Cleerly Labs is a web-based software application that is intended to be used by trained medical professionals as an interactive tool for viewing and analyzing cardiac computed tomography (CT) data for determining the presence and extent of coronary plaques (i.e. atherosclerosis in patients who underwent Coronary Computed Tomography Angiography (CCTA) for evaluation of CAD or suspected CAD. This software post processes CT images obtained using any Computed Tomography (CT) scanner. The software provides tools for the measurement and visualization of coronary arteries.

The software is not intended to replace the skill and judgment of a qualified medical practitioner and should only be used by people who have been appropriately trained in the software's functions, capabilities and limitations. Users should be aware that certain views make use of interpolated data. This is created by the software based on the original data set. Interpolated data may give the appearance of healthy tissue in situations where pathology that is near or smaller than the scanning resolution may be present.

Device Description

Cleerly Labs is a post-processing web-based software application that enables trained medical professionals to analyze 2D/3D coronary images acquired from Coronary Computed Tomography (CCTA) scans. The software is a post-processing tool that aids in determining treatment paths for patients suspected to have coronary artery disease (CAD).

Cleerly Labs utilizes machine learning and simple rule-based mathematical calculation components which are performed on the backend of the software applies deep learning methodology to identify high quality images, segment and label coronary arteries, and segment lumen and vessel walls. 2D and 3D images are presented to the user for review and manual editing. This segmentation is designed to improve efficiency for the user, and help shorten tedious, time-consuming manual tasks.

The user is then able to edit the suggested segmentation as well as adjust plaque thresholds, and demarcate stenosis, stents, and chronic total occlusions (CTOs) as well as select dominance and indicate coronary anomalies. Plaque, stenosis, and vessel measurements are output based the combination of user-editable segmentation and user-placed stent, and CTO markers. These outputs are mathematical calculations and are not machine-learning based.

Cleerly Labs provides a visualization of the Cleerly Labs analysis in the CORONARY Report. The CORONARY Report uses data previously acquired from the Cleerly Labs image analysis to generate a visually interactive and comprehensive report that details the atherosclerosis and stenosis findings of the patient. This report is not intended to be the final report (i.e., physician report) used in patient diagnosis and treatment. Cleerly Labs provides the ability to send the text report page of the CORONARY Report to the user's PACS system.

Cleerly Labs software does not perform any functions that could not be accomplished by a trained user with manual tracing method or other commercially available software. Rather, it represents a more robust semiautomatic software intended to enhance the performance of time-intensive, potentially error-prone, manual tasks, thereby improving efficiency for medical professionals in the assessment of coronary artery disease (CAD).

AI/ML Overview

The provided text details the 510(k) summary for Cleerly Labs v2.0, focusing heavily on its substantial equivalence to the predicate device, Cleerly Labs (K190868). The performance data presented for Cleerly Labs v2.0 is referenced as being reproduced from the testing done for the predicate device (K190868), as no new clinical testing was conducted for v2.0. Therefore, the information provided below pertains to the study that proved Cleerly Labs (K190868) met its acceptance criteria, as the performance claims for v2.0 are based on this prior validation.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the "Pearson Correlation Coefficient" and "Bland-Altman Agreement" values for specific volume measurements. The device performance (reported for the predicate device, K190868, and reproduced for K202280) is presented in Table 6. While explicit "acceptance criteria" numerical thresholds are not stated (e.g., "must achieve a Pearson Correlation >= 0.8"), the reported values represent the performance achieved to demonstrate substantial equivalence to expert reader results.

Output	Acceptance Criteria (Implied)	Reported Device Performance
Lumen Volume	High Pearson Correlation	0.91
	High Bland-Altman Agreement	96%
Vessel Volume	High Pearson Correlation	0.93
	High Bland-Altman Agreement	97%
Total Plaque Volume	High Pearson Correlation	0.85
	High Bland-Altman Agreement	95%
Calcified Plaque Volume	High Pearson Correlation	0.94
	High Bland-Altman Agreement	95%
Non-Calcified Plaque Volume	High Pearson Correlation	0.74
	High Bland-Altman Agreement	95%
Low-Density-Non-Calcified Plaque Volume	High Pearson Correlation	0.53
	High Bland-Altman Agreement	97%

Note: The document states, "Additionally, the performance of the software was previously compared to ground truth results produced by expert readers (K190868). Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly Labs and expert reader results are reproduced in Table 6." This indicates that these performance metrics were the basis for acceptance for the predicate device.

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

Sample Size: The document does not specify the sample size used for the test set in either the original K190868 submission or this K202280 submission.
Data Provenance: The document does not specify the country of origin of the data, nor does it explicitly state whether the data was retrospective or prospective. It only mentions that the data was from "patients who underwent Coronary Computed Tomography Angiography (CCTA)."

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

Number of Experts: The document refers to "expert readers" (plural) but does not specify the exact number of experts used to establish the ground truth.
Qualifications of Experts: The document does not provide the specific qualifications of these experts (e.g., years of experience, specific certifications). It only refers to them as "expert readers."

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) used for establishing the ground truth from the expert readers. It only states that ground truth results were "produced by expert readers."

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

No MRMC Comparative Effectiveness Study was done for Cleerly Labs v2.0. The document explicitly states: "No clinical testing was conducted to demonstrate safety or effectiveness as the device's non-clinical testing was sufficient to support the intended use of the device."
The performance data provided (Table 6) refers to the comparison of the device's measurements against expert reader results in the predicate device's validation (K190868). This is a comparison between the device and human expert ground truth, not a study evaluating human readers' improvement with AI assistance.

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

The data in Table 6, showing "Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly Labs and expert reader results," represents the standalone performance of the Cleerly Labs algorithm (or at least the initial segmented values before user editing).
The description of the software functionality notes: "Cleerly Labs utilizes machine learning... applies deep learning methodology to identify high quality images, segment and label coronary arteries, and segment lumen and vessel walls. 2D and 3D images are presented to the user for review and manual editing." The performance metrics in Table 6 likely refer to the agreement of these automated segmentations with expert results. However, the subsequent statement also says: "Plaque, stenosis, and vessel measurements are output based the combination of user-editable segmentation and user-placed stent, and CTO markers. These outputs are mathematical calculations and are not machine-learning based." This suggests the final outputs are influenced by user edits. The document doesn't explicitly clarify if the correlation values are based on the initial automated output or the final user-edited output compared to the expert ground truth. Given the context of showing an automated system's performance, it's more likely referring to the algorithm's capability.

7. Type of Ground Truth Used

The ground truth used was expert consensus (or at least expert reader results). The document states that the software's performance was "compared to ground truth results produced by expert readers."

8. Sample Size for the Training Set

The document does not specify the sample size used for the training set for the machine learning components of Cleerly Labs.

9. How the Ground Truth for the Training Set Was Established

The document does not describe how the ground truth for the training set was established. It only mentions that the machine learning components underwent validation.

Summary

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October 2, 2020

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a seal for the Department of Health & Human Services - USA. To the right of the seal, there is a blue square with the letters "FDA" in white. Next to the blue square, the words "U.S. FOOD & DRUG" are written in blue, with the word "ADMINISTRATION" written in a smaller font size below.

Cleerly, Inc. % John Smith, M.D., J.D. Partner Hogan Lovells US LLP 555 Thirteenth Street, NW WASHINGTON DC 20004

Re: K202280

Trade/Device Name: Cleerly Labs v2.0 Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: Class II Product Code: LLZ Dated: August 11, 2020 Received: August 11, 2020

Dear Dr. Smith:

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 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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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 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.

For

Thalia T. Mills, Ph.D. Director Division of Radiological Health OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known)

K202280

Device Name

Cleerly Labs v2.0 Indications for Use (Describe)

Cleerly Labs is a web-based software application that is intended professionals as an interactive tool for viewing and analyzing cardiac computed tomography (CT) data for deternining the presence and extent of coronary plaques (i.e., atherosclerosis in patients who underwent Coronary Computed Tomography (CCTA) for evaluation of CAD or suspected CAD. This software post processes CT images obtained using any Computed Tomography (CT) scanner. The software provides tools for of coronary arteries.

The software is not intended to replace the skill and judgment of a qualified medical practitioner and should only been appropriately trained in the software's functions. Users should be aware that certain views make use of internolated data. This is data that is created by the software based on the original data may give the appearance of healthy tissue in situations where pathology that is near or smaller than the scanning resolution may be present.

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

Cleerly's Cleerly Labs v2.0

1. General Information

Submitter	Cleerly, Inc.
Address	101 Greenwich St, Suite 11CNew York, NY 10006
Phone/Fax #	479-221-3262
Contact Person	Kimberly Elmore
Date Prepared	September 22, 2020

Table 1: Cleerly, Inc Information

Device Information 2.

Table 2: Cleerly Labs v2.0 Information
Trade Name	Cleerly Labs v2.0 (K202280)
Common Name	System, Image Processing, Radiological
Regulation Number	21 CFR 892.2050 Picture Archiving And CommunicationsSystem
Regulatory Class	Class II
Product Code	LLZ

Predicate Device Information 3.

Table 3: Predicate Device Information
Trade Name	Cleerly Labs (K190868)
Common Name	System, Image Processing, Radiological
Regulation Number	21 CFR 892.2050 Picture Archiving And CommunicationsSystem
Regulatory Class	Class II
Product Code	LLZ

No reference devices were used in this submission.

4. Device Description

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5. Intended Use / Indications for Use

The underlined word is the only change compared to the intended use/indications for use of the predicate device (K190868) to indicate that coronary plaques are related to atherosclerosis. This change to the indications for use is not intended to expand or modify the indications for use of the device, but rather was made to support the terminology used within the CORONARY report, which refers to coronary plaques analysis as being findings related to atherosclerosis.

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6. Software Functionality

In Cleerly Labs, users can edit the lumen and vessel walls of the suggested segmentation, and demarcate stenosis and stents, to more efficiently perform coronary analysis. Users are provided with navigation and editing/visualization tools to aid in image analysis. Plaque (i.e., atherosclerosis) and stenosis measurements are outputted based on the fully user-editable segmentation of the coronary artery. The user is also provided with the ability to indicate coronary anatomical findings.

Following the completion of study analysis, an interactive CORONARY Report is generated (the subject device of this submission). The CORONARY Report summarizes the analysis data from Cleerly Labs by reporting them as findings on atherosclerosis and stenosis, which may be used as supporting data in the evaluation of CAD. Components of the CORONARY Report include data visualization and reporting features. Table 4 below compares the key features of the subject and predicate devices.

Feature	Cleerly Labs v2.0 Device(Subject device)	Cleerly Labs Device(K190868)
Operating Platform	Client-Server Google ChromeApplication	Client-Server Google ChromeApplication
Image Input	DICOM 3.0 Compliant (or higher)	DICOM 3.0 Compliant (or higher)
Image Acquisition	CT Images	CT Images
Secured NetworkSever Integration	Yes	No
Study Analysis Tools –Navigation	Yes	Yes
Study Analysis Tools –Editing/ Visualization	Yes	Yes
2D Imaging	Yes	Yes
3D Imaging	Yes	Yes
Multiplanar Reformat(MPR)	Yes	Yes
Segmentation ofRegion of Interest	Yes	Yes
Plaque CompositionOverlay	Yes	Yes
Hounsfield Unit (HU)	Yes	Yes
DistanceMeasurements	Yes	Yes
VolumetricMeasurements	Yes	Yes
Remodeling Index	Yes	Yes
Stenosis	Yes	Yes
Coronary AnatomicalFindings	Yes	No

Table 4: Subject vs Predicate Device

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Feature	Cleerly Labs v2.0 Device(Subject device)	Cleerly Labs Device(K190868)
Coronary Report	Yes	No

7. Performance Data

Software verification and validation activities were performed in accordance with the standards identified in Table 5 below, in addition to the FDA Guidance documents, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" and "Content of Premarket Submission for Management of Cybersecurity in Medical Devices."

The software was considered as a "moderate" level of concern, since "a malfunction of, or a latent design flaw in, the Software Device could lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that would likely lead to Minor Injury."

During product development, potential hazards were controlled by a risk management plan including activities of risk analysis, risk mitigation and risk-benefit analysis. Verification, validation and usability testing data demonstrated that the device meets all of its specification, including compliance with the following standards in Table 5.

StandardDesignation Numberand Date	Standard DevelopingOrganization	Title of Standard	FDA RecognitionNumber
PS 3.1-3.20 (2016)	NEMA	Digital Imaging AndCommunications In Medicine(DICOM) Set	12-300
62304:2005/A1:2016	ANSI AAMI IEC	Medical Device Software - SoftwareLife Cycle Processes [IncludingAmendment 1 (2016)]	13-79
14971 Third Edition2019-12	ISO	Medical Devices - Application OfRisk Management To MedicalDevices	5-125
62366-1 Edition 1.02015-02	IEC	Medical Devices - Part 1: ApplicationOf Usability Engineering To MedicalDevices [IncludingCORRIGENDUM 1 (2016)]	5-114
TIR 57:2016	AAMI	Principles for medical device security- Risk management	13-83

Table 5: Standards applied to device development

Additionally, the performance of the software was previously compared to ground truth results produced by expert readers (K190868). Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly

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Labs and expert reader results are reproduced in Table 6. No algorithms or simple mathematical calculations that were already reviewed by the FDA in the original Cleerly Labs (K190868) submission were changed.

Output	Pearson CorrelationCoefficient	Bland-Altman Agreement
Lumen Volume	0.91	96%
Vessel Volume	0.93	97%
Total Plaque Volume	0.85	95%
Calcified Plaque Volume	0.94	95%
Non-Calcified Plaque Volume	0.74	95%
Low-Density-Non-CalcifiedPlaque Volume	0.53	97%

Table 6: Cleerly Labs Performance

Non-Clinical Testing

Risk assessment, performance, cybersecurity, and usability of Cleerly Labs v2.0 have been evaluated and verified using the same approach as implemented for the predicate device and in accordance with software predefined specifications and applicable performance standards through software verification and validation testing.

The following is a summary of the nonclinical testing performed:

Verification and validation testing confirmed that the software requirements fulfilled the pre-defined acceptance criteria.
. A usability test was conducted with intended users of the device to ensure the clinical acceptability of the device.
. A cybersecurity penetration test was conducted to ensure that there were no unidentified vulnerabilities and that the appropriate risk control measures were implemented to protect from known vulnerabilities when the device is subject to a source of threat.

The nonclinical verification and validation test results established that the device meets its design requirements and intended use. During the development, potential hazards were evaluated and controlled through risk management activities. The performance testing demonstrates that the device meets all its specifications.

Clinical Testing

No clinical testing was conducted to demonstrate safety or effectiveness as the device's non-clinical testing was sufficient to support the intended use of the device.

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8. Cybersecurity

Cleerly Labs has implemented security features for device and data protection. Cybersecurity requirements, risk analysis, and mitigation was addressed in accordance with FDA guidance, "Content of Premarket Submission for Management of Cybersecurity in Medical Devices".

9. Conclusions

Cleerly Labs v2.0 is as safe and effective as the original Cleerly Labs (K190868). Cleerly Labs v2.0 has the same intended uses and similar indications, technological characteristics, and principles of operation as its predicate device. The minor difference in indications do not alter the intended use of the device and do not affect its safety and effectiveness when used as labeled. In addition, the minor technological differences between Cleerly Labs v2.0 and its predicate devices raise no new issues of safety or effectiveness. No changes have been made to machine learning algorithms or simple mathematical equations. Cleerly Labs v2.0 is as safe and effective as the original Cleerly Labs (K190868). Thus, Cleerly Labs v2.0 is substantially equivalent.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).