Novo is a software only 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, interpret, and manage digital images of these slides for primary diagnosis. Novo is not intended for use with frozen sections, cytology, or non- FFPE hematopathology specimens.

It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the quality of the images obtained and, where necessary, use conventional light microscopy review when making a diagnostic decision. Novo is intended for use with the Philips Ultra Fast Scanner and the Barco PP27QHD or Philips PS27QHDCR display.

Device Description

The PathAI Novo device is a web-based software-only device that is intended to aid pathology professionals in the viewing, interpretation, and management of digital whole slide images (WSIs) of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue using the Philips IntelliSite Pathology Solution (PIPS) Ultra Fast Scanner (UFS).

The proposed device is typically operated as follows:

1. A user prepares and scans slides and reviews the slide quality in accordance with the PIPS UFS IFU and standard lab procedures. The Novo device workflow is initiated when a user uploads WSIs from the local file system to the cloud storage using Novo.
1. After uploading WSIs to cloud storage using Novo, a user builds a patient accession using the patient's medical record number (MRN), date of birth (DOB) and accession ID to support linkage of one or more slides from a single procedure using patient identifiers in Novo.
1. A pathologist uses the slide viewer to perform their primary diagnosis workflow including zooming and panning images.

After viewing all images belonging to a particular accession, the pathologist will make a diagnosis.

AI/ML Overview

The provided text describes the regulatory clearance for the "Novo" device, a software-only whole slide imaging system, and references a clinical study conducted to establish its substantial equivalence to a predicate device. However, the document primarily focuses on regulatory approval and does not contain the detailed acceptance criteria table or comprehensive study breakdown as requested in the prompt.

Therefore, the following response will extract what is available and highlight where information is missing based on your request.

Acceptance Criteria and Device Performance for Novo (as described by available information)

Based on the provided FDA 510(k) summary, details regarding specific quantifiable acceptance criteria and performance beyond a non-inferiority finding are limited. The document focuses on demonstrating substantial equivalence to a predicate device (Philips IntelliSite Pathology Solution - PIPS).

Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Metric (Inferred/Stated)	Acceptance Threshold (Inferred/Stated)	Reported Device Performance
Clinical Equivalence	Major Discordance Rate	Upper limit of 95% CI for difference in major discordance rates < 4%.	-0.1% (95% CI, -2.05, 1.78) for all organs (MD vs. MO compared to GT). Met.
Image Loading Speed	Load time for selected images	< 7 seconds	"Images load in less than 7 seconds when selected for viewing." Met.
Image Panning/Zooming Speed	Load time during panning/zooming	< 10 seconds	"Images load in less than 10 seconds when panning or zooming." Met.
Image Reproduction (Pixel-wise)	Color differences ($\Delta$E00)	Implicitly, not significantly different from PIPS/IMS with JPEG compression.	"Color differences ($\Delta$E00) between Novo and PIPS/IMS are not zero." "Novo-generated images are similar to PIPS/IMS-generated images that had been JPEG-compressed at quality 95."
Human Factors	Safety and Effectiveness	Implicitly, found safe and effective for intended users, uses, and environments.	"Novo has been found to be safe and effective for the intended users, uses, and use environments." Met.

Missing Information (Not Available in the Provided Text):

Explicit, pre-specified quantitative acceptance criteria beyond the non-inferiority margin for major discordance.
Detailed quantitative performance for features like color differences beyond a statement of similarity to JPEG-compressed images.

Study Details (Extracted from the provided text):

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

Test Set Sample Size: Not explicitly stated. The text mentions "WSIs of H&E stained FFPE tissue slides."
Data Provenance: Not specified for the test set. (e.g., country of origin, retrospective/prospective).

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

Number of Experts: Not specified.
Qualifications of Experts: Not specified. The reference diagnosis (ground truth) was the "original sign-out pathologic diagnosis using MO [manual optical] rendered at the institution," implying involvement of qualified pathologists for routine diagnosis, but specific qualifications for ground truth establishment are not given.

4. Adjudication method for the test set:

Adjudication Method: Not specified. The study compared "major discordance rates between MD [manual digital read, using Novo] and MO [manual optical] when compared to the reference (main) diagnosis, which was the original sign-out pathologic diagnosis using MO [ground truth, (GT)] rendered at the institution." This suggests a comparison against an existing diagnosis, not necessarily a separate adjudication process for the test set.

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:

MRMC Study: Yes, a clinical study was conducted. It involved human pathologists making diagnoses using both the Novo device (MD) and conventional microscopy (MO).
Effect Size of Improvement: The study focused on non-inferiority of the manual digital read (MD) using Novo compared to manual optical (MO) read. It did not measure "how much human readers improve with AI vs without AI assistance" because Novo is described as a "viewing and management" tool, not an AI-assisted diagnostic tool. Its purpose is to present the image for the pathologist's primary diagnosis, making it a replacement for conventional microscopy, not an enhancement tool for human readers in the context of an AI-assisted workflow. The primary outcome was maintaining diagnostic accuracy (non-inferiority) when switching from MO to MD.

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

Standalone Performance: No, this device is a "viewer and management" software for human pathologists. It does not perform diagnostic algorithms independently. The performance data presented (non-inferiority) is explicitly human-in-the-loop (MD: "manual digital read").

7. The type of ground truth used:

Ground Truth Type: "The original sign-out pathologic diagnosis using MO [manual optical] rendered at the institution." This can be categorized as expert consensus/clinical outcomes data based on standard practice.

8. The sample size for the training set:

Training Set Sample Size: Not applicable/Not specified. Novo is a viewing and management system, not described as an AI/machine learning algorithm that requires a "training set" in the conventional sense for a diagnostic prediction model. The "pixel-wise comparison" tests were likely technical assessments, not dependent on a "training set."

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

Ground Truth Establishment for Training Set: Not applicable, as there is no mention of an algorithm requiring a "training set" with ground truth in the provided information.

Summary

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PathAI, Inc Katy Wack VP, Clinical Development & Regulatory Affairs PathAI, Inc. 1325 Boylston Street Suite 10000. Boston, MA 02215

September 1, 2022

Re: K212361

Trade/Device Name: Novo Regulation Number: 21 CFR 864.3700 Regulation Name: Whole slide imaging system Regulatory Class: Class II Product Code: QKQ

Dear Katy Wack:

The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated August 11, 2022. Specifically, FDA is updating this SE letter for errors in the correspondent name as an administrative correction.

Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Shyam Kalavar, OHT7: Office of In Vitro Diagnostics, Phone: 301-796-6807, Email: shyam.kalavar@fda.hhs.gov.

Sincerely,

Shyam Kalavar -S

Shyam Kalavar 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

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August 11, 2022

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PathAI, LLC Katy Wack, Ph.D. VP, Clinical Development & Regulatory Affairs 120 Brookline Avenue Boston, Massachusetts 02215

Re: K212361

Trade/Device Name: Novo Regulation Number: 21 CFR 864.3700 Regulation Name: Whole Slide Imaging System Regulatory Class: Class II Product Code: QKO Dated: July 28, 2021 Received: July 30, 2021

Dear Katy Wack:

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. 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 located 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.

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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(@tda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Shyam Kalavar -S 2022.08.11 16:53:55 -04'00'

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

Enclosure

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Indications for Use

510(k) Number (if known) K212361

Device Name Novo

Indications for Use (Describe)

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

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary Novo

Date Prepared: August 11, 2022

Submitter

PathAI, Inc. 1325 Boylston Street Suite 10000 Boston, MA 02215

Contact Person

Katy Wack Phone: (617) 500-8457

DEVICE

Proprietary Name:
Common Name:
Classification Name:
Regulation Section:
Regulatory Classification:
Product Code:
Review Panel:

PREDICATE DEVICE

Proprietary Name: Philips IntelliSite Pathology Solution (PIPS) Submission Number: DEN160056

Novo

Class II OKO

The PathAI Novo Viewer Whole Slide Imaging System

21 CFR 864.3700

88 - Pathology

DEVICE DESCRIPTION

The proposed device is typically operated as follows:

1. A user prepares and scans slides and reviews the slide quality in accordance with the PIPS UFS IFU and standard lab procedures. The Novo device workflow is initiated when a user uploads WSIs from the local file system to the cloud storage using Novo.

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1. After uploading WSIs to cloud storage using Novo, a user builds a patient accession using the patient's medical record number (MRN), date of birth (DOB) and accession ID to support linkage of one or more slides from a single procedure using patient identifiers in Novo.
1. A pathologist uses the slide viewer to perform their primary diagnosis workflow including zooming and panning images.

After viewing all images belonging to a particular accession, the pathologist will make a diagnosis.

Novo operates with the following components:

Table 1: WSI scanner

Manufacturer	Model
Philips Medical Systems Nederland B.V.	Ultra Fast Scanner (UFS)

Table 2: WSI displays

Manufacturer	Model
Barco N.V.	PP27QHD
Philips	PS27QHDCR

Table 3: Computer environment/ System Requirements

System	Details
Computer System	RAM: 4.0 GBDisplay Calibration tool: MediCal QAWeb Agent for Philips and BarcoDisplays
Display	Barco (PP27QHD) or Philips (PS27QHDCR)Pixel resolution: 2560w x 1440hPanel type: Color LCDTechnology: IPS technology with a-Si Thin Film TransistorPhysical size: 648.5 mm x 423 mm x 91.3 mm (with backlight disc)
Web Browser	Google Chrome 81.0 or later
Network	Internet accessOutbound traffic enabled to port 44325 Mbps download and upload speed

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INDICATIONS FOR USE/INTENDED USE

Novo is a software only 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, interpret, and manage digital images of pathology slides for primary diagnosis. Novo is not intended for use with frozen sections, cytology, or non-FFPE hematopathology specimens.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH PREDICATE DEVICE

The following table summarizes the similarities and differences between the PathAI device and the predicate device, Philips IntelliSite Pathology Solution (PIPS).

Attribute	Predicate Device	Proposed PathAI Device
Device TradeName	Philips IntelliSite Pathology Solution(PIPS) (DEN160056)	Novo
IntendedUse/Indicationsfor Use	The Philips IntelliSite PathologySolution (PIPS) is an automated digitalslide creation, viewing, and managementsystem. The PIPS is intended for in vitrodiagnostic use as an aid to thepathologist to review and interpretdigital images of surgical pathologyslides prepared from formalin-fixedparaffin embedded (FFPE) tissue. ThePIPS is not intended for use with frozensection, 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 and safeguards toassure the validity of the interpretationof images obtained using PIPS.	Novo is a software only device intendedfor viewing and management of digitalimages of scanned surgical pathologyslides prepared from formalin-fixedparaffin embedded (FFPE) tissue. It is anaid to the pathologist to review,interpret, and manage digital images ofpathology slides for primary diagnosis.Novo is not intended for use with frozensections, cytology, or non-FFPEhematopathology specimens.It is the responsibility of a qualifiedpathologist to employ appropriateprocedures and safeguards to assure thequality of the images obtained and,where necessary, use conventional lightmicroscopy review when making adiagnostic decision. Novo is intended foruse with the Philips Ultra Fast Scanner andthe Barco PP27QHD or PhilipsPS27QHDCR display.
Product Code	PSY	OKO

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Specimen Type	Surgical pathology H&E slides preparedfrom FFPE tissue	Same
Image FileFormat	Philips UFS iSyntax File	Philips UFS iSyntax File converted todevice specific image format
ImageManipulationFunctions	Panning, zooming, color manipulationfunction, annotations, and measurements(distance & area)	Panning, zooming, notes
Type ofSoftwareApplication	Internet Browser Based	Same
DeviceComponents	Ultra Fast Scanner (UFS), ImageManagement System (IMS), Display	Image viewing Software (Novo)
Principle ofOperation	After WSI images are successfullyacquired by using PIPS UFS, the WSIimages are stored in IMS ApplicationServer & Storage software that is notprovided as part of the PIPS, but may belocated in a central server room separatefrom the workstation with the IMSviewing software and Display. Duringreview, the pathologist opens WSI imagesfrom IMS Server & Storage, performfurther QC and reads WSIimages of the slides to make a diagnosis.	After WSI images are successfullyacquired by using PIPS UFS, the WSIimages are stored in the cloud. Duringreview, the pathologist opens WSI imagefrom storage (displayed as DZI images),performs further QC and reads WSIimages of the slides to make a diagnosis.
Image Storage	Images are stored in an end userprovided image storage (PIPS IMSApplication Server & Storage) attachedto the local network	Images are stored in the cloud
End User'sInterface	PIPS Image Management System (IMS)	Novo

Substantial Equivalence Comparison

The proposed device has the same Indications for Use and similar Functional and Technological Characteristics to the predicate Image Management System (IMS) application software and is therefore substantially equivalent to the predicate device.

PERFORMANCE DATA

Performance data	Description
Pixel-wise comparison	A pixel-wise comparison test was performed tocompare images which were reproduced by Novo andthe Philips IntelliSite Pathology Solution ImageManagement System (PIPS/IMS) for the same iSyntaxfile to demonstrate identical image reproduction. Testresults show that the color differences ( $(\Delta)E00$ ) betweenNovo and PIPS/IMS are not zero. Further, testing wasconducted to compare Novo-generated images withJPEG-compressed PIPS/IMS-generated images. Test

Performance data

Description

Pixel-wise comparison

A pixel-wise comparison test was performed tocompare images which were reproduced by Novo andthe Philips IntelliSite Pathology Solution ImageManagement System (PIPS/IMS) for the same iSyntaxfile to demonstrate identical image reproduction. Testresults show that the color differences ( $(\Delta)E00$ ) betweenNovo and PIPS/IMS are not zero. Further, testing wasconducted to compare Novo-generated images withJPEG-compressed PIPS/IMS-generated images. Test

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results show that the Novo-generated images aresimilar to PIPS/IMS-generated images that had beenJPEG-compressed at quality 95. Based on the findingsfrom bench testing, an additional clinical study wasperformed to establish the safety and effectiveness ofthe device
Clinical Study	A clinical study was conducted to demonstrate thatviewing, reviewing, and diagnosing WSIs of H&Estained FFPE tissue slides using Novo [manual digitalread (MD)] is non-inferior to glass slide reads usingoptical (light) microscopy [manual optical (MO)]. Theprimary endpoint of the study was the difference inmajor discordance rates between MD and MO whencompared to the reference (main) diagnosis, which wasthe original sign-out pathologic diagnosis using MO[ground truth, (GT)] rendered at the institution.
	The differences in major discordance rates betweenMD and GT compared to MO and GT were -0.1%(95% CI, -2.05, 1.78) for all organs. The upper limit ofthe CI for the major discordance rate was 1.78%,which is less than the prespecified noninferioritythreshold of 4%, therefore meeting the primaryobjective of the study.
Turnaround time	The system requirements have been fulfilled:Images load in less than 7 seconds when selected for viewing Images load in less than 10 seconds when panning or zooming
Human factors testing	Novo has been found to be safe and effective for theintended users, uses, and use environments.

CONCLUSION

Based on the information provided in this 510(k), the proposed PathAI device is substantially equivalent to the previously cleared predicate, when used with the PIPS UFS and Barco PP27QHD or Philips PS27QHDCR display. Please note that a clinical study was conducted to establish the Substantial Equivalence of the device.

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.