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 and stenosis 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 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 Computed Tomography (CT) angiographic scans. The software is a post-processing tool that aids in determining treatment paths for patients suspected to have coronary artery disease (CAD).

To aid in image analysis, tools are provided to users to navigate and manipulate images. Manual and semi-automatic segmentation of the coronary artery images are possible using editing tools, thus providing the user the flexibility to perform the coronary analysis.

The output of the software includes visual images of coronary arteries, distance and volume measurements of the lumen wall, vessel wall, and plaque, remodeling index as well as stenosis diameter and area. These measurements are based on user segmentation.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Cleerly Labs device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on demonstrating substantial equivalence to a predicate device and fulfilling general software and medical device standards. It doesn't explicitly state "acceptance criteria" as a set of numerical thresholds the device must meet in a formal table like some AI/ML device submissions. Instead, performance is reported as correlation and agreement with expert readers, which serve as the de-facto performance metrics.

However, we can infer the acceptance criteria for performance by looking at what was reported and considered satisfactory for clearance. The Pearson Correlation Coefficients and Bland-Altman Agreements are the key performance indicators.

Performance Metric	Acceptance Criteria (Implied by reported values and clearance)	Reported Device Performance
Pearson Correlation Coefficient	High correlation (e.g., > 0.70 or > 0.80) with expert readers
Lumen Volume		0.91
Vessel Volume		0.93
Total Plaque Volume		0.85
Calcified Plaque Volume		0.94
Non-Calcified Plaque Volume		0.74
Low-Density-Non-Calcified Plaque Volume		0.53
Bland-Altman Agreement	High agreement (e.g., > 95%) with expert readers
Lumen Volume		96%
Vessel Volume		97%
Total Plaque Volume		(Missing/Garbled in text)
Calcified Plaque Volume		(Missing/Garbled in text)
Non-Calcified Plaque Volume		(Missing/Garbled in text)
Low-Density-Non-Calcified Plaque Volume		97%

Note on Missing/Garbled Bland-Altman Data: The provided text has garbled characters for several Bland-Altman agreement values, making it impossible to extract precise numbers for "Total Plaque Volume," "Calcified Plaque Volume," and "Non-Calcified Plaque Volume."

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

The document states: "Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly Labs and expert reader results is reported Table 5." and "The machine learning algorithms were evaluated by comparing the output of the software to that of the ground truth using multiple ground truthers."

Test Set Sample Size: The exact number of cases or images in the test set is not explicitly stated in the provided text.
Data Provenance (Country of origin, retrospective/prospective): This information is not explicitly stated in the provided text.

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

Number of Experts: The document mentions "multiple ground truthers" and "expert readers," but the exact number of experts is not specified.
Qualifications of Experts: It states that a "Usability test was conducted with U.S. board certified radiologists and technicians." While this refers to usability, it suggests that the "expert readers" for performance evaluation would likely hold similar, if not higher, qualifications (e.g., board-certified radiologists specializing in cardiac imaging). However, their specific specializations or years of experience are not explicitly detailed.

4. Adjudication Method for the Test Set:

The document states: "The machine learning algorithms were evaluated by comparing the output of the software to that of the ground truth using multiple ground truthers." This implies that ground truth was established by more than one expert. However, the specific adjudication method (e.g., 2+1, 3+1 consensus, average, majority vote, etc.) for resolving disagreements among these multiple ground truthers is not explicitly described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC comparative effectiveness study was not explicitly done or reported in this 510(k) summary. The study focuses on the standalone performance of the software compared to expert-established ground truth, not on how human readers improve with AI assistance versus without it. The document states, "No clinical testing was conducted to demonstrate safety or effectiveness as the device's non-clinical (bench) testing was sufficient to support the intended use of the device."

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done:

Yes, a standalone performance evaluation was done. The reported Pearson Correlation Coefficients and Bland-Altman Agreements are for the "Cleerly Labs" output compared directly to "expert reader results (ground truth)," indicating a standalone assessment of the algorithm's performance. The software is described as a post-processing tool that "aids in determining treatment paths" and provides "suggested segmentation," which users can "edit," but the performance metrics provided are for the direct output of the software.

7. The Type of Ground Truth Used:

Expert Consensus (implied): The ground truth was established by "expert readers" or "multiple ground truthers." This strongly implies that the reference standard against which the software was compared was derived from human expert interpretation, likely through a consensus process or independent readings. There is no mention of pathology or outcomes data being used as ground truth for these specific quantitative plaque metrics.

8. The Sample Size for the Training Set:

The document does not provide information regarding the sample size used for the training set. It only discusses the evaluation of "machine learning algorithms" but not their development dataset.

9. How the Ground Truth for the Training Set was Established:

The document does not provide information on how the ground truth for the training set was established. This detail is typically separate from the test set evaluation and not always included in 510(k) summaries if not directly relevant to the substantial equivalence argument for the performance study.

Summary

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November 5, 2019

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

Re: K190868

Trade/Device Name: Cleerly Labs Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: Class II Product Code: LLZ Dated: October 9, 2019 Received: October 9, 2019

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

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801); 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 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

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Indications for Use

510(k) Number (if known) K190868

Device Name Cleerly Labs

Indications for Use (Describe)

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)	Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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 Labs (K190868)

1. General Information

Table 1: Cleerly, Inc. Information

510(k) Sponsor	Cleerly, Inc.
Address	101 Greenwich St, Suite 11CNew York, NY 10006
Phone/Fax #	646-362-4255
Contact Person	Kimberly Elmore
Date Prepared	October 9, 2019

2. Device Information

Table 2: Cleerly Labs Information

Trade Name	Cleerly Labs (K190868)
Common Name	System, Image Processing, Radiological
Regulation Number	21 CFR 892.2050 Picture Archiving And CommunicationsSystem
Classification	Class II
Product Code	LLZ
Predicate Device	Autoplaque (K122429)
Reference Device	SurePlaque (K043111)

Device Description 3.

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Indications for Use 4.

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 and stenosis 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 data that 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.

ട. Software Functionality

Users of Cleerly Labs 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 image viewing tools to aid in their analysis. Plaque and stenosis measurements are output based on the combination of fully user-editable segmentation and user-placed demarcations of coronary artery characteristics.

Cybersecurity 6.

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".

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7. Comparison of Technological Characteristics to the Predicate Devices

Feature	Subject Device:Cleerly Labs (K190868)	Predicate Device:Autoplaque (K122429)
Operating Requirements
Platform	Client-Server GoogleChrome Application	Windows OS
Image Input	DICOM 3.0 Compliant (orhigher)	DICOM 3.0 Compliant (orhigher)
Image Acquisition	CT Images	CT Images
Navigation Tools	Window Width/Level Zoom Pan Rotation Tracker	Window Width/Level Zoom Pan Rotation Tracker
Visualization / EditTools	Lumen Wall Vessel Wall Segment Stenosis Centerline Plaque Chronic Total Occlusion (CTO) Stent Exclude Distance	Lumen Wall Vessel Wall Segment Stenosis Centerline Plaque Exclude Distance
2D Imaging	Yes	Yes
3D Imaging	Yes	Yes
MultiplanarReformat (MPR)	Yes	Yes
Segmentation ofregion of interest	Manual and Semi-Automatic	Manual and Semi-Automatic
Feature	Subject Device:Cleerly Labs (K190868)	Predicate Device:Autoplaque (K122429)
PlaqueCompositionOverlay	User-ModifiableThresholds:• Non-Calcified Plaque (NCP)• Calcified Plaque (CP)• Low-Density Non-Calcified Plaque (LD-NCP)	User-ModifiableThresholds:• Non-Calcified Plaque (NCP)• Calcified Plaque (CP)• Low-Density Non-CalcifiedPlaque (LD-NCP)
Quantification
Hounsfield Unit(HU)	Yes	Yes
DistanceMeasurements	• Vessel• Lesion• Length	• Vessel• Lesion• Length
VolumetricMeasurements	• Total Vessel• Total Lumen• Non-Calcified Plaque(NCP)• Low-Density Non-Calcified Plaque (LD-NCP)• Calcified Plaque (CP)• Total Plaque	• Total Vessel• Non-Calcified Plaque (NCP)• Low-Density Non-CalcifiedPlaque (LD-NCP)• Calcified Plaque (CP)• Total Plaque
Remodeling Index	Yes	Yes
Stenosis	• % Area Stenosis• % Diameter Stenosis	• % Area Stenosis• % Diameter Stenosis

Table 3: Device Features Comparison Table

Cleerly Labs Traditional 510(k) Submission

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clesrly

Performance Data 8.

Software verification and validation activities were performed in accordance with the standards identified in Table 4 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."

Cleerly Labs Traditional 510(k) Submission

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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 4.

StandardsNo	StandardOrganization	Title	Version	Date
PS 3.1-3.20	NEMA	Digital ImagingAndCommunications InMedicine (DICOM)Set	2016	06-27-2016
62304	ANSI/AAMI/IEC	Medical devicesoftware - Softwarelife cycle processes	2006+AMD1:2015Edition 1.1	06-26-2016
14971	ISO	Medical Devices -Application Of RiskManagement ToMedical Devices	2007Edition 2.0	03-01-2007
62366-1	ANSI AAMIIEC	Medical Devices -Part 1: ApplicationOf UsabilityEngineering ToMedical Device	2015Edition 1.1	02-24-2015

Table 4: Standards applied to device development

Additionally, the performance of the software was compared to ground truth results produced by expert readers. Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly Labs and expert reader results is reported Table 5.

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Output	Pearson Correlation	Bland-Altman Agreement
	Coefficient
Lumen Volume	0.91	96%
Vessel Volume	0.93	97%
Total Plaque Volume	0.85	તે તે જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો
Calcified Plaque Volume	0.94	તે તે જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો
Non-Calcified Plaque	0.74	તેરજ
Volume
Low-Density-Non-	0.53	97%
Calcified Plaque Volume

Table 5: Cleerly Labs Performance

Non-Clinical Testing:

Safety, performance, cybersecurity and usability of Cleerly Labs have been evaluated and verified in accordance with software pre-defined specifications and applicable performance standards through software verification and validation testing.

Verification and validation testing confirmed that the software requirements ● fulfilled the pre-defined acceptance criteria.
A Usability test was conducted with U.S. board certified radiologists and ● technicians to ensure the clinical acceptability of the device.
The machine learning algorithms were evaluated by comparing the output of the ● software to that of the ground truth using multiple ground truthers.
A side-by-side comparison testing was conducted to evaluate the simple rule-based ● calculations as they compared to an already cleared device with a similar intended use.
. A cybersecurity penetration testing 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 non-clinical 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 (bench) testing was sufficient to support the intended use of the device.

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9. Conclusion

Based on the information submitted in this premarket notification, and based on the indications for use, technological characteristics and performance testing comparison to the predicate, the Cleerly Labs device raises no new questions of safety or effectiveness and is substantially equivalent to the predicate in terms of safety, efficacy, and performance.

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).