The Philips IntelliSite Pathology Solution (PIPS) 5.1 is an automated digital slide creation, viewing, and management system. The PIPS 5.1 is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The PIPS 5.1 is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.

The PIPS 5.1 comprises the Imagement System (IMS) 4.2, Ultra Fast Scanner (UFS), Pathology Scanner SG20, Pathology Scanner SG60, Pathology Scanner SG300 and PP27QHD Display. The PIPS 5.1 is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS 5.1.

Device Description

The Philips IntelliSite Pathology Solution (PIPS) 5.1 is an automated digital slide creation, viewing, and management system. PIPS 5.1 consists of two subsystems and a display component:

Subsystems:
a. A scanner in any combination of the following scanner models
i. Ultra Fast Scanner (UFS)
ii. Pathology Scanner SG with different versions for varying slide capacity Pathology Scanner SG20, Pathology Scanner SG60, Pathology Scanner SG300
b. Image Management System (IMS) 4.2
Display PP27QHD

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Philips IntelliSite Pathology Solution 5.1, based on the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Acceptance Criteria	Reported Device Performance (Summary)
Technical Performance (Non-Clinical)	All technical studies (e.g., Light Source, Imaging optics, Mechanical scanner Movement, Digital Imaging sensor, Image Processing Software, Image composition, Image Review Manipulation Software, Color Reproducibility, Spatial Resolution, Focusing Test, Whole Slide Tissue Coverage, Stitching Error, Turnaround Time) must pass their predefined acceptance criteria.	All technical studies passed their acceptance criteria. Pixelwise comparison showed identical image reproduction with zero ΔE between subject and predicate device.
Electrical Safety	Compliance with IEC61010-1.	Passed.
Electromagnetic Compatibility (EMC)	Compliance with IEC 61326-2-6 (for laboratory use of in vitro diagnostic equipment) and IEC 60601-1-2.	Passed for both emissions and immunity.
Human Factors	User tasks and use scenarios successfully completed by all user groups.	Successfully completed for all user groups.
Precision Study (Intra-system)	Lower limit of the 95% Confidence Interval (CI) of the Average Positive Agreement exceeding 85%.	Overall Agreement Rate: 88.3% (95% CI: 86.7%; 89.9%). All individual scanner CIs also exceeded 85%.
Precision Study (Inter-system)	Lower limit of the 95% CI of the Average Positive Agreement exceeding 85%.	Overall Agreement Rate: 95.4% (95% CI: 94.4%; 96.5%). All individual scanner comparison CIs also exceeded 85%.
Precision Study (Inter-site)	Lower limit of the 95% CI of the Average Positive Agreement exceeding 85%.	Overall Agreement Rate: 90.7% (95% CI: 88.4%; 92.9%). All individual site comparison CIs also exceeded 85%.
Clinical Study (Non-Inferiority)	The upper bound of the 95% two-sided confidence interval for the manual digital – manual optical difference in major discordance rate is less than 4%.	Difference in major discordance rate (digital-optical) was 0.1% with a 95% CI of (-1.01%; 1.18%). The upper limit (1.18%) was less than the non-inferiority margin of 4%.

Study Details

2. Sample sized used for the test set and the data provenance:

Non-Clinical (Pixelwise Comparison):
- Sample Size: 42 FFPE tissue glass slides from different anatomic locations. Three regions of interest (ROI) were selected from each scanned image.
- Data Provenance: Not explicitly stated, but likely retrospective from existing archives given the nature of image comparison. The country of origin is not specified.
Precision Study:
- Sample Size: Not explicitly stated as a single number but implied by the "Number of Comparison Pairs" in the tables:
  - Intra-system: 3600 comparison pairs (likely 3 scanners with multiple reads/slides contributing).
  - Inter-system: 3610 comparison pairs.
  - Inter-site: 1228 comparison pairs.
- Data Provenance: Not explicitly stated, but the inter-site component suggests data from multiple locations. Retrospective or prospective is not specified.
Clinical Study:
- Sample Size: 952 cases consisting of multiple organ and tissue types.
- Data Provenance: Cases were divided over three sites. Retrospective or prospective is not specified, but the design (randomized order, washout period) suggests a prospective setup for the reading phase. The "original sign-out diagnosis rendered at the institution" implies a retrospective component for establishing the initial ground truth.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Non-Clinical (Pixelwise Comparison): No experts were explicitly mentioned for ground truth establishment; the comparison was purely technical (pixel-to-pixel).
Precision Study: The ground truth for agreement was based on the comparison of diagnoses by pathologists, but the initial "ground truth" for the slides themselves (e.g., what they actually represented) isn't detailed in terms of expert consensus.
Clinical Study:
- Initial Ground Truth: The "original sign-out diagnosis rendered at the institution, using an optical (light) microscope" served as the primary reference diagnosis. The qualifications of these original pathologists are implied to be standard for their role but not explicitly stated (e.g., "radiologist with 10 years of experience").
- Adjudication: Three adjudicators reviewed the reader diagnoses against the sign-out diagnosis to determine concordance, minor discordance, or major discordance. Their qualifications are not specified beyond being "adjudicators."

4. Adjudication method (for the test set):

Clinical Study: Three adjudicators reviewed the reader diagnoses (from both manual digital and manual optical modalities) against the original sign-out diagnosis. The method for resolving disagreements among the three adjudicators (e.g., 2+1 majority, consensus) is not specified.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Yes, a MRMC study was done, but it was for comparative non-inferiority between digital and optical methods by human readers, not explicitly for AI assistance. The study compared human pathologists reading slides using the digital system (PIPS 5.1) versus human pathologists reading slides using a traditional optical microscope.
Effect Size of AI: This study does not involve AI assistance for human readers. The device (PIPS 5.1) is a whole slide imaging system, not an AI diagnostic tool. Therefore, there is no reported effect size regarding human reader improvement with AI assistance from this study.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

No. The Philips IntelliSite Pathology Solution 5.1 is described as "an aid to the pathologist to review and interpret digital images." The clinical study clearly focuses on the performance of human pathologists using the system, demonstrating its non-inferiority to optical microscopy for human interpretation. There is no mention of a standalone algorithm performance.

7. The type of ground truth used:

Non-Clinical (Pixelwise Comparison): The "ground truth" was the direct pixel data from the predicate device, against which the subject device's reproduced pixels were compared for identity.
Precision Study: The ground truth for evaluating agreement rates was the diagnoses made by pathologists on different scans of the same slides. The ultimate truth of the disease state was implicitly tied to the original diagnostic process.
Clinical Study: The primary ground truth was "the original sign-out diagnosis rendered at the institution, using an optical (light) microscope." This represents a form of expert consensus/established diagnosis within a clinical setting.

8. The sample size for the training set:

Not Applicable / Not Provided. The provided document describes a 510(k) submission for a Whole Slide Imaging (WSI) system, which is a medical device for generating, viewing, and managing digital images of pathology slides. It acts as a digital microscope. It is not an AI algorithm or a diagnostic tool that requires a training set in the typical machine learning sense to learn a particular diagnostic task. Therefore, no training set data is relevant or provided here.

9. How the ground truth for the training set was established:

Not Applicable / Not Provided. As explained above, this device does not utilize a training set in the AI/ML context.

Summary

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June 24, 2024

Philips Medical Systems Nederland B.V. Liselotte Kornmann Associate Director Regulatory Affairs Veenpluis 6 Best, Noord Brabant 5684PC Netherlands

Re: K233204

Trade/Device Name: Philips IntelliSite Pathology Solution 5.1 Regulation Number: 21 CFR 864.3700 Regulation Name: Whole slide imaging system Regulatory Class: Class II Product Code: PSY Dated: September 28, 2023 Received: September 28, 2023

Dear Liselotte Kornmann:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Shyam Kalavar -S

Shyam Kalavar Deputy Branch Chief Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K233204

Device Name Philips IntelliSite Pathology Solution 5.1

Indications for Use (Describe)

The PIPS 5.1 comprises the Imagement System (IMS) 4.2, Ultra Fast Scanner (UFS), Pathology Scanner SG20. Pathology Scanner SG60, Pathology Scanner SG300 and PP27QHD Display. The PIPS 5.1 is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS 5.1.

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary

Philips IntelliSite Pathology Solution 5.1

This 510(k) summary of safety and effectiveness information is prepared in accordance with 21 CFR ઠુક્ષ્ઠ07.92.

Preparation date: June 21, 2024

Company identification

Philips Medical Systems Nederland B.V. Veenpluis 6 5684PC. Best The Netherlands Establishment registration number: 3012563754

Contact person

Name: Liselotte Kornmann Title: Associate Director Regulatory Affairs Digital and Computational Pathology Telephone: +31611621238 Email: liselotte.kornmann@philips.com

Device

Device Trade Name: Philips IntelliSite Pathology Solution 5.1 Device Class: Class II Product Code: PSY Classification Requlation: 21 CFR, Part 864.3700 Classification Name: Whole Slide Imaging System Classification Panel: Pathology 510(k) Submission Number: K233204

Predicate device

Device Trade Name: Philips IntelliSite Pathology Solution 5.1 510(k) Number: K203845 (September 17, 2021)

Device description

The Philips IntelliSite Pathology Solution (PIPS) 5.1 is an automated digital slide creation, viewing, and management system. PIPS 5.1 consists of two subsystems and a display component:

1. Subsystems:
- a. A scanner in any combination of the following scanner models
  - i. Ultra Fast Scanner (UFS)
  - ii. Pathology Scanner SG with different versions for varying slide capacity Pathology Scanner SG20, Pathology Scanner SG60, Pathology Scanner SG300
- b. Image Management System (IMS) 4.2
1. Display PP27QHD

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Intended Use / Indications for Use

Compared to the predicate device, the Intended Use / Indications for Use of the subject device is updated to reflect the new Pathology Scanner models and IMS and is as follows:

The PIPS 5.1 comprises the Imagement System (IMS) 4.2, Ultra Fast Scanner (UFS), Pathology Scanner SG20, Pathology Scanner SG60, Pathology Scanner SG300 and PP27QHD Display. The PIPS 5.1 is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safequards to assure the validity of the interpretation of images obtained using PIPS 5.1.

Summary of Intended Use / Indications for Use

The difference between the subject and the predicate device does not alter the intended use of the device nor do they raise any new questions regarding safety or effectiveness. Both the subject and predicate devices have the same intended in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue.

Summary of technological characteristics

The subject device employs the same technological characteristics compared to the currently marketed predicate device, with exception of the following modification implemented:

· Addition of a new Pathology Scanner SG with the following variants:
- Pathology Scanner SG20 o
- Pathology Scanner SG60 o
- Pathology Scanner SG300 o
Update of Image Management System 4.1 (IMS 4.1) to IMS 4.2 to support the ● previously cleared Ultra Fast Scanner (UFS) in K203854 and Pathology scanners SG20/SG60/SG300.
. The three pathology scanner SG models share the same imaging pipeline, which is implemented in the scan engine (Second Generation Scanner Engine-SGSE). Based on the System Design Specification documents, the differences between the three SG models are mainly the slide feeders and housing.

Item	Predicate device PIPS(K203845)	Subject device PIPS 5.1(K233204)
Intended Use /Indications forUse	The Philips IntelliSite PathologySolution (PIPS) is an automated digitalslide creation, viewing, andmanagement system. The PIPS isintended for in vitro diagnostic use asan aid to the pathologist to review andinterpret digital images of surgicalpathology slides prepared fromformalin-fixed paraffin embedded(FFPE) tissue. The PIPS is notintended for use with frozen section,	The Philips IntelliSite PathologySolution (PIPS) 5.1 is an automateddigital slide creation, viewing, andmanagement system. The PIPS 5.1 isintended for in vitro diagnostic use asan aid to the pathologist to review andinterpret digital images of surgicalpathology slides prepared fromformalin-fixed paraffin embedded(FFPE) tissue. The PIPS 5.1 is notintended for use with frozen section,
Item	Predicate device PIPS(K203845)	Subject device PIPS 5.1(K233204)
	cytology, or non-FFPEhematopathology specimens.	cytology, or non-FFPEhematopathology specimens.
	The PIPS comprises the ImageManagement System (IMS), the UltraFast Scanner (UFS), and Display. ThePIPS is for creation and viewing ofdigital images of scanned glass slidesthat would otherwise be appropriate formanual visualization by conventionallight microscopy. It is the responsibilityof a qualified pathologist to employappropriate procedures andsafeguards to assure the validity of theinterpretation of images obtained usingPIPS.	The PIPS 5.1 comprises the ImageManagement System (IMS) 4.2, theUltra Fast Scanner (UFS), PathologyScanner SG20, Pathology ScannerSG60, Pathology Scanner SG300 andPP27QHD Display. The PIPS 5.1 is forcreation and viewing of digital imagesof scanned glass slides that wouldotherwise be appropriate for manualvisualization by conventional lightmicroscopy. It is the responsibility of aqualified pathologist to employappropriate procedures andsafeguards to assure the validity of theinterpretation of images obtained usingPIPS 5.1.
Specimen type	Surgical pathology slides preparedfrom formalin-fixed, paraffin-embedded tissue	Same
Principle ofoperation	The technician loads the slides into theWSI scanner. The scanner scans theslides and generates WSI image foreach slide. The technician performsQuality Control (QC) on scanned WSIimages and rescan the slide when QCis failed. The acquired WSI images arestored in an end user provided imagestorage attached to the local network.During review, the pathologist opensWSI images acquired with the WSIscanner from the image storage,performs further QC and reads WSIimages of the slides to make adiagnosis	Same
Devicecomponents	UFS, IMS and color monitor display	UFS, Pathology Scanner SG, IMS andcolor monitor display
Whole SlideImagingScanner	UFS with loading capacity of 300	UFS with loading capacity of 300Pathology Scanner SG with loadingcapacity of 300, 60, 20
Image FileFormat	iSyntax	Same
End User'sInterface	The IMS Image Processing Pipeline isdesigned to process UFS iSyntax data	The IMS Image Processing Pipeline isdesigned to process both UFS andPathology Scanner SG iSyntax data
Monitor Display	PP27QHD	Same

Comparison of technological characteristics

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Comparison of technological characteristics

The differences between the subject and the predicate device do not raise any new questions regarding safety or effectiveness. Based on the information provided above, the subject device PIPS 5.1 is substantially equivalent to the currently marketed predicate device (K203845) in terms of technological characteristics.

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Performance Data

A. Summary of non-clinical performance data

Verification testing activities have been performed to support the substantial equivalence determination for the subject device PIPS 5.1 (including the new Pathology Scanner SG and modified IMS for Pathology Scanner SG support). Performance characteristics of the subject device PIPS 5.1 are equivalent to those of the predicate device PIPS (K203845).

Technical studies were conducted to evaluate the performance of the new Pathology Scanner SG and modified IMS for Pathology Scanner SG support, as recommended in FDA's guidance, Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices.

TPA item	Performance data description
Slide Feeder	Information was provided on the configuration of the slide feed mechanism,including a physical description of the slide, the number of slides in queue (carrier),and the class of automation. Information was provided on the user interaction withthe slide feeder, including hardware, software, feedback mechanisms, and FailureMode and Effects Analysis (FMEA).
Light Source	Descriptive information associated with the light source was provided. Testinginformation was provided to verify the spectral distribution of the light that isincident on the slide to the slide is to verify that the color reproducibility of thePathology Scanner SG is within predefined limits. The tests passed theiracceptance criteria.
Imaging optics	An optical schematic with all optical elements identified from slide (object plane) toimage sensor (micro camera) was provided. Descriptive information regarding themicroscope objective, auxiliary lens(es), and the magnification of imaging opticswas provided. Testing information regarding the magnification, relative irradiance,optical distortions, and chromatic aberrations was provided. The tests passed theiracceptance criteria.
MechanicalscannerMovement	Information and specifications on the configuration of the stage, method ofmovement, control of movement of the stage, and FMEA was provided. Test datato determine positioning accuracy and repeatability for the X-Y and Z stages wasprovided. The tests passed their acceptance criteria.
Digital Imagingsensor	Information and specifications on the sensor type, pixel information, responsivityspecifications, noise specifications, readout rate, and digital output format wereprovided. Testing to determine the correct functioning of the digital image sensor.The tests passed their acceptance criteria.
ImageProcessingSoftware	Information and specifications on the exposure control, white balance, colorcorrection, sub-sampling, pixel-offset correction, shading (flat-field) correction, andpixel-defect correction were provided.
Imagecomposition	Information and specifications on the scanning method and focus, was provided.Test data to analyze the image composition performance was provided. The testspassed their acceptance criteria.
Image fileformats	Information and specifications on the compression method, compression ratio, fileformat, and file organization were provided.
Image ReviewManipulationSoftware	Information and specifications for continuous panning, continuous zooming,discrete Z-axis displacement, comparison of slides in multiple windows, annotationtools, image enhancement, color correction, tracking of visited areas, digitalbookmarks, and shared viewing sessions was provided. Test data to analyze theimage review manipulation software was provided. The tests passed theiracceptance criteria.
Display	No changes have been introduced for the PP27QHD display. Tests results for thisdisplay in previous 510(k) remain valid.
ComputerEnvironment	Information and specifications on the computer hardware, operating system,memory, hard disk, graphics card, graphics card driver, color managementsettings, color profile, display interface and network were provided.
TPA item	Performance data description
ColorReproducibility	Test data to quantify the accuracy and precision of the color transformation fromthe slide to the display monitor was provided. The tests passed their acceptancecriteria
SpatialResolution	Test data to evaluate the spatial resolution of the image acquisition phase wasprovided. The tests passed their acceptance criteria.
Focusing Test	Test data to demonstrate that the focus quality is clinically acceptable for a varietyof histologic preparations, including different tissue types, stain intensities,specimen thicknesses, and stain types was provided. The tests passed theiracceptance criteria.
Whole SlideTissueCoverage	detected by device was provided. The tests passed their acceptance criteria. Test data to demonstrate that the entire tissue specimen on the clinical slide is
Stitching Error	Test data to evaluate the stitching quality of the high resolution image of thePathology Scanner SG. The tests passed their acceptance criteria.
TurnaroundTime	Test data to evaluate the average time required to execute zooming and panningoperations, and to refresh the display in response to user input was provided. Thetests passed their acceptance criteria.

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Electrical safety testing was conducted in accordance with IEC61010-1 with passing results. Electromagnetic compatibility testing was conducted in accordance with IEC 61326-2-6 for laboratory use of in vitro diagnostic equipment with passing results. Electromagnetic compatibility testing was conducted in accordance with IEC 60601-1-2. The test results showed "pass" for emissions and immunity.
Human factors studies were designed around user tasks, and use scenarios performed by users were conducted. For all user groups, tasks were successfully completed.

3. Pixelwise comparison with the predicate device:

The equivalence between the subject device and the predicate device has been supported by bench testing data based on pixelwise comparison. A pixelwise comparison test has been performed to compare images reproduced by the predicate device and the subject device for the same iSyntax file to demonstrate identical image reproduction for UFS Images. The subject device was tested as operating with the intended components, including the scanner, image management system and display.

Scanned images, on the predicate device, from 42 FFPE tissue qlass slides from different anatomic locations were used as the test input. Three regions of interest (ROI) from each of the scanned images were selected. For each ROI, the differences between the views generated by the subject and predicate device were evaluated with the 1976 International Commission on Illumination (CIE) color difference metric ΔE for each corresponding pixel pair. Each location has been processed and sampled at 20x and 40x magnification level on both the predicate and subject device. The client workstation, according to device specification, with PP27QHD display has been used to capture ROIs and to perform the pixelwise comparison.

The color differences of all pixels within each ROI were reported. The image data of all ROIs were also provided for verification. The test results demonstrated that all image pairs are identical with zero ΔE. The subject device has been found to adequately reproduce digital pathology images at the pixel level with respect to its intended use.

B. Summary of analytical and clinical performance data

Two studies were conducted with the PIPS 5.1 device: Analytical studies to support device precision and clinical study to support the clinical performance of the device.

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1. Precision study

Device precision was evaluated for its proposed intended use. The study was divided into the following three sub-studies:

. Scans from the same scanner (intra-system precision)
Scans from different scanners at the same site (inter-system precision) ●
Scans from different scanners located at different sites read by different pathologists ● (Inter-site reproducibility)

Intra-system study results

System	Number ofComparison Pairs	Number ofPairwise Agreements	Agreement Rate
			%	95% CI
Overall	3600	3178	88.3	(86.7; 89.9)
Scanner 1	1210	1054	87.1	(84.1; 90.0)
Scanner 2	1190	1049	88.2	(85.6; 90.7)
Scanner 3	1200	1075	89.6	(86.6; 92.4)

Inter-system study results

Systemscompared	Number ofComparison Pairs	Number ofPairwise Agreements	Agreement Rate
			%	95% CI
Overall	3610	3445	95.4	(94.4; 96.5)
Scanner 1 –Scanner 2	1200	1144	95.3	(94.0; 96.6)
Scanner 1 –Scanner 3	1207	1152	95.4	(94.1; 96.7)
Scanner 2 –Scanner 3	1203	1149	95.5	(94.2; 96.7)

Inter-site study results

Sitescompared	Number ofComparison Pairs	Number ofPairwise Agreements	Agreement Rate
			%	95% CI
Overall	1228	1114	90.7	(88.4; 92.9)
Site 1 – Site 2	407	368	90.4	(87.5; 93.1)
Site 1 – Site 3	406	371	91.4	(88.5; 94.1)
Site 2 – Site 3	415	375	90.4	(87.5; 93.1)

The data show that the studies met the acceptance criterion of the lower limit of the 95% confidence interval (CI) of the Average Positive Agreement exceeding 85%.

2. Clinical Study:

A study was conducted to demonstrate that viewing, reviewing and diagnosing digital images of surgical pathology FFPE tissue slides using the PIPS 5.1 is non-inferior to using optical (light) microscopy. The primary endpoint was the difference in major discordance rates between manual digital (MD) and manual optical (MO) modalities when compared to the reference (main) diagnosis, which is based on the original sign-out diagnosis rendered at the institution, using an optical (light) microscope. By the study protocol, a total of 952 cases consisting of multiple organ and tissue types were to be enrolled. Cases were divided over three sites. In total 11 pathologists divided over three sites read all the cases assigned to the site using both the MO and the MD modalities in a randomized order and with a washout period of four weeks in between. Three adjudicators reviewed the reader diagnosis against the sign

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out diagnosis and determined whether the diagnosis was concordant, minor discordant or major discordant. After adjudication, the major discordance rate per modality was calculated. The clinical study successfully met the primary endpoint of the study by demonstrating that viewing, reviewing, and diagnosing surgical pathology tissue slides by a pathologist supported by using PIPS 5.1 was non-inferior to using an optical microscope. The overall difference in major discordance rate (compared to the main diagnosis) for digital-optical was 0.1% with a 95% confidence interval of (-1.01%; 1.18%). As the upper limit of this confidence interval was less than the non-inferiority margin of 4%, manual digital diagnosis by a pathologist using the subject PIPS 5.1 is non-inferior to diagnosis by a pathologist using the optical microscope.

The acceptance criterion was as follows: The manual digital method would be declared noninferior to the manual optical method if the upper bound of the 95% two-sided confidence interval for the manual digital – manual optical difference in major discordance rate is less than 4%.

Substantial equivalence conclusion

The subject PIPS 5.1 is substantially equivalent to the predicate device Philips IntelliSite Pathology Solution (K203845) in terms of Intended Use / Indications for Use, technological characteristics, and safety and effectiveness.

Non-clinical and clinical performance tests demonstrated that the modifications are properly introduced, and the device conforms to its intended use, users and use environment. These tests were used to support substantial equivalence of the subject device and demonstrated that it is as safe and effective as its predicate device without raising any new safety and/or effectiveness concerns.

Regulation Number and Section

§ 864.3700 Whole slide imaging system.

(a)
Identification. The whole slide imaging system is an automated digital slide creation, viewing, and management system intended as an aid to the pathologist to review and interpret digital images of surgical pathology slides. The system generates digital images that would otherwise be appropriate for manual visualization by conventional light microscopy.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information:
(i) The indications for use must specify the tissue specimen that is intended to be used with the whole slide imaging system and the components of the system.
(ii) A detailed description of the device and bench testing results at the component level, including for the following, as appropriate:
(A) Slide feeder;
(B) Light source;
(C) Imaging optics;
(D) Mechanical scanner movement;
(E) Digital imaging sensor;
(F) Image processing software;
(G) Image composition techniques;
(H) Image file formats;
(I) Image review manipulation software;
(J) Computer environment; and
(K) Display system.
(iii) Detailed bench testing and results at the system level, including for the following, as appropriate:
(A) Color reproducibility;
(B) Spatial resolution;
(C) Focusing test;
(D) Whole slide tissue coverage;
(E) Stitching error; and
(F) Turnaround time.
(iv) Detailed information demonstrating the performance characteristics of the device, including, as appropriate:
(A) Precision to evaluate intra-system and inter-system precision using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included.
(B) Reproducibility data to evaluate inter-site variability using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included.
(C) Data from a clinical study to demonstrate that viewing, reviewing, and diagnosing digital images of surgical pathology slides prepared from tissue slides using the whole slide imaging system is non-inferior to using an optical microscope. The study should evaluate the difference in major discordance rates between manual digital (MD) and manual optical (MO) modalities when compared to the reference (
e.g., main sign-out diagnosis).(D) A detailed human factor engineering process must be used to evaluate the whole slide imaging system user interface(s).
(2) Labeling compliant with 21 CFR 809.10(b) must include the following:
(i) The intended use statement must include the information described in paragraph (b)(1)(i) of this section, as applicable, and a statement that reads, “It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using this device.”
(ii) A description of the technical studies and the summary of results, including those that relate to paragraphs (b)(1)(ii) and (iii) of this section, as appropriate.
(iii) A description of the performance studies and the summary of results, including those that relate to paragraph (b)(1)(iv) of this section, as appropriate.
(iv) A limiting statement that specifies that pathologists should exercise professional judgment in each clinical situation and examine the glass slides by conventional microscopy if there is doubt about the ability to accurately render an interpretation using this device alone.