(133 days)
Not Found
No
The description focuses on standard image processing, 3D modeling, and blood flow simulation based on physical principles, without mentioning AI or ML techniques.
No.
The device is described as a software device intended for analysis to support the functional evaluation of coronary artery disease, and its results are a supportive aid for qualified clinicians. It does not directly provide therapy.
Yes
Justification: The "Intended Use / Indications for Use" section states that the device provides "FFRangio™, a mathematically derived quantity, computed from simulated blood flow information... intended to support the functional evaluation of coronary artery disease." It further specifies that "The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology." This clearly indicates its role in the diagnostic process.
No
The device description explicitly states that the FFRangio™ system is a computer system installed on a mobile cart that includes hardware components such as a computer processing unit, user interface control station (LCD screen and keyboard/mouse), medical isolation transformer, and network isolator. While the core functionality is software-based analysis of DICOM data, the device as described is not solely software.
Based on the provided information, the CathWorks FFRangio™ device is not an In Vitro Diagnostic (IVD).
Here's why:
- Intended Use: The intended use clearly states that the device analyzes previously acquired angiography DICOM data for patients with coronary artery disease. This data is derived from imaging of the patient's anatomy, not from a sample of biological material taken from the patient.
- Device Description: The device description details a computer system that processes imaging data. There is no mention of analyzing biological samples like blood, urine, or tissue.
- Input Imaging Modality: The input is angiography DICOM data, which is an imaging modality.
- Anatomical Site: The analysis is performed on the coronary artery, which is an anatomical structure within the body, not a biological sample.
In Vitro Diagnostics (IVDs) are defined as medical devices and accessories used to perform tests on samples taken from the human body (such as blood, urine, or tissue) to provide information for diagnosis, monitoring, or screening. The CathWorks FFRangio™ device does not perform tests on such samples. It analyzes imaging data to provide information about the physiological function of the coronary arteries.
N/A
Intended Use / Indications for Use
CathWorks FFRangio™ is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional evaluation.
Product codes
OEK
Device Description
The FFRangio™ system is a computer system installed on a mobile cart that is to be located inside the catheterization room or in an adjacent technical/viewing area. The cart holds the computer processing unit, user interface control station (LCD screen and keyboard/mouse), medical isolation transformer, and network isolator. Operation requires only connections to mains and a DICOM communication port. The system supports optional visual media output to the Cath Lab main displays, so the system GUI may be observed on both the system's LCD display and on the Cath Lab's main display (boom monitor).
Mentions image processing
The first was a two-phase validation study using an earlier version of the operator interface but the same image processing and computation algorithms as the final device.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Angiography DICOM data
Anatomical Site
Coronary artery disease / Coronary arteries
Indicated Patient Age Range
Adult subjects
Intended User / Care Setting
Qualified clinicians in the catheterization room or in an adjacent technical/viewing area of the Cath Lab.
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
The second study, the FAST-FFR Trial, was the pivotal clinical study to support the substantial equivalence of the FFRangio™ system. FAST-FFR was a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFRance ™ as compared to invasive wire FFR. Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. When clinically indicated, invasive FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. On-site hospital users who were blinded to the invasive FFR used the FFRancio™ system following acquisition of the diagnostic angiograms to generate the patient's FFRancio ™. The FFRancia ™ was not used for diagnostic or clinical decisions. Co-primary endpoints were the sensitivity and specificity of the dichotomously scored FFRangio™ for predicting pressure wire-derived FFR using a cutoff value of 0.80. Secondary endpoints included the accuracy of FFRangio™ and its correlation with invasive FFR.
The FAST-FFR study was conducted at 10 sites in 5 countries in the United States, Europe and Israel, from September 2017 to June 2018, with 382 subjects enrolled of which 30 were roll-in subjects and 352 were study subjects. 124 Subjects in total were enrolled at sites in the United States (32.5%).
Subjects had an overall mean age of 64.9 ± (9.9) years and 74.6% were men. 92.5% were white and the remaining from other races. A total of 31.4% had diabetes mellitus, 69.1 % had hypertension, and 76.2% had hyperlipidemia. 45.3% of subjects presented with stable angina, 31.4% with unstable angina, and 14.1% with silent ischemia. Overall 15.4% of the patient population had CCS classification 0 and were asymptomatic.
In total, 301 adult subjects and 319 coronary lesions with both a qualifiable invasive FFR and FFRancio™ measurements were available for efficacy analysis. Of these, 54% were LAD lesions, 24% RCA, 19% LCX and 3% Ramus. 14% of lesions involved a bifurcation and 24% were calcified. Diagnostic angiograms were acquired from all four C-arm types (Phillips (27%), GE (20%), Siemens (43%) and Toshiba (10%)), and coronary pressure and flow wires used included Abbott-St. Jude (48%), Opsens (6%) or Volcano-Phillips (46%). All invasive FFR data were reviewed post-hoc by an independent FFR physiology core laboratory and all FFRangio" data were reviewed post-hoc by a core laboratory at CathWorks.
Summary of Performance Studies
Study Type: Clinical Study - Two-phase validation study (earlier version of operator interface but same image processing and computation algorithms) and FAST-FFR Trial (pivotal clinical study).
Sample Size: 203 coronary lesions in the validation study; 382 subjects enrolled (30 roll-in, 352 study subjects), 301 adult subjects and 319 coronary lesions for efficacy analysis in FAST-FFR trial.
AUC: Not explicitly stated, but sensitivity and specificity are provided.
MRMC: Not Found
Standalone Performance:
- Two-phase validation study: Sensitivity 88%, Specificity 95%, Diagnostic Accuracy 93% for FFRangio. Average intraclass correlation coefficient for two measurements of FFRangio by two operators was 0.962 (95% CI 0.95-0.971, P
§ 870.1415 Coronary vascular physiologic simulation software device.
(a)
Identification. A coronary vascular physiologic simulation software device is a prescription device that provides simulated functional assessment of blood flow in the coronary vascular system using data extracted from medical device imaging to solve algorithms and yield simulated metrics of physiologic information (e.g., blood flow, coronary flow reserve, fractional flow reserve, myocardial perfusion). A coronary vascular physiologic simulation software device is intended to generate results for use and review by a qualified clinician.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Adequate software verification and validation based on comprehensive hazard analysis, with identification of appropriate mitigations, must be performed, including:
(i) Full characterization of the technical parameters of the software, including:
(A) Any proprietary algorithm(s) used to model the vascular anatomy; and
(B) Adequate description of the expected impact of all applicable image acquisition hardware features and characteristics on performance and any associated minimum specifications;
(ii) Adequate consideration of privacy and security issues in the system design; and
(iii) Adequate mitigation of the impact of failure of any subsystem components (
e.g., signal detection and analysis, data storage, system communications and cybersecurity) with respect to incorrect patient reports and operator failures.(2) Adequate non-clinical performance testing must be provided to demonstrate the validity of computational modeling methods for flow measurement; and
(3) Clinical data supporting the proposed intended use must be provided, including the following:
(i) Output measure(s) must be compared to a clinically acceptable method and must adequately represent the simulated measure(s) the device provides in an accurate and reproducible manner;
(ii) Clinical utility of the device measurement accuracy must be demonstrated by comparison to that of other available diagnostic tests (
e.g., from literature analysis);(iii) Statistical performance of the device within clinical risk strata (
e.g., age, relevant comorbidities, disease stability) must be reported;(iv) The dataset must be adequately representative of the intended use population for the device (
e.g., patients, range of vessel sizes, imaging device models). Any selection criteria or limitations of the samples must be fully described and justified;(v) Statistical methods must consider the predefined endpoints:
(A) Estimates of probabilities of incorrect results must be provided for each endpoint,
(B) Where multiple samples from the same patient are used, statistical analysis must not assume statistical independence without adequate justification, and
(C) The report must provide appropriate confidence intervals for each performance metric;
(vi) Sensitivity and specificity must be characterized across the range of available measurements;
(vii) Agreement of the simulated measure(s) with clinically acceptable measure(s) must be assessed across the full range of measurements;
(viii) Comparison of the measurement performance must be provided across the range of intended image acquisition hardware; and
(ix) If the device uses a cutoff threshold or operates across a spectrum of disease, it must be established prior to validation, and it must be justified as to how it was determined and clinically validated;
(4) Adequate validation must be performed and controls implemented to characterize and ensure consistency (
i.e., repeatability and reproducibility) of measurement outputs:(i) Acceptable incoming image quality control measures and the resulting image rejection rate for the clinical data must be specified, and
(ii) Data must be provided within the clinical validation study or using equivalent datasets demonstrating the consistency (
i.e., repeatability and reproducibility) of the output that is representative of the range of data quality likely to be encountered in the intended use population and relevant use conditions in the intended use environment;(A) Testing must be performed using multiple operators meeting planned qualification criteria and using the procedure that will be implemented in the production use of the device, and
(B) The factors (
e.g., medical imaging dataset, operator) must be identified regarding which were held constant and which were varied during the evaluation, and a description must be provided for the computations and statistical analyses used to evaluate the data;(5) Human factors evaluation and validation must be provided to demonstrate adequate performance of the user interface to allow for users to accurately measure intended parameters, particularly where parameter settings that have impact on measurements require significant user intervention; and
(6) Device labeling must be provided that adequately describes the following:
(i) The device's intended use, including the type of imaging data used, what the device measures and outputs to the user, whether the measure is qualitative or quantitative, the clinical indications for which it is to be used, and the specific population for which the device use is intended;
(ii) Appropriate warnings specifying the intended patient population, identifying anatomy and image acquisition factors that may impact measurement results, and providing cautionary guidance for interpretation of the provided measurements;
(iii) Key assumptions made in the calculation and determination of simulated measurements;
(iv) The measurement performance of the device for all presented parameters, with appropriate confidence intervals, and the supporting evidence for this performance. Per-vessel clinical performance, including where applicable localized performance according to vessel and segment, must be included as well as a characterization of the measurement error across the expected range of measurement for key parameters based on the clinical data;
(v) A detailed description of the patients studied in the clinical validation (
e.g., age, gender, race or ethnicity, clinical stability, current treatment regimen) as well as procedural details of the clinical study (e.g., scanner representation, calcium scores, use of beta-blockers or nitrates); and(vi) Where significant human interface is necessary for accurate analysis, adequately detailed description of the analysis procedure using the device and any data features that could affect accuracy of results.
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December 19, 2018
CathWorks Ltd. % Sheila Hemeon-Heyer President Heyer Regulatory Solutions LLC 125 Cherry Lane Amherst, Massachusetts 01002
Re: K182149
Trade/Device Name: FFRangio™ System Regulation Number: 21 CFR 870.1415 Regulation Name: Coronary Vascular Physiologic Simulation Software Regulatory Class: Class II Product Code: OEK Dated: December 17, 2018 Received: December 18, 2018
Dear Sheila Hemeon-Heyer:
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) 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 mediation-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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Image /page/1/Picture/5 description: The image shows the name "Shawn W. Forrest -A" in a large, sans-serif font. The text is arranged in two lines, with "Shawn W." on the first line and "Forrest -A" on the second line. The background is plain white, with a light blue rectangular shape partially visible behind the text.
igitally signed by Shawn W. Forrest US o=ll S Government HHS. ou=FDA. ou=People 0 9 2342 19200300 100 1 1=130040334 Shawn W. Forrest -A Date: 2018.12.19 14:48:08 -05'00
Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K182149
Device Name
FFRangio™
Indications for Use (Describe)
CathWorks FFRangio™ is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional evaluation.
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) |
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510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted per the requirements of 21 CFR 807.92.
| A. | Submitter: | Heyer Regulatory Solutions LLC |
|---|---|---|
| P.O. Box 2151 | ||
| Amherst, MA 01004-2151 | ||
| Contact: Sheila Hemeon-Heyer | ||
| Sheila@heyer-regulatory.com |
- B. Manufacturer Contact: CathWorks, Ltd. llanit Frank Hakim 3 Rappaport St. Kfar Saba 4465141, ISRAEL Tel: +972 9 7467387 ilanit@cath.works
- C. Date Prepared: December 19, 2018
D. Device Name and Classification Information:
| Trade Name: | FFRangio™ System |
|---|---|
| Classification Name: | Coronary Vascular Physiologic Simulation Software |
| Device | |
| Common Name: | Digital FFR System |
| Regulation: | 21 CFR 870.1415 |
| Product Code: | QEK |
| Review Panel: | Cardiovascular |
| Class: | II |
- K161772 for FFRcT, manufactured by HeartFlow, Inc. E. Predicate Device(s):
F. Summary Device Description:
The FFRangio™ system is a computer system installed on a mobile cart that is to be located inside the catheterization room or in an adjacent technical/viewing area. The cart holds the computer processing unit, user interface control station (LCD screen and keyboard/mouse), medical isolation transformer, and network isolator. Operation requires only connections to mains and a DICOM communication port. The system supports optional visual media output to the Cath Lab main displays, so the system GUI may be observed on both the system's LCD display and on the Cath Lab's main display (boom monitor).
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FFRancio™ uses standard angiographic images (angiograms) that are retrieved from the X-ray Imaging System (C-arm) in DICOM format. The user selects the images and, following the system prompts, marks key features on the images including the target lesion, ostium location, main vessel, target vessel, and its side branches. The system then matches the corresponding vessels among the projections and generates a 3D computer model of the vessels. The 3D model is used for blood flow analysis and determination of the FFRangio.
G. Indications for Use Statement:
CathWorks FFRangio™ is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio ™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional evaluation.
H. Comparison with Predicate Device
The CathWorks FFRangio™ and the HeartFlow FFRct are both coronary physiologic simulation software devices that use data extracted from coronary imaging to provide a noninvasive assessment of fractional flow reserve (FFR). The primary difference between the two devices for the purposes of 510(k) substantial equivalence is that the FFRancio™ uses data extracted from angjographic images, while the FFRct uses data extracted from CT scans. The table below provides a technological comparison between the two devices. Discussion of the differences is provided following the table.
| | CathWorks FFRangioTM | Predicate Device
HeartFlow FFRCT2.0 |
|------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications
for Use | CathWorks FFRangioTM is a software
device for the clinical quantitative and
qualitative analysis of previously
acquired angiography DICOM data
for patients with coronary artery
disease. It provides FFRangioTM, a
mathematically derived quantity,
computed from simulated blood flow
information obtained from a 3D
computer model, generated from | HeartFlow FFRCT is a coronary
physiologic simulation software for the
clinical quantitative and qualitative
analysis of previously acquired
Computed Tomography DICOM data
for clinically stable symptomatic
patients with coronary artery disease.
It provides FFRCT, a mathematically
derived quantity, computed from
simulated pressure, velocity and blood |
5
| | CathWorks FFRangio™ | Predicate Device
HeartFlow FFRCT2.0 |
|------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | coronary angiography images.
FFRangio™ analysis is intended to
support the functional evaluation of
coronary artery disease. The results
of this analysis are provided as a
supportive aid for qualified clinicians
in the evaluation and assessment of
coronary arteries physiology. The
results of CathWorks FFRangio™ are
intended to be used by qualified
clinicians in conjunction with the
patient's clinical history, symptoms,
and other diagnostic tests, as well as
the clinician's professional evaluation. | flow information obtained from a 3D
computer model generated from static
coronary CT images. FFRCT analysis
is intended to support the functional
evaluation of coronary artery disease.
The results of this analysis are
provided to support qualified clinicians
to aid in the evaluation and
assessment of coronary arteries. The
results of HeartFlow FFRCT are
intended to be used by qualified
clinicians in conjunction with the
patient's clinical history, symptoms,
and other diagnostic tests, as well as
the clinician's professional judgment. |
| System
overview | Computer system with software that
constructs and displays a 3D
computer model of the coronary
arteries to simulate blood flow | Computer system with software that
constructs and displays a 3D computer
model of the coronary arteries to
simulate blood flow |
| Image source | Standard DICOM angiographic
images taken in Cath Lab | Previously obtained CT images |
| Software
controlled | Yes | Yes |
| On-line
processing | Yes | No |
| Sensitivity* | 93.5% (lower 95% CI, 87.8%) | 84.2% (lower 95% CI, 75.8%) |
| Specificity* | 91.2% (lower 95% CI, 86.0%) | 84.9% (lower 95% CI, 80.4%) |
*Sensitivity and specificity are the per vessel estimates as reported for the proposed and predicate device pivotal clinical studies.
Discussion of Differences
The key difference between the FFRancio™ and FFR-T devices is that FFRance™ analysis is based on standard angiograms taken in the cath lab, while FFRct uses previously obtained CT scans. This enables FFRangio™ to be used on-line in the cath lab to provide the FFR measure during the procedure. Clinical data collected in the FFRangio™ pivotal clinical study demonstrated high sensitivity and specificity. Subgroup analyses demonstrated that the FFRange ™ system is effective for both symptomatic and nonsymptomatic patients with coronary artery disease.
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l. Performance Data to Support Substantial Equivalence
The following pre-clinical testing was presented to demonstrate the appropriate functionality of the software, the basis of the computational methods, and verification of hardware functionality. Some testing (e.g., biocompatibility, shelf life, etc.) was not applicable for this software only device. Animal testing was not conducted as animal models do not permit evaluation of the technology in relevant anatomic or physiologic models reflecting diseased human coronary vessels.
Software: Software documentation consistent with FDA's quidance for the Content of Premarket Submissions for Software Contained in Medical Devices," May 11, 2005, for moderate level of concern software including a comprehensive risk analysis, software verification and validation, off-the-shelf software integrity, and cybersecurity considerations.
Electrical Safety Testing: The FFRangio™ computer system and cart were evaluated and found to be in compliance with the applicable requirements of IEC 60601-1:2005 (3ª Edition) +C1:2006 +C2:2007 +A1:2012, "Medical electrical equipment - Part 1: General requirements for basic safety and essential performance." All emissions and immunity tests were passed.
Electromagnetic Compatibility Testing: The FFRango ™ computer system was tested and found to be in compliance with the applicable requirements of IEC 60601-1-2:2014 (4th edition), "Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances -Requirements and tests."
Hardware Verification Testing: The FFRancio™ computer system and cart underwent type testing per an internal CathWorks protocol. All hardware requirements of the system were evaluated/tested and found to meet the pre-defined acceptance criteria.
Transportation Testing: The FFRangio™ computer system and cart are shipped in a padded, wooden box. Transportation testing was conducted in accordance with ASTM D4169-16. "Standard Practice for Performance Testing of Shipping Containers and Systems." All tests were passed.
Human Factors Evaluation: Usability testing of the FFRango™ system and its operator manual was conducted in accordance with ANSI/AAMI/IEC 62366-1:2015, "Application of usability engineering to medical devices" and the FDA guidance document ""Applying Human Factors and Usability Engineering to Medical Devices," February 3, 2016. Participants in the usability testing were 19 healthcare personnel including physicians, nurses, technicians, and imaging fellows. All critical tasks identified for the use of the FFRancio™ system were completed in the usability testing without any use errors. All of the questions in the knowledge-based assessment were answered correctly with the exception of one question that was answered partially correctly by one participant.
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Overall, the usability of the system was graded as a 4.5 out of 5 by the test participants. The conclusion of the testing was that the FFRangio™ system can be used safely and effectively by the intended user population. No residual use-related risks were identified.
Clinical Studies:
Two clinical studies were conducted using the FFRance™ system. The first was a twophase validation study using an earlier version of the operator interface but the same image processing and computation algorithms as the final device. The clinical validation study compared the FFRangio™ to invasive FFR obtained from patients already scheduled for coronary assessment in the cath lab. The patient's angiographic images were shipped to an off-line location, where they were processed using the FFRango™ system by two independent operators who were blinded to the invasive FFR and blinded to each other. Analysis of the results from 203 coronary lesions with data collected at four centers (one in the US, one in the EU, and two in Israel) demonstrated sensitivity, specificity, and diagnostic accuracy for FFRangio to be 88%, 95% and 93%, respectively. The average intraclass correlation coefficient for the two measurements of FFRangi ™ conducted by the two operators was 0.962 with a 95% confidence interval from 0.95 to 0.971 (P0.8 was negative. The pre-specified performance goals identified by the Sponsor and agreed upon by FDA for sensitivity and specificity were 70% and 75%, respectively. The primary endpoint for study success required that the lower bounds of the 95% confidence intervals for both sensitivity and specificity be above these performance goals.
The per vessel sensitivity of FFRangio"" was 93.5% with a lower one-sided 95% Cl of 87.8%. The per-vessel specificity of FFRangio™ was 91.2% with a lower one-sided 95% CI of 86.0%. Both of the lower one-sided confidence limits for sensitivity and specificity were significantly above the pre-specified target goals of 70% and 75%, respectively, and were considered acceptable. The results are shown in the table below.
| | Statistic | 95% CI limits | Performance goal /
criteria |
|-----------------------------|-----------|---------------|--------------------------------|
| Sensitivity | 93.5% | 87.8% - 96.6% | 70% |
| Specificity | 91.2% | 86.0% - 94.6% | 75% |
| Correlation Coefficient (R) | 0.80 | | 0.65 |
| Intercept | 0.04 | 0.03 - 0.05 | -0.20 - 0.20 |
| Slope | 0.93 | 0.92 - 0.95 | 0.80 - 1.20 |
As the FFRangio" analysis was not used in any clinical decision making and did not add any risk to the study subjects, and the trial did not include clinical follow-up, only procedure-related adverse events were captured. Only two adverse events were reported, neither of which was related to the device.
The FAST-FFR study confirmed that FFRangio™ produces accurate results, with very high sensitivity and specificity for the measurement of FFR.
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| Special Controls (abbreviated from
| regulation) | How Fulfilled |
|---|---|
| 1) Adequate software verification and | |
| validation based on comprehensive | |
| hazard analysis, with identification of | |
| appropriate mitigations, must be | |
| performed., | The FFRangio system software was designed, |
| developed and tested in accordance with ISO | |
| 62304:2006 Medical device software -- Software | |
| life cycle processes and included | |
| comprehensive hazard analysis, identification of | |
| appropriate risk mitigations, and software | |
| testing at all stages of development to verify and | |
| validate the software algorithms, system | |
| operation, privacy/security issues, and the | |
| impact of failures (e.g., inadequate image | |
| quality, image data corruption, improper | |
| operation steps). | |
| 2. Adequate non-clinical performance | |
| testing must be provided to demonstrate | |
| the validity of computational modeling | |
| methods for flow measurement. | A series of in vitro and animal studies were |
| conducted by CathWorks to validate the | |
| computational modelling methods for the | |
| FFRangio system. | |
| 3. Clinical data supporting the proposed | |
| intended use must be provided. | A multi-center clinical study was conducted to |
| validate the sensitivity and specificity of the | |
| FFRangio in the intended use population. See | |
| the detailed summary of this study presented in | |
| Section I above. | |
| (4) Adequate validation must be | |
| performed and controls implemented to | |
| characterize and ensure consistency | |
| (repeatability and reproducibility) of | |
| measurement output. | The clinical pivotal study was conducted at 10 |
| sites with multiple device users at each site. A | |
| covariate analysis showed no site interaction on | |
| the FFRangio results. | |
| A reproducibility and repeatability analysis was | |
| performed in a separate clinical validation study. | |
| (5) Human factors evaluation and | |
| validation must be provided to | |
| demonstrate adequate performance of the | |
| user interface to allow for users to | |
| accurately measure intended parameters, | |
| particularly where parameter settings that | |
| have impact on measurements require | |
| significant user intervention. | A human factors study was conducted in |
| accordance with FDA's Guidance Applying | |
| Human Factors and Usability Engineering to | |
| Medical Devices, 2016. The study evaluated the | |
| critical tasks associated with use of the device. | |
| The study results demonstrated that the | |
| intended use population was able to safety and | |
| accurately use the FFRangio system. No | |
| additional risk mitigations were identified from | |
| this study. | |
| (6) Device labeling must be provided that | |
| adequately describes the following: | |
| (i) The device's intended use, | |
| (ii) Appropriate warnings | The device instructions for use include all of the |
| elements required by this special control, | |
| including: | |
| ● Intended use statement the device | |
| mechanism of action and intended patient | |
| Special Controls (abbreviated from | |
| regulation) | How Fulfilled |
| (iii) Key assumptions | population |
| (iv) The measurement performance of the | |
| device for all presented parameters | |
| (v) A detailed description of the clinical | |
| study subjects and results | |
| (vi) A detailed description of the analysis | |
| procedure using the device and any data | |
| features that could affect accuracy of | |
| results. | • Appropriate warnings and precautions for |
| safe use of the device, including factors that | |
| could adversely affect the device output and | |
| cautions to use the device output in context | |
| with other clinical factors for patient care | |
| • Limitations describing patient populations | |
| and lesion types for which the safety and | |
| effectiveness of FFRangio has not been | |
| evaluated | |
| • Instructions for use providing guidelines for | |
| the compatible image acquisition systems | |
| and the required criteria for the images to | |
| process the FFRangio. | |
| • Detailed steps for the system operation and | |
| analysis procedures | |
| • A detailed summary of the FAST-FFR | |
| clinical study protocol |
J. Compliance with Special Controls for 21 CFR 870.1415
10
K. Conclusion
The information and testing presented in this 510(k) demonstrate that the CathWorks FFRancio™ is substantially equivalent to the HeartFlow FFRct. Performance data provided in this 510(k) demonstrate that the FFRangio™ system is safe and effective for the non-invasive assessment of FFR from standard angiographic images obtained in the coronary cath lab.