3+ | 0 | 0 | 1 | 18 | |||||||||
| % Agreement (95% CI) | |||||||||||||
| (Trichotomous) | 95.0% (88%-98%) | 88.8% (80%-94%) | 91.3% (83%-96%) |
Inter-Scanner/Intra-Reader Agreement using Region of Interests (ROIs) obtained from 3 VL4 scanners and scored by a single pathologist 2) - Trichotomous score categories
When analyzed trichotomously (0/1+, 2+ and 3+), the inter-scanner/intra-reader variability had high percent agreement across all pairwise scanner comparisons. This data indicates a very high reproducibility among scanners and further suggests that M-WSI inter-scanner variability is primarily due to the subjectivity of score interpretation of the readers and not by scanner to scanner variability.
12
9. SUMMARY OF OTHER INFORMATION
This submission included a comparison of intended use statements, proposed product labeling, software validation and summary information and labeling on predicate devices.
10. CONCLUSIONS DRAWN FROM NON-CLINICAL AND CLINICAL TESTS
Based on the information provided in this 510(k), Omnyx believes that the proposed Omnyx Manual Read of the Digital HER2 Application is substantially equivalent to the previously cleared products. The proposed device raises no new issues of safety and effectiveness. The non-clinical and clinical testing performed demonstrates that the proposed device met all the specifications and is suitable for its intended use.
13
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird-like figure.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 1, 2014
Omnyx, LLC. c/o Gail E. Radcliffe. Ph.D. Aptiv Solutions 62 Forest Street, Suite 300 Marlborough, MA 01752
Re: K131140
Trade/Device Name: OmnyxManual Read of the Digital HER2 Application Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: OEO Dated: March 12, 2014 Received: March 13, 2014
Dear Dr. Radcliffe:
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 that I DA has made a actoring administered by other Federal agencies. You must Of any I edical statutes and registments, including, but not limited to: registration and listing (21 comply with an the For 3 requirements, more of 800 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements medical device-related adverse overles (22) regulation (21 CFR Part 820); and if applicable, the as set form in the quality of ovisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2- Gail E. Radcliffe
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/ResourcesforYou/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/Resourcesfor You/Industry/default.htm.
Sincerely yours.
ReenauPhilip-S
for
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K131140
Device Name
Omnyx Manual Read of the Digital HER2 Application
Indications for Use (Describe)
The Omnyx Manual Read of the Digital HER2 Application on the Ominyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, storing, annotating, measuring, and viewing digital Whole Shide Images (WS1) from formalin-fixed, parafin-embedded (FFPE) tissue sections stained with the Dako HercepTest™
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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