Sectra Digital Pathology Module (3.3) is a software device intended for viewing and management of digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. It is an aid to the pathologist to review and interpret these digital images for the purposes of primary diagnosis.

Sectra Digital Pathology Module (3.3) is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. It is the responsibility of the pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images using Sectra Digital Pathology Module (3.3).

Sectra Digital Pathology Module (3.3) is intended for use with Leica's Aperio GT 450 DX scanner and Dell U3223QE display, for viewing and management of the ScanScope Virtual Slide (SVS) and Digital Imaging and Communications in Medicine (DICOM) image formats.

Device Description

The Sectra Digital Pathology Module (3.3) [henceforth referred to DPAT (3.3)] is a digital slide viewing system. The DPAT (3.3) is intended for use together with FDA-cleared whole-slide image scanner GT 450 DX and Dell U3223QE display.

The DPAT (3.3) can only be used as an add-on module to Sectra PACS. Sectra PACS consists of Sectra Workstation IDS7 (K081469) and Sectra Core (identified as a Class I exempt by the FDA in 2000). Sectra PACS is not part of the subject device. Sectra Workstation is the viewing workstation in which the Pathology Image Window is run. Pathology Image Window is the client component of the subject device.

The system capabilities include:

retrieving and displaying digital slides,
support for remote intranet access over computer networks,
tools for annotating digital slides and entering and editing metadata associated with digital slides, and
displaying the scanned slide images for primary diagnosis by pathologists.

The subject device is designed to accurately display colors. The monitor is not part of the subject device.

Digital pathology images originating from WSI scanners other than those listed in the Indications for Use will be marked with the disclaimer "For Non-clinical Use Only" in the Pathology Image Window.

Image acquisition will be managed by the scanner which is not part of the subject device:

The scanner delivers images with a tag in the file header that identifies the originating scanner.
The scanner includes applications for controlling the scanning process and performing related quality control (e.g., ensuring that images are sharp and cover all tissue on the slide).

The DPAT (3.3) supports reading digital slides on a Dell U32230E display monitor, enabling pathologists to make clinically relevant decisions analogous to those they make using a conventional microscope. Specifically, the system supports the pathologist in performing a primary diagnosis based on viewing the digital slide on a computer monitor. These capabilities are provided by the Pathology Image Window.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets those criteria, based on the provided text:

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Endpoint)	Reported Device Performance	Met?
Primary Endpoint: The upper bound of the 2-sided 95% CI of the difference between the overall major discrepancy rates of WSIR diagnosis and MSR diagnosis when compared to the reference diagnosis shall be ≤4%.	The upper bound of the 95% CI of the estimated difference in major discrepancy rates was 1.69%.	Yes
Secondary Endpoint: The upper bound of the 2-sided 95% CI of the major discrepancy rate between WSIR diagnosis and the reference diagnosis shall be <7%.	The upper bound of the 95% CI for the overall estimated major discrepancy rate for WSIR diagnosis was 5.25%.	Yes
Pixel-Wise Comparison: All configurations were identical, i.e., <3ΔΕ00 to reference configuration SVS/UniView/Chrome.	Based on analysis of the testing data, the 4 specified configurations (DICOM/IDS7, DICOM/UniView/Chrome, SVS/IDS7, SVS/UniView/Edge) were identical, i.e., <3∆Ε00 to reference configuration SVS/UniView/Chrome, and specifically ΔE=0 for the subject device displaying the same scanned image in both DICOM and SVS formats, in IDS7, Edge or Chrome.	Yes
Turnaround Time:
- When selecting a slide image, it should not take longer than 3 seconds until the image is fully loaded.	Reported to be "adequate for the intended use". Specific values not provided but "similar to or better than those of the predicate device."	Yes
- When panning the image (one quarter of the monitor) it should not take longer than 0.5 seconds until the image is fully loaded.	Reported to be "adequate for the intended use". Specific values not provided but "similar to or better than those of the predicate device."	Yes
Measurements: Measurement accuracy has been verified using a test image containing objects with known sizes.	Reported that measurement accuracy "has been verified" and show "almost identical results" to the predicate.	Yes

Note: While specific numerical results for turnaround time and measurement accuracy are not provided, the document states they were found to be "adequate" and "accurate" respectively, meeting the implicit acceptance criteria for these performance aspects.

Study Details

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: 258 cases.
Data Provenance: The document does not explicitly state the country of origin. The study was conducted at a "single site." It was a retrospective study, as the MSR diagnoses were "original sign-out diagnoses." The WSIR diagnoses were prospectively obtained using the device for the study.

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

Number of Experts for Ground Truth: Not directly stated as "experts for ground truth," but 3 reading pathologists determined the MSR diagnoses (which formed a basis for comparison with the reference diagnosis) and 3 reading pathologists created the WSIR diagnoses. A minimum of two adjudicators independently assessed concordance for the WSIR diagnosis against the reference diagnosis.
Qualifications of Experts: All were "pathologists." Further specific qualifications (e.g., years of experience, board certification) are not detailed in the provided text.

4. Adjudication Method for the Test Set

Adjudication Method: Minimum of two adjudicators independently assessed concordance (concordant, minor discrepancy, major discrepancy) of the WSIR diagnosis against the reference diagnosis using predefined rules. Their concordance scores for the same case were compared to determine a consensus score for major discrepancy status. This represents a form of 2-reader adjudication with consensus. The document does not explicitly mention "adjudication of ground truth" but rather adjudication of the concordance between the device's output and the reference diagnosis.

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

Was an MRMC study done? Yes, effectively. The study design involved 3 reading pathologists (multi-reader) reviewing 258 cases (multi-case) using the device (WSIR diagnosis) and comparing it to their traditional light microscopy review (MSR diagnosis), both against a reference diagnosis. While not explicitly termed an "MRMC study" in the classic sense of comparing AI-assisted vs. unassisted human performance, it acts as a comparative effectiveness study demonstrating non-inferiority of the digital pathology system to traditional microscopy.
Effect Size of Human Readers Improvement with AI vs. without AI Assistance: The study's primary endpoint was non-inferiority of the digital system (DPAT (3.3)-UniView) compared to traditional light microscopy. The estimated difference in major discrepancy rates between the two modalities (digital vs. microscope) when compared to the reference diagnosis was -0.01% (95% CI: -1.71% to 1.69%). This indicates that the digital system performed comparably to, or negligibly better than, light microscopy in terms of major discrepancy rates against a reference. It doesn't quantify improvement with AI assistance per se, but rather the non-inferiority of the digital viewing system (which is the device being cleared) to the traditional method.

6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance

Was a standalone performance study done? No, not in the sense of an AI algorithm making a diagnosis without human intervention. The device is a "software device intended for viewing and management of digital images... as an aid to the pathologist to review and interpret these digital images for the purposes of primary diagnosis." The study specifically evaluates "interpreting digital images... for the purposes of primary diagnosis" by a human pathologist using the device, not an automated diagnostic output.

7. Type of Ground Truth Used

Type of Ground Truth: The study used "original sign-out diagnoses" made using light microscopy as the "reference diagnoses." The document clarifies that major discrepancy was defined as a "difference in diagnosis that resulted in a clinically important difference in patient management." While not explicitly stated as "pathology ground truth" established post-hoc, it strongly implies a consensus or definitive diagnosis used as the gold standard derived from clinical practice.

8. Sample Size for the Training Set

Training Set Sample Size: The document does not mention the training set size for the device. The study described focuses on the performance evaluation of the final device (Sectra Digital Pathology Module 3.3) for clinical validation, not the development or training of any underlying AI or image processing models within the device.

9. How Ground Truth for the Training Set Was Established

Ground Truth for Training Set: As no training set information is provided, the method for establishing its ground truth is also not mentioned.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

April 16, 2024

Sectra AB % Peter Altman Consultant Medical Device Regulatory Services 14 Mercer Road Savannah, Georgia 31411

Re: K232208

Trade/Device Name: Sectra Digital Pathology Module (3.3) Regulation Number: 21 CFR 864.3700 Regulation Name: Whole slide imaging system Regulatory Class: Class II Product Code: QKQ Dated: July 26, 2023 Received: July 26, 2023

Dear Peter Altman:

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 (QS) 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 OS 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 (OS) 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 medical devices and radiation-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 2 OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K232208

Device Name Sectra Digital Pathology Module (3.3)

Indications for Use (Describe) For In Vitro Diagnostic Use

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

Sectra Digital Pathology Module (3.3), Sectra AB

Date Prepared: April 15, 2024

Submitter:

Sectra AB Teknikringen 20 SE-583 30 Linköping Sweden Establishment Registration Number: 9615992

Contact Person:

Name:	Edoardo Mastrovito
Title:	Quality and Regulatory Affairs Mgr.
Telephone:	+46 13 235206
Facsimile:	n/a

Device Identification:

Proprietary/Trade Name:	Sectra Digital Pathology Module
Version Number	3.3
510(k) Number:	K232208
Classification Name:	Whole Slide Imaging System
Regulation Number:	21 CFR 864.3700
Product Codes:	QKQ
Device Class:	Class II
Review Panel:	88 – Pathology
Common Name:	Digital Pathology Image Viewing and ManagementSoftware

Predicate Device Identification:

Proprietary/Trade Name:	The Aperio WebViewer DX component of the Aperio GT450 DX System
510(k) Number:	K232202
Classification Name:	Whole Slide Imaging System
Regulation Number:	21 CFR 864.3700
Product Codes:	PSY
Device Class:	Class II
Review Panel:	88 – Pathology
Common Name:	Digital Pathology Image Management System

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Device Description:

The system capabilities include:

· retrieving and displaying digital slides,
· support for remote intranet access over computer networks,
tools for annotating digital slides and entering and editing metadata associated with digital slides, and
· displaying the scanned slide images for primary diagnosis by pathologists.

The subject device is designed to accurately display colors. The monitor is not part of the subject device.

Digital pathology images originating from WSI scanners other than those listed in the Indications for Use will be marked with the disclaimer "For Non-clinical Use Only" in the Pathology Image Window.

Image acquisition will be managed by the scanner which is not part of the subject device:

· The scanner delivers images with a tag in the file header that identifies the originating scanner.
· The scanner includes applications for controlling the scanning process and performing related quality control (e.g., ensuring that images are sharp and cover all tissue on the slide).

Indications for Use/Intended Use:

For In Vitro Diagnostic Use

Sectra Digital Pathology Module (3.3) is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.

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It is the responsibility of the pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images using Sectra Digital Pathology Module (3.3).

Item	Subject Device	Predicate
Indicationsfor Use	For In Vitro DiagnosticUseSectra Digital PathologyModule (3.3) is asoftware device intendedfor viewing andmanagement of digitalimages of scannedsurgical pathology slidesprepared from formalin-fixed paraffin embedded(FFPE) tissue. It is an aidto the pathologist toreview and interpretthese digital images forthe purposes of primarydiagnosis.Sectra Digital PathologyModule (3.3) is notintended for use withfrozen section, cytology,or non-FFPEhematopathologyspecimens. It is theresponsibility of thepathologist to employappropriate proceduresand safeguards to assurethe validity of theinterpretation of imagesusing Sectra DigitalPathology Module (3.3).Sectra Digital PathologyModule (3.3) is intended	The Aperio GT 450 DX is an automated digital slidecreation and viewing system. The Aperio GT 450 DX isintended for in vitro diagnostic use as an aid to thepathologist to review and interpret digital images of surgicalpathology slides prepared from formalin-fixed paraffinembedded (FFPE) tissue. The Aperio GT 450 DX is forcreation and viewing of digital images of scanned glassslides that would otherwise be appropriate for manualvisualization by conventional light microscopy.Aperio GT 450 DX is comprised of the Aperio GT 450 DXscanner, which generates images in the Digital Imaging andCommunications in Medicine (DICOM) and in theScanScope Virtual Slide (SVS) file formats, the AperioWebViewer DX viewer, and the displays. The Aperio GT450 DX is intended to be used with the interoperablecomponents specified in Table 1.Table 1: Interoperable components of Aperio GT 450 DX
	Scanner Hardware Scanner Outputfile format InteroperableViewingSoftware InteroperableDisplays AperioGT 450 DXscanner SVS AperioWebViewer DX Barco MDPC-8127Dell UP3017Dell U3023EDell U3223QE AperioGT 450 DXscanner SVS Sectra DigitalPathology Module(3.3) Dell U3223QE Aperio GT450 DXscanner DICOM Sectra DigitalPathology Module(3.3) Dell U3223QE																	The Aperio GT 450 DX is not intended for use with frozensection, cytology, or non-FFPE hematopathology

Table 1: Summary of Technological Characteristics

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Item	Subject Device	Predicate
	for use with Leica'sAperio GT 450 DXscanner and DellU3223QE display, forviewing and managementof the ScanScope VirtualSlide (SVS) and DigitalImaging andCommunications inMedicine (DICOM)image formats.	specimens. It is the responsibility of a qualified pathologistto employ appropriate procedures and safeguards to assurethe validity of the interpretation of images obtained usingthe Aperio GT 450 DX.
Specimentype	Surgical pathology slidesprepared from FFPEtissue	Surgical pathology slides prepared from FFPE tissue
ImageStorage	Images are stored in anend user provided imagestorage attached to thelocal network.	Images are stored in an end user provided image storageattached to the local network.
Imagemanipulation functions	Panning, zooming,gamma function,annotations, andmeasurements (distance& area)	Panning, zooming, gamma function, annotations, andmeasurements (distance & area)
Imagereview anddiagnosis	During review, thepathologist opens WSIimages acquired with theWSI scanner from theimage storage, performsfurther QC and readsWSI images of the slidesto make a diagnosis.	During review, the pathologist opens WSI images acquiredwith the WSI scanner from the image storage, performsfurther QC and reads WSI images of the slides to make adiagnosis.
End User'sInterface	Pathology ImageWindow (the clientcomponent of SectraDigital PathologyModule 3.3)	Aperio WebViewer DX
Scanner	Sectra Digital PathologyModule does not includea scanner; however, it isindicated for use withAperio GT 450 DX	Aperio GT 450 DX

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Table 2: Performance data
Performance data	Description
Clinical Study	A clinical study was conducted to demonstrate that viewing,reviewing, and diagnosing whole slide images (WSIs) of FFPEtissue slides with DPAT (3.3) on Sectra Workstation UniView(referred to as DPAT (3.3)-UniView) is noninferior to diagnosesmade using light microscopy.
Pixel-WiseComparison	Pixel-wise comparison study was performed to demonstrate thatDPAT (3.3) generates identical images in the configurations thatwere not validated in the clinical study. The imaging pipelineAperio GT 450 DX/SVS/DPAT (3.3)-UniView/Chromeconfiguration was validated in the clinical study and was used asthe reference configuration in the pixelwise comparison study tovalidate the other 4 configurations as described below.

	Configuration	Imageformat	File Viewer/Browser
	DICOM/IDS7	DICOM	IDS7
	DICOM/UniView/Chrome	DICOM	UniView/Chrome
	SVS/IDS7	SVS	IDS7
	SVS/UniView/Edge	SVS	UniView/Edge

	Based on analysis of the testing data, the 4 configurations specifiedin table above were identical, i.e., <3∆Ε00 to referenceconfiguration SVS/UniView/Chrome.
Turnaround time	Provided that the system requirements are fulfilled:- When selecting a slide image, it should not take longer than 3seconds until the image is fully loaded.- When panning the image (one quarter of the monitor) it shouldnot take longer than 0.5 seconds until the image is fully loaded.
Measurements	Measurement accuracy has been verified using a test imagecontaining objects with known sizes.
Human factors testing	Human factors study designed around critical user tasks and usescenarios performed by representative users were conducted forpreviously cleared DPAT 2.2 in K193054. No new human factorstudy was performed for DPAT (3.3).

Table 2: Performance data

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Substantial Equivalence Comparison:

Similarities

Both the DPAT (3.3) and the WebViewer DX of the Aperio GT 450 DX System are softwareonly devices.

DPAT (3.3) is a web application just as the WebViewer. The color reproducibility performance of the DPAT (3.3) UniView rendering SVS images in Chrome has been shown in a clinical study to be adequate and equivalent to that of the WebViewer.

The clinical study was performed using SVS images displayed in the UniView Chrome, creating a reference pipeline that could then be used for technical testing with DICOM, IDS7, and Edge, to support the claims of the subject device. The subject device displayed the same scanned image in both DICOM and SVS formats, in IDS7, Edge or Chrome, with no difference (ΔE=0).

Color reproducibility testing based on pixel-by-pixel comparisons using a set of images from the Aperio GT 450 DX demonstrates adequate performance of the DPAT (3.3) with both SVS and DICOM images.

The subject device includes the same image manipulation functions as the predicate device: panning, zooming, annotation, and measurements.

Turnaround times for zooming and panning were tested and found to be similar to or better than those of the predicate device.
Distance measurements show almost identical results when considering that some difference is to be expected due to the measurements not being created between the exact same points in the two viewers, as well as possible differences in numerical rounding.

Differences

The subject device supports both SVS and DICOM image formats (as provided by the Aperio GT 450 DX) whereas the WebViewer supports only the SVS format. The subject device performs equally well with both SVS and DICOM images.

A clinical study was needed as there is a difference in the pixel pipeline where the subject device avoids server-side transcoding, leading to dE>3 color difference compared to the predicate device. The clinical study was performed using SVS images displayed in UniView Chrome, creating a reference pipeline that could then be used for technical testing with DICOM, IDS'7, and Edge, to support the claims of the subject device.

Summary of Studies:

Non-clinical test results:

Conducted per FDA's Guidance on Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices:

The clinical study was performed using SVS images displayed in UniView Chrome, creating a reference pipeline that could then be used for technical testing with DICOM. IDS7, and UniView in Edge, to support the claims of the subject device. The subject device displayed the same scanned image in both DICOM and SVS formats, in IDS7, Edge or Chrome, with no difference (△E=0).

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Turnaround times for panning and zooming have been determined and found to be adequate for the intended use of the subject device.

The subject device has been found to perform accurate measurements with respect to its intended use.

Clinical Study:

A clinical study was conducted to demonstrate that viewing, and diagnosing whole slide images (WSIs) of FFPE tissue slides with DPAT (3.3) on Sectra Workstation UniView [referred to as DPAT (3.3)-UniView)] is noninferior to diagnoses made using light microscopy.

Clinical accuracy was evaluated by analyzing the concordance of the diagnoses made using DPAT (3.3)-UniView (referred to as WSI review [WSIR] diagnosis) with the original sign-out diagnoses (reference diagnoses), and the concordance of traditional light microscope slide review (MSR) diagnoses with the reference diagnoses. The primary endpoint of the study was the difference in overall major discrepancy rates between the 2 modalities when compared to the reference diagnosis. The secondary endpoint of the study was the major discrepancy rate of WSIR diagnosis relative to the reference diagnosis. The acceptance criteria associated with each study endpoint were as follows:

Primary Endpoint:

The upper bound of the 2-sided 95% CI of the difference between the overall major . discrepancy rates of WSIR diagnosis and MSR diagnosis when compared to the reference diagnosis shall be ≤4%.

Secondary Endpoints:

. The upper bound of the 2-sided 95% CI of the major discrepancy rate between WSIR diagnosis and the reference diagnosis shall be <7%.
The study included 258 cases that represented a diverse mixture of pathologic diagnoses and tissue/organ types. Case slides were scanned on the Aperio GT 450 DX scanner, producing WSIs. Three (3) reading pathologists (the same pathologists who determined MSR diagnosis) at a single site reviewed all study cases using DPAT (3.3)-UniView and a Dell U3223QE monitor, as specified by the Leica Biosystems (LBS) Aperio GT 450 DX and Sectra DPAT (3.3) IFU, to determine WSIR diagnosis. A minimum of two adjudicators independently assessed concordance (concordant, minor discrepancy, major discrepancy) of the WSIR diagnosis against the reference diagnosis using predefined rules. A major discrepancy was defined as a difference in diagnosis that resulted in a clinically important difference in patient management, whereas a minor discrepancy would not be associated with a clinically important difference in patient management. The adjudicators' concordance scores for the same case were compared to determine a consensus score for major discrepancy status (no major discrepancy [concordant or minor discrepancy] or major discrepancy). The diagnosis consensus scores were used to estimate WSIR diagnosis major discrepancy rate. Deferred diagnoses were treated as missing data and excluded from the statistical analysis.

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Combining pathologists, it was planned to have 774 diagnoses (258 cases × 3 reading pathologists). Seven (7) WSIR and 10 MSR diagnoses were deferred and excluded from the statistical analysis. The estimated difference in major discrepancy rates between the 2 modalities when compared to the reference diagnosis was -0.01% (95% CI: -1.71% to 1.69%), as shown in Table 3. The upper bound of the 95% CI of the estimated difference in major discrepancy rates was 1.69% which met the predefined acceptance criteria of ≤4% for the primary endpoint. The secondary endpoint was to demonstrate that the overall major discrepancy rate between the WSIR diagnosis and the reference diagnosis did not exceed 7%; the upper bound of the 95% CI for the overall estimated major discrepancy rate for WSIR diagnosis was 5.25%, which met the predefined acceptance criteria of ≤7% as shown in Table 4.

Table 3. Overall Major Discrepancy Rates for WSIR Diagnoses and MSR Diagnoses and
the Difference Between the Overall Major Discrepancy Rates

Modality	(n/N)	DiscrepancyRate	Model EstimatedDiscrepancy Rate	95% CI
WSIRD vsReference	23/767	3.00%	2.95%	(1.64%, 5.25%)
MSRD vsReference	23/764	3.01%	2.96%	(1.65%, 5.27%)
Difference			-0.01%	(-1.71%, 1.69%)

WSIRD: WSIR diagnosis; MSRD: MSR diagnosis 1.

A generalized linear model was used to derive estimates of the major discrepancy rates and the difference 2. along with their 95% CIs.

	Table 4. Concordance Rate between WSIR Diagnoses and MSR Diagnoses

Number ofConcordances	Number of Pairs	Concordance Rate (%)	95% Confidence Interval
729	762	95.7	[94.2%, 97.1%]

The acceptance criteria were met for all study endpoints. These study results support the conclusion that DPAT (3.3)-UniView is safe and effective when used by pathologists in rendering primary diagnoses of FFPE tissue sections as compared to using light microscopy when used according to the device intended use.

Conclusion:

The proposed Sectra Digital Pathology Module (3.3) when used with the Aperio GT 450 DX scanner has similar Indications for Use, Functional, and Technological Characteristics as the WebViewer DX viewer application software of the predicate device. The results of clinical and non-clinical testing demonstrate the device is safe and effective and substantially equivalent to the Aperio predicate device (K232202).

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.