Cydar EV provides image guidance by overlaying preoperative 3D vessel anatomy, from a previously acquired contrast-enhanced, diagnostic CT scan, onto live fluoroscopic images in order to assist in the positioning of guidewires, catheters and other endovascular devices.

Cydar EV is intended to assist fluoroscopy-guided endovascular procedures in the lower thorax, abdomen and pelvis. Suitable procedures include (but are not limited to) endovascular aortic aneurysm repair (AAA and mid-distal TAA), angioplasty, stenting and embolization in the common iliac, proximal external iliac and proximal internal iliac arteries and corresponding veins.

Cydar EV is not intended for use in the X-ray guided procedures in the liver, kidneys or pelvic organs.

Device Description

Cydar EV is a Software-as-a-Service product and consists only of the software running on Cydar's cloud servers. Cydar EV provides augmented reality enhanced X-ray fluoroscopy images for use during X-ray guided surgery.

Cydar EV is a software only medical device. It defines minimum requirements to the hardware it runs on. Access to Cydar EV will be effected by a secure connection over either private networks or the public Internet.

The cloud communication, storage and processing solution is operated and maintained by specially trained Cydar Ltd staff and is based on the Ubuntu Linux operating system (versions 12.4 and 14.4). The client machines are based on Microsoft Windows 8.1, running the Google Chrome web-browser (version 47) and equipped with a video framegrabber (Foresight AccuStream Express HD+). The client machine captures a live fluoroscopy video feed from the X-rays machine's external (secondary) video port using HDMI, DVI, S-video, or analogue format. Any platform, which complies with the specified minimum hardware and software requirements and with successful system self-test and validation activities can be supported.

The Cydar EV will be marketed as a software only solution for the end-user (with recommended hardware requirements). Any special needs such as integration in a specific environment and updates / upgrades will be covered by individual service contract and fulfilled by specially trained service technicians.

AI/ML Overview

The provided text describes the non-clinical and clinical performance data for the Cydar EV device, but the acceptance criteria and related study details are not explicitly organized into a table format within the document. However, I can extract the relevant information and present it in the requested structure.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Compliance with IEC 62304 (Medical device software – Software life cycle processes)	Applied and demonstrated compliance
Compliance with IEC 62366-1 (Medical devices – Application of usability engineering to medical devices)	Applied and demonstrated compliance
Compliance with ISO 14971 (Medical devices – Application of risk management to medical devices)	Applied and demonstrated compliance
Compliance with NEMA PS 3.1-3.20 DICOM Set (2011)	Applied and demonstrated compliance
Compliance with FDA Guidance for Industry and FDA Staff – Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (issued May 11, 2005)	Demonstrated compliance
Software Verification Tests:
Registration accuracy from vertebral anatomy images	Accuracy demonstrated (calculated from images)
Overlay alignment accuracy in web browser display	Accuracy demonstrated
Information security	Demonstrated security
Responsiveness of overlays to changes in fluoroscopy imagery	Demonstrated responsiveness
Software Validation Tests:
Fulfilled intended use and commercial claims	Demonstrated by usability testing
Usability testing with representative clinical users	Demonstrated ease of use, visibility, and legibility of displays and overlays
Usability testing with system operators and IT staff	Demonstrated usability
Testing of the vessel segmentation tool	Demonstrated functionality
System availability and up-time	Demonstrated availability and up-time
Clinical Performance:
Accuracy of image guidance	Achieved accurate image guidance
Robustness of image guidance	Achieved robust image guidance
Usability of image guidance	Achieved usable image guidance
Procedure time	Addressed as a primary endpoint, but specific values are not provided in this summary.
Radiation exposure	Addressed as a primary endpoint, but specific values are not provided in this summary.
Iodinated contrast volume	Addressed as a primary endpoint, but specific values are not provided in this summary.

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

Non-clinical performance (Software verification & validation): The document does not specify a distinct "test set" sample size in terms of number of images or cases for the non-clinical tests. It refers to "images of the vertebral anatomy" for registration accuracy, but no count is given. The testing was performed by Cydar Ltd.
Clinical Performance: "The design was a multi-centre observational study." The document does not specify the exact number of participants ("subjects") for the clinical study. Data provenance is not explicitly stated as country of origin, but the sponsor, Cydar Ltd, is located in the UK. The study was "observational." It is not directly stated whether it was retrospective or prospective, but the phrasing "were scheduled to undergo an X-ray guided intervention" and "had had a pre-operative CT scan" suggests it was prospective, recruiting patients for future procedures.

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

The document does not provide details on the number or qualifications of experts used to establish ground truth for either the non-clinical or clinical test sets.

4. Adjudication method for the test set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the test sets.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

A multi-reader multi-case (MRMC) comparative effectiveness study explicitly comparing human readers with AI vs. without AI assistance is not described in this document. The clinical study was an "observational study examining safety, performance, usability, and clinical effect" of the Cydar EV device itself, rather than a comparative effectiveness study with and without the AI.

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

Yes, several aspects of the device's performance were assessed in a standalone manner as part of the "Software verification testing." This included:

Registration accuracy calculated from images of the vertebral anatomy.
Overlay alignment accuracy in the web browser display.
Information security.
Responsiveness of overlays to changes in the fluoroscopy imagery.
Testing of the vessel segmentation tool (part of software validation).
These tests evaluate the algorithm's performance independent of real-time human interaction for their specific metrics.

7. The type of ground truth used

Non-clinical performance: For registration accuracy, the ground truth was derived from "images of the vertebral anatomy" used to calculate accuracy. The exact method of establishing this ground truth (e.g., manual expert annotation, phantom measurements) is not explicitly detailed but implied to be based on established measurements. For other software tests, the ground truth was inherently defined by the expected software behavior and outputs.
Clinical Performance: The "clinical investigation was conducted to evaluate safety and efficacy" and measured "accuracy, robustness, usability, procedure time, radiation exposure, and iodinated contrast volume." The ground truth for judging "accuracy" of image guidance would likely be based on the actual positioning of guidewires/catheters relative to the true anatomy observed during the procedure, potentially confirmed by expert observation or other imaging modalities, though this is not explicitly detailed. "Usability" and "robustness" would be based on user feedback and system performance during clinical use.

8. The sample size for the training set

The document does not provide any information regarding the sample size used for the training set of the Cydar EV software. It focuses on the evaluation (test) of the final product.

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

Since no information is provided on the training set, there is no detail on how its ground truth was established.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of three human profiles facing right, stacked on top of each other. The profiles are rendered in a dark color, possibly black or a dark shade of gray. The graphic is encircled by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 7, 2016

Cydar Ltd. % Mr. Richard Vincins Vice President, OA/RA Emergo Global Consulting, LLC 816 Congress Avenue, Suite 1400 AUSTIN TX 78701

Re: K160088

Trade/Device Name: Cydar EV Regulation Number: 21 CFR 892.1650 Regulation Name: Image-intensified fluoroscopic x-ray system Regulatory Class: II Product Code: OWB Dated: May 24, 2016 Received: June 1, 2016

Dear Mr. Vincins:

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. 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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{1}------------------------------------------------

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Robert Ochs

Robert Ochs. Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K160088

్రి

Device Name Cydar EV

Indications for Use (Describe)

Cydar EV provides image guidance by overlaying preoperative 3D vessel anatomy, from a previously acquired contrastenhanced, diagnostic CT scan, onto live fluoroscopic images in order to assist in the positioning of guidewires, catheters and other endovascular devices.

Cydar EV is not intended for use in the X-ray guided procedures in the liver, kidneys or pelvic organs.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Section 5 – 510(k) Summary

Device Name: Cydar EV

K160088

1. 1. Submission Sponsor

Cydar Ltd

Bulbeck Mill

Mill Lane

Barrington

Cambridgeshire

CB22 7QY

Phone number: +44 1223 778 020

Contact: John Clarke

Title: CTO

2. Submission Correspondent

Emergo Global Consulting, LLC

816 Congress Avenue

Suite 1400

Austin, TX 78701

USA

Office Phone: +1 512 327 9997

Contact: Richard A. VINCINS, CQA, CBA, RAC(EU,US)

Title: Vice President, QA/RA

Email: project.management@emergogroup.com

{4}------------------------------------------------

3. Date Prepared

24 May 2016

4. Device Identification

Trade/Proprietary Name:	Cydar EV
Common/Usual Name:	Interventional Fluoroscopic X-Ray System
Classification Name:	Interventional Fluoroscopic X-Ray System
Regulation Number:	892.1650
Product Code:	OWB, Interventional Fluoroscopic X-Ray System
Device Class:	Class II
Classification Panel:	Radiology

5. Legally Marketed Predicate Device

K151598 - VesselNavigator - Philips Medical Systems Nederland B.V.

6. Device Description

{5}------------------------------------------------

7. Indication for Use Statement

Cydar EV is not intended for use in the X-ray guided procedures in the liver, kidneys or pelvic organs.

8. Substantial Equivalence Discussion

The following table compares the Cydar EV to the predicate device with respect to indications for use, principles of operation, technological characteristics, materials, and performance testing. The comparison of the devices provides more detailed information regarding the basis for the determination of substantial equivalence. The subject device does not raise any new issues of safety or effectiveness based on the similarities to the predicate device.

Manufacturer	Cydar Ltd	Philips Medical SystemsNederland B.V.	SignificantDifferences
Trade Name	Cydar EV(Subject device)	VesselNavigator(Predicate device)	N/A
510(k)Number	K160088	K151598	N/A
Product Code	OWB	OWB / LLZ	Similar; the ProductCode LLZ is notconsidered asproduct is not aPACS system
RegulationNumber	892.1650	892.1650 / 892.2050	Similar; theregulation number892.2050 is notconsidered asproduct is not aPACS system
RegulationName	Interventional Fluoroscopic X-Ray System	Interventional Fluoroscopic X-RaySystem / Picture Archiving and	Similar; theregulation number
Manufacturer	Cydar Ltd	Philips Medical SystemsNederland B.V.	SignificantDifferences
Trade Name	Cydar EV(Subject device)	VesselNavigator(Predicate device)
		Communications System	892.2050, PACS, isnot considered asproduct is not aPACS system
Intended use	Display of combined live 2D X-ray fluoroscopy and 3D anatomy for image guidance during surgery.	Display of combined live 2D X-ray fluoroscopy and 3D anatomy for image guidance during surgery.	Identical
3D imaging	Pre-operative	Pre-operative	Identical
X-ray fluoroscopy	Live	Live	Identical
Indications for Use	Cydar EV provides image guidance by overlaying preoperative 3D vessel anatomy, from a previously acquired contrast-enhanced, diagnostic CT scan, onto live fluoroscopic images in order to assist in the positioning of guidewires, catheters and other endovascular devices.Cydar EV is intended to assist fluoroscopy-guided endovascular procedures in the lower thorax, abdomen and pelvis. Suitable procedures include (but are not limited to) endovascular aortic aneurysm repair (AAA and mid-distal TAA), angioplasty, stenting and embolization in the common iliac, proximal external iliac and proximal internal iliac arteries and corresponding	VesselNavigator provides image guidance by superimposing live fluoroscopic images on a 3D volume of the vessel anatomy to assist in catheter maneuvering and device placement.VesselNavigator is intended to assist in the treatment of endovascular diseases during procedures such as (but not limited to) AAA, TAA, carotid stenting, iliac interventions.	Similar; indications for both devices emphasize image guidance for fluoroscopy-guided endovascular procedures
Manufacturer	Cydar Ltd	Philips Medical SystemsNederland B.V.	SignificantDifferences
Trade Name	Cydar EV(Subject device)veins.Cydar EV is not intended foruse in the X-ray guidedprocedures in the liver,kidneys or pelvic organs.	VesselNavigator(Predicate device)
Construction	Software product	Software product	Identical
Hostcomputer	Separate interventional toolsworkstation	Separate interventional toolsworkstation	Identical
RegistrationOverview	2D-3D registration is achievedby machine vision tracking ofvertebral anatomy	2D-3D registration is achieved bymanual initialization and/orcorrection followed by deadreckoning based onelectromechanical tracking oftable and C-arm	Different; thepredicate andsubject devices usedifferent methodsto perform theunderlying 2D-3Dimage registrationsthough viewing ofthe image overlayfunctionality isthen performed thesame with noadditionalquestions raised forsafety or efficacy
Registrationtarget	Vertebral anatomy	X-ray C-arm and operating table	Different; targetsreflect differentregistrationmethods with theimage overlayfunctionality beingthe same with noadditionalquestions raised forsafety or efficacy
Patientcontacting	No	No	Identical
Manufacturer	Cydar Ltd	Philips Medical SystemsNederland B.V.	SignificantDifferences
Trade Name	Cydar EV(Subject device)	VesselNavigator(Predicate device)
Energyemitted orabsorbed	No	No	Identical
Dynamicupdate on C-arm / tablemotion	Automatic	Automatic	Identical
Dynamicupdate onpatientmotion	Automatic	Semi-automatic based onmovement of the gantry	Similar; automaticresponse to patientmotion allowsregistration tocontinuously occurwith no additionalquestions raised forsafety or efficacy
AnatomicalLocation	Vascular anatomy of thechest, abdomen and pelvis.	All vascular anatomy exceptcoronaries and intracranialvessels	Similar; the subjectdevice is restrictedto anatomyconsideredimmobile withrespect to thevertebral columnwith no additionalquestions raised forsafety or efficacy
Ability tostoreroadmaps	Yes	Yes	Identical
Ability tostoresnapshots	Yes	Yes	Identical
Non-clinical performance data
IEC 62304	Applied	Applied	Identical
IEC 62366	Applied	Applied	Identical
Manufacturer	Cydar Ltd	Philips Medical SystemsNederland B.V.	SignificantDifferences
Trade Name	Cydar EV(Subject device)	VesselNavigator(Predicate device)
ISO 14971	Applied	Applied	Identical
NEMA PS 3.1-3.20DICOM	Applied	Applied	Identical

Table 5A – Comparison of Characteristics

{6}------------------------------------------------

{7}------------------------------------------------

{8}------------------------------------------------

{9}------------------------------------------------

9. Non-Clinical Performance Data

As part of demonstrating the safety and effectiveness of Cydar EV and in showing substantial equivalence to the predicate device that is the subject of this 510(k) submission, Cydar Ltd completed a number of non-clinical performance tests. The Cydar EV meets all the requirements for overall design confirming that the design output meets the design inputs and specifications for the device.

Non-clinical performance testing has been performed on Cydar EV and demonstrates compliance with the following International and FDA-recognized consensus standards and FDA guidance document:

IEC 62304:2015 Medical device software – Software life cycle processes
IEC 62366-1:2015 Medical devices – Application of usability engineering to medical devices
ISO 14971:2007 Medical devices – Application of risk management to medical devices
NEMA PS 3.1-3.20 Digital Imaging and Communications in Medicine (DICOM) Set (2011)
. Guidance for Industry and FDA Staff – Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (issued May 11, 2005).

Software verification testing has been performed in accordance with the software verification plan to cover the system requirements at system/integration and unit levels as documented in this submission as well as the identified hazard mitigations. Software verification included:

registration accuracy calculated from images of the vertebral anatomy as documented in Varnavas A, Carrell T, Penney G. "Fully automated 2D—3D registration and verification" Medical Image Analysis 26 (2015):1 08–119, and
overlay alignment accuracy in the web browser display, and
information security, and
. responsiveness of overlays to changes in the fluoroscopy imagery.

Software validation testing has been performed in accordance with the software validation plan and included:

{10}------------------------------------------------

the intended use and commercial claims, and usability testing with representative clinical users ● considering:
- o ease of use,
- o visibility and legibility of displays and overlays
. usability testing with system operators and IT staff,
testing of the vessel segmentation tool,
system availability and up-time.

All of these tests were used to support substantial equivalence of the subject device.

The test results in this 510(k) premarket notification demonstrate that Cydar EV:

. complies with the aforementioned international and FDA-recognized consensus standards and FDA guidance document, and
. meets the acceptance criteria and is adequate for its intended use.

Therefore, Cydar EV is substantially equivalent to the currently marketed predicate device VesselNavigator in terms of safety and effectiveness.

10. Clinical Performance Data

A clinical investigation was conducted to evaluate safety and efficacy of the Cydar EV to provide image guidance by overlaying preoperative (diagnostic) 3D vessel anatomy onto live fluoroscopic images in order to assist in the positioning of guidewires, catheters and other endovascular devices. Cydar EV is intended to assist fluoroscopy-guided endovascular procedures in the chest, abdomen and pelvis. Suitable procedures include (but are not limited to) endovascular aortic aneurysm repair (TAA and AAA), iliac (arterial and venous) angioplasty, stenting and embolisations. The design was a multi-centre observational study examining safety, performance, usability, and clinical effect. The overall design of the clinical study is shown as follows:

. Clinical Endpoints: Primary endpoints were the accuracy, robustness, usability, procedure time, radiation exposure, and iodinated contrast volume
Subject Inclusion/Exclusion: The trial participants were patients who:
- O were willing and able to give informed consent, and
- were aged 18 or older, and O
- were scheduled to undergo an X-ray guided intervention in an anatomic zone covered O by the technology, and
- had had a pre-operative CT scan, and O
- O were able and willing to comply with the study requirements.
Study Monitoring: Cloud monitoring and data collection was performed by Cydar Ltd

{11}------------------------------------------------

The clinical endpoint and user feedback data supported the hypothesis of clinical effectiveness. Results of the clinical investigation support the indications for use of the Cydar EV to provide image guidance by overlaying preoperative (diagnostic) 3D vessel anatomy onto live fluoroscopic images in order to assist in the positioning of guidewires, catheters and other endovascular devices by achieving accurate, robust, and usable image guidance. Clinical study conclusion confirms that the device is safe and effective as used according to the instructions for use.

11. Statement of Substantial Equivalence

The Cydar EV, as designed and manufactured, is determined to be substantially equivalent to the referenced predicate device.

Regulation Number and Section

§ 892.1650 Image-intensified fluoroscopic x-ray system.

(a)
Identification. An image-intensified fluoroscopic x-ray system is a device intended to visualize anatomical structures by converting a pattern of x-radiation into a visible image through electronic amplification. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II (special controls). An anthrogram tray or radiology dental tray intended for use with an image-intensified fluoroscopic x-ray system only is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9. In addition, when intended as an accessory to the device described in paragraph (a) of this section, the fluoroscopic compression device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.