PHILIPS HERCEPTEST DIGITAL SCORE

K130021 · Philips Medical Systems Nederland B.V. · OEO · Sep 19, 2013 · Hematology

Device Facts

• Record ID: K130021
• Device Name: PHILIPS HERCEPTEST DIGITAL SCORE
• Applicant: Philips Medical Systems Nederland B.V.
• Product Code: OEO · Hematology
• Decision Date: Sep 19, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

The Philips HER2/neu IHC Digital Manual Read 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. The Philips HER2/neu IHC Digital Manual Read is based on the Philips Digital Pathology Solution platform, which is an automated digital slide creation, management, viewing and analysis system. The Philips HER2/neu IHC Digital Manual Read is intended for use as an accessory to the Dako HercepTest™ to aid in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in formalin-fixed, paraffin-embedded 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 from whom HERCEPTIN® (Trastuzumab), PERJETA® (Pertuzumab) or KADCYLA® (Ado-Trastuzumab Emtansine) treatment is being considered. Note: The actual correlation of the Dako HercepTest™ to Herceptin®, Perjeta®, or Kadcyla®, clinical outcome has not been established. Note: The Philips HER2/neu IHC Digital Manual Read is for evaluation of digital images of immunohistochemically stained slides that would otherwise be appropriate for manual visualization by conventional microscopy. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for Dako HercepTest™ to assure the validity of the scores obtained using Philips HER2/neu IHC Digital Manual Read.

Device Story

Philips HER2/neu IHC Digital Manual Read is a digital pathology application for viewing and scoring immunohistochemically stained breast tissue slides. System components include Philips Ultra Fast Scanner (UFS) for digitizing slides into whole slide images (WSI), Philips Image Management System (IMS) for storage/management, and IMS Web Viewer for pathologist review on a Barco MDCC 2121 monitor. Scanner captures high-resolution images, decodes barcodes, and performs automatic focus, compression, and stitching. Pathologist reviews digital images on a computer monitor to perform manual scoring of HER2/neu expression, replacing traditional optical microscopy. Device facilitates clinical decision-making regarding HER2-targeted therapies (Trastuzumab, Pertuzumab, Ado-Trastuzumab Emtansine). System supports LIS integration via HL7. Benefits include digital workflow efficiency, remote viewing, and standardized image management.

Clinical Evidence

Method comparison study (n=200) compared manual digital scoring vs. manual optical microscopy across three pathologists. Results showed high percent agreement for HER2 scoring categories. Intra-pathologist precision (n=8 slides, 5 reads) showed 92.50% agreement for digital vs 87.50% for optical. Inter-pathologist precision (n=200) showed 84.78% agreement for digital vs 88.04% for optical. Instrument precision (inter-system/inter-day) showed 88.24% to 92.98% agreement. Studies confirm digital manual read performance is comparable to traditional optical methods.

Technological Characteristics

System includes automated slide scanner, server, and review workstation with dedicated Barco MDCC 2121 monitor. Imaging features include automatic focus, compression, and image stitching. Connectivity via HL7 for LIS integration. Software performs digital image management and viewing; no automated image analysis algorithms are applied (manual read only). Line-powered electrical source.

Indications for Use

Indicated for use as an accessory to Dako HercepTest™ to aid in detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in formalin-fixed, paraffin-embedded neoplastic breast tissue. Intended for assessment of breast cancer patients being considered for HERCEPTIN® (Trastuzumab), PERJETA® (Pertuzumab), or KADCYLA® (Ado-Trastuzumab Emtansine) therapy. For use by qualified pathologists.

Regulatory Classification

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

• Virtual Slide System, ScanScope® XT System (K111914)
• Olympus VS800 System, VS00 HER2 MR Application (K071671)

Submission Summary (Full Text)

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K 130021

# 6. 510(k) Summary

In accordance with the provisions of the Safe Medical Device Act of 1990, PHILIPS MEDICAL SYSTEMS NEDERLAND B.V. is providing a summary of Safety and Effectiveness information regarding the Philips HER2/neu IHC Digital Manual Read.

# 6.1. Company Identification

PHILIPS MEDICAL SYSTEMS NEDERLAND B.V. Veenpluis 4-6 Best, Netherlands 5864 PC Establishment Registration Number: 3003768277

# 6.2. Contact Person

Dirk Vossen Philips Digital Pathology Director Applications and Q&R Telephone: [phone] Email: [e-mail]

# 6.3. Preparation Date

September 19, 2013

# 6.4. Identification of Product and Classification

Device Trade Name: Philips HER2/neu IHC Digital Manual Read Classification Name: Immunohistochemistry reagents and kits Classification Panel: Pathology 88 CRF Section: 864.1860 Device Class: II Product Code: OEO

# 6.5. Predicate Devices

Legally marketed devices to which substantial equivalence is claimed is described in Table 6-1

Table 6-1 Predicate Devices Device Trade Name: Virtual Slide System, ScanScope® XT System Olympus VS800 System, VS00 HER2 MR Application Manufacturer: Aperio Technologies Olympus 510(k) Number: K111914 K071671 Classification Name: Immunohistochemistry reagents and kits Classification Panel: Pathology 88 CRF Section: 864.1860 Device Class: 11 Product Code: OEO (microscope, automated, digital image, manual interpretation)

Image /page/0/Picture/15 description: The image shows the Philips logo, which consists of the word "PHILIPS" in bold, uppercase letters above a circular emblem. The emblem features four stars, two above and two below, with wavy lines in the center, resembling water or sound waves. The logo is presented in black and white, with a simple, clean design.

All rights are reserved. Reproduction or transmission in whole or in part, in any form or by any means actronic, mechanical or otherwise, is prohibited without the prior written consent of the

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# 6.6. Device Description

The Philips HER2/neu IHC Digital Manual Read is a digital manual read application and an adjunct to primary diagnosis. The application utilizes the Philips Digital Pathology Solution (DPS) platform that includes a Philips Ultra Fast Scanner (UFS) and Philips Image Management System (IMS).

The Philips Digital Pathology Solution is an automated digital slide creation, management, sharing, 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.

The Philips UFS system digitizes slides at high resolution and generates the whole slide images (WSI). The Philips UFS also takes snapshot images of the entire glass slide as well as the glass slide label and decodes the barcode. Based on the macro image of the scanner determines which region on the slide will be scanned. All images, WSI and snapshot images together with information about the decoded barcode are sent to the Philips Image Management System (Philips IMS).

The Phillips IMS comes supplied with the Barco MDCC 2121 monitor and runs on commercially available server and workstation IT hardware which are specified by Philips and purchased by the customer. The server stores and manages the digital slide images and digital slide metadata. The server supports interoperability with other information systems such as the laboratory information systems (LIS) via a HL7 interface. The IMS Web Viewer software provides the User Interface for the pathologist to view and read the digital slides.

# 6.7. Intended Use and Indications for Use

The Philips HER2/neu IHC Digital Manual Read 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. The Philips HER2/neu IHC Digital Manual Read is based on the Philips Digital Pathology Solution platform, which is an automated digital slide creation, management, viewing and analysis system.

The Philips HER2/neu IHC Digital Manual Read is intended for use as an accessory to the Dako HercepTest™ to aid in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in formalin-fixed, paraffin-embedded 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 from whom HERCEPTIN® (Trastuzumab), PERJETA® (Pertuzumab) or KADCYLA® (Ado-Trastuzumab Emtansine) treatment is being considered. Note: The actual correlation of the Dako HercepTest™ to Herceptin®, Perjeta®, or Kadcyla®, clinical outcome has not been established.

Note: The Philips HER2/neu IHC Digital Manual Read is for evaluation of digital images of immunohistochemically stained slides that would otherwise be appropriate for manual visualization by conventional microscopy. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for Dako HercepTest™ to assure the validity of the scores obtained using Philips HER2/neu IHC Digital Manual Read.

### 6.8. Summary of Technological Characteristics Comparison

The Philips HER2/neu IHC Digital Manual Read has the same technological characteristics as the predicate devices as follows:

Specimen preparation: All systems are designed to be work on formalin embedded sectioned breast tissues samples that are stained with Dako HercepTest™.

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System components: All systems include the following major components: a computer-automated scanner that is capable of handling multiple sildes, software for the scanner, server software to maintain images acquired and software used to view and report on the specimen images.

Imaging: All systems include color digital image capture of low resolution and high resolution images that the pathologist can view. All systems include automatic focus, compression and image stitching algorithms. No image analysis algorithms are applied to these systems (i.e. digital manual read only).

Review stations: All systems include review station software and a dedicated monitor that allows case review management, viewing of specimen images including standard image processing functions such as zooming and panning, and reporting functions. All systems include integration with Laboratory Information Systems (LIS).

Electrical source: All systems have scanners that are line powered. Review stations are also line powered.

### 6.9. Performance Studies

#### 6.9.1. Nonclinical tests

Nonclinical tests were conducted on the Philips HER2/neu IHC Digital Manual Read to verify that the device met the system requirements for both the UFS and the IMS. The tests included internal and external testing for compliance to standards for in-vitro diagnostic devices, including image formats, electrical safety, electromagnetic compatibility and FCC Part 15.

### 6.9.2. Clinical tests

#### 6.9.2.1. Method Comparison (Manual Digital vs. Manual Optical)

A method comparison study was conducted to compare the pathologist scoring of breast specimens that have been stained with Dako's FDA approved HercepTest™ (P980018). The two methods compared were the traditional optical microscope ("Manual Optical") and manual reading of digital slides on a computer monitor ("Manual Digital"). This study was referred to as the "method comparison study".

A total of two hundred (200) formalin-fixed, paraffin-embedded breast tissue specimens from a tissue bank of de-identified human specimens were selected for inclusion in the study. The slides were prescreened by a pathologist to evaluate the quality of the staining and to provide a score. Slides that passed the prescreening were randomly selected to fulfill a roughly equal distribution of HercepTest™ scores in the following categories (0, 1+, 2+, 3+).

The pathologists in the study were trained in the use of the investigational device according to the labeling. The study simulated the actual environment in which the devices are to be used. The slides were scanned at three different scanners and three pathologists from two sites participated in the study. These three pathologists scored the method comparison study slide set in a randomized fashion with the following methods:

- once in a manual review on the Philips HER2/neu IHC Digital Manual Digital) .
- . once using a conventional optical microscope (Manual Optical)

The pathologists scored all slides using one of the two methods (the optical microscope or Philips HER2/neu IHC Digital Manual Read) before they started a manual review using the other method. The order of the methods was randomized over the pathologists. The washout period was at least 7 days. Analyzable data were slides that passed quality screening by the scan operator (a pathology

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technician or pathologist) after scanning and passed quality assessment by the pathologist prior to scoring.

Tables 6-2, 6-3 and 6-4 show the 4x4 tables and statistical analyses for a trichotomous categorization of HER2 scores (combining 0 and 1+ and leaving 2+ and 3+ uncombined) for the three pathologists in the study. The statistical analysis provided is a column-wise Percent Agreement (PA) with an exact 95% Confidence Interval (CI).

| | Table 6-2 - 4x4 Inter-Method comparison and trichotomous column-wise PA with Exact 95% Cl per |
|---------------------------------------|-----------------------------------------------------------------------------------------------|
| pathologist: Site 1 for Pathologist 1 | |
| | |

| Pathologist 1 | | Manual Optical Read | | | | |
|---------------------|-------|---------------------|------------------|----|----|-------|
| | | 0 | 1+ | 2+ | 3+ | Total |
| Manual Digital Read | 0 | 37 | 1 | 0 | 0 | 38 |
| | 1+ | 1 | 46 | 8 | 0 | 55 |
| | 2+ | 0 | 8 | 33 | 1 | 42 |
| | 3+ | 0 | 0 | 5 | 44 | 49 |
| | Total | 38 | 55 | 46 | 45 | 184 |
| Score | | PA | Exact 95% CI | | | |
| 0, 1+ | | 91.40% | [83.75%, 96.21%] | | | |
| 2+ | | 71.74% | [56.54%, 84.01%] | | | |
| 3+ | | 97.78% | [88.23%, 99.94%] | | | |

Table 6-3 - 4x4 Inter-Method comparison and trichotomous column-wise PA with Exact 95% CI per pathologist: Site 1 for Pathologist 2

| Pathologist 2 | | Manual Optical Read | | | | |
|---------------|--------|---------------------|-----|----|----|-------|
| | | 0 | 1 + | 2+ | 3+ | Total |
| | 0 | 23 | 0 | 0 | 0 | 23 |
| Manual | 1 + | 22 | 21 | 1 | 0 | 44 |
| Digital | 2+ | 2 | 28 | 45 | 0 | 75 |
| Read | 3+ | 0 | 0 | 5 | 43 | 48 |
| | Total | 47 | 49 | 51 | 43 | 190 |
| Score | PA | Exact 95% CI | | / | | |
| 0, 1+ | 68.75% | [58.48%, 77.82%] | | | | |
| 2+ | 88.24% | [76.13%, 95.56%] | | | | |
| 3+ | 100.0% | [91.78%, 100.0%] | | | | |

© KONINKLIJKE PHILIPS ELECTRONICS N.V. 2013. All rights reserved.

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| Pathologist 3 | | Manual Optical Read | | | | |
|---------------------------|--------|---------------------|----|----|----|-------|
| | | 0 | 1+ | 2+ | 3+ | Total |
| Manual<br>Digital<br>Read | 0 | 26 | 0 | 0 | 0 | 26 |
| | 1+ | 6 | 77 | 2 | 0 | 85 |
| | 2+ | 0 | 13 | 28 | 1 | 42 |
| | 3+ | 0 | 1 | 10 | 32 | 43 |
| | Total | 32 | 91 | 40 | 33 | 196 |
| Score | PA | Exact 95% CI | | | | |
| 0, 1+ | 88.62% | [81.64%, 93.64%] | | | | |
| 2+ | 70.00% | [53.47%, 83.44%] | | | | |
| 3+ | 96.97% | [84.24%, 99.92%] | | | | |

Table 6-4 - 4x4 Inter-Method comparison and trichotomous column-wise PA with Exact 95% CI per pathologist: Site 2 for Pathologist 3

#### 6.9.2.2. Pathologist Precision Studies

An overview of the pathologist precision studies is described in Table 6-5.

Table 6-5 Overview of pathologist precision studies

| Pathologists<br>Precision studies | Description |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intra-Pathologist | The precision study slide set was evaluated 5 times using Manual<br>Digital and 5 times using Manual Optical by one pathologist. A<br>wash-out period of at least seven days was used between the<br>pathologist's evaluations. |
| Inter-Pathologists | The slide set was evaluated once by each of three pathologists<br>using both Manual Digital and Manual Optical. This data was taken<br>from the data collected in the method comparison study. All data<br>from the method comparison was used. |

A target slide set of 8 HercepTest™ slides was used in the intra-pathologist studies consisting of two slides in each of the categories (0, 1+, 2+, 3+). In order to reduce the bias caused by repetitive viewing of the slides for the intra-pathologist precision study, the 8 target precision study slides were mixed with an additional set of 12 slides for each reading session. The 12 extra slides, hereafter called wild cards, were randomly chosen from a pool of 50 slides containing roughly equal distribution between the scoring categories. The slide order for each of the ten reads was randomized.

The inter-pathologist study used data collected from all sites in method comparison study; all data from the method comparison study was used.

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For the Intra-Pathologist precision study outliers are defined as scores that are different from the median values of the scores provided by the pathologist over 5 runs of the method. The agreement is calculated by subtracting the percentage of outliers from 100%.

The tables 6-6 and 6-7 show the number of outliers for Manual Optical and for Manual Digital Intra-Pathologist Precision.

Table 6-6 Manual Optical Intra-Pathologist Precision (number (%) of reads)

| Study | Scoring | Agreement | Number of outliers |
|-------------------------------------|----------------------|-------------|--------------------|
| Manual Optical<br>Intra-pathologist | HercepTest™<br>Score | 35 (87.50%) | 5 (12.50%) |

Table 6-7 Manual Digital Intra-Pathologist Precision (number (%) of reads)

| Study | Scoring | Agreement | Number of outliers |
|-------------------------------------|----------------------|-------------|--------------------|
| Manual Digital<br>Intra-pathologist | HercepTest™<br>Score | 37 (92.50%) | 3 (7.50%) |

Manual Digital Inter-Pathologist overall comparison and Manual Optical Inter-Pathologist overall comparison are shown in Tables 6-8 and 6-9.

#### Table 6-8 Manual Digital Inter-Pathologist Precision

| Overall agreement: Inter-Pathologist MD | |
|-----------------------------------------|-------------------------------|
| Binary Percent agreement | 84.78%, CI(95%) [80.80,88.77] |

#### Table 6-9 Manual Optical Inter-Pathologist Precision

| Overall agreement: Inter-Pathologist MO | | | |
|-----------------------------------------|------------------------------|--|--|
| Binary Percent agreement | 88.04%, CI(95%)[84.06,91.67] | | |

#### 6.9.2.3. Instrument Precision Studies

The primary objective of this study was to assess intra-instrument and inter-instrument precision for the Philips HER2/neu IHC Digital Manual Read. Precision was determined on 40 HercepTest stained tissue slides, hereafter called core slides, equally divided over the scoring categories (0, 1+, 2+, 3+) in two studies: Inter-System and Inter-Day/Intra-System as described in Table 6-10 below:

#### Table 6-10 - Overview of Instrument Precision studies

| Instrument Precision<br>studies | Description |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------|
| Inter-Day/Intra-System<br>(IDIS) | The slide set was scanned on three<br>different days on the same device and the<br>images were scored by one pathologist |
| Inter-system (Inter-S) | The slide set was scanned one time on<br>three devices and the images were<br>scored by one pathologist |

To obtain an equal distribution of the slides over the four HercepTest score categories, the specimens were pre-scored according to the HercepTest package insert by a pathologist not involved in the study..

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Two board-certified pathologists provided a HercepTest score based on the images in a blinded fashion, one pathologist for the Inter-S and one for the IDIS study. Prior to the study the pathologists were randomly allocated to either the Inter-S or IDIS study. The reads was also randomized.

To prevent possible recall bias by having the same image read more than once, a minimum washout period of one week was imposed required between the reading sessions. In addition, 32 wild card slides, approximately equally divided over the four scoring categories, were added to the reads. Different wild cards were used for different reads. The wild cards were not used in the analysis.

Table 6-11 below shows the overall 3x3 agreements (combining 0 and 1+, and leaving 2+ and 3+ uncombined) and CI(95%) for the IDIS and Inter-S studies.

| Studies | 3x3 Overall<br>Agreement | 95% Confidence Interval |
|---------|--------------------------|-------------------------|
| IDIS | 92.98% | [86.76%, 96.40%] |
| Inter-S | 88.24% | [80.55%, 93.14%] |

Table 6-11 - Overall 3x3 agreements and CI(95%) for Instrument Precision Studies

#### 6.9.3. Conclusions drawn from the nonclinical and clinical tests

The device labeling contains instructions for use as well as necessary cautions and warnings to provide for safe and effective use of the device. The Philips HER2/neu IHC Digital Manual Read is intended for the evaluation of digital images of HER2/neu immunohistochemically stained slides that would otherwise be appropriate for manual visualization by conventional microscopy. It is the responsibility of qualified pathologists to employ appropriate morphological studies and controls as specified in the package insert for Dako HercepTest™ to assure the validity of the scores obtained using the Philips HER2/neu IHC Digital Manual Read. Philips HER2/neu IHC Digital Manual Read is substantially equivalent in design and intended use to the predicate device, ScanScope® XT System from Aperio Technologies and VS800 System from Olympus, which includes digital slide scanner, image storage software and viewing software. Any differences between the Philips HER2/neu IHC Digital Manual Read and the predicate devices have no significant influence on safety or effectiveness. All of the method comparison and precision clinical studies components met the expected acceptance criteria. The nonclinical tests demonstrate that the performance of the Philips HER2/neu IHC Digital Manual Read is also substantially equivalent to the predicate devices. Therefore, Philips HER2/neu IHC Digital Manual Read raises of safety or effectiveness as compared to the predicate devices.

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#### 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 19, 2013

PHILIPS MEDICAL SYSTEMS NEDERLAND B.V. C/O MR. DIRK VOSSEN VEENPLUIS 4-6 BEST, NB 5684 PC NL

Re: K130021

Trade/Device Name: Philips Her2/neu IHC Digital Manual Read Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: OEO Dated: September 13, 2013 Received: September 16, 2013

Dear Mr. Vossen:

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.

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Page 2-Mr. Vossen

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 [phone] or [phone] or at its Internet address http://www.fda.goy/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 [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Maria:M.Chan -S

Maria M. Chan, PhD 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

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

#### 510(k) Number (if known) k 130021

#### Device Name

#### Philips HER2/neu HIC Digital Manual Read

#### Indications for Use (Describe)

The Philips HER2/new HC Digital Manual for in vitro diagnostic use as an aid to the pathologist in the display, decection, counting and classification of tissues and cells of clinical interest based on particular color, intensity, size, pattern and shape. The Philips HER2/neu IHC Digital Manual Read is based on the Philips Digital Pathology Solution platform, which is an automated digital slide creation, management, viewing and analysis system.

The Philips HER2/neu IHC Digital Manual Read is intended for use as an accessory to the Dake HercepTess™ to aid in the decetion and semi-quantitative measurement of HER2/neu (e-erbB-2) in formalin-fixed, paraffin-embedded neoplastic tissue immunistically 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 from whom HERCEPTIN® (Trastuzunab) or KADCYLA® (Ado-Trastuzumab Emtansine) treatment is being considered. Note: The actual correlation of the Dako HercepTest™ (o Herceptin®, Perjeta®, or Kadeyla®, clinical outcome has not been established.

Note: The Philips HER2/new IHC Digital Manual Read is for evaluation of digital images of immunohistochemically stained slides that would otherwise be appropriate for manual visualization by conventional microscopy. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for Daks IIc the validity of the scores obtained using Philips HER2/neu IHC Digital Manual Read.

Type of Use (Select one or both, as applicable) Z Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR-807-Subpart C)

801

# PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

diological Health (CDRH) (Signature)

Yun-fu開Huas

FORM FDA 3881 (6/13)

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