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 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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria with specific threshold values for the performance metrics. Instead, it describes clinical studies aiming to demonstrate substantial equivalence to manual optical reading. The conclusion states that "All of the method comparison and precision clinical studies components met the expected acceptance criteria." This implies that the observed agreements were considered sufficient, even if a numerical threshold wasn't articulated in the summary.

Inferred "Acceptance" (demonstrated performance) and Reported Device Performance:

Performance Metric	Reported Device Performance (Manual Digital vs. Manual Optical)
Method Comparison (Inter-Method Agreement - Trichotomous)
Pathologist 1 (Site 1) - Score 0, 1+	91.40% [83.75%, 96.21%]
Pathologist 1 (Site 1) - Score 2+	71.74% [56.54%, 84.01%]
Pathologist 1 (Site 1) - Score 3+	97.78% [88.23%, 99.94%]
Pathologist 2 (Site 1) - Score 0, 1+	68.75% [58.48%, 77.82%]
Pathologist 2 (Site 1) - Score 2+	88.24% [76.13%, 95.56%]
Pathologist 2 (Site 1) - Score 3+	100.0% [91.78%, 100.0%]
Pathologist 3 (Site 2) - Score 0, 1+	88.62% [81.64%, 93.64%]
Pathologist 3 (Site 2) - Score 2+	70.00% [53.47%, 83.44%]
Pathologist 3 (Site 2) - Score 3+	96.97% [84.24%, 99.92%]
Intra-Pathologist Precision
Manual Optical Agreement (outliers)	87.50% (12.50%)
Manual Digital Agreement (outliers)	92.50% (7.50%)
Inter-Pathologist Precision (Binary)
Manual Digital Overall Agreement	84.78% [80.80%, 88.77%]
Manual Optical Overall Agreement	88.04% [84.06%, 91.67%]
Instrument Precision (3x3 Overall Agreement)
Inter-Day/Intra-System (IDIS)	92.98% [86.76%, 96.40%]
Inter-System (Inter-S)	88.24% [80.55%, 93.14%]

2. Sample Size for Test Set and Data Provenance

Sample Size (Method Comparison Study): Two hundred (200) formalin-fixed, paraffin-embedded breast tissue specimens. Each specimen was scored by 3 pathologists using two different methods, resulting in 6 study reads per specimen. However, the 4x4 tables show totals around 184-196, indicating some slides might have been excluded due to quality issues.
Sample Size (Intra-Pathologist Precision Study): A target set of 8 HercepTest™ slides, evaluated 5 times for each method (Manual Digital and Manual Optical). To reduce bias, these 8 slides were mixed with an additional set of 12 "wild card" slides for each reading session (total of 20 slides per session).
Sample Size (Inter-Pathologist Precision Study): This study utilized the data collected from all sites in the method comparison study (i.e., all 200 specimens scored by 3 pathologists).
Sample Size (Instrument Precision Studies): 40 HercepTest™ stained tissue slides (core slides). These were augmented with 32 "wild card" slides for each reading session.
Data Provenance: The specimens were obtained from a tissue bank of de-identified human specimens. The country of origin is not specified, but the applicant is based in the Netherlands. The study simulates the use environment (three pathologists from two sites participated). The nature of the historical tissue bank makes it retrospective.

3. Number of Experts and Qualifications for Ground Truth for the Test Set

The concept of a single "ground truth" for the test set, as might be established by pathology or outcomes data, is not directly applicable here. This study primarily compares two methods of interpretation (manual optical vs. manual digital) by human pathologists.

Method Comparison Study:
- Number of "Experts": Three (3) pathologists.
- Qualifications: "The pathologists in the study were trained in the use of the investigational device according to the labeling." No further specific qualifications like years of experience or board certification are detailed for these three.
- "Ground Truth": No external "ground truth" was established a priori. The study aims to demonstrate concordance between the two reading methods by the same pathologists. The slides were prescreened by a pathologist (not necessarily one of the study pathologists) to evaluate staining quality and provide an initial score, which was used for selection to ensure a balanced distribution of scores, but this initial score was not treated as the definitive ground truth against which study observations were compared.
Intra-Pathologist Precision Study:
- Number of "Experts": One (1) pathologist.
- Qualifications: Not explicitly stated beyond "a pathologist."
- "Ground Truth": The "median values of the scores provided by the pathologist over 5 runs" were used as the reference against which outlying scores were identified for agreement calculation.
Inter-Pathologist Precision Study:
- Number of "Experts": Three (3) pathologists.
- Qualifications: Not explicitly stated beyond "pathologists."
- "Ground Truth": No external "ground truth." This study evaluated agreement among the pathologists' readings.
Instrument Precision Studies:
- Number of "Experts": Two (2) board-certified pathologists. One for Inter-S and one for IDIS.
- Qualifications: "Two board-certified pathologists."
- "Ground Truth": The specimens were "pre-scored... by a pathologist not involved in the study" to ensure equal distribution of scores, but this pre-score was not used as definitive ground truth for the analyses presented. The study assessed the consistency of interpretation of images generated by different scans/days by the assigned study pathologist.

4. Adjudication Method for the Test Set

For the method comparison and precision studies:

No explicit adjudication method (like 2+1 or 3+1) was used to establish a definitive ground truth by consensus among multiple experts.
Instead, the studies focused on concordance between the manual optical reading and the manual digital reading by the same pathologist, and then on agreement among different pathologists' readings for inter-pathologist precision.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Yes, a form of MRMC study was done in the "Method Comparison (Manual Digital vs. Manual Optical)" section. It compared the performance of human readers (pathologists) using a traditional optical microscope versus using the Philips HER2/neu IHC Digital Manual Read system.
Effect Size of AI vs. Without AI Assistance:
The device is described as "No image analysis algorithms are applied to these systems (i.e. digital manual read only)." This means the device itself does not include any AI assistance for interpretation; it is a digital display system for manual reading by a human. Therefore, there is no reported effect size of how much human readers improve with AI vs. without AI assistance because the "AI" component is absent from the interpretation process. The study demonstrates the equivalence of manual digital reading to manual optical reading.

6. Standalone (Algorithm Only) Performance

No standalone (algorithm only) performance study was done because the device is explicitly a "Digital Manual Read" application and "No image analysis algorithms are applied to these systems." The device functions as a display and management system for images that are still manually interpreted by a pathologist.

7. Type of Ground Truth Used

As elaborated in point 3, the studies did not use a single, external "ground truth" (such as unanimous expert consensus, pathology, or outcomes data) against which the device's performance was measured in an absolute sense.

Method Comparison: The "ground truth" was effectively the pathologist's own reading using the conventional optical microscope, against which their reading using the digital system was compared for agreement.
Precision Studies: The "ground truth" was either the pathologist's median score (for intra-pathologist) or the agreement among pathologists (for inter-pathologist).
For the instrument precision studies, the comparison was based on consistency of scores by a single pathologist across different scans/days/instruments.

8. Sample Size for the Training Set

The document describes a "Digital Manual Read" device, which means it is a display and management system for pathologists to manually interpret whole slide images. It explicitly states, "No image analysis algorithms are applied to these systems."
Therefore, there is no AI algorithm being "trained," and consequently, there is no "training set" of data for an AI model.

9. How Ground Truth for Training Set Was Established

As there is no AI algorithm that requires training, there is no training set and no ground truth established for a training set.

Summary

{0}------------------------------------------------

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: +316 53 181 374 Email: dirk.vossen@philips.com

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

{1}------------------------------------------------

6.6. Device Description

6.7. Intended Use and Indications for Use

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™.

{2}------------------------------------------------

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

{3}------------------------------------------------

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%]

{4}------------------------------------------------

Pathologist 3		Manual Optical Read
		0	1+	2+	3+	Total
ManualDigitalRead	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

PathologistsPrecision studies	Description
Intra-Pathologist	The precision study slide set was evaluated 5 times using ManualDigital and 5 times using Manual Optical by one pathologist. Awash-out period of at least seven days was used between thepathologist's evaluations.
Inter-Pathologists	The slide set was evaluated once by each of three pathologistsusing both Manual Digital and Manual Optical. This data was takenfrom the data collected in the method comparison study. All datafrom 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.

{5}------------------------------------------------

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 OpticalIntra-pathologist	HercepTest™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 DigitalIntra-pathologist	HercepTest™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 Precisionstudies	Description
Inter-Day/Intra-System(IDIS)	The slide set was scanned on threedifferent days on the same device and theimages were scored by one pathologist
Inter-system (Inter-S)	The slide set was scanned one time onthree devices and the images werescored 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..

{6}------------------------------------------------

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 OverallAgreement	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.

{7}------------------------------------------------

Image /page/7/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name in a circular arrangement around a symbol. The symbol consists of a stylized caduceus-like design, with three parallel lines curving upwards and to the right, resembling a stylized representation of a human form or a medical symbol.

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.

{8}------------------------------------------------

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 (800) 638 2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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

{9}------------------------------------------------

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)

{10}------------------------------------------------

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Regulation Number and Section

§ 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.