← Product Code [OEO](/submissions/HE/subpart-b%E2%80%94biological-stains/OEO) · K131140

# OMNYX IDP FOR HER2 MANUAL APPLICATION (K131140)

_Omnyx, LLC · OEO · Apr 1, 2014 · Hematology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/PA/subpart-b%E2%80%94biological-stains/OEO/K131140

## Device Facts

- **Applicant:** Omnyx, LLC
- **Product Code:** [OEO](/submissions/HE/subpart-b%E2%80%94biological-stains/OEO.md)
- **Decision Date:** Apr 1, 2014
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 864.1860
- **Device Class:** Class 2
- **Review Panel:** Hematology

## 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, 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 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.

## Device Story

System captures, manages, and displays digital whole slide images (WSI) of FFPE breast cancer tissue stained with Dako HercepTest™. Components include VL4 scanner (LED light source, tile sensor technology), data/workflow infrastructure, and histology/pathology workstations. Pathologists use high-resolution monitors to view digital images, annotate, measure, and manually score HER2 expression based on Dako HercepTest™ package insert instructions. System facilitates digital pathology workflow, replacing traditional manual microscopy for HER2 scoring. Benefits include digital storage, retrieval, and remote review capabilities. Pathologists perform scoring; system provides the digital environment for this clinical decision-making process.

## Clinical Evidence

Method comparison study (n=200 FFPE breast cancer specimens) compared manual microscopy (MM) to digital manual read (M-WSI) across 4 sites. Overall percent agreement for binary scores ranged from 89.4% to 93.0%. Intra-pathologist/inter-day precision study (n=40 slides, 3 reads) showed trichotomous agreement ranging from 62.5% to 97.5%. Inter-scanner precision study (n=80 ROIs, 3 scanners) showed trichotomous agreement between 88.8% and 95.0%.

## Technological Characteristics

System uses VL4 scanner with LED light source and tile sensor technology. Scans at 40x magnification (0.275 µm/pixel). Components include high-resolution monitors, workstations, and networked digital pathology software. Calibration required at installation and every 1300 hours. Software manages image acquisition, stitching, compression, and viewing.

## Regulatory 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.

## Special Controls

(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.

## Predicate Devices

- ScanScope® XT System for HER2 (k071671)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k131140

B. Purpose for Submission:
New Device

C. Manufacturer and Instrument Name:
Omnyx, LLC, Omnyx Manual Read of the Digital HER2 Application

D. Type of Test or Tests Performed:
Manual scoring of digital images on a computer monitor of glass slides stained immunohistochemically with the Dako HercepTest™ pharmDx™ kit.

E. System Descriptions:

1. Device Description:

The Omnyx Manual Read of the Digital HER2 Application is intended to aid pathology professionals in creating, managing, storing, annotating, measuring, and viewing digital whole slide images 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 pathology images, workflow management, and retrieval of case and image data.
- Digital Histology Workstation: The application which permits the histologist to review or enter case data and check quality of scanned images.
- Digital Pathology Workstation: The application which allows the pathologist to retrieve case data and review and annotate slide images.

In addition, the Manual Read of the Digital HER2 Application includes a specific computer and monitor.

Hardware:

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The Omnyx™ VL4 scanner is an automated imaging system that can be loaded with up to 4 slides at a time. The Digital Histology Workstation computer consists of a monitor, keyboard and mouse all provided by Omnyx. The Digital Pathology Workstation consists of a workstation computer, dual high-resolution monitors, keyboard and mouse all provided by Omnyx.

Software:

The Omnyx IDP system 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:

Glass slides with FFPE tissue sections stained with the Dako HercepTest™ are scanned and digitized using the Omnyx VL4 scanner. The Omnyx™ VL4 is an automated imaging system that captures and compresses bright field images of tissue samples. Slides are scanned at 40x (0.275 µm/pixel) magnification. The VL4 scanner calculates the region to be scanned. If not in the auto scan mode, the user can optionally check the region to be scanned by touching the slide displaying the macro image, which then displays the 'scan area' in a green overlay. If satisfied, the user can commence the scan.

The VL4 scans 25mm x 75mm and 26mm x 76mm slides.

Once a scan is complete, the scanner ensures that both the slide metadata and the compressed image are correctly associated with the unique scan identifier. The scanner then sends the image and metadata to the Digital Archive. The Digital Archive verifies that the image and metadata are correctly associated with the unique scan identifier. It then sends confirmation to the VL4 that it has completed this verification and stores the scans. The scanned images can be viewed without magnification at the VL4 touch screen, but images captured at high magnifications require an external viewing system (Omnyx Histologist or Pathologist Workstation) to view the images at the scanned resolution. The Omnyx Histology Workstation supports the histologist process from case creation to case review before release to the pathologist. The Pathologist Workstation enables the pathologist to review the digital HercepTest™ IHC whole slide image via the Omnyx Image Viewer. The Image Viewer is used by the pathologist for annotating images, making measurements and for HER2 scoring of the slides. Slides are scored by the pathologist based on the review of the digital image of the HER2 stained glass slide. HER2 scoring is performed according to the instructions in the package insert for the Dako HercepTest™ pharmDx kit™.

3. Modes of Operation:

Manual scoring of digital images on a computer monitor of glass slides stained with the Dako HercepTest™ pharmDx kit™.

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4. Specimen Identification:
Glass tissue slides are identified by barcoded slide label or manual matching of whole slide images to the slides.

5. Specimen Sampling and Handling:
HER2 IHC stained slides manually loaded onto the VL4 slide scanner. The scanner holds four sides at a time. Slides are scanned at the 40x (0.275 µm/pixel) magnification.

6. Calibration:
Calibration is performed at installation and after 1300 hours of use by the systems administrator.

7. Quality Control:
Quality control is performed by the operator before releasing the images to the pathologist for review. Slides with sub-optimal images will be rescanned.

The accuracy of the system depends on the laboratory following the quality control instructions for the Dako HercepTest™ pharmDx kit™ assay. The positive and negative control slides are also scanned along with the patient slides which are reviewed by the pathologist before scoring.

8. Software:
FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types:
Yes ☐ X or No ☐

F. Regulatory Information:

1. Regulation section:
21 CFR §864.1860, Immunohistochemistry reagents and kits

2. Classification:
Class II

3. Product code:
OEO – Automated Digital Image Manual Interpretation Microscope

4. Panel:
Pathology (88)

G. Intended Use:

1. Indication(s) 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, managing, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako

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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.

2. Special Conditions for Use Statement(s):

For prescription use only

Indicated for use with the Dako Autostainer Link 48

H. Substantial Equivalence Information:

1. Predicate Device Name(s) and 510(k) numbers:

ScanScope® XT System for HER2 – k071671

2. Comparison with Predicate Device:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | New Device
Omnyx Manual Read of the Digital HER2 Application | Predicate Device
ScanScope® XT System for HER2  |
|  Intended Use | The Omnyx Integrated Digital Pathology System (IDP) for Immunohistochemistry 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 Omnyx IDP for IHC Manual 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 | The ScanScope® System is an automated digital slide creation, management, viewing and analysis system. It is intended for IVD use as an aid to the pathologist in the display, detection, counting and classification of tissues and cells of clinical interest based on particular color, intensity, size, pattern and shape.

The 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  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | New Device
Omnyx Manual Read of the Digital HER2 Application | Predicate Device
ScanScope® XT System for HER2  |
|   | 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. | 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 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 HercepTest, it is 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 HercepTestTM to Herceptin® clinical outcome has not been established.  |
|  Sample Type | Formalin-fixed, paraffin-embedded tissue stained by immunohistochemical technique. | Same  |
|  Device components | Automated digital slide scanner, computer, color monitor, keyboard and digital pathology information management software | Same  |

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|  Differences  |   |   |
| --- | --- | --- |
|  Item | New Device
Omnyx Manual Read of the HER2 Digital Application | Predicate Device
ScanScope® XT System for HER2  |
|  Image Acquisition | Tile sensor technology | Line scanning technology  |
|  Light Source | LED | Tungsten Light  |

I. Special Control/Guidance Document Referenced (if applicable):

None

J. Performance Characteristics:

1. Analytical Performance:

a. Accuracy:

A method comparison study was performed to compare the HER2 scores under the manual microscopy method (MM) to the corresponding scores using the glass slide digital image read on a computer monitor (M-WSI).

The study used 200 formalin-fixed paraffin-embedded (FFPE) human breast cancer specimens with different levels of HER2 expression. All slides were stained with the Dako HercepTest™ pharmDx™ kit using the Dako Autostainer Link 48. There was approximately the same number of slides in each of the scoring categories (0, 1+, 2+ and 3). Slides were scanned at 2 different locations (3 different laboratories) using 3 scanners at 40x magnification. Four study sites were used with one pathologist at each site. The corresponding negative control reagent slides and the positive control slides were also scanned along with the study cases and evaluated by the study pathologists before scoring the slides. Thirteen slides were excluded from analysis due to “uncertain or no definite invasive carcinoma” (n=11), poor staining quality (n=1) and slide breakage (n=1). HER2 scoring was performed according to the instructions in the package insert for the Dako HerceptTest™ pharmDx™ kit. After a minimum of two-week washout period, the same pathologist at each site accessed the scanned images of the HER2 IHC stained slides through the Omnyx Pathologist Workstation and performed the M-WSI reads of the same slides. The table below shows the data for this study.

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Table 1: Intra-Reader/Inter-Modality comparison between MM vs. M-WSI - Discrete score categories

|   | Glass (MM)  |   |   |   |   |   |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Site 1 |   |   |   | Site 2 |   |   |   | Site 3 |   |   |   | Site 4  |   |   |
|   |   |  0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+  |
|  Digital (M-WSI) | 0 | 50 | 4 | 1 | 0 | 47 | 3 | 2 | 1 | 29 | 1 | 0 | 0 | 29 | 0 | 2  |
|   |  1+ | 6 | 26 | 7 | 0 | 5 | 25 | 5 | 0 | 25 | 7 | 0 | 0 | 16 | 54 | 5  |
|   |  2+ | 0 | 5 | 32 | 2 | 0 | 7 | 30 | 7 | 4 | 24 | 21 | 0 | 0 | 6 | 20  |
|   |  3+ | 0 | 0 | 1 | 67 | 2 | 0 | 6 | 60 | 0 | 2 | 28 | 58 | 0 | 0 | 3  |
|  % Agreement (95% CI) (Trichotomous)** |   | 93.0% (89%-96%) |   |   |   | 85.0% (79%-89%) |   |   |   | 70.9% (64%-77%) |   |   |   | 91.4% (87%-95%)  |   |   |

Note: **Scores of 0 and 1+ combined, 2+ and 3+ as separate

Table 2: Intra-Reader/Inter-Modality comparison between MM vs. M-WSI - Binary score categories

|   | Glass (MM)  |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Site 1 |   | Site 2 |   | Site 3 |   | Site 4  |   |
|   |   |  Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos  |
|  Digital (M-WSI) | Neg | 86 | 8 | 80 | 8 | 62 | 0 | 99 | 7  |
|   |  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%)  |   |

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Table 3: Inter-reader agreement rates for 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 | Neg | 80 | 12 | 61 | 31 | 85 | 3 |  |
| Pos | 8 | 99 | 1 | 106 | 22 | 78 |
| Pathologist 2 | Neg |  | 62 | 26 | 83 | 1 |  |
| Pos | 0 | 111 | 24 | 80 |
| Pathologist 3 | Neg | 58 | 0 |
| Pos | 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% CI) | 90.8% (86%-94%) | 86.9% (82%-91%) | 86.2% (80%-90%) | 89.5% (85%-93%) | 86.5% (81%-91%) | 76.8% (71%-82%) |

# b. Precision/Reproducibility:

# Intra-Pathologist/Inter-Day

The intra-reader/inter-day was performed using M-WSI reads by 3 independent pathologists. Forty HER2 stained slides with even score distribution were read by each pathologist 3 times digitally (M-WSI). The slides used in this study were a different set of clinical slides from the method comparison study. The slides were scanned on a single Omnyx VL4 scanner and the final images were used. There was a 2-week minimum washout period and 10 additional slides were added during each reading as "wildcards" (unique wildcards during each read) to minimize recall bias.

Pair-wise comparisons between the 3 reads were performed (i.e., read 1 vs. read 2, read 1 vs. read 3, and read 2 vs. read 3) and the results are shown in the tables below.

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Table 4.1: Intra-Reader/Inter-Day, Pathologist 1

|   | 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%)  |   |   |   |

Table 4.2: Intra-Reader/Inter-Day, Pathologist 2

|   | 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 | 0 |  | 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%)  |   |   |   |

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Table 4.3: Intra-Reader/Inter-Day, Pathologist 3

|   | 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 | 0 |  | 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%)  |   |   |   |

# Precision:

In the inter-scanner precision study, a single pathologist reviewed and scored 80 ROIs (Regions of Interest) which were extracted from scans of 40 slides. The four HER2 scoring categories were equally represented in this set of slides. The slides were scanned by 3 different VL4 scanners. Due to slide damage, some slides were not scanned on all three scanners. There was a washout period of at least two weeks between each set of reads. Additionally, a separate set of 60 "wildcard" ROIs were extracted from the WSIs (unique set of 20 ROIs used per read session) to be included during each reading session to reduce recall bias. The pathologist reviewed and scored each ROI. Precision among each scanner pair was determined based on the HercepTest™ scores of the 80 ROIs. The inter-scanner precision data is shown in table 5 below.

Table 5: Inter-Scanner Precision

|   | 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  |

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|  % Agreement
(95% CI)
(Trichotomous) | 95.0%
(88%-98%) | 88.8%
(80%-94%) | 91.3%
(83%-96%)  |
| --- | --- | --- | --- |

c. Linearity:
Not applicable

d. Carryover:
Not applicable.

e. Interfering Substances:
Not applicable.

2. Other Supportive Instrument Performance Data Not Covered Above:
None

K. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

L. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

---

**Source:** [https://fda.innolitics.com/submissions/PA/subpart-b%E2%80%94biological-stains/OEO/K131140](https://fda.innolitics.com/submissions/PA/subpart-b%E2%80%94biological-stains/OEO/K131140)

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