HealthPNX

K190362 · Zebra Medical Vision, Ltd. · QFM · May 6, 2019 · Radiology

Device Facts

• Record ID: K190362
• Device Name: HealthPNX
• Applicant: Zebra Medical Vision, Ltd.
• Product Code: QFM · Radiology
• Decision Date: May 6, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 892.2080
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

The Zebra Pneumothorax device is a software workflow tool designed to aid the clinical assessment of adult Chest X-Ray cases with features suggestive of Pneumothorax in the medical care environment. HealthPNX analyzes cases using an artificial intelligence algorithm to identify suspected findings. It makes case-level output available to a PACS/workstation for worklist prioritization or triage. HealthPNX is not intended to direct attention to specific portions or anomalies of an image. Its results are not intended to be used on a stand-alone basis for clinical decision-making nor is it intended to rule out Pneumothorax or otherwise preclude clinical assessment of X-Ray cases.

Device Story

HealthPNX is a radiological computer-aided triage and notification software. It automatically retrieves and processes PA/AP chest X-rays from a PACS/workstation. An AI algorithm analyzes the images to identify findings suggestive of pneumothorax. If a suspected finding is identified, the device provides a passive, case-level notification to the PACS/workstation to prioritize the study on the radiologist's worklist. The device does not mark or highlight specific image regions, nor does it remove cases from the standard-of-care worklist. It is intended to be used by radiologists to facilitate earlier review of time-sensitive cases. The device does not provide diagnostic information and is not intended for stand-alone clinical decision-making or to rule out pneumothorax.

Clinical Evidence

Pivotal performance study using a retrospective cohort of 588 anonymized chest X-ray cases (146 positive, 442 negative). Ground truth established by three US Board Certified Radiologists. Stand-alone detection accuracy: AUC 98.3% (95% CI: 97.40%-99.02%), sensitivity 93.15% (95% CI: 87.76%-96.67%), specificity 92.99% (95% CI: 90.19%-95.19%). Prospective reader study showed a statistically significant reduction in mean triage time: 8.05 minutes with HealthPNX vs. 68.98 minutes for standard of care (FIFO).

Technological Characteristics

Software-only radiological computer-aided triage and notification system. Operates on DICOM format images. Utilizes an AI algorithm for image analysis. Deployed as a workflow tool integrated with PACS/workstation. Validated per software development and verification processes.

Indications for Use

Indicated for adult patients undergoing Chest X-Ray imaging in a medical care environment to aid in the clinical assessment of cases with features suggestive of Pneumothorax.

Regulatory Classification

Identification

Radiological computer aided triage and notification software is an image processing prescription device intended to aid in prioritization and triage of radiological medical images. The device notifies a designated list of clinicians of the availability of time sensitive radiological medical images for review based on computer aided image analysis of those images performed by the device. The device does not mark, highlight, or direct users' attention to a specific location in the original image. The device does not remove cases from a reading queue. The device operates in parallel with the standard of care, which remains the default option for all cases.

Special Controls

Radiological computer aided triage and notification software must comply with the following special controls: 1. Design verification and validation must include: i. A detailed description of the notification and triage algorithms and all underlying image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, how the algorithm affects or relates to clinical practice or patient care, and any algorithm limitations. ii. A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will provide effective triage (e.g., improved time to review of prioritized images for pre-specified clinicians). iii. Results from performance testing that demonstrate that the device will provide effective triage. The performance assessment must be based on an appropriate measure to estimate the clinical effectiveness. The test dataset must contain sufficient numbers of cases from important cohorts (e.g., subsets defined by clinically relevant confounders, effect modifiers, associated diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals for these individual subsets can be characterized with the device for the intended use population and imaging equipment. iv. Standalone performance testing protocols and results of the device. v. Appropriate software documentation (e.g., device hazard analysis; software requirements specification document; software design specification document; traceability analysis; description of verification and validation activities including system level test protocol, pass/fail criteria, and results). 2. Labeling must include the following: i. A detailed description of the patient population for which the device is indicated for use. ii. A detailed description of the intended user and user training that addresses appropriate use protocols for the device. iii. Discussion of warnings, precautions, and limitations must include situations in which the device may fail or may not operate at its expected performance level (e.g., poor image quality for certain subpopulations), as applicable. iv. A detailed description of compatible imaging hardware, imaging protocols, and requirements for input images. v. Device operating instructions. vi. A detailed summary of the performance testing, including: test methods, dataset characteristics, triage effectiveness (e.g., improved time to review of prioritized images for pre-specified clinicians), diagnostic accuracy of algorithms informing triage decision, and results with associated statistical uncertainty (e.g., confidence intervals), including a summary of subanalyses on case distributions stratified by relevant confounders, such as lesion and organ characteristics, disease stages, and imaging equipment.

*Classification.* Class II (special controls). The special controls for this device are:(1) Design verification and validation must include: (i) A detailed description of the notification and triage algorithms and all underlying image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, how the algorithm affects or relates to clinical practice or patient care, and any algorithm limitations. (ii) A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will provide effective triage ( *e.g.,* improved time to review of prioritized images for pre-specified clinicians).(iii) Results from performance testing that demonstrate that the device will provide effective triage. The performance assessment must be based on an appropriate measure to estimate the clinical effectiveness. The test dataset must contain sufficient numbers of cases from important cohorts ( *e.g.,* subsets defined by clinically relevant confounders, effect modifiers, associated diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals for these individual subsets can be characterized with the device for the intended use population and imaging equipment.(iv) Stand-alone performance testing protocols and results of the device. (v) Appropriate software documentation ( *e.g.,* device hazard analysis; software requirements specification document; software design specification document; traceability analysis; description of verification and validation activities including system level test protocol, pass/fail criteria, and results).(2) Labeling must include the following: (i) A detailed description of the patient population for which the device is indicated for use; (ii) A detailed description of the intended user and user training that addresses appropriate use protocols for the device; (iii) Discussion of warnings, precautions, and limitations must include situations in which the device may fail or may not operate at its expected performance level ( *e.g.,* poor image quality for certain subpopulations), as applicable;(iv) A detailed description of compatible imaging hardware, imaging protocols, and requirements for input images; (v) Device operating instructions; and (vi) A detailed summary of the performance testing, including: test methods, dataset characteristics, triage effectiveness ( *e.g.,* improved time to review of prioritized images for pre-specified clinicians), diagnostic accuracy of algorithms informing triage decision, and results with associated statistical uncertainty (*e.g.,* confidence intervals), including a summary of subanalyses on case distributions stratified by relevant confounders, such as lesion and organ characteristics, disease stages, and imaging equipment.

Predicate Devices

• cmTriage (K183285)

Submission Summary (Full Text)

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Zebra Medical Vision Ltd. % Flair Bar VP Operations Shefayim Commercial Center, PO Box 25 Shefayim, 6099000 ISRAEL

May 6, 2019

## Re: K190362

Trade/Device Name: HealthPNX Regulation Number: 21 CFR 892.2080 Regulation Name: Radiological computer-aided triage and notification software Regulatory Class: Class II Product Code: QFM Dated: April 2, 2019 Received: April 5, 2019

Dear Flair Bar:

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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

For

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

Enclosure

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# Indications for Use

510(k) Number (if known) K190362

Device Name HealthPNX

#### Indications for Use (Describe)

The Zebra Pneumothorax device is a software workflow tool designed to aid the clinical assessment of adult Chest X-Ray cases with features suggestive of Pneumothorax in the medical care environment. HealthPNX analyzes cases using an artificial intelligence algorithm to identify suspected findings. It makes case-level output available to a PACS/workstation for worklist prioritization or triage. HealthPNX is not intended to direct attention to specific portions or anomalies of an image. Its results are not intended to be used on a stand-alone basis for clinical decision-making nor is it intended to rule out Pneumothorax or otherwise preclude clinical assessment of X-Ray cases.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------------------------------------------------------------------------------|---------------------------------------------|
| <div> <span style="text-decoration: overline;">X</span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | Over-The-Counter Use (21 CFR 801 Subpart C) |

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Image /page/3/Picture/0 description: The image shows the Zebra Medical Vision logo. The logo consists of a yellow horizontal line on the left, followed by a stylized black and white zebra stripe design. To the right of the zebra stripe design is the word "zebra" in black, with the words "MEDICAL.VISION" in smaller font below it.

# 510 (k) Summary

## 510(K) Summary - HealthPNX Zebra Medical Vision Ltd.

### 510(k) Number – K190362

- I. Applicant's Name: Zebra Medical Vision Ltd. Flair Bar Shefayim Commercial Center PO Box 25 Shefayim, 6099000 ISRAEL Telephone: [phone] Fax: [phone]
Date Prepared: April 28, 2019

- II. Device
Trade Name: HealthPNX

### Classification Name:

Radiological Computer Aided Triage and Notification Software

### Regulation Number: 21 CFR 892.2080

Classification: Class II, Radiology

Product Code: QFM

#### III. Predicate Device

The HealthPNX device is substantially equivalent to the following device:

| Proprietary Name | cmTriage |
|------------------------|--------------------------------------------------------|
| Premarket Notification | K183285 |
| Classification Name | Radiological Computer-Assisted Prioritization Software |
| Regulation Number | 21 CFR 892.2080 |
| Product Code | QFM |
| Regulatory Class | II |

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Image /page/4/Picture/0 description: The image shows the Zebra Medical Vision logo. The logo consists of a yellow horizontal line on the left, followed by a stylized black and white zebra-striped "Z" symbol. To the right of the "Z" symbol is the word "zebra" in black, with the words "MEDICAL.VISION" in smaller font below it.

#### Device Description: IV.

Zebra's HealthPNX is a radiological computer-assisted triage and notification software system. The software automatically analyzes PA/AP chest x-rays and alerts the PACS/workstation once findings suspicious of pneumothorax are identified.

The following modules compose the HealthPNX software system:

Data input and validation: After a chest x-ray has been performed, a copy of the study is automatically retrieved and processed by the HealthPNX device. Following retrieval of a study, the validation feature assesses the input data (i.e. age, modality, view) to ensure compatibility for processing by the algorithm.

HealthPNX algorithm: Once a study has been validated, the algorithm analyzes the frontal chest x-ray for detection of suspected findings suggestive of pneumothorax.

IMA Integration feature: The study analysis and the results of a successful study analysis is provided to IMA, that notifies the PACS/workstation through the worklist interface.

Error codes feature: In the case of a study failure during data validation or the analysis by the algorithm, an error is provided to the system.

The radiologist is then able to review the study earlier than in standard of care workflow.

In summary, the HealthPNX device is intended to provide a passive notification through the PACS/workstation to the radiologists indicating the existence of a case that may potentially benefit from the prioritization. It doesn't output an image and therefore it does not mark, highlight, or direct users' attention to a specific location on the original chest X ray.

The device aim is to aid in prioritization and triage of radiological medical images only.

#### V. Intended Use/Indication for Use

The Zebra Pneumothorax device is a software workflow tool designed to aid the clinical assessment of adult Chest X-Ray cases with features suggestive of Pneumothorax in the medical care environment. HealthPNX analyzes cases using an artificial intelligence algorithm to identify suspected findings. It makes case-level output available to a PACS/workstation for worklist prioritization or triage. HealthPNX is not intended to direct attention to specific portions or anomalies of an image. Its results are not intended to be used on a stand-alone basis for clinical decision-making nor is it intended to rule out Pneumothorax or otherwise preclude clinical assessment of X-Ray cases.

#### VI. Comparison of Technological Characteristics with the Predicate Device

The technological characteristics are compared below.

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Image /page/5/Picture/0 description: The image is a logo for Zebra Medical Vision. The logo consists of a stylized letter Z on the left and the word "zebra" on the right. Below the word "zebra" is the text "MEDICAL.VISION".

| Technological<br>Characteristics | HealthPNX | Predicate: cmTriage<br>(K183285) | Similarities or<br>Differences |
|----------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Indication for use | The Zebra Pneumothorax<br>device is a software<br>workflow tool designed to<br>aid the clinical assessment<br>of adult Chest X-Ray cases<br>with features suggestive of<br>Pneumothorax in the<br>medical care environment.<br>HealthPNX analyzes cases<br>using an artificial<br>intelligence algorithm to<br>identify suspected findings.<br>It makes case-level output<br>available to a<br>PACS/workstation for<br>worklist prioritization or<br>triage. HealthPNX is not<br>intended to direct attention<br>to specific portions of an<br>image or to anomalies other<br>than Pneumothorax. Its<br>results are not intended to<br>be used on a stand-alone<br>basis for clinical decision-<br>making nor is it intended to<br>rule out Pneumothorax or<br>otherwise preclude clinical<br>assessment of X-Ray cases | cmTriage is a passive notification<br>for prioritization-only, parallel-<br>workflow software tool used by<br>radiologists to prioritize specific<br>patients within the standard-of-care<br>image worklist for 2D FFDM<br>screening mammograms.<br>cmTriage uses an artificial<br>intelligence algorithm to analyze<br>2D FFDM screening mammograms<br>and flags those that are suggestive<br>of the presence of at least one<br>suspicious finding at the exam<br>level.<br>These flags are viewed by the<br>radiologist via their Picture<br>Archiving and Communication<br>System (PACS) worklist. The<br>decision to use cmTriage codes and<br>how to use cmTriage codes is<br>ultimately up to the radiologist.<br>cmTriage does not send a proactive<br>alert directly to the radiologist.<br>Radiologists are responsible for<br>reviewing each exam on a diagnostic<br>viewer according to the current<br>standard of care. cmTriage is limited to<br>the categorization of exams, does not<br>provide any diagnostic information<br>beyond triage and prioritization, does<br>not remove images from the<br>radiologist's worklist, and should not<br>be used in lieu of full patient<br>evaluation, or relied upon to make or<br>confirm diagnosis.<br>cmTriage is for prescription use only. | Similar except to<br>anatomy, imaging<br>modality and lesion<br>type |
| Notification-only,<br>parallel workflow<br>tool | Yes | Yes | Same |
| User | Radiologist | Radiologist | Same |
| Radiological<br>images format | DICOM | DICOM | Same |
| Identify patients<br>with prespecified<br>clinical condition | Yes | Yes | Same |
| Clinical condition | Pneumothorax | Breast Cancer | Different but are<br>"time sensitive<br>imaging" per 21CFR<br>892.2080 |
| Alert to finding | Passive notification flagged for<br>review | Passive notification flagged for review | Same |
| Independent of<br>standard of care<br>workflow | Yes; No cases are removed<br>from worklist | Yes; No cases are removed<br>from worklist | Same |
| Modality | X-Ray | FFDM screening mammograms | Different but both run<br>on "radiological<br>medical images" per<br>21 CFR 892.2080 |
| Body part | Chest | Breast | Different anatomical<br>sites but both<br>"operates on<br>radiological images of<br>the human body" per<br>21 CFR 892.2080 |
| Artificial<br>Intelligence<br>algorithm | Yes | Yes | Same |
| Limited to<br>analysis of<br>imaging data | Yes | Yes | Same |
| Aids prompt<br>identification of<br>cases with<br>indicated findings | Yes | Yes | Same |
| Where results are<br>received | PACS / Workstation | PACS / Workstation | Same |

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Image /page/6/Picture/0 description: The image shows the logo for Zebra Medical Vision. The logo consists of a stylized letter Z on the left, followed by the word "zebra" in a bold, sans-serif font. Below the word "zebra" are the words "MEDICAL.VISION" in a smaller font. The logo is black and white.

#### VII. Performance Data

The HealthPNX has been evaluated and verified in accordance with software specifications and applicable performance standards through Software Development and Validation & Verification Process to ensure performance according to specifications, User Requirements and Federal Regulations and Guidance documents, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices".

The performance of the HealthPNX device has been validated in a pivotal performance study that was carried out in the USA with simulated synthetic work-flow consisting of a truthed validation data-set. The data included a retrospective cohort of 588 anonymized Chest X-Ray cases from the USA and Israel, including pneumothorax positive (n=146) and negative cases (n=442), as well as

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Image /page/7/Picture/0 description: The image shows the logo for Zebra Medical Vision. The logo consists of a stylized letter Z made of black and white stripes, followed by the word "zebra" in black lowercase letters. Below the word "zebra" is the text "MEDICAL.VISION" in smaller black letters. The logo is simple and modern, and it effectively communicates the company's name and focus on medical imaging.

confounding imaging factors. The validation data set was truthed (ground truth) by three US Board Certified Radiologists (truthers). The stand-alone detection accuracy was measured on this cohort respective to ground truth. The triage effectiveness was evaluated by three different US Board Certified Radiologists (readers) that read these cases prospectively in real time with the HealthPNX device (HealthPNX prioritized work-list) and without (standard of care, "First-in-First-out" or "FIFO" queue) with a washout period separating between the two read periods with and without the HealthPNX device.

The detection accuracy met the a-priori performance goal (above 80% level of accuracy compared with ground truth). Overall, the HealthPNX was able to demonstrate an area under the curve (AUC) of 98.3% (95% CI: [97.40%, 99.02%]), which is substantially equivalent to the predicate device, and meets the required performance goal for QFM product code. Additionally, the overall agreement between HealthPNX device and ground truth was 93.03% (95% CI: [90.66%, 94.95%]). The sensitivity and specificity of the HealthPNX was 93.15% (95% CI: [87.76%, 96.67%]) and 92.99% (95% CI: [90.19%, 95.19%])(n=588), respectively.

The HealthPNX reduced triage time as compared to the standard of care (mean time 8.05 minutes (95% CI: [5.93, 10.16] minutes) vs. 68.98 minutes (95% CI: [60.53, 77.43] minutes)(n=588), with the HealthPNX compare to standard of care, respectively). This is a statistically significant reduction of triage time of time sensitive images. This establishes that the HealthPNX meets its intended use statement and is substantially equivalent to the predicate device.

In addition, we assessed the performance time of the HealthPNX that reflects the time it takes for the device to analyze the study and send a notification to the PACS worklist. The average performance time of the HealthPNX was 22.1 seconds, a timing performance that is substantially equivalent to the predicate (3.35 minutes).

### VIII. Conclusion

The subject HealthPNX device and the cmTriage predicate device are both software-only devices intended to aid in triage of radiological images, independent of care workflow. The labeling of both devices are limited to the categorization of exams and are not to be used in-lieu of full patient evaluation or relied upon to make or confirm diagnosis.

Both devices operate in parallel to the standard of care workflow in the sense that they do not change the original image, do not provide any marking, and do not remove cases from the standard of care. The minor differences between the subject device and the predicate raise no new issues of safety or effectiveness. In addition, performance testing demonstrates that the HealthPNX performs as intended . The HealthPNX device is therefore substantially equivalent to the cmTriage predicate.