(89 days)
iCAC is a software device intended for use in estimating presence and quantity of coronary artery calcium for patients aged 30 years and above during routine care. The device automatically analyzes non-contrast chest computed tomography (CT) images collected during routine care and outputs a visual representation of estimated coronary artery calcium segmentation (intended for informational purposes only) and both exact and four-category quantitative estimates of the patient's coronary artery calcium burden in Agatston units.
The output of the subject device is made available to the physician on-demand as part of his or her standard workflow. The device-generated calcium score or score group can be viewed in the patient report at the discretion of the physician, and the physician also has the option of viewing the device-generated calcium segmentation in a diagnostic image viewer. The subject device output in no way replaces the original patient report or the original chest CT scan: both are still available to be viewed and used at the discretion of the physician.
The device is intended to provide information to the physician to provide assistance during review of the patient's case. Results of the subject device are not intended to be used on a stand-alone basis and are solely intended to aid and provide information to the physician. In all cases, further action taken on a patient should only come at the recommendation of the physician after further reviewing the patient's results.
The iCAC Device (or the "subject device") is a standalone software as a medical device (SaMD) that provides adjunctive information to a radiologist for an estimate assessment of the presence and quantity of coronary artery calcium (CAC) from routine, non-contrast, non-gated chest computed tomography (CT) scans. The device can be used to leverage the high utilization of non-gated chest CT scans (from lung cancer screening programs, routine exams, etc.) to opportunistically identify and quantify coronary artery calcium in patients.
The iCAC Device takes as an input non-contrast, non-gated chest CT scans via DICOM transfer from the clinicians imaging database such as PACS or DICOM router. The device uses a deeplearning-based computer vision algorithm for its assessment. It estimates the presence and quantity of coronary artery calcium (CAC) from routine, non-contrast, non-gated chest computed tomography (CT) scans. iCAC Device can be used to leverage the high utilization of non-gated chest CT scans (from lung cancer screening programs, routine exams, etc.) to opportunistically identify and quantify coronary artery calcium in patients.
Here's an analysis of the acceptance criteria and the study proving the iCAC device's performance, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (iCAC Device) |
|---|---|
| Overall alignment between device output calcium score groups and ground truth calcium score groups ≥ 73% | 79.7% |
| Positive Predictive Value (PPV) for each of the four possible calcium score groupings ≥ 65% | 68.1% to 90.1% |
2. Sample Size and Data Provenance for the Test Set
- Sample Size: 762 paired CT studies.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the data was collected from "nine (9) geographically diverse sites."
- Retrospective or Prospective: Retrospective study.
- Data Type: Each pair consisted of one non-gated, non-contrast chest CT and one gated coronary CT.
3. Number of Experts and Qualifications for Ground Truth Establishment (Test Set)
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. It mentions "established ground truth" and "ground truth coronary calcium detection category" but provides no details on how this ground truth was determined (e.g., by human readers and their qualifications).
4. Adjudication Method for the Test Set
The document does not specify any adjudication method used for the test set (e.g., 2+1, 3+1).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not reported. The study focused on the standalone performance of the iCAC device against an established ground truth. Therefore, there is no information on how human readers improve with or without AI assistance.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was conducted. The document states: "The iCAC Device performance was validated in a stand-alone retrospective study for overall agreement of the device output compared to the established ground truth."
7. Type of Ground Truth Used
The ground truth was based on a "gated coronary CT" in each paired study, which was then used to determine the "ground truth coronary calcium detection category." While not explicitly stated as "expert consensus" or "pathology," the inclusion of gated coronary CT implies a more definitive and often clinically established method for quantifying coronary artery calcium, likely interpreted by medical professionals. The document refers to it as "established ground truth."
8. Sample Size for the Training Set
The document does not provide the sample size used for the training set. It only details the test set for validation.
9. How Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for the training set was established.
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April 25, 2023
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Bunkerhill, Inc. % John J. Smith Partner Hogan Lovells LLP 555 Thirteenth Street, NW WASHINGTON DC 20004
Re: K230223
Trade/Device Name: iCAC Device Regulation Number: 21 CFR 892.1750 Regulation Name: Computed tomography x-ray system Regulatory Class: Class II Product Code: JAK Dated: April 7, 2022 Received: April 7, 2023
Dear John Smith:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Lu Jiang
Lu Jiang, Ph.D. Assistant Director Diagnostic X-ray Systems Team DHT8B: Division of Radiological Imaging Devices and Electronic Products OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known) K230223
Device Name
iCAC Device
Indications for Use (Describe)
iCAC is a software device intended for use in estimating presence and quantity of coronary artery calcium for patients aged 30 years and above during routine care. The device automatically analyzes non-contrast chest computed tomography (CT) images collected during routine care and outputs a visual representation of estimated coronary artery calcium segmentation (intended for informational purposes only) and both exact and four-category quantitative estimates of the patient warery calcium burden in Agatston units.
The output of the subject device is made available to the physician on-demand workflow. The devicegenerated calcium score or score group can be viewed in the patient report at the discretion of the physician also has the option of viewing the device-generated calcium segmentation in a diagnostic image viewer. The subject device output in no way replaces the original patient report or the original chest CT scan: both are still available to be viewed and used at the discretion of the physician.
The device is intended to provide information to the physician to provide assistance during review of the patient's case. Results of the subject device are not intended to be used on a stand-alone basis and are solely intended to aid and provide information to the physician. In all cases, further action taken on a patient should only come at the recommendation of the physician after further reviewing the patient's results.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
□ Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY Bunkerhill's iCAC Device
Submitter Bunkerhill, Inc.
428 El Verano Ave
Palo Alto, CA 94306
Phone: (650) 842-0198 Contact Person: Nishith Khandwala
Date Prepared: February 10, 2023
Proposed Device
| Proprietary Name | iCAC Device |
|---|---|
| Classification Name | Computed tomography x-ray system |
| Regulation Number | 21 CFR 892.1750 |
| Product Code | JAK |
| Regulatory Class | II |
Predicate Device
| Proprietary Name | HealthCCSng Manufactured by Zebra Health |
|---|---|
| Premarket Notification | K210085 |
| Classification Name | Computed tomography x-ray system |
| Regulation Number | 21 CFR 892.1750 |
| Product Code | JAK |
| Regulatory Class | II |
Device Description
The iCAC Device (or the "subject device") is a standalone software as a medical device (SaMD) that provides adjunctive information to a radiologist for an estimate assessment of the presence and quantity of coronary artery calcium (CAC) from routine, non-contrast, non-gated chest computed tomography (CT) scans. The device can be used to leverage the high utilization of nongated chest CT scans (from lung cancer screening programs, routine exams, etc.) to opportunistically identify and quantify coronary artery calcium in patients.
The iCAC Device takes as an input non-contrast, non-gated chest CT scans via DICOM transfer from the clinicians imaging database such as PACS or DICOM router. The device uses a deeplearning-based computer vision algorithm for its assessment. It estimates the presence and quantity of coronary artery calcium (CAC) from routine, non-contrast, non-gated chest computed
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tomography (CT) scans. iCAC Device can be used to leverage the high utilization of non-gated chest CT scans (from lung cancer screening programs, routine exams, etc.) to opportunistically identify and quantify coronary artery calcium in patients.
Intended Use / Indications for Use
iCAC is a software device intended for use in estimating presence and quantity of coronary artery calcium for patients aged 30 years and above during routine care. The device automatically analyzes non-gated, non-contrast chest computed tomography (CT) images collected during routine care and outputs a visual representation of estimated coronary artery calcium segmentation (intended for informational purposes only) and both exact and four-category quantitative estimates of the patient's coronary artery calcium burden in Agatston units.
The output of the subject device is made available to the physician on-demand as part of his or her standard workflow. The device-generated calcium score group can be viewed in the patient report at the discretion of the physician, and the physician also has the option of viewing the device-generated calcium segmentation in a diagnostic image viewer. The subject device output in no way replaces the original patient report or the original chest CT scan: both are still available to be viewed and used at the discretion of the physician.
The device is intended to provide information to the physician to provide assistance during review of the patient's case. Results of the subject device are not intended to be used on a stand-alone basis and are solely intended to aid and provide information to the physician. In all cases, further action taken on a patient should only come at the recommendation of the physician after further reviewing the patient's results.
Summary of Technological Characteristics
At a high level, the subject and predicate devices are based on the following same technological elements:
- Both the predicate and the subject device use deep-learning algorithms to identify the o presence of coronary artery calcium deposits and quantify calcium burden in individuals of age 30 years and up.
- Both devices analyze non-gated, non-contrast chest computed tomography (CT) images . that are sent to the software in DICOM format.
- Both the predicate and the subject device quantify the calcium burden of the coronary ● arteries.
- Both devices serve as support tools to provide information to the physician. However, they 0 do not replace clinical evaluation and do not alter the standard of care.
- Both devices segment the calcium area on an image and generate a report. ●
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The following technological differences exist between the subject and predicate devices:
- The predicate device defines three (3) detection categories for reporting the calcium score o whereas the subject device defines four (4) detection categories. The subject and predicated devices differ in that the subject device reports a detection category for calcium scores of zero, while the predicate device does not explicitly distinguish zero from nonzero calcium scores.
- The predicate device does not output an exact calcium score, whereas the subject device . reports an exact calcium score.
| Characteristic | Proposed Device: iCAC | Predicate Device:HealthCCSngManufactured by ZebraMedical(K210085) | Summary |
|---|---|---|---|
| Intended Use /Indications for Use | iCAC is a software deviceintended for use inestimating presence andquantity of coronaryartery calcium for patientsaged 30 years and aboveduring routine care. Thedevice automaticallyanalyzes non-gated, non-contrast chest computedtomography (CT) imagescollected during routinecare and outputs a visualrepresentation ofestimated coronary arterycalcium segmentation(intended forinformational purposesonly) and both exact andfour-category quantitativeestimates of the patient'scoronary artery calciumburden in Agatston units.The output of the subjectdevice is made available | The HealthCCSng deviceis intended for use as anon-invasive post-processing software toevaluate calcified plaquesin the coronary arteries,which present a risk forcoronary artery disease.The software generates anestimated coronary arterycalcium detectioncategory. TheHealthCCSng deviceanalyzes existing non-cardiac-gated CT studiesthat include the heart ofadult patients above theage of 30. The devicegenerates a three-categoryoutput representing theestimated quantity ofcalcium detected togetherwith preview axial imagesof the detected calciummeant for informationalpurposes only. The device | Primary difference is incalcium scorequantification for eachcase |
| Characteristic | Proposed Device: iCAC | Predicate Device:HealthCCSngManufactured by Zebra Medical(K210085) | Summary |
| to the physician on-demand as part of his orher standard workflow.The device-generatedcalcium score or scoregroup can be viewed inthe patient report at thediscretion of thephysician, and thephysician also has theoption of viewing thedevice-generated calciumsegmentation in adiagnostic image viewer.The subject device outputin no way replaces theoriginal patient report orthe original chest CTscan; both are stillavailable to be viewedand used at the discretionof the physician. | output will be available tothe physician as part oftheir standard workflow.The HealthCCSng resultsare not intended to beused on a stand-alonebasis for risk attribution,clinical decision-makingor otherwise precludeclinical assessment of CTstudies. | ||
| The device is intended toprovide information to thephysician to provideassistance during reviewof the patient's case.Results of the subjectdevice are not intended tobe used on a stand-alonebasis and are solelyintended to aid andprovide information to thephysician. In all cases,further action taken on apatient should only comeat the recommendation ofthe physician after further | |||
| Characteristic | Proposed Device: iCAC | Predicate Device:HealthCCSngManufactured by ZebraMedical(K210085) | Summary |
| reviewing the patient'sresults. | |||
| Type ofInterpretation | Adjunctive information | Adjunctive information | Same |
| Intended User | Interpreting physicians | Interpreting physicians | Same |
| Patient population | Patients aged 30 yearsand above | Patients above the age of30 | Similar |
| Anatomical location | Chest | Chest | Same |
| Intended location | Medical facility | Medical facility | Same |
| Rx or OTC | Rx | Rx | Same |
| Measurement scale | Agatston units | Agatston units | Same |
| Product code | JAK | JAK | Same |
| Regulation number | 21 CFR §892.1750 | 21 CFR §892.1750 | Same |
| Modality | Computed tomography(CT) | Computed tomography(CT) | Same |
| Image format | DICOM | DICOM | Same |
| Contrast | Non-contrast | Non-contrast | Same |
| Supported CT scan | Non-cardiac-gated CTscan | Non-cardiac-gated CTscan | Same |
| Slice thickness | Up to 5mm | Up to 3mm | Similar, iCAC cansupport a wider variety ofscans |
| Calcificationdetection | Automatic | Automatic | Same |
| Characteristic | Proposed Device: iCAC | Predicate Device:HealthCCSngManufactured by ZebraMedical(K210085) | Summary |
| Default threshold ofcalcium | 130 HU (HounsfieldUnits) | 130 HU (HounsfieldUnits) | Same |
| Coronary arterycalcificationquantificationmethod | CAC detection category(based on Agatstonscore), exact Agatstonscore | CAC detection category(based on Agatston score) | Similar, iCAC provides amore preciserepresentation of coronarycalcium burden |
| Main image quality | DICOM | DICOM | Same |
| Annotation ofdetected calcium | Yes | Yes | Same |
| Generate patientreport | Optional to copy result toclipboard, insert in report,DICOM SecondaryCapture | Optional to copy result toclipboard, insert in report,DICOM SecondaryCapture | Same |
| Report of thecalcium score | Yes, Coronary CalciumDetection Category andexact Agatston score4 categories (for detectioncategory):• 0• 1-99• 100-399• ≥400 | Yes, Coronary CalciumDetection Category3 categories:• 0-99• 10-399• >400 | Similar, iCAC provides amore preciserepresentation of coronarycalcium burden byseparating the category 0from the other categories. |
A table comparing the key features of the subject and predicate devices is provided below.
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Performance Data
Safety and performance of the iCAC Device 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
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Requirements and Federal Regulations and Guidance documents, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices".
The iCAC Device performance was validated in a stand-alone retrospective study for overall agreement of the device output compared to the established ground truth. The pivotal testing dataset consisted of 762 paired CT studies (one non-gated, non-contrast chest CT and one gated coronary CT in each pair) from nine (9) geographically diverse sites. The sample included adequate representation from each coronary calcium detection category. The iCAC Device's overall agreement was determined by comparing the device output coronary calcium detection category to the ground truth coronary calcium detection category.
Primary acceptance criteria for the pivotal testing study were defined as 73% overall alignment between device output calcium score groups and ground truth calcium score groups and at least 65% positive predictive value (PPV) for each of the four possible calcium score groupings. The iCAC device demonstrated an overall alignment rate of 79.7% and calcium-score-group level positive predictive values of 68.1% to 90.1%, thus satisfying both the primary acceptance criteria for the pivotal testing study.
Conclusions
The iCAC Device is as safe and effective as the predicate HealthCCSng device (K210085). The iCAC Device has the same intended uses and similar indications, technological characteristics, and principles of operation as its predicate device. The minor differences in indications do not alter the intended diagnostic use of the device and do not affect its safety and effectiveness when used as labeled. In addition, the minor technological differences between the iCAC Device and its predicate devices raise no new issues of safety or effectiveness.
§ 892.1750 Computed tomography x-ray system.
(a)
Identification. A computed tomography x-ray system is a diagnostic x-ray system intended to produce cross-sectional images of the body by computer reconstruction of x-ray transmission data from the same axial plane taken at different angles. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.