(52 days)
No reference devices were used in this submission.
Yes
The device description explicitly states that Cleerly Labs "utilizes machine learning and simple rule-based mathematical calculation components" and "applies deep learning methodology".
No
Explanation: The device is a post-processing software that aids in diagnosing and analyzing cardiac conditions, not directly treating them. It provides information to medical professionals for determining treatment paths but does not perform the treatment itself.
Yes
This device is intended to be used by trained medical professionals for viewing and analyzing cardiac CT data to determine the presence and extent of coronary plaques, aiding in the evaluation of CAD or suspected CAD. This falls under the definition of a diagnostic device.
Yes
The device is described as a "web-based software application" and a "post-processing software application" that analyzes existing CT data. There is no mention of accompanying hardware or hardware components included with the device itself.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- IVD Definition: In vitro diagnostics are tests performed on samples taken from the human body, such as blood, urine, or tissue, to detect diseases, conditions, or infections. They are used to provide information for diagnosis, monitoring, or screening.
- Device Function: Cleerly Labs is a software application that processes and analyzes imaging data (CT scans) of the coronary arteries. It does not analyze biological samples taken from the patient.
- Intended Use: The intended use is to assist trained medical professionals in viewing and analyzing cardiac CT data to determine the presence and extent of coronary plaques. This is an image analysis tool, not a diagnostic test performed on a biological sample.
While the software provides information that can be used in the diagnostic process, it does so by analyzing medical images, not by performing a test on a biological specimen. Therefore, it falls outside the scope of an In Vitro Diagnostic device.
No
The letter does not affirmatively state that the FDA has reviewed and approved or cleared a Predetermined Change Control Plan (PCCP) for this device.
Intended Use / Indications for Use
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.
Product codes
LLZ
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).
Mentions image processing
Yes
Mentions AI, DNN, or ML
Yes
Input Imaging Modality
Computed Tomography Angiography (CCTA), CT
Anatomical Site
Coronary arteries
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Trained medical professionals / Not specified, implied to be clinical setting
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Software verification and validation activities were performed in accordance with specified standards and FDA Guidance documents. The software was considered a "moderate" level of concern. Risk assessment, performance, cybersecurity, and usability were evaluated and verified.
Pearson Correlation Coefficients and Bland-Altman Agreements between Cleerly Labs and expert reader results were reproduced from the predicate device (K190868).
Key results:
- Lumen Volume: Pearson Correlation 0.91, Bland-Altman Agreement 96%
- Vessel Volume: Pearson Correlation 0.93, Bland-Altman Agreement 97%
- Total Plaque Volume: Pearson Correlation 0.85, Bland-Altman Agreement 95%
- Calcified Plaque Volume: Pearson Correlation 0.94, Bland-Altman Agreement 95%
- Non-Calcified Plaque Volume: Pearson Correlation 0.74, Bland-Altman Agreement 95%
- Low-Density-Non-Calcified Plaque Volume: Pearson Correlation 0.53, Bland-Altman Agreement 97%
Non-clinical testing summary:
- Verification and validation testing confirmed software requirements.
- Usability test conducted with intended users.
- Cybersecurity penetration test conducted.
No clinical testing was conducted.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Pearson Correlation Coefficients and Bland-Altman Agreements are provided for volumetric measurements.
Predicate Device(s)
Reference Device(s)
No reference devices were used in this submission.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
0
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
1
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
2
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 11C |
| New 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 Communications |
| System | |
| 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 Communications |
| System | |
| Regulatory Class | Class II |
| Product Code | LLZ |
No reference devices were used in this submission.
4. 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).
4
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).
5. Intended Use / Indications for Use
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.
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 Chrome
Application | Client-Server Google Chrome
Application |
| Image Input | DICOM 3.0 Compliant (or higher) | DICOM 3.0 Compliant (or higher) |
| Image Acquisition | CT Images | CT Images |
| Secured Network
Sever 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 of
Region of Interest | Yes | Yes |
| Plaque Composition
Overlay | Yes | Yes |
| Hounsfield Unit (HU) | Yes | Yes |
| Distance
Measurements | Yes | Yes |
| Volumetric
Measurements | Yes | Yes |
| Remodeling Index | Yes | Yes |
| Stenosis | Yes | Yes |
| Coronary Anatomical
Findings | 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.
| Standard
Designation Number
and Date | Standard Developing
Organization | Title of Standard | FDA Recognition
Number |
|--------------------------------------------|-------------------------------------|-----------------------------------------------------------------------------------------------------------------------------|---------------------------|
| PS 3.1-3.20 (2016) | NEMA | Digital Imaging And
Communications In Medicine
(DICOM) Set | 12-300 |
| 62304:2005/A1:2016 | ANSI AAMI IEC | Medical Device Software - Software
Life Cycle Processes [Including
Amendment 1 (2016)] | 13-79 |
| 14971 Third Edition
2019-12 | ISO | Medical Devices - Application Of
Risk Management To Medical
Devices | 5-125 |
| 62366-1 Edition 1.0
2015-02 | IEC | Medical Devices - Part 1: Application
Of Usability Engineering To Medical
Devices [Including
CORRIGENDUM 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
7
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 Correlation
Coefficient | 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-Calcified
Plaque 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.
8
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.